Choose one for me Essay Example | Topics and Well Written Essays - 1000 words

Choose one for me - Essay Example Regarding my background, I am the youngest child in our family. Since my father died, my eldest brother has made most of the important decisions. At a young age, he had been in charge with a number of responsibilities. Since childhood, I have learned to show respect to my elders. My mother and older siblings have always emphasized the value of politeness. It is always nice to show gratitude to one’s parents and other relatives. I have been taught that being thankful is a way of showing good conduct. In relation to political behaviour, I have realized that my family background has influenced me to be docile to authority. I have found it almost impossible, if not totally unthinkable, to go against leaders. I have also noticed that I tend to be quite conscious of the tone of my voice when I talk to older people. Actually, people who do not display proper behaviour when communicating with authority or the elderly often irk me. It has also been natural for me to follow rules. Most of the time, I become tensed and check if I am obeying standards when a symbol of authority is nearby. In connection with my relatives, I am proud to say that my roots are from the ancient Arab tribe. Our ancestors were the first inhabitants of the Arabian Gulf. They have initiated the civilization that we are enjoying today. With this history, I have become honoured of my origin. It is also one of my values to be loyal to fellow Arabians. I can say that I regard my heritages with high esteem. This is reflected in my choice of songs. The genre I enjoy listening to is Arabian music. Moreover, I honestly think that my culture is rich with colourful rituals and customs. In addition, Arabian arts and crafts portray interesting painting, delicious dishes, and graceful calligraphy. It would be ideal for our country to continually develop and retain its high-income economy status. I believe that our leaders can do their best in governing the different

Cell-Permeable Stapled Peptides from HIV1 Gene Products

Cell-Permeable Stapled Peptides from HIV1 Gene Products Cell-Permeable Stapled Peptides Based on HIV-1 Integrase Inhibitors Derived from HIV-1 Gene Products Introduction HIV-1 Integrase (IN), is necessary enzyme for the replication of the virus into the host cells. It catalyzes the integration of viral DNA into the genome of host cells. The mechanisms employed by the enzyme are strand transfer and 3†²-end processing reactions. The enzyme is vital for the virus life cycle and as a result it is a target for anti-HIV-1 drugs. It is reported from previous studies that HIV-1 protein Vpr has inhibitory effect on Integrase activity. The inhibition is a result of protein-protein interactions. Specifically Vpr interacts through its C- terminal domain. Results from previous studies indicate that the active petptide inhibition motif is peptide 1 (Figure 1). Figure 1. Amino acid sequences of peptides 1 and 2, and outline of the study. Regarding the SAR studies, E-K pairs were introduced in i and i + 4 positions to increase the helicity, by forming salt bridges. In the same study to peptide 1 was added an octa-arginine tail, the purpose of which was to improve, cell permeability. The presence of the octa-arginine tail however resulted in increase of cytotoxicity of the peptide. The hypothesis on which the current study was based is that by finding a different way to improve cell permeability without the 8-R tail the cytotoxicity of the peptide would decrease. The idea was to make the peptide more lipophilic, by adding hydrophobic groups on the external of the a-helix, and at the same time improve its helicity. An available method to achieve that is the use of a-helix stabilized peptidomimetics. Specifically, hydrocarbon stapled peptides, in which a hydrocarbon link is formed between successive turns, via a ring closed metathesis (RCM) reaction, were used. By having a hydrocarbon linkage between positions i and i+4 in the a-helix, the helicity is improved because the two positions are covalently bound via the hydrocarbon chain, and simultaneously the lipophilicity and cell permeability of the peptide is increased because of the presence of a hydrophobic hydrocarbon chain on the external part of the a helical structure. In Figure 1 is presented an outline of the study. Design and synthesis of the peptides The lead peptide sequence used was sequence 1 (Fig.1). From previous studies it was known that residues: Phe12, Ile13, Phe15, and Ile17 are vital for IN inhibition activity. Stapling was performed between i and i+4 positions by avoiding substitution of these residues. Protected linear peptides were constructed by Fmoc-solid phase peptide synthesis. The RCM reactions of the protected linear peptides were performed on the resin by treatment with ruthenium-mediated Grubbs second catalyst in 1,2-dichloroethane. All hydrocarbon and all ether stapling was performed, however the first technique resulted in higher yields as it’s presented in Table 1. After RCM, the peptides were deprotected, acetylated, and cleaved from the resin. Purification of the stapled peptides was done by HPLC. However it is not the purpose of this paper to present experimental details. Table 1. Sequences of Designed Stapled Peptides and Their Conversion Yields of RCM Reactions CD Spectroscopy of Linear and Stapled Peptides. CD Spectroscopy was used to analyze the secondary structures of the synthetic stapled peptides, 3S−9S and 11S. Linear peptides, 4L−6L, 8L, 9L, and 11L, were used as control (Figure 3). Negative peaks at 208 and 222 nm, are characteristic for ÃŽ ±-helical structures. All stapled peptides, except 3S, formed ÃŽ ±-helices. The corresponding linear peptides on the other hand including compound 1 showed a broad negative peak around 215 nm, which indicates a ÃŽ ²-sheet structure. It is obvious that stapling of the linear peptides leads to the formation of ÃŽ ±-helices. Figure 3. CD Spectra of stapled peptides (left) and corresponding linear (right). Integrase (IN) Inhibition Assays and MT-4 Luc Assays (anti HIV). The next step was to determine the potency of the synthesized peptides using integrase inhibition assays. IC50 values were determined for stapled and linear compounds regarding both 3-end processing and strand transferring reactions (Figure 4 Left). Anti HIV activity was also screened for all peptides using MT-4 Luc Assays (Figure 4 Right). Figure 4. IC50 Values (Left). MT-4 Luc Assay (Right) All compounds had integrase inhibition activity, however lead compound 2 was way more potent. Regarding the MT-4 Luc assays compound 6S showed similar anti HIV activity as lead compound 2 at concentrations higher than 2.5 um. Compound 8S also showed significant activity at concentrations higher than 5 um. 6S and 2 have almost the same level of anti-HIV activity in cells, however 2 has much higher IN inhibitory activity in vitro than compound 6S. Imaging Experiments Stapled and linear peptides were labeled with fluorescein and imaging experiments were performed to examine their cell permeability. The stapled peptides 6S and 8S demonstrated improved cell permeability compared to the lead compound and the linear peptides. Octaarginine tail functional role investigation. The next step was to study the functional role of the (Arg) 8 tail, besides influencing cell permeability. By using 6S and 6L as lead compounds, a new set of peptides was synthesized (Figure 5). Specifically conjugates of 6S with octaarginine (17) and with the quartet repeat of arginine and glutamic acid (18). For 6L, with the quartet repeat of arginine and glutamic acid (19), and the conjugates of 6S with tetra-arginine (20), penta-arginine (21), hexa-arginine (22), and hepta-arginine (23). IC50 values were determined for the new set of peptides and also MT-4 Luc assays were performed. The presence of the octaarginine tail is necessary for the inhibitory activity however it still makes the peptides cytotoxic. Different lengths in the Arg tail were also examined. Still the octaarginine (17) conjugated peptide is the most potent but compounds 22 and 23 had good potency and lower cytotoxicity than 17, so those compounds were selected as lead compounds for further development. DNA binding experiments were also performed to examine the role of Arg8 tail, and the results indicate that 17 has high DNA binding affinity and that might influence the high inhibition activity of the peptide. Conclusions and Critical Review Stapling caused a significant increase in ÃŽ ±-helicity and cell membrane penetration, and in the expression of potent anti-HIV activity in cells. Stapling and the addition of octa-arginine caused cell membrane penetration. Stapling by itself did not involve cytotoxicity while incorporation of octa-arginine into the structures increased the cytotoxicity of the compounds. Generally it was a well-organized paper. It had good flow of information and background information was provided. The hypotheses were not stated but were easy to understand. The experiments and the data supported the conclusions and the concepts. The figures and the graphs were interpretable and accurate in supporting the conclusions related to them. However there are several interesting points to be addressed. The first point is the configuration of the new double bond formed. It would be interesting to see if the configuration of the double bond would affect the secondary structure and the helicity of the peptides. Another question that need to be addressed is why the stapled peptide 3S did fold into b sheet structure unlike the other stapled peptides which formed a helices. It would be interesting to examine the role of the substituted amino acids of 3S, in the folding of the peptide. Regarding the role of the octaarginine tail, the DNA binding experiments indicate that the octaarginine conjugated peptide has affinity for DNA binding. However it is unclear how exactly the tail affects the potency and the cytotoxicity. Further experiments are necessary to clarify that. I would suggest some NMR experiments to investigate the binding. First 1H-15N HSQC may be performed to the (Arg)8 fused peptide before and after binding with DNA. That would show which residues are involved in binding and would give data to determine the specific interaction. References: Nomura, Wataru, et al. Cell-Permeable Stapled Peptides Based on HIV-1 Integrase Inhibitors Derived from HIV-1 Gene Products. ACS chemical biology 8.10 (2013): 2235-2244.

Benjamin Franklin :: American History

Benjamin Franklin Benjamin Franklin has influenced American technology, and indirectly, lifestyles by using his proficiencies and intelligence to conduct numerous experiments, arrive at theories, and produce several inventions. Franklin's scientific and analytical mind enabled him to generate many long lasting achievements which contributed to the development and refinement of modern technology. Few national heroes, including George Washington and Thomas Jefferson, played a more significant role in shaping the American way of life than Franklin. According to Fowler, "He personified the ideal of the self-made man, and his rise from obscurity to eminence exemplified the American dream" (32). Looby adds, "The study of Franklin's image for the past two centuries shows that his legacy had a distinctive place in American culture" (85). It has been felt by many people over the years that there was no United States inventor as great as Franklin until the time of Thomas A. Edison (Blow 24). Franklin's words to a friend in Pennsylvania, Joseph Huey, best explain his attitude not only toward what he considered his civic duties, but also his investigations as a scientist or philosopher. He made some of the most famous and certainly the most practical discoveries of his time. "For my own part, when I am employed in serving others, I do not look upon myself as conferring favours, but as paying debts. In my travels, and since my settlement, I have received much kindness from men, to whom I shall never have any opportunity of making the least direct return . . . I can therefore only return on their fellow men; and I can only show my gratitude for these mercies from God, by a readiness to help his other children and my Brethren" (Dineen 6). Wright quotes Franklin as saying, "As we enjoy great advantages from the inventions of others," and, "we should be glad of an opportunity to serve others by any invention of ours" (19). Franklin summarizes his attitude toward his inventions by asking the question, "What signifies Philosophy that does not apply to some use?" (Fleming 21). Another time Franklin is quoted as saying, "Utility is in my opinion the test of value in matters of invention, and that a discovery which can be applied to no use, or is not good for something is good for nothing" (Burlingame 39). Franklin never claimed a penny for any of his inventions, devices or experiments. He even distributed detailed plans of some of his inventions so that anyone could own them.

Images of nurse and nursing Essay

The article entitled â€Å"Perceived and real barriers for men entering nursing: Implications for gender diversity,† aimed to explain the barriers, whether perceived or real, for men seeking a career in nursing. It is theorized that the public image of nursing is that of a traditional feminine career. However, in lieu with the recent nursing shortage that has been plaguing the country, it is speculated that men remain as an untapped reservoir of potential nurses and need to be targeted through recruitment strategies (Roth & Coleman, 2008). The authors established in their paper that if the barriers, whether real or perceived, can be addressed to suggest strategies that can ameliorate these barriers, then the recruitment of males into the profession may help in providing more nurses to fill the shortage. The image of nurses has been long depicted as a young female taking care of the ill and subordinate to male physicians and administrators (Roth & Coleman, 2008). These women are also perceived as not capable of making important decisions and were handmaidens to the physicians. Furthermore, it was researched that according to most students the reason why they did not choose to enter the nursing career is because of a perception that they would not attain job satisfaction and the second was that nurses were too squeamish (Roth & Coleman, 2008). Most young men believed that nursing is a profession for females and that they have fears of being perceived as gay or being feminine. Other barriers mentioned was the absence of the historical contributions of nurses who were male, considering that most nursing texts use the pronoun â€Å"she† in referring to nurses and that nursing education programs have been unsuccessful in creating an environment that is conducive for men, e. g. the lack of male professors and clinical instructors. However, there are still a few men who have chosen to enter the nursing profession and a major factor that engrossed men to the nursing profession was the influence of parents, specifically mothers, which are employed in nursing or other healthcare professions. Also, most men in the profession had previous careers and perceived their nursing career to be better than anticipated. The authors suggest that to ameliorate the current barriers, the public perceptions of nursing that create barriers for male nurses has to be challenged. Other suggestions that they presented include the increasing the number of males in the nursing academia and communicate through scholarly articles how gender diversity has enriched the profession. The discussions in schools should include more often the history of men in nursing and that they should also target nontraditional male students that are older and diverse. In response to this article, I deem that there is a truth to what the researchers have speculated that there is perceived barriers that inhibit the males from entering the nursing profession. In lieu with this, the suggested ways in how to ameliorate the situation can help in possibly encouraging the men in joining the profession. It can be noted that majority of the nurses, whether or not working in the clinical setting, students or professors teaching in the academia are females. It has been greatly noted that many male nurses have made the profession more diverse and the physical attributes of males are needed in certain nursing work. Being a nurse, whether or not one has the passion for it and considers it a calling, or was just a nurse by chance, should always bear in mind that this is a profession that only aims to care and hope for the best in the client or the patient’s wellbeing. Furthermore, I deem that the nursing profession should not have any gender biases, as it is a profession that only seeks to care for humanity, both males and females.

The Way You Speak

Yelling, making snarly comments, talking in what as well be a different language to most people are just parts of the way you speak. Depending on the situation you are going to speak differently. If you are at Work, with your friends, or with your family more than likely you talk almost as a different person. At work you should be acting professional and speaking in a more proper way. Using more of a â€Å"Yes sir† way of speaking is the way to talk.However different jobs would call for a certain way to talk. My job for example isn’t very formal or even professional. I work with people I’ve known for years, so I really don’t change the way I talk unless customers are around; then I become a completely different person. I become a cheerful, nice, and talkative person which isn’t really me at all. Loud, offensive, funny, rude, or downright wrong more than likely you’re talking with your friends.The things you say around your friends might seem mean to other people but to you and your friends it’s normal to you. For example, with my friends we say things that seem stupid and out of context to most people but to us it makes perfect sense. Every group of friends is going to speak differently, completely informal for the most part. If your family is anything like mine, nothing is off limits. I talk almost the exact same to my family as I do with my friends.Maybe less swearing, but virtually the same language. Unless I’m around my grandparents then I turn into a kid again and don’t say anything they wouldn’t approve of. Obviously every situation calls for different language, whether it be talking to someone new, your friends and family, or your boss. Every way is going to be different from the last. Friends and family usually don’t care how you talk, but your boss is a completely different story.