Linker insertion mutagenesis of the human immunodeficiency virus reverse transcriptase expressed in bacteria: definition of the minimal polymerase domain

A plasmid construct expressing the p66 version of the human immunodeficiency virus reverse transcriptase as a bacterial fusion protein was subjected to in vitro mutagenesis, and the resulting variant proteins were assayed to define the locations of the two major enzymatic activities. The DNA polymerase activity was localized to the N-terminal portion of the protein; mutations altering or eliminating the C-terminal portion had little or no effect on that activity. The results suggest that, in contrast with previous reports, the p51 subunit found in virions should exhibit DNA polymerase activity. Mutations in many parts of the protein eliminated RNase H activity, suggesting that several areas are needed for proper folding and generation of that activity

A clinical study of the prevalence and impact of allergic rhinitis in children with asthma

Background: Allergic rhinitis (AR) and asthma are highly prevalent conditions that cause major illness worldwide. Surveys have shown that approximately 60-80% of children with asthma have symptoms of AR. Objectives: To study the prevalence of AR and its impact in children with asthma. Materials and Methods: A prospective cohort study of 130 children between the age group of 5 and 15 years, with the diagnosis of asthma, who presented with symptoms and signs of AR based on AR and comorbidities training module formed the study group. A detailed history and examination were recorded in a systematically designed pro forma. Apart from the routine investigation and management, these childrens nasal smear for eosinophils was taken to confirm the diagnosis of AR. Results: Among the study group, the prevalence of AR in children with asthma was found to be 76/130 (58%), of which 43/76 (56%) had intermittent and 33/76 (44%) had persistent AR. 66% of the children with AR had persistent asthma (p<0.001). Nasal smear eosinophilia was positive in 54/76 (71%) of the children with AR. Conclusion: There is a high prevalence of AR in children with asthma. The presence of AR in children with asthma is associated with poor asthma control

Study to evaluate the effectiveness of coagulation factor concentrate prophylaxis in children with severe hemophilia

Objective: To evaluate the effectiveness of prophylaxis with coagulation factor concentrates VIII/IX (FVII/IX) in children with severe hemophilia A/B, respectively. Materials and Methods: Retrospective observational study was done on children enrolled in our hemophilia clinic, who initially received “on demand” therapy and were on prophylaxis with factor VIII/IX concentrate at the time of the study. The study group consisted of 8 children. Annual hemarthrosis rate (AHR) over a period of 1-year during on demand therapy was compared with AHR during a period of 1-year on prophylaxis with FVIII/IX. Results: There was reduction in AHR by 87% in hemophilia A and 85% in hemophilia B during prophylaxis compared to on demand therapy. There was a significant reduction in hemarthrosis/patient/year from 2.5 to 0.3 on prophylaxis with factor concentrate compared to on demand therapy. There was also reduction in other bleeding manifestation like psoas muscle bleed, oral bleeds, epistaxis, and number of target joints involved. Conclusion: Prophylaxis with coagulation factor concentrate significantly reduces the AHR, and hence, decreases the disability associated with it compared to “on demand” therapy

Isolation and characterization of a dideoxyguanosine triphosphate-resistant mutant of human immunodeficiency virus reverse transcriptase

The appearance of drug-resistant strains of viral pathogens is a major difficulty confounding current efforts to block viral infections. The identification and analysis of mutations responsible for drug resistance can provide important clues helpful in understanding the mechanisms of resistance and in the eventual development of better therapies. We have used a direct screening method to scan libraries of mutagenized genes encoding the reverse transcriptase of human immunodeficiency virus type 1, and have recovered a variant enzyme that is resistant to the chain-terminator inhibitor 2',3'-dideoxyguanosine triphosphate. The single substitution mutation in this variant conferred broad crossresistance to a variety of other antiviral compounds currently in clinical trials. Virus carrying the mutation was fully infectious in cultured human lymphocytes. The replication of the mutant virus was highly resistant to phosphonoformic acid but did not show increased resistance to the prodrug dideoxyguanosine

Primary Adenosquamous Carcinoma of Ascending Colon – A Rare Entity

Colorectal cancers (CRC) are on the rise globally with increased incidence rate 5.7/100000 cases in developing countries like India. 1 Majority (90%) of CRC are adenocarcinoma. The primary adenosquamous carcinoma (ASC) of the colon is exceedingly rare variant of adenocarcinoma with incidence of 0.025% and accounts for 0.1% of colonic epithelial malignancies. 2 The squamous differentiation accounts for its aggressiveness and poor prognosis. Here we report a rare case of primary ASC in 80year old male who presented with large bowel obstruction and peritonitis. A 80-year-old male brought to causality with history of fever, vomiting, pain in abdomen, altered sensorium since three days. The clinical examination revealed intestinal obstruction and peritonitis. Patient was immediately subjected for radiological and hematology investigations which showed signs of bowel obstruction and perforation. On emergency exploratory laparotomy, colonic perforation was identified along with an ulcer proliferative mass in ascending colon. Gross examination of right hemicolectomy revealed 9x6x3cm ulcero proliferative mass in ascending colon. The microscopic examination showed an infiltrating tumor composed of adenocarcinoma component and areas of squamous differentiation (60%) noted. Tumor was invading through muscularis propria and serosa. Final diagnosis of primary ASC was made. Colonic ASC is rare and associated with poorer prognosis. The squamous cell differentiation has greater metastatic potential than adenocarcinoma. Compared to adenocarcinoma, ASC is more likely to manifest with advanced disease and complications. Keywords: Adenosquamous, Carcinoma, Colo

FREQUENCY EVALUATION FOR MECHANICAL INTEGRATION OF SHROUDED HP ROTOR BLADES IN AN AIRCRAFT ENGINE COMPRESSOR

Frequency evaluation in rotary engine blade design is an important research area because of its critical applications in aircraft engines and land-based gas engines. A compressor blade plays an important role in increasing pressure and velocity of the fluid, which influences the efficiency of gas turbines. Due to peak centrifugal stresses, gas bending loads and vibratory stresses, flow-induced blade vibrations occur leading to blade catastrophe. The airfoil is expected to prove not only the mechanical efficiency but also mechanical integrity for a desired life. The present research focuses on the study of the vibrational behaviour of an Axial HP Shrouded Compressor blade for in-service conditions. A Computational Fluid Dynamics based model is generated with reference to NACA 65-series, to analyse the flow behaviour through a linear cascade of axial compressor blades, followed by mechanical integrity stress checks to take it further with root attachment design. The present work demonstrates the need for shrouds in compressor rotor blades for stiffening the blade to avoid resonance. The positioning of the shroud is a challenge across the blade height by achieving Frequency Separation Margins using Campbell Diagram, an industry best practice

Perspectives on tracking data reuse across biodata resources

c The Author(s) 2024. Published by Oxford University Press.Motivation: Data reuse is a common and vital practice in molecular biology and enables the knowledge gathered over recent decades to drive discovery and innovation in the life sciences. Much of this knowledge has been collated into molecular biology databases, such as UniProtKB, and these resources derive enormous value from sharing data among themselves. However, quantifying and documenting this kind of data reuse remains a challenge. Results: The article reports on a one-day virtual workshop hosted by the UniProt Consortium in March 2023, attended by representatives from biodata resources, experts in data management, and NIH program managers. Workshop discussions focused on strategies for tracking data reuse, best practices for reusing data, and the challenges associated with data reuse and tracking. Surveys and discussions showed that data reuse is widespread, but critical information for reproducibility is sometimes lacking. Challenges include costs of tracking data reuse, tensions between tracking data and open sharing, restrictive licenses, and difficulties in tracking commercial data use. Recommendations that emerged from the discussion include: development of standardized formats for documenting data reuse, education about the obstacles posed by restrictive licenses, and continued recognition by funding agencies that data management is a critical activity that requires dedicated resources

Empirical investigation to explore potential gains from the amalgamation of Phase Changing Materials (PCMs) and wood shavings

The reduction of gained heat, heat peak shifting and the mitigation of air temperature fluctuations are some desirable properties that are sought after in any thermal insulation system. It cannot be overstated that these factors, in addition to others, govern the performance of such systems thus their effect on indoor ambient conditions. The effect of such systems extends also to Heating, Ventilation and Air-conditioning (HVAC) systems that are set up to operate optimally in certain conditions. Where literature shows that PCMs and natural materials such as wood-shavings can provide efficient passive insulation for buildings, it is evident that such approaches utilise methods that are of a degree of intricacy which requires specialist knowledge and complex techniques, such as micro-encapsulation for instance. With technical and economic aspects in mind, an amalgam of PCM and wood-shavings has been created for the purpose of being utilised as a feasible thermal insulation. The amalgamation was performed in the simplest of methods, through submerging the wood shavings in PCM. An experimental procedure was devised to test the thermal performance of the amalgam and compare this to the performance of the same un-amalgamated materials. Comparative analysis revealed that no significant thermal gains would be expected from such amalgamation. However, significant reduction in the total weight of the insulation system would be achieved that, in this case, shown to be up to 20.94%. Thus, further reducing possible strains on structural elements due to the application of insulation on buildings. This can be especially beneficial in vernacular architectural approaches where considerably large amounts and thicknesses of insulations are used. In addition, cost reduction could be attained as wood shavings are significantly cheaper compared to the cost of PCMs