Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Differences in Transcript-Regulator Expression Quantitative Trait Loci

Gene expression quantitative trait loci (eQTL) are useful for identifying single nucleotide polymorphisms (SNPs) associated with diseases. At times, a genetic variant may be associated with a master regulator involved in the manifestation of a disease. The downstream target genes of the master regulator are typically co-expressed and share biological function. Therefore, it is practical to screen for eQTLs by identifying SNPs associated with the targets of a transcript-regulator (TR). We used a multivariate regression with the gene expression of known targets of TRs and SNPs to identify TReQTLs in European (CEU) and African (YRI) HapMap populations. A nominal p-value of <1×10−6 revealed 234 SNPs in CEU and 154 in YRI as TReQTLs. These represent 36 independent (tag) SNPs in CEU and 39 in YRI affecting the downstream targets of 25 and 36 TRs respectively. At a false discovery rate (FDR) = 45%, one cis-acting tag SNP (within 1 kb of a gene) in each population was identified as a TReQTL. In CEU, the SNP (rs16858621) in Pcnxl2 was found to be associated with the genes regulated by CREM whereas in YRI, the SNP (rs16909324) was linked to the targets of miRNA hsa-miR-125a. To infer the pathways that regulate expression, we ranked TReQTLs by connectivity within the structure of biological process subtrees. One TReQTL SNP (rs3790904) in CEU maps to Lphn2 and is associated (nominal p-value = 8.1×10−7) with the targets of the X-linked breast cancer suppressor Foxp3. The structure of the biological process subtree and a gene interaction network of the TReQTL revealed that tumor necrosis factor, NF-kappaB and variants in G-protein coupled receptors signaling may play a central role as communicators in Foxp3 functional regulation. The potential pleiotropic effect of the Foxp3 TReQTLs was gleaned from integrating mRNA-Seq data and SNP-set enrichment into the analysis.
The organization of societal conflicts by pavement ants Tetramorium caespitum: an agent-based model of amine-mediated decision making

Abstract Ant colonies self-organize to solve complex problems despite the simplicity of an individual ant’s brain. Pavement ant Tetramorium caespitum colonies must solve the problem of defending the territory that they patrol in search of energetically rich forage. When members of 2 colonies randomly interact at the territory boundary a decision to fight occurs when: 1) there is a mismatch in nestmate recognition cues and 2) each ant has a recent history of high interaction rates with nestmate ants. Instead of fighting, some ants will decide to recruit more workers from the nest to the fighting location, and in this way a positive feedback mediates the development of colony wide wars. In ants, the monoamines serotonin (5-HT) and octopamine (OA) modulate many behaviors associated with colony organization and in particular behaviors associated with nestmate recognition and aggression. In this article, we develop and explore an agent-based model that conceptualizes how individual changes in brain concentrations of 5-HT and OA, paired with a simple threshold-based decision rule, can lead to the development of colony wide warfare. Model simulations do lead to the development of warfare with 91% of ants fighting at the end of 1 h. When conducting a sensitivity analysis, we determined that uncertainty in monoamine concentration signal decay influences the behavior of the model more than uncertainty in the decision-making rule or density. We conclude that pavement ant behavior is consistent with the detection of interaction rate through a single timed interval rather than integration of multiple interactions.
Follicle-stimulating hormone peptide-conjugated nanoparticles for targeted shRNA delivery lead to effective gro-α silencing and antitumor activity against ovarian cancer

Abstract The distinct hormone molecules and receptors, such as follicle-stimulating hormone receptor (FSHR) in ovarian cancer, provide opportunities for more precisely targeted therapy. We previously developed FSHR-mediated nanoparticles and found that FSH peptides on the surface of nanoparticles improved the delivery of short interfering RNA (siRNA) into ovarian cancer cells. However, the high toxicity of the nanoparticles and the transient silencing of the siRNA in vivo limited further study. Here, we developed FSH peptide-conjugated nanoparticles with an increased amount of polyethylene glycol (PEG) grafting and encapsulated short hairpin RNA (shRNA) to silence the target gene, growth-regulated oncogene α (gro-α). The nanoparticle complexes exhibited good stability over three weeks. Expression of the target gene, gro-α, was significantly down-regulated by gro-α shRNA-loaded nanoparticles conjugated with FSH peptides (FSH33-G-NP) in FSHR-positive HEY cells. Cell proliferation, migration, and invasion were also inhibited by FSH33-G-NP. Tumor growth was delayed significantly in the mice treated with FSH33-G-NP. No significant loss of body weight or severe toxic effects were observed in any groups. In conclusion, gro-α shRNA-loaded nanoparticles conjugated with FSH peptides overcame the drawbacks of the in vivo application of RNAi therapeutics and polymer-based nanocarriers and showed safe antitumor efficacy. Our study might contribute to the application of FSHR-based targeted therapy and imaging in cancer.
Quantifying environmental heterogeneity : habitat size necessary for successful development of cod Gadus morhua eggs in the Baltic Sea

Spatial and temporal variability in environmental factors can exert major influences on survival and growth of living organisms. However, in many key areas of fisheries science (e.g. growth, survival and recruitment determination), environmental heterogeneity is usually ignored because of insufficient environmental or fisheries data or lack of evidence that such heterogeneity impacts response variables. For the eastern Baltic Sea (ICES Subdivisions 25 to 32), we evaluated spatial and temporal differences in conditions affecting the survival of cod Gadus morhua L. eggs at survival on four distinct spawning sites within the assessment area. We intercalibrated ways of quantifying the volume of water ('reproductive volume') at each site where salinity, oxygen and temperature conditions permitted successful egg development. We have developed and compared a time series (1952 to 1996) of reproductive volumes among the areas to identify spatial differences. The results of 2 independent volume-estimation methods are comparable, indicating that highly significant differences exist among the sites, and that the westernmost spawning ground, Bornholm Basin, has on average the highest reproductive volume and the lowest variability among the 4 sites. These findings may be useful in evaluating how spatial and temporal variability in environmental conditions affect egg hatching success and possibly recruitment in the Baltic stock.
Trust management in cognitive radio networks: A survey

Cognitive radio is proposed to solve the interference and underutilized license problems. With the development of the cognitive functionalities, classical and new security threats become challenging. To make wireless cognitive radio networks more secure and more reliable, several approaches have been proposed in the literature. In recent years, trust and reputation management (TRM) techniques are more and more considered for cognitive radio networks to secure them against the malicious and misbehaving users that try to deprive others from using the white space. The scope of this survey is to give a comprehensive overview about the existing TRM‐based mechanisms proposed for the cognitive radio networks. We expose the existing classifications of TRM techniques, then we introduce a new classification that takes into account, more exhaustively, different TRM properties and approaches.
The improvement of dry eye after cataract surgery by intraoperative using ophthalmic viscosurgical devices on the surface of cornea

Backgroud: This study aimed to investigate the protective effect of intraoperative used hydroxypropyl methylcellulose (HPMC 2%) on the ocular surface after cataract surgery. Methods: A total of 149 eyes (149 patients) diagnosed with age-related cataract, age 69.19 ± 9.74 years, were enrolled in this prospective, parallel-design, continuous, randomised controlled study. Patients were randomly assigned to receive HPMC 2% (study group) or balanced salt solution (control group) during the surgery to moisturize the cornea surface. The Ocular Surface Disease Index, Schirmer test without topical anesthetics, tear break-up time, and corneal fluorescein staining were assessed preoperatively, 1 day, 1 week, and 1 month after the surgery, respectively. Results: The Schirmer test value of male patients in the study group at 1 week postoperation was higher than that of male patients in the control group (P = .019). For patients diagnosed with dry eye before the surgery, Schirmer test value in the male patients in the study group at 1 month after surgery was higher than that in the male patients in the control group (P = .037). Furthermore, for the cluster of preoperative dry eye patients whose surgical time was longer than median, corneal fluorescein staining of the patients in the study group was superior to that of the patients in the control group (P = .032). Conclusion: Intraoperative use of HPMC 2% on the cornea surface could improve clinical outcomes of tear film and ocular surface health to some degree, especially in the patients diagnosed with dry eye before the surgery, male patients, and patients whose surgical time was relatively longer.
Morphology and Function of the Lamb Ileum following Preterm Birth

Background For infants born moderately/late preterm (32–37 weeks of gestation), immaturity of the intestine has the potential to impact both short- and long-term gastrointestinal function. The aim of this study conducted in sheep was to compare the morphology and smooth muscle contractility of the ileum in term and late preterm lambs. Materials and methods Lambs delivered preterm (132 days gestation; n = 7) or term (147 days gestation; n = 9) were milk-fed after birth and euthanased at 2 days of age. A segment of distal ileum was collected for analysis of the length and cellular composition of the villi and crypts, smooth muscle width and contractility, and mRNA expression of the cell markers Ki67, lysozyme, mucin 2, synaptophysin, chromogranin A, olfactomedin 4, axis inhibition protein 2, and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5). Results There was no difference in the proportion of inflammatory, proliferating, apoptotic, enterocyte, or goblet cells between groups, but preterm lambs exhibited a significant upregulation of the stem cell marker LGR5 (p = 0.01). Absolute villus height (term: 1,032 ± 147 µm, preterm: 651 ± 52 µm; p < 0.0001) and crypt depth (term: 153 ± 11 µm, preterm: 133 ± 17 µm; p = 0.01) were significantly shorter in the preterm ileums, with a trend (p = 0.06) for a reduction in muscularis externa width. There was no difference between groups in the contractile response to acetylcholine, but peak contractility in response to bradykinin (p = 0.02) and angiotensin II (p = 0.03) was significantly greater in the preterm lambs. Conclusion Findings demonstrate that the crypt-villus units are shorter in the ileum of late preterm offspring, but functionally mature with an equivalent cellular composition and normal contractile response to acetylcholine compared with term offspring. The exaggerated contractility to inflammatory mediators evident in the preterm ileum, however, may be of concern.
Ad Hoc Table Retrieval using Semantic Similarity

We introduce and address the problem of ad hoc table retrieval: answering a keyword query with a ranked list of tables. This task is not only interesting on its own account, but is also being used as a core component in many other table-based information access scenarios, such as table completion or table mining. The main novel contribution of this work is a method for performing semantic matching between queries and tables. Specifically, we (i) represent queries and tables in multiple semantic spaces (both discrete sparse and continuous dense vector representations) and (ii) introduce various similarity measures for matching those semantic representations. We consider all possible combinations of semantic representations and similarity measures and use these as features in a supervised learning model. Using a purpose-built test collection based on Wikipedia tables, we demonstrate significant and substantial improvements over a state-of-the-art baseline.
Extracellular vesicle budding is inhibited by redundant regulators of TAT-5 flippase localization and phospholipid asymmetry

Significance Cells must interact with their environment to survive. The lipids and proteins of the plasma membrane send and receive signals at the cell surface to respond to stimuli. When the lipid bilayer of the plasma membrane is damaged, cells release membrane-bound extracellular vesicles to repair the membrane. Cells also release signals on extracellular vesicles to communicate at a distance. Here, we identify proteins that regulate the formation of extracellular vesicles from the plasma membrane, providing additional tools to control their release that can be used to test potential functions of extracellular vesicles. Furthermore, we reveal that proteins regulating the asymmetric localization of the lipid phosphatidylethanolamine are critical for extracellular vesicle release, implicating this abundant but understudied lipid. Cells release extracellular vesicles (EVs) that mediate intercellular communication and repair damaged membranes. Despite the pleiotropic functions of EVs in vitro, their in vivo function is debated, largely because it is unclear how to induce or inhibit their formation. In particular, the mechanisms of EV release by plasma membrane budding or ectocytosis are poorly understood. We previously showed that TAT-5 phospholipid flippase activity maintains the asymmetric localization of the lipid phosphatidylethanolamine (PE) in the plasma membrane and inhibits EV budding by ectocytosis in Caenorhabditis elegans. However, no proteins that inhibit ectocytosis upstream of TAT-5 were known. Here, we identify TAT-5 regulators associated with retrograde endosomal recycling: PI3Kinase VPS-34, Beclin1 homolog BEC-1, DnaJ protein RME-8, and the uncharacterized Dopey homolog PAD-1. PI3Kinase, RME-8, and semiredundant sorting nexins are required for the plasma membrane localization of TAT-5, which is important to maintain PE asymmetry and inhibit EV release. PAD-1 does not directly regulate TAT-5 localization, but is required for the lipid flipping activity of TAT-5. PAD-1 also has roles in endosomal trafficking with the GEF-like protein MON-2, which regulates PE asymmetry and EV release redundantly with sorting nexins independent of the core retromer. Thus, in addition to uncovering redundant intracellular trafficking pathways, our study identifies additional proteins that regulate EV release. This work pinpoints TAT-5 and PE as key regulators of plasma membrane budding, further supporting the model that PE externalization drives ectocytosis.
Translational Systems Pharmacology Studies in Pregnant Women

Pregnancy involves rapid physiological adaptation and complex interplay between mother and fetus. New analytic technologies provide large amounts of genomic, proteomic, and metabolomics data. The integration of these data through bioinformatics, statistical, and systems pharmacology techniques can improve our understanding of the mechanisms of normal maternal physiologic changes and fetal development. New insights into the mechanisms of pregnancy‐related disorders, such as preterm birth (PTB), may lead to the development of new therapeutic interventions and novel biomarkers.
Red Blood Cell Distribution Width Can Predict Vasculitis Activity and Poor Prognosis in Granulomatosis with Polyangiitis

Purpose We investigated whether red blood cell distribution width (RDW) predicts vasculitis activity based on Birmingham vasculitis activity score (BVAS) or BVAS for granulomatosis with polyangiitis (GPA) at diagnosis and poor prognosis during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Materials and Methods We reviewed the medical records of 150 patients with AAV. We defined severe GPA as BVAS for GPA ≥7 (the highest quartile). Correlation and standardised correlation coefficients were analysed by linear regression tests. The differences between groups were evaluated by Mann-Whitney test. Relative risk (RR) was assessed by chi square test and Cox hazards model. Results RDW was correlated only with the vasculitis activity of GPA among patients with AAV. An increase in RDW was associated with the absence of ear nose throat (ENT) manifestation, but not proteinase 3-ANCA. Significant differences were noted in cumulative refractory free survival according to RDW ≥15.4% (p=0.007) and the absence of ENT manifestation (p=0.036). Multivariate Cox hazards analysis identified RDW ≥15.4% as the only significant predictor of refractory disease in GPA (RR 17.573). Conclusion RDW predicts vasculitis activity in GPA, and RDW ≥15.4% at diagnosis may increase the risk of severe GPA at diagnosis and predict refractory diseases during follow-up.
The temporal paradox of Hebbian learning and homeostatic plasticity

Hebbian plasticity, a synaptic mechanism which detects and amplifies co-activity between neurons, is considered a key ingredient underlying learning and memory in the brain. However, Hebbian plasticity alone is unstable, leading to runaway neuronal activity, and therefore requires stabilization by additional compensatory processes. Traditionally, a diversity of homeostatic plasticity phenomena found in neural circuits are thought to play this role. However, recent modelling work suggests that the slow evolution of homeostatic plasticity, as observed in experiments, is insufficient to prevent instabilities originating from Hebbian plasticity. To remedy this situation, we suggest that homeostatic plasticity is complemented by additional rapid compensatory processes, which rapidly stabilize neuronal activity on short timescales.
Interbirth intervals are associated with age of the mother, but not with infant mortality in Indian rhinoceroses

Abstract Rhinoceroses are among the most endangered mammals in the world. Despite a recent increase in numbers in most wild populations, poaching or political instability may exterminate large populations very quickly. Therefore, captive or ex situ rhinoceros populations can play an important role in their conservation. Previous studies identified infant mortality and interbirth intervals among the main parameters affecting the viability and survival of rhinoceros populations. In our study, we tested the recently suggested prediction that in captive Indian rhinoceros Rhinoceros unicornis, longer interbirth intervals may result in higher infant mortality. We also examined the factors that are the main predictors of infant mortality and interbith intervals using the studbook data on Indian rhinoceros born in zoos worldwide as well as data from Dudhwa National Park, India, where rhinoceroses were successfully reintroduced. We found no association between interbirth intervals and infant mortality. In both populations, the main predictor of infant mortality was mother’s parity, with higher mortality in calves born to primiparous mothers. In addition, we found that the interbirth intervals were shorter in zoos than in Dudhwa and that they increased with increase in age of the mother, which was the only factor affecting interbirth interval in both populations. Our results show that the same factors affect both parameters in both populations and thus illustrate that the reproduction and infant survival of Indian rhinoceros in zoos reflect the natural pattern. Furthermore, we suggest that in captivity, the interbirth intervals could be slightly prolonged to approach the situation in the wild.
The impact of float stitches on the resistance of conductive knitted structures

Currently, conductive yarn can be knitted into fabrics to endow the traditional textile product with special attributes, such as shielding electromagnetic waves, detecting and transferring electrical signals, replacing fingers in the operation of touch-screen panels, etc. Research on the electrical properties of conductive knitted fabrics can contribute to the development of such functional textiles. A few studies have been conducted, and it has been found that the variation of the knitted structure can impact the properties of a conductive knitted fabric. Among the properties of conductive fabrics, the resistance value is an important index to decide the performance of electrical functions. Several researchers have conducted practical experiments and theoretical analyses to predict the resistance of plain weft knitted structure. However, in addition to the plain weft knitted structure, the float structure is another important basic knitted structure. Therefore, a geometric model incorporated with a simplified resistive network is proposed for the calculation of the electrical resistance of conductive knitted fabrics with float stitches and will be studied in this paper. The aim of the model is to determine the resistive effects of conductive float stitches on knitted structures with different numbers of knitted courses and wales. The geometric model can provide a detailed mathematical description of a single knitted loop in the Cartesian coordinate system. With the simplified resistive network, the resistance of conductive float stitches in knitted fabrics can be modeled and computed. The experimental results revealed that the proposed model could approximate the equivalent electrical resistance of the conductive float stitches in knitted fabrics to an acceptable degree.
A Comprehensive Review of mTOR-Inhibiting Pharmacotherapy for the Treatment of Non-Infectious Uveitis.

BACKGROUND Non-infectious uveitis is a sight-threatening inflammatory disease that often necessitates prolonged use of high-dose corticosteroids, resulting in significant systemic side effects. There is a need for efficacious steroid-sparing immunomodulatory therapy for these patients, and the mTOR inhibitors (sirolimus and everolimus) may be contenders for this role. METHODS A comprehensive review of preclinical and clinical research on mTOR inhibitors for non-infectious uveitis was performed. Articles were identified by a search of MEDLINE (PubMed/OVID) and EMBASE (OVID) the terms (uveitis OR non-infectious uveitis) AND (mTOR inhibitor OR sirolimus OR everolimus). Assessment of study aims, methods, efficacy outcomes and adverse events was performed. RESULTS Seven pre-clinical and nine clinical studies were identified. One study in each group was on everolimus, the rest sirolimus. Preclinical studies have been performed in rabbit, rat, mouse and in-vitro models. Clinical studies range from comparative open-label trials to case reports, with reported clinical efficacy ranging from 40% to 100% depending on endpoint assessed. The overall rate of drug-related adverse events (such as ocular irritation, visual floaters, nausea and vomiting) was 0.640 events per patient-year with sirolimus, and 0.111 events per patient-year with everolimus. CONCLUSION Published evidence suggests that sirolimus and everolimus may be useful in the management of noninfectious uveitis. Both appear to be well tolerated, especially when locally administered. Further high-quality RCTs adopting standardised end-points are required to definitively determine the efficacy of each agent.