Several factors that influence the rate of human decomposition have been described in the literature, including temperature, access by insects, humidity and rainfall1. These environmental factors, as well as purge fluid released during decomposition2, can interact with evidence deposited on the clothing of a deceased individual. The present research assessed how these combined factors affect the detection and identification of blood and semen evidence, as well as subsequent DNA analysis. A 35-45 pound (lb) feeder pig (post-mortem interval (PMI) < 3 hours) was placed on a grassy area within the Boston University Outdoor Research Facility for a period of 22 days or 364.3 accumulated degree days (ADD) during late spring, with the temperature averaging 16.5 oC. Aliquots of 30 μl of either human blood or semen were pipetted onto 1 inch by 1 inch sections of a 95% cotton t-shirt. Twenty-two samples of each type were placed on top of and underneath the pig, as well as a similarly weighted bag of sand (control). One bloodstain and one semen stain were collected each day for a period of 22 days from each location, yielding 8 samples per day. Each sample was analyzed within 30 hours of collection. The blood samples beneath the control showed that environmental factors influenced the results of testing. Rain caused dilution and diffusion of the bloodstains and the color of the stains changed from red-brown to green-yellow. Kastle-Meyer (KM) testing was positive for all samples and ABAcard® HemaTrace® testing was positive for 14 of 22 samples, with the negative results occurring during days 12 - 21. Two stains that were negative at 10 minutes turned positive shortly thereafter, suggesting that a longer development time may be required for compromised samples. The blood samples placed beneath the pig yielded positive KM results on all 22 days and positive HemaTrace® results through day 10. All bloodstains placed on top of the pig and control yielded positive KM and HemaTrace® results. The blood samples from on top of the pig and control yielded full short tandem repeat (STR) profiles for each of the four days of testing (days 1, 8, 13 and 20). The blood samples from beneath the pig and control yielded full profiles on day 1 only. The three subsequent days of testing yielded a maximum of three alleles per sample, with the majority of samples failing to provide any profile at all. Semen samples from beneath the control began to show a decrease in fluorescence using an alternate light source (ALS) by day 3, and some areas of fluorescence occurred in a different location, indicating that the soluble components had diffused outward from the original region of deposition (ORD). Results for acid phosphatase (AP) and ABAcard® p-30 were mostly positive through day 16. By day 17, the ORD no longer fluoresced or yielded positive AP or p-30 results. With the exception of day 10, sperm were identified on all samples. Semen results from beneath the pig showed that even on day 1, the ORD was only weakly fluorescent and by day 4, fluorescent regions began appearing outside of the ORD. These outlying regions of fluorescence yielded positive results with AP Spot and p-30 testing, but showed few or no spermatozoa when examined microscopically. As the days passed, the ORD were no longer fluorescent and AP mapping and p-30 testing yielded negative results; however, spermatozoa could still be identified in almost all of the ORD through day 22. Semen samples collected from on top of the control showed that semen stains retained fluorescence and tested positive for AP, spermatozoa and p-30 through 22 days of testing. Semen samples collected from on top of the pig yielded similar results until day 16, when the fluorescence began to fade and AP testing did not yield traditional color changes associated with a positive result. By day 18, fluorescence was no longer visible with an ALS at 450 nm or 495 nm, however, UV light yielded positive fluorescence when used during days 19-21. Spermatozoa and p-30 were identified on samples saturated with products of decomposition, even when presumptive screening techniques were negative (450-495 nm) or showed an altered appearance (AP). Semen samples from within the ORD yielded full 16 loci profiles from beneath the pig and both on top of and beneath the control on each of the four days of testing. The samples collected from on top of the pig yielded full profiles on days 1, 6 and 14 and partial profiles on day 20. Samples from beneath the pig on days 6 and 14, which had positive presumptive results outside of the ORD, were also amplified, but failed to yield a profile.

Chemical separation undoubtedly accounts for a large proportion of process industries' activities. In the past few decades, 10-15% of the world's energy consumed was resulted from separation process. Tremendous efforts have been made in separating the components of large quantities of chemical mixtures into pure or purer forms in most industrial chemists. In addition, industrial development and population growth would lead to a further increase in the global demand for energy in the future. This makes the effective and efficient energy separation process one of the most challenging tasks in engineering. Adsorptive separation using porous materials is widely used in industry today. In order for an adsorptive separation process to be efficient, the essential requirement is a selective adsorbent that possesses high surface area and preferentially adsorbs one component (or class of similar components). Metal-organic frameworks (MOFs) are promising materials for separation purposes as their diversity, due to their building block synthesis from metal clusters and organic linker, gives rise to a wide range of porous structures. Engineering of a separation process is a multi-disciplinary problem that requires a holistic approach. In particular, material selection for industrial applications in the field of MOFs is one of the most significant engineering challenges. The complexity of a screening exercise for adsorptive separations arises from the multitude of existing porous adsorbents including MOFs. There are more than 80,000 structures that have been synthesised so far, as well as the multivariate nature of that performance criteria that need to be considered when selecting or designing an optimal adsorbent for a separation process. However, it is infeasible to assess all the potential materials experimentally to identify the promising structure for a particular application. Recently, molecular simulation and mathematical modelling have seen an ever- growing contribution to the research field of MOFs. The development of these computational tools offers a unique platform for the characterisation, prediction and understanding of MOFs, complementary to experimental techniques. In the first part of this research, Monte Carlo molecular simulation and a number of advanced mathematical methods were used to investigate newly synthesised or not well-known MOFs. These computational techniques allowed not only to characterise materials with their textural properties, but also to predict and understand adsorption performances at the atomic level. Based on the insight gained from the molecular simulation, two computational high-throughput screening approaches were designed and assessed. A multi-scale approach has been proposed and used which combined high-throughput molecular simulation, data mining and advanced visualisation, process system modelling and experimental synthesis and testing. The focus here was on two main applications. On one hand, the challenging CO/N2 separation, which is critical for the petrochemical sector, where two molecules have very similar physical properties. On the other hand, the separation of chiral molecules. For CO/N2 separation, a database of 184 Cu- Cu paddle-wheels MOFs, which contains unsaturated metal centres as strong interaction sites, was extracted from CSD (Cambridge Structural Database) MOF subset for material screening. In the case of chiral separation, an efficient high-throughput approach based on calculation of Henry's constant was developed in this research. Owning to the nature of chirality, this separation of relevance to the pharmaceutical sector is crucially important. A database of 1407 homochiral MOFs was extracted, again, from CSD MOF subset for material screening of enantioselective adsorption. The results obtained in these computational high-throughput approaches allows the screening of interesting, existing structures, and would have a huge impact on making MOFs to be industrially interesting adsorbents as well as guiding the synthesis of these materials. From the many different possibilities, the ultimate interest of this work is in developing an integrated systematic study of the structure-adsorption performance relationship working with a limited library of candidate MOF structures in order to identify promising trends and materials for the specific applications mentioned above. In summary, the overall aim of this research was exploiting different computational techniques, developing novel high-throughput approaches in order to tackle important engineering challenges.

Autophagy, referring to macroautophagy, is an evolutionarily conserved degradation pathway. Through autophagy cells can degrade damaged organelles, lipid vesicles and misfolded protein aggregates with implications in various pathological conditions, including neurodegenerative diseases, cancers, and infectious diseases. Autophagy is one of the major intracellular membrane-trafficking processes and its morphology includes the initiation, maturation, transportation and degradation of autophagosomes, where the double-membrane autophagosomes package the cargo for degradation. Therefore, understanding how autophagosomes form and are regulated is important in this field. Here we conducted a genome-wide siRNA screen using a high-throughput imaging system to identify undiscovered regulators in autophagosome formation. In this study, HEK293 cells stably expressing GFP-DFCP1 (GFP-tagged zinc finger FYVE-type containing 1) were used and amino acid starvation was used to induce autophagy. After the first round of primary screening, a small-scale screen was conducted with the same conditions including 384 candidates and additionally with these candidates HEK293 cells stably expressing GFPLC3 (GFP-tagged microtubule associated protein 1 light chain 3) were used to monitor the late steps of the autophagy process. From these rounds of screening, 39 candidates were selected and validated by investigating early autophagosome markers for their effects on autophagosome formation. Finally, five of the best candidates were confirmed based on their depletion effects on autophagy. Among these five candidates, DCAKD (dephospho-CoA kinase domain containing), WDR91 (WD repeat domain 91) and WDR65 were further investigated. Preliminary data using both RNAi and CRISPR Cas9 showed that DCAKD affected the accumulation of some early autophagy markers on initiation membranes in autophagosome formation. Interestingly, protein levels of canonical autophagy markers remained unchanged in DCAKD-deficient cells. Another candidate WDR91 showed the ability to mediate endosomal and lysosomal PtdIns3P and mildly affect autophagy initiation. WDR65 also inhibited early autophagy events. However, the detailed mechanism for these proteins are yet to be determined. In summary, our work provided more understanding on the egulation of autophagosome formation, as well as a list of potentially novel regulators.

Allt fler privata och institutionella investerare väljer att placera pengar i etiska fonder. Fondbolag världen över erbjuder sina kunder att investera i fonder som går i enighet med sina egna moraliska värderingar. Redan under 1700-talet kom idén om att investera etiskt. Syftet med denna typ av ekonomisk förvaltning har dock förändrats något de senaste decennierna. Idag råder det inget tvivel om att åsikter går isär om vilka bolag som bör få ingå i en etisk fond.Den tidigare forskningen visar att fondförvaltarna främst använder sig av två metoder när de avgör vilka bolag som skall ingå i de etiska fonderna. Dessa två metoder kallas för negativ och positiv screening. Även fondbolagen som ingick i denna uppsats använde sig av positiv respektive-negativ-screening.I den här uppsatsen undersöks de moraliska aspekter som finns kring etiskt fondsparande. Det sker även en gransking av hur fondförvaltarna väljer ut de bolag som skall ingå en etisk fond, samt vilka konsekvenser detta får för fonden ur ett moralfilosofiskt perspektiv. Denna uppsats beskriver dessa två principiellt olika tillvägagångssätt, där båda dessa påvisas vara problematiska. Detta gör att det går att det starkt går att ifrågasätta deras legitimitet.Uppsatsen har bidragit till att undersöka och beskriva huruvida dessa screeningsmetoder är etiskt hållbara genom att använda två olika moralfilosofiska infallsvinklar.Positiv screening är en allt för godtycklig metod som ger upphov till allt för många subjektiva bedömningar för fondförvaltarna. Dessutom bortser positiv screening från om företag har dåliga sidor, utan den fokuserar endast på styrkorna hos ett bolag. Detta gör att icke ansvarstagande bolag kan följa med.Negativ screening är en allt för motsägelsefull metod eftersom att den inte helt tar avstånd från de branscher som den försöker att stänga ute. Bland annat så stänger den inte ute underleverantörer till företag som exkluderas med denna metod. Fondbolagen tillåter också att vissa procent av omsättningen får komma från de branscher man försöker att stänga ute vilket gör att negativ screening förlorar sitt syfte. Dessutom är det tveksamt om fondbolagen överhuvudtaget bör utesluta spelbranschen, alkoholbranschen, eller pornografibranschen på enbart moralfilosofiska grunder.Vidare har även uppsatsen kommit fram till att det är de institutionella kunderna som driver utvecklingen framåt och att de har en stark påverkan på vilka branscher som väljs bort genom negativ screening.

No description available.

The ubiquitin-proteasome system (UPS) controls the stability, activity and localisation of most of the proteome and regulates virtually all cellular processes through modification of proteins with ubiquitin. Ubiquitin conjugation is mediated by a conserved enzymatic cascade composed of E1, E2 and E3 enzymes, which cooperate to activate and transfer ubiquitin to substrate proteins. Dysfunction of the UPS is implicated in many disease states, including cancer, neurodegeneration, immune and cardiovascular disorders. Despite the central role of the UPS in cellular regulation, our understanding of the function, interactions and specificity of proteins that comprise the UPS is still limited. One approach to dissect and to study the UPS is to identify molecular probes, which can be used to specifically interrogate catalytic mechanisms and can be potentially considered as entry points for drug discovery. This work focuses on developing novel high-throughput screening methods for inhibitors of the ubiquitin-conjugating enzymes (E2s), using a unicellular organism Saccharomyces cerevisiae and in vitro technologies. S. cerevisiae is a model organism, commonly used in research as a valuable tool for genetic investigations and other high-throughput studies. In this work, we evaluated the toxicity of exogenously expressed human E2s on yeast cells and discovered that one of the E2s, Ube2U, significantly inhibited yeast growth. This inhibition was dependent on the Ube2U ubiquitin-conjugation activity, as demonstrated with a catalytically inactive Ube2U C89A control, which did not affect yeast growth. The growth defect induced by Ube2U allowed us to develop a screening setup for inhibitors of Ube2U, where the enzyme activity was coupled to cell growth readout. Potential Ube2U inhibitors would be identified as rescuers of the slow growing Ube2U-expressing yeast phenotype. Although screening methods in yeast are relatively straightforward to set up and run, the advantages of this system, namely simplicity of the detection signal and high-throughput, are limited by the fact that yeast is not a recognised large scale screening system in pharmaceutical industry, and that it is difficult to identify the target in a complex pathway such as the UPS. In vitro technologies are needed to provide the necessary structure-activity relationship for chemical optimisation. Therefore, we developed a novel, fluorescence-based, miniaturised assay technology, suitable for biochemical investigations and screening for inhibitors of a wide range of specific ubiquitination reactions within the UPS.

Aim: To assess SELDI-TOF MS technology as a tool for biomarker discovery in the stool and serum of colorectal cancer patients. Materials and Methods: 1.Initially a technique of analysis was developed and optimised using tumour samples and matched normal mucosa, obtained from the Tayside Tissue Bank. These samples were then analysed using SELDI on a PBS II Protein Chip Mass Spectrometer to identify abundant proteins. 2. A technique of stool preparation and subsequent SELDI analysis was developed and then optimised (CM10 chip at pH4) to allow comparison of faecal samples from cancer and controls. Faecal samples were then collected from cancer patients and controls and analysed. In addition, FOB testing was carried out on all stool samples from cancer and controls and subgroup analysis of spectras was performed controlling for FOB status. 3. A test set of cancer and normal serum samples was used to optimise the method of analysis using 4 different chip surfaces at differing pH. Serum samples were collected from cancer patients and normal controls and were analysed on the H50 chip. Serum was then depleted of major proteins in an attempt to improve the detection of peaks. The mass spectra from each sample type were compared to identify any common protein peaks. Results: 1. Tumour analysis methods were optimised using an initial 4 samples of tumour and normal mucosa. Analysis of 8 further paired samples showed protein peaks at 2826, 3374, 3444, 3489 and 10854 Da which were abundant in tumour and reduced in the normal mucosa. 2. In serum analysis the initial experiment of 10 cancer versus 10 normal revealed 4 peaks on the H50 chip (3479, 3364, 3434, 3700 Da) that had significantly higher mass to charge ratios in cancer. The experiment was repeated on the H50 chip using 92 cancers and 92 controls and 5 different peaks were identified (7901, 8124, 8566, 8799 and 17 409Da) as being significant but these had higher mass to charge ratios in the controls. After depletion of the serum samples of albumin, transferrin, haptoglobin, anti-trypsin, IgG and IgA SELDI-TOF analysis showed a greatly reduced profile that yielded no meaningful spectra. 3. Stool analysis revealed 5 protein peaks (4633, 16511, 33423, 37087 and 47026 Da) in colorectal cancer patients, which were absent in stools from controls with a sensitivity of 83% when using all 5 peaks. Degradation of the spectra was observed after prolonged storage of stool samples. Conclusions: A method of stool analysis has been developed that yielded valid peaks differentiating between cancer and normal, which warrant further research through protein identification. Serum analysis was not reproducible across experiments and depletion of major proteins failed to reveal the sub-proteome raising doubts about whether discovery-based serum proteomics can accurately detect cancer. SELDI-TOF was not able to demonstrate that any of the peaks present in the tumour analysis were present in the stool or the serum samples.

Most of the prior research in the area of Islamic Investments has looked at performance; little attention has been given to the relationship between screening criteria and performance, especially in the GCC region. Therefore, this thesis examines the impact of using different screening criteria on the creation, and hence the performance of, Halal portfolios in Kuwait. In contrast to previous studies, the present study breakdowns Halal stocks in to ‘pure Halal’ (PH) and ‘Mixed Halal’ (MH), and the non-Halal stocks in to ‘Sin’ and ‘Mixed Sin’ (MS). This is to respond to the debate among Shariah scholars about the screening criteria, whether the fatwa on investing in them should be revisited and is it the right time to move towards pure Halal investments only. Specifically, this study explores the impact of tightening the current screening criteria on the creation and performance of Halal portfolios under different market conditions. Hence, broadly speaking, this thesis examine the issues associated with the creation and performance assessment of the Halal and non-Halal portfolios. For the purpose of this study, both quantitative and qualitative methods were employed. Firstly, due to the scarcity of literature, information and issues related to screening and performance were discussed with 58 face-to-face interviews with key figures in the Islamic investment funds industry in the GCC. The interviews explore whether MH are good investments from a Shariah perspective, and if there is a need to revisit the fatwa and the screening criteria. Secondly, different Halal portfolios were constructed based on the screening definitions suggested by the interviewees using a content analysis of companies’ annual reports listed in Kuwait Stock Exchange (KSE). This is to investigate the impact of applying different screens on the size of the Halal asset universe and whether it is possible to create diversified pure portfolios or at least MH that are close to pure Halal portfolios. Thirdly, quantitative methods were employed to examine whether these Halal portfolios are good investments from a financial perspective, using parametric and non-parametric statistical analysis and traditional risk-adjusted performance measures. Performance was first compared with the KSE market and a control portfolio (CP) as benchmarks then a ‘matched pair’ approach was also conducted. Finally, a general linear model (GLM) was applied to inspect whether the Shariah classification of stocks or other factors such as firm size, sector, and the global financial crisis (GFC) impact on performance. The findings from the interviews suggest that PH and MH investee companies are different types of Halal investments, and that there are a growing number of Islamic funds and individual investors that invest only in PH stocks, driven by religious motivations. Further, some interviewees seriously questioned the Shariah-compliance of MH stocks and thought of the fatwa that allows MH stocks should be revisited. Therefore, many interviewees agreed that the financial screening criteria needed to become tighter and that companies in Muslim countries should be treated differently from western ones as noted by Wilson (2005). Interviewees revealed that AAOIFI’s screening criteria are widely adopted in the GCC but most interviewees believed that the change in AAOIFI’s criteria in 2006 from total asset to market capitalization was intended to expand the Halal asset universe. Nonetheless, the analysis of companies’ annual reports finds that the use of AAOIFI (2006) during the GFC resulted in a sizeable number of MH equities being re-categorised as MS stocks, but without harming portfolios’ performance. Further, the statistical analyses suggest that there is no penalty for Halal investments during the full, the bullish or GFC periods, even after halving the screening thresholds. Differences were only identified during the bearish period, showing that some sin portfolios performed better, but overall, Halal portfolios did not underperform either the CP or the KSE index in any of the sample periods. Moreover, the GLM analysis also supports this finding that the Shariah-compliance of stocks is not the main factor affecting performance, but rather the sector they belong to and the GFC period. Hence, Islamic funds should consider allocating their investments more in the non-financial sectors rather than in the financial sector, especially during bearish markets to improve diversification. Nevertheless, there are fewer PH non-financial stocks, so, a ban on investment in MH stocks is premature, but ‘tightening’ the MH stocks’ financial screening thresholds is currently a better option. Some interviewees, also suggested that PH investors could diversify their portfolios by investing across all GCC stocks markets. Thus, Islamic fund managers need to be active fund managers focusing on certain sectors and markets in different market conditions. Halving the financial screening thresholds did not hurt MH portfolios’ performance because the loss in the number of MH stocks is compensated for by the lower interest-bearing gearing ratio of the individual companies suggested by the halved thresholds. This is supported by previous studies that report a negative relationship between stock returns and firms’ gearing, especially during market downturns (Penman et al., 2007; George and Hwang, 2010; Bhatt and Sultan, 2012). Finally, the screening analysis reveals an inadequate level of disclosure for assessing Sharia-compliance from companies’ annual reports. This highlights the need for harmonizing the Shariah screening criteria, and the development of accounting and auditing standards based on Islamic values rather than western ones to reflect the unique characteristics of Halal investment.

Thesis (MPH.) -- University of Limpopo, 2015 / Cervical cancer is a serious public health problem in both developed and developing countries. It is said to be the leading cause of death for women from developing countries as compared to other types of cancers. The aim of the study was to determine the initial clinical presentation of cervical cancer patients at the Pietersburg Hospital, Limpopo Province in South Africa. The objectives were to establish the demographic profile of cervical cancer patients, to identify the stage at initial clinical presentation, and to describe the factors that led to initial clinical presentation of cervical cancer patients at the Pietersburg Hospital in Limpopo Province, South Africa.The researcher conducted a quantitative retrospective cross-sectional survey by examining the records of cervical cancer patients seen for a period of three years from January 2012 to December 2014 at the Pietersburg. The results indicated that most patients, particularly the elderly, presented for the first time at the hospital with advanced stages of cervical cancer. Factors, such as age and place of residence contributed to this late presentation. There is a need for improved data capturing of information about marital status and parity to further assess the influence these two elements might have on the clinical presentation of cervical cancer. Furthermore, availability and facilities for screening should be improved because early detection of cervical cancer prevents progression to advanced stage of the disease. More awareness campaigns about risk factors of cervical cancer have to be implemented and a study is needed to establish why most patients with advanced stage cervical cancer are from Sekhukhune and Vhembe Districts, particularly the former Venda and Gazankulu Regions.

Postpartum depression (PPD) is a mood disorder affecting approximately 20% of women within 6 months of delivery. Untreated PPD diminishes a woman's functioning and may result in short and long-term consequences for her infant. Screening with evidence-based tools can identify prenatal and postpartum women at risk for PPD, ensure early treatment, and limit adverse maternal and infant effects. Using Rosswurm and Larrabee's evidence-based practice model, a multidisciplinary team of 7 key stakeholders, including directors and a nurse from the departments of OB/GYN, Pediatrics, and Primary Care, a psychiatrist specializing in women's health, and a member of nursing leadership, formed to guide the project. The purpose of the project was to develop a quality improvement initiative to promote antenatal and postnatal screening for PPD in the practice setting that lacked an evidence-based tool. As a federally qualified health center, the practice setting serves an ethnically and racially diverse population, particularly at risk for PPD. Project team members evaluated and graded current literature using the Johns Hopkins Evidence-Based Practice Rating Scale. The Edinburgh Postnatal Depression Scale (EPDS) was introduced and a policy and procedure developed to guide PPD screening. A formative evaluation of the policy and procedure using the AGREE instrument validated development. Project team members strongly agreed to use the EPDS as a PPD screening tool in the clinic population. A summative evaluation supported DNP student leadership of the project. The project has increased awareness of PPD and screening in the practice setting and, focused on improvements in the lives of women, infants, and their families.