Miracle-dz/UniFAR-FTUs huggingface dataset:
Sustained relief of ongoing experimental neuropathic pain by a CRMP2 peptide aptamer with low abuse potential

Abstract Uncoupling the protein–protein interaction between collapsin response mediator protein 2 (CRMP2) and N-type voltage-gated calcium channel (CaV2.2) with an allosteric CRMP2-derived peptide (CBD3) is antinociceptive in rodent models of inflammatory and neuropathic pain. We investigated the efficacy, duration of action, abuse potential, and neurobehavioral toxicity of an improved mutant CRMP2 peptide. A homopolyarginine (R9)-conjugated CBD3-A6K (R9-CBD3-A6K) peptide inhibited the CaV2.2–CRMP2 interaction in a concentration-dependent fashion and diminished surface expression of CaV2.2 and depolarization-evoked Ca2+ influx in rat dorsal root ganglia neurons. In vitro studies demonstrated suppression of excitability of small-to-medium diameter dorsal root ganglion and inhibition of subtypes of voltage-gated Ca2+ channels. Sprague-Dawley rats with tibial nerve injury had profound and long-lasting tactile allodynia and ongoing pain. Immediate administration of R9-CBD3-A6K produced enhanced dopamine release from the nucleus accumbens shell selectively in injured animals, consistent with relief of ongoing pain. R9-CBD3-A6K, when administered repeatedly into the central nervous system ventricles of naive rats, did not result in a positive conditioned place preference demonstrating a lack of abusive liability. Continuous subcutaneous infusion of R9-CBD3-A6K over a 24- to 72-hour period reversed tactile allodynia and ongoing pain, demonstrating a lack of tolerance over this time course. Importantly, continuous infusion of R9-CBD3-A6K did not affect motor activity, anxiety, depression, or memory and learning. Collectively, these results validate the potential therapeutic significance of targeting the CaV-CRMP2 axis for treatment of neuropathic pain.
Segmentation of noisy CT volume data using improved 3D Chan-Vese model

The segmentation of the image directly using the CT volume data is attaching more and more attention. However, we can hardly get satisfactory segmentation results when the image is corrupted by noise. In this paper we propose an improved 3D Chan-Vese model (CV model) for the segmentation of noisy CT volume data. When working with level sets and Dirac delta functions in CV model, a standard procedure is to reinitialize level set function φ to the Signed Distance Function (SDF). At each iteration the SDF can be used perfectly to determine the type of filters with emphasis on removing noise or preserving the details. Thus the proposed model can suppress noise and preserve the contour at the same time. Experiments demonstrate that the proposed algorithm can effectively improve the segmentation of noisy CT volume data.
Operating System Support for Parallel Processes

Author(s): Rhoden, Barret | Advisor(s): Brewer, Eric | Abstract: High-performance, parallel programs want uninterrupted access to physical resources. This characterization is true not only for traditional scientific computing, but also for high-priority data center applications that run on parallel processors. These applications require high, predictable performance and low latency, and they are important enough to warrant engineering effort at all levels of the software stack. Given the recent resurgence of interest in parallel computing as well as the increasing importance of data center applications, what changes can we make to operating system abstractions to support parallel programs? Akaros is a research operating system designed for single-node, large-scale SMP and many-core architectures. The primary feature of Akaros is a new process abstraction called the "Many-Core Process" (MCP) that embodies transparency, application control of physical resources, and performance isolation. The MCP is built on the idea of separating cores from threads: the operating system grants spatially partitioned cores to the MCP, and the application schedules its threads on those cores. Data centers typically have a mix of high-priority applications and background batch jobs, where the demands of the high-priority application can change over time. For this reason, an important part of Akaros is the provisioning, allocation, and preemption of resources, and the MCP must be able to handle having a resource revoked at any moment.In this work, I describe the MCP abstraction and the salient details of Akaros. I discuss how the kernel and user-level libraries work together to give an application control over its physical resources and to adapt to the revocation of cores at any time - even when the code is holding locks. I show an order of magnitude less interference for the MCP compared to Linux, more resilience to the loss of cores for an HPC application, and how a customized user-level scheduler can increase the performance of a simple webserver.
Variants in SNCA Gene Are Associated with Parkinson’s Disease Risk and Cognitive Symptoms in a Brazilian Sample

Genetic susceptibility contributes to the etiology of sporadic Parkinson’s Disease (PD) and worldwide studies have found positive associations of polymorphisms in the alpha-synuclein gene (SNCA) with the risk for PD. However, little is known about the influence of variants of SNCA in individual traits or phenotypical aspects of PD. Further, there is a lack of studies with Latin-American samples. We evaluated the association between SNCA single nucleotide polymorphisms (single nucleotide polymorphisms, SNPs – rs2583988, rs356219, rs2736990, and rs11931074) and PD risk in a Brazilians sample. In addition, we investigated their potential interactions with environmental factors and specific clinical outcomes (motor and cognitive impairments, depression, and anxiety). A total of 105 PD patients and 101 controls participated in the study. Single locus analysis showed that the risk allele of all SNPs were more frequent in PD patients (p < 0.05), and the associations of SNPs rs2583988, rs356219, and rs2736990 with increased PD risk were confirmed. Further, the G-rs356219 and C-rs2736990 alleles were associated with early onset PD. T-rs2583988, G-rs356219 and C-2736990 alleles were significantly more frequent in PD patients with cognitive impairments than controls in this condition. In addition, in a logistic regression model, we found an association of cognitive impairment with PD, and the practice of cognitive activity and smoking habits had a protective effect. This study shows for the first time an association of SNCA polymorphism and PD in a South-American sample. In addition, we found an interaction between SNP rs356219 and a specific clinical outcome, i.e., the increased risk for cognitive impairment in PD patients.
Effects of cholinergic enhancement on conditioning‐related responses in human auditory cortex

It has previously been shown that cholinergic blockade attenuates conditioning‐related neuronal responses in human auditory cortex. The present study was conducted to investigate the effect of cholinergic enhancement on such experience‐dependent cortical responses. The cholinesterase inhibitor physostigmine, or a placebo control, were continuously infused into healthy young volunteers, during differential aversive conditioning whilst brain activity was measured using event‐related functional magnetic resonance imaging (fMRI). Volunteers were presented with two tones, one of which (CS+) was conditioned by pairing with an electrical shock whereas the other was always presented without the shock (CS–). Conditioning‐related activations, expressed as an enhanced blood oxygenation level dependent (BOLD) response to the salient CS+, were evident in left auditory cortex under placebo but not under physostigmine. This absence of conditioning‐related activations under physostigmine was due to enhanced responses to the CS– under physostigmine as compared to placebo. We suggest that an overactive cholinergic system leads to increased processing of behaviourally irrelevant stimuli and thus attenuates differential conditioning‐related cortical activations.
An Association of GRIK3 Ser310Ala Functional Polymorphism with Personality Traits

Personality traits are under genetic control, and have been associated with genes implicated in dopaminergic, serotoninergic and noradrenergic neurotransmission systems, often with conflicting results. There have been few studies assessing the involvement of the glutamatergic pathway instead upon personality traits. In the gene family of glutamate receptors, there is a T/G polymorphism at codon 928 in the ionotropic glutamate receptor kainite 3 gene (GRIK3) that causes a serine to alanine change at position 310 in the extracellular N terminus of the protein. This polymorphism has been recently associated with susceptibility to some major psychoses such as major depression (MD). In order to test whether the functional Ser310Ala polymorphism is involved in the development of specific personality traits, and thus to MD, we conducted the first association study on 195 selected healthy Italian individuals. The personality traits were measured by the self-rating Temperament and Character Inventory (TCI) scale. The results indicated that the Ala allele in homozygosity is associated with higher scores in harm avoidance and respective subscales: anticipatory worry HA1 and shyness HA3, as well as lower scores in exploratory excitability NS1, responsibility SD1, resourcefulness SD3, helpfulness C3 and compassion C4 subscales, in addition to lower self-directedness and cooperativeness scores. This pattern of TCI scores is akin to that observed in depressed patients. Because of the small size of the sample, this work represents a pilot study, and reports the first pieces of evidence for a specific involvement of the GRIK3 gene in these traits, suggesting a role of the glutamatergic system in the genetic background of human personality traits.
The persistent exclusion of older patients from ongoing clinical trials regarding heart failure.

BACKGROUND Much clinical research of relevance to elderly patients examines individuals who are younger than those who have the disease in question. A good example is heart failure. Therefore, we investigated the extent of exclusion of older individuals in ongoing clinical trials regarding heart failure. METHODS In the context of the Increasing the PaRticipation of the ElDerly in Clinical Trials (PREDICT) study, data from ongoing clinical trials regarding heart failure were extracted from the World Health Organization Clinical Trials Registry Platform on December 1, 2008. Main outcome measures were the proportion of trials excluding patients by an arbitrary upper age limit or by other exclusion criteria that might indirectly cause limited recruitment of older individuals. We classified exclusion criteria into 2 categories: justified or poorly justified. RESULTS Among 251 trials investigating treatments for heart failure, 64 (25.5%) excluded patients by an arbitrary upper age limit. Such exclusion was significantly more common in trials conducted in the European Union than in the United States (31/96 [32.3%] vs 17/105 [16.2%]; P = .007) and in drug trials sponsored by public institutions vs those by private entities (21/59 [35.6%] vs 5/36 [13.9%]; P = .02). Overall, 109 trials (43.4%) on heart failure had 1 or more poorly justified exclusion criteria that could limit the inclusion of older individuals. A similar proportion of clinical trials with poorly justified exclusion criteria was found in pharmacologic and nonpharmacologic trials. CONCLUSION Despite the recommendations of national and international regulatory agencies, exclusion of older individuals from ongoing trials regarding heart failure continues to be widespread.
Wave Induced Mine Burial and Sediment Transport in Coastal Environment: Wave and Sediment Transport Modeling Studies

Abstract : The long-term goal of this work is to develop numerical simulation techniques for predicting wave-induced sediment transport and bed evolution in the coastal zone (order 10 meter depth outside the surf zone), at horizontal scales of tens of meters or less, and the scouring/burial around objects/obstacles (mine-like), partially buried in the bottom. This research was initially motivated by the Navy's need to improve mine countermeasures (MBP), in support of joint littoral warfare, for which a key paradigm was to locate a clear or low mine- and obstacle-density path. More generally the laboratory validated modeling tools developed in this work will help improve both our fundamental understanding of, and ability to predict physical processes governing wave-current-induced morphodynamic changes, in coastal and estuarine environments of active sediment transport (e.g., ripple migration). In the past year, our objective was to extend the capabilities, integration, numerical efficiency and ultimately predictive abilities of two coupled numerical models simulating wave-(current)-induced flows and sediment transport over the seabed and around partially buried obstacles. These models were: (i) a two-dimensional (2D) fully nonlinear and inviscid Numerical Wave Tank (2D-NWT; initially developed at the University of Rhode Island; URI; Grilli and Subramanya, 1996; Grilli and Horrillo, 1997), and (ii) a three-dimensional (3D) fully viscous Navier-Stokes, Large Eddy Simulation model, with imbedded sediment transport model (3D-NS-LES; initially developed at Stanford University, and coupled in collaboration with Prof. Street and co-workers; Zedler and Street, 2001).
Use of alveolar carbon monoxide to measure the effect of ribavirin on red blood cell survival †

A major side effect of ribavirin (RBV) treatment is anemia. While this anemia is thought to result from increased RBC turnover, RBC survival has not been determined in subjects receiving RBV due to the complexity of the techniques commonly used to quantitate RBC life span. We recently described a simple, rapid, non‐invasive technique that utilizes measurements of alveolar carbon monoxide (CO) concentration to determine RBC survival. In the present report, this method was employed to assess RBC survival in patients receiving RBV for hepatitis C. Each of the 31 measurements of RBC survival in 12 subjects with RBV‐associated anemia was below the lower limit of normal (77 days), and the average survival (46 ± 14 days) in these subjects was only about 38% of that of healthy controls (122 ± 23 days). Five hepatitis C patients not undergoing RBV treatment had normal RBC survivals (112 ± 17 days). While the mean reticulocyte percentage was significantly elevated in subjects treated with RBV, 59% of these measurements fell within the limits of normal. We conclude that RBV‐associated anemia consistently is associated with reduced RBC survival as determined from breath CO measurements and that this reduced survival frequently is not associated with an elevated reticulocyte count. Am. J. Hematol. 76:107–113, 2004. Published 2004 Wiley‐Liss, Inc.
MOTION PLANNING FOR 6-DOF ASSEMBLY PART POSITIONING AND ALIGNMENT ADJUSTMENT

In this paper, a 4-PPPS redundantly actuated parallel mechanism and its motion planning method are proposed. The mechanism can be applied to the positioning and alignment of large subassembly in engineering assembly. The optimization of the positioning and alignment trajectory is performed with the minimum energy consumption as the objective function. The system test data shows that the assembly platform and the motion planning method can satisfy the requirements of accuracy, efficiency and stability of the positioning and alignment operations.
Radioreceptor and radioimmunoassay quantitation of human growth hormone in acromegalic serum: overestimation by immunoassay and systematic differences between antisera.

ABSTRACT Circulating hGH in patients with acromegaly was measured by a radioreceptor assay (RRA) and the results compared to those obtained by radioimmunoassay (RIA) with two different antisera. With both antisera, RIA measurement exceeded RRA quantitation of hGH, the differences being neither analytic nor related to the sampling or handling of any subgroup of test sera. RIA hGH levels measured with one antiserum, raised in this laboratory, exceeded RRA levels by 42 ± 7% (p < 0.001), and with the second antiserum, distributed by the National Pituitary Agency, the difference was almost twice as great (80 ± 13%, p < 0.001). Comparison of the hGH levels measured by the two antisera also showed a significant difference (22 ± 6%, p < 0.005); individual samples differed by as much as 100%. Two peaks of hGH immunoreactivity were found when serum from acromegalic patients was filtered on Sephadex G-100. The minor peak, of larger molecular weight, was not detected by RRA. However, most of the difference between th.
Low Apgar scores in term newborns and long-term gastro-intestinal morbidity: a population-based cohort study with up to 18 years of follow-up*

Abstract Introduction: Low Apgar scores (<7) measured at age 5 minutes can predict short-term infant morbidity and mortality. Although an association exists between low Apgar scores and neuropsychological disorders, other childhood disorders were not thoroughly studied. We aimed to study the possible association between low 5-minute Apgar scores in term newborns and their long-term childhood gastrointestinal (GI) morbidity. Methods: A population-based cohort analysis was performed comparing total and different subtypes of GI-related pediatric hospitalizations among newborns with normal (≥7) and low (<7) 5-minute Apgar scores. The analysis included all term singletons born between the years 1999 and 2014 at a single tertiary regional medical center. Infants with congenital malformations, multiple gestations, and all perinatal deaths were excluded from the analysis. GI-related morbidities included hospitalizations involving a predefined set of ICD-9 codes, as recorded in the hospital computerized files. A Kaplan–Meier survival curve was constructed to compare the cumulative GI morbidity, and a Cox proportional hazards model was used to adjust for confounders. Results: The study population, including 223 244 term singletons, was followed for an average of 10.02 ± 6.0 years (0–18 years, median 10.25) following discharge from birth hospitalization. Low 5-minute Apgar scores were recorded in 585 (0.3%) newborns. Incidence of GI-related hospitalizations was higher among the low versus the normal 5-minute Apgar score group (7.4 versus 5.2%; 8.6/1000 person years (PY) versus 5.2/1000 PY, respectively; p = . 02; odds ratio =1.66, 95%CI 1.36–1.96). The association remained significant and independent while adjusting for gestational age, fetal weight, offspring gender, maternal age, maternal smoking, hypertension, and diabetes (Adjusted HR =1.57, 95%CI 1.16–2.12, p = .003). Conclusions: Low 5 minutes Apgar score is associated with an increased risk for long-term pediatric GI morbidity of the offspring. Our results suggest that Apgar scores can be used as a possible predictor for long-term pediatric morbidities and thus may necessitate appropriate surveillance in this vulnerable group of children.
Transcription de la parole conversationnelle

Cet article decrit le developpement d'un systeme de reconnaissance de la parole conversationnelle, a partir d'un systeme a l'etat de l'art pour la transcription d'emissions d'information. Nous decrivons les principales ameliorations apportees aux modeles acoustiques, aux modeles linguistiques et au decodeur. Pour la modelisation acoustique, nos travaux ont porte sur l'introduction d'une normalisation par locuteur, le recours a des techniques d'apprentissage adaptatif et d'apprentissage discriminant, et une meilleure prise en compte des variantes de prononciation. Pour la modelisation linguistique, la principale difficulte vient de la faible quantite de donnees d'apprentissage disponible. Nous introduisons deux techniques permettant de diminuer l'impact de cette situation sur les performances du systeme: la selection de textes de nature conversationnelle et un modele representant les mots dans un espace continu. La transcription est obtenue en effectuant un decodage par consensus sur un treillis de mots. Ces ameliorations ont permis de reduire le taux d'erreur de 51 % a 21 %.
Subsidy–stress response of macroinvertebrate community biomass to a phosphorus gradient in an oligotrophic wetland ecosystem

Abstract We used a subsidy–stress model as a basis for predicting macroinvertebrate community response to a steep gradient of P enrichment in the Florida Everglades, a P-limited wetland ecosystem. We tested the hypothesis that consumers were resource limited and their biomass would show a subsidy response (increase) to low-to-moderate levels of P enrichment, but a stress response (decrease) at high levels of P enrichment because dense emergent macrophytes, particularly Typha, might significantly reduce periphyton food resources. We used a spatially extensive sampling design (14 clusters of 9 sites, 126 total) that incorporated vegetation pattern to evaluate consumer responses along the P gradient. We then conducted a 1-y temporal study at 3 of the 14 clusters to evaluate how seasonal hydrological variation interacted with nutrients to influence consumer biomass. Macroinvertebrate community biomass showed a significant unimodal response to increasing P enrichment consistent with a subsidy–stress relationship. Eight of 12 major taxonomic groups (Amphipoda, Decapoda, Diptera, Empheroptera, Gastropoda, Hirudinea, Odonata, Oligochaeta) had this unimodal response, whereas 3 (Coleoptera, Hemiptera, Isopoda) increased monotonically and 1 (Trichoptera) decreased monotonically in response to P. Periphyton C:N and C:P ratios declined with increasing P, but periphyton cover was minimal at high levels of P enrichment where tall invasive macrophytes limited its growth. The temporal study revealed a subsidy–stress response except after marsh reflooding following the dry season when the most P-enriched clusters of sites had the highest consumer biomass, presumably because drought-induced senescence reduced macrophyte cover, which enabled heavy growth of periphyton. Our results suggest that an interaction between increased quality and decreased quantity of periphyton caused the subsidy–stress patterns observed. We suggest our findings could be generalized to other wetland ecosystems where nutrient enrichment leads to invasion of weedy emergent macrophytes, such as Typha, and elimination of open-canopy habitats rich in periphyton.
Reconstruction of surface potential from Kelvin probe force microscopy images

We present an algorithm for reconstructing a sample surface potential from its Kelvin probe force microscopy (KPFM) image. The measured KPFM image is a weighted average of the surface potential underneath the tip apex due to the long-range electrostatic forces. We model the KPFM measurement by a linear shift-invariant system where the impulse response is the point spread function (PSF). By calculating the PSF of the KPFM probe (tip+cantilever) and using the measured noise statistics, we deconvolve the measured KPFM image to obtain the surface potential of the sample.The reconstruction algorithm is applied to measurements of CdS-PbS nanorods measured in amplitude modulation KPFM (AM-KPFM) and to graphene layers measured in frequency modulation KPFM (FM-KPFM). We show that in the AM-KPFM measurements the averaging effect is substantial, whereas in the FM-KPFM measurements the averaging effect is negligible.