Miracle-dz/UniFAR-FTUs huggingface dataset:
Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction

A prominent feature of synaptic maturation at the neuromuscular junction (NMJ) is the topological transformation of the acetylcholine receptor (AChR)-rich postsynaptic membrane from an ovoid plaque into a complex array of branches. We show here that laminins play an autocrine role in promoting this transformation. Laminins containing the α4, α5, and β2 subunits are synthesized by muscle fibers and concentrated in the small portion of the basal lamina that passes through the synaptic cleft at the NMJ. Topological maturation of AChR clusters was delayed in targeted mutant mice lacking laminin α5 and arrested in mutants lacking both α4 and α5. Analysis of chimeric laminins in vivo and of mutant myotubes cultured aneurally demonstrated that the laminins act directly on muscle cells to promote postsynaptic maturation. Immunohistochemical studies in vivo and in vitro along with analysis of targeted mutants provide evidence that laminin-dependent aggregation of dystroglycan in the postsynaptic membrane is a key step in synaptic maturation. Another synaptically concentrated laminin receptor, Bcam, is dispensable. Together with previous studies implicating laminins as organizers of presynaptic differentiation, these results show that laminins coordinate post- with presynaptic maturation.
Foodborne Cereulide Causes Beta-Cell Dysfunction and Apoptosis

Aims/Hypothesis To study the effects of cereulide, a food toxin often found at low concentrations in take-away meals, on beta-cell survival and function. Methods Cell death was quantified by Hoechst/Propidium Iodide in mouse (MIN6) and rat (INS-1E) beta-cell lines, whole mouse islets and control cell lines (HepG2 and COS-1). Beta-cell function was studied by glucose-stimulated insulin secretion (GSIS). Mechanisms of toxicity were evaluated in MIN6 cells by mRNA profiling, electron microscopy and mitochondrial function tests. Results 24 h exposure to 5 ng/ml cereulide rendered almost all MIN6, INS-1E and pancreatic islets apoptotic, whereas cell death did not increase in the control cell lines. In MIN6 cells and murine islets, GSIS capacity was lost following 24 h exposure to 0.5 ng/ml cereulide (P<0.05). Cereulide exposure induced markers of mitochondrial stress including Puma (p53 up-regulated modulator of apoptosis, P<0.05) and general pro-apoptotic signals as Chop (CCAAT/-enhancer-binding protein homologous protein). Mitochondria appeared swollen upon transmission electron microscopy, basal respiration rate was reduced by 52% (P<0.05) and reactive oxygen species increased by more than twofold (P<0.05) following 24 h exposure to 0.25 and 0.50 ng/ml cereulide, respectively. Conclusions/Interpretation Cereulide causes apoptotic beta-cell death at low concentrations and impairs beta-cell function at even lower concentrations, with mitochondrial dysfunction underlying these defects. Thus, exposure to cereulide even at concentrations too low to cause systemic effects appears deleterious to the beta-cell.
Arterial Structure and Function in Mild Primary Hyperparathyroidism Is Not Directly Related to Parathyroid Hormone, Calcium, or Vitamin D

Objective Elevated levels of calcium and parathyroid hormone (PTH), characteristics of primary hyperparathyroidism (PHPT), may be associated with cardiovascular morbidity and mortality in the general population. We evaluated the possible vascular effects of these risk factors in patients with mild PHPT by using standard methods and new imaging techniques. Design A prospective case-control study. Subjects and Methods Forty-eight patients with mild PHPT without any known cardiovascular risk factors were studied at baseline and at one year after parathyroidectomy (PTX) in comparison with 48 healthy age- and gender-matched controls. We measured biochemical variables, augmentation index (AIx), aortic pulse wave velocity (PWVao), radial (IMTrad) and common carotid artery (IMTcca) intima media thicknesses, and the grayscale median (IM-GSM) of the latter. Results No significant differences were observed between PHPT patients and controls at baseline for AIx (28.6±12.2 vs. 27.7±12.8%), IMTrad (0.271±0.060 vs. 0.255±0.053 mm), IMTcca (0.688±0.113 vs. 0.680±0.135 mm), or IM-GSM (82.3±17.2 vs. 86.5±15.3), while PWVao was slightly higher in patients (8.68±1.50 vs. 8.13±1.55, p<0.05). Systolic blood pressure (SBP), calcium, and PTH were higher in patients compared with controls, and decreased after PTX, while vitamin D was lower in patients and increased after PTX. While AIx, PWVao, IMTrad, and IMTcca were related to SBP, neither correlated to vitamin D levels. Only PWVao correlated weakly to plasma PTH (r = 0.29, p<0.01) and ionized calcium (r = 0.22, p<0.05) but showed no relation when age and SBP were adjusted for. Conclusion We found normal arterial function despite high calcium, PTH, and low vitamin D levels, in patients with mild PHPT without cardiovascular risk factors. The cardiovascular risk associated with low vitamin D and/or high PTH and calcium levels may be explained by their coupling to blood pressure and other risk factors rather than direct effects on arterial structure.
Statistical Applications in Genetics and Molecular Biology A Non-Homogeneous Dynamic Bayesian Network with Sequentially Coupled Interaction Parameters for Applications in Systems and Synthetic Biology

An important and challenging problem in systems biology is the inference of gene regulatory networks from short non-stationary time series of transcriptional profiles. A popular approach that has been widely applied to this end is based on dynamic Bayesian networks (DBNs), although traditional homogeneous DBNs fail to model the non-stationarity and time-varying nature of the gene regulatory processes. Various authors have therefore recently proposed combining DBNs with multiple changepoint processes to obtain time varying dynamic Bayesian networks (TV-DBNs). However, TV-DBNs are not without problems. Gene expression time series are typically short, which leaves the model over-flexible, leading to over-fitting or inflated inference uncertainty. In the present paper, we introduce a Bayesian regularization scheme that addresses this difficulty. Our approach is based on the rationale that changes in gene regulatory processes appear gradually during an organism's life cycle or in response to a changing environment, and we have integrated this notion in the prior distribution of the TV-DBN parameters. We have extensively tested our regularized TV-DBN model on synthetic data, in which we have simulated short non-homogeneous time series produced from a system subject to gradual change. We have then applied our method to real-world gene expression time series, measured during the life cycle of Drosophila melanogaster, under artificially generated constant light condition in Arabidopsis thaliana, and from a synthetically designed strain of Saccharomyces cerevisiae exposed to a changing environment.
Research Opportunities for Use of Organic Dyes & Dye-Doped Polymers in Optoelectronics and Photonics

Presently the major focus of research in nonlinear optical materials is diverted on three areas of interest which include: (1) Optical switching for all-optical devices, (2) Optical limiting for the protection of Eyes and photo detectors, and (3) Optical phase conjugation. All-optical switches which can break the transmission speed limits of electro-optical, acousto-optical, thermo-optical, and micro-electro-mechanical switches, can function as effective tools to solve these problems. The third-order nonlinear optical (NLO) effect based all-optical switches can be used to control light to bring changes in refractive index and hence phase difference when signal light passes through the sample and thus carry out the function of “on” or “off’ of optical switches. Optical limiting is a process of controlling the intensity of laser beam beyond certain specified intensity and has applications in sensor and eye protection. Optical phase conjugation using degenerate four-wave mixing configuration has been demonstrated and analyzed in many organic and inorganic materials using a light beam of pulsed or continuous wave (CW) lasers. However, organic dyes, dye-doped polymer films, and nanomaterials-doped polymers show many favourable chemicals, physical and optical device related issues necessary to make an organic all optical switch foroptoelectronic and Photonics. In this paper, we have suggested the use of organic dyes, dye doped polymers, and nanomaterials-doped polymers for some of the new areas of further research and commercialization of the inventions.
Associations between medical cannabis and prescription opioid use in chronic pain patients: A preliminary cohort study

Background Current levels and dangers of opioid use in the U.S. warrant the investigation of harm-reducing treatment alternatives. Purpose A preliminary, historical, cohort study was used to examine the association between enrollment in the New Mexico Medical Cannabis Program (MCP) and opioid prescription use. Methods Thirty-seven habitual opioid using, chronic pain patients (mean age = 54 years; 54% male; 86% chronic back pain) enrolled in the MCP between 4/1/2010 and 10/3/2015 were compared to 29 non-enrolled patients (mean age = 60 years; 69% male; 100% chronic back pain). We used Prescription Monitoring Program opioid records over a 21 month period (first three months prior to enrollment for the MCP patients) to measure cessation (defined as the absence of opioid prescriptions activity during the last three months of observation) and reduction (calculated in average daily intravenous [IV] morphine dosages). MCP patient-reported benefits and side effects of using cannabis one year after enrollment were also collected. Results By the end of the 21 month observation period, MCP enrollment was associated with 17.27 higher age- and gender-adjusted odds of ceasing opioid prescriptions (CI 1.89 to 157.36, p = 0.012), 5.12 higher odds of reducing daily prescription opioid dosages (CI 1.56 to 16.88, p = 0.007), and a 47 percentage point reduction in daily opioid dosages relative to a mean change of positive 10.4 percentage points in the comparison group (CI -90.68 to -3.59, p = 0.034). The monthly trend in opioid prescriptions over time was negative among MCP patients (-0.64mg IV morphine, CI -1.10 to -0.18, p = 0.008), but not statistically different from zero in the comparison group (0.18mg IV morphine, CI -0.02 to 0.39, p = 0.081). Survey responses indicated improvements in pain reduction, quality of life, social life, activity levels, and concentration, and few side effects from using cannabis one year after enrollment in the MCP (ps<0.001). Conclusions The clinically and statistically significant evidence of an association between MCP enrollment and opioid prescription cessation and reductions and improved quality of life warrants further investigations on cannabis as a potential alternative to prescription opioids for treating chronic pain.
Probabilistic combination of multiple modalities to detect interest

This paper describes a new approach to combine multiple modalities and applies it to the problem of affect recognition. The problem is posed as a combination of classifiers in a probabilistic framework that naturally explains the concepts of experts and critics. Each channel of data has an expert associated that generates the beliefs about the correct class. Probabilistic models of error and the critics, which predict the performance of the expert on the current input, are used to combine the expert's beliefs about the correct class. The method is applied to detect the affective state of interest using information from the face, postures and task the subjects are performing. The classification using multiple modalities achieves a recognition accuracy of 67.8%, outperforming the classification using individual modalities. Further, the proposed combination scheme achieves the greatest reduction in error when compared with other classifier combination methods.
Allele-Specific Induction of IL-1β Expression by C/EBPβ and PU.1 Contributes to Increased Tuberculosis Susceptibility

Mycobacterium tuberculosis infection is associated with a spectrum of clinical outcomes, from long-term latent infection to different manifestations of progressive disease. Pro-inflammatory pathways, such as those controlled by IL-1β, have the contrasting potential both to prevent disease by restricting bacterial replication, and to promote disease by inflicting tissue damage. Thus, the ultimate contribution of individual inflammatory pathways to the outcome of M. tuberculosis infection remains ambiguous. In this study, we identified a naturally-occurring polymorphism in the human IL1B promoter region, which alters the association of the C/EBPβ and PU.1 transcription factors and controls Mtb-induced IL-1β production. The high-IL-1β expressing genotype was associated with the development of active tuberculosis, the severity of pulmonary disease and poor treatment outcome in TB patients. Higher IL-1β expression did not suppress the activity of IFN-γ-producing T cells, but instead correlated with neutrophil accumulation in the lung. These observations support a specific role for IL-1β and granulocytic inflammation as a driver of TB disease progression in humans, and suggest novel strategies for the prevention and treatment of tuberculosis.
Face direction-based human-computer interface using image observation and EMG signal for the disabled

The paralytic caused by the high-level spinal cord injury needs a human-computer interface (HCI) for expressing their intention. In this paper, we propose a novel method to estimate face direction angle using both image observation and electromyogram (EMG) signal from neck muscles. The EMG signal to neck muscle is linear to the face direction angle, but it is undetectable in relatively small angle. Using the image observation, the small face angle is estimated by the geometric relationship between pupils and the face. If two measurements obtained by the EMG signal and the image observation are available, the face direction angle is estimated accurately by a linear interpolation method. We implemented a camera viewing direction control system using the face direction interface, and showed that the proposed method can be used to construct an HCI system for the disabled people with severe motor disabilities.
Intraocular Microsurgical Forceps (20, 23, and 25 gauge) Membrane Peeling Forces Assessment

Background. To assess the peeling forces exerted by different calibers of microsurgical forceps on an experimental model of epiretinal membrane. Methods. A model of epiretinal membrane was constructed using thin cellulose paper and heptanes-isopropyl alcohol 1% mixture. The model was mounted on a force censoring device. Subsequently, flaps were created with three different microsurgical forceps of different calibers. We recorded the number of attempts, the duration of the event, and the pushing and the pulling forces during the peeling. The results were compared by a one-way ANOVA and a Fisher unprotected least significant difference test with an alpha value of 0.05 for statistically significance. Results. There was a statistical significant difference on the pulling and pushing forces between the 25 gauge (13.79 mN; −13.27 mN) and the 23 (6.63 mN; −5.76 mN) and 20 (5.02 mN; −5.30 mN) gauge, being greater in the first (P < 0.001). There were no differences in the duration of all events, meaning that all the forces were measured within the same period of time. Conclusions. The 25 gauge microsurgical forceps exerted the greatest mechanical stress over our simulated epiretinal membrane model and required more attempts to create a surgical suitable flap. The clinical implication of this finding is still to be determined.
Increased cardiac work provides a link between systemic hypertension and heart failure

The spontaneously hypertensive rat (SHR) is an established model of human hypertensive heart disease transitioning into heart failure. The study of the progression to heart failure in these animals has been limited by the lack of longitudinal data. We used MRI to quantify left ventricular mass, volume, and cardiac work in SHRs at age 3 to 21 month and compared these indices to data from Wistar‐Kyoto (WKY) controls. SHR had lower ejection fraction compared with WKY at all ages, but there was no difference in cardiac output at any age. At 21 month the SHR had significantly elevated stroke work (51 ± 3 mL.mmHg SHR vs. 24 ± 2 mL.mmHg WKY; n = 8, 4; P < 0.001) and cardiac minute work (14.2 ± 1.2 L.mmHg/min SHR vs. 6.2 ± 0.8 L.mmHg/min WKY; n = 8, 4; P < 0.001) compared to control, in addition to significantly larger left ventricular mass to body mass ratio (3.61 ± 0.15 mg/g SHR vs. 2.11 ± 0.008 mg/g WKY; n = 8, 6; P < 0.001). SHRs showed impaired systolic function, but developed hypertrophy to compensate and successfully maintained cardiac output. However, this was associated with an increase in cardiac work at age 21 month, which has previously demonstrated fibrosis and cell death. The interplay between these factors may be the mechanism for progression to failure in this animal model.
Lower bounds for external memory dictionaries

We study trade-offs between the update time and the query time for comparison based external memory dictionaries. The main contributions of this paper are two lower bound trade offs between the I/O complexity of member queries and insertions: If N < M insertions perform at most Δ · <i>N</i>/<i>B</i> I/O<inf><sc>s</sc></inf>, then (1) there exists a query requiring N/(M. ·~<sup><i>O</i>(Δ)</sup>) I/O<sc>s</sc>, and (2) there exists a query requiring Ω(log<inf>Δlog<sup>2</sup>N</inf> ~ I/O<sc>s</sc> when Δ is <i>O</i>(<i>B</i>/log<inf>3</inf> <i>N</i>) and <i>N</i> is at least <i>M</i><sup>2</sup>. For both lower bound we describe data structures which give matching upper bounds for a wide range of parameters, thereby showing the lower bounds to be tight within these ranges.
Keratinocyte Antiviral Response to Poly(dA:dT) Stimulation and Papillomavirus Infection in a Canine Model of X-Linked Severe Combined Immunodeficiency

X-linked severe combined immunodeficiency (XSCID) is caused by a genetic mutation within the common gamma chain (γc), an essential component of the cytokine receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. XSCID patients are most commonly treated with bone marrow transplants (BMT) to restore systemic immune function. However, BMT-XSCID humans and dogs remain at an increased risk for development of cutaneous papillomavirus (PV) infections and their associated neoplasms, most typically cutaneous papillomas. Since basal keratinocytes are the target cell for the initial PV infection, we wanted to determine if canine XSCID keratinocytes have a diminished antiviral cytokine response to poly(dA:dT) and canine papillomavirus-2 (CPV-2) upon initial infection. We performed quantitative RT-PCR for antiviral cytokines and downstream interferon stimulated genes (ISG) on poly(dA:dT) stimulated and CPV-2 infected monolayer keratinocyte cultures derived from XSCID and normal control dogs. We found that XSCID keratinocytes responded similarly to poly(dA:dT) as normal keratinocytes by upregulating antiviral cytokines and ISGs. CPV-2 infection of both XSCID and normal keratinocytes did not result in upregulation of antiviral cytokines or ISGs at 2, 4, or 6 days post infection. These data suggest that the antiviral response to initial PV infection of basal keratinocytes is similar between XSCID and normal patients, and is not the likely source for the remaining immunodeficiency in XSCID patients.
Online Prediction of Time Series Data With Kernels

Kernel-based algorithms have been a topic of considerable interest in the machine learning community over the last ten years. Their attractiveness resides in their elegant treatment of nonlinear problems. They have been successfully applied to pattern recognition, regression and density estimation. A common characteristic of kernel-based methods is that they deal with kernel expansions whose number of terms equals the number of input data, making them unsuitable for online applications. Recently, several solutions have been proposed to circumvent this computational burden in time series prediction problems. Nevertheless, most of them require excessively elaborate and costly operations. In this paper, we investigate a new model reduction criterion that makes computationally demanding sparsification procedures unnecessary. The increase in the number of variables is controlled by the coherence parameter, a fundamental quantity that characterizes the behavior of dictionaries in sparse approximation problems. We incorporate the coherence criterion into a new kernel-based affine projection algorithm for time series prediction. We also derive the kernel-based normalized LMS algorithm as a particular case. Finally, experiments are conducted to compare our approach to existing methods.
ECOLOGY OF ORGANISMS IN URBAN ENVIRONMENTS Urban drivers of plant-pollinator interactions

Summary 1. Plant–pollinator interactions are affected by global change, with largely negative impacts on pollination and plant reproduction. Urban areas provide a unique and productive study system for understanding the impacts of many global change drivers on plant–pollinator interactions. 2. We review the mechanistic pathways through which urban drivers alter plant–pollinator interactions. The literature on urban drivers of plant–pollinator interactions is small but growing and has already produced exciting insights about how population processes or pollinator behaviour interacts with landscape urban drivers to affect pollination outcomes. 3. Habitat loss and fragmentation can change flower visitation rates and pollination success through changes in pollinator foraging behaviour or through population-level effects on pollinators. Urban environments, where impermeable surface provides an inhospitable matrix, may allow researchers to identify habitat fragments more clearly than in many other environments. 4. Recent studies have found that non-native plants are not differently preferred by pollinators relative to native plants, therefore removing the basis for expecting pollinator-mediated competition between native and non-native plants in urban habitats. However, non-native species together with managed vegetation may have powerful effects in urban habitats via changes in community-level plant phenology and consequent changes in pollinator phenology. 5. The current level of climate warming has not caused plants and pollinators to become detectably temporally separated, although at the same time, diversity among species’ phenological responses could buffer plant–pollinator interactions from climate variation. Due to the urban warming effect, cities provide a promising system for better understanding the warming effects on plant–pollinator interactions. 6. Environmental contaminants such as soil nitrogen and heavy metal pollution have been examined with respect to plant–pollinator interactions in small-scale, mechanistic studies. The extent to which environmental contaminants drive plant–pollinator interactions in actual urban landscapes is, however, currently unknown. 7. Important knowledge gaps that require research attention include understanding the consequences of plant and pollinator trait filtering on plant–pollinator interactions, and expanding the literature to include underrepresented biomes and pollinator taxa.