Miracle-dz/UniFAR-FTUs huggingface dataset:
Transient expression of Ym1, a heparin‐binding lectin, during developmental hematopoiesis and inflammation

Ym1, a secretory protein transiently produced by activated peritoneal macrophages elicited by parasitic infections, has been identified as a novel heparin‐binding lectin. X‐ray crystallography study revealed that Ym1 has a β/α barrel structure with a carbohydrate‐binding cleft similar to that of triose‐phosphate isomerases. To further delineate the physiological significance of Ym1, we examined its expression patterns during mouse embryonic development and inflammation states elicited by agents other than parasitic infections in the peritoneal cavity and brain. This is the first report revealing prominent expression of Ym1 in early myeloid precursor cells of hematopoietic tissues—initially in the yolk sac and subsequently in fetal liver, spleen, and bone marrow. In nonhematopoietic systems, Ym1 was not detected in most of the tissues examined, with the exception of lung. Although no expression was detected up to gestation day 16.5 (E16.5), an increasing level of Ym1 expression in lung was detected from E18.5 on and persisted through adulthood. While most resident macrophages in various tissues examined are Ym1‐negative, transient expression of Ym1 may be induced in their activated counterparts during inflammation in response to different stimuli in vivo, ranging from various chemical agents to brain injuries. The temporal and spatial expression in myeloid precursors and its transient induction in activated macrophages support the notion that Ym1 may be involved in hematopoiesis and inflammation. In addition, its putative functional association with heparin/heparan sulfate is discussed.
Astrocyte activation and reactive gliosis

Astrocytes become activated (reactive) in response to many CNS pathologies, such as stroke, trauma, growth of a tumor, or neurodegenerative disease. The process of astrocyte activation remains rather enigmatic and results in so‐called “reactive gliosis,” a reaction with specific structural and functional characteristics. In stroke or in CNS trauma, the lesion itself, the ischemic environment, disrupted blood‐brain barrier, the inflammatory response, as well as in metabolic, excitotoxic, and in some cases oxidative crises—all affect the extent and quality of reactive gliosis. The fact that astrocytes function as a syncytium of interconnected cells both in health and in disease, rather than as individual cells, adds yet another dimension to this picture. This review focuses on several aspects of astrocyte activation and reactive gliosis and discusses its possible roles in the CNS trauma and ischemia. Particular emphasis is placed on the lessons learnt from mouse genetic models in which the absence of intermediate filament proteins in astrocytes leads to attenuation of reactive gliosis with distinct pathophysiological and clinical consequences. © 2005 Wiley‐Liss, Inc.
Trust, Satisfaction, and Online Repurchase Intention: The Moderating Role of Perceived Effectiveness of E-Commerce Institutional Mechanisms

The effects of e-commerce institutional mechanisms on trust and online purchase have traditionally been understood in the initial online purchase context. This study extends this literature by exploring the role of e-commerce institutional mechanisms in the online repurchase context. In doing so, it responds to the emerging call for understanding the institutional context under which customer trust operates in an e-commerce environment. Specifically, this study introduces a key moderator, perceived effectiveness of e-commerce institutional mechanisms (PEEIM), to the relationships between trust, satisfaction, and repurchase intention. Drawing on the theory of organizational trust, and based on a survey of 362 returning online customers, we find that PEEIM negatively moderates the relationship between trust in an online vendor and online customer repurchase intention, as it decreases the importance of trust to promoting repurchase behavior. We also find that PEEIM positively moderates the relationship between customer satisfaction and trust as it enhances the customer's reliance on past transaction experience with the vendor to reevaluate trust in the vendor. Consistent with the predictions made in the literature, PEEIM does not directly affect trust or repurchase intention. Academic and practical implications and future research directions are discussed.
AP-1 family members act with Sox9 to promote chondrocyte hypertrophy

An analysis of Sox9 binding profiles in developing chondrocytes identified marked enrichment of an AP-1-like motif. Here, we have explored the functional interplay between Sox9 and AP-1 in mammalian chondrocyte development. Among AP-1 family members, Jun and Fosl2 were highly expressed within prehypertrophic and early hypertrophic chondrocytes. Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) showed a striking overlap in Jun- and Sox9-bound regions throughout the chondrocyte genome, reflecting direct binding of each factor to the same enhancers and a potential for protein-protein interactions within AP-1- and Sox9-containing complexes. In vitro reporter analysis indicated that direct co-binding of Sox9 and AP-1 at target motifs promoted gene activity. By contrast, where only one factor can engage its DNA target, the presence of the other factor suppresses target activation consistent with protein-protein interactions attenuating transcription. Analysis of prehypertrophic chondrocyte removal of Sox9 confirmed the requirement of Sox9 for hypertrophic chondrocyte development, and in vitro and ex vivo analyses showed that AP-1 promotes chondrocyte hypertrophy. Sox9 and Jun co-bound and co-activated a Col10a1 enhancer in Sox9 and AP-1 motif-dependent manners consistent with their combined action promoting hypertrophic gene expression. Together, the data support a model in which AP-1 family members contribute to Sox9 action in the transition of chondrocytes to the hypertrophic program. Summary: Genome-wide interaction analyses and mechanistic studies demonstrate that Sox9 and AP-1 family members collaborate to regulate the hypertrophic chondrocyte transition during skeletal development in mice.
Neural tube defects—disorders of neurulation and related embryonic processes

Neural tube defects (NTDs) are severe congenital malformations affecting 1 in every 1000 pregnancies. ‘Open’ NTDs result from failure of primary neurulation as seen in anencephaly, myelomeningocele (open spina bifida), and craniorachischisis. Degeneration of the persistently open neural tube in utero leads to loss of neurological function below the lesion level. ‘Closed’ NTDs are skin‐covered disorders of spinal cord structure, ranging from asymptomatic spina bifida occulta to severe spinal cord tethering, and usually traceable to disruption of secondary neurulation. ‘Herniation’ NTDs are those in which meninges, with or without brain or spinal cord tissue, become exteriorized through a pathological opening in the skull or vertebral column (e.g., encephalocele and meningocele). NTDs have multifactorial etiology, with genes and environmental factors interacting to determine individual risk of malformation. While over 200 mutant genes cause open NTDs in mice, much less is known about the genetic causation of human NTDs. Recent evidence has implicated genes of the planar cell polarity signaling pathway in a proportion of cases. The embryonic development of NTDs is complex, with diverse cellular and molecular mechanisms operating at different levels of the body axis. Molecular regulatory events include the bone morphogenetic protein and Sonic hedgehog pathways which have been implicated in control of neural plate bending. Primary prevention of NTDs has been implemented clinically following the demonstration that folic acid (FA), when taken as a periconceptional supplement, can prevent many cases. Not all NTDs respond to FA, however, and adjunct therapies are required for prevention of this FA‐resistant category. WIREs Dev Biol 2013, 2:213–227. doi: 10.1002/wdev.71
DataSteward: Using Dedicated Compute Nodes for Scalable Data Management on Public Clouds

A large spectrum of scientific applications, some generating data volumes exceeding petabytes, are currently being ported on clouds to build on their inherent elasticity and scalability. One of the critical needs in order to deal with this "data deluge" is an efficient, scalable and reliable storage. However, the storage services proposed by cloud providers suffer from high latencies, trading performance for availability. One alternative is to federate the local virtual disks on the compute nodes into a globally shared storage used for large intermediate or checkpoint data. This collocated storage supports a high throughput but it can be very intrusive and subject to failures that can stop the host node and degrade the application performance. To deal with these limitations we propose DataSteward, a data management system that provides a higher degree of reliability while remaining non-intrusive through the use of dedicated compute nodes. DataSteward harnesses the storage space of a set of dedicated VMs, selected using a topology-aware clustering algorithm, and has a lifetime dependent on the deployment lifetime. To capitalize on this separation, we introduce a set of scientific data processing services on top of the storage layer, that can overlap with the executing applications. We performed extensive experimentations on hundreds of cores in the Azure cloud: compared to state-of-the-art node selection algorithms, we show up to a 20% higher throughput, which improves the overall performance of a real life scientific application up to 45%.
Early commitment of yeast pre-mRNA to the spliceosome pathway

Pre-mRNA splicing in vitro is preceded by complex formation (spliceosome assembly). U2 small nuclear RNA (snRNA) is found in the earliest form of the spliceosome detected by native gel electrophoresis, both in Saccharomyces cerevisiae and in metazoan extracts. To examine the requirements for the formation of this early complex (band III) in yeast extracts, we cleaved the U2 snRNA by oligonucleotide-directed RNase H digestion. U2 snRNA depletion by this means inhibits both splicing and band III formation. Using this depleted extract, we were able to design a chase experiment which shows that a pre-mRNA substrate is committed to the spliceosome assembly pathway in the absence of functional U2 snRNP. Interactions occurring during the commitment step are highly resistant to the addition of an excess of unlabeled substrate and require little or no ATP. Sequence requirements for this commitment step have been analyzed by competition experiments with deletion mutants: both the 5' splice site consensus sequence and the branch point TACTAAC box sequence are necessary. These experiments strongly suggest that the initial assembly process requires a trans-acting factor(s) (RNA and/or proteins) that recognizes and stably binds to the two consensus sequences of the pre-mRNA prior to U2 snRNP binding.
Adaptive differences in gene expression in European flounder (Platichthys flesus)

Population structure was previously believed to be very limited or absent in classical marine fishes, but recently, evidence of weakly differentiated local populations has been accumulating using noncoding microsatellite markers. However, the evolutionary significance of such minute genetic differences remains unknown. Therefore, in order to elucidate the relationship between genetic markers and adaptive divergence among populations of marine fishes, we combined cDNA microarray and microsatellite analysis in European flounders (Platichthys flesus). We demonstrate that despite extremely low levels of neutral genetic divergence, a high number of genes were significantly differentially expressed between North Sea and Baltic Sea flounders maintained in a long‐term reciprocal transplantation experiment mimicking natural salinities. Several of the differentially regulated genes could be directly linked to fitness traits. These findings demonstrate that flounders, despite little neutral genetic divergence between populations, are differently adapted to local environmental conditions and imply that adaptation in gene expression could be common in other marine organisms with similar low levels of population subdivision.
Population Pharmacokinetics and Pharmacodynamics of Efavirenz, Nelfinavir, and Indinavir: Adult AIDS Clinical Trial Group Study 398

ABSTRACT The present population pharmacokinetic (PK) and pharmacodynamic (PD) study modeled the effects of covariates including drug adherence and the coadministration of protease inhibitors (PIs) on the pharmacokinetics of efavirenz (EFV) and the relationship between EFV exposure and virological failure in patients who failed initial PI treatment in Adult AIDS Clinical Trial Group (AACTG) study 398. We also report on the population PKs of the PIs nelfinavir (NFV) and indinavir (IDV). AACTG study 398 patients received EFV, amprenavir, adefovir dipivoxil, and abacavir and were randomized to take, in addition, one of the following: NFV, IDV, saquinavir (SQV), or placebo. The PK databases consisted of 531 EFV concentrations (139 patients), 219 NFV concentrations (75 patients), and 66 IDV concentrations (11 patients). Time to virological failure was ascertained for all patients in the PK databases. PK data were fit with a population PK model that assumed exclusive hepatic elimination (the well-stirred model). Notable findings with respect to EFV PK and PD are as follows. (i) The hepatic clearance of EFV is unaltered by NFV, IDV, or SQV coadministration. (ii) The hepatic clearance of EFV appears to be 28% higher in white non-Hispanics than in African Americans and Hispanics (P = 0.03). (iii) Higher adherence scores (as measured with the Medication Event Monitoring System) are associated with marginally increased levels of exposure to EFV. (iv) In patients with no prior experience with nonnucleoside reverse transcriptase inhibitors (NNRTIs), a given percent increase in the oral clearance (CL/F) of EFV is associated with a greater percent increase in the hazard of virological failure (P < 0.0003). Among NNRTI-experienced patients, however, hazard is relatively uncorrelated with EFV CL/F.
Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists

Phenytoin (PHT), valproic acid, and modern antiepileptic drugs (AEDs), eg, remacemide, loreclezole, and safinamide, are only effective within a maximum of 70%–80% of epileptic patients, and in many cases the clinical use of AEDs is restricted by their side effects. Therefore, a continuous need remains to discover innovative chemical entities for the development of active and safer AEDs. Ligands targeting central histamine H3 receptors (H3Rs) for epilepsy might be a promising therapeutic approach. To determine the potential of H3Rs ligands as new AEDs, we recently reported that no anticonvulsant effects were observed for the (S)-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propanamide (1). In continuation of our research, we asked whether anticonvulsant differences in activities will be observed for its R-enantiomer, namely, (R)-2-(4-(3-(piperidin-1-yl)propoxy)benzylamino)propaneamide (2) and analogs thereof, in maximum electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced convulsion models in rats having PHT and valproic acid (VPA) as reference AEDs. Unlike the S-enantiomer (1), the results show that animals pretreated intraperitoneally (ip) with the R-enantiomer 2 (10 mg/kg) were moderately protected in MES and STR induced models, whereas proconvulsant effect was observed for the same ligand in PTZ-induced convulsion models. However, animals pretreated with intraperitoneal doses of 5, 10, or 15 mg/kg of structurally bulkier (R)-enantiomer (3), in which 3-piperidinopropan-1-ol in ligand 2 was replaced by (4-(3-(piperidin-1-yl)propoxy)phenyl)methanol, and its (S)-enantiomer (4) significantly and in a dose-dependent manner reduced convulsions or exhibited full protection in MES and PTZ convulsions model, respectively. Interestingly, the protective effects observed for the (R)-enantiomer (3) in MES model were significantly greater than those of the standard H3R inverse agonist/antagonist pitolisant, comparable with those observed for PHT, and reversed when rats were pretreated with the selective H3R agonist R-(α)-methyl-histamine. Comparisons of the observed antagonistic in vitro affinities among the ligands 1–6 revealed profound stereoselectivity at human H3Rs with varying preferences for this receptor subtype. Moreover, the in vivo anticonvulsant effects observed in this study for ligands 1–6 showed stereoselectivity in different convulsion models in male adult rats.
Long-term increases in excitability in the CA1 region of rat hippocampus induced by beta-adrenergic stimulation: possible mediation by cAMP

The cellular mechanisms underlying beta-adrenergic potentiation in the CA1 region of the rat hippocampus were examined. A 10 min treatment with isoproterenol (ISO) induced a long-term depolarization of the pyramidal neurons that persisted for at least 30 min of washout; the ISO-induced decrease in the calcium-activated potassium conductance (afterhyperpolarization, or AHP) was similarly prolonged. The long-term excitability changes induced by ISO did not depend upon the calcium concentration of the medium and could be elicited in medium containing as little as 240 microM calcium. The persistent increase in population spike induced by ISO was mimicked by superfusion with several cAMP analogs and by forskolin (which directly activates adenylate cyclase), but not by the inactive dideoxyforskolin. Forskolin and cAMP analogs also induced decreases in AHPs that could be quite prolonged, but did not depolarize pyramidal neurons as consistently as did ISO. We hypothesize that activation of beta-adrenergic receptors in the CA1 region of hippocampus may induce an alteration of the hippocampal “state” that can persist for as long as several hours, during which the induction of other forms of plasticity may be enhanced.
The Spread of Influenza A(H1N1)pdm09 Virus in Madagascar Described by a Sentinel Surveillance Network

Background The influenza A(H1N1)pdm09 virus has been a challenge for public health surveillance systems in all countries. In Antananarivo, the first imported case was reported on August 12, 2009. This work describes the spread of A(H1N1)pdm09 in Madagascar. Methods The diffusion of influenza A(H1N1)pdm09 in Madagascar was explored using notification data from a sentinel network. Clinical data were charted to identify peaks at each sentinel site and virological data was used to confirm viral circulation. Results From August 1, 2009 to February 28, 2010, 7,427 patients with influenza-like illness were reported. Most patients were aged 7 to 14 years. Laboratory tests confirmed infection with A(H1N1)pdm09 in 237 (33.2%) of 750 specimens. The incidence of patients differed between regions. By determining the epidemic peaks we traced the diffusion of the epidemic through locations and time in Madagascar. The first peak was detected during the epidemiological week 47-2009 in Antananarivo and the last one occurred in week 07-2010 in Tsiroanomandidy. Conclusion Sentinel surveillance data can be used for describing epidemic trends, facilitating the development of interventions at the local level to mitigate disease spread and impact.
Cross-layer modeling and analysis on delayed ACK in IEEE 802.11

The general size of ACK packets which are essential components for reliable communications is relatively small in comparison with that of data packets. However, transmissions of ACK packets and data packets require the same amount of communication resource in terms of MAC, and the increase in the number of ACK packets reduces opportunities for the transmissions of data packets. Therefore, delayed ACK was proposed to reduce the number of ACK packets, and the receiver can send fewer ACK packets to the sender by using delayed ACK. On the contrary, in terms of transport layer, ACK packets have an important role of not only the notification of data reception but also increasing the size of sender's congestion window. Thus, the decrease in the number of ACK packets may be a serious impediment to the fast increase in the sender's congestion window. Consequently, a comprehensive cross-layer approach is essential to analyze the effect of delayed ACK in IEEE 802.11. In this paper, we conduct the modeling and the analysis on delayed ACK using the cross-layer approach and verify the modeling and the analysis through simulations. Based on the result of them, we present the direction for decision of optimal delayed ACK maximum count to maximize the performance of communications and network.
Analysis and design of current-fed high step up quasi-resonant DC-DC converter for fuel cell applications

A Soft-Switching DC-DC Converter with low voltage and current stresses on switches and high voltage gain is proposed in this paper. The voltage and current stresses of switches are considerably reduced. As a result a reduction of switching losses in turn ON and OFF states of switching is obtained. Also, using soft-switching method results lower losses. In the result of ZCS in output diodes, reverse recovery problem of diodes is alleviated. Because of total reduction of losses, efficiency is improved. The proposed converter is a quasi-resonant converter controlled by pulse width modulation (PWM) method.
Speed binning with path delay test in 150-nm technology

What would it take to reduce speed binning's dependency on functional testing? One answer is a structural at-speed test approach that can achieve the same effectiveness as functional testing. The authors of this article offer a formula to relate structural critical-path testing frequency to system operation frequency. They demonstrate that there can be a high correlation between frequencies resulting from structural testing and those resulting from functional testing.
The use of the BERCI DCI® Video Laryngoscope for teaching novices direct laryngoscopy and tracheal intubation *

Traditional teaching of laryngoscopy is difficult due to the trainer and trainee lacking a shared view. The Karl Storz BERCI DCI® Video Laryngoscope provides a video image for the trainer and a direct view identical to that of a standard laryngoscope for the trainee. Forty‐nine novice subjects were randomly assigned to a control group (n = 24) taught using a standard Macintosh laryngoscope or a study group (n = 25) taught using the Video Laryngoscope. Following training all subjects were assessed using a standard laryngoscope. Under simulated difficult airway conditions the study group performed better in terms of number of attempts (p = 0.02), number of repositioning manoeuvres required (p = 0.046) and teeth trauma (p = 0.034). The study group were more confident of the success of their tube placement (p = 0.035), found it easier than the control group (p = 0.042) and had improved knowledge of airway anatomy (p = 0.011). We conclude that video laryngoscopy confers benefits in the teaching of tracheal intubation.