Direct observation of molecular cooperativity near the glass transition

We describe direct observations of molecular cooperativity near the glass transition in poly-vinyl-acetate (PVAc), through nanometer-scale probing of dielectric fluctuations. Molecular clusters switched spontaneously between two to four distinct configurations, producing complex random-telegraph-signals (RTS). Analysis of the RTS and their power spectra shows that individual clusters exhibit both transient dynamical heterogeneity and non-exponential kinetics.Comment: 14 pages pdf, need Acrobat Reade

Skin Lesion Analyser: An Efficient Seven-Way Multi-Class Skin Cancer Classification Using MobileNet

Skin cancer, a major form of cancer, is a critical public health problem with 123,000 newly diagnosed melanoma cases and between 2 and 3 million non-melanoma cases worldwide each year. The leading cause of skin cancer is high exposure of skin cells to UV radiation, which can damage the DNA inside skin cells leading to uncontrolled growth of skin cells. Skin cancer is primarily diagnosed visually employing clinical screening, a biopsy, dermoscopic analysis, and histopathological examination. It has been demonstrated that the dermoscopic analysis in the hands of inexperienced dermatologists may cause a reduction in diagnostic accuracy. Early detection and screening of skin cancer have the potential to reduce mortality and morbidity. Previous studies have shown Deep Learning ability to perform better than human experts in several visual recognition tasks. In this paper, we propose an efficient seven-way automated multi-class skin cancer classification system having performance comparable with expert dermatologists. We used a pretrained MobileNet model to train over HAM10000 dataset using transfer learning. The model classifies skin lesion image with a categorical accuracy of 83.1 percent, top2 accuracy of 91.36 percent and top3 accuracy of 95.34 percent. The weighted average of precision, recall, and f1-score were found to be 0.89, 0.83, and 0.83 respectively. The model has been deployed as a web application for public use at (https://saketchaturvedi.github.io). This fast, expansible method holds the potential for substantial clinical impact, including broadening the scope of primary care practice and augmenting clinical decision-making for dermatology specialists.Comment: This is a pre-copyedited version of a contribution published in Advances in Intelligent Systems and Computing, Hassanien A., Bhatnagar R., Darwish A. (eds) published by Chaturvedi S.S., Gupta K., Prasad P.S. The definitive authentication version is available online via https://doi.org/10.1007/978-981-15-3383-9_1

An interdisciplinary intervention for older Taiwanese patients after surgery for hip fracture improves health-related quality of life

Abstract Background The effects of intervention programs on health-related quality of life (HRQOL) of patients with hip fracture have not been well studied. We hypothesized that older patients with hip fracture who received our interdisciplinary intervention program would have better HRQOL than those who did not. Methods A randomized experimental design was used. Older patients with hip fracture (N = 162), 60 to 98 years old, from a medical center in northern Taiwan were randomly assigned to an experimental (n = 80) or control (n = 82) group. HRQOL was measured by the SF-36 Taiwan version at 1, 3, 6, and 12 months after discharge. Results The experimental group had significantly better overall outcomes in bodily pain (β = 9.38, p = 0.002), vitality (β = 9.40, p < 0.001), mental health (β = 8.16, p = 0.004), physical function (β = 16.01, p < 0.001), and role physical (β = 22.66, p < 0.001) than the control group at any time point during the first year after discharge. Physical-related health outcomes (physical functioning, role physical, and vitality) had larger treatment effects than emotional/mental- and social functioning-related health outcomes. Conclusions This interdisciplinary intervention program may improve health outcomes of elders with hip fracture. Our results may provide a reference for health care providers in countries using similar programs with Chinese/Taiwanese immigrant populations. Trial registration NCT01052636http://deepblue.lib.umich.edu/bitstream/2027.42/78259/1/1471-2474-11-225.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78259/2/1471-2474-11-225.pdfPeer Reviewe

Methods for the study of ionic currents and Ca(2+)-signals in isolated colonic crypts

Isolated epithelial cells from intestinal mucosae are a suitable object for the study of the regulation of ion transport in the gut. This regulation possesses a great importance for human and veterinary medicine, as diarrheal diseases, which often are caused by an inadequate activation of intestinal anion secretion, are one of the major lethal diseases of children or young animals. The aim of this paper is to describe a method for the isolation of intact colonic crypts, e.g. for the subsequent investigation of the regulation of anion secretion by the intracellular second messenger, Ca(2+) using electrophysiological and imaging techniques

Development of a mathematical model for predicting electrically elicited quadriceps femoris muscle forces during isovelocity knee joint motion

<p>Abstract</p> <p>Background</p> <p>Direct electrical activation of skeletal muscles of patients with upper motor neuron lesions can restore functional movements, such as standing or walking. Because responses to electrical stimulation are highly nonlinear and time varying, accurate control of muscles to produce functional movements is very difficult. Accurate and predictive mathematical models can facilitate the design of stimulation patterns and control strategies that will produce the desired force and motion. In the present study, we build upon our previous isometric model to capture the effects of constant angular velocity on the forces produced during electrically elicited concentric contractions of healthy human quadriceps femoris muscle. Modelling the isovelocity condition is important because it will enable us to understand how our model behaves under the relatively simple condition of constant velocity and will enable us to better understand the interactions of muscle length, limb velocity, and stimulation pattern on the force produced by the muscle.</p> <p>Methods</p> <p>An additional term was introduced into our previous isometric model to predict the force responses during constant velocity limb motion. Ten healthy subjects were recruited for the study. Using a KinCom dynamometer, isometric and isovelocity force data were collected from the human quadriceps femoris muscle in response to a wide range of stimulation frequencies and patterns. % error, linear regression trend lines, and paired t-tests were used to test how well the model predicted the experimental forces. In addition, sensitivity analysis was performed using Fourier Amplitude Sensitivity Test to obtain a measure of the sensitivity of our model's output to changes in model parameters.</p> <p>Results</p> <p>Percentage RMS errors between modelled and experimental forces determined for each subject at each stimulation pattern and velocity showed that the errors were in general less than 20%. The coefficients of determination between the measured and predicted forces show that the model accounted for ~86% and ~85% of the variances in the measured force-time integrals and peak forces, respectively.</p> <p>Conclusion</p> <p>The range of predictive abilities of the isovelocity model in response to changes in muscle length, velocity, and stimulation frequency for each individual make it ideal for dynamic applications like FES cycling.</p

Phenotypic Detection of Clonotypic B Cells in Multiple Myeloma by Specific Immunoglobulin Ligands Reveals their Rarity in Multiple Myeloma

In multiple myeloma, circulating “clonotypic” B cells, that express the immunoglobulin rearrangement of the malignant plasma cell clone, can be indirectly detected by PCR. Their role as potential “feeder” cells for the malignant plasma cell pool remains controversial. Here we established for the first time an approach that allows direct tracking of such clonotypic cells by labeling with patient-specific immunoglobulin ligands in 15 patients with myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood or bone marrow by PCR. Epitope-mimicking peptides from random libraries were selected on each patient's individual immunoglobulin and used as ligands to trace cells expressing the idiotypic immunoglobulin on their surface. We established a flow cytometry and immunofluorescence protocol to track clonotypic B cells and validated it in two independent monoclonal B cell systems. Using this method, we found clonotypic B cells in only one out of 15 myeloma patients. In view of the assay's validated sensitivity level of 10−3, this surprising data suggests that the abundance of such cells has been vastly overestimated in the past and that they apparently represent a very rare population in myeloma. Our novel tracing approach may open perspectives to isolate and analyze clonotypic B cells and determine their role in myeloma pathobiology

A New Anti-Depressive Strategy for the Elderly: Ablation of FKBP5/FKBP51

The gene FKBP5 codes for FKBP51, a co-chaperone protein of the Hsp90 complex that increases with age. Through its association with Hsp90, FKBP51 regulates the glucocorticoid receptor (GR). Single nucleotide polymorphisms (SNPs) in the FKBP5 gene associate with increased recurrence of depressive episodes, increased susceptibility to post-traumatic stress disorder, bipolar disorder, attempt of suicide, and major depressive disorder in HIV patients. Variation in one of these SNPs correlates with increased levels of FKBP51. FKBP51 is also increased in HIV patients. Moreover, increases in FKBP51 in the amygdala produce an anxiety phenotype in mice. Therefore, we tested the behavioral consequences of FKBP5 deletion in aged mice. Similar to that of naïve animals treated with classical antidepressants FKBP5−/− mice showed antidepressant behavior without affecting cognition and other basic motor functions. Reduced corticosterone levels following stress accompanied these observed effects on depression. Age-dependent anxiety was also modulated by FKBP5 deletion. Therefore, drug discovery efforts focused on depleting FKBP51 levels may yield novel antidepressant therapies

Insights into the Ecology and Evolutionary Success of Crocodilians Revealed through Bite-Force and Tooth-Pressure Experimentation

BackgroundCrocodilians have dominated predatory niches at the water-land interface for over 85 million years. Like their ancestors, living species show substantial variation in their jaw proportions, dental form and body size. These differences are often assumed to reflect anatomical specialization related to feeding and niche occupation, but quantified data are scant. How these factors relate to biomechanical performance during feeding and their relevance to crocodilian evolutionary success are not known.Methodology/Principal FindingsWe measured adult bite forces and tooth pressures in all 23 extant crocodilian species and analyzed the results in ecological and phylogenetic contexts. We demonstrate that these reptiles generate the highest bite forces and tooth pressures known for any living animals. Bite forces strongly correlate with body size, and size changes are a major mechanism of feeding evolution in this group. Jaw shape demonstrates surprisingly little correlation to bite force and pressures. Bite forces can now be predicted in fossil crocodilians using the regression equations generated in this research.Conclusions/SignificanceCritical to crocodilian long-term success was the evolution of a high bite-force generating musculo-skeletal architecture. Once achieved, the relative force capacities of this system went essentially unmodified throughout subsequent diversification. Rampant changes in body size and concurrent changes in bite force served as a mechanism to allow access to differing prey types and sizes. Further access to the diversity of near-shore prey was gained primarily through changes in tooth pressure via the evolution of dental form and distributions of the teeth within the jaws. Rostral proportions changed substantially throughout crocodilian evolution, but not in correspondence with bite forces. The biomechanical and ecological ramifications of such changes need further examination