Miracle-dz/UniFAR-FTUs huggingface dataset:
Sphingosine Phosphate Lyase Regulates Murine Embryonic Stem Cell Proliferation and Pluripotency through an S1P2/STAT3 Signaling Pathway

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that activates a family of G protein coupled-receptors (GPCRs) implicated in mammalian development, angiogenesis, immunity and tissue regeneration. S1P functions as a trophic factor for many cell types, including embryonic stem cells (ESCs). Sphingosine phosphate lyase (SPL) is an intracellular enzyme that catalyzes the irreversible degradation of S1P. We found SPL to be highly expressed in murine ESCs (mESCs). To investigate the role of SPL in mESC biology, we silenced SPL in mESCs via stable transfection with a lentiviral SPL-specific short hairpin RNA (shRNA) construct. SPL-knockdown (SPL-KD) mESCs showed a 5-fold increase in cellular S1P levels, increased proliferation rates and high expression of cell surface pluripotency markers SSEA1 and OCT4 compared to vector control cells. Compared to control mESCs, SPL-KD cells showed robust activation of STAT3 and a 10-fold increase in S1P2 expression. Inhibition of S1P2 or STAT3 reversed the proliferation and pluripotency phenotypes of SPL-KD mESCs. Further, inhibition of S1P2 attenuated, in a dose-dependent fashion, the high levels of OCT4 and STAT3 activation observed in SPL-KD mESCs. Finally, we showed that SPL-KD cells are capable of generating embryoid bodies from which muscle stem cells, called satellite cells, can be isolated. These findings demonstrate an important role for SPL in ESC homeostasis and suggest that SPL inhibition could facilitate ex vivo ESC expansion for therapeutic purposes.
Postoperative Changes in Sleep-disordered Breathing and Sleep Architecture in Patients with Obstructive Sleep Apnea

Background:Anesthetics, analgesics, and surgery may profoundly affect sleep architecture and aggravate sleep-related breathing disturbances. The authors hypothesized that patients with preoperative polysomnographic evidence of obstructive sleep apnea (OSA) would experience greater changes in these parameters than patients without OSA. Methods:After obtaining approvals from the Institutional Review Boards, consented patients underwent portable polysomnography preoperatively and on postoperative nights (N) 1, 3, 5, and 7 at home or in hospital. The primary and secondary outcome measurements were polysomnographic parameters of sleep-disordered breathing and sleep architecture. Results:Of the 58 patients completed the study, 38 patients had OSA (apnea hypopnea index [AHI] >5) with median preoperative AHI of 18 events per hour and 20 non-OSA patients had median preoperative AHI of 2. AHI was increased after surgery in both OSA and non-OSA patients (P < 0.05), with peak increase on postoperative N3 (OSA vs. non-OSA, 29 [14, 57] vs. 8 [2, 18], median [25th, 75th percentile], P < 0.05). Hypopnea index accounted for 72% of the postoperative increase in AHI. The central apnea index was low (median = 0) but was significantly increased on postoperative N1 in only non-OSA patients. Sleep efficiency, rapid eye movement sleep, and slow-wave sleep were decreased on N1 in both groups, with gradual recovery. Conclusions:Postoperatively, sleep architecture was disturbed and AHI was increased in both OSA and non-OSA patients. Although the disturbances in sleep architecture were greatest on postoperative N1, breathing disturbances during sleep were greatest on postoperative N3.
Actions of Endogenous Opioids on NMDA Receptor-Independent Long-Term Potentiation in Area CA3 of the Hippocampus

The opioid peptides represent a major class of neurotransmitter in the vertebrate nervous system and are prevalent in the hippocampus. There is considerable interest in the physiological function of the opioids contained in the mossy fiber pathway. The release of opioids from mossy fibers shows a strong frequency dependence. Long-term potentiation (LTP) at this synapse, an NMDA receptor-independent form of LTP, also depends on high-frequency synaptic activity, and this has led to speculation that endogenous opioids may be a critical factor in LTP induction. Previous reports using extracellular recordings have provided evidence for and against a role for opioids in mossy fiber LTP. Using single-cell recording techniques, we have tested the hypothesis that endogenous opioids are required for mossy fiber LTP induction. We recorded from a defined population of synapses that had EPSCs with fast rise times, short latencies, and monophasic decays, consistent with a proximally terminating synapse. The opioid antagonist naloxone prevented mossy fiber LTP in the rat, but had no effect on the commissural/associational system, a nonopioid-containing pathway. The action of naloxone was not mediated through disinhibition because GABAA receptors were pharmacologically blocked in these experiments. We also tested the hypothesis that variations in postsynaptic receptor subtype distribution between species might explain previous controversies regarding the role of endogenous opioids. In contrast to the rat, LTP of the mossy fiber field potential in guinea pig was not blocked by naloxone. Our data suggest that opioids may be the presynaptically released, frequency-dependent, associative factor for mossy fiber LTP induction.
Leptospirosis in India

' 4 Porter It has occurred sporadically the same the city. No two cases were seen in n ouse nor in the vicinity. come imder The six cases which have, so < ' onal incid^ observation had the following seasonal ^ ce Two cases occurred in 1933 and 2 }n December 1937, 1 m January Jn April 1938. Clinical features Three cases had a fatal termination and all became delirious before death. Acute onset, severe headache, agonizing pain all over the body, specially in the lumbar region, cramps in the calf muscles, conjunctival congestion, and marked jaundice were constant features. Four cases had bleeding from the gums and one of these also had epistaxis, melscna and patchy haemorrhages under the skin. There was suppression of urine in two cases. The urine of three patients was examined, this showed evidence of marked renal irritation, albumen, urinary deposits, casts (chiefly hyaline and granular), leucocytes and red blood cells. All the specimens were very highly coloured on account of the presence of bile. One of the patients developed lobar pneumonia but in no other case was there any evidence of respiratory complication. As none of our patients were seen before the sixth day of illness, the degree of pyrexia at the early stage could not be determined. Low-grade fever persisted for two weeks or more in all the three cases that recovered.
Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina

OBJECTIVE—Pathogenic mechanisms underlying diabetes-induced retinal dysfunction are not fully understood. The aim of the present study was to show the relationship of the renin-angiotensin system (RAS) with the synaptic vesicle protein synaptophysin and neuronal activity in the diabetic retina. RESEARCH DESIGN AND METHODS—C57BL/6 mice with streptozotocin-induced diabetes were treated with the angiotensin II type 1 receptor (AT1R) blocker telimsartan or valsartan, and retinal function was analyzed by electroretinography. Retinal production of the RAS components and phosphorylation of ERK (extracellular-signal regulated kinase) were examined by immunoblotting. Retinal mRNA and protein levels of synaptophysin were measured by quantitative RT-PCR and immunoblot analyses, respectively. In vitro, synaptophysin levels were also evaluated using angiotensin II–stimulated PC12D neuronal cells cultured with or without the inhibition of ERK signaling or the ubiquitin-proteasome system (UPS). RESULTS—Induction of diabetes led to a significant increase in retinal production of angiotensin II and AT1R together with ERK activation in the downstream of AT1R. AT1R blockade significantly reversed diabetes-induced electroretinography changes and reduction of synaptophysin protein, but not mRNA, levels in the diabetic retina. In agreement with the AT1R-mediated posttranscriptional downregulation of synaptophysin in vivo, in vitro application of angiotensin II to PC12D neuronal cells caused the UPS–mediated degradation of synaptophysin protein via AT1R, which proved to be induced by ERK activation. CONCLUSIONS—These data indicate the first molecular evidence of the RAS-induced synaptophysin degradation and neuronal dysfunction in the diabetic retina, suggesting the possibility of the AT1R blockade as a novel neuroprotective treatment for diabetic retinopathy.
Universality in Complex Wishart ensembles: The 2 cut case

We studied the universality of Wishart ensembles whose covariance matrix has 2 distinct eigenvalues. We studied the asymptotic limit when the number of both eigenvalues goes to infinity and obtained universality results. In this case, the limiting eigenvalue distribution can be supported on 1 or 2 disjoint intervals. We obtained a necessary and sufficient condition on the parameters such that the limiting distribution is supported on 2 disjoint intervals and have computed the eigenvalue density in the limit. Furthermore, by using Riemann-Hilbert analysis, we have shown that under proper rescaling of the eigenvalues, the limiting correlation kernel is given by the sine kernel and the Airy kernel in the bulk and the edge of the spectrum respectively. As a consequence, the behavior of the largest eigenvalue in this model is described by the Tracy-Widom distribution.
Detecting Erroneous Sentences using Automatically Mined Sequential Patterns

This paper studies the problem of identifying erroneous/correct sentences. The problem has important applications, e.g., providing feedback for writers of English as a Second Language, controlling the quality of parallel bilingual sentences mined from the Web, and evaluating machine translation results. In this paper, we propose a new approach to detecting erroneous sentences by integrating pattern discovery with supervised learning models. Experimental results show that our techniques are promising.
Phase I and Pharmacokinetic Study of Sunitinib in Pediatric Patients with Refractory Solid Tumors: A Children's Oncology Group Study

Purpose: Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor. The purpose of this study was to determine the recommended phase 2 dose, pharmacokinetics, pharmacodynamic effects, and preliminary antitumor activity of sunitinib in a pediatric population. Experimental Design: Patients who were 2 to 21 years of age with refractory solid tumors were eligible if they had measurable or evaluable disease and met baseline organ function requirements. Patients received sunitinib once daily for 28 days followed by a 14-day break between each cycle. Dose levels of 15 and 20 mg/m2/d were evaluated, with dose escalation based on a 3 + 3 design. Sunitinib pharmacokinetics and biomarkers of angiogenesis were also evaluated during the first cycle. Results: Twenty-three patients were treated (median age 13.9 years; range, 3.9–20.6 years). The most common toxicities were neutropenia, thrombocytopenia, elevated liver transaminases, gastrointestinal symptoms, and fatigue. Two patients developed dose-limiting reductions in cardiac ejection fraction prompting a protocol amendment to exclude patients with previous exposure to anthracyclines or cardiac radiation. In patients without these cardiac risk factors, the maximum tolerated dose (MTD) was 15 mg/m2/d. Steady-state plasma concentrations were reached by day 7. No objective responses were observed. Four patients with sarcoma and glioma had stable disease for 2 to 9 cycles. Conclusions: Cardiac toxicity precluded determination of a recommended dose for pediatric patients with previous anthracycline or cardiac radiation exposure. The MTD of sunitinib for patients without risk factors for cardiac toxicity is 15 mg/m2/d for 28 days followed by a 14-day break. Clin Cancer Res; 17(15); 5113–22. ©2011 AACR.
POPULATION DYNAMICS AND EPIDEMIOLOGY OF TOXOCARA CANIS IN DANISH RED FOXES

Toxocara canis, an intestinal helminth of canids with zoonotic potential, was found in 618 (59%) of 1,040 red foxes (Vulpes vulpes) collected from all Danish provinces (1997–2002). The prevalence and average worm burden were significantly higher for cubs than older foxes and in males than in females. A multiple logistic regression demonstrated that the prevalence was influenced significantly by sex and age of foxes in addition to location, season, and year of collection. The highest prevalence and worm burden were found in rural areas. The size and number of female worms was positively correlated to the fecal egg excretion. The length and fecundity of the worms was significantly higher in male foxes, and a general intensity dependence was suggested from a negative correlation between worm numbers and worm lengths. As compared to intestinal recovery of worms, somatic larvae were recovered from 20% of muscle samples and fecal eggs in 41% of fecal samples. The consistent finding of T. canis larvae in somatic tissues of naturally infected foxes is new.
Bilinear recurrences and addition formulae for hyperelliptic sigma functions

Abstract The Somos 4 sequences are a family of sequences satisfying a fourth order bilinear recurrence relation. In recent work, one of us has proved that the general term in such sequences can be expressed in terms of the Weierstrass sigma function for an associated elliptic curve. Here we derive the analogous family of sequences associated with an hyperelliptic curve of genus two. We show that the sequences associated with such curves satisfy bilinear recurrences of order 8. The proof requires an addition formula which involves the genus two Kleinian sigma function with its argument shifted by the Abelian image of the reduced divisor of a single point on the curve. The genus two recurrences are related to a Bäcklund transformation (BT) for an integrable Hamiltonian system, namely the discrete case (ii) Hénon-Heiles system.
The Limits of Price Discrimination

We analyze the welfare consequences of a monopolist having additional information about consumers' tastes, beyond the prior distribution; the additional information can be used to charge different prices to different segments of the market, i.e., carry out "third degree price discrimination. " We show that the segmentation and pricing induced by the additional information can achieve every combination of consumer and producer surplus such that: (i) consumer surplus is non-negative, (ii) producer surplus is at least as high as profits under the uniform monopoly price, and (iii) total surplus does not exceed the efficient gains from trade. As well as characterizing the welfare impact of price discrimination, we examine the limits of how prices and quantities can change under price discrimination. We also examine the limits of price discrimination in richer environments with quantity discrimination and limited ability to segment the market.
Oesophageal and sternohyal muscle fibres are novel Pax3-dependent migratory somite derivatives essential for ingestion

Striated muscles that enable mouth opening and swallowing during feeding are essential for efficient energy acquisition, and are likely to have played a fundamental role in the success of early jawed vertebrates. The developmental origins and genetic requirements of these muscles are uncertain. Here, we determine by indelible lineage tracing in mouse that fibres of sternohyoid muscle (SHM), which is essential for mouth opening during feeding, and oesophageal striated muscle (OSM), which is crucial for voluntary swallowing, arise from Pax3-expressing somite cells. In vivo Kaede lineage tracing in zebrafish reveals the migratory route of cells from the anteriormost somites to OSM and SHM destinations. Expression of pax3b, a zebrafish duplicate of Pax3, is restricted to the hypaxial region of anterior somites that generate migratory muscle precursors (MMPs), suggesting that Pax3b plays a role in generating OSM and SHM. Indeed, loss of pax3b function led to defective MMP migration and OSM formation, disorganised SHM differentiation, and inefficient ingestion and swallowing of microspheres. Together, our data demonstrate Pax3-expressing somite cells as a source of OSM and SHM fibres, and highlight a conserved role of Pax3 genes in the genesis of these feeding muscles of vertebrates.
The Sensitivity of Polar Ozone Depletion to Proposed Geoengineering Schemes

The large burden of sulfate aerosols injected into the stratosphere by the eruption of Mount Pinatubo in 1991 cooled Earth and enhanced the destruction of polar ozone in the subsequent few years. The continuous injection of sulfur into the stratosphere has been suggested as a “geoengineering” scheme to counteract global warming. We use an empirical relationship between ozone depletion and chlorine activation to estimate how this approach might influence polar ozone. An injection of sulfur large enough to compensate for surface warming caused by the doubling of atmospheric CO2 would strongly increase the extent of Arctic ozone depletion during the present century for cold winters and would cause a considerable delay, between 30 and 70 years, in the expected recovery of the Antarctic ozone hole.
Morphine or Ibuprofen for Post-Tonsillectomy Analgesia: A Randomized Trial

BACKGROUND: Pediatric sleep disordered breathing is often caused by hypertrophy of the tonsils and is commonly managed by tonsillectomy. There is controversy regarding which postsurgical analgesic agents are safe and efficacious. METHODS: This prospective randomized clinical trial recruited children who had sleep disordered breathing who were scheduled for tonsillectomy +/− adenoid removal. Parents were provided with a pulse oximeter to measure oxygen saturation and apnea events the night before and the night after surgery. Children were randomized to receive acetaminophen with either 0.2–0.5 mg/kg oral morphine or 10 mg/kg of oral ibuprofen. The Objective Pain Scale and Faces Scale were used to assess effectiveness on postoperative day 1 and day 5. The primary endpoint was changes in respiratory parameters during sleep. RESULTS: A total of 91 children aged 1 to 10 years were randomized. On the first postoperative night, with respect to oxygen desaturations, 86% of children did not show improvement in the morphine group, whereas 68% of ibuprofen patients did show improvement (14% vs 68%; P < .01). The number of desaturation events increased substantially in the morphine group, with an average increase of 11.17 ± 15.02 desaturation events per hour (P < .01). There were no differences seen in analgesic effectiveness, tonsillar bleeding, or adverse drug reactions. CONCLUSIONS: Ibuprofen in combination with acetaminophen provides safe and effective analgesia in children undergoing tonsillectomy. Post-tonsillectomy morphine use should be limited, as it may be unsafe in certain children.
Time-dependent CYP inhibition

Time-dependent inhibition (TDI) of CYP refers to a change in potency during an in vitro incubation or dosing period in vivo. Potential mechanisms include the formation of inhibitory metabolites and mechanism-based inhibition (MBI). In vitro experiments are configured to assess TDI and MBI is inferred, at least initially. MBI is more profound after multiple-dosing and the recovery period is independent of continued drug exposure. Advances in in vitro–in vivo extrapolations for competitive inhibition and the potential relationship between MBI and reactive metabolite-mediated toxicity, have redirected emphasis to CYP TDI. In contrast, with reversible inhibition, strategies for projecting the risks from TDI are less developed and the traditional I/Ki model often yields a dramatic underprediction. This review explores the contribution of TDI to drug–drug interactions and idiosyncratic drug toxicity.
Augmented Reality Experiences in Therapeutic Pedagogy: A Study with Special Needs Students

Information and Communication Technologies (ICTs) have played a major role in shaping our society, affecting nearly all aspects of our daily lives. In educational contexts, the ongoing technological revolution we are experiencing naturally calls for a transformation of traditional teaching and learning processes. The integration and efficient use of emergent technologies have become fundamental challenges in the educational domain. In this paper, we evaluate the use of Augmented Reality (AR) technology in a classroom with middle school special-needs students. Our primary goal is to quantitatively assess whether AR helps special-needs students to improve their results, performance, motivation, and other aspects of the learning process. Information was collected via pre and post questionnaires distributed to participants before and after an intervention. Our results serve as basis for improving future educational AR-related projects and materials.
IMPACT OF KM PRACTICES ON FIRMS ’ PERFORMANCE : A MEDIATING ROLE OF BUSINESS PROCESS CAPABILITY AND ORGANIZATIONAL LEARNING

This study tends to examine the mediating role of business process capabilities and organizational learning in order to validate the KM practices driven performance. A mediating model is proposed and confirmatory factor analysis is performed through structural equation modeling to assess the overall measurement model. The results of the study confirm that KM practices have positive and significant association on overall performance of firms and as well intermediate measures (business process capability and organizational learning) have positive and significant connection with KM practices and overall performance of firms. Further, the results of the study reveal that KM practices are partially rooted through business process capabilities and completely mediated by organizational learning. It suggests that both intermediate measures are complementary for KM practices driven performance more specifically the organizational learning. The results of the study postulate that KM practices provide foundation to KM-driven performance, where business process capability and organization learning are two important drivers for value creation process. An organization has bundle of knowledge resources and capabilities, so it should dedicate its efforts to identify and implement more KM practices as well for the improvement of business process capabilities and organizational learning to better realized KM-oriented performance.
Reclassification of Hart and Northwest Africa 6047: Criteria for distinguishing between CV and CK3 chondrites

The single parent body model for the CV and CK chondrites (Greenwood et al. ) was challenged by Dunn et al. ( ), who argued that magnetite compositions could not be reconciled by a single metamorphic sequence (i.e., CV3 → CK3 → CK4–6). Cr isotopic compositions, which are distinguishable between the CV and CK chondrites, also support two different parent bodies (Yin et al. ). Despite this, there are many petrographic and mineralogical similarities between the unequilibrated (petrologic type 3) CK chondrites and the CV chondrites (also type 3), which may result in misclassification of samples. Hart and Northwest Africa 6047 (NWA 6047) are an excellent example of this. In this study, we revisit the classification of Hart and NWA 6047 using magnetite compositions, petrography, and compositions of olivine, the most ubiquitous mineral in both CV and CK chondrites. Not only do our results suggest that NWA 6047 and Hart were misclassified, but our assessment of CV and CK3 chondrites has also led to the development of criteria that can be used to distinguish between CV and CK3 chondrites. These criteria include: abundances of Cr2O3, TiO2, NiO, and Al2O3 in magnetite; Fa content and NiO abundance of matrix olivine; FeO content of chondrules; and the chondrule:matrix ratio. Classification as a CV chondrite is also supported by the presence of igneous chondrule rims, calcium‐aluminum‐rich inclusions, and an elongated petrofabric. However, none of these petrographic characteristics can be used conclusively to distinguish between CV and CK3 chondrites.