Estimation of Correlation between Various Types of Pixel Intensities in a Single Spot

In cDNA microarray experiments, the measurement of interest is signal intensity ratio of spots. Each spot have four types of pixel intensities namely red foreground, green foreground, red background and green background. The uncertainty associated with the intensity ratio of a spot depends on the correlations between intensities of these pixels. In this article, we propose a method to estimate correlations between various types of pixel intensities within a spot using a modified form of Moran’s I spatial autocorrelation. We estimate these correlations for eight selected spots from image files downloaded from the Gene Expression Omnibus (GEO) database. These estimated correlations are used for finding the uncertainty associated with each of the selected eight spots using the theory of error propagation. We observed that the estimated uncertainty associated with intensity ratio of a spot is less if we consider the correlation between various pixel intensities compared to assuming zero correlation

The rural health care problem in the Sisonke District : St Apolinaris Hospital.

Thesis (MBA)-University of KwaZulu-Natal, 2007.With the advent of democracy in South Africa, there has been a growing awareness of the poor levels of health care that have been provided to rural areas in previous years. While members of the private sector can afford medical treatment equalling that provided in first world countries, the poor, who rely on the public sector, must rely on the services that are provided by their district hospital system. The remote St Apollinaris Hospital provides health care for approximately 150 000 of the 308 000 people who inhabit the Sisonke District. This hospital is unable to attract and maintain adequate human resource capital due to its remote location, it is frequently confronted with logistical problems. While St Apollinaris Hospital does function within the budgetary constraints of the Department of Health, there seems no effective mechanism by which the problems of this institute can be identified and dealt with. As St Apollinaris Hospital services almost half the district population, any improvement in the hospital's functioning and service delivery will have a direct impact on the health status of this rural area. This study aimed at identifying the shortfalls that were present at the St Apollinaris Hospital and focused on the management and administrative components, as well as human resources and equipment resources, which may contribute to the suboptimal health care of patients. This study was a qualitative observational cross sectional study with some quantitative aspects. As all workers and managers that were present were interviewed, there was no need for a sampling methodology. The sample size consisted of 128 general employees and eight top managers. A response rate of 85% was achieved which allowed the researcher to draw conclusions about all workers at the St Apollinaris Hospital. An inventory of the hospital's equipment was conducted using the Department of Health's essential equipment list. The out patients utilizing the hospital's services were analyzed to determine the effectiveness of the current referral pattern and the financial records of the hospital were analyzed to determine the effectiveness of the budgeting process. Understaffing was one of the most serious problems that the hospital had to contend with as 81% of employees identified this problem. 51% of employees stated that understaffing presented itself on a daily basis. The next problem faced was the low levels of equipment with there being a range of 35 to 69% of essential equipment present. There was no equipment pool. 90% of workers stated that the lack of equipment resulted in them becoming frustrated and 85% of workers stated that they believed that the low levels of equipment resulted in compromised patient care. The recommendations that were made include St Apollinaris Hospital instituting a long term and short term recruitment strategy to help with the understaffing that may be present. A full equipment plan needs to be instituted at St Apollinaris Hospital. Attention should be paid to bringing the essential equipment up to the prescribed levels as soon as possible. An equipment pool should be established and maintained. More research is needed with regard to the outpatient and financial components of this study

AT 2023prq: A Classical Nova in the Halo of the Andromeda Galaxy

The classical nova, AT 2023prq, was discovered on 2023 August 15 and is located at a distance of 46 kpc from the Andromeda Galaxy (M 31). Here we report photometry and spectroscopy of the nova. The 'very fast' ($t_{2,r^{\prime}}\sim3.4$ d) and low luminosity ($M_{r^{\prime}}\sim-7.6$) nature of the transient along with the helium in its spectra would indicate that AT 2023prq is a 'faint-and-fast' He/N nova. Additionally, at such a large distance from the centre of M 31, AT 2023prq is a member of the halo nova population.Comment: 3 pages, 1 figure; Published in Research Notes of the American Astronomical Societ

Navigating drug repurposing for Chagas disease: advances, challenges, and opportunities

Chagas disease is a vector-borne illness caused by the protozoan parasite Trypanosoma cruzi (T. cruzi). It poses a significant public health burden, particularly in the poorest regions of Latin America. Currently, there is no available vaccine, and chemotherapy has been the traditional treatment for Chagas disease. However, the treatment options are limited to just two outdated medicines, nifurtimox and benznidazole, which have serious side effects and low efficacy, especially during the chronic phase of the disease. Collectively, this has led the World Health Organization to classify it as a neglected disease. To address this problem, new drug regimens are urgently needed. Drug repurposing, which involves the use of existing drugs already approved for the treatment of other diseases, represents an increasingly important option. This approach offers potential cost reduction in new drug discovery processes and can address pharmaceutical bottlenecks in the development of drugs for Chagas disease. In this review, we discuss the state-of-the-art of drug repurposing approaches, including combination therapy with existing drugs, to overcome the formidable challenges associated with treating Chagas disease. Organized by original therapeutic area, we describe significant recent advances, as well as the challenges in this field. In particular, we identify candidates that exhibit potential for heightened efficacy and reduced toxicity profiles with the ultimate objective of accelerating the development of new, safe, and effective treatments for Chagas disease

Association of Usage of Online Journals with Impact Factors: A Descriptive Analytical Study

A case study of association between usage of online journals and their impact factors was conducted for the subscribed journals of the Health Sciences Library of Manipal Academy of Higher Education, Manipal. The publisher-generated usage statistics were collected and tabulated for the period 2010-2015. The full text usage was considered as the criteria for identification of the extent of usage of online journals from different publishers. The Journal Impact Factor (JIF) of these journals were retrieved in 2015 from Journal Citation Report to check whether association existed between the most used and the least used journals with their impact factor. The study identified two lists of journals, the most used and the least used journals, from among the subscribed online journals through the usage analysis. ‘Mann Whitney U test’ was performed to check the association between the usage of online journals and their impact factors. It was observed that there is a statistically significant difference (p\u3c0.001) in the impact factors of the most used journals and the least used journals, which indicated that an association existed between the IFs and the usage. The application of the outcome measures of the study provide a benchmark for the online journal collection for the libraries that explore the usage of its online resources. Study also propositions the means for increasing the usage of subscribed online journals

Inhibition of HSP90 distinctively modulates the global phosphoproteome of Leishmania mexicana developmental stages

Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that plays a central role in the folding and maturation of a large array of client proteins. In the unicellular parasite Leishmania, the etiological agent of the neglected tropical disease leishmaniasis, treatment with HSP90 inhibitors leads to differentiation from promastigote to amastigote stage, resembling the effects of established environmental triggers, low pH and heat shock. This indicates a crucial role for HSP90 in the life cycle control of Leishmania. However, the underlying molecular mechanisms remain unknown. Using a combination of treatment with the classical HSP90 inhibitor tanespimycin, phosphoproteome enrichment, and tandem mass tag (TMT) labeling-based quantitative proteomic mass spectrometry (MS), we systematically characterized the perturbing effect of HSP90 inhibition on the global phosphoproteome of Leishmania mexicana across its life cycle stages and showed that the HSP90 inhibition causes substantially distinct molecular effects in promastigote and amastigote forms.While phosphorylation of HSP90 and its co-chaperone HSP70 was decreased in amastigote, the opposite effect was observed in promastigotes. Our results showed that kinase activity and microtubule motor activity are highly represented in the negatively affected phosphoproteins of the promastigotes, whereas ribosomal proteins, protein folding, and proton channel activity are preferentially enriched in the perturbed amastigote phosphoproteome. Additionally, cross-comparison of our results with HSP90 inhibition-affected RNA-binding proteins showed that RNA helicase domains were distinctively enriched among the upregulated amastigote phosphoproteins. In addition to providing robust identification and quantification of 1,833 phosphorylated proteins across three life cycle stages of L. mexicana, this study reveals the dramatically different ways the HSP90 inhibition stress modulates the phosphoproteome of the pathogenic amastigote and provides in-depth insight into the scope of selective molecular targeting in the therapeutically relevant amastigote stage

Developing chemical biology approaches for the activity-based investigations of reversible protein phosphorylation-mediating enzymes

Ph.DDOCTOR OF PHILOSOPH

Inhibiting the reproduction of SARS-CoV-2 through perturbations in human lung cell metabolic network

Viruses rely on their host for reproduction. Here, we made use of genomic and structural information to create a biomass function capturing the amino and nucleic acid requirements of SARS-CoV-2. Incorporating this biomass function into a stoichiometric metabolic model of the human lung cell and applying metabolic flux balance analysis, we identified host-based metabolic perturbations inhibiting SARS-CoV-2 reproduction. Our results highlight reactions in the central metabolism, as well as amino acid and nucleotide biosynthesis pathways. By incorporating host cellular maintenance into the model based on available protein expression data from human lung cells, we find that only few of these metabolic perturbations are able to selectively inhibit virus reproduction. Some of the catalysing enzymes of such reactions have demonstrated interactions with existing drugs, which can be used for experimental testing of the presented predictions using gene knockouts and RNA interference techniques. In summary, the developed computational approach offers a platform for rapid, experimentally testable generation of drug predictions against existing and emerging viruses based on their biomass requirements

Hydrodynamic simulations of the KT Eridani nova super-remnant

A nova super-remnant (NSR) is an immense structure associated with a nova that forms when frequent and recurrent nova eruptions sweep up surrounding interstellar material (ISM) into a high density and distant shell. The prototypical NSR, measuring over 100 pc across, was discovered in 2014 around the annually erupting nova M31N 2008-12a. Hydrodynamical simulations demonstrated that the creation of a dynamic NSR by repeated eruptions transporting large quantities of ISM is not only feasible but that these structures should exist around all novae, whether the white dwarf (WD) is increasing or decreasing in mass. But it is only the recurrent nova (RNe) with the highest WD masses and accretion rates that should host observable NSRs. KT Eridani is, potentially, the eleventh RNe recorded in the Galaxy and is also surrounded by a recently unveiled H{\alpha} shell tens of parsecs across, consistent with a NSR. Through modelling the nova ejecta from KT Eri, we demonstrate that such an observable NSR could form in approximately 50,000 years, which fits with the proper motion history of the nova. We compute the expected H{\alpha} emission from the KT Eri NSR and predict that the structure might be accessible to wide-field X-ray facilities.Comment: 9 pages, 7 figures; Accepted for publication in Monthly Notices of the Royal Astronomical Societ

On an apparent dearth of recurrent nova super-remnants in the Local Group

The Andromeda Galaxy is home to the annually erupting recurrent nova (RN) M31N 2008-12a (12a); the first nova found to host a nova super-remnant (NSR). A NSR is an immense structure surrounding a RN, created from many millions of eruptions sweeping up material in the local environment to form a shell tens of parsecs across. Theory has demonstrated that NSRs should be found around all RNe, even those systems with long periods between eruptions. Befittingly, the second NSR was found around the Galactic classical (and long suspected recurrent) nova, KT Eridani. In this Paper, we aim to find more of these phenomena through conducting the first ever survey for NSRs in M31 and the Large Magellanic Cloud (LMC). We find that the surroundings of fourteen RNe in M31 as well as the surroundings of the four RNe in the LMC do not show any evidence of vast parsec-scale structures in narrowband (Hα and [S II]) images, unlike the one clearly seen around 12a, and therefore conclude that observable NSRs are either rare structures, or they are too faint (or small) to be detected in our existing datasets. Yet, the NSR surrounding 12a would also likely to have been overlooked in our study if it were approximately one magnitude fainter. Searches for NSRs around other RNe 'masquerading' as classical novae may prove to be fruitful as would whole surveys of other Local Group galaxies