Miracle-dz/UniFAR-FTUs huggingface dataset:
Signal transducer and activator of transcription-6 (STAT6) inhibition suppresses renal cyst growth in polycystic kidney disease

Autosomal-dominant (AD) polycystic kidney disease (PKD) is a leading cause of renal failure in the United States, and currently lacks available treatment options to slow disease progression. Mutations in the gene coding for polycystin-1 (PC1) underlie the majority of cases but the function of PC1 has remained poorly understood. We have previously shown that PC1 regulates the transcriptional activity of signal transducer and activator of transcription-6 (STAT6). Here we show that STAT6 is aberrantly activated in cyst-lining cells in PKD mouse models. Activation of the STAT6 pathway leads to a positive feedback loop involving auto/paracrine signaling by IL13 and the IL4/13 receptor. The presence of IL13 in cyst fluid and the overexpression of IL4/13 receptor chains suggests a mechanism of sustained STAT6 activation in cysts. Genetic inactivation of STAT6 in a PKD mouse model leads to significant inhibition of proliferation and cyst growth and preservation of renal function. We show that the active metabolite of leflunomide, a drug approved for treatment of arthritis, inhibits STAT6 in renal epithelial cells. Treatment of PKD mice with this drug leads to amelioration of the renal cystic disease similar to genetic STAT6 inactivation. These results suggest STAT6 as a promising drug target for treatment of ADPKD.
Mitochondrial Genome Rearrangements in the Scleractinia/Corallimorpharia Complex: Implications for Coral Phylogeny

Corallimorpharia is a small Order of skeleton-less animals that is closely related to the reef-building corals (Scleractinia) and of fundamental interest in the context of understanding the potential impacts of climate change in the future on coral reefs. The relationship between the nominal Orders Corallimorpharia and Scleractinia is controversial—the former is either the closest outgroup to the Scleractinia or alternatively is derived from corals via skeleton loss. This latter scenario, the “naked coral” hypothesis, is strongly supported by analyses based on mitochondrial (mt) protein sequences, whereas the former is equally strongly supported by analyses of mt nucleotide sequences. The “naked coral” hypothesis seeks to link skeleton loss in the putative ancestor of corallimorpharians with a period of elevated oceanic CO2 during the Cretaceous, leading to the idea that these skeleton-less animals may be harbingers for the fate of coral reefs under global climate change. In an attempt to better understand their evolutionary relationships, we examined mt genome organization in a representative range (12 species, representing 3 of the 4 extant families) of corallimorpharians and compared these patterns with other Hexacorallia. The most surprising finding was that mt genome organization in Corallimorphus profundus, a deep-water species that is the most scleractinian-like of all corallimorpharians on the basis of morphology, was much more similar to the common scleractinian pattern than to those of other corallimorpharians. This finding is consistent with the idea that C. profundus represents a key position in the coral <-> corallimorpharian transition.
Six Years Follow-up of the Levels of TNF-α and IL-6 in Patients with Complex Regional Pain Syndrome Type 1

In an earlier study, levels of the proinflammatory cytokines TNF-α and IL-6 are higher in blisters fluid from the complex regional pain syndrome type 1 (CRPS1) side obtained at 6 and 30 months (median) after the initial event. The aim of this follow-up study is to determine the involvement of these cytokines in long lasting CRPS1. Twelve CRPS1 patients, with median disease duration of 72 months, participated. The levels of TNF-α and IL-6 were measured in blister fluid; disease activity was reevaluated by measuring pain and differences in temperature, volume, and mobility between both extremities. Differences in levels of IL-6 and TNF-α and mobility between both sides were significantly decreased. Pain and differences in temperature and volume were not significantly altered. No correlation was found between the cytokines and the disease characteristics. These results indicate that IL-6 and TNF-α are only partially responsible for the signs and symptoms of CRPS1.
Determinism and Reproducibility in Large-Scale HPC Systems

The ability to reproduce simulation results ( external determinism ) goes a long way towards enhancing the trustworthiness of high performance computing simulations. The ability to replay schedules ( internal determinism ) greatly facilitates reproducing bugs, and helps reduce wasted programmer productivity. In this paper, we consider these issues in the context of software libraries and APIs used in today’s mainstream high performance computing (HPC) systems as well as expected to be used in upcoming high-end systems. After cataloging the main sources of external and internal nondeterminism, we summarize two thrusts in our current research: (1) mechanisms to control internal nondetermin-ism by active schedule control, and (2) techniques that may help assess the extent of result nondeterminism in ﬂoating point calculations.
Cardiac Responses during Stimulation of the Dorsal Motor Nucleus and Nucleus Ambiguus in the Cat

Studies were performed to determine the role of the dorsal motor nucleus (DMN) and nucleus ambiguus (NA) in cardiac control in cats. Heart rate (HR), mean arterial blood pressure (MABP), ventricular contractility, left ventricular end-diastolic pressure (LVEDP), and right ventricu- lar end-diastolic pressure (RVEDP) were monitored in anesthetized, paralyzed and /J-blocked animals. The rate of rise of the rising limb of the left ventricular pressure curve (dP/dt) and the output of a strain gauge sutured to the right ventricle (SGF) served as indices of ventricular contractility. Pacing electrodes were inserted into the ventricular myocardium and stimulating electrodes were stereotaxi- cally placed in the DMN and NA. The nuclei were stimulated with and without cardiac pacing, before and after ipsilateral vagotomy. DMN stimulation produced decreases in MABP, dP/dt, and SGF, no HR change, and increases in LVEDP and RVEDP. HR and MABP decreased and dP/dt, SGF, LVEDP, and RVEDP increased with NA stimulation. The responses to NA stimulation were abolished by ventricular pacing. The responses to stimulating either nucleus were abolished by ipsilateral vagotomy. The decreases in dP/dt and SGF with DMN activation were not secondary to preload decreases since LVEDP and RVEDP increased during stimulation. However, since the dP/dt and SGF changes during NA stimulation were abolished by cardiac pacing, the responses were secondary to bradycardia. The data suggest cardiac vagal preganglionic somata are organized according to physiological function. Cell bodies of the DMN control ventricular contractility whereas NA somata are involved in HR control. Circ Res 46: 606-611, 1980
Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

The objective of this work was to prepare an oil/water glimepiride (GM) microemulsion (ME) for oral administration to improve its solubility and enhance its bioavailability. Based on a solubility study, pseudoternary phase diagrams, and Box–Behnken design, the oil/water GMME formulation was optimized and prepared. GMME was characterized by dynamic laser light scattering, zeta potential, transmission electron microscopy, and viscosity. The in vitro drug release, storage stability, pharmacodynamics, and pharmacokinetics of GMME were investigated. The optimized GMME was composed of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol (cosurfactant), and increased GM solubility up to 544.6±4.91 µg/mL. The GMME was spherical in shape. The particle size and its polydispersity index were 38.9±17.46 nm and 0.266±0.057, respectively. Meanwhile, the GMME was physicochemically stable at 4°C for at least 3 months. The short-term efficacy in diabetic mice provided the proof that blood glucose had a consistent and significant reduction at a dose of 375 µg/kg whether via IP injection or IG administration of GMME. Compared with the glimepiride suspensions or glimepiride-meglumine complex solution, the pharmacokinetics of GMME in Wistar rats via IG administration exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability. There was a good correlation of GMME between the in vitro release values and the in vivo oral absorption. ME could be an effective oral drug delivery system to improve bioavailability of GM.
Social Media and Social Work: The Challenges of a New Ethical Space

ABSTRACT Social media and other online technologies have transformed communication between social workers and service users, with many practitioners engaging and working with clients through social networking sites. While there are numerous ethical issues associated with online practice related to conﬁdentiality, dual relationships, and boundary crossing, there is lack of clarity about how to deal with such issues. This article uses a case example to develop a nuanced understanding of ethical issues and ethical behaviour in online spaces. We argue that social workers need to link their knowledge of the complex interplay between discourses that underpin daily practice like those related to power, permanency, authorship, audience, embodiment, and professionalism to social media created spaces. In doing this, social workers must retain their commitment to ethical values and critical reflective practice. We conclude with recommendations for education, research, and practice.
Advection-dominated Inflow/Outflows from Evaporating Accretion Disks

In this Letter we investigate the properties of advection-dominated accretion flows (ADAFs) fed by the evaporation of a Shakura-Sunyaev accretion disk (SSD). In our picture, the ADAF fills the central cavity evacuated by the SSD and extends beyond the transition radius into a coronal region. We find that, because of global angular momentum conservation, a significant fraction of the hot gas flows away from the black hole, forming a transsonic wind, unless the injection rate depends only weakly on radius (if r2 ∝ r-ξ, ξ < 1/2). The Bernoulli number of the inflowing gas is negative if the transition radius is ≲100 Schwarzschild radii, so matter falling into the hole is gravitationally bound. The ratio of inflowing to outflowing mass is ≈1/2, so in these solutions the accretion rate is of the same order as in standard ADAFs and much larger than in advection-dominated inflow/outflow models. The possible relevance of evaporation-fed solutions to accretion flows in black hole X-ray binaries is briefly discussed.
Licensing Trouble

This article addresses a proposal by Katzir (2011) that licensors are crucially involved in definiteness and gender marking in Danish, Icelandic, and Greek. We identify several morphological patterns in Icelandic and Danish that are predicted to be impossible under Katzir’s theory and argue that these languages do not support the existence of licensors. Instead, we propose an account within the framework of Distributed Morphology, arguing that the patterns of gender and definiteness marking seen in these languages are the result of competition for insertion between well-motivated Vocabulary items. In a sense, then, we argue for a more traditional and theoretically simpler analysis of agreement in the languages.
Units of analysis in syllabus design: The case for task

While rarely the case in practice, proposals for language teaching ideally involve theoretically coherent, empirically grounded choices among options in each of six areas: needs identification, syllabus design, methodology design, materials writing, testing, and program evaluation. Saying that the decisions should be theoretically coherent means that they should follow from our current understanding of how the process we are trying to facilitate works in this case, our theory of how people learn second languages. We are obliged to have recourse to theory when making some decisions for the . simple reason that, while a good deal about second language acquisition (SLA) has been discovered empirically, many aspects of what has been observed are incomplete or only partially understood. It would be preferable, of course, to base all the choices on empirical findings as to what works or is most effective in the classroom, but the current state of knowledge does not permit that. Where is one to begin?
A randomization-based perspective of analysis of variance: a test statistic robust to treatment effect heterogeneity

Fisher randomization tests for Neyman's null hypothesis of no average treatment effects are considered in a finite population setting associated with completely randomized experiments with more than two treatments. The consequences of using the F statistic to conduct such a test are examined both theoretically and computationally, and it is argued that under treatment effect heterogeneity, use of the F statistic can severely inflate the type I error of the Fisher randomization test. An alternative test statistic is proposed, its asymptotic distributions under Fisher's and Neyman's null are derived, and its advantages demonstrated.
Fibulin-2 Is a Driver of Malignant Progression in Lung Adenocarcinoma

The extracellular matrix of epithelial tumors undergoes structural remodeling during periods of uncontrolled growth, creating regional heterogeneity and torsional stress. How matrix integrity is maintained in the face of dynamic biophysical forces is largely undefined. Here we investigated the role of fibulin-2, a matrix glycoprotein that functions biomechanically as an inter-molecular clasp and thereby facilitates supra-molecular assembly. Fibulin-2 was abundant in the extracellular matrix of human lung adenocarcinomas and was highly expressed in tumor cell lines derived from mice that develop metastatic lung adenocarcinoma from co-expression of mutant K-ras and p53. Loss-of-function experiments in tumor cells revealed that fibulin-2 was required for tumor cells to grow and metastasize in syngeneic mice, a surprising finding given that other intra-tumoral cell types are known to secrete fibulin-2. However, tumor cells grew and metastasized equally well in Fbln2-null and -wild-type littermates, implying that malignant progression was dependent specifically upon tumor cell-derived fibulin-2, which could not be offset by other cellular sources of fibulin-2. Fibulin-2 deficiency impaired the ability of tumor cells to migrate and invade in Boyden chambers, to create a stiff extracellular matrix in mice, to cross-link secreted collagen, and to adhere to collagen. We conclude that fibulin-2 is a driver of malignant progression in lung adenocarcinoma and plays an unexpected role in collagen cross-linking and tumor cell adherence to collagen.
Re-evaluation of G-quadruplex propensity with G4Hunter

Critical evidence for the biological relevance of G-quadruplexes (G4) has recently been obtained in seminal studies performed in a variety of organisms. Four-stranded G-quadruplex DNA structures are promising drug targets as these non-canonical structures appear to be involved in a number of key biological processes. Given the growing interest for G4, accurate tools to predict G-quadruplex propensity of a given DNA or RNA sequence are needed. Several algorithms such as Quadparser predict quadruplex forming propensity. However, a number of studies have established that sequences that are not detected by these tools do form G4 structures (false negatives) and that other sequences predicted to form G4 structures do not (false positives). Here we report development and testing of a radically different algorithm, G4Hunter that takes into account G-richness and G-skewness of a given sequence and gives a quadruplex propensity score as output. To validate this model, we tested it on a large dataset of 392 published sequences and experimentally evaluated quadruplex forming potential of 209 sequences using a combination of biophysical methods to assess quadruplex formation in vitro. We experimentally validated the G4Hunter algorithm on a short complete genome, that of the human mitochondria (16.6 kb), because of its relatively high GC content and GC skewness as well as the biological relevance of these quadruplexes near instability hotspots. We then applied the algorithm to genomes of a number of species, including humans, allowing us to conclude that the number of sequences capable of forming stable quadruplexes (at least in vitro) in the human genome is significantly higher, by a factor of 2–10, than previously thought.
Integrating Traditional Medicine into Modern Inflammatory Diseases Care: Multitargeting by Rhus verniciflua Stokes

Despite the fact that numerous researches were performed on prevention and treatment of inflammation related diseases, the overall incidence has not changed remarkably. This requires new approaches to overcome inflammation mediated diseases, and thus traditional medicine could be an efficacious source for prevention and treatment of these diseases. In this review, we discuss the contribution of traditional medicine, especially Rhus verniciflua Stokes, to modern medicine against diverse inflammation mediated diseases. Traditionally, this remedy has been used in Eastern Asia for the treatment of gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of Rhus verniciflua Stokes against such disorders and diseases. Various chemical constituents have been identified from this plant, including phenolic acid, and flavonoids. Cell-based studies have exhibited the potential of this as antibacterial, antioxidant, neuroprotective, anti-inflammatory, growth inhibitory, and anticancer activities. Enormous animal studies have shown the potential of this against proinflammatory diseases, neurodegenerative diseases, diabetes, liver diseases, and chemical insults. At the molecular level, this medicinal plant has been shown to modulate diverse cell-signaling pathways. In clinical studies, Rhus verniciflua Stokes has shown efficacy against various cancer patients such as colorectal, gastric, hepatic, renal, pancreatic, and pulmonary cancers. Thus, this remedy is now exhibiting activities in the clinic.
Plasminogen/Plasmin Modulates Bone Metabolism by Regulating the Osteoblast and Osteoclast Function*

The contribution of plasminogen (Plg)/plasmin, which have claimed to be the main fibrinolytic regulators in the bone metabolism, remains unclear. This study evaluated how the absence of Plg affects the function of osteoblast (OB) and osteoclast (OC). There was a larger population of pre-OCs in bone marrow-derived cells from the Plg−/− mice than the population of that from the WT mice. In addition, the absence of Plg suppressed the expression of osteoprotegerin in OBs. Moreover, an exogenous plasmin clearly induced the osteoprotegerin expression in Plg−/− OBs. The osteoclastogenesis of RAW264.7 mouse monocyte/macrophage lineage cells in co-culture with OBs from the Plg−/− mice was significantly accelerated in comparison with that in co-culture with OBs from the WT mice. Intriguingly, the accelerated OC differentiation of RAW264.7 cells co-cultured with Plg−/− OBs was clearly suppressed by the treatment of an exogenous plasmin. Consequently, Plg−/− mice display decreased bone mineral density. These findings could eventually lead to the development of new clinical therapies for bone disease caused by a disorder of the fibrinolytic system.
Successful Graduate Students’ Perceptions of Characteristics of Online Learning Environments

The purpose of this study was to examine issues related to online graduate course effectiveness, and graduate student perceptions of characteristics of online learning environments and their effectiveness, and to explore the relationship between graduate student perceptions and student success in online courses. The research methodology employed was that of survey research, using the Graduate Student Online Learning Environment Survey instrument, targeted at graduate students enrolled in online courses at the University of Tennessee in Knoxville. A total of 238 graduate students participated in this study. Findings revealed that approximately 87.4% of graduate students reported positive online learning experiences. Participants identified themselves as highly self-directed learners. Several critical individual characteristics including marital status, employment status, student status, future enrollment planning, enrollment in online programs, and number of online courses played a moderating role in online graduate students’ online course learning. However, based on the data from this study, no relationships were found among levels of age, gender, race/ethnicity, and previous online course experience and graduate students’ online course learning perceptions. Only a small portion (3.4%) of graduate students who responded to the survey reported online course non-completion in the fall semester of 2014.
Link prediction in weighted networks: The role of weak ties

Plenty of algorithms for link prediction have been proposed and were applied to various real networks. Among these algorithms, the weights of links are rarely taken into account. In this letter, we use local similarity indices to estimate the likelihood of the existence of links in weighted networks, including Common Neighbor, Adamic-Adar Index, Resource Allocation Index, and their weighted versions. We have tested the prediction accuracy on real social, technological and biological networks. Overall speaking, the resource allocation index performs best. To our surprise, sometimes the weighted indices perform even worse than the unweighted indices, which reminds us of the well-known Weak-Ties Theory. Further experimental study shows that the weak ties play a significant role in the link prediction, and to emphasize the contributions of weak ties can remarkably enhance the prediction accuracy for some networks. We give a semi-quantitative explanation based on the motif analysis. This letter provides a start point for the possible weak-ties theory in information retrieval.
Comparison between Capsule Endoscopy and Magnetic Resonance Enterography for the Detection of Polyps of the Small Intestine in Patients with Familial Adenomatous Polyposis

Objective. The objective of this study was to assess the utility of magnetic resonance enterography (MRE) compared with capsule endoscopy (CE) for the detection of small-bowel polyps in patients with familial adenomatous polyposis (FAP). Methods. Patients underwent MRE and CE. The polyps were classified according to size of polyp: <5 mm (small size), 5–10 mm (medium size), or >10 mm (large size). The location (jejunum or ileum) and the number of polyps (1–5, 6–20, >20) detected by CE were also assessed. MRE findings were compared with the results of CE. Results. Small-bowel polyps, were detected by CE in 4 of the 6 (66%) patients. Three patients had small-sized polyps and one patient had medium-sized polyps. CE detected polyps in four patients that, were not shown on MRE. Desmoid tumors were detected on anterior abdominal wall by MRE. Conclusion. In patients with FAP, CE can detect small-sized polyps in the small intestine not seen with MRE whereas MRE yields additional extraintestinal information.