Miracle-dz/UniFAR-FTUs huggingface dataset:
GFAP-BDP as an acute diagnostic marker in traumatic brain injury: results from the prospective transforming research and clinical knowledge in traumatic brain injury study.

Reliable diagnosis of traumatic brain injury (TBI) is a major public health need. Glial fibrillary acidic protein (GFAP) is expressed in the central nervous system, and breakdown products (GFAP-BDP) are released following parenchymal brain injury. Here, we evaluate the diagnostic accuracy of elevated levels of plasma GFAP-BDP in TBI. Participants were identified as part of the prospective Transforming Research And Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study. Acute plasma samples (<24 h post-injury) were collected from patients presenting with brain injury who had CT imaging. The ability of GFAP-BDP level to discriminate patients with demonstrable traumatic lesions on CT, and with failure to return to pre-injury baseline at 6 months, was evaluated by the area under the receiver operating characteristic curve (AUC). Of the 215 patients included for analysis, 83% had mild, 4% had moderate, and 13% had severe TBI; 54% had acute traumatic lesions on CT. The ability of GFAP-BDP level to discriminate patients with traumatic lesions on CT as evaluated by AUC was 0.88 (95% confidence interval [CI], 0.84-0.93). The optimal cutoff of 0.68 ng/mL for plasma GFAP-BDP level was associated with a 21.61 odds ratio for traumatic findings on head CT. Discriminatory ability of unfavorable 6 month outcome was lower, AUC 0.65 (95% CI, 0.55-0.74), with a 2.07 odds ratio. GFAP-BDP levels reliably distinguish the presence and severity of CT scan findings in TBI patients. Although these findings confirm and extend prior studies, a larger prospective trial is still needed to validate the use of GFAP-BDP as a routine diagnostic biomarker for patient care and clinical research. The term "mild" continues to be a misnomer for this patient population, and underscores the need for evolving classification strategies for TBI targeted therapy. (ClinicalTrials.gov number NCT01565551; NIH Grant 1RC2 NS069409).
Characterization and Modeling of Nonlinearities in In-Plane Gap Closing Electrostatic Energy Harvester

This paper investigates in detail a micro scale in-plane gap closing electrostatic energy harvester with strong nonlinearities in squeeze-film damping, electromechanical coupling, and impacts on end-stops. The device shows softening response on increasing the bias voltage and saturation behavior on impact with end-stops at high enough acceleration amplitude. We demonstrate that a lumped model can adequately describe the measured nonlinear behavior for a range of operating conditions with nonlinear fluid damping force and impact force included in the model. While modeling capacitances, a finite-element method (FEM) is used to analyze fringing field effects on the capacitance variation for gap closing electrodes. The nominal capacitance is obtained from FEM analysis, for a range of under-cut values in the fabrication process treated as a free parameter in the model. The device modeled for linear and nonlinear squeeze-film damping force highlights the importance of nonlinear damping force to understand the device behavior over the range of operating conditions. With the compliant end-stops treated as spring-dampers and with proper choice of end-stop damping-coefficient, the model successfully captures the end-stop nonlinearities for a particular operating point and reproduces the dynamic pull-in phenomena at 8 V bias, and rms acceleration 0.6 g , as observed in the experiments. Thus, the model described in this paper reproduces the subtle nonlinear effects dominating the dynamics of an in-plane gap closing electrostatic energy harvester.
Simvastatin reduces burn injury-induced splenic apoptosis via downregulation of the TNF-α/NF-κB pathway.

OBJECTIVE Recent studies have suggested that epidermal burn injuries are associated with inflammation and immune dysfunction. Simvastatin has been shown to possess potent anti-inflammatory properties. Thus, we hypothesized that simvastatin protects against burn-induced apoptosis in the spleen via its anti-inflammatory activity. METHODS Wild-type, tumor necrosis factor alpha knockout (TNF-α KO) and NF-κB KO mice were subjected to full-thickness burn injury or sham treatment. The mice then were treated with or without simvastatin, and the spleen was harvested to measure the extent of apoptosis. Expression levels of TNF-α and NF-κB were also determined in spleen tissue and serum. RESULTS Burn injury induced significant splenic apoptosis and systemic cytokine production. Simvastatin protected the spleen from apoptosis, reduced cytokine production in the serum, and increased the survival rate. Simvastatin decreased burn-induced TNF-α and NF-κB expression in the spleen and serum. TNF-α and NF-κB KO mice demonstrated lower levels of apoptosis in spleen in response to burn injury. Simvastatin did not further decrease burn-caused apoptosis and mortality in either strain of KO mice. CONCLUSIONS Simvastatin reduces burn-induced splenic apoptosis via downregulation of the TNF-α/NF-κB pathway.
Mental illness stigma, secrecy and suicidal ideation

Aims. Whether the public stigma associated with mental illness negatively affects an individual, largely depends on whether the person has been labelled ‘mentally ill’. For labelled individuals concealing mental illness is a common strategy to cope with mental illness stigma, despite secrecy's potential negative consequences. In addition, initial evidence points to a link between stigma and suicidality, but quantitative data from community samples are lacking. Methods. Based on previous literature about mental illness stigma and suicidality, as well as about the potential influence of labelling processes and secrecy, a theory-driven model linking perceived mental illness stigma and suicidal ideation by a mediation of secrecy and hopelessness was established. This model was tested separately among labelled and unlabelled persons using data derived from a Swiss cross-sectional population-based study. A large community sample of people with elevated psychiatric symptoms was examined by interviews and self-report, collecting information on perceived stigma, secrecy, hopelessness and suicidal ideation. Participants who had ever used mental health services were considered as labelled ‘mentally ill’. A descriptive analysis, stratified logistic regression models and a path analysis testing a three-path mediation effect were conducted. Results. While no significant differences between labelled and unlabelled participants were observed regarding perceived stigma and secrecy, labelled individuals reported significantly higher frequencies of suicidal ideation and feelings of hopelessness. More perceived stigma was associated with suicidal ideation among labelled, but not among unlabelled individuals. In the path analysis, this link was mediated by increased secrecy and hopelessness. Conclusions. Results from this study indicate that among persons labelled ‘mentally ill’, mental illness stigma is a contributor to suicidal ideation. One explanation for this association is the relation perceived stigma has with secrecy, which introduces negative emotional consequences. If our findings are replicated, they would suggest that programmes empowering people in treatment for mental illness to cope with anticipated and experienced discrimination as well as interventions to reduce public stigma within society could improve suicide prevention.
MR imaging-guided radio-frequency thermal ablation of the lumbar vertebrae in porcine models.

PURPOSE To test the hypotheses that (a) magnetic resonance (MR) imaging-guided radio-frequency (RF) thermal ablation of the vertebrae is feasible in porcine models, (b) procedure safety depends on the location of ablation within the vertebra, and (c) MR imaging allows accurate monitoring of induced thermal lesion size and shape. MATERIALS AND METHODS Ten percutaneous MR imaging-guided RF thermal ablations were randomized over various lumbar vertebral levels and locations in seven pigs. Animals were followed up for 2, 7, or 14 days before sacrifice. Thermal lesion size and shape as measured on MR images obtained immediately after ablation and at follow-up were compared with gross pathologic findings. Mean absolute differences between lesion diameters at pathologic examination and MR imaging were evaluated by using a paired t test, as were differences between lesion-to-vertebra contrast-to-noise ratios obtained for each sequence. Clinical and imaging data were correlated with histologic findings. RESULTS Successful RF electrode placement in the targeted part of the vertebra was achieved in all procedures. Ablations performed away from neural elements were safe to perform. Pedicular ablations resulted in radiculopathy, whereas ablations performed directly over the posterior cortex resulted in paraplegia. Lesion sizes measured on T2-weighted images were closest to those measured at gross pathologic examination (mean absolute difference, 0.72 mm +/- 0.83 [SD]), followed by those measured on contrast material-enhanced T1-weighted (1.27 mm +/- 0.83) and short inversion time inversion-recovery (STIR) (1.5 mm +/- 1.84) images. Size measurements obtained on T2-weighted images were significantly closer to gross pathologic measurements than were those obtained on contrast-enhanced T1-weighted images (P =.013) but were not different from those obtained on STIR (P =.27) images. The contrast-to-noise ratio was significantly higher for contrast-enhanced T1-weighted images than for T2-weighted (P <.001) or STIR (P <.001) images. CONCLUSION MR imaging-guided RF thermal ablation of the vertebrae is feasible in porcine models, but the safety of the procedure depends on the location of ablation within the vertebra. MR imaging allows accurate monitoring of thermal lesion size and shape.
Genome-wide Fitness Profiles Reveal a Requirement for Autophagy During Yeast Fermentation

The ability of cells to respond to environmental changes and adapt their metabolism enables cell survival under stressful conditions. The budding yeast Saccharomyces cerevisiae (S. cerevisiae) is particularly well adapted to the harsh conditions of anaerobic wine fermentation. However, S. cerevisiae gene function has not been previously systematically interrogated under conditions of industrial fermentation. We performed a genome-wide study of essential and nonessential S. cerevisiae gene requirements during grape juice fermentation to identify deletion strains that are either depleted or enriched within the viable fermentative population. Genes that function in autophagy and ubiquitin-proteasome degradation are required for optimal survival during fermentation, whereas genes that function in ribosome assembly and peroxisome biogenesis impair fitness during fermentation. We also uncover fermentation phenotypes for 139 uncharacterized genes with no previously known cellular function. We demonstrate that autophagy is induced early in wine fermentation in a nitrogen-replete environment, suggesting that autophagy may be triggered by other forms of stress that arise during fermentation. These results provide insights into the complex fermentation process and suggest possible means for improvement of industrial fermentation strains.
Transient fault detection via simultaneous multithreading

Smaller feature sizes, reduced voltage levels, higher transistor counts, and reduced noise margins make future generations of microprocessors increasingly prone to transient hardware faults. Most commercial fault-tolerant computers use fully replicated hardware components to detect microprocessor faults. The components are lockstepped (cycle-by-cycle synchronized) to ensure that, in each cycle, they perform the same operation on the same inputs, producing the same outputs in the absence of faults. Unfortunately, for a given hardware budget, full replication reduces performance by statically partitioning resources among redundant operations. We demonstrate that a Simultaneous and Redundantly Threaded (SRT) processor-derived from a a Simultaneous Multithreaded (SMT) processor-provides transient fault coverage with significantly higher performance. An SRT processor provides transient fault coverage by running identical copies for the same program simultaneously as independent threads. An SRT processor provides higher performance because it dynamically schedules its hardware resources among the redundant copies. However, dynamic scheduling makes is difficult to implement lockstepping, because corresponding instructions from redundant threads may not execute in the same cycle or in the same order. This paper makes four contributions to the design of SRT processors. First, we introduce the concept of the sphere of replication, which abstract both the physical redundancy of a lockstepped system and the logical redundancy of an SRT processor. This framework aids in identifying the scope of fault coverage and the input and output values requiring special handling. Second, we identify two viable spheres of replication in an SRT processor, and show that one of them provides fault detection while checking only committed stores and uncached loads. Third, we identify the need for consistent replication of load values, and propose and evaluate two new mechanisms for satisfying this requirement. Finally, we propose and evaluate two mechanisms-slack fetch and branch outcome queue-that enhance the performance of an SRT processor by allowing one thread to prefetch cache misses and branch results for the other thread. Our results with 11 SPEC95 benchmarks show that an SRT processor can outperform an equivalently sized, on-chip, hardware-replicated solution by 16% on average, with maximum benefit of up to 29%.
A proof of threshold saturation for spatially-coupled LDPC codes on BMS channels

Low-density parity-check (LDPC) convolutional codes have been shown to exhibit excellent performance under low-complexity belief-propagation decoding [1], [2]. This phenomenon is now termed threshold saturation via spatial coupling. The underlying principle behind this appears to be very general and spatially-coupled (SC) codes have been successfully applied in numerous areas. Recently, SC regular LDPC codes have been proven to achieve capacity universally, over the class of binary memoryless symmetric (BMS) channels, under belief-propagation decoding [3], [4]. In [5], [6], potential functions are used to prove that the BP threshold of SC irregular LDPC ensembles saturates, for the binary erasure channel, to the conjectured MAP threshold (known as the Maxwell threshold) of the underlying irregular ensembles. In this paper, that proof technique is generalized to BMS channels, thereby extending some results of [4] to irregular LDPC ensembles. We also believe that this approach can be expanded to cover a wide class of graphical models whose message-passing rules are associated with a Bethe free energy.
Leisure, functional disability and depression among older Chinese living in residential care homes

Objectives: Previous research has rarely examined the intervening and buffering effects of leisure on the relationship between age-related stress and health among institutionalized elders, especially in the Chinese context. This study thus examines the extent to which participation in leisure activities mediates and moderates the impact of functional disability on depression among older adults living in residential care homes in China. Method: A total of 1429 participants (858 men) aged over 60 living in residential care homes, of which 46.1% experienced depression using a cut-off score ≥ 5 on the 15-item Geriatric Depression Scale, were selected from a national survey across China by using the probability proportional to size sampling method. Results: The findings showed that depression was positively predicted by functional disability and negatively predicted by participation in leisure activities. The results of the mediation analysis showed that participation in leisure activities partially mediated the relationship between functional disability and depression. Functional disability predicted depression both directly and indirectly through its negative influence on participation in leisure activities. Participation in leisure activities also significantly buffered the relationship between functional disability and depression such that the impact of functional disability was weaker for those who participated in leisure activities more frequently. Conclusion: These results provide support for the mediating and moderating roles of leisure in the stress–health relationship among institutionalized elders. To enhance residents’ psychological health, residential care homes are recommended to organize more leisure activities.
Insulin-induced remission in new-onset NOD mice is maintained by the PD-1–PD-L1 pathway

The past decade has seen a significant increase in the number of potentially tolerogenic therapies for treatment of new-onset diabetes. However, most treatments are antigen nonspecific, and the mechanism for the maintenance of long-term tolerance remains unclear. In this study, we developed an antigen-specific therapy, insulin-coupled antigen-presenting cells, to treat diabetes in nonobese diabetic mice after disease onset. Using this approach, we demonstrate disease remission, inhibition of pathogenic T cell proliferation, decreased cytokine production, and induction of anergy. Moreover, we show that robust long-term tolerance depends on the programmed death 1 (PD-1)–programmed death ligand (PD-L)1 pathway, not the distinct cytotoxic T lymphocyte–associated antigen 4 pathway. Anti–PD-1 and anti–PD-L1, but not anti–PD-L2, reversed tolerance weeks after tolerogenic therapy by promoting antigen-specific T cell proliferation and inflammatory cytokine production directly in infiltrated tissues. PD-1–PD-L1 blockade did not limit T regulatory cell activity, suggesting direct effects on pathogenic T cells. Finally, we describe a critical role for PD-1–PD-L1 in another powerful immunotherapy model using anti-CD3, suggesting that PD-1–PD-L1 interactions form part of a common pathway to selectively maintain tolerance within the target tissues.
mRNA expression of ephrins and Eph receptor tyrosine kinases in the neonatal and adult mouse central nervous system

Ephrins and Eph receptors are a family of molecules that have been implicated in axonal pathfinding. A unique feature of B‐class ephrins and Eph receptors is their ability to transmit bidirectional signals in both ephrin‐ and Eph receptor‐expressing cells upon cell–cell contact. These signals can lead to cytoskeletal alterations that have been attributed to regulating neuronal growth responses. Examination of gene‐target knockout mice has supported this hypothesis, revealing numerous developmental defects in the nervous systems of mice mutant for both B‐class ephrins and Eph receptors. To examine the potential scope of action for these genes in the nervous system, we have used in situ hybridization to study the mRNA expression of ephrins (B1, B2, and B3) and Eph receptors (B1, B2, B3, A4) in neonatal and adult mice. We found ephrins and Eph receptors to be expressed throughout the CNS. Expression was observed in the epithelium and migratory regions of the neonate and adult tissues as well as in discrete regions of high plasticity, including the adult olfactory bulb, hippocampus, and cerebellum. These studies suggest additional potential roles for these molecules in the postnatal and adult CNS and will serve as a guide in the detailed evaluation of mutant mice. © 2002 Wiley‐Liss, Inc.
Elastic Free Energy Drives the Shape of Prevascular Solid Tumors

It is well established that the mechanical environment influences cell functions in health and disease. Here, we address how the mechanical environment influences tumor growth, in particular, the shape of solid tumors. In an in vitro tumor model, which isolates mechanical interactions between cancer tumor cells and a hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft-reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor shape robustly occurs when the tumors grow in hydrogels that are stiffer than the tumors, but when they grow in more compliant hydrogels they remain closer to spherical in shape. Using large scale, nonlinear elasticity computations we show that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor-hydrogel system. Having eliminated a number of other candidate explanations, we hypothesize that minimization of the elastic free energy is the reason for predominance of the experimentally observed ellipsoidal shape. This result may hold significance for explaining the shape progression of early solid tumors in vivo and is an important step in understanding the processes underlying solid tumor growth.
Particle break-up during heat treatment of 3000 series aluminium alloys

Abstract In wrought aluminium alloys, the fragmentation of coarse, iron bearing intermetallic particles by hot rolling is an important development in industrial processing. Here a model 3000 series alloy is used to show that fragmentation can occur prior to hot rolling, during the homogenisation heat treatment. Some fragmented particles display a curved morphology of break-up that results from matrix wetting of two phase (or 'duplex') interfaces in Al6(Fe,Mn) particles partially transformed to an α-Al–(Fe,Mn)–Si phase. In contrast, samples rapidly heated to temperature in a fluidised bath show an angular break-up indicative of tensile stresses induced by thermal expansion mismatch between the intermetallic particles and aluminium matrix. Although this break-up should not be industrially significant, the transformation induced break-up by wetting may be. More generally, internal boundaries resulting from the transformation to α-Al–(Fe,Mn)–Si phase may be mechanically weak fracture initiation points during hot rolling.