Miracle-dz/UniFAR-FTUs huggingface dataset:
Calcium concentration dynamics produced by synaptic activation of CA1 hippocampal pyramidal cells

The spatial and temporal dynamics of many electrophysiological and biochemical processes in nerve cells are in turn dependent on the concentration dynamics of the second messenger calcium. We have used microfluorimetry of the calcium indicator fura-2 (Grynkiewicz et al., 1985) to measure and characterize synaptically activated calcium changes in individual CA1 pyramidal cells contained within guinea pig hippocampal slices. One component of the calcium changes was largely produced by influx through voltage-dependent Ca2+ channels (VDCCs). It consisted of large transient accumulations in the proximal-apical and basal dendrites; the amplitude was smaller in the distal-apical dendrites and the soma. This spatial profile was insensitive to the method of cell activation: stimulation of inputs located at different positions on the dendritic tree as well as antidromic stimulation produced only slight modifications. This component was not blocked by the NMDA antagonist 5-amino-4-phosphonovalerate (AP5) (Collingridge et al., 1983), was greatly reduced by Cd2+, partially reduced by nifedipine, and was increased by Bay-K 8644, providing the evidence that it was largely produced by influx through VDCCs. Blocking postsynaptic Na+ channels with QX-314 greatly reduced the accumulation amplitude, and spatial differences between proximal-dendritic and distal-dendritic regions were less pronounced, suggesting that active sodium conductances contribute significantly to the spatial activation of calcium conductances. Residual spatial differences that persist in QX-314 experiments are consistent with the idea that VDCCs have decreased density on distal-apical dendrites. A second component of accumulation was induced by ionic currents through NMDA receptor channels. It was blocked by AP5, unaffected by QX-314, attenuated and slowed down by elevated calcium buffering, and spatially localized to regions receiving activated synaptic inputs. The magnitude of this component was strongly dependent on the frequency and amplitude of synaptic activation. At high frequency, it was generally very large, often saturating the fura-2 (> 2 microM). Measurements made with the indicator furaptra also showed large localized AP5-sensitive fluorescence changes. Our results suggest that in dendritic regions near activated input fibers calcium levels may reach 2–10 microM. In general, our measurements of calcium dynamics provide an experimental basis for evaluating the spatial distribution of calcium conductances, the spatial distribution of calcium-activated electrophysiological and biochemical processes, and the spatial uniformity of calcium buffering and removal systems in CA1 hippocampal pyramidal cells. The time course and amplitude of Ca2+ transients we measured suggest that activation of Ca(2+)-dependent conductances [e.g., IK(Ca)] will be markedly different for different cellular regions. (ABSTRACT TRUNCATED AT 400 WORDS)
Genetic Variants Within the LPIN1 Gene, Encoding Lipin, Are Influencing Phenotypes of the Metabolic Syndrome in Humans

OBJECTIVE— Lipin, a novel molecular protein expressed by adipocytes, has marked effects on adipose tissue mass, insulin sensitivity, and glucose homeostasis. Thus, we hypothesized that genetic variants within LPIN1 are associated with traits of the metabolic syndrome. RESEARCH DESIGN AND METHODS— A total of 15 single nucleotide polymorphisms (SNPs) covering the LPIN1 gene region were genotyped in an age- and sex-stratified sample of the general population (Monitoring Trends and Determinants on Cardiovascular Diseases Study Augsburg; DNA and phenotypes of 1,416 Caucasians). Ten SNPs were also genotyped for replication in an independent sample of 1,030 subjects recruited throughout Germany. The metabolic syndrome was defined via the sum of its core components and, additionally, by a factor score derived from factor analysis. Permutation-based methods were used to test the association between genetic LPIN1 variants and metabolic traits for empirical significance. RESULTS— Linkage disequilibrium (LD) analysis revealed three LD blocks encompassing LPIN1. We identified three associated three-marker haplotypes: one common haplotype (26.8% frequency) increases the risk for the metabolic syndrome (odds ratio 1.6 [95% CI 1.2–2.2]), while the other two, being less common (5.7 and 4.0%), are strongly associated with lower blood pressure levels (systolic blood pressure 127 ± 18 vs. 135 ± 20 mmHg; P = 0.0001), a lower BMI (24.6 ± 3.6 vs. 26.9 ± 4.1 kg/m2; P = 3.7 × 10−7) and waist circumference (82 ± 12 vs. 90 ± 12 cm; P = 3.2 × 10−8), lower A1C levels (5.1 ± 0.7 vs. 5.3 ± 0.9%; P = 0.0002), as well as a lower metabolic syndrome factor score (−0.67 ± 1.00 vs. 0.04 ± 1.24; P = 1.4 × 10−7). Furthermore, the frequencies of arterial hypertension (23.7 vs. 46.4%; P = 0.00001), obesity (12.9 vs. 30.8%; P = 0.0003), diabetes (2.2 vs. 8.2%; P = 0.041), and the presence of three or more metabolic syndrome components (3.3 vs. 13.7%; P = 0.002) were significantly lower than in subjects not carrying one of these protective haplotypes. Strong associations were also observed in the replication sample using the same haplotypes but with effects in the opposite direction. CONCLUSIONS— These data suggest that allelic variants of the LPIN1 gene have significant effects in human metabolic traits and thus implicate lipin in the pathophysiology of the metabolic syndrome.
Non-invasive imaging in the diagnosis and management of Takayasu’s arteritis

Objectives: Takayasu’s arteritis (TA) is a rare disease, in which early diagnosis and assessment of treatment efficacy remain a problem. Signs and symptoms may be non-specific and conventional blood tests unreliable, with vascular inflammation often persisting in the face of a normal acute phase response. The current “gold standard” investigation, x ray angiography, is invasive and only identifies late, structural changes in vessels. Recently, non-invasive imaging methods have shown promise in the assessment of patients with TA. Methods: The invasive and non-invasive imaging performed on all patients in the rheumatology department at the Hammersmith Hospital between May 1996 and May 2002 who fulfilled the ACR criteria for TA were reviewed. All patients were clinically active at diagnosis and were treated with high dose oral prednisolone and additional oral or intravenous immunosuppression. Results: Non-invasive imaging methods ([18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) and magnetic resonance imaging (MRI)) provided important additional information about disease activity ([18F]FDG-PET) and progression of vessel wall thickening (MRI) when compared with x ray angiography. Conclusions: Non-invasive imaging methods provide useful additional information towards the diagnosis and management of TA. Such techniques may allow earlier diagnosis and more accurate assessment of response to treatment than conventional clinical assessment and/or angiography. Non-invasive imaging is likely to be useful in the management of other large vessel vasculitides.
Platelet‐derived extracellular vesicles in plateletpheresis concentrates as a quality control approach

Platelet‐derived extracellular vesicles (PL‐EVs) are present in plateletpheresis concentrates (PCs) and may influence the quality of PCs. The aim of the study was to analyze PC‐derived PL‐EVs and to correlate them with standard quality control (QC) variables of PCs and with donor‐specific laboratory variables.
Carboxyl-Terminal Truncated HBx Regulates a Distinct MicroRNA Transcription Program in Hepatocellular Carcinoma Development

Background The biological pathways and functional properties by which misexpressed microRNAs (miRNAs) contribute to liver carcinogenesis have been intensively investigated. However, little is known about the upstream mechanisms that deregulate miRNA expressions in this process. In hepatocellular carcinoma (HCC), hepatitis B virus (HBV) X protein (HBx), a transcriptional trans-activator, is frequently expressed in truncated form without carboxyl-terminus but its role in miRNA expression and HCC development is unclear. Methods Human non-tumorigenic hepatocytes were infected with lentivirus-expressing full-length and carboxyl-terminal truncated HBx (Ct-HBx) for cell growth assay and miRNA profiling. Chromatin immunoprecipitation microarray was performed to identify the miRNA promoters directly associated with HBx. Direct transcriptional control was verified by luciferase reporter assay. The differential miRNA expressions were further validated in a cohort of HBV-associated HCC tissues using real-time PCR. Results Hepatocytes expressing Ct-HBx grew significantly faster than the full-length HBx counterparts. Ct-HBx decreased while full-length HBx increased the expression of a set of miRNAs with growth-suppressive functions. Interestingly, Ct-HBx bound to and inhibited the transcriptional activity of some of these miRNA promoters. Notably, some of the examined repressed-miRNAs (miR-26a, -29c, -146a and -190) were also significantly down-regulated in a subset of HCC tissues with carboxyl-terminal HBx truncation compared to their matching non-tumor tissues, highlighting the clinical relevance of our data. Conclusion Our results suggest that Ct-HBx directly regulates miRNA transcription and in turn promotes hepatocellular proliferation, thus revealing a viral contribution of miRNA deregulation during hepatocarcinogenesis.
Managing missed interactions in distributed virtual environments

A scalable distributed virtual environment (DVE) may be achieved by ensuring virtual world objects communicate their actions to only those objects that fall within their influence, reducing the need to send and process unnecessary messages. A missed interaction may be defined as a failure to exchange messages to appropriately model object interaction. A number of parameters under the control of a DVE developer may influence the possibility of missed interactions occurring (e.g., object velocities, area of influence). However, due to the complexities associated with object movement and the deployment environment (e.g., non-deterministic object movement, network latency), identifying the value for such parameters to minimise missed interactions while maintaining scalability (minimal message passing) is not clear. We present in this paper a tool which simulates a DVE and provides developers with an indication of the appropriate values for parameters when balancing missed interactions against scalability.
Location-Based Routing for Vehicular Ad-Hoc Networks

Communication between vehicles is likely to be one key area where mobile ad-hoc networks will be used in the near future. Currently there are several projects ([1, 3]) that investigate this application area, while car manufacturers and their suppliers aim at the development of products within the next few years. This raises the question what kind of routing algorithm is suited for communication between vehicles. Existing performance studies for various ad-hoc routing protocols do not use movement patterns which resemble the movement of cars and are thus not well suited to answer this question. We have conducted an extensive simulation study based on realistic vehicle movement patterns. Our main aim was to investigate how a topology-based approach compares to a location-based routing scheme when applied to vehicular networks. As representatives we have chosen DSR [4] as a topology-based approach and GPSR [5] complemented with a simple location service as a location-based scheme. For a general discussion of topology-based and location-based ad-hoc routing please refer to [2] and [6]. Vehicular ad-hoc networks have several unique characteristics. The main challenge is the high speed with which nodes move in respect to each other. If oncoming traffic is included in the forwarding of packets, then relative speeds of 250 km/h to 300 km/h are common. This implies a very high rate of topology changes. Also it is not clear if one single partition spans sufficient distance to enable meaningful applications such as emergency warnings or vehicle-to-vehicle entertainment. On the other hand it is safe to assume that battery power is not an issue for vehicular ad-hoc networks. Location-based approaches further benefit from the fact that vehicles are aware of their geographical positions through the use of on-board navigation systems.
Analysis and experimental demonstration of simplex coding technique for SNR enhancement of OTDR

We demonstrate SNR improvement of OTDR using simplex codes by experiment, for the first time. For this, we proposed a practical algorithm and derived detailed equations. An in-house OTDR board was developed to verify the proposed algorithm, and the experimental results showed excellent agreement with theory. In addition, we analyzed the SNR variation of the simplex code OTDR, caused by band-limited receiver characteristics.
Neurovascular Unit in Chronic Pain

Chronic pain is a debilitating condition with major socioeconomic impact, whose neurobiological basis is still not clear. An involvement of the neurovascular unit (NVU) has been recently proposed. In particular, the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB), two NVU key players, may be affected during the development of chronic pain; in particular, transient permeabilization of the barrier is suggested by several inflammatory- and nerve-injury-based pain models, and we argue that the clarification of molecular BBB/BSCB permeabilization events will shed new light in understanding chronic pain mechanisms. Possible biases in experiments supporting this theory and its translational potentials are discussed. Moving beyond an exclusive focus on the role of the endothelium, we propose that our understanding of the mechanisms subserving chronic pain will benefit from the extension of research efforts to the NVU as a whole. In this view, the available evidence on the interaction between analgesic drugs and the NVU is here reviewed. Chronic pain comorbidities, such as neuroinflammatory and neurodegenerative diseases, are also discussed in view of NVU changes, together with innovative pharmacological solutions targeting NVU components in chronic pain treatment.
DR*W201/P65 Tetramer Visualization of Epitope-Specific CD4 T-Cell during M. tuberculosis Infection and Its Resting Memory Pool after BCG Vaccination

Background In vivo kinetics and frequencies of epitope-specific CD4 T cells in lymphoid compartments during M. tuberculosis infection and their resting memory pool after BCG vaccination remain unknown. Methodology/Findings Macaque DR*W201 tetramer loaded with Ag85B peptide 65 was developed to directly measure epitope-specific CD4 T cells in blood and tissues form macaques after M. tuberculosis infection or BCG vaccination via direct staining and tetramer-enriched approach. The tetramer-based enrichment approach showed that P65 epitope-specific CD4 T cells emerged at mean frequencies of ∼500 and ∼4500 per 107 PBL at days 28 and 42, respectively, and at day 63 increased further to ∼22,000/107 PBL after M. tuberculosis infection. Direct tetramer staining showed that the tetramer-bound P65-specific T cells constituted about 0.2–0.3% of CD4 T cells in PBL, lymph nodes, spleens, and lungs at day 63 post-infection. 10-fold expansion of these tetramer-bound epitope-specific CD4 T cells was seen after the P65 peptide stimulation of PBL and tissue lymphocytes. The tetramer-based enrichment approach detected BCG-elicited resting memory P65-specific CD4 T cells at a mean frequency of 2,700 per 107 PBL. Significance Our work represents the first elucidation of in vivo kinetics and frequencies for tetramer-bound epitope-specific CD4 T cells in the blood, lymphoid tissues and lungs over times after M. tuberculosis infection, and BCG immunization.
Quetiapine for the treatment of bipolar II depression: Analysis of data from two randomized, double-blind, placebo-controlled studies

Objective. To investigate the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar II disorder. Methods. A post-hoc evaluation was conducted in 351patients with bipolar II depression combined from two similarly designed double-blind, randomized, placebo-controlled, 8-week studies of quetiapine (300 or 600mg/day) that included patients with bipolar I or II disorder (DSM-IV) exhibiting moderate to severe depression. The primary endpoint was change from baseline to week 8 in MADRS total score. Secondary endpoints included HAM-D, HAM-A, and CGI. Results: In patients with bipolar II disorder, improvement in mean MADRS total score from baseline was significantly greater with quetiapine 300 (n=107) and 600mg/day (n=106) from the first assessment (week 1) through week 8 compared with placebo (n=108). The mean change from baseline at week 8 for quetiapine 300 and 600mg/day versus placebo was −17.1 and −17.9 versus −13.3 (P=0.005 and P=0.001 versus placebo), respectively. Change in HAM-D, HAM-A, and CGI were also significantly greater for quetiapine groups versus placebo. Common adverse events in the quetiapine groups included dry mouth, sedation, and somnolence. Conclusion. Quetiapine demonstrated significant efficacy as monotherapy, compared with placebo, for the treatment of acute depressive episodes in bipolar II disorder.
Group Sparse Coding with a Laplacian Scale Mixture Prior

We propose a class of sparse coding models that utilizes a Laplacian Scale Mixture (LSM) prior to model dependencies among coefficients. Each coefficient is modeled as a Laplacian distribution with a variable scale parameter, with a Gamma distribution prior over the scale parameter. We show that, due to the conjugacy of the Gamma prior, it is possible to derive efficient inference procedures for both the coefficients and the scale parameter. When the scale parameters of a group of coefficients are combined into a single variable, it is possible to describe the dependencies that occur due to common amplitude fluctuations among coefficients, which have been shown to constitute a large fraction of the redundancy in natural images [1]. We show that, as a consequence of this group sparse coding, the resulting inference of the coefficients follows a divisive normalization rule, and that this may be efficiently implemented in a network architecture similar to that which has been proposed to occur in primary visual cortex. We also demonstrate improvements in image coding and compressive sensing recovery using the LSM model.
Prognostic factors of retroperitoneal soft tissue sarcomas: analysis of 132 cases.

BACKGROUND Retroperitoneal sarcoma is a rare disease with poor prognosis. The aim of this study was to investigate the prognostic factors of the disease. METHODS Between January 1988 and December 2003, 132 patients with retroperitoneal sarcoma were surgically treated in our hospital, 79 of them were followed up for 1 - 122 months (median: 19 months). Their clinicopathological data including tumor size, histological subtype, grade and resection margin status, were studied. The Kaplan-Meier method and log-rank test were used to analyze the disease-specific survival rates after the resection. RESULTS Among the 132 patients, 98 (74.2%) received macroscopic complete resection, 29 (22.0%) incomplete resection, and 5 (3.8%) surgical biopsy. In the 79 patients who were followed up, macroscopic clear resection of retroperitoneal sarcoma (n = 49) was associated with a significantly higher survival rate compared with unclear resection (n = 30, P < 0.001). The median survival period was 31 months (95% CI, 20.09 - 41.91; actuarial 1-year survival, 85.7%) in the patients with the tumor completely resected and 11 months (95% CI, 6.71 - 15.29; actuarial 1-year survival, 46.7%) in those with incomplete resection. Patients with high-grade sarcomas had a significantly shorter survival time (n = 39; median: 24, 95% CI: 5.71 - 42.29) than those with low-grade sarcomas (n = 40; median: 15; 95% CI: 8.80 - 21.20; P < 0.01). Moreover, compared with the patients with the tumor sized < 15 cm in diameter (n = 53), the survival rate was lower in those with a sarcoma sized > 15 cm (n = 26). (Median: 12, 95% CI: 8.26 - 15.74 vs median: 24, 95% CI: 17.25 - 30.75; P < 0.05). Furthermore, the survival of the patients with liposarcomas (n = 29, median: 29, 95% CI: 12.84 - 45.16), leiomyosarcomas (n = 14, median: 11, 95% CI: 6.11 - 15.89), and others (n = 36, median: 22, 95% CI: 14.95 - 29.05) varied significantly (P < 0.05). CONCLUSION Completeness of resection, tumor volume, grade, and subtype are prognostic factors of retroperitoneal soft tissue sarcomas.
APC gene: database of germline and somatic mutations in human tumors and cell lines

A database (http://perso.curie.fr/tsoussi ) is described, in which over 1000 mutations in the human APC gene of tumors (colon cancer predominantly) are compiled from the literature. It includes both molecular information about the mutations and clinical data about the patients. Software has been designed to analyse all this information in the database.
A Probabilistic Approach toward Conjugacy Classes in the Finite General Linear and Unitary Groups

The conjugacy classes of the nite general linear and unitary groups are used to de ne probability measures on the set of all partitions of all natural numbers. Probabilistic algorithms for growing random partitions according to these measures are obtained. These algorithms are applied to prove group theoretic results which are typically proved by techniques such as character theory and Moebius inversion. Among the theorems studied are Steinberg's count of unipotent elements, Rudvalis' and Shindoda's work on the xed space of a random matrix, and Lusztig's count of nilpotent matrices of a given rank. Generalizations of these algorithms based on Macdonald's symmetric functions are given.
Thyroid associated orbitopathy

Thyroid associated orbitopathy, also known as Graves’ orbitopathy, is typically a self-limiting autoimmune process associated with dysthyroid states. The clinical presentation may vary from very mild disease to severe irreversible sight-threatening complications. Despite ongoing basic science and clinical research, the pathogenesis and highly effective therapeutic strategies remain elusive. The present article reviews the pathophysiology, clinical presentation, and management of this common, yet poorly understood disease, which remains a challenge to the ophthalmologist.
$L_{1/2}$ Regularization: A Thresholding Representation Theory and a Fast Solver

The special importance of L1/2 regularization has been recognized in recent studies on sparse modeling (particularly on compressed sensing). The L1/2 regularization, however, leads to a nonconvex, nonsmooth, and non-Lipschitz optimization problem that is difficult to solve fast and efficiently. In this paper, through developing a threshoding representation theory for L1/2 regularization, we propose an iterative half thresholding algorithm for fast solution of L1/2 regularization, corresponding to the well-known iterative soft thresholding algorithm for L1 regularization, and the iterative hard thresholding algorithm for L0 regularization. We prove the existence of the resolvent of gradient of ||x||1/21/2, calculate its analytic expression, and establish an alternative feature theorem on solutions of L1/2 regularization, based on which a thresholding representation of solutions of L1/2 regularization is derived and an optimal regularization parameter setting rule is formulated. The developed theory provides a successful practice of extension of the well- known Moreau's proximity forward-backward splitting theory to the L1/2 regularization case. We verify the convergence of the iterative half thresholding algorithm and provide a series of experiments to assess performance of the algorithm. The experiments show that the half algorithm is effective, efficient, and can be accepted as a fast solver for L1/2 regularization. With the new algorithm, we conduct a phase diagram study to further demonstrate the superiority of L1/2 regularization over L1 regularization.