Quantifying the Pressure-dependence of Work of Adhesion in Silicon-Diamond Contacts

Continuum mechanics models for contacting surfaces assume a constant interfacial energy, or work of adhesion, between materials. Recent studies have challenged this assumption, instead demonstrating that stress-dependent chemical reactions across the interface modify the work of adhesion. Here, we perform 77 adhesion tests on diamond-silicon contacts using in situ TEM and atomistic simulations to quantify how the adhesion changes as a function of applied pressure. The results show a 7-fold increase in work of adhesion (from approximately 1 to 7 J/m2) with an increase in mean applied pressure from 0 to 11 GPa, where the most significant increase occurs above 5 GPa. We rule out alternative explanations for the changing work of adhesion, such as electron-beam artifacts, bulk shape change by inelastic deformation, and time-dependent processes such as creep. Therefore, these results confirm the presence of stress-driven chemical reactions in the contact and quantify the resulting change in adhesion of these materials with applied pressure

A Method for Quantitative Real-Time Evaluation of Measurement Reliability When Using Atomic Force Microscopy-Based Metrology

In atomic force microscopy (AFM) and metrology, it is known that the radius of the scanning tip affects the accuracy of the measurement. However, most techniques for ascertaining tip radius require interruption of the measurement technique to insert a reference standard or to otherwise image the tip. Here we propose an inline technique based on analysis of the power spectral density (PSD) of the topography that is being collected during measurement. By identifying and quantifying artifacts that are known to arise in the power spectrum due to tip blunting, the PSD itself can be used to determine progressive shifts in the radius of the tip. Specifically, using AFM images of an ultrananocrystalline diamond, various trends in measured PSD are demonstrated. First, using more than 200 different measurements of the same material, the variability in the measured PSD is demonstrated. Second, using progressive scans under the same conditions, a systematic shifting of the mid-to-high-frequency data is visible. Third, using three different PSDs, the changes in radii between them were quantitatively determined and compared to transmission electron microscopy (TEM) images of the tips taken immediately after use. The fractional changes in tip radii were detected; the absolute values of the tip radii could be matched between the two techniques, but only with careful selection of a fitting constant. Further work is required to determine the generalizability of the value of this constant. Overall, the proposed approach represents a step towards quantitative and inline determination of the radius of the scanning tip and thus of the reliability of AFM-based measurements

DOXORUBICIN INDUCED COGNITION IMPAIRMENT IN RAT MODEL

 Objective: Doxorubicin (DOX) is a chemotherapeutic agent commonly used to treat a variety of cancers despite having well documented adverse sideeffects in organs like heart, liver, and kidney. The damage caused to brain, if any, and to what extent is, however, still not clear and the present studywas undertaken to estimate the possible role of DOX inducing cognitive impairment in Wistar rats.Methods: The study carried out in two groups of Wistar rats (n=6) with one group receiving DOX, and the other only normal saline used as control.During and after the experimentation period cognitive level of each rat was measured using Barnes maze (BM) till 8 weeks. At the end of theobservation period (after 8th week), a series of biochemical and histopathological studies were carried out after sacrificing the animals.Results: Errors to reach target and time taken to reach the target was found in BM experiment, elevated levels of antioxidants and hemoglobin wasfound reduced significantly in the DOX treated group when compared to the controls while histopathology of brain cells of DOX treated group alsoshowed reduction in hippocampal cellularity and cell death in hippocampal area suggesting evidence of oxidative damage caused by DOX treatment.Conclusion: Parameters in this study which not only conclusively show the damage caused to brain by DOX, but also estimates the changes caused toeach indicator by this drug.Keywords: Chemotherapy, Brain, Hippocampus, Oxidative stress

High genomic diversity and heterogenous origins of pathogenic and antibiotic-resistant Escherichia coli in household settings represent a challenge to reducing transmission in low-income settings

Escherichia coli; is present in multiple hosts and environmental compartments as a normal inhabitant, temporary or persistent colonizer, and as a pathogen. Transmission of; E. coli; between hosts and with the environment is considered to occur more often in areas with poor sanitation. We performed whole-genome comparative analyses on 60; E. coli; isolates from soils and fecal sources (cattle, chickens, and humans) in households in rural Bangladesh. Isolates from household soils were in multiple branches of the reconstructed phylogeny, intermixed with isolates from fecal sources. Pairwise differences between all strain pairs were large (minimum, 189 single nucleotide polymorphisms [SNPs]), suggesting high diversity and heterogeneous origins of the isolates. The presence of multiple virulence and antibiotic resistance genes is indicative of the risk that; E. coli; from soil and feces represent for the transmission of variants that pose potential harm to people. Analysis of the accessory genomes of the Bangladeshi; E. coli; relative to; E. coli; genomes available in NCBI identified a common pool of accessory genes shared among; E. coli; isolates in this geographic area. Together, these findings indicate that in rural Bangladesh, a high level of; E. coli; in soil is likely driven by contributions from multiple and diverse; E. coli; sources (human and animal) that share an accessory gene pool relatively unique to previously published; E. coli; genomes. Thus, interventions to reduce environmental pathogen or antimicrobial resistance transmission should adopt integrated One Health approaches that consider heterogeneous origins and high diversity to improve effectiveness and reduce prevalence and transmission.; IMPORTANCE; Escherichia coli; is reported in high levels in household soil in low-income settings. When; E. coli; reaches a soil environment, different mechanisms, including survival, clonal expansion, and genetic exchange, have the potential to either maintain or generate; E. coli; variants with capabilities of causing harm to people. In this study, we used whole-genome sequencing to identify that; E. coli; isolates collected from rural Bangladeshi household soils, including pathogenic and antibiotic-resistant variants, are diverse and likely originated from multiple diverse sources. In addition, we observed specialization of the accessory genome of this Bangladeshi; E. coli; compared to; E. coli; genomes available in current sequence databases. Thus, to address the high level of pathogenic and antibiotic-resistant; E. coli; transmission in low-income settings, interventions should focus on addressing the heterogeneous origins and high diversity

Elucidating type 2 diabetes mellitus risk factor by promoting lipid metabolism with gymnemagenin: An in vitro and in silico approach

Introduction: Adipose tissue functions as a key endocrine organ which releases multiple bioactive substances and regulate obesity-linked complications. Dysregulation of adipocyte differentiation, triglyceride metabolism, adipokines production and lipid transport contributes to impaired lipid metabolism resulting in obesity, insulin resistance and type 2 diabetes. Gymnema sylvestre plant is frequently used in Ayurveda for treatment of diabetes and obesity. Gymnemagenin is a major bioactive compound of Gymnema sylvestre. The present study was undertaken to elucidate the role of gymnemagenin in lipid metabolism by in vitro and computational approaches.Methods: A panel of twelve genes viz., Fasn, Lipe, Lpl, Pparg, Plin2, Cidea, Scd1, Adipoq, Lep, Ccl2, Fabp4, and Slc2a4, essential in lipid metabolism were selected and gene expression pattern and triglyceride content were checked in adipocytes (3T3L1 cells) with/without treatment of gymnemagenin by Real time PCR and colorimetric estimation, respectively. Mode of action of gymnemagenin on Pparg and Fabp4 was accomplished by computational studies. Gene set enrichment and network pharmacology were performed by STRING and Cytoscape. Molecular docking was performed by AutoDock vina by POAP pipeline. Molecular dynamics, MM-PBSA were done by Gromacs tool.Results:In vitro study showed that gymnemagenin improved triglyceride metabolism by up regulating the expression of lipase genes viz., Lipe and Lpl which hydrolyse triglyceride. Gymnemagenin also up regulated the expression of anti-inflammatory gene Adipoq. Importantly, gymnemagenin treatment up regulated the expression of Pparg gene and the downstream target genes (Plin2, Cidea, and Scd1) which are associated with adipogenesis. However, gymnemagenin has no effect on expression of Fabp4, codes for a lipid transport protein. In silico study revealed that gymnemagenin targeted 12 genes were modulating 6 molecular pathways involved in diabetes and obesity. Molecular docking and dynamics revealed that gymnemagenin stably bind to active site residue of Pparg and failed to bind to Fabp4 active site compared to its standard molecules throughout 100 ns MD production run. Gymnemagenin scored binding free energy of −177.94 and −25.406 kJ/mol with Pparg and Fabp4, respectively.Conclusion: Gymnemagenin improved lipid metabolism by increasing triglyceride hydrolysis (lipolysis), up regulating the crucial gene of adipogenesis and increasing the expression of anti-inflammatory adipokine proving its therapeutic importance as anti-obesity and anti-diabetic phytocompound

Antimicrobial activity of leaf and root methanolic extracts from Vinca pusilla Murr.

Vinca pusilla Murr. is a traditional medicinal plant used to treat several diseases. To substantiate the traditional medicinal utility of the plant, the present study aims at screening the antimicrobial activity of methanolic extracts of leaves and roots against five Gram positive, five Gram negative bacterial and four fungal strains. The minimum inhibitory concentration (MIC) were determined by two fold dilution assay. The results indicated that, leaf and root extracts were more effective on Bacillus subtilis and Staphylococcus aureus strains (MIC < 1 mg/mL). The tested organisms were sensitive to root extract compared to leaf extract. Fungal strains were resistant than the bacterial strains to both the extracts. Thus the present study illustrates the antimicrobial potential of the plant.

Matching atomistic simulations and in situ experiments to investigate the mechanics of nanoscale contact

Many emerging devices and technologies rely on contacts between nanoscale bodies. Recent analytical theories, experiments, and simulations of nanocontacts have made conflicting predictions about the mechanical response as these contacts are loaded and separated. The present investigation combined in situ transmission electron microscopy (TEM) and molecular dynamics (MD) simulation to study the contact between a flat diamond indenter and a nanoscale silicon tip. The TEM was used to pre-characterize the materials, such that an atomistic model tip could be created with identically matched materials, geometry, crystallographic orientation, loading conditions, and degree of amorphization. A large work of adhesion was measured in the experiment and attributed to unpassivated surfaces and a large compressive stress applied before separation, resulting in covalent bonding across the interface. The simulations modeled atomic interactions across the interface using a Buckingham potential in order to reproduce the experimental work of adhesion without explicitly modeling covalent bonds, thereby enabling larger time- and length-scale simulations than would be achievable with a reactive potential. Then, the experimental and simulation tips were loaded under similar conditions with real-time measurement of contact area and deformation, yielding three primary findings. First, the results demonstrated that significant variation in the value of contact area can be obtained from simulations, depending on the technique used to determine it. Therefore, care is required in comparing measured values of contact area between simulations and experiments. Second, the contact area and deformation demonstrated significant hysteresis, with larger values measured upon unloading as compared to loading. Therefore, continuum predictions, in the form of a Maugis-Dugdale contact model, could not be fit to full loading/unloading curves. Third, the load-dependent contact area could be accurately fit by allowing the work of adhesion in the continuum model to increase with applied force from 1.3 to 4.3 J/m^2. The most common mechanisms for hysteretic behavior—which are viscoelasticity, capillary interactions, and plasticity—can be ruled out using the TEM and atomistic characterization. Stress-dependent formation of covalent bonds is suggested as a physical mechanism to describe these findings, which is qualitatively consistent with trends in the areal density of in-contact atoms as measured in the simulation. The implications of these results for real-world nanoscale contacts are that significant hysteresis may cause significant and unexpected deviations in contact size, even for nominally elastic contact

Ethyl gallate isolated from phenol-enriched fraction of Caesalpinia mimosoides Lam. Promotes cutaneous wound healing: a scientific validation through bioassay-guided fractionation

The tender shoots of Caesalpinia mimosoides Lam. are used ethnomedically by the traditional healers of Uttara Kannada district, Karnataka (India) for the treatment of wounds. The current study was aimed at exploring phenol-enriched fraction (PEF) of crude ethanol extract of tender shoots to isolate and characterize the most active bio-constituent through bioassay-guided fractionation procedure. The successive fractionation and sub-fractionation of PEF, followed by in vitro scratch wound, antimicrobial, and antioxidant activities, yielded a highly active natural antioxidant compound ethyl gallate (EG). In vitro wound healing potentiality of EG was evidenced by a significantly higher percentage of cell migration in L929 fibroblast cells (97.98 ± 0.46% at 3.81 μg/ml concentration) compared to a positive control group (98.44 ± 0.36%) at the 48th hour of incubation. A significantly higher rate of wound contraction (98.72 ± 0.41%), an elevated tensile strength of the incised wound (1,154.60 ± 1.42 g/mm2), and increased quantity of connective tissue elements were observed in the granulation tissues of the 1% EG ointment treated animal group on the 15th post-wounding day. The accelerated wound healing activity of 1% EG was also exhibited by histopathological examinations through Hematoxylin and Eosin, Masson’s trichome, and Toluidine blue-stained sections. Significant up-regulation of enzymatic and non-enzymatic antioxidant contents (reduced glutathione, superoxide dismutase, and catalase) and down-regulation of oxidative stress marker (lipid peroxidation) clearly indicates the effective granular antioxidant activity of 1% EG in preventing oxidative damage to the skin tissues. Further, in vitro antimicrobial and antioxidant activities of EG supports the positive correlation with its enhanced wound-healing activity. Moreover, molecular docking and dynamics for 100 ns revealed the stable binding of EG with cyclooxygenase-2 (−6.2 kcal/mol) and matrix metalloproteinase-9 (−4.6 kcal/mol) and unstable binding with tumor necrosis factor-α (−7.2 kcal/mol), suggesting the potential applicability of EG in inflammation and wound treatment

Risk factors for detection, survival, and growth of antibiotic-resistant and pathogenic Escherichia coli in household soils in rural Bangladesh

Soils in household environments in low- and middle-income countries may play an important role in the persistence, proliferation, and transmission of; Escherichia coli; Our goal was to investigate the risk factors for detection, survival, and growth of; E. coli; in soils collected from household plots.; E. coli; was enumerated in soil and fecal samples from humans, chickens, and cattle from 52 households in rural Bangladesh. Associations between; E. coli; concentrations in soil, household-level risk factors, and soil physicochemical characteristics were investigated. Susceptibility to 16 antibiotics and the presence of intestinal pathotypes were evaluated for 175; E. coli; isolates. The growth and survival of; E. coli; in microcosms using soil collected from the households were also assessed.; E. coli; was isolated from 44.2% of the soil samples, with an average of 1.95 log; 10; CFU/g dry soil. Soil moisture and clay content were associated with; E. coli; concentrations in soil, whereas no household-level risk factor was significantly correlated. Antibiotic resistance and pathogenicity were common among; E. coli; isolates, with 42.3% resistant to at least one antibiotic, 12.6% multidrug resistant (≥3 classes), and 10% potentially pathogenic. Soil microcosms demonstrate growth and/or survival of; E. coli; , including an enteropathogenic extended-spectrum beta-lactamase (ESBL)-producing isolate, in some, but not all, of the household soils tested. In rural Bangladesh, defined soil physicochemical characteristics appear more influential for; E. coli; detection in soils than household-level risk factors. Soils may act as reservoirs in the transmission of antibiotic-resistant and potentially pathogenic; E. coli; and therefore may impact the effectiveness of water, sanitation, and hygiene interventions.; IMPORTANCE; Soil may represent a direct source or act as an intermediary for the transmission of antibiotic-resistant and pathogenic; Escherichia coli; strains, particularly in low-income and rural settings. Thus, determining risk factors associated with detection, growth, and long-term survival of; E. coli; in soil environments is important for public health. Here, we demonstrate that household soils in rural Bangladesh are reservoirs for antibiotic-resistant and potentially pathogenic; E. coli; strains and can support; E. coli; growth and survival, and defined soil physicochemical characteristics are drivers of; E. coli; survival in this environment. In contrast, we found no evidence that household-level factors, including water, sanitation, and hygiene indicators, were associated with; E. coli; contamination of household soils

Fecal Colonization With Multidrug-Resistant E. coli Among Healthy Infants in Rural Bangladesh

Third generation cephalosporins (3GC) are one of the main choices for treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Due to their overuse, an increasing trend of resistance to 3GC has been observed in developing countries. Here, we describe fecal colonization of 3GC-resistant (3GCr) Escherichia coli in healthy infants (1–12 months old) living in rural areas of Bangladesh. We found that stool samples of 82% of infants (n = 100) were positive for 3GCr E. coli with a mean ± standard deviation of 6.21 ± 1.32 log10 CFU/g wet weight of stool. 3GCr E. coli encompasses an average one third (33%) of the total E. coli of stool. Almost 77% (n = 63) of these 3GCr E. coli were MDR (or resistant to ≥3 classes of antibiotics). Around 90% (n = 74) of 3GCr E. coli were extended spectrum beta-lactamase (ESBL)-producing in which blaCTX–M–group–1 was the predominant (96%, n = 71) ESBL-gene followed by blaTEM (41%, n = 30) and blaOXA–1 (11%, n = 8). A significant proportion (26.5%, n = 22) of 3GCr E. coli was pathogenic, comprising two types, enteroaggregative (EAEC, n = 19) and enteropathogenic (EPEC, n = 3). Colonization of 3GCr E. coli in infant guts was not associated with demographic characteristics such as age, sex, mode of delivery, maternal and infant antibiotic use, disease morbidity, and feeding practices. The high rate of colonization of 3GCr E. coli in infants’ guts is a serious public health concern which needs immediate attention and warrants further studies to explore the cause