Miracle-dz/UniFAR-FTUs huggingface dataset:
The Programmed Death-1 (PD-1) Pathway Regulates Autoimmune Diabetes in Nonobese Diabetic (NOD) Mice

Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on activated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated the role of this pathway in the development of autoimmune diabetes. PD-1 or PD-L1 but not PD-L2 blockade rapidly precipitated diabetes in prediabetic female nonobese diabetic (NOD) mice regardless of age (from 1 to 10-wk-old), although it was most pronounced in the older mice. By contrast, cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) blockade induced disease only in neonates. Male NOD mice also developed diabetes after PD-1–PD-L1 pathway blockade, but NOR mice, congenic to NOD but resistant to the development of diabetes, did not. Insulitis scores were significantly higher and frequency of interferon γ–producing GAD-reactive splenocytes was increased after PD-1–PD-L1 pathway blockade compared with controls. Interestingly, PD-L1 but not PD-L2 was found to be expressed on inflamed islets of NOD mice. These data demonstrate a central role for PD-1–PD-L1 interaction in the regulation of induction and progression of autoimmune diabetes in the NOD mouse and provide the rationale to develop new therapies to target this costimulatory pathway in this disease.
AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity (*)

Adipose differentiation is accompanied by changes in cellular morphology, a dramatic accumulation of intracellular lipid and activation of a specific program of gene expression. Using an mRNA differential display technique, we have isolated a novel adipose cDNA, termed adipoQ. The adipoQ cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a collagenous region (Gly-X-Y repeats), and a globular domain. The globular domain of adipoQ shares significant homology with subunits of complement factor C1q, collagen α1(X), and the brain-specific factor cerebellin. The expression of adipoQ is highly specific to adipose tissue in both mouse and rat. Expression of adipoQ is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain adipoQ mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for adipoQ. Furthermore, the expression of adipoQ mRNA is significantly reduced in the adipose tissues from obese mice and humans. Whereas the biological function of this polypeptide is presently unknown, the tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue.
populations : a review Evolutionary dynamics of group interactions on structured

(55 articles) biocomplexity Articles on similar topics can be found in the following collections Email alerting service here right-hand corner of the article or click Receive free email alerts when new articles cite this article-sign up in the box at the top Evolutionary dynamics of group interactions on structured populations: a review. Interactions among living organisms, from bacteria colonies to human societies, are inherently more complex than interactions among particles and non-living matter. Group interactions are a particularly important and widespread class, representative of which is the public goods game. In addition, methods of statistical physics have proved valuable for studying pattern formation, equilibrium selection and self-organization in evolutionary games. Here, we review recent advances in the study of evolutionary dynamics of group interactions on top of structured populations, including lattices, complex networks and coevolutionary models. We also compare these results with those obtained on well-mixed populations. The review particularly highlights that the study of the dynamics of group interactions, like several other important equilibrium and non-equilibrium dynamical processes in biological, economical and social sciences, benefits from the synergy between statistical physics, network science and evolutionary game theory.
Purkinje neuron physiology is altered by the inflammatory factor interleukin-6

The cytokine interleukin-6 (IL-6) is produced by cells of the central nervous system (CNS) during a variety of neuroinflammatory states, in which it is thought to play a role in neuroprotection and/or neuropathology associated with neurological disease. In addition, CNS expression of IL-6 during non-pathological conditions may also occur, although the conditions for such IL-6 production remain elusive. Expression of IL-6 and its receptor and signal transducing elements by neurons and glia within the cerebellum implicate a role of IL-6 in modulating cerebellar function under normal conditions and in contributing to pathology and pathophysiology within the cerebellum during CNS disease states. Evidence for such a role of IL-6 comes from studies using transgenic mice that chronically express IL-6 within the CNS. These mice exhibit profound cerebellar pathology and significant alterations of Purkinje neuron electrical and synaptic activity. Additional evidence comes fromin vitro studies using primary cultures of cerebellar cortex that have been chronically exposed to exogenously applied IL-6. Consistent with the IL-6 transgenic mice, chronic IL-6 treated Purkinje neurons in culture exhibit alterations of endogenous electrophysiological properties as well as changes in intracellular Ca2+ homeostasis and signaling. Despite these changes in Purkinje neuron physiology, chronic IL-6 does not affect the survival or morphology of Purkinje neurons in culture. Thus, by itself, IL-6 is able to modulate key components of cerebellar circuitry during periods of chronic expression, such as during neuroinflammation, and may be an important player in the movement disorders associated with a number of CNS disease states.
The Aksay segment of the northern Altyn Tagh fault: Tectonic geomorphology, landscape evolution, and Holocene slip rate

[1] Millennial slip rates have been determined for the Altyn Tagh fault (ATF) at three sites near Aksay (∼94°E) in northeastern Tibet by dating fluvial channels and terrace riser offsets with radiocarbon and 10Be-26Al surface exposure dating. Up to nine main surfaces are defined on the basis of morphology, elevation, and dating. The abandonment age of some surfaces is constrained by radiocarbon dating, which typically coincides with the youngest cosmogenic ages for a particular surface. Older surface exposure ages are taken to represent the duration of terrace emplacement. Cumulative offsets range from 20 to 260 m and fall in distinct groups, indicative of climatically modulated regional landscape formation. Most samples are younger than ∼14 ka and postdate the Last Glacial Maximum. The end of the early Holocene optimum marks the boundary between the ages of the two main terrace levels at 5–6 ka. At this longitude the ATF is divided into a northern and southern branch. The northern ATF should thus yield a minimum rate for the ATF system. Slip rate estimates using the abandonment age of the overlying level for fill terraces or channels and the emplacement of the underlying level for strath terraces give 30 consistent results, yielding an average Holocene rate of 17.8 ± 3.6 mm/yr. It is ∼9 mm/yr less than the long-term rate obtained near Tura at ∼87°E (26.9 ± 6.9 mm/yr), in keeping with the inference of an eastward decreasing rate on the ATF, due to increased thrusting to the south. However, it remains twice the rate determined by GPS studies.
Analysis of the characteristics of persistent postural-perceptual dizziness: A clinical-based study in China

Abstract Objective: Persistent postural-perceptual dizziness (PPPD) is a common cause of chronic dizziness, but only a few studies have reported its clinical characteristics, and no related research has been performed in China. Therefore, the purpose of this study was to analyze the characteristics of PPPD for the first time in China. Design: Data was collected from all patients during standard clinical practice, and further to evaluate the characteristics of PPPD comparing with the control group. Study sample: A total of 43 patients diagnosed with PPPD were selected as the study group for analysis. Results: Women were significantly more represented in the study group than men, and in the majority of cases the age of onset was in middle-age, and sleep quality was clearly decreased compared with controls, with more statistically significantly higher levels of anxiety. Personality analysis identified that neuroticism was significantly higher than in controls. Conclusions: In this sample we showed that PPPD was more represented in female patients, the age of onset was 40–60 years old, the majority of patients had sleep disorders, anxiety was the main mood disorder to be identified, and personality analysis found that neurotic personality may be the risk factor for developing PPPD. Further large scale studies are suggested in China.
simTD: a car-to-X system architecture for field operational tests [Topics in Automotive Networking]

Car-to-car and car-to-infrastructure communications are considered as a key technology for safe and intelligent mobility in the future. In the German project simTD, car-to-x communication is shifting from a pure research topic toward a first deployment of such a system: the goal of simTD is to test car-to-x applications in a real metropolitan field trial. The simTD scenario includes vehicles, roadside units, and infrastructural facilities for traffic and test management. Besides these domains, several third parties are involved to provide access to additional services. The main communication partners are furthermore distributed over a wide area including highway, suburban, and urban scenarios. As a result, such a system requires a commonly accepted architecture of the individual components and a seamless communication network for reliable and efficient information interchange. In this article we propose the simTD system architecture and the components necessary for successful deployment in the large-scale field trial.
Detection of unique people in news programs using multimodal shot clustering

In this paper, we describe an approach that uses a combination of visual and audio features to cluster shots belonging to the same person in video programs. We use color histograms extracted from keyframes and faces, as well as cepstral coefficients derived from audio to calculate pairwise shot distances. These distances are then normalized and combined to a single confidence value which reflects our certainty that two shots contain the same person. We then use an agglomerative clustering algorithm to cluster shots based on these confidence values. We report the results of our system on a data set of approximately 8 hours of programming.
Revisiting the scissor‐like mechanism of activation for the erythropoietin receptor

An interpretation of alternative crystal structures of the erythropoietin receptor, with and without ligand, led to the proposal of a scissor‐like mechanism of activation. This model has been propagated in the literature and is still being used to interpret crystal structures of related type‐I cytokine receptors. Here, we assess whether the model remains compatible with current knowledge on the family of type‐I cytokine receptors, and consider whether the model, as initially presented, is truly supported by the crystal structures on which it was originally based.
Neoadjuvant Chemotherapy Use in Bladder Cancer: A Survey of Current Practice and Opinions

Objectives. Level 1 evidence supports the use of neoadjuvant chemotherapy (NAC) to improve overall survival in muscle invasive bladder cancer; however utilization rates remain low. The aims of our study were to determine factors associated with NAC use, to more clearly define reasons for low utilization, and to determine the current rate of NAC use among urologic oncologists. Materials and Methods. Active members of the Society for Urologic Oncology were provided a 20-question survey. Descriptive statistical analysis was conducted for each question and univariate analysis was performed. Results. We achieved a response rate of 21%. Clinical T3/T4 disease was the most often selected reason for recommending NAC (87%). Concerns with recommending NAC were age and comorbidities (54%) followed by delay in surgery (35%). An association was identified between urologic oncologists who discussed NAC with >90% of their patients and medical oncologists “always” recommending NAC (P = 0.0009). NAC utilization rate was between 30 and 57%. Conclusions. Amongst this highly specialized group of respondents, clinical T3-T4 disease was the most common reason for implementation of NAC. Respondents who frequently discussed NAC were more likely to report their medical oncologist always recommending NAC. Reported NAC use was higher in this surveyed group (30–57%) compared with recently published rates.
The 27–year decline of coral cover on the Great Barrier Reef and its causes

The world’s coral reefs are being degraded, and the need to reduce local pressures to offset the effects of increasing global pressures is now widely recognized. This study investigates the spatial and temporal dynamics of coral cover, identifies the main drivers of coral mortality, and quantifies the rates of potential recovery of the Great Barrier Reef. Based on the world’s most extensive time series data on reef condition (2,258 surveys of 214 reefs over 1985–2012), we show a major decline in coral cover from 28.0% to 13.8% (0.53% y−1), a loss of 50.7% of initial coral cover. Tropical cyclones, coral predation by crown-of-thorns starfish (COTS), and coral bleaching accounted for 48%, 42%, and 10% of the respective estimated losses, amounting to 3.38% y−1 mortality rate. Importantly, the relatively pristine northern region showed no overall decline. The estimated rate of increase in coral cover in the absence of cyclones, COTS, and bleaching was 2.85% y−1, demonstrating substantial capacity for recovery of reefs. In the absence of COTS, coral cover would increase at 0.89% y−1, despite ongoing losses due to cyclones and bleaching. Thus, reducing COTS populations, by improving water quality and developing alternative control measures, could prevent further coral decline and improve the outlook for the Great Barrier Reef. Such strategies can, however, only be successful if climatic conditions are stabilized, as losses due to bleaching and cyclones will otherwise increase.
Hard to look on the bright side: neural correlates of impaired emotion regulation in depressed youth

Abstract The cognitive regulation of emotion is impaired in major depressive disorder and has been linked to an imbalance of pre-frontal–subcortical brain activity. Despite suggestions that this relationship represents a neurodevelopmental marker of depression, few studies have examined the neural correlates of emotion regulation in depressed youth. We combined a ‘cognitive reappraisal’ paradigm with functional magnetic resonance imaging to study the neural correlates of emotional regulation in a large sample of non-medicated depressed adolescents and young adults (n = 53) and healthy controls (n = 64). As compared with healthy controls, young people with depression were less able to reduce negative affect during reappraisal, which corresponded to blunted modulation of amygdala activity. While in healthy individuals amygdala activation was modulated by age, no such relationship was observed in depressed individuals. Heightened activation of the ventromedial pre-frontal cortex (vmPFC) and reduced activation of the dorsal midline cortex was also found for the depressed group. Overall, these findings suggest that brain systems that support cognitive reappraisal are functionally altered in youth depression. We argue that excessive engagement of the vmPFC in particular, may be central to understanding how the process of putting a ‘positive spin’ on negative emotional material may be altered in depressed youth.
Extracellular vesicles released by fibroblasts undergoing H-Ras induced senescence show changes in lipid profile

Cells release extracellular vesicles (EVs) in their environment and cellular lipids play an important role in their formation, secretion and uptake. Besides, there is also evidence that EV transferred lipids impact on recipient’s cell signaling. Cellular senescence is characterized by a state of permanent proliferation arrest and represents a barrier towards the development of neoplastic lesions. A peculiar feature of senescence is the release of many soluble factors, the so-called Senescence-Associated Secretory Phenotype, which play a key role in triggering paracrine senescence signals. Recently, evidences have suggested that this phenotype includes not only soluble factors, but also EVs. To identify lipid signatures associated with H-Ras-induced senescence in EVs, we expressed active H-Ras (H-RasV12) in human fibroblasts and investigated how it affects EV release and lipid composition. An enrichment of hydroxylated sphingomyelin, lyso- and ether-linked phospholipids and specific H-Ras-induced senescence signatures, e.g. sphingomyelin, lysophosphatidic acid and sulfatides, were found in EVs compared to cells. Furthermore, H-RasV12 expression in fibroblasts was associated with higher levels of tetraspanins involved in vesicle formation.
Analysis of prognostic factors after the first relapse of Hodgkin's disease in 187 patients

Patients in the first relapse of Hodgkin's disease comprise a heterogeneous group regarding their primary treatment and their clinical characteristics. Because therapeutic options for these patients vary from radiotherapy to combined modality or high dose therapy, we wanted to identify the prognostic factors that would optimize the treatment choice among the different options available.
A new Procedure for Large Scale Production and Freezing of Lymphokine Activated Killer (LAK) Cells to be used in Adoptive Immunotherapy of Cancer

A new procedure for activation of peripheral blood lymphocytes (PBL) with recombinant interleukin 2 (rIL2) is described. PBL obtained by leukapheresis were subjected to NH4Cl (ACK) treatment to clear erythrocyte contamination; Ficoll separation was not performed. PBL were subsequently seeded in 10-floor multitrays (Cell Factory™, CF), gasified and incubated at 37 °C for 3-4 days in a humidified 5% CO2 atmosphere. This procedure achieved an activation (evaluated as cytotoxicity and proliferation) comparable with that obtained by culturing PBL in small flasks. Optimal activation of PBL was achieved in CF even in the presence of granulocyte contamination of up to 40%. It was also possible to freeze, thaw and recover most of the frozen cells and their cytotoxic activity. With this procedure therefore large quantities of lymphokine activated killer cells (LAK) can be easily produced to be used in adoptive immunotherapy trials.
Performance-Driven Crosstalk Elimination at Postcompiler Level—The Case of Low-Crosstalk Op-Code Assignment

Significant advances in very large-scale integration process technology have scaled the feature size down. One effect of this scaling down is that coupling capacitances have grown reciprocal in the square of the scaling factor. This crosstalk effect will not only increase the power consumption but also lengthen the propagation delay. Since the data sequences on an instruction bus are known during the compile time, this paper presents two compiler algorithms, rescheduling and renaming, for performance improvement by eliminating crosstalk effects on an instruction bus. The results show that our crosstalk-eliminating postcomplier algorithms significantly reduce the dynamic instruction overhead from 11.50% to 0.52% by eliminating the 4middotC crosstalk. Due to the effective 4middotC crosstalk elimination, our proposed method can improve the instruction fetch time up to 9.59%
A Highly Adaptive Distributed Routing Algorithm f or Mobile Wireless Networks

We present a new distributed routing protocol for mobile, multihop, wireless networks. The protocol is one of a family of protocols which we term “link reversal” algorithms. The protocol’s reaction is structured as a temporally-ordered sequence of diffusing computations; each computation consisting of a sequence of directed link reversals. The protocol is highly adaptive, efficient and scalable; being best-suited for use in large, dense, mobile networks. In these networks, the protocol’s reaction to link failures typically involves only a localized “single pass” of the distributed algorithm. This capability is unique among protocols which are stable in the face of network partitions, and results in the protocol’s high degree of adaptivity . This desirable behavior is achieved through the novel use of a “physical or logical clock” to establish the “temporal order” of topological change events which is used to structure (or order) the algorithm’s reaction to topological changes. We refer to the protocol as the Temporally-Ordered Routing Algorithm (TORA).
Slowly conducting afferents activated by innocuous low temperature in human skin

1 Microneurography was used to search for primary afferents responsive to innocuous low temperature in human nerves supplying the hairy skin of the hand or foot. Eighteen units were identified as cold‐specific units: they displayed a steady‐state discharge at skin temperatures in the range 28‐30 °C, they were sensitive to small changes in temperature, and they responded vigorously when a cool metal probe touched their receptive fields (RFs). They were insensitive to mechanical stimuli and sympathetic activation. Their RFs comprised one, or at most two, spots less than 5 mm in diameter. 2 Nine units were characterised in detail by a series of 10 s cooling and warming pulses from a holding temperature of 35 °C. The threshold temperature for activation by cooling was 29.4 ± 2.0 °C (mean ±s.d.). Adaptation of the responses to supra‐threshold cooling pulses was partial: mean peak and plateau firing rates were maximal on steps to 15 °C (35.9 and 19.9 impulses s−1, respectively). Three of these units also displayed a paradoxical response to warming, with a mean threshold of 42.3 °C. 3 Sixteen of the eighteen cold‐specific units were also studied by electrical stimulation of their RFs. They conducted in the velocity range 0.8‐3.0 m s−1. When stimulated at 2 Hz, their latency increased according to a characteristic time course, reaching a plateau within 3 min (mean slowing (±s.d.) 5.2 ± 1.1 %) and recovering quickly (50 % recovery in 17.8 ± 4.5 s). 4 To reconcile these findings with previous studies of reaction times and the effects of nerve compression on sensation, it is concluded that either human cold‐specific afferent fibres are incompletely myelinated ‘BC’ fibres, or else there are C as well as Aδ cold fibres, with the C fibre group contributing little to sensation.