Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Stem Cells Research Article

INTRODUCTION Modeling embryonic development in pluripotent stem cell (PSC) differentiation cultures has proven to be the most effective approach for the efficient generation of differentiated cells types in vitro (Murry and Keller, 2008). For pancreatic development, the crucial steps that need to be accurately modeled include the induction of definitive endoderm, the patterning and specification of endoderm to a pancreatic fate and the generation of mature endocrine/exocrine cells (Wells and Melton, 1999). Studies using different model systems have shown that induction of definitive endoderm is dependent on signaling through the nodal pathway
IFATS Collection: The Conditioned Media of Adipose Stromal Cells Protect Against Hypoxia‐Ischemia‐Induced Brain Damage in Neonatal Rats

Adipose tissue stroma contains a population of mesenchymal stem cells, which support repair when administered to damaged tissues, in large part through secreted trophic factors. We directly tested the ability of media collected from cultured adipose‐derived stem cells (ASCs) to protect neurons in a rat model of brain hypoxic‐ischemic (HI) injury. Concentrated conditioned medium from cultured rat ASCs (ASC‐CM) or control medium was infused through the jugular vein of neonatal Sprague‐Dawley rats subjected to HI injury. The ASC‐CM was administered either 1 hour before or 24 hours after induction of injury. Analysis at 1 week indicated that administration at both time points significantly protected against hippocampal and cortical volume loss. Analysis of parallel groups for behavioral and learning changes at 2 months postischemia demonstrated that both treated groups performed significantly better than the controls in Morris water maze functional tests. Subsequent post‐mortem evaluation of brain damage at the 2‐month time point confirmed neuronal loss to be similar to that observed at 1 week for all groups. We have identified several neurotrophic factors in ASC‐CM, particularly insulin‐like growth factor‐1 and brain‐derived neurotrophic factor, which are important factors that could contribute to the protective effects of ASCs observed in studies with both in vitro and in vivo neuronal injury models. These data suggest that delivery of the milieu of factors secreted by ASCs may be a viable therapeutic option for treatment of HI, as well as other brain injuries. STEM CELLS 2009;27:478–488
Characteristics of 5015 Salivary Gland Neoplasms Registered in the Hiroshima Tumor Tissue Registry over a Period of 39 Years

Salivary gland neoplasms are uncommon, and their epidemiology in Japan has not been well described. We conducted a retrospective review of salivary gland tumors registered in the Hiroshima Tumor Tissue Registry over a period of 39 years. The subjects were 5015 cases ranging in age from 6 to 97 (mean, 54.3) years old. The incidence of both benign tumors and malignant tumors increased with age until 60–69 years and then declined. Among the 5015 salivary gland neoplasms, 3998 (80%) were benign and 1017 (20%) were malignant. Pleomorphic adenoma (PA) was the most frequent benign tumor (68%), followed by Warthin tumor (26%). Adenoid cystic carcinoma (ACC) (27%) and mucoepidermoid carcinoma (MEC) (26%) were the two most frequent malignant tumors. Characteristically, there was a very low incidence of polymorphous adenocarcinoma in Japan. The average annual age-adjusted incidence rate per 100,000 population was 3.3 for benign tumors and 0.8 for malignant tumors. This is the large-scale multi-institutional analysis to describe the characteristics of salivary gland neoplasms, based on the pathological tissue registry data. We hope that the present data can contribute to early diagnosis and effective treatment of salivary gland tumors and to cancer prevention.
Risk factors for complex partial seizures: A population‐based case‐control study

This investigation is to our knowledge the first population‐based case‐control study of risk factors for complex partial seizures (CPS). Included in the study were all patients with onset of complex partial seizures before age 35, who were residents of Rochester, Minnesota, at the time of diagnosis between 1935 and 1979, and who were also born in Rochester (n = 82). Two control subjects were matched to each patient, and for both patients and control subjects, the unique records‐linkage system for residents of Rochester was used to obtain information about possible risk factors. A history of epilepsy or febrile seizures in the mother, febrile seizures, neonatal convulsions, cerebral palsy, head trauma, and viral encephalitis were significantly more common in patients than in control subjects (p < 0.05). None of the prenatal or perinatal factors investigated were found to be associated with complex partial seizures, except for being small for gestational age at birth. This factor lost significance after adjustment for cerebral palsy.
Does Pollution Drive Achievement? The Effect of Traffic Pollution on Academic Performance

ABSTRACT We examine the effect of traffic pollution on student outcomes by leveraging variation in wind patterns for schools the same distance from major highways. We compare within-student changes in achievement for students transitioning between schools near highways, where one school has greater levels of pollution because it is downwind of a highway. As students graduate from elementary/middle school to middle/high school, their test scores decrease, behavioral incidents increase, and absence rates increase when they attend a downwind school, relative to when they attend an upwind school in the same zip code. Even within zip codes, microclimates can contribute to inequality.
Photocoagulation of the Retinal Nonperfusion Area Prevents the Expression of the Vascular Endothelial Growth Factor in an Animal Model.

Purpose The purpose of this study was to evaluate whether photocoagulation of the retinal nonperfusion area suppresses ocular vascular endothelial growth factor (VEGF) expression in a rabbit retinal vein occlusion (RVO) model. Methods The retinas of pigmented rabbits were made ischemic by a laser on the main branch of retinal veins following intravenous injection of Rose Bengal. The eyes were enucleated before treatment and at 1, 7, and 14 days after laser occlusion. VEGF protein levels in the vitreous humor, sensory retina, and retinal pigment epithelium-choroid were measured with enzyme-linked immunosorbent assay. In situ hybridization of VEGF messenger RNA was performed to detect the location of VEGF expression in the sensory retina. Results In the vitreous body, the VEGF protein level in the RVO group, but not that in the RVO + panretinal photocoagulation group, significantly increased on day 14. In the retina, the VEGF protein level in the RVO + panretinal photocoagulation group was significantly higher than that in the RVO group on day 1, but was significantly lower than that in the RVO group on days 7 and 14. In the in situ hybridization analysis, the RVO group showed a high expression of VEGF in the inner nuclear and ganglion cell layers on days 7 and 14. In contrast, VEGF expression in the RVO + panretinal photocoagulation group was strongly suppressed in both the inner nuclear and ganglion cell layers on days 7 and 14. Conclusions This study is the first using an animal RVO model to demonstrate that laser photocoagulation of the retinal nonperfusion area suppresses VEGF-A expression in the retina.
A Feature Analysis Approach to Mass Detection in Mammography Based on RF-SVM

A new approach to mass detection in mammography is presented. The main obstacle of building a mass detection system is the similar appearance between masses and density tissues in breast. Hence, the various features of the extracted regions of interest (ROIs) are analyzed by synthesis. Then the support vector machine (SVM), which is designed later to distinguish masses from normal areas, is employed to classify these ROIs exactly. To further improve the performance of SVM, the relevance feedback (RF) is introduced to filter out the false positives. The experimental results illustrate that SVM classifier can effectively detect the mass areas, and the RF-SVM scheme can be efficiently incorporated into this learning framework to further improve detection performance.
The effect of age on the key parameters in the Chicago classification: a study using high‐resolution esophageal manometry in asymptomatic normal individuals

High‐resolution manometry using the Chicago classification, which utilizes parameters including integrated relaxation pressure (IRP), distal contractile integral (DCI), and contractile front velocity (CFV), shows better diagnostic ability than previous conventional criteria. However, the current normal cut‐off values for the Chicago classification are based on individuals aged 19–48 years and do not include older people. Here, we aimed to assess the normal values for the Chicago classification in individuals aged 20–67 years and compare the parameters across age groups.
Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed

Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.
Secure Initialization of Multiple Constrained Wireless Devices for an Unaided User

A number of protocols and mechanisms have been proposed to address the problem of initial secure key deployment in wireless networks. Most existing approaches work either with a small number of wireless devices (i.e., two) or otherwise rely on the presence of an auxiliary device (such as a programmable camera, computer, or Faraday cage). In this paper, we design a solution that allows a user unaided initialization (free from auxiliary devices) of a relatively large number of wireless devices. The proposed solution is based on a novel multichannel Group message Authentication Protocol (GAP), in which information is transmitted over both a radio and a visible light channel (VLC). A notable feature of GAP is that the information to be authenticated is independent of the short authentication string\o be verified by the user (an indirect binding protocol [28]). This, as we show, results in a lower communication cost compared to existing direct binding protocols. The advantage in terms of the communication cost of our GAP protocol is especially important for power-constrained devices, such as wireless sensor motes. Another appealing feature of GAP is that it is secure in the attacker model where the VLC is semiauthentic, whereas existing protocols consider VLC to be authentic. This is made possible by using joint Manchester-Berger unidirectional error-detection codes that are secure and easy to interpret by a nonspecialist and unaided end user. Our overall key deployment mechanism has minimal hardware requirements: one LED, one button and, of course, a radio transceiver, and is thus suitable for initializing devices with constrained interfaces, such as (multiple) wireless sensor motes. We demonstrate the feasibility of the proposed method via a preliminary usability study. The study indicates that the method has reasonably low execution time, minimal error rate, and is user friendly.
Database Isolation and Filtering against Data Corruption Attacks

Various attacks (e.g., SQL injections) may corrupt data items in the database systems, which decreases the integrity level of the database. Intrusion detections systems are becoming more and more sophisticated to detect such attacks. However, more advanced detection techniques require more complicated analyses, e.g, sequential analysis, which incurs detection latency. If we have an intrusion detection system as a filter for all system inputs, we introduce a uniform processing latency to all transactions of the database system. In this paper, we propose to use a "unsafe zone" to isolate user's SQL queries from a "safe zone" of the database. In the unsafe zone, we use polyinstantiations and flags for the records to provide an immediate but different view from that of the safe zone to the user. Such isolation has negligible processing latency from the user's view, while it can significantly improve the integrity level of the whole database system and reduce the recovery costs. Our techniques provide different integrity levels within different zones. Both our analytical and experimental results confirm the effectiveness of our isolation techniques against data corruption attacks to the databases. Our techniques can be applied to database systems to provide multizone isolations with different levels of QoS.
Influence of polymorphisms within the methotrexate pathway genes on the toxicity and efficacy of methotrexate in patients with juvenile idiopathic arthritis.

AIMS We investigated whether several polymorphisms within the methotrexate (MTX) pathway genes were related to the toxicity and efficacy of MTX in 92 Japanese patients with articular-type juvenile idiopathic arthritis (JIA). METHODS Eight gene polymorphisms within the MTX pathway genes, namely, RFC, BCRP, MTHFR (two), FPGS, γ-glutamyl hydrolase (GGH; two) and ATIC, were genotyped using TaqMan assays. Liver dysfunction was defined as an increase in alanine transaminase to five times the normal upper limit. Non-responders to MTX were defined as patients refractory to MTX and were therefore treated with biologics. RESULTS The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction (P=0.028, odds ratio=6.90, 95% confidence interval 1.38-34.5), even after adjustment for the duration of MTX treatment. A longer interval from disease onset to treatment (8.5 and 21.3 months, P=0.029) and rheumatoid factor positivity (P=0.026, odds ratio=2.87, 95% confidence interval 1.11-7.39) were associated with lower efficacy of MTX. CONCLUSIONS The non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction, presumably because the C allele of GGH C16T may reduce the activity of GGH. The time interval before MTX treatment and rheumatoid factor positivity were associated with the efficacy of MTX treatment. The pharmacogenetics of the MTX pathway genes affects the toxicity and efficacy of MTX in Japanese JIA patients.
Anti‐IB, an Expected “New” Antibody Detecting a Joint Product of the I and B Genes 1

Since the original description, in 1956, of the I antigen by WIENER, UNGER, COHEN and FELDMAN [14] it has become increasingly apparent that there is an association between the I and the ABO antigens. The autoimmune anti-I (Steg) described by RACE and SANGER [9] reacts, on an average, more strongly with 0 cells than with cells of other ABO groups. ROSENFIELD, SCHROEDER, BALLARD, VAN DER HART, MOES and VAN LOGHEM [lo] have shown that the antibody with anti-H specificity that is not neutralizable by saliva from a group 0 secretor usually has anti-IH specificity while SCHMIDT and MCGINNISS [12] consider the relationship between I and 0 to be closer than the relationship between I and H from working with anti-0, anti-H and anti-I sera. TIPPETT, NOADES, SANGER, RACE, SAUSAIS, HOLMAN and BUTTIMER [13] describe an anti-IA, formed by a group A, subject which reacts more strongly with A, than with A, or 0 cells while NEWTON [7] has recently found a serum from an A, subject that contains both anti-A, and anti-IA the latter of which reacts much more strongly with A, than with 0 cells. In 1965, SALMON, HOMBERG, LIBERGE and DELARUE [ll] made a series of eluates from red cells of patients with acquired hemolytic anemia. In one instance they found in the eluate of a group A, patient an anti-I that reacted only with cells producing I and H or I and A. In the eluate from the red cells of a group AB patient they found an anti-I which would react with cells producing I and H; I and A or I and B. SALMON et al. interpret these findings as indicating that the
Depression-Biased Reverse Plasticity Rule Is Required for Stable Learning at Top-Down Connections

Top-down synapses are ubiquitous throughout neocortex and play a central role in cognition, yet little is known about their development and specificity. During sensory experience, lower neocortical areas are activated before higher ones, causing top-down synapses to experience a preponderance of post-synaptic activity preceding pre-synaptic activity. This timing pattern is the opposite of that experienced by bottom-up synapses, which suggests that different versions of spike-timing dependent synaptic plasticity (STDP) rules may be required at top-down synapses. We consider a two-layer neural network model and investigate which STDP rules can lead to a distribution of top-down synaptic weights that is stable, diverse and avoids strong loops. We introduce a temporally reversed rule (rSTDP) where top-down synapses are potentiated if post-synaptic activity precedes pre-synaptic activity. Combining analytical work and integrate-and-fire simulations, we show that only depression-biased rSTDP (and not classical STDP) produces stable and diverse top-down weights. The conclusions did not change upon addition of homeostatic mechanisms, multiplicative STDP rules or weak external input to the top neurons. Our prediction for rSTDP at top-down synapses, which are distally located, is supported by recent neurophysiological evidence showing the existence of temporally reversed STDP in synapses that are distal to the post-synaptic cell body.
Mobile Web Apps

With smartphones being the primary handheld device for more than a billion people, mobile Web apps are a necessity in both technical and commercial fields. There are several approaches to developing mobile Web apps, but given the fast speed of mobile software evolution, in which the leading companies become marginal in months and new gadgets continually appear, it's crucial to understand the basic technologies. Authors Nicolás Serrano, Josune Hernantes, and Gorka Gallardo examine current development approaches that can enhance the decision-making process.
Fluoxetine prevents acetylcholine‐induced excitotoxicity blocking human endplate acetylcholine receptor

Introduction: Fluoxetine is an open channel blocker of fetal muscle acetylcholine (ACh) receptor (AChR) and slow‐channel mutant AChRs. It is used commonly to treat patients with slow‐channel congenital myasthenic syndromes. Fluoxetine effects on adult wild‐type endplate AChR are less characterized, although muscle AChR isoforms are differentially modulated by some drugs. Methods: Excitotoxicity assays and patch clamp recordings were performed in human embryonic kidney 293 (HEK) cells expressing wild‐type or slow‐channel mutant human AChRs. Results: Fluoxetine (2–10 μM) abolished ACh‐induced death and decreased ACh‐activated whole‐cell currents in cells expressing all AChR types. In outside‐out patches, fluoxetine rapidly curtailed ACh evoked unitary activity and macroscopic currents. The effect was increased if fluoxetine was applied before ACh. Conclusions: Fluoxetine is an open channel blocker, but it also affects AChR in the closed state. AChR blockade likely underlies the rescue of HEK cells from ACh‐induced death. Muscle Nerve 49: 90–97, 2014
The Rate of Concentration Change and How It Determines the Resolving Power of Olfactory Receptor Neurons

The response characteristics of olfactory receptor neurons (ORNs) and their corollary, the differential sensitivity and the resolving power, are fundamental to understand olfactory coding and the information extracted from a fluctuating olfactory signal. Previous work has focused on the temporal resolution of odor pulses presented for very brief periods at varying concentrations. The time course of the odor pulses as a stimulus parameter has not been considered. The present study investigated the precision of the ON and OFF ORNs on the antennae of the cockroach to discriminate increments and decrements of continuously rising and falling odor concentrations. Stimulation consisted of ramp-like upward and downward concentration changes in a trapezoid fashion. By varying ramp steepness, we examined the effect of the rate of concentration change. Both ORNs were clearly dependent on continuously rising and falling odor concentrations. As the rate of upward and downward concentration changes increases, differential sensitivity improves. Since the scatter of responses around the stimulus-response functions also increases, the resolving power for concentration increments and decrements deteriorates. Thus, the slower the rate of concentration change, the higher the precision in differentiating small concentration changes. Intuitively, the inverse relationship between the rate of concentration change and the resolving power is not surprising because accuracy requires time. A high degree of precision at slow concentration rates enables the cockroach to use information about the onset and offset slopes of odor pulses in addition to the pulse height to encode the spatial-temporal structure of turbulent odor plumes.
Quantized Antenna Combining for Multiuser MIMO-OFDM With Limited Feedback

A method for reducing feedback in a downlink multiuser MIMO-OFDM cellular system, with zero forcing beamforming at the base (BS) and antenna combining at each mobile (MS) is proposed. The method consists of partitioning the subcarriers into groups, choosing the quantized channel vector that better represents each group in terms of average quantization error. Numerical results show that savings up to 93% in overhead bits are obtained for SNR equal to 15 dB, with reductions in channel capacity that goes from 30% to 50% depending on the codebook size used for quantization.
USING PARALLEL MARKOV CHAIN MONTE CARLO TO QUANTIFY UNCERTAINTIES IN GEOTHERMAL RESERVOIR CALIBRATION

We introduce a parallel rejection scheme to give a simple but reliable way to parallelise the Metropolis-Hastings algorithm. This method can be particularly useful when the target density is computationally expensive to evaluate and the acceptance rate of the Metropolis-Hastings is low. We apply the resulting method to quantify uncertainties of inverse problems, in which we aim to calibrate a challenging nonlinear geothermal reservoir model using real measurements from well tests. We demonstrate the parallelised method on various well-test scenarios. In some scenarios, the sample-based statistics obtained by our scheme shows clear advantages in providing robust model calibration and prediction compared with those obtained by nonlinear optimisation methods.