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The respiratory tract has a resident microbiome with low biomass and limited diversity. This results in difficulties with sample preparation for sequencing due to uneven bacteria-to-host DNA ratio, especially for small tissue samples such as mouse lungs. We compared effectiveness of current procedures used for DNA extraction in microbiome studies. Bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected to test different forms of sample pre-treatment and extraction methods to increase bacterial DNA yield and optimize library preparation. DNA extraction using a pre-treatment method of mechanical lysis (lung tissue) and one-step centrifugation (BALF) increased DNA yield and bacterial content of samples. In contrast, a significant increase of environmental contamination was detected after phenol chloroform isoamyl alcohol (PCI) extraction and nested PCR. While PCI has been a standard procedure used in microbiome studies, our data suggests that it is not efficient for DNA extraction of frozen low biomass samples. Finally, a DNA Enrichment kit was tested and found to improve the 16S copy number of lung tissue with a minor shift in microbial composition. Overall, we present a standardized method to provide high yielding DNA and improve sequencing coverage of low microbial biomass frozen samples with minimal contamination. [ABSTRACT FROM AUTHOR]

Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is incurable and ultimately fatal. Few therapeutic options are available to patients. In this study, we explored differences in microbiome composition associated with ALS. Methods: We compared the gut microbiome and inflammatory marker profiles of ALS patients (n = 10) to those of their spouses (n = 10). Gut microbiome profiles were determined by 16S rRNA gene sequencing. Results: The gut microbial communities of the ALS patients were more diverse and were deficient in Prevotella spp. compared with those of their spouses. In contrast, healthy couples (n = 10 couples of the opposite sex) recruited from the same geographic region as the patient population did not exhibit these differences. Stool and plasma inflammatory markers were similar between ALS patients and their spouses. Predictive analysis of microbial enzymes revealed that ALS patients had decreased activity in several metabolic pathways, including carbon metabolism, butyrate metabolism, and systems involving histidine kinase and response regulators. Conclusions: ALS patients exhibit differences in their gut microbial communities compared with spouse controls. Our findings suggest that modifying the gut microbiome, such as via amelioration of Prevotella spp. deficiency, and/or altering butyrate metabolism may have translational value for ALS treatment. [ABSTRACT FROM AUTHOR]

The ability of Escherichia coli surviving a cold shock lies mainly with the induction of a few Csps termed as 'Major cold shock proteins'. Regardless of high sequence similarity among the nine homologous members, CspC appears to be functionally diverse in conferring the cell adaptability to various stresses based on fundamental properties of the protein including nucleic acid binding, nucleic acid melting and regulatory activity. Spanning three different stress regulons of acid, oxidative and heat, CspC regulates gene expression and transcript stability of stress proteins and bestows upon the cell tolerance to lethal‐inducing agents ultimately helping it adapt to severe environmental assaults. While its exact role in cellular physiology is still to be detailed, understanding the transcriptional and translational control will likely provide insights into the mechanistic role of CspC under stress conditions. To this end, we review the knowledge on stress protein regulation by CspC and highlight its activity in response to stressors thereby elucidating its role as a major Csp player in response to one too many environmental triggers. The knowledge presented here could see various downstream applications in engineering microbes for industrial, agricultural and research applications in order to achieve high product efficiency and to aid bacteria cope with environmentally harsh conditions. [ABSTRACT FROM AUTHOR]

• HLA-DPB1*04:01:01:01 showed the strongest association with GPA and either in homozygous or in heterozygous state, is the most frequent allele among GPA patients in northern India. • This study identified five significant associated HLA alleles with GPA of which C*15:02 was novel. • DRB1*03:01–DQB1*02:01–DPB1*04:01 and DRB1*07:01–DQB1*02:02–DPB1*04:01 are the most frequent haplotypes present in GPA patients. • K69 amino acid residue of the antigen binding domain of HLA-DPB1*04:01:01:01 showed very strong interaction with the two reported super antigen epitops of Staphylococcus aureus. Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease. Major contributions of HLA genes have been reported; however, HLA typing-based diagnosis or risk prediction in GPA has not been established. We have performed a sequencing-based HLA genotyping in a north Indian GPA cohort and controls to identify clinically relevant novel associations. PR3-ANCA-positive 40 GPA patients and 40 healthy controls from north India were recruited for the study. Targeted sequencing of HLA-A , -B , -C ,- DRB1 , -DQB1, and -DPB1 was performed. Allelic and haplotypic associations were tested. Molecular docking of susceptibility HLA alleles with reported super-antigen epitopes was performed. The association of substituted amino acids located at the antigen-binding domain of HLA was evaluated. Genetic association of five HLA-alleles was identified in GPA. The novel association was identified for C*15:02 (p = 0.04; OR = 0.27(0.09–0.88)). The strongest association was observed for DPB1*04:01 (p < 0.0001; OR = 6.2(3.08–11.71)), previously reported in European studies. 35 of 40 GPA subjects had at least one DPB1*04:01 allele, and its significant risk was previously not reported from the Indian population. Significantly associated haplotypes DRB1*03:01–DQB1*02:01–DPB1*04:01 (p = 0.02; OR = 3.46(1.11–12.75)) and DRB1*07:01–DQB1*02:02–DPB1*04:01 (p = 0.04; OR = 3.35(0.95–14.84)) were the most frequent in GPA patients. Ranging from 89 % to 100 % of GPA patients with organ involvement can be explained by at least one DPB1*04:01 allele. A strong interaction between the HLA and three epitopes of the reported super antigen TSST-1 of Staphylococcus aureus was confirmed. Our study highlighted the potential applicability of HLA typing for screening and diagnosis of GPA. A large multi-centric study and genotype-phenotype correlation analysis among GPA patients will enable the establishment of HLA-typing based GPA diagnosis. [ABSTRACT FROM AUTHOR]

The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is poorly understood due to a lack of an animal model that recapitulates severe human disease. Here, we report a Syrian hamster model that develops progressive lethal pulmonary disease that closely mimics severe coronavirus disease 2019 (COVID-19). We evaluated host responses using a multi-omic, multiorgan approach to define proteome, phosphoproteome, and transcriptome changes. These data revealed both type I and type II interferon-stimulated gene and protein expression along with a progressive increase in chemokines, monocytes, and neutrophil-associated molecules throughout the course of infection that peaked in the later time points correlating with a rapidly developing diffuse alveolar destruction and pneumonia that persisted in the absence of active viral infection. Extrapulmonary proteome and phosphoproteome remodeling was detected in the heart and kidneys following viral infection. Together, our results provide a kinetic overview of multiorgan host responses to severe SARSCoV- 2 infection in vivo. [ABSTRACT FROM AUTHOR]

This review is focused on the cellular dynamics and genomic programming of plasma cell (PC) precursors that arise during germinal center (GC) B cell responses in secondary lymphoid organs (SLOs) and give rise to PCs in the bone marrow. Considerable progress has been made in the phenotypic characterization of circulating and bone marrow PC precursors as well as their differentiated short‐lived (SLPC) and long‐lived (LLPC) counterparts, in the context of model antigen and vaccine responses. Importantly, it has been possible to infer the temporal dynamics of generation of PC precursors during a GC response. However, the nature of the PC precursors at their site of generation in SLOs, and their signaling and genomic states, remain to be elucidated. Our synthesis draws upon experimental studies conducted in murine models as well as in humans, the latter complemented with cell culture manipulations of PCs and their precursors. By integration of the studies in murine and human systems, which are being accelerated by new genomic methodologies, we highlight insights and hypotheses concerning the generation of PCs. This framework can be extended and explored from both fundamental and translational standpoints. [ABSTRACT FROM AUTHOR]

A temperature downshift results in stabilized secondary structure formation in mRNA that halts translation to which Escherichia coli responds by synthesizing a set of proteins termed as cold shock proteins (Csps). To cope with the sudden temperature drop, gene expression patterns are reprogrammed to induce Csps at the cost of other proteins. Out of the nine homologous proteins in the CspA family, CspA, CspB, CspG, and CspI have major roles in protecting the cell under a cold shock. Additionally, a subset of Csps has conferred the organism an ability to adapt to various stresses along the lines of nutrient deprivation, oxidative, heat, acid, and antibiotic stresses. Stressors like C group translational inhibitors stall the translational apparatus and produce a response similar to that observed under a temperature downshift. Conditions set by the antibiotic therefore elicit a cold shock response and induce the major Csps, thereby pointing out to a common mechanism existing between the two. In the current review, we briefly describe the induction of E. coli Csps under an antibiotic stress acquired from data published previously and help establish the role of Csps in protecting the cell against the inducing agents and as a participant in the organisms' complex stress response network. [ABSTRACT FROM AUTHOR]

Migraine is the sixth most prevalent disease worldwide but the mechanisms that underlie migraine chronicity are poorly understood. Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on dynamic microtubules. Histone-deacetylase-6 (HDAC6) decreases microtubule dynamics by deacetylating its primary substrate, a-tubulin. We use validated mouse models of migraine to show that HDAC6-inhibition is a promising migraine treatment and reveal an undiscovered cytoarchitectural basis for migraine chronicity. The human migraine trigger, nitroglycerin, produced chronic migraine-associated pain and decreased neurite growth in headache-processing regions, which were reversed by HDAC6 inhibition. Cortical spreading depression (CSD), a physiological correlate of migraine aura, also decreased cortical neurite growth, while HDAC6-inhibitor restored neuronal complexity and decreased CSD. Importantly, a calcitonin gene-related peptide receptor antagonist also restored blunted neuronal complexity induced by nitroglycerin. Our results demonstrate that disruptions in neuronal cytoarchitecture are a feature of chronic migraine, and effective migraine therapies might include agents that restore microtubule/neuronal plasticity. [ABSTRACT FROM AUTHOR]

Langerhans cells (LCs), residing in the epidermis, are able to induce potent immunogenic responses and also to mediate immune tolerance. We propose that tolerogenic and immunogenic responses of LCs are directed by signaling from the epidermis and involve counter‐acting gene circuits that are coupled to a core maturation gene module. We base our analysis on recent genetic and genomic findings facilitating the understanding of the molecular mechanisms controlling these divergent immune functions. Comparing gene regulatory network (GRN) analyses of various types of dendritic cells (DCs) including LCs we integrate signaling‐dependent (TGFβ, EpCAM, β‐Catenin) and transcription factor (IRF4, IRF1, NFκB) regulated gene circuits that appear to orchestrate the distinctive LC functional states. Our model proposes, that while epidermal signaling in the steady‐state promotes LC tolerogenic function, the disruption of cell‐cell contacts coupled with inflammatory signaling induces LC immunogenic programing. The conceptual framework emphasizes the sensing of discrete epidermal and inflammatory cues by resident LCs in dictating their genomic programing and cell state dynamics. [ABSTRACT FROM AUTHOR]

Rapid industrialization and profligate use of resources in the present era has led to increase in the concentration of toxic heavy metal ions in water bodies and has become a serious environmental concern. Starch hydrogels and aerogels with engineered functionality, porosity, regeneration characteristics, and high surface to volume ratio have rendered them potential candidates for the adsorption of heavy metal ions from wastewater streams. However, grafting, crosslinking, and composting of the starch aerogels and hydrogels to tailor them in response to various stimuli such as ionic strength, pH, and temperature has added an advantage in the treatment of wastewater containing heavy metal ions. This review critically analyses the various synthesis routes for the production of starch‐based aerogels and hydrogels with physico‐chemical characteristics (amylose content, gelatinization temperature, surface area, density, and porosity) and their applicability to adsorb heavy metal (Cd, Cu, Co, Ni, Cr, Pb, Zn, Fe, and Co) ions from wastewater. Future prospects in the development of economical and robust starch‐based aerogels and hydrogels in terms of their stability and reusability have also been discussed. [ABSTRACT FROM AUTHOR]

In this evidence-based review article, we focus our attention on most common pediatric tachy-arrhythmias. The objective is to familiarize pediatricians with electrocardiogram (ECG) interpretation, assist the pediatrician in recognition and management of common pediatric tachy-arrhythmias. [ABSTRACT FROM AUTHOR]

Electrocardiogram interpretation in pediatrics is based on the evolutionary changes with maturation, and clinical manifestations. Systematic approach is warranted for precise interpretation during baseline rhythm and in arrhythmia. The knowledge and detection of normal variants and abnormal findings is of utmost importance and can guide pediatric cardiology referrals for consultations. In this paper on pediatric arrhythmias, the epidemiology, natural history, clinical manifestations, diagnosis and management options of common arrhythmias and ectopies will be discussed. [ABSTRACT FROM AUTHOR]

Electrocardiogram interpretation in pediatrics is based on the evolutionary changes with maturation, and clinical manifestations. Systematic approach is warranted for precise interpretation during baseline rhythm and in arrhythmia. The knowledge and detection of normal variants and abnormal findings is of utmost importance and can guide pediatric cardiology referrals for consultations. In this paper on pediatric arrhythmias, the epidemiology, natural history, clinical manifestations, diagnosis and management options of common arrhythmias and ectopies will be discussed. [ABSTRACT FROM AUTHOR]

In this evidence-based review article, we focus our attention on most common pediatric tachy-arrhythmias. The objective is to familiarize pediatricians with electrocardiogram (ECG) interpretation, assist the pediatrician in recognition and management of common pediatric tachy-arrhythmias. [ABSTRACT FROM AUTHOR]

On 31st December 2019, China informed local WHO office of "cases of pneumonia of unknown etiology detected in Wuhan. As of 6th May 2020, there are nearly 3.6 million cases of corona virus infection and approximately 0.25 million deaths worldwide. The real-time data regarding the actual number of cases, as it originates from the epicenter is the key to the estimation of the case fatality rate, hospitalization rates, expected timeline of arrival of contagion, and other epidemiological data. The novel virus has no available literature pertaining to its epidemiological parameters, on which experts can base their estimates and hence the challenge in planning for epidemic management. Bolstering this challenge are the reports alleging under-reporting by Chinese authorities. Alleged toned down numbers could have led to erroneously low estimates contributing to inadequate public health response globally. We conducted a simulation on epidemiological model of COVID-19 to find out expected time off arrival of infections and mortality in different countries and compared this to actual data. [ABSTRACT FROM AUTHOR]

Over the past 20 years, a series of reports written by groups of senior researchers and administrators have recommended changes to improve the training environments for graduate students and postdoctoral researchers in the United States. However, academic institutions and departments have largely failed to implement these recommendations, which has exacerbated the problems faced by these trainees. Here, based on input from trainees at different career stages, we outline seven practical changes that academic institutions and departments can make to improve their training environments. [ABSTRACT FROM AUTHOR]

On 31st December 2019, China informed local WHO office of "cases of pneumonia of unknown etiology detected in Wuhan. As of 6th May 2020, there are nearly 3.6 million cases of corona virus infection and approximately 0.25 million deaths worldwide. The real-time data regarding the actual number of cases, as it originates from the epicenter is the key to the estimation of the case fatality rate, hospitalization rates, expected timeline of arrival of contagion, and other epidemiological data. The novel virus has no available literature pertaining to its epidemiological parameters, on which experts can base their estimates and hence the challenge in planning for epidemic management. Bolstering this challenge are the reports alleging under-reporting by Chinese authorities. Alleged toned down numbers could have led to erroneously low estimates contributing to inadequate public health response globally. We conducted a simulation on epidemiological model of COVID-19 to find out expected time off arrival of infections and mortality in different countries and compared this to actual data. [ABSTRACT FROM AUTHOR]

We present a comprehensive photometric study of RR Lyrae stars in the M3 globular cluster, utilizing a vast data set of 3140 optical (UBVRI) CCD images spanning 35 yr from astronomical data archives. We have successfully identified previously known 238 RR Lyrae stars from the photometric data, comprising 178 RRab, 49 RRc, and 11 RRd stars. Multiband periodogram was used to significantly improve the long-term periods of 65 per cent of RR Lyrae stars in our sample, thanks to the unprecedentedly long temporal coverage of the observations. The light curve templates were used to obtain accurate and precise mean magnitudes and amplitudes of all RR Lyrae variables. We combined optical (UBVRI) and near-infrared (NIR, JHKs) photometry of RR Lyrae variables to investigate their location in the colour-magnitude diagrams as well as the pulsation properties such as period distributions, Bailey diagrams and amplitude ratios. The period–luminosity relations in R and I bands and Period–Wesenheit relations were derived after excluding outliers identified in CMDs. The Period–Wesenheit relations calibrated via the theoretically predicted relations were used to determine a distance modulus of |$\mu = 15.04 \pm 0.04 \, {\rm (stats)} \pm 0.19 \, {\rm {(syst.)}}$|  mag (using metal-independent WBV Wesenheit) and |$\mu = 15.03 \pm 0.04 \, {\rm (stats)} \pm 0.17 \, {\rm {(syst.)}}$|  mag (using metal-dependent WVI Wesenheit). Our distance measurements are in excellent agreement with published distances to M3 in the literature. We also employed an artificial neural network based comparison of theoretical and observed light curves to determine physical parameters (mass, luminosity, and effective temperature) for 79 non-Blazhko RRab stars that agree with limited literature measurements. [ABSTRACT FROM AUTHOR]

Cytoskeletal proteins and post-translational modifications play a role in mood disorders. Post-translational modifications of tubulin also alter microtubule dynamics. Furthermore, tubulin interacts closely with Gas, the G-protein responsible for activation of adenylyl cyclase. Postmortem tissue derived from depressed suicide brain showed increased Gas in lipid-raft domains compared with normal subjects. Gas, when ensconced in lipid rafts, couples less effectively with adenylyl cyclase to produce cAMP, and this is reversed by antidepressant treatment. A recent in vitro study demonstrated that tubulin anchors Gas to lipid rafts and that increased tubulin acetylation (due to F1DAC6 inhibition) and antidepressant treatment decreased the proportion of Gas complexed with tubulin. This suggested that deacetylated-tubulin might be more prevalent in depression. This study examined tubulin acetylation in whole-tissue homogenate, plasma membrane, and lipid-raft membrane domains in tissue from normal control subjects, depressed suicides, and depressed nonsuicides (human males/females). While tissue homogenate showed no changes in tubulin acetylation between control, depressed suicides, and depressed nonsuicides, plasma membrane-associated tubulin showed significant decreases in acetylation from depressed suicides and depressed nonsuicides compared with controls. No change was seen in expression of the enzymes responsible for tubulin acetylation or deacetylation. These data suggest that, during depression, membrane-localized tubulin maintains a lower acetylation state, permitting increased sequestration of Gxs in lipid-raft domains, where it is less likely to couple to adenylyl cyclase for cAMP production. Thus, membrane tubulin may play a role in mood disorders, which could be exploited for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Prophylactic or therapeutic antibiotic use along with chemotherapy treatment potentially has a long-standing adverse effect on the resident gut microbiota. We have established a case-control cohort of 32 pediatric and adolescent acute lymphoblastic leukemia (ALL) patients and 25 healthy siblings (sibling controls) to assess the effect of chemotherapy as well as antibiotic prophylaxis on the gut microbiota. We observe that the microbiota diversity and richness of the ALL group is significantly lower than that of the control group at diagnosis and during chemotherapy. The microbiota diversity is even lower in antibiotics-exposed ALL patients. Although the gut microbial diversity tends to stabilize after 1-year post-chemotherapy, their abundances were altered because of chemotherapy and prophylactic antibiotic treatments. Specifically, the abundances of mucolytic gram-positive anaerobic bacteria, including Ruminococcus gnavus and Ruminococcus torques, tended to increase during the chemotherapy regimen and continued to be elevated 1 year beyond the initiation of chemotherapy. This dysbiosis may contribute to the development of gastrointestinal complications in ALL children following chemotherapy. These findings set the stage to further understand the role of the gut microbiome dynamics in ALL patients and their potential role in alleviating some of the adverse side effects of chemotherapy and antibiotics use in immunocompromised children. [ABSTRACT FROM AUTHOR]

Delayed sowing and imprecise application of irrigation water to cotton has been the major hurdle in sustaining cotton yield in north-western India. Therefore, studies were initiated to ascertain the impact of heavy or normal level of presowing irrigation (PSI), scheduling time of first postsowing irrigation (POSI) under two sowing dates (SDs) on cotton arranged in a split block design replicated thrice. PSIh (100 mm) recorded 23.2% higher seed cotton yield over PSIn (70 mm) owing to better yield attributes and higher stand. First POSI at 4 weeks after sowing (WAS) resulted the highest yield (3072 kg ha−1), while one at 6 WAS (POSI6) recorded least due to poor population and reduced yield attributes. Water productivity under POSI6 was lesser by 29.1%, 25.2%, and 16.2% as compared to POSI3, POSI4, and POSI5, respectively. April sown crop out yielded the May sown cotton crop by 939 kg ha−1 due to better yield attributes. Nitrogen factor productivity (NFP) among SD remained higher by 23.3% for April as compared to May sowing. PSIh exhibited better NFP over PSIn. POSI6 recorded least NFP by 24.4%, 28.5%, and 16.3% as compared to POSI3, POSI4, and POSI5, respectively and was indicative of relatively poor utilization of N under delayed schedules. Therefore, planting in April after heavy PSI and scheduling first POSI at 4 WAS is best strategy for sustaining cotton yield and maximizing farmer profitability. [ABSTRACT FROM AUTHOR]

This paper proposes a fair calculation approach for the cost and emission of generators. Generators also have reactive power requirements along with the active power demand to meet up the total power demand. In this paper, firstly the reactive power is calculated considering the random active power operating points on the capability curve of a generator then the cost for reactive power generation as well as emission are calculated. In order to develop the mathematical function for the reactive power cost and reactive power emission, a curve-fitting technique is applied, which gives the generalised reactive power cost and reactive power emission functions. At the end, the problem is formulated as a multiobjective problem, considering conflicting objectives such as combined active- reactive economic dispatch and combined active-reactive emission dispatch. The problem is converted from the multiobjective load dispatch problem (MOLDP) into a scalar problem, using the weighting method and the best compromised solution has been calculated using the particle swarmoptimization (PSO) technique. Afuzzy cardinal method has been applied to choose the best solution. In order to demonstrate the efficiency of developed functions the proposed method is applied on a 3 generator unit system and a 10 generator unit system, the results obtained show its validity and effectiveness. [ABSTRACT FROM AUTHOR]

The "China Dream" is a native imagination of a great renewal of the Chinese nation. Mao Zedong had a dream to save the nation and promised the Chinese people utopian socialism tomorrow at the cost of sacrifices that needed to be borne today. Deng Xiaoping brought in economic reforms so that the Chinese people could dream of becoming rich. Xi Jinping's China Dream has focussed upon China's sphere of influence extending beyond its regional space. While Xi Jinping's "China Dream" revolves around connectivity and infrastructure, using shades of affirmative, assertive and aggressive nationalism, as necessary, his Belt and Road Initiative (BRI) is likely to affect over 68 countries, 65% of the world's population, and 40% of global GDP. At the regional level, China's 55-km-long Zhuhai-Macau-Hong Kong Bridge is geared to transform the political geography of the South China Sea sub-region. This paper attempts to contextualise the notion of the contemporary "China Dream" and deconstruct the implications of Xi Jinping's aggressive "infrastructure diplomacy" upon Taiwan, Hong Kong and Macau. [ABSTRACT FROM AUTHOR]

Background: Molecular docking studies on protein-peptide interactions are a challenging and time-consuming task because peptides are generally more flexible than proteins and tend to adopt numerous conformations. There are several benchmarking studies on protein-protein, protein-ligand and nucleic acid-ligand docking interactions. However, a series of docking methods is not rigorously validated for protein-peptide complexes in the literature. Considering the importance and wide application of peptide docking, we describe benchmarking of 6 docking methods on 133 protein-peptide complexes having peptide length between 9 to 15 residues. The performance of docking methods was evaluated using CAPRI parameters like FNAT, I-RMSD, L-RMSD. Result: Firstly, we performed blind docking and evaluate the performance of the top docking pose of each method. It was observed that FRODOCK performed better than other methods with average L-RMSD of 12.46 Å. The performance of all methods improved significantly for their best docking pose and achieved highest average L-RMSD of 3.72 Å in case of FRODOCK. Similarly, we performed re-docking and evaluated the performance of the top and best docking pose of each method. We achieved the best performance in case of ZDOCK with average L-RMSD 8.60 Å and 2.88 Å for the top and best docking pose respectively. Methods were also evaluated on 40 protein-peptide complexes used in the previous benchmarking study, where peptide have length up to 5 residues. In case of best docking pose, we achieved the highest average L-RMSD of 4.45 Å and 2.09 Å for the blind docking using FRODOCK and re-docking using AutoDock Vina respectively. Conclusion: The study shows that FRODOCK performed best in case of blind docking and ZDOCK in case of re-docking. There is a need to improve the ranking of docking pose generated by different methods, as the present ranking scheme is not satisfactory. To facilitate the scientific community for calculating CAPRI parameters between native and docked complexes, we developed a web-based service named PPDbench (http://webs.iiitd.edu.in/raghava/ppdbench/). [ABSTRACT FROM AUTHOR]

Physiological stress can bring major molecular and cellular change to a living cell which further decide its survival or tolerance to the stress exposure. Cyanobacteria like Anabaena has been shown to tolerate high levels of different stresses like oxidative, desiccation, UV, and gamma radiation. They are able to withstand and recover remarkably without any lethal mutation when exposed to high doses of gamma radiation or prolonged duration of desiccation. In the present work, the modifications in protein profiles of Anabaena 7120 cells after exposure to 6 kGy of 60Co γ-rays and 6 days of desiccation, and the proteome dynamics during post stress recovery were investigated. Differentially expressed proteins during stress and recovery were identified by MALDI-ToF or LC-MS, which generated a partial proteome map of Anabaena 7120. Anabaena cells went through protein recycling—phase of protein degradation following by their resynthesis, which helped them to recover remarkably. The data suggests an overlap in proteome changes during recovery against radiation and desiccation stress. [ABSTRACT FROM AUTHOR]

The efficient use of gamma isotopes as tracer elements in medical field for diagnosis and radiotherapy emphasises the need of protecting healthy organs/tissues using appropriate shielding materials. Keeping in mind the ease of fabricating different shield structure as per the requirement, some fusible alloys composed of 48 Cd, 49 In, 50 Sn, 82 Pb and 83 Bi in different proportions were chosen. The shielding effectiveness of these fusible alloys were compared and analysed in terms of different parameters viz. density (ρ), mass attenuation coefficient (μ m ), effective atomic number (Z eff ), electron density (N e ), mean free path (mfp), half value layer (HVL), tenth value layer (TVL) and exposure buildup factor. All the selected fusible alloys possess higher values for density, effective atomic number and lower values for melting points, mean free path and exposure buildup factors. [ABSTRACT FROM AUTHOR]

Granulomatosis with polyangiitis (GPA) is a rare systemic ANCA (Anti-neutrophil cytoplasmic antibodies) associated vasculitis (AAV). In the last couple of decades, GPA has emerged as a disease of concern due to rapid increase in the prevalence and incidence especially in developing countries. Unknown aetiology and rapid progression have made GPA a critical disease. Thus, establishing specific tools to facilitate early and faster disease diagnosis and efficient disease management has immense importance. GPA may develop in genetically predisposed individuals on receiving the external stimulus (i.e. microbial pathogen, pollutant etc.) that triggers the immune response. B-cell activating factor (BAFF) produced by the neutrophils, promotes the B-cell maturation and survival which leads to increased ANCA production. Abnormal B-cell and T-cell proliferation and their cytokine response plays a major role in disease pathogenesis and granuloma formation. ANCA interacts with neutrophils and induces the neutrophil extracellular traps (NETs) formation and reactive oxygen species (ROS) production which leads to the endothelial cell injury. This review article summarizes the critical pathological events and how cytokines and immune cells shape the GPA pathogenesis. Decoding this complex network would facilitate in developing tools for diagnosis, prognosis and disease management. Recently developed specific monoclonal antibodies (MAbs) targeting cytokines and immune cells are being used for safer treatment and achieving longer remission. [ABSTRACT FROM AUTHOR]

Arsenic in water at low concentration (1–5 mg/L) presents difficulty in its removal by adsorption due to low concentration gradient. In the present study, silica was extracted from rice husk ash via sol–gel method and loaded with iron oxide using co-precipitation method. The maximum removal As(III) percentage (97.5%) was achieved using 0.1 g/L of adsorbent with a contact time of 90 min at pH = 7.0. Modelling of the experimental data with Freundlich isotherm and pseudo-second-order kinetic models showed the highest regression coefficient (R2 > 0.95). Adsorption was spontaneous at all temperatures (∆G° value). Film and intraparticle diffusivities followed power-law model with initial concentration. FTIR spectra (at 825 cm−1) indicated the presence of monodentate arsenic complexes. The presence of PO43- ions affected the As(III) removal from water. The synthesised adsorbent exhibited excellent reusability up to three adsorption-desorption cycles. [ABSTRACT FROM AUTHOR]

BACKGROUND: The frequency of dengue outbreak is increasing in Southeast Asian countries these days and since there are no specific drugs against the dengue virus; therefore, treatment consists of mainly symptomatic and supportive care. AIMS: Platelet transfusion forms one of the major parts of treatment therapy in dengue; therefore, this study was initiated to elicit the effect of introduction of single-donor apheresis platelets (SDAPs) in dengue management. SETTINGS AND DESIGN: This is a retrospective study conducted on 622 clinically suspected cases of dengue infection who received platelet transfusions between August 2013 and December 2015 in a teaching hospital of North India. MATERIALS AND METHODS: Clinical data, reports of hematological investigation, transfusion request forms, platelet requirements, and data obtained from daily follow-up and blood bank records were analyzed using IBM SPSS version 20. RESULTS: Average platelet count at which platelet transfusion initiated was 25,703/cumm. Average number of random donor platelets (RDPs) transfused significantly decreased in 2015 (2013 vs. 2015 is 5.4 vs. 4.3) due to the transfusion of SDAP to patients with very low platelet count and those with superimposed high-risk factors. Mean length of stay in hospital was similar for patients receiving RDP only and for those receiving RDP and SDAP both (5.48 vs. 5.54) while that for patients receiving SDAP only was quite lower (3.6). Overall cost of stay was higher for those receiving SDAP transfusions. CONCLUSION: Decision for initiating platelet transfusions and calculating its dose for dengue patients is highly variable, but transfusing high-dose platelets such as SDAP at an appropriate stage can reduce further requirement of platelet transfusions, fasten the recovery, reduce the hospital stay, lower the risk of transfusion-associated adverse reactions, and can further minimize the associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

In the present paper, the structural, optical and electrical properties of nanocrystalline Zn x Te 100−x (x = 0, 5, 20, 30, 40, 50) thin films (average thickness ~ 350 nm), deposited by thermal evaporation, have been studied. The X-ray diffraction results revealed that single phase Zn x Te 100−x was obtained at x = 50. Fourier transform infrared spectra also revealed the formation of zinc blende phase at x = 50. Energy dispersive X-ray spectroscopy confirms the elemental composition. Field emission scanning electron micrographs confirmed the uniform deposition of all thin films. UV–Vis–NIR results revealed that the optical band gap, calculated by Tauc's plots, increases with increase in Zn content. This may be due to the alloying effect. Temperature dependent dark conductivity showed that conductivity is thermally activated process having single activation energy in the measured temperature range (300–375 K). The dark conductivity and activation energy decreased with increase in Zn content. The explanations of variation in the properties of ZnTe with increase in Zn percentage have been provided. [ABSTRACT FROM AUTHOR]

Presence of low concentrations (1-2%) of ethanol during irradiation exhibited significant protection against DNA damage caused by very high doses (2-12 kGy) of 60Co-gamma-rays in vitro. Radiation-induced DNA damage was substantially reduced in different types of DNA molecules (chromosomal DNA from Anabaena 7120 or Deinococcus radiodurans or bacteriophage Lambda, and plasmid pBluescript DNA) when irradiated in the presence of ethanol, thus indicating the generic nature of ethanol protection. The radioprotection appeared to be a consequence of the well known ability of ethanol to scavenge hydroxyl radicals. Addition of ethanol during 6 kGy irradiation also reduced DNA damage in vivo and improved post-irradiation growth recovery of Anabaena 7120 cultures. To our knowledge, this is the first instance of ability of very low ethanol concentrations to protect DNA from damage triggered by extremely high doses of 60Co-gamma rays. [ABSTRACT FROM AUTHOR]

Moth bean (Vigna aconitifolia) is a drought-resistant legume, cultivated in arid and semi-arid regions of India and Africa. Starch was isolated from moth bean seeds using the wet-milling method and was treated in 2.2N HCl for durations ranging from 0 to 120 h. Amylose content (18.3%) and swelling power (8.8 g/g) showed progressive decrease with duration in acid treatment. X-ray diffraction showed typical "C" patterns for native and acid-treated starches. Microscopy images revealed an irregular, polygonal structure of the starch granules. Cracks were also observed in the centre of starch granules. Pasting properties showed a drastic decrease of more than 90% in peak viscosity after 4 h of duration and the graph of viscosity versus time almost showed a flat profile after 4 h. [ABSTRACT FROM AUTHOR]

Background: One of the major challenges in the field of system biology is to understand the interaction between a wide range of proteins and ligands. In the past, methods have been developed for predicting binding sites in a protein for a limited number of ligands. Results: In order to address this problem, we developed a web server named 'LPIcom' to facilitate users in understanding protein-ligand interaction. Analysis, comparison and prediction modules are available in the "LPIcom' server to predict protein-ligand interacting residues for 824 ligands. Each ligand must have at least 30 protein binding sites in PDB. Analysis module of the server can identify residues preferred in interaction and binding motif for a given ligand; for example residues glycine, lysine and arginine are preferred in ATP binding sites. Comparison module of the server allows comparing protein-binding sites of multiple ligands to understand the similarity between ligands based on their binding site. This module indicates that ATP, ADP and GTP ligands are in the same cluster and thus their binding sites or interacting residues exhibit a high level of similarity. Propensity-based prediction module has been developed for predicting ligand-interacting residues in a protein for more than 800 ligands. In addition, a number of web-based tools have been integrated to facilitate users in creating web logo and two-sample between ligand interacting and non-interacting residues. Conclusions: In summary, this manuscript presents a web-server for analysis of ligand interacting residue. This server is available for public use from URL http://crdd.osdd.net/raghava/lpicom. [ABSTRACT FROM AUTHOR]

Cellular robustness is an important trait for industrial microbes, because the microbial strains are exposed to a multitude of different stresses during industrial processes, such as fermentation. Thus, engineering robustness in an organism in order to push the strains toward maximizing yield has become a significant topic of research. We introduced the deinococcal response regulator DR1558 into Escherichia coli (strain Ec-1558), thereby conferring tolerance to hydrogen peroxide (H2O2). The reactive oxygen species (ROS) level in strain Ec-1558 was reduced due to the increased KatE catalase activity. Among four regulators of the oxidative-stress response, OxyR, RpoS, SoxS, and Fur, we found that the expression of rpoS increased in Ec-1558, and we confirmed this increase by Western blot analysis. Electrophoretic mobility shift assays showed that DR1558 bound to the rpoS promoter. Because the alternative sigma factor RpoS regulates various stress resistance-related genes, we performed stress survival analysis using an rpoS mutant strain. Ec-1558 was able to tolerate a low pH, a high temperature, and high NaCl concentrations in addition to H2O2, and the multistress tolerance phenotype disappeared in the absence of rpoS. Microarray analysis clearly showed that a variety of stress-responsive genes that are directly or indirectly controlled by RpoS were upregulated in strain Ec-1558. These findings, taken together, indicate that the multistress tolerance conferred by DR1558 is likely routed through RpoS. In the present study, we propose a novel strategy of employing an exogenous response regulator from polyextremophiles for strain improvement. [ABSTRACT FROM AUTHOR]

Background: In the era of next-generation sequencing where thousands of genomes have been already sequenced; size of protein databases is growing with exponential rate. Structural annotation of these proteins is one of the biggest challenges for the computational biologist. Although, it is easy to perform BLAST search against Protein Data Bank (PDB) but it is difficult for a biologist to annotate protein residues from BLAST search. Results: A web-server StarPDB has been developed for structural annotation of a protein based on its similarity with known protein structures. It uses standard BLAST software for performing similarity search of a query protein against protein structures in PDB. This server integrates wide range modules for assigning different types of annotation that includes, Secondary-structure, Accessible surface area, Tight-turns, DNA-RNA and Ligand modules. Secondary structure module allows users to predict regular secondary structure states to each residue in a protein. Accessible surface area predict the exposed or buried residues in a protein. Tight-turns module is designed to predict tight turns like beta-turns in a protein. DNA-RNA module developed for predicting DNA and RNA interacting residues in a protein. Similarly, Ligand module of server allows one to predicted ligands, metal and nucleotides ligand interacting residues in a protein. Conclusions: In summary, this manuscript presents a web server for comprehensive annotation of a protein based on similarity search. It integrates number of visualization tools that facilitate users to understand structure and function of protein residues. This web server is available freely for scientific community from URL http://crdd.osdd.net/raghava/starpdb. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) causes enormous social and economic disruption and hampers nation's development. DOTS strategy under RNTCP is one of the largest public health programs found to be beneficial against TB. Adverse drug reactions lead to decrease in patient compliance and adherence. Good patient adherence to the treatment regimen is the foundation stone to effective antitubercular therapy. Noncompliance is cited as the major problem to the control of the tuberculosis at the level of public health which finally leads to drug resistance in case of TB. Aim and Objectives: To identify the occurrence and pattern of Adverse Drug Reactions (ADRs) associated with anti-tubercular drugs in TB patients under DOTS therapy during Intensive phase of treatment. Materials and methods: A prospective observational study was conducted in 2 randomly selected DOTS centers of Jalandhar. A total of 102 patients of categories I and II who were registered in third quarter of 2014 were selected for study. The follow up period was during the intensive phase of DOTS regimen. All patients on ATT were followed up at the end of 1 week, 1 month and after the completion of intensive phase or if/ when self reporting was done due to adverse drug reactions. Detection and monitoring of adverse drug reaction was done by interviewing patients, consulting with physicians about the patient's clinical problems, reviewing laboratory test and medical records. The data so collected was entered and analyzed using SPSS 21 software. Results: The Incidence of adverse drug reaction was observed in 20.4% i.e. 21 out of 102 patients. Total number of adverse reactions developed in 21 patients were 31, with most common being GIT system (38.7%), followed by skin problems (29%). History of alcoholism, associated co-morbidities, pulmonary TB and DOTS treatment Category II were found to be significantly associated with occurrence of ADRs. Conclusion: The present study highlighted the importance of developing strategies to ameliorate ADRs both to improve the quality of patient care and to control TB safely. In addition, a proper educational counseling may promote more ADR reporting by patients. These strategies may improve the patient adherence to treatment and therapeutic outcome. [ABSTRACT FROM AUTHOR]

Background: In the past, many methods have been developed for peptide tertiary structure prediction but they are limited to peptides having natural amino acids. This study describes a method PEPstrMOD, which is an updated version of PEPstr, developed specifically for predicting the structure of peptides containing natural and non-natural/ modified residues. Results: PEPstrMOD integrates Forcefield-NCAA and Forcefield-PTM force field libraries to handle 147 non-natural residues and 32 types of post-translational modifications respectively by performing molecular dynamics using AMBER. AMBER was also used to handle other modifications like peptide cyclization, use of D-amino acids and capping of terminal residues. In addition, GROMACS was used to implement 210 non-natural side-chains in peptides using SwissSideChain force field library. We evaluated the performance of PEPstrMOD on three datasets generated from Protein Data Bank; i) ModPep dataset contains 501 non-natural peptides, ii) ModPep16, a subset of ModPep, and iii) CyclicPep contains 34 cyclic peptides. We achieved backbone Root Mean Square Deviation between the actual and predicted structure of peptides in the range of 3.81-4.05 Å. Conclusions: In summary, the method PEPstrMOD has been developed that predicts the structure of modified peptide from the sequence/structure given as input. We validated the PEPstrMOD application using a dataset of peptides having non-natural/modified residues. PEPstrMOD offers unique advantages that allow the users to predict the structures of peptides having i) natural residues, ii) non-naturally modified residues, iii) terminal modifications, iv) post-translational modifications, v) D-amino acids, and also allows extended simulation of predicted peptides. This will help the researchers to have prior structural information of modified peptides to further design the peptides for desired therapeutic property. [ABSTRACT FROM AUTHOR]

A field experiment was conducted during kharif 2012 to assess the effects of sowing time (1, 10, 20, and 30 July) and planting geometry (30 cm × 10 cm and 22.5 cm × 10 cm) on the growth, phenology and thermal indices of mungbean varieties (PAU 911 and ML 818). The crop sown on 1 July recorded higher plant height and dry matter accumulation (DMA) and required higher thermal indices viz. accumulated growing degree days (AGDD), accumulated photothermal units (APTU) and accumulated heliothermal units (AHTU) to complete various phenological stages as compared to all other sowing times. Mungbean variety PAU 911 took lesser days to complete various phenological stages and required lesser AGDD, AHTU and APTU as compared to ML 818. Plants in planting geometry of 30 cm × 10 cm recorded significantly higher DMA and attained significantly higher AGDD, AHTU and APTU as compared to in 22.5 cm × 10 cm geometry. [ABSTRACT FROM AUTHOR]

This study addresses the effects of compliance of an occupant seated in an adaptive seat suspension equipped with a magnetorheological energy absorber, and exposed to intense vertical shocks. A 50th percentile male occupant, exposed to shock conditions characterized by sink rates varying from 5 to 10??m/s, was considered. The compliance effects were examined by comparing the response of a multiple degree-of-freedom biodynamic lumped-parameter model derived from the response of a Hybrid II anthropomorphic test dummy representing a compliant-occupant model to the response of an equivalent rigid-occupant model under the same shock conditions. An experimentally validated nonlinear mathematical model of a magnetorheological energy absorber was integrated with both the compliant and rigid models of the occupants. In addition, three different control techniques were investigated based on controlling the onset of magnetorheological-energy-absorber stroking load: constant stroking-load control, terminal trajectory control, and optimal control. The internal damping of a compliant occupant proved to be a crucial parameter in determining the biodynamic response for all control techniques. An assessment of the potential of injury was conducted based on the established injury criteria for compliant occupants to evaluate the applicability of the control techniques. [ABSTRACT FROM AUTHOR]

We present a new technique to generate the light curves of RRab stars in different photometric bands (I and V bands) using artificial neural networks (ANN). A pre-computed grid of models was used to train the ANN, and the architecture was tuned using the I -band light curves. The best-performing network was adopted to make the final interpolators in the I and V bands. The trained interpolators were used to predict the light curve of RRab stars in the Magellanic Clouds, and the distances to the Large Magellanic Cloud and Small Magellanic Cloud were determined based on the reddening independent Wesenheit index. The estimated distances are in good agreement with the literature. The comparison of the predicted and observed amplitudes, and Fourier amplitude ratios showed good agreement, but the Fourier phase parameters displayed a few discrepancies. To showcase the utility of the interpolators, the light curve of the RRab star EZ Cnc was generated and compared with the observed light curve from the Kepler mission. The reported distance to EZ Cnc was found to be in excellent agreement with the updated parallax measurement from Gaia EDR3. Our ANN interpolator provides a fast and efficient technique to generate a smooth grid of model light curves for a wide range of physical parameters, which is computationally expensive and time-consuming using stellar pulsation codes. [ABSTRACT FROM AUTHOR]

Due to the advancements in 5 G technologies, high-definition, and the internet of things (IoT), the capacity demand of optical networks has been exponentially increased. Optical communication networks offer several metrics such as high transmission capacity, low transmission loss, better anti-interference, robustness, etc which offers new opportunities to the communication field. To satisfy the increasing demands of optical networks, effective network resource utilization become essential. So, it is needed to design proper planning tools with superior accuracy for quality of transmission (QoT) in optical networks. Recently, artificial intelligence (AI) techniques pose new opportunities for resolving these issues and machine learning (ML) algorithms offer better performance over the analytical approaches. With this motivation, this paper presents a novel AI based cognitive QoT prediction (AI-CQoT) model for optical communication networks. The proposed AI-CQoT model aims to predict the QoT for the quality of service (QoS) link setup using AI techniques with the transmission equation based synthetic data generation. The proposed model uses the Label weighting extreme learning machine (LW-ELM) model for the prediction process which includes a link and signal characteristics as input features. Besides, the LW-ELM model is trained by the use of transmission equations. For improving the predictive performance of the LW-ELM model, the parameters such as weight matrix W and penalty factor C are optimally tuned by the use of the shuffled shepherd optimization (SSO) algorithm. A detailed experimental validation is performed to highlight the improved performance of the AI-CQoT model and the results are investigated in terms of different performance measures. [ABSTRACT FROM AUTHOR]

We present a study of three-dimensional structure of the Small Magellanic Cloud (SMC). The V- and I-band light curves of the fundamental mode RR Lyrae (RRab) stars obtained by the Optical Gravitational Lensing Experiment-III project were utilized in order to comprehend the SMC structure. The [Fe/H]-P-ϕ31 relation of Jurcsik & Kovacs is exploited to obtain the metallicities. From the three-dimensional RRab distance distributions, north-east arm and main body of the galaxy are identified. Combining metallicities with spatial distribution of these tracers, no radial metallicity gradient in the SMC has been detected. Dividing the entire sample into three parts: north-eastern, central and south-western, we find that the central part has a significantly larger line of sight depth as compared to rest of the parts, indicating that the SMC may have a bulge. Results obtained from the I-band data seem to be reliable and were further substantiated using the Smolec relation. Distribution of SMC RRab stars was modelled as a triaxial ellipsoid. Errors in structural parameters of the SMC ellipsoid were obtained from Monte Carlo simulations. We estimated the axes ratios of the galaxy as 1.00 ± 0.000: 1.310 ± 0.029: 8.269 ± 0.934, the inclination of the longest axis with line of sight i = 2°.265 ± 0°.784 and the position angle of the line of nodes 6= 74?307 ± 0?509 from the variance weighted I-band determinations. [ABSTRACT FROM AUTHOR]

Rifampicin (RIF) was encapsulated into solid lipid nanoparticles (SLNs) to overcome its poor and unreliable oral bioavailability. Novel microemulsification method with high drug loading (50%) and entrapment efficiency (∼67%) was developed (Indian Patent Application 3356/DEL/2013). RIF-SLNs were characterized using TEM, AFM, DSC and XRD. Near neutral SLNs (zeta −3.5 ± 0.8), with average particle size of 130.0 ± 22.6 nm showed 70.12% release in phosphate buffer pH 6.8 in 9 days. Single oral dose (50 mg/kg) pharmacokinetic studies in Wistar rats indicated 8.14 times higher (in comparison to free RIF) plasma bioavailability with sustained levels for 5 days. Pharmacodynamic parameters viz . T MIC (120 h; time for which plasma levels were above MIC of 0.2 μg/ml), AUC 0–∞ /MIC (1868.9 h) and C max /MIC (75.6) for RIF-SLNs were greater than free RIF by 2.5, 8.2 and 6.6 times, respectively. Similar LD 50 (1570 mg/kg) and absence (or reversal in satellite group) of adverse events in repeat dose (three doses; highest dose was up to 50 times the human therapeutic dose) toxicity studies confirmed safety of RIF-SLNs. Improved pharmacokinetic profile of RIF-SLNs can be translated to a reduced dose and dosage frequency of RIF, thus resulting in lower or no hepatotoxicity commonly associated with its use. [ABSTRACT FROM AUTHOR]

Background: Epidermal Growth Factor Receptor (EGFR) is a well-characterized cancer drug target. In the past, several QSAR models have been developed for predicting inhibition activity of molecules against EGFR. These models are useful to a limited set of molecules for a particular class like quinazoline-derivatives. In this study, an attempt has been made to develop prediction models on a large set of molecules (~3500 molecules) that include diverse scaffolds like quinazoline, pyrimidine, quinoline and indole. Results: We train, test and validate our classification models on a dataset called EGFR10 that contains 508 inhibitors (having inhibition activity IC50 less than 10 nM) and 2997 non-inhibitors. Our Random forest based model achieved maximum MCC 0.49 with accuracy 83.7% on a validation set using 881 PubChem fingerprints. In this study, frequency-based feature selection technique has been used to identify best fingerprints. It was observed that PubChem fingerprints FP380 (C(~O) (~O)), FP579 (O = C-C-C-C), FP388 (C(:C) (:N) (:N)) and FP 816 (ClC1CC(Br)CCC1) are more frequent in the inhibitors in comparison to non-inhibitors. In addition, we created different datasets namely EGFR100 containing inhibitors having IC50 < 100 nM and EGFR1000 containing inhibitors having IC50 < 1000 nM. We trained, test and validate our models on datasets EGFR100 and EGFR1000 datasets and achieved and maximum MCC 0.58 and 0.71 respectively. In addition, models were developed for predicting quinazoline and pyrimidine based EGFR inhibitors. Conclusions: In summary, models have been developed on a large set of molecules of various classes for discriminating EGFR inhibitors and non-inhibitors. These highly accurate prediction models can be used to design and discover novel EGFR inhibitors. In order to provide service to the scientific community, a web server/standalone EGFRpred also has been developed (http://crdd.osdd.net/oscadd/egfrpred/). [ABSTRACT FROM AUTHOR]

Quantitative comparison of biodynamic responses, simulated using the Patil or Liu lumped parameter models, were carried out with respect to experimental anthropomorphic test dummy response data obtained from the Sikorsky advanced composite airframe program helicopter crash test. The biodynamic responses obtained from these models were characterized by large offsets from the experimental peak magnitudes, large perturbations in biodynamic displacements, and delayed response. The inability to accurately predict biodynamic response using either model led to development of a new four-degree-of-freedom nonlinear biodynamic model corresponding to a Hybrid II 50th-perccntile male occupant, the parameters of which were identified by minimizing the least-square error between the simulated and advanced composite airframe program experimental responses. The new model accurately predicts peak magnitude, overall shape, and duration of the biodynamic transient response, with minimal phase shift. The biodynamic model was further validated using data from the crashworthy composite fuselage drop experiment conducted by Fasanella and Jackson ("Impact Testing and Simulation of a Crashworthy Composite Fuselage Section with Energy-Absorbing Seats and Dummies," Journal o f the American Helicopter Society, Vol. 49, No. 2, 2004, pp. 140-148). The biodynamic model overpredicted the peak lumbar loads by 1.06% when compared to the pilot s anthropomorphic test dummy response from the Sikorsky advanced composite airframe program experiment, and it predicted lumbar loads within ±10% when compared to crashworthy composite fuselage experiments. [ABSTRACT FROM AUTHOR]

Background This study evaluates the concept of optimizing ventricular pacing in regard to functional cardiac response. Lead implant based on physiologic variables of contractility at various sites was performed in patients with and without congenital heart disease (CHD). Since right ventricular apical pacing may adversely alter contractility and myocellular function, septal and outflow tract pacing have been advocated. However, there are few studies in the young and essentially none in those with CHD. Methods A total of 113 consecutive patients with and without repaired CHD, aged two to 51 (median 16), some with preexisting epicardial pacemakers, underwent transvenous pacemaker implant using standard sensing/pacing indices plus measurements of pressures, QRS, and contractility responses at each of five predefined potential ventricular implant sites: apex, inflow-, low-, mid-, and infundibular/outflow-septal with each patient serving as his/her own control. Implant was at the site of best contractility with active-fixation, low-threshold steroid-eluting leads. Results Measured contractility indices varied up to 31% (mean 12%) between sites per patient. Septal regions (mid-, inflow-, and low-) were associated with the most optimal and right ventricular epicardial showed the worst contractility (P < 0.05) responses. Apex was optimal in some CHD patients. Threshold and sensing were comparable up to 11 years (mean 7) postimplant regardless of septal site. Conclusion There is no single 'sweet spot' for optimal ventricular pacing, and the best implant sites are patient and CHD variable. Current lead designs ensure chronic stability/performance regardless of site. Proactive contractility-guided pacing implant can optimize chronic paced ventricular function. [ABSTRACT FROM AUTHOR]