Wednesday, April 29, 2020
Rap Lyrics Essays - Music, Universal Music Group, Performing Arts
Rap Lyrics Poetry is language that is more intense than the ordinary language. The elements of poetry make it recognizable that there are techniques and styles that add to this intensity. These elements can be found in the lyrics of many rap songs, especially within the lyrics of "What's It Gonna Be" by Busta Rhymes and Janet Jackson. Rhyme is the most practiced element of poetry. It is defined as being the repetition of sounds in language. You can find this repetition within many verses of "What's it Gonna Be". For example, in verse one "Baby just tell me how you feel, we livin it and just givin it to you real". The two ending words "feel" and "real" gives the song a rhyming effect. Another example of rhyme is in lines eight and nine of verse one. These lines say, " To my people who regulatin the dance floors, better step in yo business and handle yours. "Floors" and "yours" also add the rhyming effect of this song. The rhyme in "What's it Gonna Be" classifies this song as being somewhat poetic. Poetry communicates experience, and experience comes to us largely through the senses (seeing, hearing, smelling, feeling, and touching). Imagery is a mental and visual impression that appeals to one of the five senses. Visual imagery is a sense thats expressed throughout "What's it Gonna Be". For example, verse two line twelve says, "Paintin a picture I see it's hot on the window". "See" is the keyword in line twelve that shows visual imagery. Hearing is another sense that's used frequently within this song. For example, the chorus says "Gonna make, gonna make, your body scream out yeah!" This verse is very effective in expressing the sense of hearing. When it is read, the exclamation mark brings this verse alive. If the exclamation mark wasn't there the keyword "scream" still classifies this as an example of imagery. Voice is another element of poetry that this song seems to have. The speakers in "What's it Gonna Be" are Busta Rhymes and Janet Jackson. The chorus is sung by Janet and the verses are rapped by Busta Rhymes. The tone of "What's it Gonna Be" is somewhat excited and fast paced. When you read the chorus it gives you an energetic feeling. For example, "Gonna make, gonna make, your body wet. Gonna make, gonna make, your body scream out yeah!" When reading this the commas and exclamation mark speeds up the pace of the song. Theme is the overall idea expressed within a story, song, or poem. The primary theme of "What's it Gonna Be" is sex. Busta Rhymes and Janet are telling the listeners of this song all the things they can do sexually. An example of this is, "And makin you women say (ahh) baby come on". Busta Rhymes has a somewhat "cocky" approach to sex. Janet Jackson also has this same "cocky" approach. For example, "Gonna make, gonna make, your body cream". When Janet refers to "cream" she's saying that she can make someone reach their sexual peak. Overall this song's theme has a very strong sexual meaning. Figurative language is defined as words that mean something other than the actual meaning. The majority of rap songs have a large amount of figurative language. "What's it Gonna Be" has a abundant amount of this. For example, "full fledge hittin with Busta Rhymes and Janet and you know its...". The word "hittin" means sex, so in other words this verse is saying "full fledge sex with Busta Rhymes and Janet". Another example of figurative language is, "Making you people just wanna bounce and get busy". "Bounce" refers to leaving and "get busy" means having sexual intercourse, so this verse says "making you people just wanna leave and have sex". In conclusion, "What's it Gonna Be" has very strong poetic elements. This song had rhythm, theme, imagery, and voice. Actually I couldn't find that many figures of speech, such as a metaphor or a simile, but I could find some figurative language. Overall I feel that this assignment made me realize how poetic some rap songs can be. This assignment also made me become familiar at recognizing the elements of poetry.
Friday, March 20, 2020
Overview of the Sepoy
Overview of the Sepoy A sepoy was the name given to an Indian infantryman employed by the armies of the British East India Companyà from 1700 to 1857 and later by the British Indian Army from 1858 to 1947. That change of control in colonial India, from the BEIC to the British government, actually came about as a result of the sepoys - or more specifically, because of the Indian Uprising of 1857, which is also known as the Sepoy Mutiny. Originally, the word sepoyà was used somewhat derogatorily by the British because it denoted a relatively untrained local militiaman. Later in the British East India Companys tenure, it was extended to mean even the ablest of native foot-soldiers. Origins and Perpetuations of the Word The term sepoy comes from the Urdu word sipahi, which is itself derived from the Persian word sipah, meaning army or horseman. For much of Persian history - from at least the Parthian era on, - there was not much distinction between a soldier and a horseman. Ironically, despite the words meaning, Indian cavalrymen in British India were not called sepoys, but sowars. In the Ottoman Empire in what is now Turkey, the word sipahià was still used for cavalry troopers. However, the British took their usage from the Mughal Empire, which used sepahi toà designate Indian infantry soldiers. Perhaps as the Mughals were descended from some of the greatest cavalry fighters of Central Asia, they did not feel that Indian soldiers qualified as real cavalrymen. In any case, the Mughals armed their sepoys with all the latest weapons technology of the day. They carried rockets, grenades, and matchlock rifles by the time of Aurangzebà who reigned from 1658 to 1707.à British and Modern Usage When the British began to use sepoys, they recruited them from Bombay and Madras, but only men from the higher castes were considered eligible to serve as soldiers. Sepoys in British units were supplied with weapons, unlike some of those who served local rulers. The pay was approximately the same, regardless of the employer, but the British were much more punctual about paying their soldiers regularly. They also provided rations rather than expecting the men to steal food from local villagers as they passed through a region. After the Sepoy Mutiny of 1857, the British were hesitant to trust either Hindu or Muslim sepoys again. The soldiers from both major religions had joined the uprising, fueled by rumors (perhaps accurate) that the new rifle cartridges supplied by the British were greased with pork and beef tallow. Sepoys had to tear the cartridges open with their teeth, which meant that Hindus were ingesting sacred cattle, while Muslims were accidentally eating unclean pork. After this, the British for decades recruited most of their sepoys from among the Sikh religion instead. The sepoys fought for the BEIC and theà British Rajà not only within greater India ââ¬â¹but also in Southeast Asia, the Middle East, East Africa, and even Europe during World War I and World War II. In fact, more than 1 million Indian troops served in the name of the U.K. during the First World War. Today, the armies of India, Pakistan, Nepal, and Bangladesh all still use the word sepoy to designate soldiers at the rank of private.
Wednesday, March 4, 2020
How to avoid bias when hiring new employees
How to avoid bias when hiring new employees At this point, you could probably recite employment discrimination law in your sleep. You know what you have to avoid, by law- religion, race, family status, etc. Not news to you. But while youââ¬â¢re already working hard to avoid straight-up discrimination into the hiring process, are you allowing its quieter, insidious cousin- bias- to sneak in through the back door and affect your hiring decisions?Understand the difference between conscious and unconscious bias.Bias is a part of human nature, to varying degrees. Itââ¬â¢s simply prejudice toward something or against another. And when bias is explicit, or conscious, it is pretty straightforward. Itââ¬â¢s thoughts and statements like:I donââ¬â¢t like people who are _______.à I prefer to associate with people who _______.à I want to hire someone who thinks like me on this particular topic.hbspt.cta.load(2785852, '9e52c197-5b5b-45e6-af34-d56403f973c5', {});à Basically, itââ¬â¢s a clear predisposition that you ackno wledge (even if only to yourself). Ideally, you donââ¬â¢t let these conscious prejudices sway your hiring, but at least itââ¬â¢s a known quantity that you can acknowledge and work on.Unconscious bias is a bit tougher. Itââ¬â¢s prejudice against people or ideas that you may not even realize you have. Unconscious bias includes assumptions or things that you might accept as ââ¬Å"trueâ⬠without realizing that theyââ¬â¢re stereotypes or generalizations. This includes thoughts and statements like:Women arenââ¬â¢t good at the hard sciences.[Cultural group] arenââ¬â¢t very hard workers.Men just arenââ¬â¢t very empathetic.[Cultural group] are good at math.See how those work? They may seem like theyââ¬â¢re based on ââ¬Å"how the world works,â⬠but really theyââ¬â¢re assumptions and prejudices that may have very little to do with the actual person in front of you, applying for a job.If youââ¬â¢re curious about your own biases and learning more about h ow this implicit bias works, the Harvard-developed Implicit Association Test (IAT) can shed some light (though you might want to be mentally prepared to learn some not-ideal things about yourself).Having unconscious bias doesnââ¬â¢t make you a bad person, or necessarily a racist/sexist/whatever-ist. It just means you need to do two things:Understand how your unconscious biases might be affecting decisions like hiring.Overcoming that to make sure youââ¬â¢re hiring based entirely on qualifications and fitness for the job, not assumptions.Making hiring based on biases may not be illegal (depending on what the bias is, and whether it affects a protected class), but in todayââ¬â¢s diverse, more-aware world, it can absolutely hurt your hiring and your company. You want to make sure youââ¬â¢re recruiting great people, full stop, but also that youââ¬â¢re doing right by your applicants. Overcoming bias also helps you with diversifying your hires, and bringing new perspectives to your company.Bias is a function of human nature, which means itââ¬â¢s not going away anytime soon. You canââ¬â¢t train it away, you canââ¬â¢t ignore it away, and you canââ¬â¢t policy-write it away. So that means you have to be more creative: make sure youââ¬â¢re taking it out of the hiring process as much as possible. Letââ¬â¢s look at some of the ways you can help eliminate- or at least reduce- bias in the process.Rethink your job descriptions.You might not think of job description wording as a potential source of bias, butâ⬠¦itââ¬â¢s the first place to look. Research has shown that women are less likely to apply for jobs that have ââ¬Å"masculine-codedâ⬠language, and vice versa (though to a lesser extent). And these are words you might not typically think of as one gender or another, but they carry unconscious connotations along the lines of ââ¬Å"men are aggressive, dynamic leadersâ⬠and ââ¬Å"women are consensus-builders and team members .â⬠Some examples of masculine-coded words:IndependentDrivenLeadingActiveSome examples of feminine-coded words:SupportCooperateHonestInterpersonalNone of these words are bad for a job description, per se, but itââ¬â¢s important to be aware of the connotations they can carry. If youââ¬â¢re concerned about your own job descriptions, this Gender Decoder for Job Ads can help you figure out what language you might be using that unconsciously discourages some applicants from even applying.Come up with an impersonal resume review system.Studies have shown that resumes can be rife with opportunities for unconscious bias- starting at the literal top of the document. Researchers have found that something as simple as a name that is easily recognizable as a particular ethnic group or gender can trigger bias in the hiring decisions. Some companies are removing that temptation by making sure names, photos, and any identifying info is removed from a resume before a hiring manager or rec ruiter reads it, but you donââ¬â¢t necessarily have to go to those lengths. It can be as easy as making sure you have a scoring system that ensures youââ¬â¢re evaluating resumes on the same playing field. For example: a certain number of points for a particular educational credential, or points assigned for different levels of experience. That way, each candidate gets a score based solely on whatââ¬â¢s in the resume- and not based on who you think the person is.Recruit more broadly.One of the biggest sources of bias in the hiring process isnââ¬â¢t racial, cultural, or gender-based: itââ¬â¢s education-based. Companies tend to be biased toward big names on resumes: Stanford, Ivy League, Wharton, etc. We gravitate toward those because theyââ¬â¢re well-known as top quality schools, but think about it: do you really need someone who paid for top-shelf education, or do you really need someone who brings the right skill set and experience to the job? Itââ¬â¢s probably the latter. The brand name doesnââ¬â¢t actually guarantee applicant quality, so open your mind to other schools, and make sure youââ¬â¢re looking at the full context. You may be dazzled by Candidate A, with the Yale pin on her jacket, but miss that Candidate B, with the State U education, has some stellar qualifications as well.If itââ¬â¢s that Yale has a great Computer Science program and thatââ¬â¢s what you want in your candidate, do some research on other top Computer Science programs, and look for candidates from those schools as well- schools that may not have quite the word-of-mouth impression that the Ivies have. Like with the personal biases, creating a name-agnostic point system (where certain educational qualifications, not necessarily the school names), are weighted.Set your criteria up front.Before you read a single resume or set up an interview, make sure youââ¬â¢re clear on the criteria you want to use to fill the position. Set your expectations of educa tion level, experience, skills beforehand- ideally in writing. If you use that rubric to evaluate candidates equally, youââ¬â¢re less likely to let ââ¬Å"gut feelingsâ⬠or other subjective reasons sway your hiring decision.Keep evaluating.Once youââ¬â¢ve done your best to eliminate bias in your hiring, itââ¬â¢s important to keep an eye on the process to make sure that bias isnââ¬â¢t sneaking back in, and that your efforts are effective. For example, if youââ¬â¢re trying to get more gender diversity in your applicants, but still find that youââ¬â¢re getting (or hiring) male candidates at the same rate as before, itââ¬â¢s time to go back and revisit the process again. Are there any more unconsciously biased phrases in the job description? Are you unconsciously giving preference to Male Candidate over Female Candidate for an arbitrary reason, or for a legitimate reason? Make sure youââ¬â¢re honest about the decisions youââ¬â¢re making, and why. And reme mber: itââ¬â¢s not that youââ¬â¢re a bad recruiter or a prejudiced person if you find that bias might be affecting your hiring decisions. Weââ¬â¢re all subject to bias at one time or another. But itââ¬â¢s never too late to acknowledge the sway that these biases can have (even when we think weââ¬â¢re being fair), and to be mindful about how to make the process more fair for everyone.
Sunday, February 16, 2020
Why computer talents become computer hackers Article
Why computer talents become computer hackers - Article Example In addition, the lack of moral values plays a role in encouraging them to engage in destructive activities. Young people are rebellious in nature. For those with computer talents, hacking provides an effective channel for demonstrating their rebellion. However, an individualââ¬â¢s judgment determines if they will engage in hacking. Many students who have an inclination to use their computer skills for illegal activities tend to attack school systems. The failure of high schools and colleges to punish these activities appropriately misses a significant opportunity to correct this behavior (Xu, Hu & Zhang 69). As a result, the young men and women perceive themselves to be invisible. In conclusion, it is possible to prevent young people having computer skills from engaging in hacking. They are driven to the activity out of curiosity (Xu, Hu & Zhang 69). A few young hackers engage in the activity for material or financial gain. Consequently, any effort to combat the rise of hacking in the modern society must involve effective measures to channel the curiosity among young people into a productive
Monday, February 3, 2020
Chinese women in globalized economy( Chinese women in marriage, family Assignment
Chinese women in globalized economy( Chinese women in marriage, family planning, and family responsibilities) - Assignment Example The Chinese traditional society regarded women as second class citizens who did not have the rights and freedoms that were enjoyed by men. It is not until 1949 that women began enjoying their rights. There were no equal education opportunities for boys and girls in traditional China as girls were regarded as passing members of the family who would be married off and therefore lacked long term economic benefits (Croll, 2005). According to Chatterjee (2003), the societal structures were modelled in a manner that placed women in an inferior position with a minor role of taking care of children and in-laws. They were expected to demonstrate humility in their subservient role. Women were regarded as ââ¬Ëpassive and unambitiousââ¬â¢ and hence were considered to be of no value to economic development in China. Some Chinese folktales depict the societyââ¬â¢s view of women that degraded womenââ¬â¢s status through such phrases as ââ¬Ëgirls are maggots in riceââ¬â¢ while argum ents of the greater value of geese than girls was a common semantic among many traditional Chinese families (Cheraghi, 2013). Croll (2005) observes that infant mortality was higher in girls than boys among underprivileged traditional Chinese families as a result of contempt by the parents and other community members. Becoming pregnant out of wedlock was regarded as an abomination for the girl and the family to the society yet the man involved went unpunished. Suicide was therefore common among unfortunate girls who got pregnant before marriage. Chinese parents ensured that girls were married off as soon as the mature, which made their stay at home transitory. No family could therefore ââ¬Ëwasteââ¬â¢ resources contributing to the intellectual development. Women were forced in to unhappy pre-arranged marriages for which they had no option. Cruel in-laws made it worse for women as they were not allowed go back to
Saturday, January 25, 2020
Role of E6AP in Malignancies and Tumorigenesis
Role of E6AP in Malignancies and Tumorigenesis INTRODUCTION Leukemia is a malignant hematological disorder characterized by proliferation of abnormal white cells that infiltrate the bone marrow, peripheral blood and other important organs. Leukemia arising from myeloid cells is known as Myeloid Leukemia which may either be chronic myeloid leukemia (CML) and/or acute myeloid leukemia (AML). AML is a complex disease caused by mutations, deregulated gene expression and epigenetic modifications leading to increased proliferation and decreased differentiation of hematopoietic progenitor cells. Several important molecular markers have been discovered in AML to better characterize patients. C/EBPà ± is an important regulator of Granulopoiesis. Several groups have reported mutations in the C/EBPà ± gene in a subset of patients with AML presenting with normal karyotypes. A significant percentage of AML patients without chromosomal translocations have demonstrated abnormalities in C/EBPà ± protein or function, suggesting that loss of transcriptional control is a common mechanism of leukemogenesis. Even in the setting of other proleukemogenic genetic abnormalities, such as the (8; 21) translocation, C/EBPà ± has been demonstrated to be aberrantly regulated, in this case by down regulation of expression. Functional alterations of C/EBPà ± in AML include mutations of the C/EBPà ± gene and deregulated expression of C/EBPà ± by chromosomal translocations. Further, post-transcriptional or post-translational suppression of C/EBPà ± has been demonstrated to be involved in hematopoietic malignancies. AML is also characterized as, a malignant disease of hematopoietic system in which cells accumulate in an undifferentiated state due to mutations that prevent their normal differentiation and allow undifferentiated cells to survive and proliferate. The molecular changes that occur in AML usually lead to either abnormal cell proliferation (FLT3 and Ras mutations) or block in differentiation (AML1/ETO, PML/RAR alpha, C/EBPalpha mutation s) or suppression of apoptosis (bcl2 overexpression). Despite of block in differentiation, native AML cells often show some morphological signs of differentiation that allow a classification into different subsets, and further differentiation may be induced by exposure to various soluble mediators, e.g., all trans-retinoic acid (ATRA) and several cytokines in t(15;17). All-trans retinoic acid (ATRA) is a derivative of vitamin A and it affects cellular development including haematopoiesis, in particular granulocytic differentiation. ATRA could induce a dose-dependent differentiation of HL-60 promyeloblasts to mature, functioning neutrophils. ATRA induces growth inhibition, differentiation, and apoptosis in cancer cells, including acute promyelocytic leukemia (APL). In APL, expression of promyelocytic leukemia protein retinoic acid receptor (PMLRARà ±) fusion protein, owing to the t (15; 17) reciprocal translocation, leads to a block in the promyelocytic stage of differentiation. E3 Ubiquitin ligases are a large family of proteins engaged in the regulation of protein turnover and activity through a multistep proteolytic cascade, called ubiquitination. Ubiquitination of a target protein involves 2 distinct steps: covalent attachment of multiple ubiquitin molecules to the protein substrates and degradation of the polyubiquitylated proteins by the 26S proteasome system. The first step is mediated by a cascade of 3 enzymes: ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin ligase (E3) [1, 2]. Ubiquitin is a 76-amino acid polypeptide that is highly conserved among eukaryotic organisms. It is first activated in an ATP-dependent manner via binding to E1 through a thioester bond between a cysteine residue at the active site of E1 and the C-terminal glycine (G76) of ubiquitin. Activated ubiquitin in an E1-ubiquitin complex is then transferred to E2, which also participates in the formation of a thioester bond between its active site cy steine residue and the G76 of ubiquitin. Finally, ubiquitin is covalently attached to the target protein through an is opeptide bond between the G76 of ubiquitin and the à µ-amino group of an internal lysine residue of the target protein, in a reaction catalyzed by E3 ligase. Subsequent to the linkage of ubiquitin to the target protein, a polyubiquitin chain is formed in which the C-terminus of each ubiquitin moiety is linked to a specific lysine residue (most commonly Lys48) of the previous ubiquitin to form K48-linked polyubiquitylated conjugates which are rapidly recognized by the 19S regulatory subunit of the 26S proteasome and degraded by the 20S core particle [1-3]. There are approximately 600 E3 ligases in the human genome that can be classified into 3 major types the N-end rule ubiquitin ligases; HECT-type; and the RING-type, on the basis of domain structure and substrate recognition[1]. The N-end rule ubiquitin E3 ligases target protein substrates bearing specific destabilizing N-terminal residues, including Arg, Lys, His (type I) and Phe, Trp, Leu, Tyr, Ile (type II)[1]. The second type HECT (homology to E6AP C-Terminus) E3-ubiquitin protein ligases, found from yeast to humans range in size from 80kDa to more than 500kDa. They are characterised by the HECT domain, a C-terminal region of approximately 350 amino acids in length with significant similarity to C-terminus of E6AP. Unlike RING E3s which act as scaffolds facilitating interaction between E2s and substrates, HECT E3 ligases form an intermediate thioester bond with the ubiquitin C-terminus through an evolutionarily conserved cysteine residue before catalyzing substrate ubiquitination. Hence, HECT E3s play a direct catalytic role in the final attachment of ubiquitin moieties to target proteins. The N-terminus is highly variable and may be involved in substrate recognition. On the basis of distinct amino acid sequence motifs within the N-terminus, human HECT E3s can be classified into 3 sub-families: HECT E3s with RLDs (RCC1-like domains, termed as HERC (HECT and RCC-1like domain E3s), HECT E3s with WW domains (called Nedd4/Nedd4- like E3s), and HECT E3s that neither contain RLDs nor WW domains (called SI(ngle)- HECT E3s). E6AP, the prototype of HECT E3 family belongs to the third sub-family of HECT E3 ligases [3-5]. The third and the largest type of E3 ligase is the RING (Really Interesting New Gene) family. RING-based E3 ligases are specified by over 600 human genes surpassing 518 protein kinase genes. These are characterised by a classic C3H2C3 or C3HC4 RING finger domain with a characteristic linear sequence Cys-X2-Cys-X9-39-Cys-X1-3-His-X2-3-Cys/His-X2-Cys-X4-48-Cys-X2-Cys, where X can be any amino acid. The RING domain provides a docking site for the E2 enzyme, which mediate transfer of ubiquitin to the substrate, facilitating assembly of mono- or polyubiquitylated conjugates via different lysine residues of ubiquitin. The resulting modifications have a diverse range of biological functions, from proteasome-dependent proteolysis (Lys48- and Lys 11-linked polyubiquitin) to post-translational regulation of protein function, structure, assembly, and/or localization (Lys 63 and other linkages)[1, 6]. E3 ligases can also be classified into single subunit E3s (e.g. Mdm2, Cbl) and multi-subunit complexes (APC, SCF). E3 enzymes bind their target substrates through various protein-protein interaction domains (e.g. WD 40 repeats). However, for substrate recognition post-translational modifications such as phosphorylation or proteolytic cleavage are required[7]. The modified motif in the substrate is called degron. There are many different types of degrons (e.g. phosphodegron, PEST). Once modified, a degron in a substrate might be recognized by a specific E3 ligase, which forms the basis for its subsequent ubiquitination[8]. Through ubiquitin-mediated covalent modification of diverse range of cellular proteins, E3 ubiquitin ligases regulate several cellular functions or biological processes such as cell cycle progression, Oncogenesis, signal transduction, transcription regulation, DNA repair, endocytois, transport and development via proteolytic or non-proteolytic mechanisms [2, 9]. A direct molecular link between cell-cycle control, Oncogenesis and E3 ubiquitin ligase activity was supported by several clinical findings and wealth of experimental data on E6AP, SKP2 and FBW7, Nedd 4-1, Pirh2, CDC20, CDH1 and also on other E3 ligases [3, 10, 11]. Understanding the physiological role of E6-AP, the founding member of the HECT E3 family, is of interest because inactivation of UBE3A gene encoding E6AP has been associated with Angelman Syndrome, a hereditary neurological disorder. Moreover, in the case of cervical cancer, the E6/E6-AP complex not only targets p53 for ubiquitin-mediated degradation, but also targets other proteins, which is necessary for HPV-induced cervical carcinogenesis[12]. E6-AP forms a stable complex with the adaptor protein E6. The dimeric complex binds to and targets p53 for ubiquitin-mediated proteolysis, thus eventually interfering with the negative growth regulating activities of this tumor suppressor protein [13-15]. In addition, the expression of E6-AP protein is decreased in human invasive breast and prostate cancers compared with their adjacent normal tissues. This down-regulation of E6-AP is accompanied by the elevation of ER in breast and AR in prostate carcinomas[16]. Furthermore, in vivo data fro m E6-AP-knockout animals indicated that the expression levels of ER and AR are increased in E6-AP-null mammary and prostate glands, respectively, when compared with that of normal control animals, suggesting that E6-AP modulates the protein levels of ER in breast and AR in prostate glands [17]. E6AP, a 100-kDa cellular protein is a member of functionally related E3-ubiquitin-protein ligases defined by the domain homologous to the carboxy terminus hect domain.20 E3 ligases ubiquitinate and degrade several regulatory proteins including p53, p27, promyelocytic leukemia retinoic acid receptor à ± and others, which serve as tumor suppressors and cell-cycle inhibitors. E6AP promotes C/EBPà ± ubiquitination leading to its proteasome-mediated degradation and thus functional inactivation. E6AP negatively regulate Granulopoiesis by targeting C/EBPà ± for degradation via ubiquitin proteasome pathway. Promyelocytic leukemia tumor suppressor (PML) has been recently identified as a target of catalytically active form of E6AP. PML tumor suppressor is essential for the formation of PML nuclear bodies. Recent studies have implicated role of PML and PML nuclear bodies in the regulation of growth inhibition, senescence and apoptosis. PML is down regulated in multiple human cancers and experimental data has correlated reduced PML activity and expression to E3 ubiquitin ligase activity of E6AP, regulating protein turnover and activity[18]. Recently, Annexin I involved in the inhibition of cell proliferation, regulation of cell differentiation, anti-inflammatory effects, cell death signalling, carcinogenesis has been identified as a novel target of E6AP in addition to classical substrates, including p53 tumor suppressor, PDZ domain-containing protein scribble, a transcriptional repressor of the gene encoding hTERT[19]. In addition, studies have also implicated the role of E6AP ubiquitin ligase activity in ubiquitin-dependent degradation of Peroxiredoxin1 and presumably open avenues to investigate the functional link between lack of E6AP expression and stability of Peroxiredoxin 1with regard to the pathogenesis of Angelman syndrome[20]. p53 is targeted for proteasomal degradation by mdm2 which is a p53 target gene containing E3 ubiquitin ligase activity[21]. While mdm2 targets p53 for degradation, mdm2 is self -ubiquitinated and degraded. Cyclin dependent kinase inhibitor p21waf/cip, another p53 target gene, is degraded by proteasome and GSK3 (glycogen synthase kinase 3) mediated phosphorylation [22]. Rb (Retinoblastoma) protein is a tumor suppressor and negatively regulates G1/S transition by interacting with E2F transcription factor. Rb protein is degraded in an ubiquitin dependent manner [23]. In addition, free E2F is also degraded in ubiquitin dependent manner by the 26S proteasome. Thus, collectively HECT domain containing E3 ligases are important for homeostasis of protein levels and defects in their function may lead to various diseases including cancer. Thus, wealth of experimental data and clinical findings identifying many substrates targeted by E3 ubiquitin ligases, indicate that the deregulation of Ubiquitin proteasome system in cell cycle control is tightly linked to malignancies and tumorigenesis. Due to the above relevance and role of E6AP in malignancies and tumorigenesis The project is based on the expression, purification and validation of GST tagged protein that is GST- E6AP. The current study includes Cell culture: HL-60 cells, a human promyelocytic leukemia cell line. HL-60 cells treated with 1uM ATRA for 0,24 and 48 hours. GST- E6AP Protein expression and purification: GST-E6AP Pull down: Objectives: 1) Expression of GST and GST-E6AP plasmids in BL21 strain of E.Coli 2) Purification of GST and GST-E6AP proteins from BL21 strain of E.Coli 3) Validation of expression through western blotting 4) To detect GST-E6AP protein interaction with whole cell lysates of HL-60 cells treated with 1à ¼M ATRA for 0, 24 and 48 hrs GOMTI NAGAR EXTENSION, LUCKNOW
Friday, January 17, 2020
Calox Case
Business Marketing CALOX CASE Section 1 Overview: The main player is Mike Brown who is the international sales manager for Calox Machinery Corporation. Brownââ¬â¢s situation is to decide between staying with his current New Zealand distributer Glade Industries or to switch to Calox New Zealand, Ltd. The main player for the new company is Geoff Wiggins who created G. W Diggers which he then sold and is now called Glade. Mr. Wiggins is now in charge of the new company Brown is highly considering to switch to. * Decision on which company to go with.Glade has ââ¬Å"gotten its act togetherâ⬠offers a new team of 3 sales executives opposed to Geoff Wiggins ââ¬Å"one man showâ⬠* Legal risks * If the new company fails than Calox is basically screwed. Section 2: Since both companies are battling for your business then a smart marketing ploy would be to try to get the best deal/package out of them. See what each company is willing to do so you keep them around. Alternating the prices to benefit your company and see which one is willing to accept. Give Glade a call and have them pitch to you how theyââ¬â¢re new team is going to increase sales and how they plan to market.Wiggins on the other hand resume speaks for himself but you can call him and ask how can he market better than Gladeââ¬â¢s 3 members. Lastly, another option would be favorable contract negotiation. Try to get a guarantee that the distributer will remain in business with Calox for x amount of years and see whoââ¬â¢s most willing. Section 3: facts 1. After Colax sent a letter that they were dropping Glade, Glade came back saying the restructured their sales staff with 3 new skilled employees and have already commenced targeting Wescotââ¬â¢s (major competitor) employees.On the other hand Mike Brown met face to face with Geoff Wiggins. What Brown got out of the interview was that Geoff is very affable, technically knowledgeable, and an excellent marketing person. Also Geoff founded what is now Glade and during his reign had about a 50% share of the New Zealand market. 2. Legal risks- ââ¬Å"sole distributer agreementâ⬠is what Glade and Colax had. However, in the case it is unclear of the potential severity of the legal risk. If the relationship is terminated and Glade sued than the amount of the case would probably be 10,000.With that being said itââ¬â¢s still a problem and it isnââ¬â¢t guaranteed they wonââ¬â¢t get sued for a lot more. Section 4: My recommendation to this case is to switch with Mr. Wiggins company. Clearly, Glade is in a downfall. Their company is a mess and canââ¬â¢t market Colaxââ¬â¢s products effectively. Wiggins on the other hand knows the market extremely well. Colax has had business with him in the past when he originated what is Gladeââ¬â¢s today. During Wiggins reign he had about a 50% share of the New Zealand market. Once Wiggins left Glade, the company has been in a downwards spiral.For these reasons I would terminate my agreement with Glade give them their 60 day termination notice and then sign the deal with Wiggins. The legal aspect of it is tricky. But, after reading the case and what the lawyers said was there was not really a probable claim since the agreement was signed when Wiggins was in charge and Gladeââ¬â¢s was called G. W. Diggers. The lawyers are not a 100% sure but they are likely that Colax could be threatened to pay approximately 10,000 dollars. With all this being said, Wiggins and Calox New Zealand, Ltd. would be the move I would recommend. Case closed! Enjoy your Labor Day vacation Mr. Brown.
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