Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional regulation of lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) expression in murine macrophages: role of interferon regulatory factors 1 (IRF-1) and 2 (IRF-2)

Activation of TLRs is most closely associated with induction of pro-inflammatory gene expression; however, expression of many other genes, including the TLR genes themselves, has also been shown to be modulated following TLR engagement. A large family of nuclear transcription factors, the interferon regulatory factors (IRFs), have been implicated in TLR signaling leading to pro-inflammatory gene expression. Given that IRF-1 and IRF-2 counter-regulate the transcriptional activity of many genes, we hypothesized that IRF-1 and IRF-2 might also regulate TLR gene expression following LPS stimulation of murine macrophages. mRNA derived from medium- or LPS-treated primary peritoneal macrophages was analyzed for TLR gene expression using quantitative real-time PCR. In wild-type macrophages, LPS up-regulated expression of TLRs 1—3 and 6—9 steady-state mRNA, while TLR4 mRNA was modestly downregulated. IRF-2—/ — macrophages responded to LPS with dysregulated expression of TLR3, TLR4, and TLR5 mRNA, whereas IRF-1 deficiency dampened LPS-induced mRNA expression for TLR3, TLR6, and TLR9. Functional studies revealed aberrant TLR3 signaling in IRF-2—/ — macrophages. Collectively, these findings reveal an additional level of complexity associated with TLR transcriptional regulation and suggest that the trans-acting factors, IRF-1 and IRF-2, contribute to the innate immune response to infections by regulating TLR gene expression.
Estimating Acute Cardiorespiratory Effects of Ambient Volatile Organic Compounds

Background: The health effects of ambient volatile organic compounds (VOCs) have received less attention in epidemiologic studies than other commonly measured ambient pollutants. In this study, we estimated acute cardiorespiratory effects of ambient VOCs in an urban population. Methods: Daily concentrations of 89 VOCs were measured at a centrally-located ambient monitoring site in Atlanta and daily counts of emergency department visits for cardiovascular diseases and asthma in the five-county Atlanta area were obtained for the 1998–2008 period. To understand the health effects of the large number of species, we grouped these VOCs a priori by chemical structure and estimated the associations between VOC groups and daily counts of emergency department visits in a time-series framework using Poisson regression. We applied three analytic approaches to estimate the VOC group effects: an indicator pollutant approach, a joint effect analysis, and a random effect meta-analysis, each with different assumptions. We performed sensitivity analyses to evaluate copollutant confounding. Results: Hydrocarbon groups, particularly alkenes and alkynes, were associated with emergency department visits for cardiovascular diseases, while the ketone group was associated with emergency department visits for asthma. Conclusions: The associations observed between emergency department visits for cardiovascular diseases and alkenes and alkynes may reflect the role of traffic exhaust, while the association between asthma visits and ketones may reflect the role of secondary organic compounds. The different patterns of associations we observed for cardiovascular diseases and asthma suggest different modes of action of these pollutants or the mixtures they represent.
Locomotor sensitization is expressed by ghrelin and D1 dopamine receptor agonist in the nucleus accumbens core in amphetamine pre‐exposed rat

Ghrelin modulates mesolimbic dopaminergic pathways in the brain in addition to its role in feeding. We investigated what roles ghrelin in the nucleus accumbens (NAcc) core may play in mediating locomotor activating effects of amphetamine (AMPH). First, when rats were administered with AMPH (1 mg/kg, i.p.) following a bilateral microinjection of ghrelin (0.1 or 0.5 μg/side) into the NAcc core, their locomotor activity was significantly enhanced, while these effects were blocked by co‐microinjection of ghrelin receptor antagonist (0.5 μg/side) into this site. Second, we pre‐exposed rats to saline or amphetamine (1 mg/kg, i.p.) every 2 to 3 days for a total of four times. After 2 weeks of drug‐free withdrawal period, we examined the effect of saline, ghrelin (0.5 μg/side), D1 dopamine receptor agonist, SKF81297 (0.5 μg/side) or ghrelin (0.5 μg/side) + SKF81297 (0.5 μg/side) directly microinjected into the NAcc core on locomotor activity. When we measured rats' locomotor activity for 1 hour immediately following microinjections, only ghrelin + SKF81297 produces sensitized locomotor activity, while all others have no effects. These results suggest that ghrelin may have a distinct role in the NAcc core to provoke the sensitized locomotor activity induced by psychomotor stimulants, and further, it may produce these effects by interaction with D1 dopamine receptors.
Depressive-like behavior, its sensitization, social buffering, and altered cytokine responses in rhesus macaques moved from outdoor social groups to indoor housing

ABSTRACT Psychosocial stressors appear to promote the onset of depressive illness through activation and sensitization of inflammatory mechanisms. Here, adult male rhesus monkeys brought from large outdoor social groups to indoor housing for 8 days reliably exhibited a hunched, depressive-like posture. When rehoused indoors a second 8 days about 2 weeks later, monkeys housed alone, but not those with an affiliative partner, showed sensitization of the depressive-like hunched posture. Housing indoors also affected circulating pro-inflammatory cytokines: IL-1β showed increased responsiveness to immune challenge, and IL-1β and TNF-α showed reduced suppression by dexamethasone. Sensitivity of the anti-inflammatory cytokine IL-10 to immune challenge exhibited a relative increase from the first to the second round of indoor housing in animals housed in pairs, and a relative decrease in animals housed alone. Cytokine levels during indoor housing were positively correlated with duration of depressive-like behavior. Plasma cortisol levels increased but did not differentiate housing conditions or rounds. Results demonstrate a rapid induction and sensitization of depressive-like behavior to indoor individual housing, social buffering of sensitization, and associated inflammatory responses. This paradigm may provide a practical nonhuman primate model for examining inflammatory-mediated consequences of psychosocial stressors on depression and possible social buffering of these effects.
Non-Negative Multiple Matrix Factorization with Social Similarity for Recommender Systems

A key problem in online social networks is the identification of users' link information and the analysis of how these are reflected in the recommender systems. The basis to tackle this issue is user similarity measures. In this paper, we propose non-negative multiple matrix factorization with social similarity for recommender systems, considering the similarities between users, the relationships of users-resources and tags-resources. On this basis, we comparatively analyzed different performances of the recommendation with every similarity measure between users. In addition, our method can also recommend friends, resources, and tags to users. Experimental results on Lastfm and Delicious datasets show that the proposed method can significantly improve the recommendation accuracy compared with the art collaborative filtering methods.
Modulations of cognitive flexibility in obsessive compulsive disorder reflect dysfunctions of perceptual categorization

BACKGROUND Despite cognitive inflexibility is trait like in obsessive compulsive disorder (OCD) patients and underlies clinical symptomatology, it is elusive at what stage of information processing deficits, leading to cognitive inflexibility, emerges. We hypothesize that inhibitory control mechanisms during early stimulus categorization and integration into a knowledge system underlie these deficits. METHODS We examined N = 25 adolescent OCD patients and matched healthy controls (HC) in a paradigm manipulating the importance of the knowledge system to perform task switching. This was done using a paradigm in which task switches were signaled either by visual stimuli or by working memory processes. This was combined with event-related potential recordings and source localization. RESULTS Obsessive compulsive disorder patients showed increased switch costs in the memory as compared with the cue-based block, while HC showed similar switch costs in both blocks. At the neurophysiological level, these changes in OCD were not reflected by the N2 and P3 reflecting response-associated processes but by the P1 reflecting inhibitory control during sensory categorization processes. Activation differences in the right inferior frontal gyrus and superior temporal gyrus are associated with the P1 effect. CONCLUSIONS Cognitive flexibility in adolescent OCD patients is strongly modulated by working memory load. Contrary to common sense, not response-associated processes, but inhibitory control mechanisms during early stimulus categorization processes are likely to underlie cognitive inflexibility in OCD. These processes are associated with right inferior frontal and superior temporal gyrus mechanisms.
A scoping review of the evidence for efficacy of acupuncture in companion animals

Abstract Acupuncture has become increasingly popular in veterinary medicine. Within the scientific literature there is debate regarding its efficacy. Due to the complex nature of acupuncture, a scoping review was undertaken to identify and categorize the evidence related to acupuncture in companion animals (dogs, cats, and horses). Our search identified 843 relevant citations. Narrative reviews represented the largest proportion of studies (43%). We identified 179 experimental studies and 175 case reports/case series that examined the efficacy of acupuncture. Dogs were the most common subjects in the experimental trials. The most common indication for use was musculoskeletal conditions, and the most commonly evaluated outcome categories among experimental trials were pain and cardiovascular parameters. The limited number of controlled trials and the breadth of indications for use, outcome categories, and types of acupuncture evaluated present challenges for future systematic reviews or meta-analyses. There is a need for high-quality randomized controlled trials addressing the most common clinical uses of acupuncture, and using consistent and clinically relevant outcomes, to inform conclusions regarding the efficacy of acupuncture in companion animals.
2-D Index Map Coding for HEVC Screen Content Compression

This paper introduces a 2-D index map coding of the palette mode in screen content coding extension of the High-Efficiency Video Coding (HEVC SCC) standard to further improve the compression performance. In contrast to the current 1-D search using RUN to represent the length of matched string, we bring the block width and height to describe the arbitrary rectangle shape. We also use the block vector displacement to signal the matched block distance efficiently. By enlarging the search range from current coding tree unit (CTU) to a small neighbor CTU window (i.e., 3×5 CTUs), it provides the coding efficiency comparable to the case that full-frame intra block copy is used. It is more practical to use the local search window in real life considering the trade-off between the coding efficiency and implementation cost.
Structural characterization of nonactive site, TrkA-selective kinase inhibitors

Significance Signal transduction through Tropomyosin-related kinase A (TrkA), a receptor tyrosine kinase, is a target for inhibition of chronic pain and could lead to a new class of drugs against pain. Selectivity against kinases can be difficult to achieve, especially against members of the same kinase family. Structures of the compounds bound to TrkA show a binding site comprised of the kinase, which is conserved among the Trk family, and the juxtamembrane (JM), which is not well conserved. Depending on their chemical substructure, the region of the juxtamembrane that interacts with the compounds can be different, leading to differences in specificity. This study emphasizes the importance of including residues beyond the catalytic domain for small-molecule screening, importance of screening by affinity, and structural characterization to understand binding interactions. Current therapies for chronic pain can have insufficient efficacy and lead to side effects, necessitating research of novel targets against pain. Although originally identified as an oncogene, Tropomyosin-related kinase A (TrkA) is linked to pain and elevated levels of NGF (the ligand for TrkA) are associated with chronic pain. Antibodies that block TrkA interaction with its ligand, NGF, are in clinical trials for pain relief. Here, we describe the identification of TrkA-specific inhibitors and the structural basis for their selectivity over other Trk family kinases. The X-ray structures reveal a binding site outside the kinase active site that uses residues from the kinase domain and the juxtamembrane region. Three modes of binding with the juxtamembrane region are characterized through a series of ligand-bound complexes. The structures indicate a critical pharmacophore on the compounds that leads to the distinct binding modes. The mode of interaction can allow TrkA selectivity over TrkB and TrkC or promiscuous, pan-Trk inhibition. This finding highlights the difficulty in characterizing the structure-activity relationship of a chemical series in the absence of structural information because of substantial differences in the interacting residues. These structures illustrate the flexibility of binding to sequences outside of—but adjacent to—the kinase domain of TrkA. This knowledge allows development of compounds with specificity for TrkA or the family of Trk proteins.
Effect of age-related hearing loss on the click-rate-induced facilitation of acoustic reflex thresholds

Abstract Objective: This investigation was designed to evaluate the effect of age-related hearing loss on the click-rate-induced improvement in the acoustic reflex thresholds. Design: Case–control study. Study sample: Data from five different adults ear-groups (15 ears each) were included in the study: 1. Younger with normal hearing. 2. Older with normal hearing. 3. Older with mild high-frequency loss. 4. Older with moderate high-frequency loss. 5. Older with low- and high-frequency loss. Ipsilateral acoustic reflex thresholds were obtained from the left and/or right ear/s by presenting clicks at the repetition rates of 50, 100, 150, 200 and 300 clicks/s. The rate-induced facilitation (RIF) was calculated by subtracting the lowest acoustic reflex threshold from the highest reflex threshold obtained across the various click-rates. Results: The click-RIF is significantly reduced in older individuals compared to younger adults. There is no significant difference in RIF across the four older adult groups suggesting that an age-related, mild to moderate hearing loss has no significant effect on the click RIF of the acoustic reflex thresholds. Conclusions: Click-RIF may allow us to document the effect of ageing on temporal processing within the auditory brainstem area, in a time-efficient and objective manner using commercially available equipment.
Real-Time Whole-Genome Sequencing for Surveillance of Listeria monocytogenes, France

During 2015–2016, we evaluated the performance of whole-genome sequencing (WGS) as a routine typing tool. Its added value for microbiological and epidemiologic surveillance of listeriosis was compared with that for pulsed-field gel electrophoresis (PFGE), the current standard method. A total of 2,743 Listeria monocytogenes isolates collected as part of routine surveillance were characterized in parallel by PFGE and core genome multilocus sequence typing (cgMLST) extracted from WGS. We investigated PFGE and cgMLST clusters containing human isolates. Discrimination of isolates was significantly higher by cgMLST than by PFGE (p<0.001). cgMLST discriminated unrelated isolates that shared identical PFGE profiles and phylogenetically closely related isolates with distinct PFGE profiles. This procedure also refined epidemiologic investigations to include only phylogenetically closely related isolates, improved source identification, and facilitated epidemiologic investigations, enabling identification of more outbreaks at earlier stages. WGS-based typing should replace PFGE as the primary typing method for L. monocytogenes.
Bottom-up Process Improvement Tricks

Most everyone in our field acknowledges that software process improvement cannot succeed unless management is committed to implementing it. Fortunately, the move to SPI can be a two-way street, initiated as easily from the bottom up as from the top down. Taking this bottom-up approach, I present some tricks that practitioners down in the trenches can use to win upper management's approval of and support for SPI.
Bioinformatics Resources and Tools for Conformational B-Cell Epitope Prediction

Identification of epitopes which invoke strong humoral responses is an essential issue in the field of immunology. Localizing epitopes by experimental methods is expensive in terms of time, cost, and effort; therefore, computational methods feature for its low cost and high speed was employed to predict B-cell epitopes. In this paper, we review the recent advance of bioinformatics resources and tools in conformational B-cell epitope prediction, including databases, algorithms, web servers, and their applications in solving problems in related areas. To stimulate the development of better tools, some promising directions are also extensively discussed.
Can recursive bisection alone produce routable, placements?

This work focuses on congestion-driven placement of standard cells into rows in the fixed-die context. We summarize the state-of-the-art after two decades of research in recursive bisection placement and implement a new placer, called Capo, to empirically study the achievable limits of the approach. From among recently proposed improvements to recursive bisection, Capo incorporates a leading-edge multilevel min-cut partitioner [7], techniques for partitioning with small tolerance [8], optimal min-cut partitioners and end-case min-wirelength placers [5], previously unpublished partitioning tolerance computations, and block splitting heuristics. On the other hand, our “good enough” implementation does not use “overlapping” [17], multi-way partitioners [17, 20], analytical placement, or congestion estimation [24, 35]. In order to run on recent industrial placement instances, Capo must take into account fixed macros, power stripes and rows with different allowed cell orientations. Capo reads industry-standard LEF/DEF, as well as formats of the GSRC bookshelf for VLSI CAD algorithms [6], to enable comparisons on available placement instances in the fixed-die regime. Capo clearly demonstrates that despite a potential mismatch of objectives, improved mincut bisection can still lead to improved placement wirelength and congestion. Our experiments on recent industrial benchmarks fail to give a clear answer to the question in the title of this paper. However, they validate a series of improvements to recursive bisection and point out a need for transparent congestion management techniques that do not worsen the wirelength of already routable placements. Our experimental flow, which validates fixed-die placement results by violation-free detailed auto-routability, provides a new norm for comparison of VLSI placement implementations.
High Thermoelectric Power Factor in IntermetallicCoSiArising from Energy Filtering of Electrons by Phonon Scattering

While highly conductive, intermetallic compounds are typically poor thermoelectrics, due to a small Seebeck coefficient. $B20$-type CoSi, however, exhibits an anomalously large, negative Seebeck coefficient. First-principles calculations reveal the underlying reason to be the strong energy dependence of carrier lifetimes due to phonon scattering, which leads to effective energy filtering of holes and low-energy electrons. The phenomenon originates from a band structure with both heavy and massless fermions near the Fermi level, and is thus intrinsic to the material. This insight opens an avenue for discovering and designing high-performance thermoelectrics for energy recovery.
Small‐Molecule‐Induced and Cooperative Enzyme Assembly on a 14‐3‐3 Scaffold

Scaffold proteins regulate cell signalling by promoting the proximity of putative interaction partners. Although they are frequently applied in cellular settings, fundamental understanding of them in terms of, amongst other factors, quantitative parameters has been lagging behind. Here we present a scaffold protein platform that is based on the native 14‐3‐3 dimeric protein and is controllable through the action of a small‐molecule compound, thus permitting study in an in vitro setting and mathematical description. Robust small‐molecule regulation of caspase‐9 activity through induced dimerisation on the 14‐3‐3 scaffold was demonstrated. The individual parameters of this system were precisely determined and used to develop a mathematical model of the scaffolding concept. This model was used to elucidate the strong cooperativity of the enzyme activation mediated by the 14‐3‐3 scaffold. This work provides an entry point for the long‐needed quantitative insights into scaffold protein functioning and paves the way for the optimal use of reengineered 14‐3‐3 proteins as chemically inducible scaffolds in synthetic systems.
Causal somatic mutations in urine DNA from persons with the CLOVES subgroup of the PIK3CA‐related overgrowth spectrum

Congenital lipomatous overgrowth with vascular, epidermal, and skeletal (CLOVES) anomalies and Klippel‐Trenaunay (KTS) syndromes are caused by somatic gain‐of‐function mutations in PIK3CA, encoding a catalytic subunit of phosphoinositide 3‐kinase. Affected tissue is needed to find mutations, as mutant alleles are not detectable in blood. Because some patients with CLOVES develop Wilms tumor, we tested urine as a source of DNA for mutation detection. We extracted DNA from the urine of 17 and 24 individuals with CLOVES and KTS, respectively, and screened 5 common PIK3CA mutation hotspots using droplet digital polymerase chain reaction. Six of 17 CLOVES participants (35%) had mutant PIK3CA alleles in urine. Among 8 individuals in whom a mutation had been previously identified in affected tissue, 4 had the same mutant allele in the urine. One study participant with CLOVES had been treated for Wilms tumor. We detected the same PIK3CA mutation in her affected tissue, urine, and tumor, indicating Wilms tumors probably arise from PIK3CA mutant cells in patients with CLOVES. No urine sample from a participant with KTS had detectable PIK3CA mutations. We suggest that urine, which has the advantage of being collected non‐invasively, is useful when searching for mutations in individuals with CLOVES syndrome.