Deception Point Page 39

â€Å"My source is not your concern. But if you spend some time studying these figures, you will clearly see that Senator Sexton does not have the kind of money he is currently spending. After Katherine died, he squandered the vast majority of her legacy on bad investments, personal comforts, and buying himself what appears to be certain victory in the primaries. As of six months ago, your candidate was broke.† Gabrielle sensed this had to be a bluff. If Sexton were broke, he sure wasn't acting it. He was buying advertising time in bigger and bigger blocks every week. â€Å"Your candidate,† Tench continued, â€Å"is currently outspending the President four to one. And he has no personal money.† â€Å"We get a lot of donations.† â€Å"Yes, some of them legal.† Gabrielle's head shot up. â€Å"I beg your pardon?† Tench leaned across the desk, and Gabrielle could smell her nicotine breath. â€Å"Gabrielle Ashe, I am going to ask you a question, and I suggest you think very carefully before you answer. It could affect whether you spend the next few years in jail or not. Are you aware that Senator Sexton is accepting enormous illegal campaign bribes from aerospace companies who have billions to gain from the privatization of NASA?† Gabrielle stared. â€Å"That's an absurd allegation!† â€Å"Are you saying you are unaware of this activity?† â€Å"I think I would know if the senator were accepting bribes of the magnitude you are suggesting.† Tench smiled coldly. â€Å"Gabrielle, I understand that Senator Sexton has shared a lot of himself with you, but I assure you there is plenty you do not know about the man.† Gabrielle stood up. â€Å"This meeting is over.† â€Å"On the contrary,† Tench said, removing the remaining contents of the folder and spreading it on the desk. â€Å"This meeting is just beginning.† 44 Inside the habisphere's â€Å"staging room,† Rachel Sexton felt like an astronaut as she slid into one of NASA's Mark IX microclimate survival suits. The black, one-piece, hooded jumpsuit resembled an inflatable scuba suit. Its two-ply, memory-foam fabric was fitted with hollow channels through which a dense gel was pumped to help the wearer regulate body temperature in both hot and cold environments. Now, as Rachel pulled the tight-fitting hood over her head, her eyes fell on the NASA administrator. He appeared as a silent sentinel at the door, clearly displeased with the necessity for this little mission. Norah Mangor was muttering obscenities as she got everyone outfitted. â€Å"Here's an extra pudgy,† she said, tossing Corky his suit. Tolland was already half into his. Once Rachel was fully zipped up, Norah found the stopcock on Rachel's side and connected her to an infusion tube that coiled out of a silver canister resembling a large scuba tank. â€Å"Inhale,† Norah said, opening the valve. Rachel heard a hiss and felt gel being injected into the suit. The memory foam expanded, and the suit compressed around her, pressing down on her inner layer of clothing. The sensation reminded her of sticking her hand underwater while wearing a rubber glove. As the hood inflated around her head, it pressed in on her ears, making everything sound muffled. I'm in a cocoon. â€Å"Best thing about the Mark IX,† Norah said, â€Å"is the padding. You can fall on your ass and not feel a thing.† Rachel believed it. She felt like she was trapped inside a mattress. Norah handed Rachel a series of tools-an ice ax, tether snaps, and carabiners, which she affixed to the belt harnessed on Rachel's waist. â€Å"All this?† Rachel asked, eyeing the gear. â€Å"To go two hundred yards?† Norah's eyes narrowed. â€Å"You want to come or not?† Tolland gave Rachel a reassuring nod. â€Å"Norah's just being careful.† Corky connected to the infusion tank and inflated his suit, looking amused. â€Å"I feel like I'm wearing a giant condom.† Norah gave a disgusted groan. â€Å"Like you'd know, virgin boy.† Tolland sat down next to Rachel. He gave her a weak smile as she donned her heavy boots and crampons. â€Å"You sure you want to come?† His eyes had a protective concern that drew her in. Rachel hoped her confident nod belied her growing trepidation. Two hundred yards†¦ not far at all. â€Å"And you thought you could find excitement only on the high seas.† Tolland chuckled, talking as he attached his own crampons. â€Å"I've decided I like liquid water much better than this frozen stuff.† â€Å"I've never been a big fan of either,† Rachel said. â€Å"I fell through the ice as a kid. Water's made me nervous ever since.† Tolland glanced over, his eyes sympathetic. â€Å"Sorry to hear that. When this is over, you'll have to come out and visit me on the Goya. I'll change your mind about water. Promise.† The invitation surprised her. The Goya was Tolland's research ship-well-known both from its role in Amazing Seas as well as its reputation as one of the strangest-looking ships on the ocean. Although a visit to the Goya would be unnerving for Rachel, she knew it would be hard to pass up. â€Å"She's anchored twelve miles off the coast of New Jersey at the moment,† Tolland said, struggling with his crampon latches. â€Å"Sounds like an unlikely spot.† â€Å"Not at all. The Atlantic seaboard is an incredible place. We were gearing up to shoot a new documentary when I was so rudely interrupted by the President.† Rachel laughed. â€Å"Shooting a documentary on what?† â€Å"Sphyrna mokarran and megaplumes.† Rachel frowned. â€Å"Glad I asked.† Tolland finished attaching his crampons and looked up. â€Å"Seriously, I'll be filming out there for a couple weeks. Washington's not that far from the Jersey coast. Come out when you get back home. No reason to spend your life afraid of the water. My crew would roll out the red carpet for you.† Norah Mangor's voice blared. â€Å"Are we going outside, or should I get you two some candles and champagne?† 45 Gabrielle Ashe had no idea what to make of the documents now spread out before her on Marjorie Tench's desk. The pile included photocopied letters, faxes, transcripts of phone conversations, and they all seemed to support the allegation that Senator Sexton was in covert dialogue with private space companies. Tench pushed a couple of grainy black-and-white photographs toward Gabrielle. â€Å"I assume this is news to you?† Gabrielle looked at the photos. The first candid shot showed Senator Sexton getting out of a taxi in some kind of underground garage. Sexton never takes taxis. Gabrielle looked at the second shot-a telephoto of Sexton climbing into a parked white minivan. An old man appeared to be in the van waiting for him. â€Å"Who is that?† Gabrielle said, suspicious the photos might be faked. â€Å"A big shot from the SFF.† Gabrielle was doubtful. â€Å"The Space Frontier Foundation?† The SFF was like a â€Å"union† for private space companies. It represented aerospace contractors, entrepreneurs, venture capitalists-any private entity that wanted to go into space. They tended to be critical of NASA, arguing that the U.S. space program employed unfair business practices to prevent private companies from launching missions into space. â€Å"The SFF,† Tench said, â€Å"now represents over a hundred major corporations, some very wealthy enterprises who are waiting eagerly for the Space Commercialization Promotions Act to be ratified.† Gabrielle considered it. For obvious reasons the SFF was a vocal supporter of Sexton's campaign, although the senator had been careful not to get too close to them because of their controversial lobbying tactics. Recently the SFF had published an explosive rant charging that NASA was in fact an â€Å"illegal monopoly† whose ability to operate at a loss and still stay in business represented unfair competition to private firms. According to the SFF, whenever AT T needed a telecomm satellite launched, several private space companies offered to do the job at a reasonable $50 million. Unfortunately, NASA always stepped in and offered to launch AT T's satellites for a mere twenty-five million, even though it cost NASA five times that to do the job! Operating at a loss is one way NASA keeps its grip on space, the SFF lawyers accused. And taxpayers pick up the tab.

Twilight 12. BALANCING

12. BALANCING â€Å"Billy!† Charlie called as soon as he got out of the car. I turned toward the house, beckoning to Jacob as I ducked under the porch. I heard Charlie greeting them loudly behind me. â€Å"I'm going to pretend I didn't see you behind the wheel, Jake,† he said disapprovingly. â€Å"We get permits early on the rez,† Jacob said while I unlocked the door and flicked on the porch light. â€Å"Sure you do,† Charlie laughed. â€Å"I have to get around somehow.† I recognized Billy's resonant voice easily, despite the years. The sound of it made me feel suddenly younger, a child. I went inside, leaving the door open behind me and turning on lights before I hung up my jacket. Then I stood in the door, watching anxiously as Charlie and Jacob helped Billy out of the car and into his wheelchair. I backed out of the way as the three of them hurried in, shaking off the rain. â€Å"This is a surprise,† Charlie was saying. â€Å"It's been too long,† Billy answered. â€Å"I hope it's not a bad time.† His dark eyes flashed up to me again, their expression unreadable. â€Å"No, it's great. I hope you can stay for the game.† Jacob grinned. â€Å"I think that's the plan – our TV broke last week.† Billy made a face at his son. â€Å"And, of course, Jacob was anxious to see Bella again,† he added. Jacob scowled and ducked his head while I fought back a surge of remorse. Maybe I'd been too convincing on the beach. â€Å"Are you hungry?† I asked, turning toward the kitchen. I was eager to escape Billy's searching gaze. â€Å"Naw, we ate just before we came,† Jacob answered. â€Å"How about you, Charlie?† I called over my shoulder as I fled around the corner. â€Å"Sure,† he replied, his voice moving in the direction of the front room and the TV. I could hear Billy's chair follow. The grilled cheese sandwiches were in the frying pan and I was slicing up a tomato when I sensed someone behind me. â€Å"So, how are things?† Jacob asked. â€Å"Pretty good.† I smiled. His enthusiasm was hard to resist. â€Å"How about you? Did you finish your car?† â€Å"No.† He frowned. â€Å"I still need parts. We borrowed that one.† He pointed with his thumb in the direction of the front yard. â€Å"Sorry. I haven't seen any†¦ what was it you were looking for?† â€Å"Master cylinder.† He grinned. â€Å"Is something wrong with the truck?† he added suddenly. â€Å"No.† â€Å"Oh. I just wondered because you weren't driving it.† I stared down at the pan, pulling up the edge of a sandwich to check the bottom side. â€Å"I got a ride with a friend.† â€Å"Nice ride.† Jacob's voice was admiring. â€Å"I didn't recognize the driver, though. I thought I knew most of the kids around here.† I nodded noncommittally, keeping my eyes down as I flipped sandwiches. â€Å"My dad seemed to know him from somewhere.† â€Å"Jacob, could you hand me some plates? They're in the cupboard over the sink.† â€Å"Sure.† He got the plates in silence. I hoped he would let it drop now. â€Å"So who was it?† he asked, setting two plates on the counter next to me. I sighed in defeat. â€Å"Edward Cullen.† To my surprise, he laughed. I glanced up at him. He looked a little embarrassed. â€Å"Guess that explains it, then,† he said. â€Å"I wondered why my dad was acting so strange.† â€Å"That's right.† I faked an innocent expression. â€Å"He doesn't like the Cullens.† â€Å"Superstitious old man,† Jacob muttered under his breath. â€Å"You don't think he'd say anything to Charlie?† I couldn't help asking, the words coming out in a low rush. Jacob stared at me for a moment, and I couldn't read the expression in his dark eyes. â€Å"I doubt it,† he finally answered. â€Å"I think Charlie chewed him out pretty good last time. They haven't spoken much since – tonight is sort of a reunion, I think. I don't think he'd bring it up again.† â€Å"Oh,† I said, trying to sound indifferent. I stayed in the front room after I carried the food out to Charlie, pretending to watch the game while Jacob chattered at me. I was really listening to the men's conversation, watching for any sign that Billy was about to rat me out, trying to think of ways to stop him if he began. It was a long night. I had a lot of homework that was going undone, but I was afraid to leave Billy alone with Charlie. Finally, the game ended. â€Å"Are you and your friends coming back to the beach soon?† Jacob asked as he pushed his father over the lip of the threshold. â€Å"I'm not sure,† I hedged. â€Å"That was fun, Charlie,† Billy said. â€Å"Come up for the next game,† Charlie encouraged. â€Å"Sure, sure,† Billy said. â€Å"We'll be here. Have a good night.† His eyes shifted to mine, and his smile disappeared. â€Å"You take care, Bella,† he added seriously. â€Å"Thanks,† I muttered, looking away. I headed for the stairs while Charlie waved from the doorway. â€Å"Wait, Bella,† he said. I cringed. Had Billy gotten something in before I'd joined them in the living room? But Charlie was relaxed, still grinning from the unexpected visit. â€Å"I didn't get a chance to talk to you tonight. How was your day?† â€Å"Good.† I hesitated with one foot on the first stair, searching for details I could safely share. â€Å"My badminton team won all four games.† â€Å"Wow, I didn't know you could play badminton.† â€Å"Well, actually I can't, but my partner is really good,† I admitted. â€Å"Who is it?† he asked with token interest. â€Å"Um†¦ Mike Newton,† I told him reluctantly. â€Å"Oh yeah – you said you were friends with the Newton kid.† He perked up. â€Å"Nice family.† He mused for a minute. â€Å"Why didn't you ask him to the dance this weekend?† â€Å"Dad!† I groaned. â€Å"He's kind of dating my friend Jessica. Besides, you know I can't dance.† â€Å"Oh yeah,† he muttered. Then he smiled at me apologetically. â€Å"So I guess it's good you'll be gone Saturday†¦ I've made plans to go fishing with the guys from the station. The weather's supposed to be real warm. But if you wanted to put your trip off till someone could go with you, I'd stay home. I know I leave you here alone too much.† â€Å"Dad, you're doing a great job.† I smiled, hoping my relief didn't show. â€Å"I've never minded being alone – I'm too much like you.† I winked at him, and he smiled his crinkly-eyed smile. I slept better that night, too tired to dream again. When I woke to the pearl gray morning, my mood was blissful. The tense evening with Billy and Jacob seemed harmless enough now; I decided to forget it completely. I caught myself whistling while I was pulling the front part of my hair back into a barrette, and later again as I skipped down the stairs. Charlie noticed. â€Å"You're cheerful this morning,† he commented over breakfast. I shrugged. â€Å"It's Friday.† I hurried so I would be ready to go the second Charlie left. I had my bag ready, shoes on, teeth brushed, but even though I rushed to the door as soon as I was sure Charlie would be out of sight, Edward was faster. He was waiting in his shiny car, windows down, engine off. I didn't hesitate this time, climbing in the passenger side quickly, the sooner to see his face. He grinned his crooked smile at me, stopping my breath and my heart. I couldn't imagine how an angel could be any more glorious. There was nothing about him that could be improved upon. â€Å"How did you sleep?† he asked. I wondered if he had any idea how appealing his voice was. â€Å"Fine. How was your night?† â€Å"Pleasant.† His smile was amused; I felt like I was missing an inside joke. â€Å"Can I ask what you did?† I asked. â€Å"No.† He grinned. â€Å"Today is still mine.† He wanted to know about people today: more about Ren? ¦e, her hobbies, what we'd done in our free time together. And then the one grandmother I'd known, my few school friends – embarrassing me when he asked about boys I'd dated. I was relieved that I'd never really dated anyone, so that particular conversation couldn't last long. He seemed as surprised as Jessica and Angela by my lack of romantic history. â€Å"So you never met anyone you wanted?† he asked in a serious tone that made me wonder what he was thinking about. I was grudgingly honest. â€Å"Not in Phoenix.† His lips pressed together into a hard line. We were in the cafeteria at this point. The day had sped by in the blur that was rapidly becoming routine. I took advantage of his brief pause to take a bite of my bagel. â€Å"I should have let you drive yourself today,† he announced, apropos of nothing, while I chewed. â€Å"Why?† I demanded. â€Å"I'm leaving with Alice after lunch.† â€Å"Oh.† I blinked, bewildered and disappointed. â€Å"That's okay, it's not that far of a walk.† He frowned at me impatiently. â€Å"I'm not going to make you walk home. We'll go get your truck and leave it here for you.† â€Å"I don't have my key with me,† I sighed. â€Å"I really don't mind walking.† What I minded was losing my time with him. He shook his head. â€Å"Your truck will be here, and the key will be in the ignition – unless you're afraid someone might steal it.† He laughed at the thought. â€Å"All right,† I agreed, pursing my lips. I was pretty sure my key was in the pocket of a pair of jeans I wore Wednesday, under a pile of clothes in the laundry room. Even if he broke into my house, or whatever he was planning, he'd never find it. He seemed to feel the challenge in my consent. He smirked, overconfident. â€Å"So where are you going?† I asked as casually as I could manage. â€Å"Hunting,† he answered grimly. â€Å"If I'm going to be alone with you tomorrow, I'm going to take whatever precautions I can.† His face grew morose†¦ and pleading. â€Å"You can always cancel, you know.† I looked down, afraid of the persuasive power of his eyes. I refused to be convinced to fear him, no matter how real the danger might be. It doesn't matter, I repeated in my head. â€Å"No,† I whispered, glancing back at his face. â€Å"I can't.† â€Å"Perhaps you're right,† he murmured bleakly. His eyes seemed to darken in color as I watched. I changed the subject. â€Å"What time will I see you tomorrow?† I asked, already depressed by the thought of him leaving now. â€Å"That depends†¦ it's a Saturday, don't you want to sleep in?† he offered. â€Å"No,† I answered too fast. He restrained a smile. â€Å"The same time as usual, then,† he decided. â€Å"Will Charlie be there?† â€Å"No, he's fishing tomorrow.† I beamed at the memory of how conveniently things had worked out. His voice turned sharp. â€Å"And if you don't come home, what will he think?† â€Å"I have no idea,† I answered coolly. â€Å"He knows I've been meaning to do the laundry. Maybe he'll think I fell in the washer.† He scowled at me and I scowled back. His anger was much more impressive than mine. â€Å"What are you hunting tonight?† I asked when I was sure I had lost the glowering contest. â€Å"Whatever we find in the park. We aren't going far.† He seemed bemused by my casual reference to his secret realities. â€Å"Why are you going with Alice?† I wondered. â€Å"Alice is the most†¦ supportive.† He frowned as he spoke. â€Å"And the others?† I asked timidly. â€Å"What are they?† His brow puckered for a brief moment. â€Å"Incredulous, for the most part.† I peeked quickly behind me at his family. They sat staring off in different directions, exactly the same as the first time I'd seen them. Only now they were four; their beautiful, bronze-haired brother sat across from me, his golden eyes troubled. â€Å"They don't like me,† I guessed. â€Å"That's not it,† he disagreed, but his eyes were too innocent. â€Å"They don't understand why I can't leave you alone.† I grimaced. â€Å"Neither do I, for that matter.† Edward shook his head slowly, rolling his eyes toward the ceiling before he met my gaze again. â€Å"I told you – you don't see yourself clearly at all. You're not like anyone I've ever known. You fascinate me.† I glared at him, sure he was teasing now. He smiled as he deciphered my expression. â€Å"Having the advantages I do,† he murmured, touching his forehead discreetly, â€Å"I have a better than average grasp of human nature. People are predictable. But you†¦ you never do what I expect. You always take me by surprise.† I looked away, my eyes wandering back to his family, embarrassed and dissatisfied. His words made me feel like a science experiment. I wanted to laugh at myself for expecting anything else. â€Å"That part is easy enough to explain,† he continued. I felt his eyes on my face but I couldn't look at him yet, afraid he might read the chagrin in my eyes. â€Å"But there's more†¦ and it's not so easy to put into words -â€Å" I was still staring at the Cullens while he spoke. Suddenly Rosalie, his blond and breathtaking sister, turned to look at me. No, not to look – to glare, with dark, cold eyes. I wanted to look away, but her gaze held me until Edward broke off mid-sentence and made an angry noise under his breath. It was almost a hiss. Rosalie turned her head, and I was relieved to be free. I looked back at Edward – and I knew he could see the confusion and fear that widened my eyes. His face was tight as he explained. â€Å"I'm sorry about that. She's just worried. You see†¦ it's dangerous for more than just me if, after spending so much time with you so publicly†¦Ã¢â‚¬  He looked down. â€Å"If?† â€Å"If this ends†¦ badly.† He dropped his head into his hands, as he had that night in Port Angeles. His anguish was plain; I yearned to comfort him, but I was at a loss to know how. My hand reached toward him involuntarily; quickly, though, I dropped it to the table, fearing that my touch would only make things worse. I realized slowly that his words should frighten me. I waited for that fear to come, but all I could seem to feel was an ache for his pain. And frustration – frustration that Rosalie had interrupted whatever he was about to say. I didn't know how to bring it up again. He still had his head in his hands. I tried to speak in a normal voice. â€Å"And you have to leave now?† â€Å"Yes.† He raised his face; it was serious for a moment, and then his mood shifted and he smiled. â€Å"It's probably for the best. We still have fifteen minutes of that wretched movie left to endure in Biology – I don't think I could take any more.† I started. Alice – her short, inky hair in a halo of spiky disarray around her exquisite, elfin face – was suddenly standing behind his shoulder. Her slight frame was willowy, graceful even in absolute stillness. He greeted her without looking away from me. â€Å"Alice.† â€Å"Edward,† she answered, her high soprano voice almost as attractive as his. â€Å"Alice, Bella – Bella, Alice,† he introduced us, gesturing casually with his hand, a wry smile on his face. â€Å"Hello, Bella.† Her brilliant obsidian eyes were unreadable, but her smile was friendly. â€Å"It's nice to finally meet you.† Edward flashed a dark look at her. â€Å"Hi, Alice,† I murmured shyly. â€Å"Are you ready?† she asked him. His voice was aloof. â€Å"Nearly. I'll meet you at the car.† She left without another word; her walk was so fluid, so sinuous that I felt a sharp pang of jealousy. â€Å"Should I say ‘have fun,' or is that the wrong sentiment?† I asked, turning back to him. â€Å"No, ‘have fun' works as well as anything.† He grinned. â€Å"Have fun, then.† I worked to sound wholehearted. Of course I didn't fool him. â€Å"I'll try.† He still grinned. â€Å"And you try to be safe, please.† â€Å"Safe in Forks – what a challenge.† â€Å"For you it is a challenge.† His jaw hardened. â€Å"Promise.† â€Å"I promise to try to be safe,† I recited. â€Å"I'll do the laundry tonight – that ought to be fraught with peril.† â€Å"Don't fall in,† he mocked. â€Å"I'll do my best.† He stood then, and I rose, too. â€Å"I'll see you tomorrow,† I sighed. â€Å"It seems like a long time to you, doesn't it?† he mused. I nodded glumly. â€Å"I'll be there in the morning,† he promised, smiling his crooked smile. He reached across the table to touch my face, lightly brushing along my cheekbone again. Then he turned and walked away. I stared after him until he was gone. I was sorely tempted to ditch the rest of the day, at the very least Gym, but a warning instinct stopped me. I knew that if I disappeared now, Mike and others would assume I was with Edward. And Edward was worried about the time we'd spent together publicly†¦ if things went wrong. I refused to dwell on the last thought, concentrating instead on making things safer for him. I intuitively knew – and sensed he did, too – that tomorrow would be pivotal. Our relationship couldn't continue to balance, as it did, on the point of a knife. We would fall off one edge or the other, depending entirely upon his decision, or his instincts. My decision was made, made before I'd ever consciously chosen, and I was committed to seeing it through. Because there was nothing more terrifying to me, more excruciating, than the thought of turning away from him. It was an impossibility. I went to class, feeling dutiful. I couldn't honestly say what happened in Biology; my mind was too preoccupied with thoughts of tomorrow. In Gym, Mike was speaking to me again; he wished me a good time in Seattle. I carefully explained that I'd canceled my trip, worried about my truck. â€Å"Are you going to the dance with Cullen?† he asked, suddenly sulky. â€Å"No, I'm not going to the dance at all.† â€Å"What are you doing, then?† he asked, too interested. My natural urge was to tell him to butt out. Instead, I lied brightly. â€Å"Laundry, and then I have to study for the Trig test or I'm going to fail.† â€Å"Is Cullen helping you study?† â€Å"Edward,† I emphasized, â€Å"is not going to help me study. He's gone away somewhere for the weekend.† The lies came more naturally than usual, I noted with surprise. â€Å"Oh.† He perked up. â€Å"You know, you could come to the dance with our group anyway – that would be cool. We'd all dance with you,† he promised. The mental image of Jessica's face made my tone sharper than necessary. â€Å"I'm not going to the dance, Mike, okay?† â€Å"Fine.† He sulked again. â€Å"I was just offering.† When the school day had finally ended, I walked to the parking lot without enthusiasm. I did not especially want to walk home, but I couldn't see how he would have retrieved my truck. Then again, I was starting to believe that nothing was impossible for him. The latter instinct proved correct – my truck sat in the same space he'd parked his Volvo in this morning. I shook my head, incredulous, as I opened the unlocked door and saw the key in the ignition. There was a piece of white paper folded on my seat. I got in and closed the door before I unfolded it. Two words were written in his elegant script. Be safe. The sound of the truck roaring to life frightened me. I laughed at myself. When I got home, the handle of the door was locked, the dead bolt unlocked, just as I'd left it this morning. Inside, I went straight to the laundry room. It looked just the same as I'd left it, too. I dug for my jeans and, after finding them, checked the pockets. Empty. Maybe I'd hung my key up after all, I thought, shaking my head. Following the same instinct that had prompted me to lie to Mike, I called Jessica on the pretense of wishing her luck at the dance. When she offered the same wish for my day with Edward, I told her about the cancellation. She was more disappointed than really necessary for a third-party observer to be. I said goodbye quickly after that. Charlie was absentminded at dinner, worried over something at work, I guessed, or maybe a basketball game, or maybe he was just really enjoying the lasagna – it was hard to tell with Charlie. â€Å"You know, Dad†¦Ã¢â‚¬  I began, breaking into his reverie. â€Å"What's that, Bell?† â€Å"I think you're right about Seattle. I think I'll wait until Jessica or someone else can go with me.† â€Å"Oh,† he said, surprised. â€Å"Oh, okay. So, do you want me to stay home?† â€Å"No, Dad, don't change your plans. I've got a million things to do†¦ homework, laundry†¦ I need to go to the library and the grocery store. I'll be in and out all day†¦ you go and have fun.† â€Å"Are you sure?† â€Å"Absolutely, Dad. Besides, the freezer is getting dangerously low on fish – we're down to a two, maybe three years' supply.† â€Å"You're sure easy to live with, Bella.† He smiled. â€Å"I could say the same thing about you,† I said, laughing. The sound of my laughter was off, but he didn't seem to notice. I felt so guilty for deceiving him that I almost took Edward's advice and told him where I would be. Almost. After dinner, I folded clothes and moved another load through the dryer. Unfortunately it was the kind of job that only keeps hands busy. My mind definitely had too much free time, and it was getting out of control. I fluctuated between anticipation so intense that it was very nearly pain, and an insidious fear that picked at my resolve. I had to keep reminding myself that I'd made my choice, and I wasn't going back on it. I pulled his note out of my pocket much more often than necessary to absorb the two small words he'd written. He wants me to be safe, I told myself again and again. I would just hold on to the faith that, in the end, that desire would win out over the others. And what was my other choice – to cut him out of my life? Intolerable. Besides, since I'd come to Forks, it really seemed like my life was about him. But a tiny voice in the back of my mind worried, wondering if it would hurt very much†¦ if it ended badly. I was relieved when it was late enough to be acceptable for bedtime. I knew I was far too stressed to sleep, so I did something I'd never done before. I deliberately took unnecessary cold medicine – the kind that knocked me out for a good eight hours. I normally wouldn't condone that type of behavior in myself, but tomorrow would be complicated enough without me being loopy from sleep deprivation on top of everything else. While I waited for the drugs to kick in, I dried my clean hair till it was impeccably straight, and fussed over what I would wear tomorrow. With everything ready for the morning, I finally lay in my bed. I felt hyper; I couldn't stop twitching. I got up and rifled through my shoebox of CDs until I found a collection of Chopin's nocturnes. I put that on very quietly and then lay down again, concentrating on relaxing individual parts of my body. Somewhere in the middle of that exercise, the cold pills took effect, and I gladly sank into unconsciousness. I woke early, having slept soundly and dreamlessly thanks to my gratuitous drug use. Though I was well rested, I slipped right back into the same hectic frenzy from the night before. I dressed in a rush, smoothing my collar against my neck, fidgeting with the tan sweater till it hung right over my jeans. I sneaked a swift look out the window to see that Charlie was already gone. A thin, cottony layer of clouds veiled the sky. They didn't look very lasting. I ate breakfast without tasting the food, hurrying to clean up when I was done. I peeked out the window again, but nothing had changed. I had just finished brushing my teeth and was heading back downstairs when a quiet knock sent my heart thudding against my rib cage. I flew to the door; I had a little trouble with the simple dead bolt, but I yanked the door open at last, and there he was. All the agitation dissolved as soon as I looked at his face, calm taking its place. I breathed a sigh of relief – yesterday's fears seemed very foolish with him here. He wasn't smiling at first – his face was somber. But then his expression lightened as he looked me over, and he laughed. â€Å"Good morning,† he chuckled. â€Å"What's wrong?† I glanced down to make sure I hadn't forgotten anything important, like shoes, or pants. â€Å"We match.† He laughed again. I realized he had a long, light tan sweater on, with a white collar showing underneath, and blue jeans. I laughed with him, hiding a secret twinge of regret – why did he have to look like a runway model when I couldn't? I locked the door behind me while he walked to the truck. He waited by the passenger door with a martyred expression that was easy to understand. â€Å"We made a deal,† I reminded him smugly, climbing into the driver's seat, and reaching over to unlock his door. â€Å"Where to?† I asked. â€Å"Put your seat belt on – I'm nervous already.† I gave him a dirty look as I complied. â€Å"Where to?† I repeated with a sigh. â€Å"Take the one-oh-one north,† he ordered. It was surprisingly difficult to concentrate on the road while feeling his gaze on my face. I compensated by driving more carefully than usual through the still-sleeping town. â€Å"Were you planning to make it out of Forks before nightfall?† â€Å"This truck is old enough to be your car's grandfather – have some respect,† I retorted. We were soon out of the town limits, despite his negativity. Thick underbrush and green-swathed trunks replaced the lawns and houses. â€Å"Turn right on the one-ten,† he instructed just as I was about to ask. I obeyed silently. â€Å"Now we drive until the pavement ends.† I could hear a smile in his voice, but I was too afraid of driving off the road and proving him right to look over and be sure. â€Å"And what's there, at the pavement's end?† I wondered. â€Å"A trail.† â€Å"We're hiking?† Thank goodness I'd worn tennis shoes. â€Å"Is that a problem?† He sounded as if he'd expected as much. â€Å"No.† I tried to make the lie sound confident. But if he thought my truck was slow†¦ â€Å"Don't worry, it's only five miles or so, and we're in no hurry.† Five miles. I didn't answer, so that he wouldn't hear my voice crack in panic. Five miles of treacherous roots and loose stones, trying to twist my ankles or otherwise incapacitate me. This was going to be humiliating. We drove in silence for a while as I contemplated the coming horror. â€Å"What are you thinking?† he asked impatiently after a few moments. I lied again. â€Å"Just wondering where we're going.† â€Å"It's a place I like to go when the weather is nice.† We both glanced out the windows at the thinning clouds after he spoke. â€Å"Charlie said it would be warm today.† â€Å"And did you tell Charlie what you were up to?† he asked. â€Å"Nope.† â€Å"But Jessica thinks we're going to Seattle together?† He seemed cheered by the idea. â€Å"No, I told her you canceled on me – which is true.† â€Å"No one knows you're with me?† Angrily, now. â€Å"That depends†¦ I assume you told Alice?† â€Å"That's very helpful, Bella,† he snapped. I pretended I didn't hear that. â€Å"Are you so depressed by Forks that it's made you suicidal?† he demanded when I ignored him. â€Å"You said it might cause trouble for you†¦ us being together publicly,† I reminded him. â€Å"So you're worried about the trouble it might cause me- if you don't come home?† His voice was still angry, and bitingly sarcastic. I nodded, keeping my eyes on the road. He muttered something under his breath, speaking so quickly that I couldn't understand. We were silent for the rest of the drive. I could feel the waves of infuriated disapproval rolling off of him, and I could think of nothing to say. And then the road ended, constricting to a thin foot trail with a small wooden marker. I parked on the narrow shoulder and stepped out, afraid because he was angry with me and I didn't have driving as an excuse not to look at him. It was warm now, warmer than it had been in Forks since the day I'd arrived, almost muggy under the clouds. I pulled off my sweater and knotted it around my waist, glad that I'd worn the light, sleeveless shirt – especially if I had five miles of hiking ahead of me. I heard his door slam, and looked over to see that he'd removed his sweater, too. He was facing away from me, into the unbroken forest beside my truck. â€Å"This way,† he said, glancing over his shoulder at me, eyes still annoyed. He started into the dark forest. â€Å"The trail?† Panic was clear in my voice as I hurried around the truck to catch up to him. â€Å"I said there was a trail at the end of the road, not that we were taking it.† â€Å"No trail?† I asked desperately. â€Å"I won't let you get lost.† He turned then, with a mocking smile, and I stifled a gasp. His white shirt was sleeveless, and he wore it unbuttoned, so that the smooth white skin of his throat flowed uninterrupted over the marble contours of his chest, his perfect musculature no longer merely hinted at behind concealing clothes. He was too perfect, I realized with a piercing stab of despair. There was no way this godlike creature could be meant for me. He stared at me, bewildered by my tortured expression. â€Å"Do you want to go home?† he said quietly, a different pain than mine saturating his voice. â€Å"No.† I walked forward till I was close beside him, anxious not to waste one second of whatever time I might have with him. â€Å"What's wrong?† he asked, his voice gentle. â€Å"I'm not a good hiker,† I answered dully. â€Å"You'll have to be very patient.† â€Å"I can be patient – if I make a great effort.† He smiled, holding my glance, trying to lift me out of my sudden, unexplained dejection. I tried to smile back, but the smile was unconvincing. He scrutinized my face. â€Å"I'll take you home,† he promised. I couldn't tell if the promise was unconditional, or restricted to an immediate departure. I knew he thought it was fear that upset me, and I was grateful again that I was the one person whose mind he couldn't hear. â€Å"If you want me to hack five miles through the jungle before sundown, you'd better start leading the way,† I said acidly. He frowned at me, struggling to understand my tone and expression. He gave up after a moment and led the way into the forest. It wasn't as hard as I had feared. The way was mostly flat, and he held the damp ferns and webs of moss aside for me. When his straight path took us over fallen trees or boulders, he would help me, lifting me by the elbow, and then releasing me instantly when I was clear. His cold touch on my skin never failed to make my heart thud erratically. Twice, when that happened, I caught a look on his face that made me sure he could somehow hear it. I tried to keep my eyes away from his perfection as much as possible, but I slipped often. Each time, his beauty pierced me through with sadness. For the most part, we walked in silence. Occasionally he would ask a random question that he hadn't gotten to in the past two days of interrogation. He asked about my birthdays, my grade school teachers, my childhood pets – and I had to admit that after killing three fish in a row, I'd given up on the whole institution. He laughed at that, louder than I was used to – bell-like echoes bouncing back to us from the empty woods. The hike took me most of the morning, but he never showed any sign of impatience. The forest spread out around us in a boundless labyrinth of ancient trees, and I began to be nervous that we would never find our way out again. He was perfectly at ease, comfortable in the green maze, never seeming to feel any doubt about our direction. After several hours, the light that filtered through the canopy transformed, the murky olive tone shifting to a brighter jade. The day had turned sunny, just as he'd foretold. For the first time since we'd entered the woods, I felt a thrill of excitement – which quickly turned to impatience. â€Å"Are we there yet?† I teased, pretending to scowl. â€Å"Nearly.† He smiled at the change in my mood. â€Å"Do you see the brightness ahead?† I peered into the thick forest. â€Å"Um, should I?† He smirked. â€Å"Maybe it's a bit soon for your eyes.† â€Å"Time to visit the optometrist,† I muttered. His smirk grew more pronounced. But then, after another hundred yards, I could definitely see a lightening in the trees ahead, a glow that was yellow instead of green. I picked up the pace, my eagerness growing with every step. He let me lead now, following noiselessly. I reached the edge of the pool of light and stepped through the last fringe of ferns into the loveliest place I had ever seen. The meadow was small, perfectly round, and filled with wildflowers – violet, yellow, and soft white. Somewhere nearby, I could hear the bubbling music of a stream. The sun was directly overhead, filling the circle with a haze of buttery sunshine. I walked slowly, awestruck, through the soft grass, swaying flowers, and warm, gilded air. I halfway turned, wanting to share this with him, but he wasn't behind me where I thought he'd be. I spun around, searching for him with sudden alarm. Finally I spotted him, still under the dense shade of the canopy at the edge of the hollow, watching me with cautious eyes. Only then did I remember what the beauty of the meadow had driven from my mind – the enigma of Edward and the sun, which he'd promised to illustrate for me today. I took a step back toward him, my eyes alight with curiosity. His eyes were wary, reluctant. I smiled encouragingly and beckoned to him with my hand, taking another step back to him. He held up a hand in warning, and I hesitated, rocking back onto my heels. Edward seemed to take a deep breath, and then he stepped out into the bright glow of the midday sun.

Talent Managment Process Essay Example | Topics and Well Written Essays - 500 words

Talent Managment Process - Essay Example An operational talent management is among the most valuable assets an organization can possess and if the processes associated with talent management are performed in a professional manner, it has the capacity to become the driving force of the company towards economic success. Talent management entails three main aspects that include the acquisition of talent, its development and retention once it has already been acquired (Elegbe 24). Nonetheless, numerous other sub-processes are components of talent management that include the identification of talent, its sourcing and evaluation among others. In the cases where the management of talent is implemented in the proper manner, strategic effects can be seen all over the company and an appropriate talent management entails more than merely attracting, nurturing and retaining the employees who are talented. Human resource functions as a framework for a number of specialty well-designed areas in regard to expertise which require proper appreciation and discipline. In most of the cases, these well-designed areas are considered to include workforce and succession planning, the management of performances as well as compensating and giving benefits to the employees who perform exceptionally. In order to be able to manage talent in an efficient and effective manner, all these aspects have to be consolidated fully and they must work together in a smooth manner. In the initial stages, workforce and succession planning maps out the path for future talent requirements by quantity and qualifying requirements in accordance to the strategy of the company. On the hand, management is tasked with the delivery of an overview if the talent that is already in existence while talent acquisition and recruitment is supposed to make sure that the identified gaps has been closed as far as the talent map is co ncerned. Overall, the

Critically assess the view that banks in emerging markets weathered Essay

Critically assess the view that banks in emerging markets weathered the recent financial crisis (2007-09) better than banks h - Essay Example Critics would surely credit their phenomenal growth due to the global economic shift that has taken place during this period where China has become the world’s manufacturing center and back office. While these two happenings have indeed helped in the growth of Chinese banks, one should not lose sight of the equally important fact that while banks in developed western economies crumbled during the global meltdown during 2007-2009, Chinese banks weathered this economic turmoil without any apparent signs of wear and tear (The winners' dilemma, 2010). Reliance on old fashioned mores of banking Banks in India, China and Brazil still prefer to do banking in the so-called old fashioned manner of carrying out business. They depend almost entirely on deposits they can mobilize and never lend out more than they collect through deposits. Also, they never depend on economically unstable international financial instruments that promise huge possibilities of return but are forever volatile and dependent on a host of economic factors that are linked to health of diverse economies of the western hemisphere. If there is turmoil in one developed economy, its impact spread across the entire banking sector via these volatile international financial instruments (Rambo in cuffs, 2010). This conservative approach to banking is also reflected in the comparatively meager salaries and perks that chief executives of banks in emerging economies receive as remuneration. An example might put things in proper perspective. The chief executive of Chinese bank ICBC, the world’s largest bank in terms of market capitalization, received only $134,000 in 2009 which is way behind the remuneration of his peers in western banks (The bigger and bigger picture, 2010). Role of Governments of emerging countries The biggest difference between developed and emerging economies with regard to banking is the extent of involvement of government in banking activities. While governments of developed economies hardly have any say in how banks would be run, governments of emerging economies actively participate in the business of banking. This might initially seem to be an unwarranted governmental intervention in the mechanism of free market but on deeper analysis it becomes clear that governmental involvement shielded banks in emerging economies to a considerable extent from global turmoil during 2007-2009 (Mutually assured existence, 2010). In the matter of growth and expansion Chinese banks have beaten their emerging economy counterparts hands down. The profits of China Construction Bank, the second largest bank in the world, have grown to $16 billion which is decidedly higher than the profits of JPMorgan, Wells Fargo and Goldman Sachs, the three largest banks in United States of America. With such large scale expansion, the problem of bad debts has also increased more than proportionately. Chinese government has taken certain explicit steps to prevent bad debts from eating a way into the financial soundness of banks. In April 2010, Liu Mingkang, head of banking regulatory authority in China, issued clear instructions to

Martin Luther King jr Essay Example | Topics and Well Written Essays - 2000 words

Martin Luther King jr - Essay Example grew up in a society where there was a lot of segregation but he rose up against the social injustices in various ways that even saw him to be recognized as a Nobel Prize winner in the year 1964. This essay will discuss the major inspirations imparted by Rev. Dr. Martin Luther King Jr. in his career and other activities that aimed at terminating social injustices in the U.S. To start with, Martin Luther King Jr. started reformation towards social justice at early stages in his life, something not very common to many people. Martin Luther King Jr. was born in a family of religious leaders, who advocated for social justice and fairness in the society. As a result, the young Martin Luther King Jr., initially named as Michael King was exposed to social issues that affected American populations. According to the Martin Luther King Jr. Research and Education Institute, the activism of his father against racial discrimination as well as the depression period in the country made Martin Luther King Jr. to be acquainted with the social injustices and economic inequalities in the country (1). Therefore, the nature of the early life of Martin Luther King Jr. made him to develop agitation for fairness to people in the society. What inspires most in this story is that Martin Luther King Jr. did not stop at that but took an initiative against the prevailing injustices . The Martin Luther King Jr. Research and Education Institute points out that following the inspiration from his father as well as other religious leaders, Martin Luther King Jr. took an initiative of being ordained as a church leader and started his political activism by writing letters to editors of national newspapers while still at Morehouse College (1). This is quite inspiring because very few students can take such a bold step at their tender ages as in the case of Martin Luther King Jr. Of more significance, Martin Luther King Jr. was confident to criticize any issue that seemed not right in the

Assignments Assignment Example | Topics and Well Written Essays - 250 words

Assignments - Assignment Example Pellian government has the full rights to expropriate oil because they observe environmental conversation. The government does not allow spilling of toxic chemicals to the villages. They play their role as citizen’s watchdog. The appropriate level of compensation Pellian government has to offer should exceed the profit earned in that financial year. BIT rules state that, a firm should pay compensation immediately. The government has to offer AmeriGas immediately at the day of expropriation. This is in accordance with the international laws. BIT rules protect other minor oil corporations from exploitation from the major oil firms. A compensation covering profits and capital is the best model to clear expropriation. Under the bilateral treaty; Pellian government offered $65 million in compensation to AmeriGasCo. This was a reflection of the profits earned (Sands 372). The fee imposed upon chip manufacturing operation is not consistent with the treatment obligations under BIT. The fee is less than the fair market value. Bilateral treaty advocates for reasonable rate fees that could match the economy, from the date of expropriation. Firms spend money on microchips, which is against the conditions of

The effect on the 1990 Clean Air Act on the Twin Cities Research Paper

The effect on the 1990 Clean Air Act on the Twin Cities - Research Paper Example Air Quality in the Twin Cities Midway through the 20th century, the United States started growing concerned with air quality, especially in larger cities. Beginning with the Air Pollution Control Act of 1955, the government would continue to pass Acts that would help research and regulate air pollution. In 1963 the first version of the Clean Air Act was passed following the research gained by the 1955 Act. This CAA set up regulations and standards to monitor air pollution, giving the newly formed Environmental Protection Agency the power to enforce these standards. Today, our focus will be a later version of this Act. The Clean Air Act of 1990 and the subsequent tighter standards for air quality set by the EPA caused the state of Minnesota to fall out of compliance. This paper will discuss the effect of the 1990 Clean Air Act on the Twin Cities. History of the Clean Air Act Beginning first with an overview of the Clean Air Act’s history, the Clean Air Act of 1990 was a set of amendments added to the already recognized piece of legislation from 1963. The 1963 legislation created a special section of the United States Public Health Service that would focus on air pollution research, monitoring and regulation techniques. Following research done, the 1967 Air Quality Act was passed which furthered government attention to both interstate transports’ effect on air pollution and ways to monitor air pollution in an ambient or localized way. In 1970 several amendments were added to the Clean Air Act of 1963 which greatly expanded federal authority. All of this authority was actually transferred to the newly created Environmental Protection Agency, or EPA. The EPA, an agency under the jurisdiction of the U.S. Public Health Service, was backed by governmental funding and authority to control air pollution from both mobile and stationary sources, in private and public industries (Gerbec, et al., 1995). For example, after the CAA of 1970, the EPA began regulat ing industries that were shown to be the causes of most public pollution. It began requiring auto makers to create emissions traps, in the form of catalytic converters, to ensure pollutants that create smog would not be unleashed(Smith, 1993).. The EPA also targeted the oil refineries who sold gasoline, requiring them to sell purer gasoline to higher risked areas – along with banning many types of gasoline that are leaded. Finally, the manufacturing sites of coal had to alter their smokestacks and install â€Å"scrubbers† that would prevent pollutants from being released into the atmosphere (Cooper, 2000). By targeting these industries, the EPA hoped to greatly reduce the amount of air pollution near these industrial centers. However, the EPA did not stop with industrial regulation. The agency also gave responsibility to state governments to regulate and enforce pollution-reducing methods. In the 1970 Clean Air Act, the EPA was given greater authority over state govern ments to mandate four new mandatory regulation programs that were mainly focused with air pollution. These four programs included the National Ambient Air Quality Standards, or NAAQS, the State Implementation Plans, or SIPs, the New Source Performance Standards, or NSPS, and finally the National Emission Standards for Hazardous Air Pollutants, or NESHAPs. Therefore a system of localized authority was created. Each

History Research paper- Primary source analysis comprasion Paper

History - Primary source analysis comprasion - Research Paper Example the witnesses who made John Adams to be successful in deposing most of them, and eventually defending the soldiers successfully (www.gilderlehrman.org, 2012). By early 1770, Boston had about 15’000 a person with about 4000 British soldiers and the tension was rising. On the evening of March 5th, crowds pelted stones at British soldiers which resulted to the firing at the crowds by the soldiers, killing five inhabitants of the city. The historic engraving by John Revere â€Å"The Bloody Massacre in King-Street,† was produced. This was one of the war propaganda tools at the time. It is however not an accurate representation of the events that actually happened. The engraving shows the soldiers lined up shooting into the crowd and a poem Revere may have actually written. Revere is said to have based his engraving on the actual work of Henry Pelham. The following is observed from the engraving. The British soldiers have lined up with one of them giving the orders to shoot. This suggested the British soldiers were the aggressors. The crowd is seen reacting to the aggression when in fact they are the one who had started the attack. The expression of the soldiers on their faces is sharp while that of the colonists is innocent. These made the British look mean and as if they were enjoying the violence. In another feature of the engraving is that the laborers were dressed decently elevating their stature and how they were perceived by the general population. This clearly shows the biasness of the engraving by leaning on the side of the colonists themselves and portraying the British soldiers in bad light. This bias is also represented by the illustration of the sky which seems to shed light on the atrocities being committed by the soldiers. The unreliability of the engraving is also seen in the Illustration of Crispus Attucks who was an African American but is seen as otherwise not African American. Painting further depiction of the weather conditions at the time of

Compare and Contrast 2 Movies with Platos Allegory Essay Example for Free

Compare and Contrast 2 Movies with Platos Allegory Essay Humans depend on their five senses to confirm the authenticity of the reality that surrounds them, but how would they react when their comfort zone they call â€Å"the truth† is wrong? In Plato’s Allegory of the Cave, Plato answers that question with a series of symbols. The same symbolic meanings can be found in the 1999 film of The Matrix (directed by Andy and Larry Wachowski) where the protagonist Thomas A. Anderson is a man living two lives. Thomas is an average computer programmer by day but hacker Neo by night. Thomas is an obedient citizen; on the other hand, Neo has never been satisfied with the reality that has been spoon fed to him since he was born and has been searching for the truth through computers. When Neo is targeted by the police, Morpheus (a legendary computer hacker) contacts Neo and awakens him to the real world. Because of the obvious similarities, the dimensions present in The Matrix could be compared with Plato’s Allegory of the Cave. In The Matrix, Morpheus makes a perplexing point of â€Å"If real is what you feel, smell, taste and see, then ‘real’ is simply electrical signals interpreted by your brain† (The Matrix) and continues to question â€Å"what is real? † (The Matrix). This argument then leads to Morpheus revealing the real post-apocalyptic world where machines who call themselves the â€Å"Sentinels† rule over humans. Morpheus explains that the Sentinels created a reality stimulator (the â€Å"Matrix†) to control humans. The Matrix is built to feed humans a false world and is manipulated by artificial knowledge. This make-belief world befits Plato’s representation of the ignorant world â€Å"the cave†. In Plato’s Allegory of the Cave, the cave is to symbolize the warped world that the everyday people would perceive as the one and only â€Å"reality†. Not forgetting the ultimate truth, Plato symbolizes it with the â€Å"world above the cave†. In The Matrix, the dark, machine-ruled world is The Matrix[’s] rendition of the world above the cave. Wanting to share the truth, Morpheus opens the door of the ultimate truth to Neo by giving him the choice between the blue and the red pill. If Neo was to choose the blue pill, it was a choice to continue living in the Matrix’s blissful ignorant illusion whereas if he chose the red pill, he will be able to embrace the hidden truth. Morpheus’ red pill is a portrayal of â€Å"the tunnel† in Plato’s Allegory of the Cave. The red pill and â€Å"the tunnel† are to symbolize the path to more information and to become more open-minded. After choosing the red pill, this path awakens Neo to the new world and Morpheus trains and teaches Neos mind to be strong enough to comprehend and differentiate the truth from the Matrix. Neo’s training of the truth is a depiction of Socrates the freed prisoner being pulled to the light because both dimensions are to symbolize the education the one has to go through to further understand the world and its surroundings. In Plato’s allegory, Socrates journey suggests that without the assistance of education and with the little knowledge one has, one is incapable of comprehending new information which makes the â€Å"tunnel† essential for enlightenment. After learning the ultimate truth through Morpheus’ education process, Neo realizes that the spoon that fed him information his whole life was a lie and that â€Å"there is no spoon† (The Matrix). Eventually Neo reacts to the world’s reality with acceptance and he believes that he lives in â€Å"a world where anything is possible† (The Matrix). Neo acknowledges and stomachs the actuality of the Matrix; however, Cypher (another â€Å"disciple of the truth† Morpheus had trained) loathes the truth and would much rather revert back to an ignorant Matrix citizen. As a portrayal of Plato’s allegory’s â€Å"rejection of the truth†, Cypher teams up with Agent Smith (the antagonist of the film) to catch Morpheus and prevent the spread of knowledge. The reasoning behind Agent Smith rejection of the truth and role to silence Morpheus is because the Sentinels (the robots that rule earth) believe that if the humans realize the false world that surrounds them, the humans might revolt which will inevitably lead to the dethroning of the Sentinels. Agent Smith’s role is The Matrix[’s] representation of Plato’s â€Å"guards†, because â€Å"the guards† are responsible for keeping the ignorant prisoners (which, in The Matrix[’s] terms, are the humans) from learning about the real world. Agent Smith’s hatred towards the real world is evident when he says â€Å"I hate this place, this zoo, this prison, this reality†¦Ã¢â‚¬  (The Matrix). Both Agent Smith’s and Cypher’s â€Å"rejection of the truth† leads to Cypher’s betrayal to Morpheus’ trust and consequently leads to several valued â€Å"disciples of the truth† deaths. Cypher’s double-crossing unfaithfulness progresses the plot and the flow of The Matrix[’s] and Plato’s Allegory of the Cave[’s] story leads to the â€Å"execution of Socrates† (ie. Neo’s death). The â€Å"execution of Socrates† is Plato’s metaphor of the information censorship when the ultimate truth is not accepted by the general public. Although Neo is revived in The Matrix, his death is essential because it is the a representation of the general public’s rejection to the one and only hope to understanding the ultimate truth and it also shows the consequences of the general public’s lack of better judgment. Neo was not revived until Trinity and the other â€Å"disciples of the truth† portrayed their hope and acceptance for Neo. When Neo was revived, Neo was able to defeat Agent Smith (â€Å"the guard†) and is now able to spread the legitimacy of the Matrix. Even though Plato ended his allegory with the â€Å"execution of Socrates† to better convince his audience that any information censorship will lead to no progression, The Matrix revived Neo to depict what could of happened to Socrates if the truth was accepted (which eventually be the general public’s acceptance of the truth). After analyzing and comparing The Matrix and Plato’s Allegory of the Cave, one can see that the two are very similar and are trying to get the same messages across. Through character development, themes, and symbolism both allegories were able to demonstrate the path to knowledge is often concealed by the faulty ideology the complacent majority desperately cling unto. Without the willingness to evolve and buildup of what we, as humans, know to further understand the misinterpreted world (ie. The reality), no positive progression will occur.

Dead Man Walking Essay Example for Free

Dead Man Walking Essay When a criminal is constantly nagged and abused, condemned and ostracized by society, he turns into a viler and bitter individual. The inner core of every human being is essentially divine, even that of the worst villain. It just needs to be revealed to him to help him align himself with his true personality. This process is inner revelation. . It is only the blazing fire of Divine Knowledge that can illumine him from within. This instrumentality of Divine Knowledge can make him a worthy individual and citizen. This being the truth, one finds it difficult to agree with Gregory Baum that religion is often ambiguous in its effect on society. He further asserts that religion can be used to justify unjust social circumstances. Such possibility occurs when the tenets of religion are misunderstood and implemented wrongly. Misapplications will produce unfavorable results. Moreover, the interpretations of moral and ethical values need to be molded as per the demands of the time, and the prevailing social conditions. Poverty is the one big reason due to which an individual takes to the path of crime. The rich have a role to play here. â€Å"†¦the message to the rich is that they must be intelligent enough from time to time to help the poor, because this is the way by which they will become richer still. †(4) Sister Helen Prejean, author Dead Man Walking takes the right stand on social issues, presently capital punishment, and thus serves the true cause of Catholic Church. What is it to undergo the death penalty†¦. The best part of the death is the surprise element of it. But in case of legal death penalty, the suffering begins from day one the arrest of the individual, and when the realization dawns on him that he is liable for death penalty. He hopes against hopes that he will survive somehow. The suffering gradually increases, till that stunning moment when he is finally sentenced to death. Then he â€Å"would wait and weep and wear out. †(8) The condemned one begins to die at every moment thereafter. Patrick Sonnier, who had killed two teenagers, was one such individual. Now there are five parties concerned in the final scene of the drama of execution. The condemned prisoner, his family, the State, the Prison Administration and the men whose job is to execute the prisoner to snuff out his life! In 1982, Sister Helen Prejean became the spiritual advisor to Patrick Sonnier, months before his death in the electric chair of Louisianas Angola State Prison. The ‘battle’ between the spiritual principles and the ‘State Killing’ of a man with the God-given soul commenced. Christianity stands for love and pardon. The Catholic nun condemns capital punishment on moral grounds. An imperfect society doesn’t own the right to award death penalty. Many serious crimes are committed in a state of momentary anger. Has death penalty put an end to murders and rapes? The remedy to arrest the trend of heinous crimes lays elsewhere. Helen Prejean’s book is topical and it has international importance. Another startling and well-substantiated revelation in the book is poor African-Americans in the â€Å"Death Belt’ are most likely to be executed. If their crimes are against whites, the chances of death penalty are even more. Sociologists-where are you? What do you think of this serious anomaly? â€Å"Thou hast made me endless, such is thy pleasure. †(1) You have no right to extinguish the life which you have not kindled. This book saw the light of the day under strange circumstances. Prejean writes, â€Å"When Chava Colon from the Prison Coalition asks me one January day in 1982 to become a pen pal to a death-row inmate, I say, Sure. The invitation seems to fit with my work in St. Thomas, a New Orleans housing project of poor black residents. Not death row exactly, but close. Death is rampant here-from guns, disease, and addiction. Medical care scarcely exists. †(Prejean, 1994, p. 3) The third and the fourth sentences of the book in chapter 1, give firm indications about the fertile ground for the crimes. Prejean is a Catholic Nun. She is asked to be associated with an about-to-be-hanged criminal. How Divine Forces will tackle the Satan? Her first mental reaction was, â€Å"I wonder what I can say to this man. What will he have to say to me? †(Prejean 1994, p. 4)Now the question is how the Catholic Church and social reformation and rehabilitation of the poor and the downtrodden are compatible. The practical problem is, â€Å"The mandate to practice social justice is unsettling because taking on the struggles of the poor invariably means challenging the wealthy and those who serve their interests. † Comfort the afflicted and afflict the comfortable-thats what Dorothy Day, a Catholic social activist said is the heart of the Christian gospel. 1 (Prejean 1994, p. 5) Rabindranath Tagore writes, â€Å"thou keepest company with the companionless among the poorest, the lowliest, and the lost. † (2) â€Å"These are poor societies which have too little, but where is the rich society that says, â€Å"Halt! We have enough! †(5) But when religion develops an agenda to tackle the social problems, several practical situations come to the fore. Social issues are interlinked to politics and economics. Nuns are not social workers in the pure sense, they are religious preachers. They are there to tell you about your personal relationship with God, kindness to others, inner peace and the promised heaven, at the end of this life. Politics is not a respected ‘profession’ in any country of the world. Religious preachers are ill-equipped to deal with the segments of administration like, bureaucracy, police, politics and judiciary. The continuous interaction is difficult, for every church-going individual may have one problem or the other Sister Marie Augusta Neal, S. N. D. deN, set her thinking straight and changed her perception, as for remaining on the side of poor. She quoted the religious authority for her stand. She was s sociologist. She argued how fighting for the glaring inequalities in the world and the religious preaching needs to work together. Apolitical does not mean that you have to side with oppression. For every argument of Prejean, she had well-founded counter arguments, based on religious revelations of Lord Jesus. The Gospels record that Jesus preached good news to the poor, she said, and an essential part of that good news was that they were to be poor no longer. â€Å"Which meant they were not to meekly accept their poverty and suffering as Gods will, but, instead, struggle to obtain the necessities of life which were rightfully theirs. †(Prejean, 1994 p. 6. â€Å"Give me the strength never to disown the poor or bend my knees before insolent might. (3) Conclusion: Reading more religious texts is not the solution to the vexed problems of the day, including crimes, â€Å"More education can help us only if it produces more wisdom. †(6). Religious tenets are the revelations of the Perfect Masters (Divine Personalities or Realized Souls), so there is no question of ambiguities in them. Ambiguities are in our understanding. Gregory Baum is one such individual. Mind-level thinking fails to understand the revelations of the souls which have transcended the mind-barrier. In that level it is perfection all around. Initially, Prejean had problems of understanding the religious tenets. As would be seen from the passages analyzed above, she was able to cross that confusing barrier of the mind, and then her religion began to inspire her to secure social and spiritual justice and she realized that fight for social justice is the divine ordained duty! It is the highest spiritual demand! Adhering to religious principles doesn’t mean that you need to suffer in poverty, â€Å"where he pattern of living and working are not only profoundly unsatisfactory but also in a process of accelerating decay. †(7) This decay leads to serious crimes. References: Dead Man Walking: An Eyewitness Account Of The Death Penalty In The United States: by Helen Prejean (Author) Paperback: 288 pages Publisher: Vintage; 1st Vintage Books edition (May 31, 1994) ISBN-10: 0679751319 ISBN-13: 978-0679751311 Tagore, Rabindranath . Book: Gitanjali; Macmillan Co. Ltd, London-1962. 1) P. 1, (2) P. 8, (3) P. 28, (8) p. 84 Schumancher, E. F: Book: Small is Beautiful: Publisher: Radha Krishna, Daryaganj, New Delhi (India) (4) P. 19, (5) P. 21 (6) p. 73 (7) p. 159

Use of HPV Vaccines for Cervical Cancer Prevention

Use of HPV Vaccines for Cervical Cancer Prevention HPV Vaccines: Will They Prevent Cervical cancer Introduction Human papilloma viruses (HPV) belong to the papillomaviridae family, they are double stranded DNA viruses. HPV is the most common sexually transmitted infection (STI) in the world (Urman et al. 2008). HPV is strongly associated with cervical cancer; more than 99% what are the other causes/factors please of cervical cancer cases are positive for HPV DNA and indeed, cervical cancer is the second most common malignancy in the world (Wang et al. 2007). In developed countries the incidence of cervical cancer has been reduced significantly by the introduction of a cervical screening programme. In developing countries where 83% of mortalities due to cervical cancer occur, there are no such programmes (Parkin et al. 2006). Can the introduction of a vaccine against HPV further reduce globally the incidence of cervical cancer? Many diseases caused by viruses are controlled in the developed world by ongoing successful vaccination programmes; Polio, Measles, Mumps and Rubella are a few examples. Smallpox caused by Variola virus was eradicated in 1979 through a successful worldwide vaccination programme. The factors that affect the Polio and MMR vaccine programmes success and those that affected the successful smallpox programme may also be contributory to the success of the HPV vaccination program. Vaccination of HPV is complex and multi factorial. This investigation studies a number of factors including: Vaccine efficacy Vaccine Cost/affordability/practicality of administration Production and Distribution Government backing and financial commitment Other support organisations such as the WHO, UNICEF, Gates Foundation, Social factors Media effects Public awareness Safety, and perceived fears Currently two prophylactic vaccines against HPV types 16 and 18, the most prevalent causes of HPV have been approved by the food and drug administration (FDA). Many developed countries have already introduced vaccination programmes using one of these vaccines. Can the vaccines and programme prevent cervical cancer? In order to effectively understand the implication of such a vaccination programme we must first fully examine the causative agent (HPV) and the consequential potential diseases including the biology, history and prevalence. Human Papillomavirus Approximately 200 types of HPV are identified of which around 40 infect the genital tract (McCance 2004). The majority of HPV types cause no symptoms, some types can cause warts and a minority may lead to cancer. Genital HPVs are transmitted via sexual contact, mainly intercourse, with an infected individual, and the risk of developing an HPV infection generally increases with the number of sexual partners, the sexual history of that partner or the introduction of a new sexual partner. Studies have shown that at least one type of HPV infection occurs soon after sexual debut, with around 30% of women infected with at least one high risk type within two years (Winer et al 2003; Winer et al 2008). HPVs are classified as either high risk or low risk, on the basis of association with cervical cancer. There are 15 types classified as high risk and three as probable high risk. High risk types include 16,18,31,33,35,39,,45,51,52,56,58,59,68,73,probable high risk types include 26,53,66 Low risk types include 6,11,40,42,43,54,61,70,72,81 and CP6108. More than 99% of cervical cancers are associated with HPV, of these 70% are associated with HPV type 16 and 18, with HPV 16 causing 50% and HPV 18 causing more than 15% in Europe (Smith et al..2007). HPV 16 is thus the single, most common high risk HPV. Interestingly HPV types 16 and 18 also cause 80% of anal cancer and 30% of vaginal and why the difference in % oper area research needed here.vulvar cancer and are associated with cancers of the, oropharynx and some rare cancers of the head and neck. (add reference form cervical cancer burden worldwide paper) The majority of HPV infections are asymptomatic, self limiting, and transient, with 70% of new HPV high risk type infections cleared within one year (with the median duration of an infection at 8 months) and 90% within two years (Ho et al 1998). The transient infection usually causes no clinical problems. A small proportion of high risk type infections persist due to host immune evasion, an evasion that results not only from restriction of HPVs to sites that are relatively inaccessible to host defences but also due to several mechanisms of preventing immune response what are these mechanisms please (a sk Dick if this is what he means . This persistence is the most important factor in the development of pre cancerous and cancerous lesions. The time span between infection by HPV and the development of pre cancerous lesions or cervical carcinoma varies from one to ten years (Moscicki et al 2006) and up to 20 years from other sources. HPV show little evidence of dramatic adaptability with phylogenic studies suggesting that the biology of HPVs has remained the same for over 200,000 years (Halpren et al 2000). While HPVs show historically the influence of point mutations, inserts, deletions and duplications, the predominant pattern of mutation within a given type is point mutation, with large scale rearrangements within the most conserved genes of HPVs such as L1 being rare (Myers et al 1996). Intra patient variation within HPV types is uncommon due to their low mutation rate. This low mutation rate is directly linked to the HPV replication strategy that requires host cell machinery, which has stringent proof reading mechanisms that avoid the incorporation of errors, conferring slow mutagenesis. All HPVs exhibit extreme specificity for infection of epithelial cells and do not infect or express their gene products in the underlying dermis. Although the mechanism of infection is not fully understood, the HPV epitheliotrophy resides for the most part in the interaction of specific transcription factors with the viral regulatory region known as the long control region (LCR). Infection with HPV can result in hyperproliferation of the host cell, and with certain high risk HPV types it may lead to transformation and immortalization. This is because high risk HPVs express two or more protein products (E6, E7 and E5) that transiently disrupt the cell cycle and stimulate cell division, knocking out at the same time the cellular mechanisms for growth inhibition. For a productive infection, HPVs require terminally differentiated cells. This HPV biology feature has impeded studies on the full reproduction life cycle because of the lack of highly efficient models of epithelial terminal di fferentiation in vitro. Most of the different stages in the HPV life cycle have been established using genetic engineering and molecular biology strategies. The dsDNA of HPV exists in a non enveloped icosahedral shaped virion 52-55 nm in diameter. The dsDNA genome is circularised and around 8000base pairs in length (Fig1). The genome encodes eight proteins, six early E1, E2, E4, E5, E6, E7, and two late structural proteins L1 and L2 and the previously mentioned noncoding LCR. Fig 1 HPV type 16 Genome structure, gene and functional domain location http://www.dnachip-link.com/Eng/library/HPV.aspusg 15/11/20009 Fig 1 shows the dsDNA genome of HPV type 16, and the location of the early and late genes along with the LCR that contains the origin of replication. An initial infection requires the access of infectious particles to the basal layer of the epithelium. Some HPVs require a break in the stratified epithelium to achieve this. Such breaks are not necessarily obvious and may occur under conditions where the skin is exposed to water or abraded, or subjected to an environment where micro traumas may occur such as possibly in aswiming pool or ect (must put an example)(in fig 2 shows as a cut). Following infection and uncoating it is thought that the virus maintains its genome as an episome in low copy numbers within basal cells of the epithelium. Although the pattern of gene expression in these cells is not well understood, it is generally thought that viral proteins E1 and E2 are expressed to maintain the viral DNA episome (Wilson et al.2002) and possibly to facilitate the segregation of genomes during cell division (You et all.2004). It is not known whether viral transformation proteins E6 and E7 are also expressed in the basal layer, but it does appear that initial infection is followed by a proliferative phase that results in the increase in the number of basal cells harbouring viral episomes. In normal uninfected epithelium, basal cells leave the cell cycle soon after migration into the superbasal cell layers where they undergo a process of terminal differentiation. During infection E6 and E7 are expressed in these cells stopping normal differentiation (Sherman et all.1997). E6 and E7 are believed to work together to achieve this and in lesions caused by high risk HPV types. During a natural infection the ability of E7 to stimulate S-phase progression is limited to a subset of differentiated cells with low levels of p21/p27, or which express high enough levels of E7 to overcome the block in S-phase entry. The viral E6 protein is thought to prevent apoptosis in response to unscheduled S-phase entry brought on by E7. The association of E6 with p53 and the inactivation of p53 mediated growth suppression and apoptosis is well documented, E6 may also associate with other pro-apoptotic proteins including bak (Thomas and Banks,1998) and bax (Li and Dou,2000). E6 is thus considered a predisposing factor in the development of HPV associated cancers, allowing the accumulation of chance errors in host DNA to go unchecked. Furthermore the E6 protein of high risk HPVs can stimulate cell proliferation independently of E7 via a c-terminal PDZ ligand binding domain. E6 PDZ is enough to mediate superbasal cell proliferation and may contribute to the formation of metastatic tumours by disrupting normal cell adhesion (Nguyen et al.2003) Amplification of the viral genome and the ability to package these genomes into infectious particles is essential for the production of infectious virions. For most HPV types this occurs in the mid or upper epithelial layers following an increase in activity of the late promoter. The late promoter gene is located within the E7 open reading frame, and the upregulation of the late promoter is thought to lead to increased expression of proteins involved in viral DNA replication, without directly affecting the expression of E6 or E7 necessary for S-phase entry. The amplification of the viral genome begins in a subset of cells in the proliferative compartment and requires the expression of all viral early gene products, these include E4 and E5 whose role in replication is not yet clearly understood. Binding of E2 to the HPV upstream regulator region is essential for viral DNA replication that is dependent on the differentiated state of epithelial cells. E2 recruits the E1 DNA helicase to the viral origin of replication. Throughout the virus life cycle, the relative levels of viral proteins are controlled by promoter usage and by differential splice site selection, with an increase in E1 and E2 allowing an increase in viral copy numbers in the upper epithelial layers. Current models suggest that a small increase in promoter activation during differentiation may lead to an increase in the level of E1 and E2 and a subsequent increase in genome copy number. The newly replicated genome could then serve as a further template for expression of E1 and E2, facilitating the amplification of viral genome and in turn further expression of E1 and E2 replication proteins. Viral DNA remains latent (not integrated) in basal cells of benign lesions. Replication occurs in the differentiating cells where capsid proteins and viral particles are found. Viral DNA is integrated in cancer cells, which contain no replicating virus. Once viral genome replication is completed, the expression of two virally encoded structural proteins, expressed in the upper layers of infected epithelia may occur. L1 the major capsid protein is expressed after L2 in a sub set of cells that express E4 (fig 2), this allows the assembly of infectious particles in the upper layers of the epithelium (Florin et al.,2002). A successful infection requires the virus to escape from the infected skin cell and survive extracellularly prior to re-infection. HPVs are non-lytic and are as such not released until the infected cells reach the epithelial surface. The intracellular retention of HPV antigen until the cell reaches the uppermost epithelial layers may contribute the compromised immune detection, especially as the virus has molecular mechanisms that limit the presentation of viral epitopes to the immune system in the lower epithelial layers (Ashrafi et al 2002). What are these mechanisms Figure 2 Papillomavirus type 16 Life Cycle and gene expression location within epithelium Taken from, The papillomavirus life cycle by John Doorbar published in the journal of clinical virology 32S (2005) S7-S15 Figure 2 diagrammatic representation of the skin with HPV type 16 gene expression incorporated, colour of arrows are representative of genes expressed within epithelial cells. The frequent detection of high risk HPV DNA in cervical lesions in the absence of any obvious disease, may be explained by the presence of the virus in a latent state, with only very few cells able to support the productive virus life cycle during epithelial cell differentiation. Following immune regression, HPV DNA is thought to remain in the basal epithelial cells waiting to be reactivated once levels of immune surveillance decline there are conflicting opinions (Zhang et al.1999). If regression is not achieved lesions may persist and in some instances progress to cancer. The number of lesion that progress to cancer is very low when compared to the prevalence of high risk HPV infection in the general public. The Progression of productive lesion to high grade lesions may result from the deregulation ( what happen to allow thes proteins to be deregulated intergrattion loss of E2 adn p53 association, be specific add biochemistry here please. in the expression of transforming proteins E6 and E7. The inability of a cell to support the whole virus life cycle is often associated with the development of cancerous lesions. The transformation zone (Fig 3) is particularly susceptible to cervical cancer; it appears that high risk types of HPV such as type 16 cannot complete their life cycle at this site Progression from CIN3 to cancer usually occurs in lesions that contain integrated copies of the viral genome in which E7 expression is elevated. Suggesting that retention of E6 and E7genes and the loss of E2 and E4 genes (that exert negative effect on cell growth) usually accompanies the development of invasive cancer. (reference) Remember for CIN refer to in that section or here but Cin must be corrulated with what causes the cancer and with whats happening with the virus that causes the change in CIN or the causes in CIN to occur. Cervical cancerisa considerable contributor to morbidity and mortality. Being the second most common cancer worldwide and the twelfth most common cancer in women in the UK. Cervical cancer in 2002 was the cause of 274,000 deaths worldwide (the most current data available)REF THIS FIGURE and continues to causes more than 1000 deaths in the UK each year. There are two main types of cervical cancer squamous cell cancer (the most common) and adenocarcinoma, although they are often mixed. They are named after the types of cell that become cancerous through neoplasia. Squamous cells are flat cells covering the cervix; adenomatous cells are found in the passageway from the cervix to the womb. Other rarer cancers of the cervix include small cell cancer. Deaths from cervical cancer in the UK have fallen over the last 20 years mainly because of the NHS cervical screening programme that reduced the mortality rates by 62% between 1987-2006. Screening may detect changes in the cells of the cervix at a pre-cancerous stage. Fig 3 TITTLE Showing location of transformation zone. Cell samples are examined for abnormalities, these abnormality are described in a standard format covering cytology and/or histology. What are these standard format CIN 1 CIN2 CIN3 LISL LGSIL HSIL HGSIL USE FIG 4 and explain whats happening with the proteins expressed and genome intergration where CIN number progression is concerned please. MUST DO From Lowy Schiller, J Clin Invest, 116:1167-73, 2006 Low grade squamous intraepithelial lesion (LSIL or LGSIL) indicates possiblecone biopsy, or laser ablation. High grade squamous intraepithelial lesion (HSIL or HGSIL) indicates moderate or severeCIN 2 or CIN3 (fig 3). While cervical screening has reduced the mortality significantly in the developed world cervical cancer is still a significant burden worldwide. Fig 4 Taken from, The popillomavirus life cycle by John Doorbar published in the journal of clinical virology 32S (2005) S7-S15 Fig. 5. CIN 1 resembles productive infections caused by other HPV types and as such is the most benign form of cervical intraepithelial neoplasia , it is confined to the basal 1/3 of the epithelium, CIN 2 Moderate dysplasia confined to the basal 2/3 of the epithelium,CIN3 Sever dysplasia that spans more than 2/3 of the epithelium, and may involve the full thickness. INCIDENCE An estimated 493,000 new cases and 274,000 deaths in 2002 were caused by cervical cancer. The vast majority, some 83% of these cases, occur in developing countries, where cervical cancer amounts to 15% of female cancers with a risk before age 65 of 1.5%. In developed countries cervical cancer accounts for only 3.6%, with a risk of 0.8% before age 65. REF The highest incidence rates are observed in Sub-Saharan Africa, Melanesia, Latin America and the Caribbean, South-Central Asia, and South East Asia (fig 6) Fig 6 Worldwide Burden of HPV related Cervical Cancer Figures from 2002. Parkin MD et al 2006 The burden of HPV-related cervical cancers The vast majority of cervical cancers are squamous cell carcinoma adenocarcinomas being less common (fig 6). Generally the proportion of adenocarcinoma cases is higher in areas with low incidence of cervical cancer, accounting for up to 25% of cases in western countries (fig 6). This higher incidence of adenocarcinoma may be partially explained by cytological screening, which historically, had little effect in reducing the risk of adenocarcinoma of the cervix, because these cancers, and their precursors, occur within the cervical canal, and were not readily sampled by scraping of the epithelium of the ectocervix. Fig 5 Fig 5 showing the higher % of adenocarcinoma in counties that have screening programmes such as the UK and Denmark What is this showing? Make it clear.do you really need it. MORTALITY RATES Mortality rates are substantially lower than incidence rates. Worldwide 55% (could you double chek that this is the case please misses) of all those that develop the disease die, the figures vary significantly from the developed to the developing world. Low risk regions of the west such as Europe have a death rate of 37% while in developing countries where many cases present at relatively advanced stages, death rates are significantly higher increasing to 70%. Cervical screening programmes in the developed world identify pre-cancerous lesions at a stage where they can be easily treated accounting for the difference in mortality rates. TITTLE IF and figure number staying and refer to in text As cervical cancer affects a relatively high number of young women, it is a significant cause of years of life lost (YLL) in the developing world. Yang et al 2004 found that cervical cancer was responsible for the 2.7 million (age weighted) years of lives lost world wide in 2000, and that it is the single biggest cause of years of life lost from cancer in the developing world. In Latin America, Eastern Europe and the Caribbean, cervical cancer makes a greater contribution to YLL than disease such as Tuberculosis or AIDS. HPV is also associated with many other forms of cancer that could possibly be prevented with use of HPV vaccines; cancers of the penis, anus, vulva, vagina, oropharynx and some rare cancers of the head and neck are included. However cancer of the cervix is by far the most significant, in terms of incidence and mortality (table 1). Cancer of the vulva and vagina have a significantly lower incidence rate compared to cervical cancer, however since 80% of the incidence are caused by HPV types 16 or 18 women vaccinated against these types would also be protected against these forms of cancer. Incidence of squamous cell carcinoma of the anus are twice as common in females as males with HPV types 16 and 18 accounting for 83% of all cases. There is a particularly high incidence of anal cancer among homosexual males, shown by the high incidence rate in populations such as Sanfransisco, where gay incidence are higher than average (fig 7). Globally cancer of the penis is relatively rare accounting for 0.5% of cancers in men (table 1). HPV DNA is detectable in 40-50% of all penile cancers and serological studies have confirmed the role of HPV 16 and 18 (IARC 2005). Cancers of the mouth and oropharynx caused by HPV are very low at 0.06% of all cancers with 0.05% being caused by HPV types 16/18. Due to the small size of most studies and the absence of comparable measurements of prevalence of infection in normal subjects conducted for cancers of the vulva, vagina, penis and anus true prevalence is difficult to quantify. The figures shown in table 1, imply that we are dealing with a virus that discriminates primarily through disease aginst women, in particular young women. Gay men, however are also clearly an at risk group. Currently only young women are vaccinated aginst HPV types 16 and 18, however the JCVI (joint committee on vaccination and immunisation) have noted that the vaccines has not been conclusively trialled on men, and that there is insufficient evidence that the vaccine available would protect against anal, penile or head and neck cancer. However when more data becomes available they will consider vaccinating, high risk groups such as men who have sex with men. Add what this implies for prophylactic use of vaccine with other cancers cause by HPV And what you think about the ue of vaccine on highrisk men and its effectivity against other cancers caused by HPV types 16 and 18. Fig 7 TITTLE add Figure 6 showing that cancer of the anus are more prevalent in women than men with the major noted exception being San Francisco, where the increased incidence can be explained by a large number of homosexual men. Table 3 VACCINATION An effective vaccine should stimulate a suitable range of immune responses, mimic or improve on the protection gained from a wild type infection with little side effects. Critically the vaccine should be inexpensive, easily administered, transported and stored to further reduce cost and maximise convenience, this is especially relevant in the case of HPV vaccine as those that are not protected by the screening programmes of the developed world would benefit the most, ease of administration and storage is paramount in the developing world as stability and healthcare is more sporadic, and people are often more remote. There are many different kinds of vaccines available, and different vaccines have a variety qualities and limitations. Live attenuated vaccines contain a version of the pathogenic microbe that is avirulent, they often elicit an excellent cellular and antibody response with good longevity that can be lifelong with few doses. However there is always the possibility that the vaccine may revert to its virulent form, causing disease. For this reason a live attenuated vaccine is not appropriate for use against oncogenic HPV types. Recombinant vaccines can include one or more proteins that may illicit an immune response. A process has been developed to allow the removal of the genome from an attenuated or avirulent viral vector allowing the insertion of selected genetic material or proteins from another virus. The carrier viruses then ferry that viral DNA into host cells where the genes are expressed. Recombinant vaccines closely mimic a natural infection and therefore illicit a strong immune system. Inactivated vaccines are produced by killing the disease causing microbe by chemical (formaldehyde eg just double check), heat or radioactive means. These vaccines are more stable than live vaccines, and as there is no risk of reversion to virulence. They are also safer than live vaccines. Most inactivated vaccines stimulate a weaker immune response than live vaccines and several doses or boosters may be required to maintain immunity. DNA vaccines dispense with both the whole organism and its parts. They only include the essential part of the microbes genetic material. In particular, DNA vaccines use the genes that code for immunogens. Researchers have found that when the genes for a microbes antigens are introduced into the body, some cells will take up that DNA. The DNA then instructs those cells to make the antigen molecules. The cells secrete the antigens and display them on their surfaces. In other words, the bodys own cells become vaccine-making factories, creating the antigens necessary to stimulate the immune system. A DNA vaccine against a microbe would evoke a strong antibody response to the free antigen secreted by cells, and also stimulate a strong cellular response against the microbial antigens displayed on cell surfaces. The DNA vaccine is unable to cause disease Use of HPV Vaccines for Cervical Cancer Prevention Use of HPV Vaccines for Cervical Cancer Prevention HPV Vaccines: Will They Prevent Cervical cancer Introduction Human papilloma viruses (HPV) belong to the papillomaviridae family, they are double stranded DNA viruses. HPV is the most common sexually transmitted infection (STI) in the world (Urman et al. 2008). HPV is strongly associated with cervical cancer; more than 99% what are the other causes/factors please of cervical cancer cases are positive for HPV DNA and indeed, cervical cancer is the second most common malignancy in the world (Wang et al. 2007). In developed countries the incidence of cervical cancer has been reduced significantly by the introduction of a cervical screening programme. In developing countries where 83% of mortalities due to cervical cancer occur, there are no such programmes (Parkin et al. 2006). Can the introduction of a vaccine against HPV further reduce globally the incidence of cervical cancer? Many diseases caused by viruses are controlled in the developed world by ongoing successful vaccination programmes; Polio, Measles, Mumps and Rubella are a few examples. Smallpox caused by Variola virus was eradicated in 1979 through a successful worldwide vaccination programme. The factors that affect the Polio and MMR vaccine programmes success and those that affected the successful smallpox programme may also be contributory to the success of the HPV vaccination program. Vaccination of HPV is complex and multi factorial. This investigation studies a number of factors including: Vaccine efficacy Vaccine Cost/affordability/practicality of administration Production and Distribution Government backing and financial commitment Other support organisations such as the WHO, UNICEF, Gates Foundation, Social factors Media effects Public awareness Safety, and perceived fears Currently two prophylactic vaccines against HPV types 16 and 18, the most prevalent causes of HPV have been approved by the food and drug administration (FDA). Many developed countries have already introduced vaccination programmes using one of these vaccines. Can the vaccines and programme prevent cervical cancer? In order to effectively understand the implication of such a vaccination programme we must first fully examine the causative agent (HPV) and the consequential potential diseases including the biology, history and prevalence. Human Papillomavirus Approximately 200 types of HPV are identified of which around 40 infect the genital tract (McCance 2004). The majority of HPV types cause no symptoms, some types can cause warts and a minority may lead to cancer. Genital HPVs are transmitted via sexual contact, mainly intercourse, with an infected individual, and the risk of developing an HPV infection generally increases with the number of sexual partners, the sexual history of that partner or the introduction of a new sexual partner. Studies have shown that at least one type of HPV infection occurs soon after sexual debut, with around 30% of women infected with at least one high risk type within two years (Winer et al 2003; Winer et al 2008). HPVs are classified as either high risk or low risk, on the basis of association with cervical cancer. There are 15 types classified as high risk and three as probable high risk. High risk types include 16,18,31,33,35,39,,45,51,52,56,58,59,68,73,probable high risk types include 26,53,66 Low risk types include 6,11,40,42,43,54,61,70,72,81 and CP6108. More than 99% of cervical cancers are associated with HPV, of these 70% are associated with HPV type 16 and 18, with HPV 16 causing 50% and HPV 18 causing more than 15% in Europe (Smith et al..2007). HPV 16 is thus the single, most common high risk HPV. Interestingly HPV types 16 and 18 also cause 80% of anal cancer and 30% of vaginal and why the difference in % oper area research needed here.vulvar cancer and are associated with cancers of the, oropharynx and some rare cancers of the head and neck. (add reference form cervical cancer burden worldwide paper) The majority of HPV infections are asymptomatic, self limiting, and transient, with 70% of new HPV high risk type infections cleared within one year (with the median duration of an infection at 8 months) and 90% within two years (Ho et al 1998). The transient infection usually causes no clinical problems. A small proportion of high risk type infections persist due to host immune evasion, an evasion that results not only from restriction of HPVs to sites that are relatively inaccessible to host defences but also due to several mechanisms of preventing immune response what are these mechanisms please (a sk Dick if this is what he means . This persistence is the most important factor in the development of pre cancerous and cancerous lesions. The time span between infection by HPV and the development of pre cancerous lesions or cervical carcinoma varies from one to ten years (Moscicki et al 2006) and up to 20 years from other sources. HPV show little evidence of dramatic adaptability with phylogenic studies suggesting that the biology of HPVs has remained the same for over 200,000 years (Halpren et al 2000). While HPVs show historically the influence of point mutations, inserts, deletions and duplications, the predominant pattern of mutation within a given type is point mutation, with large scale rearrangements within the most conserved genes of HPVs such as L1 being rare (Myers et al 1996). Intra patient variation within HPV types is uncommon due to their low mutation rate. This low mutation rate is directly linked to the HPV replication strategy that requires host cell machinery, which has stringent proof reading mechanisms that avoid the incorporation of errors, conferring slow mutagenesis. All HPVs exhibit extreme specificity for infection of epithelial cells and do not infect or express their gene products in the underlying dermis. Although the mechanism of infection is not fully understood, the HPV epitheliotrophy resides for the most part in the interaction of specific transcription factors with the viral regulatory region known as the long control region (LCR). Infection with HPV can result in hyperproliferation of the host cell, and with certain high risk HPV types it may lead to transformation and immortalization. This is because high risk HPVs express two or more protein products (E6, E7 and E5) that transiently disrupt the cell cycle and stimulate cell division, knocking out at the same time the cellular mechanisms for growth inhibition. For a productive infection, HPVs require terminally differentiated cells. This HPV biology feature has impeded studies on the full reproduction life cycle because of the lack of highly efficient models of epithelial terminal di fferentiation in vitro. Most of the different stages in the HPV life cycle have been established using genetic engineering and molecular biology strategies. The dsDNA of HPV exists in a non enveloped icosahedral shaped virion 52-55 nm in diameter. The dsDNA genome is circularised and around 8000base pairs in length (Fig1). The genome encodes eight proteins, six early E1, E2, E4, E5, E6, E7, and two late structural proteins L1 and L2 and the previously mentioned noncoding LCR. Fig 1 HPV type 16 Genome structure, gene and functional domain location http://www.dnachip-link.com/Eng/library/HPV.aspusg 15/11/20009 Fig 1 shows the dsDNA genome of HPV type 16, and the location of the early and late genes along with the LCR that contains the origin of replication. An initial infection requires the access of infectious particles to the basal layer of the epithelium. Some HPVs require a break in the stratified epithelium to achieve this. Such breaks are not necessarily obvious and may occur under conditions where the skin is exposed to water or abraded, or subjected to an environment where micro traumas may occur such as possibly in aswiming pool or ect (must put an example)(in fig 2 shows as a cut). Following infection and uncoating it is thought that the virus maintains its genome as an episome in low copy numbers within basal cells of the epithelium. Although the pattern of gene expression in these cells is not well understood, it is generally thought that viral proteins E1 and E2 are expressed to maintain the viral DNA episome (Wilson et al.2002) and possibly to facilitate the segregation of genomes during cell division (You et all.2004). It is not known whether viral transformation proteins E6 and E7 are also expressed in the basal layer, but it does appear that initial infection is followed by a proliferative phase that results in the increase in the number of basal cells harbouring viral episomes. In normal uninfected epithelium, basal cells leave the cell cycle soon after migration into the superbasal cell layers where they undergo a process of terminal differentiation. During infection E6 and E7 are expressed in these cells stopping normal differentiation (Sherman et all.1997). E6 and E7 are believed to work together to achieve this and in lesions caused by high risk HPV types. During a natural infection the ability of E7 to stimulate S-phase progression is limited to a subset of differentiated cells with low levels of p21/p27, or which express high enough levels of E7 to overcome the block in S-phase entry. The viral E6 protein is thought to prevent apoptosis in response to unscheduled S-phase entry brought on by E7. The association of E6 with p53 and the inactivation of p53 mediated growth suppression and apoptosis is well documented, E6 may also associate with other pro-apoptotic proteins including bak (Thomas and Banks,1998) and bax (Li and Dou,2000). E6 is thus considered a predisposing factor in the development of HPV associated cancers, allowing the accumulation of chance errors in host DNA to go unchecked. Furthermore the E6 protein of high risk HPVs can stimulate cell proliferation independently of E7 via a c-terminal PDZ ligand binding domain. E6 PDZ is enough to mediate superbasal cell proliferation and may contribute to the formation of metastatic tumours by disrupting normal cell adhesion (Nguyen et al.2003) Amplification of the viral genome and the ability to package these genomes into infectious particles is essential for the production of infectious virions. For most HPV types this occurs in the mid or upper epithelial layers following an increase in activity of the late promoter. The late promoter gene is located within the E7 open reading frame, and the upregulation of the late promoter is thought to lead to increased expression of proteins involved in viral DNA replication, without directly affecting the expression of E6 or E7 necessary for S-phase entry. The amplification of the viral genome begins in a subset of cells in the proliferative compartment and requires the expression of all viral early gene products, these include E4 and E5 whose role in replication is not yet clearly understood. Binding of E2 to the HPV upstream regulator region is essential for viral DNA replication that is dependent on the differentiated state of epithelial cells. E2 recruits the E1 DNA helicase to the viral origin of replication. Throughout the virus life cycle, the relative levels of viral proteins are controlled by promoter usage and by differential splice site selection, with an increase in E1 and E2 allowing an increase in viral copy numbers in the upper epithelial layers. Current models suggest that a small increase in promoter activation during differentiation may lead to an increase in the level of E1 and E2 and a subsequent increase in genome copy number. The newly replicated genome could then serve as a further template for expression of E1 and E2, facilitating the amplification of viral genome and in turn further expression of E1 and E2 replication proteins. Viral DNA remains latent (not integrated) in basal cells of benign lesions. Replication occurs in the differentiating cells where capsid proteins and viral particles are found. Viral DNA is integrated in cancer cells, which contain no replicating virus. Once viral genome replication is completed, the expression of two virally encoded structural proteins, expressed in the upper layers of infected epithelia may occur. L1 the major capsid protein is expressed after L2 in a sub set of cells that express E4 (fig 2), this allows the assembly of infectious particles in the upper layers of the epithelium (Florin et al.,2002). A successful infection requires the virus to escape from the infected skin cell and survive extracellularly prior to re-infection. HPVs are non-lytic and are as such not released until the infected cells reach the epithelial surface. The intracellular retention of HPV antigen until the cell reaches the uppermost epithelial layers may contribute the compromised immune detection, especially as the virus has molecular mechanisms that limit the presentation of viral epitopes to the immune system in the lower epithelial layers (Ashrafi et al 2002). What are these mechanisms Figure 2 Papillomavirus type 16 Life Cycle and gene expression location within epithelium Taken from, The papillomavirus life cycle by John Doorbar published in the journal of clinical virology 32S (2005) S7-S15 Figure 2 diagrammatic representation of the skin with HPV type 16 gene expression incorporated, colour of arrows are representative of genes expressed within epithelial cells. The frequent detection of high risk HPV DNA in cervical lesions in the absence of any obvious disease, may be explained by the presence of the virus in a latent state, with only very few cells able to support the productive virus life cycle during epithelial cell differentiation. Following immune regression, HPV DNA is thought to remain in the basal epithelial cells waiting to be reactivated once levels of immune surveillance decline there are conflicting opinions (Zhang et al.1999). If regression is not achieved lesions may persist and in some instances progress to cancer. The number of lesion that progress to cancer is very low when compared to the prevalence of high risk HPV infection in the general public. The Progression of productive lesion to high grade lesions may result from the deregulation ( what happen to allow thes proteins to be deregulated intergrattion loss of E2 adn p53 association, be specific add biochemistry here please. in the expression of transforming proteins E6 and E7. The inability of a cell to support the whole virus life cycle is often associated with the development of cancerous lesions. The transformation zone (Fig 3) is particularly susceptible to cervical cancer; it appears that high risk types of HPV such as type 16 cannot complete their life cycle at this site Progression from CIN3 to cancer usually occurs in lesions that contain integrated copies of the viral genome in which E7 expression is elevated. Suggesting that retention of E6 and E7genes and the loss of E2 and E4 genes (that exert negative effect on cell growth) usually accompanies the development of invasive cancer. (reference) Remember for CIN refer to in that section or here but Cin must be corrulated with what causes the cancer and with whats happening with the virus that causes the change in CIN or the causes in CIN to occur. Cervical cancerisa considerable contributor to morbidity and mortality. Being the second most common cancer worldwide and the twelfth most common cancer in women in the UK. Cervical cancer in 2002 was the cause of 274,000 deaths worldwide (the most current data available)REF THIS FIGURE and continues to causes more than 1000 deaths in the UK each year. There are two main types of cervical cancer squamous cell cancer (the most common) and adenocarcinoma, although they are often mixed. They are named after the types of cell that become cancerous through neoplasia. Squamous cells are flat cells covering the cervix; adenomatous cells are found in the passageway from the cervix to the womb. Other rarer cancers of the cervix include small cell cancer. Deaths from cervical cancer in the UK have fallen over the last 20 years mainly because of the NHS cervical screening programme that reduced the mortality rates by 62% between 1987-2006. Screening may detect changes in the cells of the cervix at a pre-cancerous stage. Fig 3 TITTLE Showing location of transformation zone. Cell samples are examined for abnormalities, these abnormality are described in a standard format covering cytology and/or histology. What are these standard format CIN 1 CIN2 CIN3 LISL LGSIL HSIL HGSIL USE FIG 4 and explain whats happening with the proteins expressed and genome intergration where CIN number progression is concerned please. MUST DO From Lowy Schiller, J Clin Invest, 116:1167-73, 2006 Low grade squamous intraepithelial lesion (LSIL or LGSIL) indicates possiblecone biopsy, or laser ablation. High grade squamous intraepithelial lesion (HSIL or HGSIL) indicates moderate or severeCIN 2 or CIN3 (fig 3). While cervical screening has reduced the mortality significantly in the developed world cervical cancer is still a significant burden worldwide. Fig 4 Taken from, The popillomavirus life cycle by John Doorbar published in the journal of clinical virology 32S (2005) S7-S15 Fig. 5. CIN 1 resembles productive infections caused by other HPV types and as such is the most benign form of cervical intraepithelial neoplasia , it is confined to the basal 1/3 of the epithelium, CIN 2 Moderate dysplasia confined to the basal 2/3 of the epithelium,CIN3 Sever dysplasia that spans more than 2/3 of the epithelium, and may involve the full thickness. INCIDENCE An estimated 493,000 new cases and 274,000 deaths in 2002 were caused by cervical cancer. The vast majority, some 83% of these cases, occur in developing countries, where cervical cancer amounts to 15% of female cancers with a risk before age 65 of 1.5%. In developed countries cervical cancer accounts for only 3.6%, with a risk of 0.8% before age 65. REF The highest incidence rates are observed in Sub-Saharan Africa, Melanesia, Latin America and the Caribbean, South-Central Asia, and South East Asia (fig 6) Fig 6 Worldwide Burden of HPV related Cervical Cancer Figures from 2002. Parkin MD et al 2006 The burden of HPV-related cervical cancers The vast majority of cervical cancers are squamous cell carcinoma adenocarcinomas being less common (fig 6). Generally the proportion of adenocarcinoma cases is higher in areas with low incidence of cervical cancer, accounting for up to 25% of cases in western countries (fig 6). This higher incidence of adenocarcinoma may be partially explained by cytological screening, which historically, had little effect in reducing the risk of adenocarcinoma of the cervix, because these cancers, and their precursors, occur within the cervical canal, and were not readily sampled by scraping of the epithelium of the ectocervix. Fig 5 Fig 5 showing the higher % of adenocarcinoma in counties that have screening programmes such as the UK and Denmark What is this showing? Make it clear.do you really need it. MORTALITY RATES Mortality rates are substantially lower than incidence rates. Worldwide 55% (could you double chek that this is the case please misses) of all those that develop the disease die, the figures vary significantly from the developed to the developing world. Low risk regions of the west such as Europe have a death rate of 37% while in developing countries where many cases present at relatively advanced stages, death rates are significantly higher increasing to 70%. Cervical screening programmes in the developed world identify pre-cancerous lesions at a stage where they can be easily treated accounting for the difference in mortality rates. TITTLE IF and figure number staying and refer to in text As cervical cancer affects a relatively high number of young women, it is a significant cause of years of life lost (YLL) in the developing world. Yang et al 2004 found that cervical cancer was responsible for the 2.7 million (age weighted) years of lives lost world wide in 2000, and that it is the single biggest cause of years of life lost from cancer in the developing world. In Latin America, Eastern Europe and the Caribbean, cervical cancer makes a greater contribution to YLL than disease such as Tuberculosis or AIDS. HPV is also associated with many other forms of cancer that could possibly be prevented with use of HPV vaccines; cancers of the penis, anus, vulva, vagina, oropharynx and some rare cancers of the head and neck are included. However cancer of the cervix is by far the most significant, in terms of incidence and mortality (table 1). Cancer of the vulva and vagina have a significantly lower incidence rate compared to cervical cancer, however since 80% of the incidence are caused by HPV types 16 or 18 women vaccinated against these types would also be protected against these forms of cancer. Incidence of squamous cell carcinoma of the anus are twice as common in females as males with HPV types 16 and 18 accounting for 83% of all cases. There is a particularly high incidence of anal cancer among homosexual males, shown by the high incidence rate in populations such as Sanfransisco, where gay incidence are higher than average (fig 7). Globally cancer of the penis is relatively rare accounting for 0.5% of cancers in men (table 1). HPV DNA is detectable in 40-50% of all penile cancers and serological studies have confirmed the role of HPV 16 and 18 (IARC 2005). Cancers of the mouth and oropharynx caused by HPV are very low at 0.06% of all cancers with 0.05% being caused by HPV types 16/18. Due to the small size of most studies and the absence of comparable measurements of prevalence of infection in normal subjects conducted for cancers of the vulva, vagina, penis and anus true prevalence is difficult to quantify. The figures shown in table 1, imply that we are dealing with a virus that discriminates primarily through disease aginst women, in particular young women. Gay men, however are also clearly an at risk group. Currently only young women are vaccinated aginst HPV types 16 and 18, however the JCVI (joint committee on vaccination and immunisation) have noted that the vaccines has not been conclusively trialled on men, and that there is insufficient evidence that the vaccine available would protect against anal, penile or head and neck cancer. However when more data becomes available they will consider vaccinating, high risk groups such as men who have sex with men. Add what this implies for prophylactic use of vaccine with other cancers cause by HPV And what you think about the ue of vaccine on highrisk men and its effectivity against other cancers caused by HPV types 16 and 18. Fig 7 TITTLE add Figure 6 showing that cancer of the anus are more prevalent in women than men with the major noted exception being San Francisco, where the increased incidence can be explained by a large number of homosexual men. Table 3 VACCINATION An effective vaccine should stimulate a suitable range of immune responses, mimic or improve on the protection gained from a wild type infection with little side effects. Critically the vaccine should be inexpensive, easily administered, transported and stored to further reduce cost and maximise convenience, this is especially relevant in the case of HPV vaccine as those that are not protected by the screening programmes of the developed world would benefit the most, ease of administration and storage is paramount in the developing world as stability and healthcare is more sporadic, and people are often more remote. There are many different kinds of vaccines available, and different vaccines have a variety qualities and limitations. Live attenuated vaccines contain a version of the pathogenic microbe that is avirulent, they often elicit an excellent cellular and antibody response with good longevity that can be lifelong with few doses. However there is always the possibility that the vaccine may revert to its virulent form, causing disease. For this reason a live attenuated vaccine is not appropriate for use against oncogenic HPV types. Recombinant vaccines can include one or more proteins that may illicit an immune response. A process has been developed to allow the removal of the genome from an attenuated or avirulent viral vector allowing the insertion of selected genetic material or proteins from another virus. The carrier viruses then ferry that viral DNA into host cells where the genes are expressed. Recombinant vaccines closely mimic a natural infection and therefore illicit a strong immune system. Inactivated vaccines are produced by killing the disease causing microbe by chemical (formaldehyde eg just double check), heat or radioactive means. These vaccines are more stable than live vaccines, and as there is no risk of reversion to virulence. They are also safer than live vaccines. Most inactivated vaccines stimulate a weaker immune response than live vaccines and several doses or boosters may be required to maintain immunity. DNA vaccines dispense with both the whole organism and its parts. They only include the essential part of the microbes genetic material. In particular, DNA vaccines use the genes that code for immunogens. Researchers have found that when the genes for a microbes antigens are introduced into the body, some cells will take up that DNA. The DNA then instructs those cells to make the antigen molecules. The cells secrete the antigens and display them on their surfaces. In other words, the bodys own cells become vaccine-making factories, creating the antigens necessary to stimulate the immune system. A DNA vaccine against a microbe would evoke a strong antibody response to the free antigen secreted by cells, and also stimulate a strong cellular response against the microbial antigens displayed on cell surfaces. The DNA vaccine is unable to cause disease