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Study Focus: In this paper, the thermal behavior of a semi-spherical fin embedded in a porous medium is examined. The heat transfer coefficient is considered to be temperature-dependent and follows a power-law relationship.Modeling Approach: Heat transmission through the porous medium is modeled using Darcy’s law, with the flow velocity as a key factor.Methodology: The Legendre wavelet collocation method (LWCM) is employed to solve the governing equations and predict the temperature distribution within the fin. Results obtained from LWCM are compared to those from the least squares method and numerical methods, showing good agreement and validating the proposed method. The effects of various parameters on the temperature distribution in the fin are analyzed and presented through figures and tables. Conclusion:: The study concludes that the Legendre wavelet collocation method is an efficient and powerful technique for obtaining analytical solutions for heat transfer problems in porous media.

Abstract Introduction Early studies exploring the physiological effects of space travel have indicated the body's capacity for reversible adaptation. However, the impact of long‐duration spaceflight, exceeding 6 months, presents more intricate challenges. Effects on the Cardiovascular (CV) System Extended exposure to microgravity and radiation profoundly affects the CV system. Notable phenomena include fluid shifts toward the head and modified arterial pressure. These changes disrupt blood pressure regulation and elevate cardiac output. Additionally, the loss of venous compression leads to a reduction in central venous pressure. Fluid and Plasma Volume Changes The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%–15% decline in plasma volume. Cardiac Muscle and Hematocrit Variations Intriguingly, despite potential increases in cardiac workload, cardiac muscle atrophy and perplexing variations in hematocrit levels have been observed. The mechanism underlying atrophy appears to involve a shift in protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin‐mediated mechanisms. Arrhythmias and QT Interval Prolongation Instances of arrhythmias have been recurrently documented, although generally nonlethal, in both Russian and American space missions. Long‐duration spaceflight has been associated with the prolongation of the QT interval, particularly in extended missions. Radiation Effects Exposure of the heart to the proton and heavy ion radiation pervasive in deep space contributes to coronary artery degeneration, augmented aortic stiffness, and carotid intima thickening through collagen‐mediated processes. Moreover, it accelerates the onset of atherosclerosis and triggers proinflammatory responses. Reentry and Postflight Challenges Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. Conclusion Consequently, careful monitoring of these cardiac risks is imperative for forthcoming missions. While early studies illuminate the adaptability of the body to space travel's challenges, the intricacies of long‐duration missions and their effects on the CV system necessitate continued investigation and vigilance to ensure astronaut health and mission success.

IntroductionMycobacterium tuberculosis (Mtb) has the capability to dodge the immune system by escaping into alternate physiological forms by forming drug tolerant populations under the immune pressure in the host. New drugs are urgently needed to treat these non-replicating persisters. In the past, aminoglycoside antibiotics have played a pivotal role in TB chemotherapy.MethodsHere, we explored the therapeutic potential of a monosubstituted deoxystreptamine aminoglycoside, apramycin (APR) which is different in its chemical structure from the other clinically relevant aminoglycoside antibiotics that are all disubstituted, e.g., amikacin (AMI). We determined the APR MIC as 0.25-1 µg/ml for sensitive and multidrug-resistant Mtb (MDRTB), including amikacin (AMI) resistant strains.ResultsIn standard time-kill kinetic assays, the bactericidal activity of APR was similar to that of AMI demonstrating dose-dependent killing of planktonic Mtb. However, in biofilm and macrophage intracellular killing assays, APR appeared significantly more potent than AMI. Further, APR monotherapy was efficacious in a mouse chronic TB lung infection model (~0.92 log10 CFU/lung reduction). APR combination therapy with the current 1st line standard of care (SoC) antibiotic combination of isoniazid (H), rifampicin (R), ethambutol (E), and pyrazinamide (Z) was found to be additive (HREZ=1.88 vs. HREZ-APR=2.78 log10CFU/lung reduction).DiscussionThe results indicate the potential of apramycin-based combinations for the treatment of human tuberculosis.

Abstract Antimicrobial resistance is a global health threat that requires the development of new treatment concepts. These should not only overcome existing resistance but be designed to slow down the emergence of new resistance mechanisms. Targeted protein degradation, whereby a drug redirects cellular proteolytic machinery towards degrading a specific target, is an emerging concept in drug discovery. We are extending this concept by developing proteolysis targeting chimeras active in bacteria (BacPROTACs) that bind to ClpC1, a component of the mycobacterial protein degradation machinery. The anti-Mycobacterium tuberculosis (Mtb) BacPROTACs are derived from cyclomarins which, when dimerized, generate compounds that recruit and degrade ClpC1. The resulting Homo-BacPROTACs reduce levels of endogenous ClpC1 in Mycobacterium smegmatis and display minimum inhibitory concentrations in the low micro- to nanomolar range in mycobacterial strains, including multiple drug-resistant Mtb isolates. The compounds also kill Mtb residing in macrophages. Thus, Homo-BacPROTACs that degrade ClpC1 represent a different strategy for targeting Mtb and overcoming drug resistance.

Despite the strict rejection of casteism by the Sikh faith, caste-based hierarchies are still a prevalent factor amongst Sikh diasporas within the UK. On the basis of ethnographic fieldwork amongst women whose caste is considered to occupy a lower status, this paper examines their experiences and explores how, over time, this has contributed to the construction of their identity. This article situates the women within a nexus of complex social and cultural factors, illuminating the representations of caste, gender and intergenerational change within Nottingham. An intersectional standpoint provided an analytical value in accentuating the sites where gender, caste and the mediation of honour intersected. The research shows a heterogeneity in the self-positioning of women vis-à-vis caste identity and shows a marked difference in attitudes between generations, denoting a depreciation in the significance of caste. Ultimately, while the respondents were conscious of their caste and of the historical prejudice against their caste, it is significant that they did not live their lives through it, as they internalised Sikhi as their core identity.

A novel organic acid-modified starch and carboxymethyl cellulose (CMC) based films plasticized with glycerol were prepared from unconventional tikhur starch (Curcuma angustifolia) by solution casting. Wet milling was used in the laboratory to extract starch from the tikhur rhizome. Carboxymethyl cellulose, at a concentration of (0.2 g−1 starch dry basis) was blended with the starch to improve its film-forming properties. Three different treatments with varying organic acids (lactic, citric, and acetic acid) with a concentration of 5% w/w of starch (2 ppm) in a film-forming solution were given. The effect of organic acid incorporation on the antibacterial, morphological, structural, thermal, and crystalline properties of developed films was studied. The minimum inhibitory concentration values of the three organic acids against gram-negative (E. coli) and gram-positive (S. aureus) bacteria were measured using the tube dilution method. The MIC results revealed that lactic acid and citric acid are effective against both gram-negative and gram-positive bacteria, while acetic acid showed more effectiveness against gram-negative bacteria (E. coli). MBC results revealed that organic acids have potent bactericidal activity. Citric acid resulted in higher inhibition for gram-positive bacteria (S. aureus) compared to gram-negative bacteria (E. coli.). While acetic acid showed higher inhibition for E. coli. than S. aureus. Lactic acid displayed similar inhibition against both S. aureus and E. coli. Among different organic acids, lactic acid incorporation resulted in a more homogeneous, transparent, and thermally stable film. As evidenced by the micrographs, the lactic acid incorporation resulted in a compact film structure without any visible cracks. While X-ray diffraction showed an increase in crystalline properties due to organic acid modification. In this study, it was indicated that modification with organic acids (polycarboxylic acids) effectively improved the overall properties of developed films depending on the type of organic acid used. The developed films have the potential to replace harmful synthetic films in food packaging.

Non-tuberculous Mycobacteria (NTM), previously classified as environmental microbes, have emerged as opportunistic pathogens causing pulmonary infections in immunocompromised hosts. The formation of the biofilm empowers NTM pathogens to escape from the immune response and antibiotic action, leading to treatment failures. NF1001 is a novel thiopeptide antibiotic first-in-class compound with potent activity against planktonic/replicating and biofilm forms of various NTM species. It is potent against both drug-sensitive and -resistant NTM. It has demonstrated a concentration-dependent killing of replicating and intracellularly growing NTM, and has inhibited and reduced the viability of NTM in biofilms. Combination studies using standard-of-care (SoC) drugs for NTM exhibited synergetic/additive effects, but no antagonism against both planktonic and biofilm populations of Mycobacterium abscessus and Mycobacterium avium. In summary, the activity of NF1001 alone or in combination with SoC drugs projects NF1001 as a promising candidate for the treatment of difficult-to-treat NTM pulmonary diseases (NTM-PD) and cystic fibrosis (CF) in patients.

Gamma ray shielding ability of WO3 borate glasses is analyzed by using the Phy-X/PSD software. Mass attenuation coefficient of glasses gets enhanced with addition of tungsten oxide resulting in lowering of the values of MFP, HVL, TVL and EBF at 10 mol % of tungsten as compared to many commercial and radiation shielding glasses/concretes. The higher value of FNRCS (∑R) in studied glasses than concretes shows their neutron shielding ability. The sample with highest value of tungsten is most suitable for making radiation shielding materials. The OPD, OMV, n¯c, nb and dbb values indicate the rigid and stable glass structure due to the formations of stable BO4 groups. Poisson ratio confirms high cross density and stability of prepared glasses as its value decreases from 0.233 to 0.226. The increased values of elastic constants and VHN are also in the favour of higher stability and rigidity of the glasses due to addition of WO3. All of these parameters are in good relation with each other and support the shielding power of the studied glasses.

Aim of present study was to estimate quantitative changes in nutraceutical properties of cookies. Refined wheat flour and raw/roasted flaxseed flour blends (100:00, 90:10, 80:20, and 70:30) were prepared and subjected for baking to prepare cookies. Effect of addition of raw/roasted flaxseed flour at different proportions on nutritional, physicochemical (weight, diameter, thickness and spread ratio) and phytochemical (total phenolic content and total flavonoids content) properties were studied. Antioxidant capacity was measured by using TEAC assay. Colour and texture measurement was undertaken with the help of HunterLab colorimeter and Texture Analyzer (TA-XT2) respectively. Refined wheat flour was found to have 4.26% protein and 0.04% fiber which were further increased to about 9.25% and 2.37% respectively after addition of raw flaxseed flour in 70:30 proportions. Baking process at higher temperature resulted in decrease in TPC and TFC while increase in antioxidant capacity. Hardness, resilience, chewiness and springiness of cookies decreased and cohesiveness, gumminess and fracturability increased with increasing amount of flaxseed flour in cookies. Keywords: Flaxseed flour, Baking, Cookies characteristics, Phytochemicals

Aim: With the increased demand to undertake dental aesthetic and reconstructive procedures, it is imperative for all dental clinicians to have an understanding of body dysmorphic disorder (BDD). Patient's preoccupations with perceived defect in appearance or excessive concern about minimal flaws are among diagnostic criteria of BDD. Such patients are difficult to please and often undergo cosmetic procedures such as orthodontic treatment. Methodology: Literature search in PubMed/MEDLINE was conducted from 1891 to 2015. A manual search of relevant articles and review was done and relevant data was collected and analysed. Results: One of the most common areas of preoccupation is the dento-facial region, with up to 20% of patients diagnosed with BDD expressing specific concern regarding their dental appearance. Conclusion: BDD patients often request multiple aesthetic procedures, but remain unsatisfied with their treatment results.

One of the major impediments in anti-tubercular drug discovery is the lack of a robust grammar that governs the in-vitro to the in-vivo translation of efficacy. Mycobacterium tuberculosis (Mtb) is capable of growing both extracellular as well as intracellular; encountering various hostile conditions like acidic milieu, free radicals, starvation, oxygen deprivation, and immune effector mechanisms. Unique survival strategies of Mtb have prompted researchers to develop in-vitro equivalents to simulate in-vivo physiologies and exploited to find efficacious inhibitors against various phenotypes. Conventionally, the inhibitors are screened on Mtb under the conditions that are unrelated to the in-vivo disease environments. The present study was aimed to (1). Investigate cidality of Mtb targets using a non-chemical inhibitor antisense-RNA (AS-RNA) under in-vivo simulated in-vitro conditions.(2). Confirm the cidality of the targets under in-vivo in experimental tuberculosis. (3). Correlate in-vitro vs. in-vivo cidality data to identify the in-vitro condition that best predicts in-vivo cidality potential of the targets. Using cidality as a metric for efficacy, and AS-RNA as a target-specific inhibitor, we delineated the cidality potential of five target genes under six different physiological conditions (replicating, hypoxia, low pH, nutrient starvation, nitrogen depletion, and nitric oxide).In-vitro cidality confirmed in experimental tuberculosis in BALB/c mice using the AS-RNA allowed us to identify cidal targets in the rank order of rpoB>aroK>ppk>rpoC>ilvB. RpoB was used as the cidality control. In-vitro and in-vivo studies feature aroK (encoding shikimate kinase) as an in-vivo mycobactericidal target suitable for anti-TB drug discovery. In-vitro to in-vivo cidality correlations suggested the low pH (R = 0.9856) in-vitro model as best predictor of in-vivo cidality; however, similar correlation studies in pathologically relevant (Kramnik) mice are warranted. In the acute infection phase for the high fidelity translation, the compound efficacy may also be evaluated in the low pH, in addition to the standard replication condition.

Aberrant glycosylation is one of the major hallmarks of cancer with altered gene expression signatures of sialyltransferases. ST3Gal-I, a sialyltransferase, is known to play a crucial role in sialylation of T antigen in bladder cancer and it has reported elevated expression in breast carcinogenesis with increased tumor progression stages. The aim of the current study is to develop new monoclonal antibodies (mAbs) against human ST3Gal-I and evaluate their diagnostic potential. We developed a repertoire of stable hybridoma cell lines producing high-affinity IgG antibodies against recombinant human ST3Gal-I, expressed in E. coli BL21-DE3 strain. In order to demonstrate the diagnostic value of the mAbs, various clones were employed for the immunohistochemistry analysis of ST3Gal-I expression in cancerous tissues. Antibodies generated by 7E51C83A10 clone demonstrated a strong and specific fluorescence staining in breast cancer tissue sections and did not exhibit significant background in fibroadenoma sections. In conclusion, the mAbs raised against recombinant ST3Gal-I recognize cellular ST3Gal-I and represent a promising diagnostic tool for the immunodetection of ST3Gal-I expressing cells. Specific-reactivity of clone 7E51C83A10 mAbs towards ST3Gal-I was also confirmed by immunoblotting. Therefore, our observations warrant evaluation of ST3Gal-I as a potential marker for cancer diagnosis at larger scale.

Exposure to Mycobacterium tuberculosis (Mtb) aerosols is a major threat to tuberculosis (TB) researchers, even in bio-safety level-3 (BSL-3) facilities. Automation and high-throughput screens (HTS) in BSL3 facilities are essential for minimizing manual aerosol-generating interventions and facilitating TB research. In the present study, we report the development and validation of a high-throughput, 24-well 'spot-assay' for selecting bactericidal compounds against Mtb. The bactericidal screen concept was first validated in the fast-growing surrogate Mycobacterium smegmatis (Msm) and subsequently confirmed in Mtb using the following reference anti-tubercular drugs: rifampicin, isoniazid, ofloxacin and ethambutol (RIOE, acting on different targets). The potential use of the spot-assay to select bactericidal compounds from a large library was confirmed by screening on Mtb, with parallel plating by the conventional gold standard method (correlation, r2 = 0.808). An automated spot-assay further enabled an MBC90 determination on resistant and sensitive Mtb clinical isolates. The implementation of the spot-assay in kinetic screens to enumerate residual Mtb after either genetic silencing (anti-sense RNA, AS-RNA) or chemical inhibition corroborated its ability to detect cidality. This relatively simple, economical and quantitative HTS considerably minimized the bio-hazard risk and enabled the selection of novel vulnerable Mtb targets and mycobactericidal compounds. Thus, spot-assays have great potential to impact the TB drug discovery process.

Methylmercury (MeHg), an environmental toxicant primarily found in fish and seafood, poses a dilemma to both consumers and regulatory authorities, given the nutritional benefits of fish consumption versus the possible adverse neurological damage. Several studies have shown that MeHg toxicity is influenced by a number of biochemical factors, such as glutathione (GSH), fatty acids, vitamins, and essential elements, but the cellular mechanisms underlying these complex interactions have not yet been fully elucidated. The objective of this paper is to outline the cellular response to dietary nutrients, as well as to describe the neurotoxic exposures to MeHg. In order to determine the cellular mechanism(s) of toxicity, the effect of pretreatment with biochemical factors (e.g., N-acetyl cysteine, (NAC); diethyl maleate, (DEM); docosahexaenoic acid, (DHA); selenomethionine, SeM; Trolox) and MeHg treatment on intercellular antioxidant status, MeHg content, and other endpoints was evaluated. This paper emphasizes that the protection against oxidative stress offered by these biochemical factors is among one of the major mechanisms responsible for conferring neuroprotection. It is therefore critical to ascertain the cellular mechanisms associated with various dietary nutrients as well as to determine the potential effects of neurotoxic exposures for accurately assessing the risks and benefits associated with fish consumption.

The enzyme Polyphosphate Kinase (PPK) catalyses the reversible transfer of the terminal γ-Pi of ATP to form a long chain Polyphosphate (PolyP). Using an IPTG inducible mycobacterial vector, the vulnerability of this gene has been evaluated by antisense knockdown experiments in M. tuberculosis. Expression profiling studies point to the fact that down regulation of PPK caused cidality during the late phase in contrast to its bacteriostatic mode immediately following antisense expression. PPK thus seems to be a suitable anti-tubercular drug target. The enzyme which is a tetramer has been cloned in E. coli and purified to homogeneity. An enzyme assay suitable for High Throughput Screening was optimized by using the statistical Taguchi protocol and the kinetic parameters determined. The enzyme displayed a strong product inhibition by ADP. In order to accurately estimate the product inhibition, progress curve analysis of the enzyme reaction was monitored. The kinetic equation describing the progress curve was suitably modified by taking into account the product inhibition. The reversible nature of the enzyme indicated a possibility of a two way ATP↔ADP switch operating in the bacteria as a response to its growth requirement.

In order to identify novel high value antibacterial targets it is desirable to delineate whether the inactivation of the target enzyme will lead to bacterial death or stasis. This knowledge is particularly important in slow growing organisms, like mycobacteria, where most of the viable anti-tubercular agents are bactericidal. A bactericidal target can be identified through the conditional deletion or inactivation of the target gene at a relatively high cell number and subsequently following the time course of survival for the bacteria. A simple protocol to execute conditional inactivation of a gene is by antisense expression. We have developed a mycobacteria specific IPTG inducible vector system and monitored the effect of antisense inhibition of several known essential genes in mycobacteria by following their survival kinetics. By this method, we could differentiate between genes whose down regulation lead to bacteriostatic or bactericidal effect. Targets for standard anti-tubercular drugs like inhA for isoniazid, rpoB and C for rifampicin, and gyr A/B for flouroquinolones were shown to be bactericidal. In contrast targets like FtsZ behaved in a bacteriostatic manner. Induction of antisense expression in embB and ribosomal RNA genes, viz., rplJ and rpsL showed only a marginal growth inhibition. The specificity of the antisense inhibition was conclusively shown in the case of auxotrophic gene ilvB. The bactericidal activity following antisense expression of ilvB was completely reversed when the growth media was supplemented with the isoleucine, leucine, valine and pantothenate. Additionally, under these conditions the expression of several genes in branched chain amino acid pathway was severely suppressed indicating targeted gene inactivation.

This paper examines trades-related and university educational attainment (by age 25) of immigrant and Canadian-born Alberta youth while controlling for gender, family socio-economic status, high school grades, and parental encouragement regarding higher education. Data from the longitudinal Alberta School-Work Transitions Study (1996-2003) reveal significant differences between immigrants and non-immigrant young adults in terms of trades-related post-secondary education (PSE). Multinomial logit analysis shows that Alberta immigrant youth are significantly more likely than their Canadian-born counterparts to attain trades-related PSE credentials by age 25. Important factors explaining these differences include parental encouragement and high school grades.

This paper attempts to shed light on the role of language in keeping religion relevant to the individual and society in present times. In the context of postmodernity, religion has become more of a meaning system to address the existential questions of the individual. Religious institutions have had to accommodate the changes brought about by a detraditionalized, decentralized, and rationalized social climate. Although these wider changes are mediated by language, scholars in the past have tended to place more emphasis on the epistemological status and nature of religious beliefs than on religious language itself. Hence, this study sets out to explore (through the critical discourse analysis framework) how language renews itself with a close analysis of the textual and intertextual linguistic features to capture the "zeitgeist" of the times. Six religious sermons (discourses) from three major faiths in Malaysia were recorded. The recordings were then transcribed verbatim and the data analyzed. Activity theory and its principle of contradictions provide an appropriate theoretical, methodological, and heuristic tool to unpack the role of language in the formation of religious meaning systems. Contradictions related to the clergy, language used in sermons in terms of modes, quotations, vocabulary, and personal narratives; religious meaning systems, norms and values, and the social world at large have been identified. It is believed that this understanding of contradictions will aid in uncovering the role of language in reconciling religious meaning systems with the challenges of a postmodern world.