Monthly Archives: April 2016

Restrictions on Videogames

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With the controversies surrounding videogames and their contents effect on people growing up around them, the argument popped up of how regulated they should be to protect societies values. On September 16, 1994 the Entertainment Software Ratings Board, or ESRB as it’s more commonly called, was created to introduce a ratings system in order to inform the consumer of the item they want to purchase. This was in reaction to several controversial videogames being released that were bought for the wrong audience because there was nothing to inform the customer of the content, although the titles Death Race or Mortal Kombat should have been a good indication of what was to be expected. Nevertheless after public backlash the ESRB was created and is still around today creating labels for games everywhere. This rating system that is implemented is much akin to the Motion Picture Association of America film rating system used to rate cinematic movies, both animated and live action.

In order to discuss how we should deal with the regulation of videogames, we must first decide what exactly to classify videogames as. Are they just a game meant to be played and used, or are they something more than that? Many people argue whether or not videogames are considered art and the debate is still out there so I’m going to do a simple breakdown of videogames as they exist today and how they hold up to a widely held definition of art. Merriam-Webster defines art as “something that is created with imagination and skill and that is beautiful or that expresses important ideas or feelings.” Videogames fit perfectly within that definition. They involve complex worlds, characters, and storylines that have to be near flawless and allow exploration of the player, not to mention all of the game mechanics and balancing that has to happen in order to complete the game and make it a pleasant experience for the player. While some games are meant to just be played through and give just a couple of hours of enjoyment and not leave an impact, it is becoming more and more common for games to involve the player themselves and the creators love bringing satire into their games and having the player get involved in the issue. Some games are even entirely created around that fact. Other games however might not include social satire, but instead invoke strong feelings within a player by showing a grand cut scene of an area to get an emotional response or even by showing a characters death. The emotional response that a game creator can get is usually greater than that can be achieved by any other type of median due to the involvement the player has in that world. Another great thing about videogames as a type of art is that the game creator is able to let someone wander around and get immersed by the world that they have created. The player sees and hears the world the way the game creator intended.

Since videogames are a form of art, however untraditionally, we must look at precedence to see if and how art has been regulated before deciding how videogames should be regulated. As far as I could read, and not having a major in art or art history, art currently has no regulations placed upon it. However, with this being said I feel that I must also add that it has historically been controlled by governments in a way that would promote certain ideas or to silence others. So then why when art today is unregulated should we lock down on videogames and strictly control what is produced by game companies?

Many people say that videogames lead to an increase in youth violence and there have been about 300 studies done that back this allegation up. In fact, many mass shooters are linked to playing violent videogames. With all this evidence it seems pretty obvious why the populace is let to believe that violent videogames are a huge problem in today’s youth. However, the studies conducted were all considered flawed in their procedures, had external forces on the study, or were conducted with bias making them scientifically null and void along with being an inaccurate reference. As far as the link to mass shooters and violent videogames, an ABC news survey in 2007 revealed that 91 percent of children play videogames and the number is steadily increasing. With that large percentage of children playing videogames it makes sense that the mass shooters would also play videogames just out of probability, and that’s without adding in their mental state. Most mass shooters are socially introverted and it would make sense for them to retreat into a world that they can control and hide in. It would also stand to reason that someone who is already violent would tend to gravitate towards violent types of videogames. While there is a connection to mass shooters and violent videogames, there is no causation. As far as the overall tendencies of videogames causing widespread youth violence, according to the Bureau of Justice Statistics, youth violence in America has dropped drastically from just under 4% in 1980 to under 1% in 2013.

Another argument that could be used against videogames, violent videogames in particular, is that children are the primary target of videogame developers. This is not the truth however. According to recent research done by the ESRB only 25% of gamers are under the age of 18 while 49% are from ages 19-49 and 26% are ages 50+. People under the age of 18 are actually the smallest demographic of gamers out there, and games with the most mature content, rated “M” games, only consist of 17 percent of the total sales. A very low number considering that it is specifically targeted at 75% of the gaming population (ages 18+).

There are also many positive aspects of the videogame industry that are actually beneficial to society. Videogames have been proven to improve hand-eye coordination, problem solving, creativity, learning abilities, and even help people become more sociable due to the widespread sweep of online and multiplayer gaming in today’s games. This area in itself could turn into at least a ten page essay, but with my current primary focus being with talking about the regulation of videogames, I feel that it is much more pertinent to address why videogames might be a detriment to society and prove otherwise.

Videogames are a form of expression for both the game developer and the gamer themselves and thus is a form of art. Art is supposed to be a free exchange of thoughts and ideas expressed creatively, and thus in order to keep art true then there must be no restrictions placed on it. It is meant to start a discussion, bring up controversies, or to just bring out a particular emotion be it happy or terrified. With this being said however, I do not advocate for the disbanding of the ESRB or the removal of the rating system as certain forms of art are not meant for everybody. The same way you wouldn’t show a 6 year old the painting Saturn Devouring His Son by Francisco Goya, you would also refrain that child from playing a game from the Call of Duty franchise which their whole aim is to accurately depict warfare and immerse the player in it. The current restrictions placed on videogames are perfectly fine as they do not infringe upon the game developers creativity, but they also provide protection to the consumer by letting them know the content of the game they intend to buy as well as stop underage kids from buying videogame content that is not suited for them, and lets the parents themselves censor what their kids play.

 

 

 

 

 

Merriam-Webster. Merriam-Webster, n.d. Web. 09 Feb. 2016.

Jenkins, Henry. “Reality Bytes: Eight Myths about Video Games Debunked” Writing Arguments: A Rhetoric With Readings Ninth Edition.ed. John Ramage, John Bean, June Johnson. Pierce. 449-452. Print.

“How Much Do You Know About Video Games? Share.” Video Game Industry Statistics. N.p., n.d. Web. 10 Feb. 2016.

“Youth Perpetrators of Serious Violent Crimes.” Http://www.childstats.gov/. N.p., n.d. Web. 10 Feb. 2016.

The Evolution of Rhetoric Through the Advancements of Technology

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Rhetoric is constantly evolving and will never reach a point where it cannot be improved. Ever since humans were able to communicate, the basic thing that needs to be improved upon in rhetoric is how the information or message is transferred and received, so the improvement of availability and clarity are the main things to focus on when trying to improve how rhetoric is passed along.

Availability means having the ability to readily write down thoughts and ideas as quickly and conveniently as possible and being able to also have easy access to other people’s thoughts and ideas that they have written down or shared. Before the development of the first written language (cuneiform) all information was passed around orally. Oral communication is fine, and is still used today, as long as the information is coming from a primary source and is not being communicated through long distances (time or length). As the information gets transmitted orally from one person to another and so on and so forth the information gets distorted and lost in the transfer from one person to another. A good example of this happening is the telephone game. One person comes up with a phrase (i.e. “Cadre are patrolling the stoops from 2300-2315.”), and they proceed to tell the phrase to a person who then relays it to the next person and so on and so forth until it reaches back to the initial person and the phrase is now “RDC and Cadre are patrolling the stoops making us push from SRC to taps.” The same is also true with time. As time progresses, people’s memories fail to fully recollect information and parts of the phrase will be forgotten, changed, or even the whole phrase could get lost or forgotten. This seems undoubtedly true with rat bible knowledge and then your complete lack of recollection will be graciously pointed out by cadre and/or RDC. In order to clearly pass on a verbal message sentence structure is vital. If a sentence is put together incorrectly when spoken then the meaning could be misunderstood or completely incoherent to the point where the message cannot possibly be derived.

With the development of written languages information can now relatively withstand the test of time, which means that as long as the object it is written on still exists then the information also still exists. The downside was that early forms of writing were carved into rock, which meant that it was a laborious, difficult, and an intensive process to write anything down. It also meant that the information could not be moved or easily accessed by everyone because of its immobility. Because of this only a very select few people could read and write. These select few consisted of prominent state and religious figures. This is a nice first step, but the idea is to make the information available to everybody, not a select few. However this was improved with the invention of papyrus and paper, which helped increase the effect of literacy. It made writing lighter and easier making it so that texts could travel through cities and even countries as long as the paper was cared for correctly. Literacy expanded to almost all religious figures (i.e. priests) and state figures (i.e. noblemen). It was also easier to write and put your thoughts down on paper as long as you had a quill and ink to write with. Coupled with paper, the biggest innovation in literacy is the invention of the printing press. Before the printing press it took dozens of monks days to copy a book by hand making books expensive and hard to come by, but with the invention of the printing press books could be made a lot faster, a lot cheaper, and more uniform. Because of these advantages of the printing press, books were much more readily available meaning that the lower classes could afford them and then they learned to read and write as well. This was the biggest spread of literacy in terms of availability to date. It is the reason why most people in the world are able to read and write, and is very uncommon to run across someone who is unable to. Now that language was in a written format it needed new rules to be made on top of sentence structure to ensure the clarity of the message. Those rules consisted of punctuation, spelling, and other early forms of grammar that we, today, learn at a very young age. These new rules ensure that everyone’s writing is uniform enough so that anyone who can read that language can read any writing of the same language.

Another thing that helped with the advancement of literacy is how texts were stored. Libraries gathered many different texts together in one place so that people can come together from other places and learn. Libraries have existed since around 2600 BC and the most famous of these ancient libraries is the Library of Alexandria (3rd century BC). Libraries are still the main icon when people think of knowledge and learning even today. It just proves how effective it is to accumulate knowledge in one place for the masses of people is in terms of education and literacy.

A great modern advancement that rivals that of the printing press (in terms of rhetoric anyways) is the internet. It is a readily available collection of most of mankind’s knowledge and literacy all compiled into one place and weighs as much as whichever device you use to access it. It’s a huge advantage to literacy because it’s always readily available and easy to access as long as you can afford it. And with the increase in technological advancements devices to access the internet are steadily becoming cheaper and more available to anyone. A large downside on the other hand is that just about anyone can publish anything on the internet, and nobody is there to check and make sure that the facts are correct. So when you are reading an article online it is very possible that you are being misled by the author, intentionally or unintentionally, and all the information that you have just retained is false. This is a lot less of a problem if you are able to authenticate the work. A good thing to look for is references and if those references, because that means that the author has researched and studied the subject before writing about it and it is usually a trustworthy source.

In rhetoric, clarity is a necessity when trying to use rhetoric to convey an idea or thought to someone else. If they can’t understand what you’re trying to convey then they won’t be able to learn or do what you are trying to convey to them. Without clarity in rhetoric, rhetoric itself becomes invaluable because nobody can actually obtain anything from it. To solve this problem society has created grammar which sets down a bunch of rules to guide how we communicate. Without it there would be incoherent sentences everywhere and nobody would end up having the same way of communication like we have now. Grammar lets you express stylistic writings, spelling, and punctuation to add emphasis in a paper or just separation. Grammar is constantly changing to suit society and is never set in stone. Just over the past couple of years passive verbs such as “were” and “was” have been replaced by got”. So instead of the sentence being “the rats were RDC’d”, the sentence would now be “the rats got RDC’d”. That is just one example of many on how our usage of language and grammar constantly changes with society.

Rhetoric has changed a lot since it was first developed and will continue to develop even further in the future. Grammar changes with society’s needs of communication and will always be in constant evolution. Accessibility of rhetoric will also continue to change as new technology continues to make it easier and cheaper to access and also more portable to the extent that you are not bounded by your Wi-Fi signal. It is exciting that we live in a time where we are at the beginning of a major revolution of rhetoric where the internet gives everyone their own private Library of Alexandria.

A Review of Atrial Septal Defects and Ventricular Septal Defects in Congenital Heart Disease and Possible Gene Therapy of the GATA4 Gene Using Retroviruses

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A Review of Atrial Septal Defects and Ventricular Septal Defects in Congenital Heart Disease and Possible Gene Therapy of the GATA4 Gene Using Retroviruses

Fisher, G.D., Johnson, L.K., Purdy, C.D., and Sanders, J.P.

2015

December 11th, 2015

Help Received: Group Project

Congenital Heart Disease (CHD) is a condition that disrupts the functionality and structure of the human heart. CHD is a growing issue, resulting in 8.1 per 1000 live births in North America, and 9.3 per 1000 live births in Asia. Globally, CHD results in 1.35 million infants born each year (Fahed et al. 2014). CHD is brought about by the inheritance of genetic predispositions, or the environment’s influence on the activation of those predispositions in the course of embryogenesis. Of all of the types of CHD present in the population, the most common are Ventricular Septal Defects (VSD) and Atrial Septal Defects (ASD).  

These septal defects can develop into structural issues in the ventricular and atrial septums of the heart. VSD and ASD are characterized by the perforation and weakness of the fibers composing these septums, which results in incomplete septal closure or leakage. This may result in the mixture of non-oxygenated and oxygenated blood in the chambers of the heart (Aasal et al., 2014). Both septal defects display the same phenotypes, which includes: lethargy, labored heart rate, increased muscle fatigue, poor circulation, higher BMI, and lowered ability to process oxygen. Further symptoms include ventricular and atrial dysfunction, pulmonary hypertension, and arrhythmias of the heart (Geva, et. al., 2014). These phenotypes are due to a molecular cascade, which controls the expression of both VSD and ASD.

VSD, on a cellular level, is characterized by a distinct molecular cascade which has been directly linked to the formation of the heart during embryogenesis (Broderick, et. al., 2012). Patients with VSD and ASD have cardiomyocytes that are incapable of building complete or robust actin fibers, and as a result, never form strong smooth muscle fibers. This is due to  lowered activity in a protein known as Vasodilator-stimulated phosphoprotein (VASP), which is responsible for recruiting profilin bound actin monomers for cell usage in creating actin fibers (Ali, et. al., 2015). Overexpression of VASP protein through hypomethylation leads to ASD (Gertler, et. al., 1996). Similarly, underexpression of VASP protein through hypermethylation leads to VSD. If cardiomyocytes are incapable of generating complete actin fibers that are durable enough to withstand the stress of usage, blood will be able to leak through the septal wall. This leaking leads to the common symptoms of CHD, specifically septal defects.

Heart development requires precise control of gene expression patterns, and disruption of transcriptional networks in heart development causes CHD (Wamstad et al., 2012). The disruption of this cascade usually begins with a mutation in both the Nkx2-5 and GATA4 genes, which are precursors of the molecular cascade directly involved with cardiogenesis (Misra, et.al., 2012). When operating normally, these genes regulate each other along with the expression of the Tbx-5 gene (Krause, et. al., 2004). The Tbx-5 gene, in turn, secretes a transcription factor which increases the expression of two genes, NPR-A and NPR-B (Krause, et. al., 2004). NPR-A and NPR-B both code for receptor proteins that, when bound with Atrial Natruiretic Peptide (ANP) protein, stimulates a catabolic metabolism in the cell responsible for breaking down GTP (Lowe, et. al., 1990). GTP is then broken down by the cell into cyclic guanosine monophosphate (cGMP), which is designed to bind with cGMP-dependent protein kinase (PKG) (cGMP-PKG signalling pathway, 2015). This complex that is formed then stimulates the VASP gene to be expressed more, allowing for the cardiomyocyte to build proper actin fibers,generating healthy smooth muscle for the heart. (Ali, et. al., 2015) As long as GATA4 or Nkx2-5 is mutated in an inhibitory fashion, then this entire cascade will be severely suppressed in the embryo, and VSD will likely be expressed. (Bouchard, et. al., 2008)

A patient with an inherited allele for heart disease, the wild type allele, results in the complete function of the VASP protein and, as a result, the proper formation of the ventricular septum. The mutated allele alters the function of at least one of the genes involved in the GATA4 signalling pathway. (Broderick, et. al., 2012) This alteration can inhibit the cascade directly, leading to the lowered effectiveness or activity of the VASP protein, and may directly cause ventricular septal defects in patients. There are several recorded mutations of GATA4 which directly lead to the disfunction of the gene, both in its expression and its ability to be read. The mutation rs804280 of GATA4 has been associated with VSD through the reduction of readability in GATA4; because of this inhibitory mutation, the molecular cascade leading to the secretion of the VASP protein would be stopped and ultimately cardiogenesis would be altered. (Mattapally, et. al., 2015) G296S is yet another mutation of GATA4, but this mutation is a missense mutation that leads to the lowered interaction of GATA4 with Tbx-5, creating a disconnect in the molecular cascade,which results in little to no VASP secretion, ultimately generating a VSD phenotype. (Misra, et. al., 2012)

The development of patients with VSD and ASD may be strongly affected by environmental factors that they were exposed to in utero. Similarly, smoking in the mother, exposure to Bisphenol A (BPA), and air pollution have also been correlated with the incidence of congenital heart disease being developed in offspring.  Maternal exposure to BPA during pregnancy may induce the ventricular septal variation of CHD by binding to the NPR-A and NPR-B receptors in an embryo, inhibiting the stimulation of guanyl-cyclase metabolism thereby stunting or stopping the molecular cascade necessary for cardiogenesis in the offspring. (Kang, et.al., 2014) BPA is an estrogen mimic, which is a precursor to the nitric oxide (NO) molecule through nitric oxide synthase (NOS). BPA induces oxidative stress on the NOS, causing a under or over expression of NO. (Chouhan et al. 2015) This molecule is used in the excitement of the cGMP-PKG complex and helps with binding affinity to the VASP protein. With low nitric oxide levels, binding of the VASP protein and the cGMP-PKG complex can not be completed correctly, leading to a misuse of the VASP protein.  A plausible line of effect has also been drawn between perfluoroctanes (PFO’s), a chemical emission and common air pollutant, and the development of VSD in embryo’s. PFO’s inhibit the activity of Pol β, a polymerase used to correct mutations in DNA through excision repair. If this enzyme is inhibited, the mutation of a gene in the molecular cascade used in cariogenesis could lead to a lack of VASP protein activity, and consequently the malformation of the ventricular septum. (Nakamura, et. al., 2007)

Changes in genomes are not the only alterations that may lead to the creation of the VSD phenotype in offspring. The alteration of an epigenome may also create congenital heart disease through the silencing or overexpression of key genes. Smoking during pregnancy can alter the epigenome of the respective embryo through DNA methylation. (Lee, et. al., 2013) Chemical components of cigarette smoke have been proven to recruit DNA methyltransferase (DNMT) to cells exposed to the smoke. DNMT’s are enzymes involved with DNA methylation, and may methylate key genes involved with the molecular cascade that guides cardiogenesis in embryos. (Jin, et. al., 2013) If DNMT’s hypermethylate VASP, causing gene silencing, then the cascade leading to VASP protein activity will be inhibited or nullified, and ventricular septal formation will not execute properly. (Lee, et. al., 2013) VSD may also be induced and inheritable due to methylation of genes during folliculogenesis (maturation of the ovarian follicle) in diabetic conditions. Mothers with diabetes during pregnancy expose their oocytes to diabetic extracellular environments, which are poor in nutrients; this effectively lowers the overall metabolism of the cell, and as a result, the cells have lowered enzymatic activity and poor gene expression. (Ge, et. al., 2013) Lowered gene expression in these cells leads to the lack of secretion of proteins that are instrumental in the operation of cardiogenesis. Epigenetic alterations, like smoking may also create other septal defects, such as ASD. The hypomethylation of any genes in the molecular cascade leading to VASP brought on by exposure to cigarette smoke has been shown to create Atrial Septal Defects (ASD) in embryos, rather than VSD (Gertler, et. al., 1996).

 

Cure

This cure is a theoretical, one-treatment solution, specifically in patients who suffer from VSD due to a mutated copy of the gene GATA4. In light of the molecular cascade caused by GATA4, illustrated in the flow chart attached, and its imperative role in the proper conduction of cardiogenesis, this cure seeks to nullify the negative effects of a faulty copy of the GATA4 gene. It has been designed to work only for fetuses who exhibit ASD and VSD as a result of a broken copy of GATA4.

This would entail the use of a retrovirus carrying the correct copy of GATA4 being injected directly into the fetus’ heart using an amniocentesis needle. The cardiac catheterization or the amniocenteis needle in this case, is used when there is no ability to perform surgery, because of the pregnancy it would be a less invasive alternative for altering the heart of the fetus.(Minette et al. 2006)  This needle would incorporate the correct form of the gene into the dividing cells of the heart as the fetus grows through the use of transduction.  Because the original copy of GATA4 in the fetus is broken, the insertion of a correctly functioning gene copy should allow for the cells to express GATA4, in turn generating the cascade that leads to genesis of a properly formed septum. Although development of the heart is already structurally completed by the time of treatment, most of the growth of the organ remains. Due to this potential in cell development, the constitution of the ventricular septum may still be partially compensated for in its structure by the expression of the remaining correct copies of GATA4 (Moorman, et. al., 2003).

Patient progress should be documented and monitored using ultrasound or any viable high resolution three dimensional imaging system in order to clearly track the continuing development of the heart. A 40-MHz ultrasound could show the progress over the development and show structural integrity of the given area, this has already been shown in a recent study on mice that this could work (Srinivasan et al. 1998)

In an ideal setting and outcome, the ventricular septum should show gradual thickening over a long period of time. Secondarily, the level of blood oxygenation in the patient should be a good indicator of effectiveness of ventricular septal thickening. This is due to the lack of blood mixing through the ventricular septum, as was previously occurring in trace amounts before treatment. A good response to treatment in the patient should be characterized by the oxygenation of the arterial blood in the patient should be much higher after a month or so of cell growth.

Not all patients will be eligible for this kind of treatment, unfortunately. Patients affected with CHD who do not suffer from a septal defect, will not be able to be treated by this proposed cure. While this treatment may not be universal in its application, it is a viable way to administer a gene therapy to a developing child that may be afflicted with the disease. Of course, there must be reasonable evidence that the child is going to be afflicted with VSD when it is born, due to the dangerous nature of the procedure, and the likelihood of terminating the pregnancy should the procedure fail.

Gene expression flowchart of CHD

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