203 research outputs found
Pap smear screening: a retrospective study
No full textBackground: Cervical cancer is the seventh cancer in overall frequency, but the second most common cancer among women worldwide. The objective was to study the population undergoing pap-smear screening.Methods: It is retrospective study conducted in general hospital, GMERS Medical College Gotri, Gujarat, India. Total 1003 patients who attended OPD have undergone routine pap smear screening over period of 6 months from January 2016 to June 2016. Cytotological examination was done and test results were classified according to Bethesda system.Results: Abnormal tests were found in 36 patients.Conclusions: Pap smear a routine screening test offered to every woman who comes to our OPD irrespective of her complaints. Every woman at least once in her lifetime should go for pap-smear examination. It is effective screening test for cervical carcinoma. It is cost effective test with high specificity and very easy to perform so it becomes the method of choice for cervical carcinoma screening. With proper follow up patients with abnormal tests are screened and appropriate treatment is being offered to patients.</jats:p
The Near Future of Parcel Delivery: Selecting Sustainable Solutions for Parcel Delivery
No full textThe GHG-emissions of the transport sector are still increasing. This trend isaccompanied by the strong growth of the e-commerce sector, leading to moretransport movements on our road networks. In order to mitigate theexternalities of the e-commerce related parcel delivery market and try tomake it more sustainable, the following research question has been drafted:How could the last mile parcel delivery process become more sustainable,i.e. how to minimise traffic impacts and emissions, while maintaining thesocial and economic benefits of e-commerce and home deliveries?To answer the research question, this study follows a Multi-Actor Multi-Criteria Approach (MAMCA), which is defined especially for large projectsthat require high stakeholder involvement. Based on a stakeholder analysisand an analysis of their points of view, a sustainability framework has beendefined. This framework consists of a set of criteria along which several‘more sustainable’ last mile alternatives have been assessed. The mostimportant criteria are the reduction of GHG emissions, delivery time, costsand customer satisfaction.This study assesses the costs and benefits of the implementation of cargobikes, electric vans, Urban Consolidation Centres (UCCs), crowdsourcingsystems, and evening and night time deliveries. First, a Simple Multi-Attribute Rating Technique (SMART) method is applied to identify thealternative(s) that offer the highest utility (most benefits). According to theSMART analysis, parcel lockers, UCCs (with electric transport) and nightdelivery are the most beneficial alternatives for a sustainable last mile in alldifferent cases (best-, middle- and worst-cases). After implementing thesealternatives in a Discrete-Event Simulation (DES) model and conductingcarefully designed experiments with it, the conclusion can be drawn thatimplementing or expanding the parcel locker infrastructure significantlyenhances the operational efficiency. Furthermore, these lockers can easily bereplenished by night, which reduces the traffic impact of parcel delivery evenfurther.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Transport and LogisticsPolicy Analysi
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
Conservation of the Low-shear Modeled Microgravity Response in Enterobacteriaceae and Analysis of the trp Genes in this Response
No full textabstract: Low fluid shear force, including that encountered in microgravity models, induces bacterial responses, but the range of bacteria capable of responding to this signal remains poorly characterized. We systematically analyzed a range of Gram negative Enterobacteriaceae for conservation of the low-shear modeled microgravity (LSMMG) response using phenotypic assays, qPCR, and targeted mutations. Our results indicate LSMMG response conservation across Enterobacteriacae with potential variance in up- or down-regulation of a given response depending on genus. Based on the data, we analyzed the role of the trp operon genes and the TrpR regulator in the LSMMG response using targeted mutations in these genes in S. Typhimurium and E. coli. We found no alteration of the LSMMG response compared to WT in these mutant strains under the conditions tested here. To our knowledge, this study is first-of-kind for Citrobacter, Enterobacter, and Serratia, presents novel data for Escherichia, and provides the first analysis of trp genes in LSMMG responses. This impacts our understanding of how LSMMG affects bacteria and our ability to modify bacteria with this condition in the future.The final version of this article, as published in he Open Microbiology Journal, can be viewed online at: https://benthamopen.com/ABSTRACT/TOMICROJ-8-5
COLOR OF CREATORSHIP - Author\u27s Response
No full textThis essay is the author\u27s response to three reviews of The Color of Creatorship written by notable intellectual property scholars and published in the IP Law Book Review
Measuring microfinance access : building on existing cross-country data
No full textGiven the acknowledged need for a new effort to expand the set of available data on direct access to financial services, including a focus on access by those at low income, Honohan provides a selective review of the diverse sources of data that exist and considers how best to build on them. He proposes a basic framework within which to consider the analysis of the interesting questions: (1) How does access affect poverty and productivity? and (2) What hinders access? The author discusses existing and potential contribution of household and business user surveys, surveys of providers and their regulators, and surveys of experts, and assesses their relative strengths.Banks&Banking Reform,Environmental Economics&Policies,Health Economics&Finance,Poverty Assessment,Governance Indicators
Diversity and disparity?: motherhood wage gaps, attainment and assimilation levels for first- and second-generation immigrants
No full textThis dissertation examines gender- and immigrant nativity-based inequalities in educational and occupational attainment, earnings and wages. It uses an intersectional theoretical framework. The first chapter asks whether mothers have lower wages than women without children, and whether any disparities vary by mothers’ nativities. The second chapter asks how second-generation immigrants’ educational and occupational attainment and earnings compare to their parents’ generation, and to a group of their nonimmigrant peers. Findings are that both first-generation immigrant and nonimmigrant mothers experience wage gaps. Corrections for additional characteristics that might differ between mothers and nonmothers reduce the sizes of gaps. Corrections for characteristics linked to decisions to immigrate increase gaps for a group of recent immigrants. Within most second-generation pan ethnic Latino and Asian groups and country of origin groups from Mexico, Cuba, the Dominican Republic, the Philippines, China and India, women’s outcome attainment levels exceed those of their mothers by more than men’s outcome attainment levels do compared to their fathers. However, gender earnings gaps persist, with men having higher earnings than women across pan ethnic groups. Additionally, despite some assimilation across generations, many disparities remain between second-generation immigrants and nonimmigrants.Ph.D.Includes bibliographical referencesby Anjali Srivastav
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
An analysis of drug migration during drying of granules as an underlying cause of content non-uniformity in wet granulation
No full textGranulation is an integral step during pharmaceutical manufacturing of solid doses, which is usually followed by unit operations such as drying, milling, tableting and coating. Granulation is typically carried out to alleviate problems in powder handling, content non-uniformity, segregation and poor flow properties of powders. However, previous work carried out by Oka et. al. (Oka, Emady et al. 2015) points out that sometimes a wet granulation process might fail to give us a robust product, especially in case of a low dose drug product. Multiple factors such as segregation, wettability properties of formulation ingredients and active pharmaceutical ingredient (API) solubility in the binder solution were found to impact the distribution and consequent availability of the drug in the finished dosage form. The focus of this work is to understand the effect of the solubility of an API on its distribution within granule cores and across granule size classes upon drying. When a wet granule containing a water-soluble API is dried, it is likely that the dissolved API will migrate towards the periphery of the granule as the solvent evaporates. Consequently, the migrated active can deposit itself on the outer crust of the granule upon recrystallization from the evaporating binder solvent. Subsequent powder handling may lead to attrition of this deposited active, thereby creating super-potent fines and resulting in severe non-homogeneity and product losses (Oka, Emady et al. 2015). In the case of pharmaceutical granulation, a greater extent of API migration can not only compromise the structural integrity of the granules (Poutiainen, Honkanen et al. 2012) but also lead to poor flow and incomplete granulation resulting in content nonuniformity. This thesis investigates the extent of drug (active) migration in granules made via high shear wet granulation subject to the viscosity of the binder solution, particle size of the excipient and granule porosity. X-ray micrtomography was used to analyze the spatial distribution of the recrystallized API. Due to the complexity of a qualitative comparison between granules having different sizes, shape and porosities, a quantification technique that is independent of these differences is warranted. The extent of capillary migration in the resulting granules was analyzed by dividing the μ-CT images into conical sections and quantifying the distribution of the active across these conical cross-sections. Computational tools have been used to define a dimensionless radial distribution function (RDF) to quantify the spatial distribution of the active ingredient in granules produced under different processing conditions. Statistical analysis was performed to quantify the extent of aforementioned variables on the extent of migration. Thus, a comprehensive investigation into the causes of drug migration was carried out in this study to ascertain which factors or combination of factors have the most prominent effect on the extent of migration of a water soluble API during granule drying. Hence, this study aims to identify the optimal operating conditions and drying parameters to design a robust wet granulation process and subsequently address content non-uniformity issues in pharmaceutical processes.M.S.Includes bibliographical referencesby Anjali Katari
Comparison of Canal Transportation and Centric Ability of Two Nickel-Titanium Rotary Systems Using Cone Beam Computed Tomography: An In Vitro Study
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