Mcintyresimmons7946

Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, particularly, on the interface of cells and material of the implants. We defined the phenotypic response of human bone marrow-derived mesenchymal stem cells (hMSCs) to 2176 randomly generated surface topographies by probing basic functions such as migration, proliferation, protein synthesis, apoptosis, and differentiation using quantitative image analysis. Clustering the surfaces into 28 archetypical cell shapes, we found a very strict correlation between cell shape and physiological response and selected seven cell shapes to describe the molecular mechanism leading to phenotypic diversity. Transcriptomics analysis revealed a tight link between cell shape, molecular signatures, and phenotype. For instance, proliferation is strongly reduced in cells with limited spreading, resulting in down-regulation of genes involved in the G2/M cycle and subsequent quiescence, whereas cells with large filopodia are related to activation of early response genes and inhibition of the osteogenic process. In this paper we were aiming to identify a universal set of genes that regulate the material-induced phenotypical response of human mesenchymal stem cells. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Here we are proposing an approach to tackle this question.Plastic deformation in crystalline materials consists of an ensemble of collective dislocation glide processes, which lead to strain burst emissions in micro-scale samples. To unravel the combined role of crystalline structure, sample size and temperature on these processes, we performed a comprehensive set of strict displacement-controlled micropillar compression experiments in conjunction with large-scale molecular dynamics and physics-based discrete dislocation dynamics simulations. The results indicate that plastic strain bursts consist of numerous individual dislocation glide events, which span over minuscule time intervals. The size distributions of these events exhibit a gradual transition from an incipient power-law slip regime (spanning [Formula see text] 2.5 decades of slip sizes) to a large avalanche domain (spanning [Formula see text] 4 decades of emission probability) at a cut-off slip magnitude [Formula see text]. This cut-off slip provides a statistical measure to the characteristic mean dislocation swept distance, which allows for the scaling of the avalanche distributions vis-à-vis the archetypal dislocation mechanisms in face-centered cubic (FCC) and body-centered cubic (BCC) metals. Our statistical findings provide a new pathway to characterizing metal plasticity and towards comprehension of the sample size effects that limit the mechanical reliability in small-scale structures.To combat the pandemic of the coronavirus disease 2019 (COVID-19), numerous governments have established phone hotlines to prescreen potential cases. These hotlines have struggled with the volume of callers, leading to wait times of hours or, even, an inability to contact health authorities. Symptoma is a symptom-to-disease digital health assistant that can differentiate more than 20,000 diseases with an accuracy of more than 90%. We tested the accuracy of Symptoma to identify COVID-19 using a set of diverse clinical cases combined with case reports of COVID-19. We showed that Symptoma can accurately distinguish COVID-19 in 96.32% of clinical cases. When considering only COVID-19 symptoms and risk factors, Symptoma identified 100% of those infected when presented with only three signs. Lastly, we showed that Symptoma's accuracy far exceeds that of simple "yes-no" questionnaires widely available online. In summary, Symptoma provides unparalleled accuracy in systematically identifying cases of COVID-19 while also considering over 20,000 other diseases. Furthermore, Symptoma allows free text input, furthered with disease-specific follow up questions, in 36 languages. Combined, these results and accessibility give Symptoma the potential to be a key tool in the global fight against COVID-19. The Symptoma predictor is freely available online at https//www.symptoma.com .An amendment to this paper has been published and can be accessed via a link at the top of the paper.Cortisol is a biomarker for stress monitoring; however, the biomedical and clinical relevance is still controversial due to the complexity of cortisol secretion mechanisms and their circadian cycles as well as environmental factors that affect physiological cortisol level, which include individual mood and dietary intake. To further investigate this multifaceted relationship, a human pilot study examined cortisol concentration in sweat and saliva samples collected from 48 college-aged participants during aerobic exercise sessions along with mental distress and nutrition surveys. Enzyme-linked immunosorbent assays determined highly significant differences between apocrine-dominant sweat (AP), saliva before exercise (SBE), and saliva after exercise (SAE) cortisol concentration (AP-SBE p = 0.0017, AP-SAE p = 0.0102). A significantly greater AP cortisol concentration was detected in males compared to females (p = 0.0559), and significant SAE cortisol concentration differences were also recorded between recreationance algorithm developments for cortisol biosensing systems to mitigate stress-based illnesses and improve an individual's quality of life.Different types of adipose tissue can be accurately localized and quantified by tomographic imaging techniques (MRI or CT). One common shortcoming for the abdominal subcutaneous adipose tissue (ASAT) of obese subjects is the technically restricted imaging field of view (FOV). This work derives equations for the conversion between six surrogate measures and fully segmented ASAT volume and discusses the predictive power of these image-based quantities. Clinical (gender, age, anthropometry) and MRI data (1.5 T, two-point Dixon sequence) of 193 overweight and obese patients (116 female, 77 male) from a single research center for obesity were analyzed retrospectively. Six surrogate measures of fully segmented ASAT volume (VASAT) were considered two simple ASAT lengths, two partial areas (Ap-FH, Ap-ASIS) and two partial volumes (Vp-FH, Vp-ASIS) limited by either the femoral heads (FH) or the anterior superior iliac spine (ASIS). Least-squares regression between each measure and VASAT provided slope and intercept for the computation of estimated ASAT volumes (V~ASAT). Goodness of fit was evaluated by coefficient of determination (R2) and standard deviation of percent differences (sd%) between V~ASAT and VASAT. Best agreement was observed for partial volume Vp-FH (sd% = 14.4% and R2 = 0.78), followed by Vp-ASIS (sd% = 18.1% and R2 = 0.69) and AWFASIS (sd% = 23.9% and R2 = 0.54), with minor gender differences only. Other estimates from simple lengths and partial areas were moderate only (sd% > 23.0% and R2  less then  0.50). Gender differences in R2 generally ranged between 0.02 (dven) and 0.29 (Ap-FH). The common FOV restriction for MRI volumetry of ASAT in obese subjects can best be overcome by estimating VASAT from Vp-FH using the equation derived here. The very simple AWFASIS can be used with reservation.Cancer immunotherapies using monoclonal antibodies to block inhibitory checkpoints are showing durable remissions in many types of cancer patients, although the majority of breast cancer patients acquire little benefit. Human melanoma and lung cancer patient studies suggest that immune checkpoint inhibitors are often potent in patients that already have intratumoral T cell infiltrate; although it remains unknown what types of interventions can result in an intratumoral T cell infiltrate in breast cancer. Using non-T cell-inflamed mammary tumors, we assessed what biological processes and downstream inflammation can overcome the barriers to spontaneous T cell priming. Here we show a specific type of combination therapy, consisting of oncolytic virus and chemotherapy, activates necroptosis and limits tumor growth in autochthonous tumors. Combination therapy activates proinflammatory cytokines; intratumoral influx of myeloid cells and cytotoxic T cell infiltrate in locally treated and distant autochthonous tumors to render them susceptible to immune checkpoint inhibitors.Detailed balance is a cornerstone of our understanding of artificial light-harvesting systems. For next generation organic solar cells, this involves intermolecular charge-transfer (CT) states whose energies set the maximum open circuit voltage VOC. We have directly observed sub-gap states significantly lower in energy than the CT states in the external quantum efficiency spectra of a significant number of organic semiconductor blends. Taking these states into account and using the principle of reciprocity between emission and absorption results in non-physical radiative limits for the VOC. We propose and provide compelling evidence for these states being non-equilibrium mid-gap traps which contribute to photocurrent by a non-linear process of optical release, upconverting them to the CT state. This motivates the implementation of a two-diode model which is often used in emissive inorganic semiconductors. The model accurately describes the dark current, VOC and the long-debated ideality factor in organic solar cells. Additionally, the charge-generating mid-gap traps have important consequences for our current understanding of both solar cells and photodiodes - in the latter case defining a detectivity limit several orders of magnitude lower than previously thought.Heparin and low molecular weight heparin (LMWH) have recently been considered useful treatment tools for inflammation. Heparin has antifibrotic activity, mediated by cellular secretion of hepatocyte growth factor (HGF). HGF has antifibrotic properties demonstrated in experimental models of lung, kidney, heart, skin, and liver fibrosis. The ability of LMWH for HGF secretion is similar to that of normal heparin. Poly (lactic-co-glycolic acid) (PLGA) is widely used for sustained drug release, because of its biocompatibility and low toxicity. LMWH-loaded PLGA microparticles are prepared by a conventional water-in-oil-in-water emulsion method. Interstitial pneumonia is a life-threatening pathological condition that causes respiratory failure when it progresses. In the present study, we investigated the therapeutic effect of LMWH-loaded PLGA microparticles in a mouse model of bleomycin-induced lung fibrosis. The ratios of fibrotic area to total area were significantly lower in mice administered LMWH-loaded microparticles than in mice administered bleomycin alone. Santacruzamate A molecular weight The microparticle administration did not further enhance the gene expression for inflammatory cytokines. In a cell culture study, HGF secretion by mouse and human lung fibroblasts was significantly increased by LMWH addition. We conclude that LMWH showed anti-inflammatory activity, through the effects of LMWH-loaded PLGA microparticles on cells at sites of inflammation.We aimed to classify early normal-tension glaucoma (NTG) and glaucoma suspect (GS) using Bruch's membrane opening-minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer (RNFL), and the color classification of RNFL based on a deep-learning model. Discriminating early-stage glaucoma and GS is challenging and a deep-learning model may be helpful to clinicians. NTG accounts for an average 77% of open-angle glaucoma in Asians. BMO-MRW is a new structural parameter that has advantages in assessing neuroretinal rim tissue more accurately than conventional parameters. A dataset consisted of 229 eyes out of 277 GS and 168 eyes of 285 patients with early NTG. A deep-learning algorithm was developed to discriminate between GS and early NTG using a training set, and its accuracy was validated in the testing dataset using the area under the curve (AUC) of the receiver operating characteristic curve (ROC). The deep neural network model (DNN) achieved highest diagnostic performance, with an AUC of 0.966 (95%confidence interval 0.