System engineering Coursework Example | Topics and Well Written Essays - 250 words - 1

System engineering - Coursework Example Sometimes change is usually unpredictable, coming at time that an organisation does not anticipate it. In such a scenario, the way an organisation handles the change determines the adaptability that determines the recovery of the organisation. Various recommendations have been given on how to manage change in systems engineering. To effectively deal with change in systems engineering, it is recommended to follow a simple guideline. First identify the areas that change is required in the processes and justify the need for change. Secondly, assess and evaluate the possibility of positive results from a change in terms of dealing with stakeholders needs or coming up with a better product. Thirdly, change managers should implement the change in a process that does not disrupt the whole system. When a change is finally in place, it should be practiced to replace the previous process and made the norm. This should then be followed by periodic monitoring of the change as it is being impleme nted and evaluation of the whole process (Habhouba, Cherkaoui, and Desrochers, p.

History final in-class essays Essay Example | Topics and Well Written Essays - 1500 words

History final in-class essays - Essay Example These empires are one of the most important empires because they provide a lot of information and important documents concerning the Islamic culture and beliefs (Bryce, 2013). To begin with, the Ottoman Empire was formed around the beginning of 14th century and was the first empire to be formed among these three empires. It covers areas such as the North Africa region, Egypt, Syria, Arabia, Iraq, and the Balkans region. It was founded by a sultan known as Sultan Selim in 1512 and its boundaries covers Atlantic Ocean region to the whole Persian Gulf (Dinc & Yetim, 2012). The empire went in first battle of the Lepanto at around 1571 and later went in a battle where it was defeated in 1683 in Vienna. In addition, the empire is remembered as one of the great Islamic empires that brought modernization in the late 19th century that. Although it failed to improve the economic, political, and social process in its regions, it was seen to provide bigger impact on the cultural Islamic historic al life (Carnegie, 2013). The empire ruled until around 1600, where it reached its peak and later started to decline due to some internal lack of organization. Again, the decline was due to enemy pressure that was inflicted to the empire by the Europe and Asia enemies of the empire. Although the empire faced various challenges, it was it came to an end in 1918 after World War I. The empire is remembered as one of the great Islamic empires that gave rise to the present day country called Turkey. Again, the empire is also remembered as one of the empires that provided the link between the medieval revolution and the current Islamic historical information (Guidetti, 2013). The second great Islamic empire is known as the Safavid Empire that was founded in 1501 as a result of political changes in Persia. The empire is come from the name Safavid that was the name of Sufi order formed by the Sunnite mystic. Although Safi-ad-Din died in around 1334 the empire name was passed to Shiism at ar ound 1400 hence the name the Shiite Safavid Empire. Ismail became the head of Safavid in 1487 and ruled up to 1501 where he declared himself the Shah of Iran and established a dynasty that united and brought together Iran people and ruled them up to late 1722. Iran became more influenced by the western culture in the early 19th century leading to modernization, which brought about the Islamic religion of today. Besides the empire although formed in 1501was one of the great Islamic empires that was originated as a result of religious sect and acquired most of political as well as military characteristic. This empire was officially the empire of Shiite and some of the religious diversity he has led to conflict between it and the Sunni neighbors. Besides this is one the empires that ruled within the shortest time and was greatly affected by the invaders such as the Afghans which attacked them in around 1722. The empire is greatly remembered for its nationalism and it led to the formati on of the present day Iran country (Behbudi, 2013). The third empire is the Mughal Empire that was based in India and was founded in 1526 (Garcia-Rivero, 2013). The empire faced many challenges and was affected British empires. In addition, the empire gained from the succession of strong rulers that gave him the Hindu population

Staphylococcus Aureus: Structure and Functions

Staphylococcus Aureus: Structure and Functions Introduction 1.1 Staphylococcus aureus Staphylococcus aureus is an opportunistic yet versatile pathogen that can infect almost all types of tissue in the human body. 33-50% of healthy individuals were reported to be S. aureus carriers. The diseases resulting from S. aureus infection range from superficial infections; invasive infections such as endocarditis to the life threatening septic shock and toxic shock. The presence of foreign material greatly increases the risk of infection by providing a base for attachment and biofilm formation. S. aureus appears as clustered gram positive cocci under the microscope. Criteria used to identify this organism include the production of golden pigment on nutrient agar; being positive for coagulase; mannitol fermentation and the production of deoxyribonuclease. The virulence of the infecting strain and the nature of the host immune response are important determinants for the outcome of severe S. aureus infection . 1.1.1 S. aureus genome and regulation of gene expression S. aureus has a 2.8-2.9 Mbp circular genome. House-keeping genes and genes associated with central metabolism and some virulence determinants (e.g. protein A) are highly conserved among strains and make up the majority of S. aureus genome. The rest more variable regions mainly consists of mobile elements such as pathogenicity islands (SaPI, 7 identified), genomic islands (ÃŽ ½SaÃŽ ± and ÃŽ ½SaÃŽ ²), Staphylococcal chromosomal cassettes (SCC) and bacteriophages. S. aureus expresses an array of adhesins, immunomodulatory molecules; anti-inflammatory proteins and as many as 30 toxins to invade, evade and cause host tissue damage. Many of the virulence factors discussed below are encoded by genes located in the variable region. Their expression is under the control of a complicated and interconnected regulatory network . Four main gene regulators have been identified, including the two component regulatory system (agr, sae); the transcription factors (SarA and its homologous); the nutrient regulated CodY regulator and alternative transcription factor ÏÆ'B. agr is an auto-inducible quorum-sensing system, promoting expression of extracellular virulence factors and down-regulating cell surface proteins. ÏÆ'B has been shown to participate in the general stress response, and may be involved in antibiotic resistance; pigmentation; biofilm and micro-colony formation (referenced in ). Many surface proteins/adhesin have been shown to be positively influenced by ÏÆ'B, while the expression of most exoproteins and toxins were down-regulated. Activity ofthe agr system is influenced by other gene regulators and may be regulated by cell density. The transcription of agr components were found to be promoted by SarA and gene products of the sar locus and repressed by CodY. To add up the complexity, transcription o f the Sar locus was controlled by three promoters that can be differently activated during in vitro growth. One of these promoters was demonstrated to be ÏÆ'B dependent . It is generally regarded that exponential growth in vitro is correlated with the colonization phase of infection. Correspondingly, genes encoding surface proteins were found to be expressed earlier, starting during the transition from stationary to exponential growth while the expression of secreted proteins started at late-exponential growth phase. The in vivo situation of infection is likely to be more dynamic. Different stimuli trigger combined and coordinated action of the regulatory network, reflecting the particular state of bacterial growth, host defense and environmental nutrition. For example, phagocytosis by neutrophil triggered differential expression of 21.8-39.1% of S. aureus genes â€Å"at any time† following the event. The suppressive effect of CodY on S. aureus virulence factors lead to the possible suggestion that S. aureus may maintain its virulence factor to low level to ‘co-exist harmlessly with the host until a invading opportunity arise. In any case , it would be interesting to see how host immunological activity ‘feedback on S. aureus regulation of its virulence factors, especially immune evasion molecules. 1.1.2 Antibiotic resistance The rapid spreading of antibiotic resistant S. aureus strains through human communities presents a major challenge for conventional treatment. In 2005, it was reported that methicillin-resistant S. aureus (MRSA) infection caused more death than AIDS in USA. S. aureus demonstrated amazing ability to â€Å"co-evolve† with the development of antibiotics. The first generation penicillin uses ÃŽ ²-lactam to bind penicillin-binding proteins (PBP, bacterial transpeptidase) and inhibits bacterial cell wall synthesis. S. aureus resists this class of antibiotics by producing ÃŽ ²-lactamases (aka penicillinase) that cleaves ÃŽ ²-lactam. Second generation of penicillin, such as methicillin was developed. The structure of their ÃŽ ²-lactam has been modified to resist ÃŽ ²-lactamases. S. aureus soon acquired the mecA operon that encodes a modified PBP (PBP 2a), which showed reduced susceptibility for ÃŽ ²-lactam and thus granted resistance to all ÃŽ ²-lactam containing antibiotics. mecA is located on the staphylococcal chromosome cassette mec (SCCmec), a mobile genetic element that allows horizontal transfer of mecA between strains. MRSA infection shows increasing prevalence in all continents, primarily in healthcare-environments (HA-MRSA). Alarmingly, these strains have been shown to exhibit resistance to other types of commonly used non-lactam antibiotics such as ciprofloxacin and erythromycin. Vancomycin, a peptidoglycan polymerization inhibitor, is now considered as the last-line antibiotics for MRSA treatment. However, strains of vancomycin-intermediate S. aureus (VISA) have emerged. Notably, these strains have developed thicker cell walls that require higher concentrations of vancomycin to be effective (minimal inhibitory concentration MIC over 4ug/ml). A vancomycin resistant S. aureus (VRSA) strain has been reported recently (MIC >32 ÃŽ ¼g/ml). This complete resistance is most likely due to the horizontal transfer of the vancomycin resistant gene (VanA) from En terococcus faecalis. Development of effective new antibiotics against S. aureus has met with only limited success, urging the development of alternative therapies based on better understanding of the pathogenicityof S. aureus . 1.2 Adhesin / ECM interaction as key to S. aureus colonization/invasion Colonization is always the first step in bacterial infection and is an important component in pathogenesis. The wide range of tissues that S. aureus can infect reflects its ability to adhere and therefore colonize many different biological niches. S. aureus is now recognized as an invasive organism, targeting non-professional phagocytes such as keratinocytes, epithelial cells, endothelial cells and osteoblasts. The tasks of initial colonization and invasion are assisted by S. aureus surface anchored and secreted adhesive molecules known as MSCRAMM, microbial surface components recognizing adhesive matrix molecules and SERAM, secretable expanded repertoire adhesive molecules. The majority of MSCRAMM and SERAM bind extracellular matrix (ECM) proteins such as fibrinogen and fibronectin. In general, the interaction with ECM proteins is regarded as providing a ‘foothold for S. aureus to establish and to exacerbate infection. However, it has been reported that in some animal models l oss of fibronectin binding proteins (FnBPs) led to an increase in bacterial virulence, indicating a role of the ECM protein in limiting bacterial dissemination or enhancing bacterial clearance. Due to overlap in target specificity; functional redundancy and the difference in experiment settings, the exact contribution of each isolated staphylococcal adhensin protein remains ambiguous. Nevertheless, fibronectin (Fn) and fibrinogen (Fg) are the most popular targets of known S. aureus adhesins. The interaction between FnBPs and Fn is thought to play a key role in S. aureus internalization by non-phagocytic cells, as FnBP-coated latex beads and non-invasive bacteria expressing FnBPs were readily taken into the human cells (293 cells). Internalization provides several benefits for the bacterium: firstly, protection from host serum defense mechanisms and antibiotics ; secondly, access to nutrient-rich environments after escape from phagocytic vessels; thirdly, facilitating the crossing of the endothelial/epithelial layer and spreading of the infection; and lastly, establishing intracellular bacterial reservoirs for recurrent infection. S. aureus produces two related FnBPs (namely A and B) that contain almost identical Fn-binding domains in the close proximity to their cell-wall-spanning domain. The Fn-binding repeats of FnBPA were crystallized in complex with the N-terminal F1 modules of Fn. FnBPA peptide is inserted along the triple-stranded ÃŽ ² sheets of the Fn F1 module to form an antiparallel tandem ÃŽ ² zipper. Since the C-terminus of Fn interacts with ÃŽ ±5ÃŽ ²1 integrin that are expressed on most host cell surfaces, S. aureus can attach to the host cell through a Fn bridge. The attachment was shown to trigger the accumulation of actin and focal-contact-associated proteins (e.g. tensin) at the bacteria contact site and initiate internalization in a protein tyrosin kinase FAK-dependent manner. It was predicted that one FnBP can bind six to nine Fn molecules. This multivalent interaction was suggested to be important in mediating internalization . The bindings of Fg by the clumping factors (ClfA and ClfB) and FnBPA are mediated by a shared protein structure called the A domain and by a â€Å"dock, lock and latch† mechanism. Interestingly, Clf A is expressed during stationary phase and binds to the ÃŽ ³ chain of Fg. ClfB is expressed at the exponential growth phase and binds to the C-terminus of Fg AÃŽ ± chain. This portion of Fg has been reported to be involved in the coagulation process and wound healing . Fn and Fg interactions have been blamed particularly in S. aureus wound infection and infective endocarditis in humans. Fg binding alone could initiate experimental endocarditis in mice and has been correlated with valve colonization. However, cell invasion and persistence of the infection only occurred when the Fn-binding ability was enabled (via FnBPs). Both interactions were statistically correlated to disease severity. Binding to Fg and Fn simultaneously significantly accelerated the rate of internalization into cultured endothelial cells. In this regard FnBPA that is capable of binding both proteins may play an important role in establishing endocarditis . Platelets accumulation on the heart valve is another critical factor for the development of infective endocarditis. S. aureus-induced platelet aggregation is a complicated and multifactorial process and was suggested to be dependent on Fg or fibrin. FnBPA, ClfA, ClfB and SdrE (serine-aspartate repeat protein) were shown to be able to cause platelet aggregation independently of other S. aureus surface proteins. ClfA displayed the strongest aggregation effect among the last three. SdrE required the presence of plasma to cause aggregation, although the mediator was not identified. ClfA was proposed to interact with platelet indirectly through an Fg bridge or directly with platelet surface protein p118. Other studies have argued that ClfA-specific IgG also participated in platelet activation by cross-linking ClfA to platelet FcÃŽ ³RIIa receptor . 1.3 S. aureus toxinsdirect damage of host cells S. aureus produces a range of cytotoxins, including the ÃŽ ² barrel pore forming toxin (e.g. ÃŽ ± hemolysin); the two component pore forming leukocidins and the exfoliative toxin. Besides the effects of reducing viable phagocytes and weakening host immune system, S. aureus cytotoxins are currently believed to contribute to bacterial dissemination. Lysis of host cells might also provide nutrients for proliferating bacteria, especially iron from hemolysis . These toxins have different prevalence in different diseases. Exfoliative toxin (ET) operates at the epidermal layer of the skin and causes staphylococcal scalded-skin syndrome. ET-A acts as serine protease and specifically cleaves Desmoglian-1 (Dsg-1). Dsg-1 is a cell-cell adhesion molecule expressed on epidermal keratinocytes. Cleavage of Dsg-1 disrupts the superficial layer of epidermis and helps bacterial invasion. ÃŽ ±-hemolysin (Hla) is strongly implicated in S. aureus lung infections. Active and passive immunization of Hla strongly protected mice against S. aureus pneumonia. Hla is released as a water soluble monomer and oligomerises on the host cell membrane to insert the hydrophobic stem domains. Seven Hla monomers are required to form a pore which eventually leads to cell lysis. At sub-lethal concentrations of Hla, host cells produce pro-inflammatory cytokines like IL-8; IL-6; vasoregulators (PGI2, PGE2 and thromboxane), which could have detrimental systemic effect. The exp ression of twenty S. aureus virulence factors were disrupted individually or in combination and the virulence of the resultant deletion mutants were compared in a mice pneumonia model. Deletion of argA, which encodes a component of the arg gene regulation system, resulted in almost complete loss of virulence. Only the Hla deletion mutant produced comparable effects, indicating the importance of Hla in causing lung tissue damage. Human neutrophils can resist Hla lysis but these cells are targeted by Leukocidins. Leukocidins are thought to act in the similar way as Hla. Among the leukocidins, Panton-valentine leukocidin (PVL) is found in all CA-MRSA (community acquired-MRSA) isolates and strongly associated with CA-MRSA infection. However in mouse models of abscess, sepsis, and pneumonia, the severity of diseases caused by PVL- deletion strains were not significantly different from that caused by the wt strains. More surprisingly, PVL-expressing S. aureus strains did not lyse human ne utrophils better than that without PVL. However, it is not clear how these experimental conditions resemble the amount and time of PVL production during infection in human. Another significant problem is that PVL might be human specific and might not work in mice. Nevertheless, a new class of leukocidal molecules, the ÃŽ ± type phenol-soluble modulin (PSMÃŽ ±), was produced at a considerably high level by CA-MRSA. They were shown to contribute to the increased neutrophil lysis, skin lesion formation and mortality rate of experimental animals caused by CA-MRSA infection . 1.4 Interaction of S. aureus with host immune system 1.4.1 Brief overview of host defense against S. aureus Host defense against S. aureus mainly relies on the innate immune system, in particular, neutrophil mediated killing. The integrity of skin and mucosal layer is the first line of defense against invading bacteria. They also encounter antimicrobial substances released by epithelial cells and phagocytes (e.g. defensins; cathelicidins and lysosome). Defensins and cathelicidin are positively charged antimicrobial peptides that could permeate the bacterial membrane. Lysozyme is produced by many cell types and secreted into various tissues. It cleaves bacterial cell wall peptidoglycan at ÃŽ ² 1-4 glycosidic linkage between N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG). Innate pattern recognition receptors (e.g. Toll-like receptor 2) and immunoglobulin also detect the presence of S. aureus. The latter is recognized by C1q and initiates the complement classical pathway (CP) or directly activates phagocytosis through Fc receptor expressed on neutrophils or monocytes. The human comp lement system is discussed in more detail below. One outcome of complement activation is the production of anaphylatoxin C3a and C5a. Together with formyl methionine peptides produced by bacteria, these chemoattractants are sensed by their receptors expressed on leukocytes and attract leukocytes to the sites of infection. Leukocyte recruitment is accomplished through highly coordinated interactions between adhesins on leukocytes and endothelial cells. Leukocytes change from rolling in the blood stream to firm adhesion to the endothelium and then transmigrate through the endothelial layer. Subsequent migration of leukocytes to infection sites is mediated by integrin interacting with ECM proteins. Once they reach the infection site, the phagocytes recognize antibodies or complement fragments deposited on the bacterial surface through their respective receptors. Phagocytosis then occurs. The phagosome is fused to the lysosome to form the phagolysosome for enzyme-mediated and oxygen fre e radical mediated destruction . 1.4.2 The human complement system The human complement system is a sequentially activated proteolytic cascade that involves more than 30 fluid phase and surface bound proteins. It is one of the key elements of the innate immune system that connects bacterial recognition, leukocyte chemotaxis; phagocytosis as well as adaptive immunity . Three main activation pathways are utilized to recognize foreign and danger signals. The classical pathway (CP) senses antigen bound antibody by C1q. Bacterial carbohydrate ligand is recognized by mannose binding lectin (MBL) or ficolins and initiates the lectin pathway (LP). Upon ligand recognition, both pathways use their specific proteases to cleave C4 and then C2. The resultant C4b2a (the C3 convertase) converts C3 to C3a and C3b. The Alternative pathway (AP) starts by direct binding of C3b to the bacterial surface generated by spontaneous lysis of C3 to C3b called â€Å"tick-over†. Factor B that associates with surface-bound C3b is subsequently cleaved to Bb and forms the alternative pathway C3 convertase C3bBb. The amplification loop of C3 activation is started. C3 cleavage is the central event and merging point in the three pathways. Accumulation of surface bound C3b changes the substrate specificity of C3 convertase to C5. C5 cleavage produces C5a and C5b. The latter m ediates the formation of the membrane attack complex C5b-9 (MAC), which inserts into the target cell membrane and ultimately causes lysis of target cells. C3a and C5a are powerful anaphylotoxin that trigger neutrophil homing. The overall picture of this complex system is depicted in Fig. 1.1 MASP: mannose-binding lectin–associated serine proteases. Figure adapted from Walport et al 2001 (Ref.). Three main outcomes of complement activation are: 1, chemotaxis of leukocytes via C5a and C3a; 2, C3b mediated phagocytosis via complement receptors on phagocytes; and 3, lysis of bacteria by MAC. It is also suggested by recent studies that the C3b presented on bacterial surface are critical factors for B cell activation and the production of specific antibodies. Although the MAC complex cannot function on gram positive bacteria like S. aureus, leukocytes mediated killing is critical for fighting against S. aureus infection . 1.4.3 S. aureus Immune evasion molecules 1.4.3.1 Resistance to antimicrobial substances S. aureus circumvents antimicrobial substances by three main strategies: 1, changing surface charges; 2, modifying the substrates of antimicrobial substances and 3, inactivating antimicrobial substances. S. aureus employs two enzymes to change the highly negatively charged teichoic acid in its cell wall (WTA). DltABCD (Dlt operon) adds D-alanine to WTA and the multiple peptide resistance factor F (Mprf) participates in the modification of membrane phosphatidylglycerol with L-lysine. Both modifications increase bacterial surface charges and thus reduce the attraction to the cationic defensins. dlt or MprF defective strains were killed more efficiently by neutrophil oxygen-independent killing. The former was much less able to cause arthritis and mortality in mice sepsis and arthritis models . S. aureus avoids lysozyme cell wall cleavage by modifying its cell wall peptidoglycan. O-acetyltransferase (OatA) was proposed to mediate this response. OatA catalyses the acetylation of muramic acid, which results in the addition of an acetyl group on S. aureus peptidoglycan. An oatA- strain was sensitive to lysozyme, while complementary expression of the enzyme restored its resistance . Two enzymes have been reported to directly inactivate antimicrobial peptides. Aureolysin (a metalloproteinase) could cleave and therefore inactivate cathelicidin LL-37. Staphylokinase (SAK), a secreted plasminogen binding protein, was reported to form a complex with ÃŽ ± defensin and almost completely blocked its antimicrobial activity. This activity was independent of plasminogen binding. S. aureus strains that produce SAK had a higher survival rate in vitro and higher virulence in a mouse arthritis model . 1.4.3.2 Prevent phagocytosis and opsonision 1.4.3.2.1 General anti-opsonin molecules S. aureus clinical isolates produce a capsular polysaccharide outer cell wall. Serotypes 5 and 8 of the capsular polysaccharide are associated with increased virulence. The capsule is anti-opsonic via blocking of surface deposition of opsonins and their receptor/ligand interaction. Immunoglobulins are targeted by protein A (SpA) and its homologues Sbi (S. aureus IgG-binding protein), SSL7 (Staphylococcal superantigen-like protein 7) and SAK. SpAis a 42 kDa surface anchored molecule. It has four to five IgG binding units that could interact with IgG Fc portion. This interaction presents IgG to leukocytes Fc receptor in the wrong orientation and therefore prevents recognition. In the present of IgG, strains expressing high level of SpA were shown to be more resistant to leukocyte phagocytosis than SpA-poor strains, especially when the sole source of opsonin was purified IgG. Opposite results occurred with IgG-deficient serum, indicating SpA confers protection against neutrophil through IgG interaction. Sbi contains two IgG binding sites at the N-terminal domain. The significance of the Sbi/IgG interaction remains to be fully established. SAK forms a complex with plasminogen and converts plasminogen to plasmin. Plasmin cleaves IgG and C3b deposited on S. aureus resulting in reduced recognition by phagocytes and likely impaired initiation of C1q mediated CP activation . 1.4.3.3 Complement inhibition S. aureus is now recognized as ‘a master of complement evasion. Unlike other bacteria which use host factors to ‘disguise the bacteria or inhibit complement activation, S. aureus produces a group of proteins to attack the key elements of the complement cascades. The list of anti-complement virulence factors is growing. So far, five complement inhibitors have been demonstrated and well characterized: SCIN; Efb; Ehp; SSL7 and Sbi. Interestingly, SCIN, Efb, Ehp and Sbi all use a triple ÃŽ ± helix bundle as their functional domain while their modes of action are markedly different (Fig. 1.2). SSL7 belongs to the SSL protein family. Its function will be discussed in context with other members of the family in a later section. 1.4.3.3.1 SCIN SCIN (staphylococcal complement inhibitor) is a human-specific 9.8 kDa secreted protein with a trip ÃŽ ± helix structure (Fig. 1.2) and is produced by 90% of S. aureus strains. SCIN was shown to inhibit all three complement activation pathways. In the presence of SCIN, the deposition of C3b and MAC were prevented, so was the C2b and Ba release. However the amount of surface bound C3 convertases (both forms) were increased, suggesting SCIN had a stabilizing effect on this complex. SCIN bound to surface-immobilized C3b directly and the binding site was predicted to involve the C3b MG7 and MG8 domain and the area nearby. This was confirmed by the co-crystallized SCIN-C3bBb complex. In vitro binding studies suggested the complex was likely to form in a 1:1 or 2:2 ratio. Indeed in the crystal structure, the complex appeared as a SCIN2C3b2Bb2 heterodimer that was bridged by the two SCIN molecules cross-linking the two C3b fragments. However this cross-linkage was not critical in SCIN compl ement inhibition as monomeric interaction also resulted in stable and inhibited C3 convertase. Native C3 could still associate with the SCIN-C3 convertase complex, but the production of C3b was largely inhibited, suggesting the convertase was likely trapped in a dysfunctional yet stable state by SCIN. Moreover, SCIN exerted a partial competition for factor B binding to C3b and a complete competition for factor H/C3b binding. The significance of the inhibition on factor H was not clear although reducing iC3b (inactive product of the cleavage of C3b) mediated downstream signaling could be beneficial for the bacterium. Physiologically, C3 convertase decays shortly after assembly. This disassociation is required for further cleavage of C2 and factor B. Thus SCIN functions by preventing C3 convertase decay; hindering conformational activation of C3 convertase and possibly by blocking C3b/iC3b mediated signaling . 1.4.3.3.2 Efb Efb (extracellular fibrinogen-binding protein) and the recently discovered Ehp (Efb-homologous protein aka Ecb) have been shown to inhibit C3b deposition in AP and C5 convertase activity in all three pathways. The efb gene is present in 85% of S. aureus isolates sequenced to date. Its inhibitory effects on complement mediated lysis and neutrophil activation in response to C5a have been demonstrated. The Efb complement binding domain (Efb-c) is also a triple ÃŽ ± helix huddle, although the arrangement is different from SCIN (Fig.1.2). It binds both C3 and C3b via the C3d fragment. However, which of the C3 forms is the primary target of Efb is debated. Structural-biochemical analysis suggested the binding affinity of Efb-C to native C3 was higher than that to C3b. The binding was proposed to induce conformational changes in C3 and prevent proper cleavage of the molecule. This view was challenged by Jongerius et al based on the observation that C3 cleavage was not influenced by Efb-C in CP/LP. Instead, they suggested Efb-C attacked complement intermediates that contain C3b. Therefore, in CP/LP, C3 convertase (C4b2a) was not affected by Efb but C5 convertase (C4b2aC3b) was inhibited, as evidenced by the decreased C5a production. Ehp was found to contain two C3d binding sites and showed higher levels of inhibition compared to Efb, though the mechanism of action was proposed to be similar. Nevertheless, the C3d fragment carries another important task: mediating interaction with complement receptor 2 (CR2) on B cells and facilitating B cell activation. Both Efb-C and Ehp were shown to completely inhibit C3d:CR2 interaction and its stimulatory effect on a B lymphoma cell line. The predicted binding site of CR2 on C3d was in close proximity to the residues that have been shown to be involved in Efb-C:C3d and Ehp:C3d binding. The exact competition mechanism remains to be confirmed . 1.4.3.3.3 Sbi Sbi is another secreted S. aureus protein that targets C3 activation. Sbi binds C3b but has a stronger affinity to C3dg. The binding was shown to be improved when the C3a domain was also present. These observations suggested the C3dg and C3a portion of C3 were important for Sbi/C3 interaction. By comparing binding profiles of different domains of Sbi, the C3 binding site was proposed to be located in its fourth domain (Sib IV). Interestingly, Sbi IV alone inhibited AP activation in a dose-dependent manner. However when the third domain was also present, incubation of human serum with this recombinant protein induced activation of complement, as shown by the degradation of native C3. A distinctive C3 derivative was present in Sbi-III-IV treated serum, whose molecular weight and migration behavior on two dimensional SDS-PAGE correspond to a transacylation product of C3b and Sbi. The cleavage of C3 activates an internal thioester moiety in the C3b fragment, which allows C3b to form cova lent bonds with hydroxyl groups in close proximity (e.g. bacterial surface). Thus it was proposed the Sbi III-IV provided a fluid-phase transacylation target for C3 cleavage and cause non-effective activation of the alternative pathway. Since mutational study confirmed the Sbi-IV was responsible for the complement inhibitiory effect, Sbi-III was proposed to be important in consumptive complement activation. Once again, Sbi IV adopts the triple helix structure, arranged in a similar fashion as Efb-c and Ehp (Fig. 1.2). Just like Efb and Ehp, the binding of C3dg to CR2 was inhibited by Sbi-III-IV, implying that Sbi may also influence adaptive immunity . 1.4.3.4 Preventing phagocyte extravasation and chemotaxis 1.4.3.4.1 CHIPS; FLIPr and FLIPr-like CHIPS (the chemotaxis inhibitory protein of S. aureus) was identified for its ability to prevent neutrophil chemotaxis to formylated peptide and C5a. CHIPS encodes a 121-amino acids (aa) secreted protein and presents in 62% of S. aureus clinical isolates. Postma et al demonstrated that CHIPS selectively and directly bound to C5a receptor (C5aR) and formylated peptide receptor (FPR) expressed on cell surface and competed with their respective ligands for binding. Receptor activation, as measured by the Ca2+ influx and murine neutrophil migration to the injury site, was inhibited. The two receptors were shown to interact with different areas on CHIPS. The N-terminal 6 residues of CHIPS, F1 and F3 in particular, were identified as the FPR binding sites. While the C5aR-binding domain was mapped to residues 31-121, which forms a packed structure similar to the ÃŽ ² grasp domain. Arginine 44 and lysine 95 were shown to be critical for its antagonizing activity. C5aR binds CHIPS through its N-terminus residues 10-18. These residues were suggested to be either involved directly in C5a binding or were required to stabilize the interaction. Therefore, CHIPS may function by direct competing with C5a or by disrupting the formation of the stable ligand/receptor complex . Two more S. aureus proteins were found to inhibit neutrophil chemotaxis. The secreted FPR-like 1 inhibitory protein (FLIPr) and its homologue FLIPr-like bound FPR and FPR-like 1 receptor (FPRL1). The N-terminal 6 residues of both proteins were important in both interactions but the phenylalanine was not critical for FRP binding. The inhibition of FPRL-1 by both proteins occurred in the nanomolar range. FLIPr-like was shown to be a potent inhibitor for FPR with activity comparable to CHIPS. However, animal infection models with chips or flipr isogenic deletion strains has not been reported. The contribution of CHIPS in bacterial infection is yet to be determined . 1.4.3.4.2 Map Map (MHC class II analog protein a.k.a. Eap) is a multifunctional 60-70 kDa secreted protein expressed by 97% of S. aureus isolates. It is an anti-inflammatory molecule that reduces leukocyte availability and function. Map can interact with a wide range of host ligands, including Fg, Fn and ICAM-1 (intercellular adhesion molecule-1). Map largely blocked ICAM-1 mediated firm adhesion and transmigration of neutrophil. In a peritonitis mice model, intraperitoneal injection of Map or pre-treatment of mice with Map showed 50-75% inhibition of neutrophil recruitment. Neutrophil infiltration in mice infected with a map- strain was 2-3 folds higher than that seen with a map+ strain, demonstrating Map inhibits ICAM-1 mediated neutrophil migration in vivo. Interaction of Map with ICAM-1 may modify signal transduction in leukocytes. NF-ÃŽ ºB activation and tissue factor release in THP-1 cells were diminished by Map treatment. A substantial amount of IL-6 and TNF-ÃŽ ± and a smaller amount of IL- 4 were released from Map treated human CD14+ PBMC in vitro. Anti-ICAM-1 antibody blocked the action, suggesting the induction was also mediated by ICAM-1. It is not clear if cellular processes other than cytokine production are also influenced, although Maps effect on PBMCs appears to be dose dependent . In addition to the cytokine changes, T cell function was impaired by Map. Mice treated with Map showed significantly reduced T cell mediated delayed-type hypersensitivity (DTH) and T cell proliferation. Adoptive transfer of T cells from Map-treated mice to untreated recipients prevented the recipients from developing DTH when challenged with allergen. The Map

Knowing the Strength of Your Buying Power :: Nike Public Relations Retail Media Essays

Knowing the Strength of Your Buying Power Reliable news sources have publicly exposed the grim working conditions of people employed by contractors making Nike products in Indonesia, Haiti and Vietnam. Nike’s association with the exploitation of third world workers has fueled a worldwide boycott on their products. Positive public relations are very important to Nike, who has positioned themselves through expensive advertising campaigns as a very strong competitor in the market of athletic shoes. Those running Nike are very aware that any negative association with the company’s name will be detrimental to its success. Nike’s name has become synonymous with the successful slogan â€Å"just do it.† Their association with sweatshops is contradictory and ruinous to their self promoted image as the champions of personal achievement. Nike must maintain a positive public image in order to continue to seduce consumers into choosing them over the competitor. So, when enough people were paying attention to Nike’s unscrupulous business practices, Nike was pushed to respond. Through the boycott, concerned consumers were able to get Nike to acknowledge and address the inhumane conditions at the factories they subcontract work to. Although there has not yet been complete resolve with Nike, concerned consumers have shown their power to be heard. Through consumer action we can create positive changes personally and politically. Many publications -- the New York Times, the Washington Post, the Sydney Morning Herald, Life Magazine -- have reported on the unjust treatment of workers making Nike products. There are reports of children sewing soccer balls for 60 cents a day, workers being beaten, sexually harassed, collapsing from exhaustion, being fired on the account of taking sick leave, working in hazardous conditions, being paid below a livable wage and the list goes on. This kind of flagrant exploitation is illegal in America. We have created laws to protect the unempowered worker from being taken advantage of by the empowered boss. On American soil, we are forced by the law to conduct business with a certain amount of moral decency and through these enforced labor laws we have developed a social understanding and agreement on humane treatment in business. But, because American workers have restricted overtime hours and a higher living wage then those in third world countries, manufacturing goods here is more costly. So, to increase profit margins, many U.

Adoption and Identity Formation

Adoption has many effects on families; identity formation is one the most important stages that a child has to form during the ages of adolescence. It is a lifelong process but it is mainly formed between the ages of 13 to 18. Forming an identity can be very difficult for an adopted child because leaving all the struggles that they will be already facing, the formation of identity will add another conflict in their lives. Parents can help adopted children by establishing a sense of identity and by exposing them to cultural background.If a child has issues or problems when forming their identity, than they might end up being in identity confusion. In this research, the main question that is going to be answered is; â€Å"How des Adoption Affect Identity Formation in a Negative way? The adoptive parents do not usually think of identity formation of the adopted child, they try to make their kids get assimilated into the new environment and encourage them to totally forget about their p ast which disables them to answer the question; â€Å"Who am I†.It is also a fact that the usage of drug and alcohol are seen very often on adopted adolescents. The focus in this literature review is going to be on the adopted adolescents and their process of identity formation. The main methods that will be implemented in this research will be conducting interviews, collecting surveys and making group observations. There will be many limitations while conducting my research. First of all, a detailed study cannot be done due to the shortage of time.There are also not much quantitative research groups and the participants are very limited. Solutions to these limitations could be getting started as soon as possible to not be worried about the limitation of time. Finding enough participants to complete my survey would also be helpful. Interviews are also a huge contribution and even though the sample groups are limited, there will be enough participants that are going to be take n into consideration.

The Art of Rhetoric in the Metamorphoses

The Art of Rhetoric in the Metamorphoses Among the numerous passages covered in The Metamorphoses of Ovid, there are many stories regarding the origins of the Earth, the activities of the Roman gods, and some of Rome’s significant rulers and founders. Within each of these stories, Ovid injects an overall idea that can be taken away from the text. Many of these overall ideas are themes and lessons, but also there are arts that are illustrated to the reader such as poetry, singing, or weaving. One idea in particular that Ovid portrays is the art of Rhetoric in Greco-Roman culture.Rhetoric was used in Greco-Roman culture often as a means of putting together words in a certain order to persuade or inform your audience of a specific idea. The two stories regarding the discussion between Ajax and Ulysses over Achilles armor exemplifies the idea of rhetoric. Ovid uses the episodes of Ajax and Ulysses in book thirteen f the Metamorphoses to illustrate to the readers the art of rhetori c. Ovid draws upon previous texts covered in class such as Homer’s Odyssey and Virgil’s Aeneid to form some of his stories in the Metamorphoses. However, Ovid’s style of writing is much different than that of Homer and Virgil.Homer and Virgil both write about post Trojan War events, but from two different perspectives, the Greeks and the Trojans respectively. Despite their difference in perspective, their style is the same in that they both focus on the glorification of war. They both portray violent events vividly and give praise to war heroes. Ovid, on the other hand, talks about certain parts in the Odyssey and the Aeneid that Homer and Virgil did not discuss such as the rescue of Achaemenides, the crewman Ulysses left behind on the island of Polyphemus, in book fourteen.Ovid seems to dismiss the glorification of war and briefly pass over violent scenes or portray them in a different, more comical, manner. Rather Ovid focuses on the arts of Greco-Roman cultur e. Ovid focuses on stories of Mythology concerning poetry, singing, crafting, and even the art of rhetoric. Rhetoric is â€Å"the study and practice of effective communication,† (Nordquist). There are three types of rhetoric employed: epideictic, judicial, and deliberative. These three branches of rhetoric can be used in various ways to communicate to your audience.Epideictic rhetoric is the commemoration or blame of an individual. Epideictic rhetoric is often used in â€Å"funeral orations, obituaries, graduation and retirement speeches, letters of recommendation, and nominating speeches at political conventions,† (Nordquist). Judicial rhetoric is â€Å"primarily employed by lawyers in trials decided by a judge or jury,† (Nordquist). Deliberative rhetoric is the use of communication to persuade or dissuade an individual or audience of a statement or action.Ovid does not only use the three branches of rhetoric however, he also shows the use of a technique called amplification and minimization through Ajax and Ulysses which is essentially amplifying good qualities and minimizing bad qualities. The technique of amplification and minimization goes hand in hand with deliberative and epideictic rhetoric. Ovid employs all three branches of rhetoric in his stories of Ajax and Ulysses to demonstrate their arguments and to illustrate the art of rhetoric itself. The bulk of Ovid’s illustration of rhetoric is contained within the stories of Ajax and Ulysses in book thirteen.After the Trojan War is over, the Greeks set aside Achilles’ armor and decide, through a debate, who the receiver of the armor will be. The two in debate over the armor are Ajax and Ulysses. Both employ deliberative rhetoric as their means of persuading the audience to decide who will keep the armor, but they also use the other branches as well to strengthen their argument. The discussion between the two as a whole is a deliberative and judicial rhetoric battle, but both make use of epideictic rhetoric to strengthen their positions.Ajax is the first to present his argument. Immediately Ajax makes use of epideictic rhetoric by slandering Ulysses’ actions, â€Å"he was one who did not hesitate to beat retreat when he was forced to face the torches Hector threw, while I withstood those deadly flames: the fleet was only rescued because of me,† (Ovid 427). Ajax gives evidence that Ulysses was a coward by exposing his retreat in the face of Hector. He also uses amplification and minimization to show how detrimental it was that Ulysses fled, and how great it was that Ajax held his position.Ajax then uses another epideictic statement when he brings in his heritage: And even if you were to doubt my courage, it’s I who claim the nobler lineage. I am the son of Telamon, the friend who helped the sturdy Hercules destroy the walls of Troy and, then, in Jason’s ship, sailed off and reached the distant coast of Colchis. And Telamon was born of Aeacus, who is a judge whitin the silent world—precisely in the place where Sisyphus, the son of Aeolus, must struggle with the weight of his great stone; and Aeacus was born of Jove—as Jove himself admits. (Ovid 427-428) Once again Ajax draws upon a feature that will increase his deservingness.Throughout the rest of his presentation, Ajax continually employs epideictic rhetoric to commemorate his actions and defame those of Ulysses. The use of only one dimension of the three branches of rhetoric by Ajax shows that the body of his presentation is insulting Ulysses. This weakens Ajax’s argument, â€Å"Many amateur rhetors think of debate as an ‘us-versus-them’ sort of affair, and that the readers who disagree are the enemy whose inferior arguments must be ground into the dirt. Accordingly, they mistakenly believe that ridiculing or attacking these mistaken beliefs is the most effective way to ‘win’ the argument,† (Whe eler).The constant insults diminish in value in their numerous quantities. Ulysses is fortunate to present after Ajax. Ajax is at a disadvantage because of his eagerness to present first. This gives Ulysses a chance to gather his argument and also turn what Ajax says against him. Ulysses begins in a different manner. Ulysses sets the tone of somberness by recalling Achilles, â€Å"If things had gone as you and I had wished, o Greeks, we would hat ask who should succeed to this extraordinary weaponry; Achilles, you’d still have your arms, and we would still have you,† (Ovid 432).Ulysses uses epideictic rhetoric not to depreciate Ajax’s deeds, but to honor Achilles as one does at a funeral. Soon after Ulysses honors Achilles, he begins to strengthen his image through more epideictic rhetoric just as Ajax did. Ulysses draws upon his own lineage on page 433 claiming to be descendent of not only Jove but Mercury as well. He also minimizes Ajax’s lineage by cla iming that one of Ajax’s ancestors was an exiled criminal. Ulysses then moves on to say, â€Å"Just judge by deeds—and deeds alone . . . it’s only one’s worth that weighs,† (Ovid 433).Ulysses defeats Ajax’s argument about his kinship to Achilles, but then claims that the victor should be determined by his actions not his external goods. Aristotle, in Nicomachean Ethics, talks about the importance of external goods, but he says that the goods of the mind (deeds and actions) are more important. So Ulysses goes on to give a myriad of good deeds he has performed such as convincing Achilles to return to battle, going as an ambassador into Troy to try to negotiate the return of Helen, the plan for the Trojan horse, and inciting the warriors and Ajax with courage when they ere on the brink of retreat.As an entirety, Ajax is only able to spill insults and talk down about Ulysses, but Ulysses is able to combat all of Ajax’s insults and turn th em against him. Also going second plays into Ulysses’ favor because Ajax has no opportunity for rebuttal whereas Ulysses does. Therefore Ulysses is declared the victor of the argument and wins on the basis of his rhetorical skills. Ovid pays more respect to the battle between two rhetors than he does to two warriors clearly through the great detail he goes into in the discussion between Ulysses and Ajax.Instead of depicting great violent battle scenes, he depicts a great rhetoric argument between two individuals. Ovid briefly touches on the Trojan War itself, but takes great measure in illustrating the use of rhetoric in the discussion after the War.Bibliography Ovid, Metamorphoses Nordquist, Richard. About. com, â€Å"Rhetoric. † Accessed November 28, 2011. http://grammar. about. com/od/rs/g/rhetoricterm. htm. Wheeler, Dr. L. Kip. â€Å"Rhetoric. † Last modified September 26,2011. Accessed November 28, 2011. http://web. cn. edu/kwheeler/resource_rhet. html.