285 research outputs found
The story of the Soni Ventorum Wind Quintet
No full textThesis (D. Mus. Arts)--University of Washington, 2000The Soni Ventorum Wind Quintet has been the wind quintet-in-residence at the University of Washington School of Music since 1968. Officially founded in 1962, when its members were on the faculty of the Conservatory of Music of Puerto Rico, the group has had a long and stable history. Through their concerts, tours, and recordings, the Soni Ventorum Wind Quintet has established an international reputation. Over the years, many distinguished composers have written works especially for the Soni Ventorum, thus expanding the repertoire of the wind quintet.This study traces the history of the Soni Ventorum Wind Quintet mainly through interviews with the quintet members themselves. This history includes antecedent quintets in which members of the Soni Ventorum Wind Quintet participated (namely, a student quintet at the Curtis Institute, The American Wind Ensemble of Vienna, and the U.S. Seventh Army Symphony Wind Quintet). It covers the founding of the Soni Ventorum Wind Quintet in 1962 at the Conservatory of Music in Puerto Rico through their tenure from 1968 through the present as the wind quintet-in-residence at the University of Washington in Seattle. It gives an account of the establishment of the Soni Ventorum's recording career, their approach to sound and ensemble, their many tours, participation in festivals and competitions, and personnel. The study details the Soni Ventorum's collaborations with colleagues at the University of Washington School of Music, especially the many composers who wrote pieces for the group. One chapter covers ensemble pieces that have been written for the members of the Son! Ventorum Wind Quintet, while another presents wind quintet and quartet arrangements that were prepared by the quintet members themselves. The final chapter provides biographies of the members of the Soni Ventorum Wind Quintet.The Introduction to the study is a brief history of wind quintets. The study concludes with detailed appendices cataloguing the Soni Ventorum Wind Quintet's repertoire, concerts, residencies, tours and a complete discography.At the time of this writing, the author is aware of no other work detailing the history of an established wind quintet
Glycodelin-A As The Regulator Of CD8+ T-Lymphocyte Activity : Implications In Primate Pregnancy
No full textThe ability of our immune system to mount a response against non-self-antigens legitimates the semi-allogenic fetus as a target for maternal immune attack. Yet, in a normal pregnancy the fetus stays well protected due to the concerted action of several diverse mechanisms which either suppress the fetal allogenicity or spatio-temporally inhibit maternal immune cells’ growth and functions.
One such factor which aids in the establishment, progression and maintenance of pregnancy is the 28 kDa dimeric sialylated glycoprotein Glycodelin-A (GdA). Synthesized by the endometrium and decidua, this protein has myriad functions, the most important being that of immunosuppression. GdA is inhibitory to all hematopoietic cells and also induces programmed cell death in activated T cells and monocytes via the intrinsic mitochondrial pathway. In the Introductory chapter of this thesis, details about GdA and the other isoforms of the glycodelin family of proteins have been presented which highlight the involvement of glycodelins in primate pregnancy, with emphasis on GdA and its pleiotropic functions associated with reproduction in females.
Activated T-lymphocytes against paternal antigens are found in the uterine compartment and in the maternal circulation throughout pregnancy. Activated CD8+ T-lymphocytes have been reported to pre-dominate the uterine T-lymphocyte population during pregnancy and unlike the CD4+ T cells, are retained until term. Studies show that activated CD8+ T-lymphocytes are necessary for the establishment and progression of early pregnancy. However, how these lymphocytes harbouring cytotoxic activity are regulated at the later stages of pregnancy is poorly defined. We attempted to uncover a possible mechanism of regulation of CTL (cytotoxic T lymphocyte) activity (if any) during primate pregnancy by GdA.
In the absence of established human CD8+ T cell lines, we first standardized the generation of CTLs in-vitro from hPBMCs (human peripheral blood mononuclear cells) by alloactivating them with an ovarian carcinoma cell line OVCAR-3 utilized as a mimic of an allograft. The details of the rationale behind using this method for generating CTLs and the alloactivation methodology have been put together in the Chapter 1 of this thesis. The activation of hPBMCs was confirmed by the surface expression of an early activation marker CD69 and tritiated thymidine incorporation. Differentiation of CD8+ T cells into effector cells was confirmed by the upregulation of perforin and granzyme transcripts by real time RT-PCR analysis. Target-cell specific cytolytic activity of the CTLs was assessed by using a cytotoxicity measurement assay- JAM test, details of which also form a part of chapter 1.
Having generated effective CTLs in vitro, we tested the effect of GdA on CTL activity. Our findings, on the effect of GdA on CTLs have also been discussed in the Chapter 1. We observed that the cytolytic activity of CTLs was significantly reduced by GdA treatment albeit at a dose three to four times higher than that required for inhibiting CD8+ T cell proliferation, implying that a mechanism of temporal regulation of CTL activity operated at the feto-maternal interface, thereby contributing to the establishment and progression of pregnancy.
Interestingly, in our quest to uncover the mechanism of inhibition of CTL activity by GdA, we found that the inhibition of proliferation was comparable in both CD4+ and CD8+ T-lymphocytes at all dosages of GdA, but unlike CD4 + T cells CD8 + T cells were resistant to GdA-induced apoptosis even at high dosage of GdA. Hence we could rule out that the loss of CTL activity upon GdA treatment was due to CD8+ T cell death. Further, we assessed the functional competence of alloactivated CTLs by quantitating the mRNA transcripts of key cytolytic molecules; perforin and granzyme B, in GdA treated alloactivated hPBMCs and found that there was a significant reduction in the mRNA of these cytolytic molecules. Additionally, we also found that GdA treated CD8+ T cells exhibited impaired release of the cytolytic molecules by the process of degranulation, measured by the surface exposure of LAMPs (Lysosome associated membrane proteins) on the surface of cells by flow cytometry and as seen by the retention of perforin protein in them assessed by intracellular staining and flow cytometry. Intrigued by the observations, we probed for the regulators of perforin and granzymes in CTLs. EOMES (Eomesodermin) and T- Bet are well known transcription factors which control the differentiation of CD8+ T cells into effector and memory cell CD8+ T cell type. Interestingly we found that the expression of EOMES was significantly reduced in activated GdA treated hPBMCs, both at the transcriptional and translational level, however T-Bet did not show any variation in expression upon GdA treatment. All the above findings have been compiled in Chapter 2 along with our studies on the possibility of GdA to induce a tolerogenic phenotype in T cells. We found there was no difference in the mRNA level and surface expression of CD103 and CD28 in alloactivated PBMCs, while FOXP3 mRNA did not show any variation upon GdA treatment, indicating that GdA does not induce a tolerogenic phenotype in T-lymphocytes, further confirming our data that the decreased cytolytic activity of CTLs upon GdA treatment was not due to tolerance but due to impaired function
Interestingly, IL-2/IL-2R signaling is known to directly regulate perforin and granzyme expression as well as it plays a role in the expression of T-Bet and EOMES. Therefore, as a read out of IL-2 signaling we checked for the surface expression of the high affinity IL-2R subunit, CD25. As expected, CD25 expression was more pronounced in CD4+ T cells and consistent with published reports in literature that GdA suppresses IL-2 synthesis, we also observed a significant reduction in the CD25bright population in both the T cell subsets (CD4+ and CD8+) upon GdA treatment (addressed in Chapter 3). This finding supports a mechanism of action of GdA, wherein the cytolytic activity of CTLs is compromised by the downregulation of EOMES, triggered by the low IL-2 levels. This translates to aberrant synthesis of key cytolytic molecules perforin and granzyme B, leading to low efficiency CTLs, which are further disabled by defective degranulation machinery induced by GdA. We did not look into the mechanistic aspects of how GdA suppresses degranulation, which can be addressed later as a part of another study.
Building up on our observations, and taking cues from existing literature, that IL-2 regulates the expression of pro and anti-apoptotic protein levels within activated cells, we looked at the expression profile of Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic) in activated PBMCs upon GdA treatment. There was a significant reduction in the total mRNA and protein level of Bcl-2, while a very significant increase in Bax mRNA and protein was observed. Chapter 3 of the thesis also presents this data and explains a plausible mechanism of the inhibitory effect of GdA on T-lymphocytes.
In Chapter 2, we have also addressed the probable reasons for the differences in the responses of CD4+ and CD8+ T-lymphocytes to GdA. Interestingly, surface glycan profile of CD4+ and CD8+ T-lymphocytes upon activation and the surface expression of the most probable receptor for GdA i.e. CD7 was comparable in both the T cell subsets, indicating that possibly the downstream signaling events leading to GdA-induced apoptosis and not the surface binding of GdA may vary in CD4+ and CD8+ T-lymphocytes, due to which we observed a difference in the extent of apoptosis induced in
these cell types by GdA although the inhibition of proliferation in both the subsets was comparable.
In summary, this study is the first to provide evidence for a possible mechanism of temporal regulation of CTL activity at the feto-maternal interface, where activated CD8+ T cells are abundantly present. We can say with much confidence that binding of GdA to T-lymphocytes causes sub-optimal IL-2 signaling which translates into reduced expression of EOMES and hence downregulation of perforin and granzyme B, leading to impaired CTL activity in CD8+ T-lymphocytes, which is further weakened by the impaired release of the cytolytic molecules from them. Insufficient IL-2 signaling in the presence of GdA can also be a cause of inhibition of proliferation in T-lymphocytes, while the resulting decrease in anti-apoptotic protein Bcl-2 and increase in pro-apoptotic protein Bax seem to contribute to the induction of apoptosis in CD4+ T cell.
It will be interesting to explore the mediators involved in the IL-2 signaling pathway that are differentially regulated in CD4+ and CD8+ T cells which confer resistance in CD8+ T cells to GdA-induced apoptosis and also the mechanism by which GdA regulates the degranulation of cytolytic vesicles in CTLs needs to be worked out
A critical analysis of Section 197 of the Labour Relations Act 66 of 1995 as amended taking into consideration the elements of Section 197, the definition and case law.
No full textMaster of Law in Labour Law. University of KwaZulu-Natal, Durban 2016.Section 197 of the Labour Relations Act 66 of 1995 regulates the transfer of a business as a going concern. However, it caused much debate and litigation. Previously, section 197 allowed for the automatic transfers of employees when there was transfer of the whole or part of a business, trade or undertaking. The employees could not refuse to be transferred.
There has been much debate and litigation on this issue, mainly on the issue of transfers in the context of outsourcing. This resulted in section 197 of the Labour Relations Act 66 of 1995 being amended in 2002. With the amendments, the new employer is automatically substituted in place of the old employer in respect of all contracts of employment. The section aims to protect employees against loss of employment while facilitating the transfer process.
Despite the amendment, there has been much academic and judicial debate on the issue. The Constitutional Court settled this issue in Aviation Union of SA & another v SA Airways (Pty) Ltd & others (2011) 32 ILJ 2861 (CC) wherein it was held that a transfer takes place when there is a termination of a service contract and the award of a new contract to a third party. The Aviation case sets a precedence and is being applied in various cases. For section 197 to apply, there must be a transfer of an identifiable business by the old employer to the old employer as a going concern. Each case must be determined on the facts.
The effects and conditions of transfers are further discussed stating the consequences that flow and the remedies available to employees. The conditions of the transferred employees should not on a whole be less unfavorable. This is further examined in the context of transfers within the South African Local Government structures and how the unions failed to utilize their power and collective bargaining to their advantage to ensure that they members were protected during the process
Glycodelin A suppresses the cytolytic activity of CD8(+) T lymphocytes
No full textMaternal tolerance to the semi-allogenic fetus is brought about by several mechanisms in humans Glycodelin A (GdA) secreted by the uterine mucosa and decidua is induced to high levels by progesterone between 12 and 16 weeks of pregnancy The glycoprotein an immunomodulator has been shown to be inhibitory to the survival and functions of almost all the immune cells CD8(+) T cells which predominate the T lymphocyte population in the decidua are relatively less studied We attempted to find out the possible mechanism if any of regulation of the cytolytic function of CD8(+) T cells during pregnancy Alloactivated CD8(+) T cells harbouring specific cytolytic activity against target cells exhibited compromised activity upon treatment with high concentrations of GdA Interestingly unlike the CD4(+) T cells CD8(+) T cells were resistant to GdA-induced apoptosis The inhibition of cytotoxic T lymphocyte activity was brought about by the downregulation of transcription of the cytolytic effector molecules granzyme B and perform and the degranulation of cytolytic vesicles These results suggest a protective role played by GdA during pregnancy by regulating the cytolytic activity of CD8(+) T cells (C) 2010 Elsevier Ltd All rights reserve
PULSE-SMART: Pulse-Based Arrhythmia Discrimination Using a Novel Smartphone Application
No full textCo-author Apurv Soni is a medical student in the MD/PhD Program at UMass Medical School.BACKGROUND: Atrial fibrillation (AF) is a common and dangerous rhythm abnormality. Smartphones are increasingly used for mobile health applications by older patients at risk for AF and may be useful for AF screening. OBJECTIVES: To test whether an enhanced smartphone app for AF detection can discriminate between sinus rhythm (SR), AF, premature atrial contractions (PACs), and premature ventricular contractions (PVCs). METHODS: We analyzed two hundred and nineteen 2-minute pulse recordings from 121 participants with AF (n = 98), PACs (n = 15), or PVCs (n = 15) using an iPhone 4S. We obtained pulsatile time series recordings in 91 participants after successful cardioversion to sinus rhythm from preexisting AF. The PULSE-SMART app conducted pulse analysis using 3 methods (Root Mean Square of Successive RR Differences; Shannon Entropy; Poincare plot). We examined the sensitivity, specificity, and predictive accuracy of the app for AF, PAC, and PVC discrimination from sinus rhythm using the 12-lead EKG or 3-lead telemetry as the gold standard. We also administered a brief usability questionnaire to a subgroup (n = 65) of app users. RESULTS: The smartphone-based app demonstrated excellent sensitivity (0.970), specificity (0.935), and accuracy (0.951) for real-time identification of an irregular pulse during AF. The app also showed good accuracy for PAC (0.955) and PVC discrimination (0.960). The vast majority of surveyed app users (83%) reported that it was "useful" and "not complex" to use. CONCLUSION: A smartphone app can accurately discriminate pulse recordings during AF from sinus rhythm, PACs, and PVCs.MD/Ph
Association of common mental disorder symptoms with health and healthcare factors among women in rural western India: results of a cross-sectional survey
No full textFirst author Apurv Soni is a medical student in the MD/PhD Program at UMass Medical School.OBJECTIVES: Information about common mental disorders (CMD) is needed to guide policy and clinical interventions in low-income and middle-income countries. This study's purpose was to characterise the association of CMD symptoms with 3 inter-related health and healthcare factors among women from rural western India based on a representative, cross-sectional survey. SETTING: Surveys were conducted in the waiting area of various outpatient clinics at a tertiary care hospital and in 16 rural villages in the Anand district of Gujarat, India. PARTICIPANTS: 700 Gujarati-speaking women between the ages of 18-45 years who resided in the Anand district of Gujarat, India, were recruited in a quasi-randomised manner. PRIMARY AND SECONDARY OUTCOMES MEASURES: CMD symptoms, ascertained using WHO's Self-Reporting Questionnaire-20 (SRQ-20), were associated with self-reported (1) number of healthcare visits in the prior year; (2) health status and (3) portion of yearly income expended on healthcare. RESULTS: Data from 658 participants were used in this analysis; 19 surveys were excluded due to incompleteness, 18 surveys were excluded because the participants were visiting hospitalised patients and 5 surveys were classified as outliers. Overall, 155 (22·8%) participants screened positive for CMD symptoms (SRQ-20 score ≥8) with most (81.9%) not previously diagnosed despite contact with healthcare provider in the prior year. On adjusted analyses, screening positive for CMD symptoms was associated with worse category in self-reported health status (cumulative OR=9.39; 95% CI 5·97 to 14·76), higher portion of household income expended on healthcare (cumulative OR=2·31; 95% CL 1·52 to 3.52) and increased healthcare visits in the prior year (incidence rate ratio=1·24; 95% CI 1·07 to 1·44). CONCLUSIONS: The high prevalence of potential CMD among women in rural India that is unrecognised and associated with adverse health and financial indicators highlights the individual and public health burden of CMD.MD/Ph
Glycodelin-A interferes with IL-2/IL-2R signalling to induce cell growth arrest, loss of effector functions and apoptosis in T-lymphocytes
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