Miracle-dz/UniFAR-FTUs huggingface dataset:
The Long Journey of mTOR Inhibitors and the Long Path That Is Still Ahead.

R (sirolimus) was isolated in 1975 from actinomycete Streptomyces hygroscopicus in a soil sample collected during a Canadian expedition to Easter Island (Rapa Nui). The target of rapamycin (TOR) was discovered in 1994 in the yeast Saccharomyces, is a ubiquitous and highly conserved enzyme complex in a pathway with a key role in physiological homeostasis. Deregulation of its activity is associated with a variety of diseases. The first phase I study of ascending doses of sirolimus in stable kidney transplant recipients receiving cyclosporine and prednisone was published in 1996. Subsequent phase II and III clinical trials led to regulatory approval by the Food and Drug Administration in 1999 for the prophylaxis of rejection after kidney transplantation in combination with cyclosporine and steroids. Everolimus followed the same path and was subsequently approved for kidney, heart, and liver transplantation. Sirolimus and everolimus analogs were approved for prevention of intrastent restenosis (pharmacological stents) and for the treatment of some cancers, highlighting the central role of the pathway in disparate disease states. This supplement summarizes recent data and provides critical analysis of the accumulated knowledge of the biological effects of mTOR inhibition. Zaza et al describe the effects of mTOR inhibition on protein synthesis, the cell cycle, lipid metabolism, energymetabolism, autophagy, angiogenesis, glucose metabolism, cytoskeleton remodeling, epithelial to mesenchymal transition, and immune cells development and function. The use of mTOR inhibitors in different types of organ transplantation is also reviewed. Flechner provides a critical analysis of randomized clinical trials on different strategies of using mTOR inhibitors after kidney transplantation. Nashan summarizes data on liver transplants, with the focus on calcineurin inhibitor (CNI) minimization to preserve native renal function. Zuckermann discusses recent data on the use of mTOR inhibitors in heart transplantation, under CNI minimization and conversion strategies aiming to preserve renal function and to prevent the development of graft vasculopathy, CMV infection, and malignancy. Berney et al discuss both the beneficial and deleterious effects of mTOR inhibitors on β cells and how sirolimus and everolimus-based
Constraints on the Efficacy of Mucosal Tolerance in Treatment of Human and Animal Arthritic Diseases

Abstract: Mucosal administration of an autoantigen has been shown to be a powerful way of inducing tolerance in both animal and human arthritis clinical trials. Bovine or chicken type II collagen has been administered orally to rheumatoid arthritis patients, resulting in some, although in many cases rather limited, clinical improvement. Animal studies have revealed that the mechanisms that underlie induction of mucosal tolerance include clonal deletion, suppression of the proinflammatory Th1 cells, and the induction of regulatory T cells. These cells, defined as a persistently CD25‐expressing subset of CD4+ cells, are frequently anergic, may produce anti‐inflammatory cytokines such as IL‐10 and TGF‐β, and are likely to be agents of bystander suppression. A key feature that may affect the induction of these cells and other suppressive mechanisms is the dose of antigen administered. The results from human clinical trials suggest a daily dose of significantly less than 1 mg is optimal. Similarly data from collagen‐induced arthritis studies reveal an optimal dose above and below which there is little or no immune suppression. Indeed, the incorrect dose can prime the immune response and aggravate disease. The timing and frequency of administration is also vital to the level of immune tolerance induced and the control of the pathological process. This and other findings derived from animal studies are discussed here in relation to the results from human clinical trials.
SINs and SOMs: neural microcircuits for size tuning in the zebrafish and mouse visual pathway

In many animals, a fast and reliable circuit for discriminating between predator-sized objects and edible (prey-sized) objects is necessary for survival. How are receptive fields (RFs) in visual brain areas organized to extract information about size? Recent studies from the zebrafish optic tectum and the mouse visual cortex suggest de novo shaping of RFs by subtypes of inhibitory neurons. Del Bene et al. (2010) describe a population of GABAergic neurons in the zebrafish optic tectum (superficial interneurons, SINs) that are necessary for size filtering during prey capture. Adesnik et al. (2012) describe a somatostatin-expressing interneuron population (SOMs) that confers surround suppression on layer II/III pyramidal cells in mouse V1. Strikingly both the SINs and the SOMs, display size-dependent response properties. Increasing visual stimulus size increases excitatory input to these neurons. Dampening SIN or SOM activity alters tuning of neighboring circuits such that they lose preference for small objects. Both results provide exciting evidence for mechanisms of size filtering in visual circuits. Here we review the roles of the SINs and the SOMs and speculate on the similarity of such spatial filters across species.
Perceptual Effects of Noise in Digital Video Compression

We present results of subjective viewer assessment of video quality of MPEG-2 compressed video containing wide-band Gaussian noise. The video test sequences consisted of seven test clips (both classical and new materials) to which noise with a peak-signal-to-noise-ratio (PSNR) of from 28 dB to 47 dB was added. We used software encoding and decoding at five bit-rates ranging from 1.8 Mb/s to 13.9 Mb/s. Our panel of 32 viewers rated the difference between the noisy input and the compression-processed output. For low noise levels, the subjective data suggests that compression at higher bit-rates can actually improve the quality of the output, effectively acting like a low-pass filter. We define an objective and a subjective measure of scene criticality (the difficulty of compressing a clip) and find the two measures correlate for our data. For difficult-to-encode material (high criticality), the data suggest that the effects of compression may be less noticeable at mid-level noise, while for easy-to-encode video (low criticality), the addition of a moderate amount of noise to the input led to lower quality scores. This suggests that either the compression process may have reduced noise impairments or a form of masking may occur in scenes that have high levels of spatial detail.
Handling Sparsity via the Horseshoe

This paper presents a general, fully Bayesian framework for sparse supervised-learning problems based on the horseshoe prior. The horseshoe prior is a member of the family of multivariate scale mixtures of normals, and is therefore closely related to widely used approaches for sparse Bayesian learning, including, among others, Laplacian priors (e.g. the LASSO) and Student-t priors (e.g. the relevance vector machine). The advantages of the horseshoe are its robustness at handling unknown sparsity and large outlying signals. These properties are justied theoretically via a representation theorem and accompanied by comprehensive empirical experiments that compare its performance to benchmark alternatives.
Modulation of Postendocytic Sorting of G Protein-Coupled Receptors

Recycling of the mu opioid receptor to the plasma membrane after endocytosis promotes rapid resensitization of signal transduction, whereas targeting of the delta opioid receptor (DOR) to lysosomes causes proteolytic down-regulation. We identified a protein that binds preferentially to the cytoplasmic tail of the DOR as a candidate heterotrimeric GTP-binding protein (G protein)–coupled receptor-associated sorting protein (GASP). Disruption of the DOR-GASP interaction through receptor mutation or overexpression of a dominant negative fragment of GASP inhibited receptor trafficking to lysosomes and promoted recycling. The GASP family of proteins may modulate lysosomal sorting and functional down-regulation of a variety of G protein–coupled receptors.
Development of image analysis techniques as a tool to detect and quantify morphological changes in anaerobic sludge: I. Application to a granulation process

Image analysis techniques were developed and applied to quantify the process of anaerobic granulation in an expanded granular sludge blanket reactor (EGSB) fed with a synthetic substrate based on glucose [60–30% COD (chemical oxygen demand)] and volatile fatty acids (40–70% COD) over 376 days. In a first operation period that lasted 177 days, the aggregation of dispersed sludge was quantitatively monitored through the recognition and quantification of aggregates and filaments. A parameter defined as the ratio between the filaments' length and the aggregates projected area (LfA) has proven to be sensitive to detect changes in the aggregation status of the anaerobic sludge. The aggregation time—defined as the moment when a balance between filaments' length and aggregates' size was established—was recognized through the LfA. The percentage of projected area of aggregates within three size ranges (0.01–0.1 mm, 0.1–1 mm, and >1 mm, equivalent diameter) reflected the granular size spectrum during the aggregation process. When sudden increases on the upflow velocity and on the organic loading rate were applied to the previously formed granules, the developed image analysis techniques revealed to be good indicators of granular sludge stability, since they were sensitive to detected filaments release, fragmentation, and erosion that usually leads to washout. The specific methanogenic activities in the presence of acetate, propionate, butyrate, and H2/CO2 increased along the operation, particularly relevant was the sudden increase in the specific hydrogenophilic activity, immediately after the moment recognized as aggregation time. © 2004 Wiley Periodicals, Inc.
Design and Implementation of Foot-Mounted Inertial Sensor Based Wearable Electronic Device for Game Play Application

Wearable electronic devices have experienced increasing development with the advances in the semiconductor industry and have received more attention during the last decades. This paper presents the development and implementation of a novel inertial sensor-based foot-mounted wearable electronic device for a brand new application: game playing. The main objective of the introduced system is to monitor and identify the human foot stepping direction in real time, and coordinate these motions to control the player operation in games. This proposed system extends the utilized field of currently available wearable devices and introduces a convenient and portable medium to perform exercise in a more compelling way in the near future. This paper provides an overview of the previously-developed system platforms, introduces the main idea behind this novel application, and describes the implemented human foot moving direction identification algorithm. Practical experiment results demonstrate that the proposed system is capable of recognizing five foot motions, jump, step left, step right, step forward, and step backward, and has achieved an over 97% accuracy performance for different users. The functionality of the system for real-time application has also been verified through the practical experiments.
Impaired Cerebral Autoregulation in Patients With Malignant Hypertension

Background—In patients with a malignant hypertension, immediate parenteral treatment with blood pressure–lowering agents such as intravenous sodium nitroprusside (SNP) is indicated. In this study, we evaluated static and dynamic cerebral autoregulation (CA) during acute blood pressure lowering with SNP in these patients. Methods and Results—In 8 patients with mean arterial pressure (MAP) >140 mm Hg and grade III or IV hypertensive retinopathy at hospital admission, middle cerebral artery blood velocity (MCA V) and blood pressure were monitored. Dynamic CA was expressed as the 0.1-Hz MCA Vmean to MAP phase lead and static CA as the MCA Vmean to MAP relationship during SNP treatment. Eight normotensive subjects served as a reference group. In the patients, the MCA Vmean to MAP phase lead was lower (30±8° versus 58±5°, mean±SEM; P<0.05), whereas the transfer gain tended to be higher. During SNP treatment, target MAP was reached within 90 minutes in all patients. The MCA Vmean decrease was 22±4%, along with a 27±3% reduction in MAP (from 166±4 to 121±6 mm Hg; P<0.05) in a linear fashion (averaged slope, 0.82±0.15% cm · s−1 · % mm Hg−1; r=0.70±0.07). Conclusions—In patients with malignant hypertension, dynamic CA is impaired. An MCA Vmean plateau was not detected during the whole SNP treatment, indicating loss of static CA as well. This study showed that during the whole rapid reduction in blood pressure with SNP, MCA Vmean decreases almost one on one with MAP.
Cognitive WMNs : A Distributed Mechanism for Leasing Cellular Network Bandwidth

We study flow optimization in cognitive Wireless Mesh Networks (WMN) that lease bandwidth from a collocated cellular network (CN). We develop a distributed mechanism that such WMNs can use to optimize their traffic given their own utilities and costs and the costs that the CN is charging for the use of its channels. We evaluate the mechanism in a synthetic scenario using the topology of an actual deployed WMN and timevarying traffic requirements induced from actual vehicle mobility traces. Simulations show that the mechanism can track well the changes in the problem parameters, continuously keeping close to the optimum operation point.
The CD8+ T-Cell Response to Lymphocytic Choriomeningitis Virus Involves the L Antigen: Uncovering New Tricks for an Old Virus

ABSTRACT CD8+ T-cell responses control lymphocytic choriomeningitis virus (LCMV) infection in H-2b mice. Although antigen-specific responses against LCMV infection are well studied, we found that a significant fraction of the CD8+ CD44hi T-cell response to LCMV in H-2b mice was not accounted for by known epitopes. We screened peptides predicted to bind major histocompatibility complex class I and overlapping 15-mer peptides spanning the complete LCMV proteome for gamma interferon (IFN-γ) induction from CD8+ T cells derived from LCMV-infected H-2b mice. We identified 19 novel epitopes. Together with the 9 previously known, these epitopes account for the total CD8+ CD44hi response. Thus, bystander T-cell activation does not contribute appreciably to the CD8+ CD44hi pool. Strikingly, 15 of the 19 new epitopes were derived from the viral L polymerase, which, until now, was not recognized as a target of the cellular response induced by LCMV infection. The L epitopes induced significant levels of in vivo cytotoxicity and conferred protection against LCMV challenge. Interestingly, protection from viral challenge was best correlated with the cytolytic potential of CD8+ T cells, whereas IFN-γ production and peptide avidity appear to play a lesser role. Taken together, these findings illustrate that the LCMV-specific CD8+ T-cell response is more complex than previously appreciated.
The Effect of Spinal Bupivacaine in Combination with Either Epidural Clonidine and/or 0.5% Bupivacaine Administered at the Incision Site on Postoperative Outcome in Patients Undergoing Lumbar Laminectomy

Spinal anesthesia has numerous advantages over general anesthesia for patients undergoing lumbar laminectomy and microdisk surgery. In this study, we evaluated the addition of epidural clonidine and/or bupivacaine, injected at the incision site, on postoperative outcome variables in patients undergoing lower spine procedures using spinal anesthesia. One hundred twenty patients having lumbar spine surgery received bupivacaine spinal anesthesia supplemented by 150 &mgr;g of epidural clonidine with or without incisional bupivacaine, epidural placebo plus incisional bupivacaine, or placebo with incisional saline. Demographic data, intraoperative hemodynamics, blood loss, pain, nausea, urinary retention, hospital discharge, and other variables were compared by using either analysis of variance or &khgr;2 analysis. Demographics were similar. IV fluids, blood loss, incidence of intraoperative bradycardia, and hypotension were not different among groups. Postanesthesia care unit pain scores were lower and demand for analgesics was less in patients who received both the clonidine and subcutaneous bupivacaine. Patients who received epidural clonidine also had improved postoperative hemodynamics. Hospital discharge, urinary retention, and other variables were not different. We conclude that epidural clonidine as a supplement to spinal anesthesia produced no perioperative complications and improved postoperative pain and hemodynamic stability in patients undergoing lower spine procedures.
Structural Antitumoral Activity Relationships of Synthetic Chalcones

Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2’-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2’-hydroxychalcones, showed the mayor structure-activity pattern along the series.
Occupational exposure to organic solvents and breast cancer in women

Background Although studies in rodents suggest possible associations between exposure to organic solvents and breast cancer, the evidence in humans is limited. Methods We evaluated job histories of 2383 incident breast cancer cases diagnosed during 2000–2003, and 2502 controls who participated in a large population-based case-control study in Poland. Industrial hygienists reviewed occupational histories and developed exposure metrics for total organic solvents and benzene. Unconditional logistic regression analyses estimated ORs and 95% CIs as the measure of association with breast cancer, controlling for breast cancer risk factors. Stratified analyses examined the potential modification by known breast cancer risk factors. Associations were also evaluated by oestrogen and progesterone receptor status and by other clinical characteristics of the tumours using polytomous regression analyses. Results Women who ever worked at jobs with organic solvents exposure had a small, non-significant increase in breast cancer risk (OR=1.16; 95% CI 0.99 to 1.4). A significant association was present for oestrogen receptor- and progesterone receptor-negative tumours (OR 1.40; 95% CI 1.1 to 1.8), but there was no association with tumours with both positive receptors (OR 0.97; 95% CI 0.8 to 1.2 (p heterogeneity: 0.008)). We did not observe trends with increasing level of exposure. Known breast cancer risk factors did not modify the association between organic solvents and breast cancer risk. No association with breast cancer was found for benzene exposure (OR 1.00; 95% CI 0.8 to 1.3). Conclusion Our study provides weak evidence for a possible association between occupational exposure to organic solvents as a class and breast cancer risk. The association might be limited to hormone receptor-negative tumours.
Improving Performance of Matrix Multiplication and FFT on GPU

In this paper we discuss about our experiences in improving the performance of two key algorithms: the single-precision matrix-matrix multiplication subprogram (SGEMM of BLAS) and single-precision FFT using CUDA. The former is computation-intensive, while the latter is memory bandwidth or communication-intensive. A peak performance of 393 Gflops is achieved on NVIDIA GeForce GTX280 for the former, about 5% faster than the CUBLAS 2.0 library. Better FFT performance results are obtained for a range of dimensions. Some common principles are discussed for the design and implementation of many-core algorithms.
Slow and Smooth: A Bayesian theory for the combination of local motion signals in human vision

In order to estimate the motion of an object, the visual system needs to combine multiple local measurements, each of which carries some degree of ambiguity. We present a model of motion perception whereby measurements from di erent image regions are combined according to a Bayesian estimator | the estimated motion maximizes the posterior probability assuming a prior favoring slow and smooth velocities. In reviewing a large number of previously published phenomena we nd that the Bayesian estimator predicts a wide range of psychophysical results. This suggests that the seemingly complex set of illusions arise from a single computational strategy that is optimal under reasonable assumptions. Copyright c Massachusetts Institute of Technology, 1998 This report describes research done at the Center for Biological and Computational Learning and the Department of Brain and Cognitive Sciences of the Massachusetts Institute of Technology. Support for the Center is provided in part by a grant from the National Science Foundation under contract ASC{9217041. The work was also supported by NEI R01 EY11005 to E. H. Adelson
Human activity recognition in the context of industrial human-robot interaction

Human activity recognition is crucial for intuitive cooperation between humans and robots. We present an approach for activity recognition for applications in the context of human-robot interaction in industrial settings. The approach is based on spatial and temporal features derived from skeletal data of human workers performing assembly tasks. These features were used to train a machine learning framework, which classifies discrete time frames with Random Forests and subsequently models temporal dependencies between the resulting states with a Hidden Markov Model. We considered the following three groups of activities: Movement, Gestures, and Object handling. A dataset has been collected which is comprised of 24 recordings of several human workers performing such activities in a human-robot interaction environment, as typically seen at small and medium-sized enterprises. The evaluation shows that the approach achieves a recognition accuracy of up to 88% for some activities and an average accuracy of 73%.
Path planning of line follower robot

This paper presents the development of a line follower wheeled mobile robot. In this project, LM3S811 which is ARM cortex-3 based microcontroller is chosen as the main controller to react towards the data received from infra-red line sensors to give fast, smooth, accurate and safe movement in partially structured environment. A dynamic PID control algorithm has been proposed to improve the navigation reliability of the wheeled mobile robot which uses differential drive locomotion system. The experimental results show that the dynamic PID algorithm can be performed under the system real-time requirements.
Polynomial observer design for unknown inputs polynomial fuzzy systems: A Sum of Squares approach

This paper deals with a polynomial fuzzy observer (PFO) design for a class of nonlinear continuous systems that can be modeled as polynomial fuzzy systems (PFS) subject to unknown inputs. The proposed polynomial observer is developed to ensure the asymptotic convergence of the observing error using the Lyapunov method and numerical tools. Sufficient design conditions are given in Sum Of Squares (SOS) formulation which can be numerically solved via the SOSTOOLS software and a semidefinite program (SDP) solver. Finally, a numerical example is given to illustrate the effectiveness of the proposed approach.