Cryptococcus Neophormans Vacine strategy

Workshop #4

Azat Duisembay

Yerbol Nurmaganbetov

We will develop a vaccine about opportunistic bacteria called Cryptococcus Neophormans. Cryptococcus Neophormans (CN) is yeast pathogen that access to organism by respiratory track. If crosses Blood-brain barrier, CN can cause meningitis and encephalitis. As a result patient may die. 

a vaccine formula

Vaccine will consist from Glucuronoxylomannan antigen with adjuvant.

Since patient infected with HIV, they have low level of CD4. We decided to increase number of CD4 cells by injection of genetically engineered CD4 and oral prescription of maraviroc or vicriviroc

mechanism of action,

Since the main problem in AIDS is the enormous decrease in CD4 cell number, we decided to fight against it. It is very hard to amplify and recover the lost CD4 cells, but we still can save the ones that are alive. Then, we rely on their further activation of other immune cells.

HIV recognizes CD4 cells via the CCR5 receptors that are on cells. People lacking those receptors do not acquire AIDS. There are CCR5 co-receptor antagonists that inhibit the interaction of CCR5 receptor of CD4 cell and gp-120 glycoprotein of the HIV. Thus it can avoid fusion of the virus with CD4 [1].

1.     Currently, there are known 4 antagonists. 2 of them are relatively quite trustable. They are maraviroc and vicriviroc. Maraviroc is approved by FDA in 2007. However, vicriviroc is in the III stage of clinical trial now[1]. Using of this drug may lead to higher number of CD4 cells in patient

2.     In addition we can add gene-modified autologous CD4 T cells. CD4 cell genetically modified by Zinc finger nuclease, which targets both CCR5 and CXCR4. As a result CD4 cell do not express both CCR5 and CXCR4.  Clinical trial showed that patient who received altered CD4 cells had stable level of those cells. [3] Modified cell can be specific for CN antigen.

Glucuronoxylomannan is antigen specific for CN [4]. After increasing the number of CD4 cells, it is possible to induce active immunity in the HIV infected individual. Glucuronoxylomannan can be added to adjuvant such as ALUM. ALUM is able to activate DC more efficiently and activate B cell for immunoglobulin production. First of all any antigen presenting cell will engulf antigen with adjuvant, for example DC. Then DC will present antigen on the surface of the MHCII. Then DC will move to secondary lymph node, where will show Antigen to injected CD4 (Th) cells. CD4 cell then will search for specific B cell and activate them. B cell previously identified Antigen by BCR and internalized it. So, B cell now has Antigen on the surface of MHC for T cell recognition. After interaction with CD28, CD40L and different cytokines B cell becomes activated. Consequently, vaccinated patient will obtain memory B cell, which will protect organism from CN. Moreover, thanks to the class switching, it’s expected that anti- Glucuronoxylomannan dimeric IgA will be produced. Dimeric IgA will prevent CN infection in Lung.  

In addition, we believe that Glucuronoxylomannan can activate B cell through T cell independent activation. It is known that T cell independent activation can be induced by polysaccharides and Glucuronoxylomannan is polysaccharide. However, T cell independent activation produce mostly IgM and do not for memory cells. For that reason immunity will be temporal.

Injected CD4 cell can facilitate in formation memory CD8 T cell. CD4 cell will activate naive CD8, it will then change to effector cell and consequently to memory cell.

Antigen proceeded by phagolysosome of DC, degrade to smaller peptides by proteasome. After that, TAP proteins transport peptide to ER. In ER peptides bind to MHC-I. ER transports MHC-I (with peptide) molecule to Golgi complex. Golgi complex transports MHC-I to membrane, where it display it.  DC then present MHC-I to CD8 cell and activate it. After that person will have activated CD8 T cell.

In overall effect, patient will have strong memory B and T cell response against Cryptococcus Neophormans, even if he/she still infected with HIV.

regimen, route of delivery

Vaccine (antigen + adjuvant) will be delivered intravenously once. Maraviroc is taken twice a day orally [2]. Genetically modified CD4 cells will be delivered intravenously for one time.

possible side effects

This solution has its own side effects such as hepatotoxicity or malignancy [1].

References:

[1] Emmelkamp JM, Rockstroh, 2007, JKCCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature. Eur J Med Res. 2007 Oct 15;12(9):409-17. Retrieved on Nov 12, 2015 from http://www.ncbi.nlm.nih.gov/pubmed/17933722

[2] HIGHLIGHTS OF PRESCRIBING INFORMATION, 2007 https://www.viivhealthcare.com/media/32064/us_selzentry.pdf

[3] Bruce et al., Gene transfer in humans using a conditionally replicating lentiviral vector, 2006, retrieved from http://www.pnas.org/content/103/46/17372

[4] Marta et al., Serum Cryptococcal Antigen in Patients with AIDS, 2015, retrieved from from http://cid.oxfordjournals.org/

Azat Duisembay “Effect of internet addiction to brain and behavior”

Over the many years internet became part of your lives. From virtuality in the past internet is now quite real entity. As real entity it can impact your lives through Facebook, YouTube, skype, streams, online gaming and etc. As can be seen from the documental movie “” internet can be quite addictive. Internet provide variety of options to spend time and people just escape reality by using internet. Unfortunately, it has some consequence. Online gaming, such as league of legends and DOTA2, and internet itself can impact to the physiology by affecting to the brain structure and behavior. It affects every generation and effects different countries at different rate. For example, 11.6% in Turkey, 10.8% in  China and 10.7% in South Korea addicted to internet from the age from 12 to 19. As a consequence, in DSM-5 (Diagnostic and Statistical Manual of Mental Disorders), which is official guide of mental disorders, includes internet gaming disorder as psychological disorder. In this paper I will try to examine mechanism of the brain and behavioral changes after internet addiction. I will discuss paper written by Kimberly et al., which makes analogy between internet addiction, alcohol abuse and gambling. In addition, neuroimaging picture of the person brain addicted to internet was discussed in the article by Daria and Mark. Finally, association between internet addiction and psychological disorders, such as depressive disorder will be discussed and give personal opinion of that issue.

Currently about three billion users in the internet. Unfortunately, internet can lead to addiction among population. Internet addiction is one of the recently emergent disease. For example, it can associate to depression, ADHD, social anxiety and hostility. Hikikamori phenomenon from Japan, when people socially withdrawn from the society for more than six month. Socially, withdrawn people usually excessively use internet. Many of them become addictive to online gaming. Gaming and internet use can lead to the strong daily behavior. Behavior can change brain structure by phenomenon called brain plasticity. Brain plasticity allows new neuronal connections to form, while destroying the old ones. Changes in the brain structure can be studied by neuroimaging techniques, such as PET, MRI, CT and SPECT. As a result, brain and behavior changes may lead to changes in personality. Person may develop or become predisposed to certain psychological diseases.

Internet addition was associated with negative behavioral and psychological symptoms. In this paper I tried to identify neuroimaging studies that give insight to the specific brain changes and brain areas involved in person addicted to internet. fMRI studies identified that several brain areas were activated in both female and male participants. For example, the right insula, which participate in person arousal, bilateral premotor cortices, which prepare organism for reward, and right dorsolateral prefrontal cortex, which is responsible for changes in behavior and reward maximization, were activated in the 22 healthy participants. [Hoeft et al.] All participants were involved in online gaming. In addition, further research identified that in gamers, who plays World of Warcraft more than 30 hours per week, have high craving for online gaming. On the other hand high craving for that online gaming was correlated with increased activity of the anterior cingulate cortex. The anterior cingulate cortex involved in reward anticipation, emotion and decision making.  EEG identified that internet addicted individuals have a longer reaction time that normal individual [Dong et al]. SPECT and PET neuroimaging techniques identified with decreased availability of dopaminergic receptors in brain region called striata. In overall, neuroimaging studies identified that internet addiction associated with dopaminergic activity and reward centers. In addition, internet addiction can be associated with several psychological disorders. According to Ko et al., attention-deficit hyperactivity disorder (ADHD) can be associated with internet addiction. Bernardi and Pallanti found that 14 % of internet addicted adults have ADHD. Children has even higher statistics, when 7 out 12 addicted children have ADHD. People who suffer from ADHD become easily bored and can’t focus attention. In addition, Ha et al., found that in Korea people have association between internet addition and depression. Depression on the other hand can lead to suicidal thoughts. Ko and colleagues identified that people with depression for more than two-year period more likely to develop internet addiction. According to Bernard and Pallanti, 15% of internet addicted individuals have social anxiety disorder. Societal anxiety disorders associates with alienation from the family and school, and with fear to communicate with people face to face. In media, I often can find debates about hostility and gaming. In truth no causal relationship could be found. Hostility can be result of rejection and alienation from society, but internet addiction is a consequence of alienation. Kimberley stated that internet addiction can be compared to gambling for several reasons. First of all, addicted people stay longer on-line than initially planned. Then, people may risk job, educational opportunities and relationship for internet only. Person become depressed and moody, if internet cut down from them.  The same signs and symptoms of control difficulties can be found in pathological gambling. Moreover, like in alcohol consumption addicted person may hide episodes of internet usage.   Online world can provide alternative for everything that addicted person left in real life. Like virtual money in game or on-line relationship with people all around the world.

From the finding above it can be concluded that after excessive internet usage can effect on the brain structure. Main changes involved dopaminegertic receptors. Dopamine receptors in individual addicted to internet decrease over time. I will not mention the exact mechanism, but decreased number of receptors requires more dopamine for activation than from the first activation. Which means that for the first time person need less alcohol to achieve the same pleasure, than for the 10^th or 20^th exposure to the alcohol. The same works for internet. Addicted person needs more and more online time than initially. Addicted person loose sense of time and get a lot of dopamine. Actually, user become 100% concentrated on the internet. Then, user inter the flow state, where he or she loose sense of time and space, an even if person have important issues to do in the real life user do not care about anything. Internet addiction can be associated with different psychological diseases, such as depression. However, association between depression and internet addiction do not mean causal relationship. Internet addiction do not cause depression and depression do not cause internet addiction. During the depression, person need social support and control of situation. Internet on the other hand can provide depressed individual with control of the virtual world. Virtual world can also provide people with social support via chats and specialized sites. Virtual world can be used to escape reality and repress unconscious thoughts. Another question is socially withdrawn people like hikikamory, who do not communicate with outside world. Internet provide opportunity for those people to live a normal life, to buy food to communicate with people without face to face contact and earn money from home. Internet also provides social support for people. However, if social phobia do not disappear after time, person may become heavily dependent on the internet. Moreover, people with ADHD get easily bored and can’t focus attention. Internet provide for those individual different entertainments, such as YouTube, and different sites so they can easily change their attention. People with ADHD become dependent on internet for all possibilities and internet on the other hand reinforce symptoms of ADHD. From the information mentioned above, it can be concluded that internet addiction do not cause different psychological disorders, but disorders may predispose people to internet addiction. Treating disorders can benefit severity of internet addiction. The internet is easy way to escape reality and cope with social and emotional difficulties. This kind of coping strategy may lead to addiction. Internet dependent individual like gambling player may have severe problem in real life. For example, financial difficulties, worsened relationship with family members. This all can be result of uncontrollable internet usage. Internet addiction is not just disease, is a behavior that can be caused by another problems. It can effect on the people around people and can effect whole countries. People who heavily dependent on internet may develop attention seeking. It can be explained by simple behavior. For example, well known Pavlov dog who was trained to salivate to the bell ring before exposure to the food. By the same mechanism internet can modify the behavior of the internet addicted individual. For example, user post something what people do not like and get “dislikes”, user stops do that kind of post. So dislike in that case is punishment which modifies behavior. On the “likes” reinforce behavior, and heavily dependent person may modify his or her behavior by internet preferences. In one book I read that we are generations of observers. We observe constantly and everything, in YouTube or social networks. Observation is part of our entity life and it is a nature processes. Our brain make it possible to learn for the environment from observation by the help of mirror neurons. Have you eve noticed? when someone hurt himself in YouTube, you literally feel his pain, or if someone lough a lot, you start to lough too. It is when your mirror neurons works. Social networks such as Facebook allows us to learn from others and modify our behavior. For example, I can see picture of the movie star started some viral picture, such as selfie on the hands. Then, people try to make the same picture over and over. Actually selfie become more popular recent years, because people started to modify their behavior after internet become flooded with that photos. By the same principle person addicted to the internet may constantly modify his or her behavior. From that point I can bring this discussion to different pathways. If we will examine the live of person in the developed or developing countries, it can be notes that internet become part of our daily life. Internet become real entity from the virtual. We all think, obsessed and we love internet for all possibilities it give to us. Possibilities in education, job and entertainment. For example, daily job of many employees can start from mail checking. Student is required to check moodle regularly for assignments and lectures. Even school in Kazakhstan now has their own web sites. Inevitably, that kind of site checks set our behavior and it becomes daily routine. Everyone think that it is normal to surf in the internet in free time. If we will closely identify addiction symptoms, we will find that it includes societal sacrifices, obsession, and risks taking for using internet, withdrawal symptoms, when internet level become less than required. All of those symptoms can be observed in the individual in modern era. Internet addiction is not just disease, we biologically predisposed to observe through internet and it becomes part of our life. Consequently, observations made in the internet, not only video but any biased opinion of other writer, can shape our behavior.      

In conclusion, I discussed how internet can change the brain structure of the individual addicted to the internet. It was found that it affect to the dopominegertic receptor and different reward centers. Basically, internet can affect to own brain through the same mechanism as any drug and alcohol. It can explain why in other papers I found that people addicted to drugs, alcohol and internet has almost the same symptoms. In addition, association between psychological disorders and internet addiction was made. Sometimes internet can reinforce behavior of psychologically ill individual, but it is also possible that individual can psychological symptoms (behavior) can lead to internet addiction. Finally, internet addiction is part of our daily life and we constantly using it. So, internet can easily change our behavior, because we biologically predisposed to learn from internet observation.

     

Reference:

Daria and Mark, brain sci.Internet and Gaming Addiction: A Systematic Literature Review of Neuroimaging Studies, 2012

Ko et al., european psychiatry,  The association between Internet addiction and psychiatric disorder: A review of the literature, 2010     

Kimberly et al., cyberpsychology and behacior, Internet Addiction:The Emergence of a New Clinical Disorder, 1998

 Andy Furlong, sociological reviewThe Japanese hikikomori phenomenon: acute social withdrawal among young people 2008

Dong, G.; Zhou, H.; Zhao, X. Male Internet addicts show impaired executive control ability: Evidence from a color-word Stroop task. Neurosci. Lett. 2011, 499, 114–118

Hoeft, F.; Watson, C.L.; Kesler, S.R.; Bettinger, K.E.; Reiss, A.L. Gender differences in the mesocorticolimbic system during computer game-play. J. Psychiatr. Res. 2008, 42, 253–258.

League of legends

I learned several things such as:

Deep focus in the problem. Epic win emotion is used by problem solving behavior. We motivated to collaborate and to get up after failure. Game never give you what you can’t achieve, not what we have in real life. Gamers get instant feedback. 10 000 hours we become experts. We like people better if we played with them. Gamers do hard job, always optimistic, they building hew knowledge.

League of legends is one of the most popular game in the world, more people play this game that overall population of France. E game industry has own rue and industry. Personally, I believe that most of the children is internet addicted and addicted to the game. People may play about 19 hours a day. In addition, gamers very dedicated to their game may develop serious health problem, due to sedentary life style and unhealthy food habits.

Cosplay is also part of the game industry. For now gamers and cosplayers are not accepted by older generation. In addition, game industry in the west is comparably similar and at the same time different from the east game industry. Main difference is PC café in the east, while in west gamer prefer to lay in the rooms. In conclusion, Egaming is part of

2. Use Dovey & Kennedy to explain identity negotiated when playing games--why is identity part of a "cybernetic loop?" What is a "cyborg" and why is the concept important in studying games?How do players form an identity in games, and what is unique about the use of identity.

Cyborg is the hybrid between human and machine. “In short we are cyborgs” (108 p.) Author states that people and machine interact with each other by cybernetic loop. Loop is basically feedback of machine on the action of the gamer. It is possible to obtain sensory feedback from the game through avatar. Finally, after several hours of the game, avatar becomes representative of gamer actions.  

Game mechanics in the everyday life, such as level and coins. In addition, gameplay to sustain interest by sustain gamer to learn game mechanics. So people get in return possibility to play game.

In addition, gameplay is used to create non-coercive environment. Finally, use game mechanics to engage in game, forget about time and anything to put gamers in the flow state. So, they become more productive.

Ludification is to put cultural processes in the game.

Example, education is force you to do something, but education was gamified at the beginning by levels and coins for example.   

1. What are the unique aspects of digital games? Use the Dovey & Kennedy reading to explain what games are, what gameplay is, and how they construct the identity of the "player." How is power negotiated in gaming, and what are the unique aspects of embodiment while playing games? Think of a time when you played a game. Why did you play and how did you feel while playing; did you feel for or less powerful?

“Gameplay is therefore an experience that requires, develops and reflects back a particular kind of technicity” (115 p.) This mean that technology and experience gained from the game is interrelated. Moreover, gameplay is a mechanics of the game which allows certain actions.

Game and simulation is basically the same things. In CMC simulation is more like possibilities. So, gaming is simulation with game parts. Gaming can be simulative use simulation part but not necessary simulation.

Game designers used game simulation to create a game for people with autism. Some times those people can’t to communicate with each other. So game designers put autists in the game situations with anxiety and emotions.

Game and gameplay can be used to construct user identity by using avatar from the game. In the book you can find example of “ridick”. In this game, like in other games, gamer experience the game by obtaining the feedback from the gameplay through avatar.

Embodiment in the game can be achieved through the loop interaction between player and the technology. Gamers get habituated to the game platform, such PS4, PS3, PC, XBOX1 and etc. Finally, gamer feels specific gadget as part of the body.   

Reason why people use game, because it is safe and we can learn possibilities from people. For example, in military simulation is used to training. Training soldiers to interact with civilians.

It is known that game can produce the state of flow. In flow state gamer forget about time, food and everything else. Gamer can think about the game. In addition, feeling of the game can be changed by using gadjet, as can be seen from the above.

Costranova said that gaming is petri dish and rat maze, because game is about surveillance. If people see game it is natural and not dangerous to watch you. Shadow economy happening in the game society. Moreover, game provide communicative structure and    

1. The creation of hybrid spaces is a difficult concept to grasp. In short, it begins a process of injecting data into spaces and creating a social environment where the virtual is always present and visualized in the lives of daily users. Hybrid space can come and go, and it is experienced when a user or institution begins using locational data, applications and networked terminals/devices to influence everyday spatiality. Think about The Internet of Things, which ensures the creation of hybrid space in everyday environments. Explain what makes hybrid space different from cyberspace and give examples of both. How is the way we see virtuality changing as hybrid spaces and The Internet of Things becomes more common? What changes does hybrid space bring about in the everyday spatiality of people? Have you been through a hybrid space?

"The idea of virtual reality as a simulation (or illusion) of reality opposes the virtual to the real and consists of what we call the ‘‘technological virtual.’’"

In the article of Adriana and Sutko, concept of virtual reality is discussed from the different perspectives. Devices such as mobile phone give Virtual reality in which people can exist in both actual location as well as location pointed by the mobile phone. Then, authors explain that virtual reality exist only by interaction of the computer and a user. In addition, according to Plato virtual reality is the copy of the actual reality. Reality can be real when represented, even if not real as the object. In addition, according to Aristotle virtual is potential, while reality is actualized potential. Finally, according to the Hayles Virtuality appear when information intercept with material object. From the class discussion and given article it was clear that internet can quite real entity and hybrid space can be changed as internet becomes more real.

“Ubiquitous computing” means portable, networked and personal. Space is not stable thing, because our understanding of space constantly changing. We though a space as something hold everything. However, there are no space without people, math, logic and etc. abstractive space do not exist without society and through science we can manipulate the space. Abstract space can be filled with personal Ideas, like me, I and my. “Connections with other users may lead to connections with others places” (Location-aware mobile media and urban sociability P.8). This also reinforce the idea that space can be disrupted and it is not constant. 

 “that argue that people gain control over public spaces with location-aware technologies” (Locational Privacy in Public Spaces: Media Discourses on Location-Aware Mobile Technologies P.8). Hybrid space = If you remove data from the space, data will be meaningless.  We put data to the space our self and create hybrid space. As I understood public space and hybrid space can be the same entity. For that reason, it is possible to imply that people can manipulate hybrid space by the gadgets.

Hybrid space can change spatiality of the person in several ways. First, it can be come independent of the specific location. Secondly, Location of the person can be located in specific place, like in FACEBOOK. Finally, GPS can locate that orientation of the person in the real word and show it the hybrid space.

Different cultures interpret time differently. It heavily dependent on the way people interact with each other in the society. Like mayan calendar was extremely precise for them. But their understanding of space and time was different from Romanian. 

Social space

Hybrid: technological understanding is also abstract understanding. In tech. understanding data us uses you in abstract data and transfers you in abstract data. Spaciality is your body movement in the space.

Hybrid space redefines “ the virtual”. Because we use computers it constantly represent us, others and our space. In a real data is all around them. In addition, virtual as somewhere you go and virtual is constructed by symbols. For example, Zizck in reality CMC is the same as real world. We see internet becomes a physical, and if it misses life becomes different. According to Deleuze Virtual as a set of possibility. This means that virtually is about simulation and visualization of the possibilities.  It exists because you think about it then you desire to have something, more possibility that this thing is really exist. I am constantly present in hybrid space, because I use internet. Internet is also hybrid space.

1. What informs the creation of commonality in CMC environments? On the Indian discussion board, what were some trends concerning the creation of commonality? Additionally, what were some of the issues that users faced?

The main thig that informs the creation of commonality is creation of national identity. Indian discussion was good example of commonality creation. As I understand people where joining by in different discussion group where they fell they belong. However, issues faced by commonality was more important to me. Even if it is my subjective opinion. As I understand in discussion people tried to concentrate on the differences between the people, rather than on similarities. For example discussion of the Hinduism and Islam. In Indian discussion, people created almost the same conflict , that took place between Pakistan and India. Moreover, there are no strict geographical location in CMC. Usually, people restricted in some geographical area and can not communicate with each other. However, people In CMC do not restricted by geographical area and commonality form purely from interests and thoughts.