Miracle-dz/UniFAR-FTUs huggingface dataset:
A Small-Molecule Inhibitor of Enterocytic Microsomal Triglyceride Transfer Protein, SLx-4090: Biochemical, Pharmacodynamic, Pharmacokinetic, and Safety Profile

First-generation microsomal triglyceride transfer protein (MTP) inhibitors were designed to inhibit hepatic MTP and provide a novel treatment of dyslipidemia. Effective at lowering low-density lipoprotein-cholesterol (LDL-C), these inhibitors also elevate liver enzymes and induce hepatic steatosis in animals and humans. MTP is highly expressed in the enterocytes, lining the lumen of the jejunum, and is critical in the production of chylomicrons assembled from lipid/cholesterol and their transfer into systemic circulation. 6-(4′-Trifluoromethyl-6-methoxy-biphenyl-2-ylcarboxamido)-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid phenyl ester (SLx-4090) (IC50 value ∼8 nM) was designed to inhibit only MTP localized to enterocytes. In Caco-2 cells SLx-4090 inhibited apolipoprotein B (IC50 value ∼9.6 nM) but not apolipoprotein A1 secretion. Administered orally to rats SLx-4090 reduced postprandial lipids by >50% with an ED50 value ∼7 mg/kg. SLx-4090 was not detected in the systemic or portal vein serum of the animals (lower limit of quantitation ∼5 ng/ml) after single or multiple oral doses in fasted rodents. When coadministered with tyloxapol, SLx-4090 did not inhibit the secretion of hepatic triglycerides (TG), consistent with the absence of systemic exposure. Chronic treatment with SLx-4090 in mice maintained on a high-fat diet decreased LDL-C and TG and resulted in weight loss without the elevation of liver enzymes or an increase in hepatic fat. The compound did not result in toxicity when administered to rats for 90 days at a dose of 1000 mg/kg per day. These data support the concept that the inhibition of enterocytic MTP could serve as a useful strategy in the treatment of metabolic disorders.
Shifts in Economic Geography and their Causes

This paper analyses some of the forces that are changing the spatial distribution of activity in the world economy. It draws on the 'new economic geography' literature to argue the importance of increasing returns to scale and cumulative causation processes in shaping the productivity and comparative advantage of different regions. In the presence of such increasing returns there may be persistent spatial disparities in productivity. Economic development will tend to be 'lumpy', with some regions (countries, or smaller areas such as cities) experiencing rapid growth and others being left behind.
Decidualization and Syndecan-1 Knock Down Sensitize Endometrial Stromal Cells to Apoptosis Induced by Embryonic Stimuli

Human embryo invasion and implantation into the inner wall of the maternal uterus, the endometrium, is the pivotal process for a successful pregnancy. Whereas disruption of the endometrial epithelial layer was already correlated with the programmed cell death, the role of apoptosis of the subjacent endometrial stromal cells during implantation is indistinct. The aim was to clarify whether apoptosis plays a role in the stromal invasion and to characterize if the apoptotic susceptibility of endometrial stromal cells to embryonic stimuli is influenced by decidualization and Syndecan-1. Therefore, the immortalized human endometrial stromal cell line St-T1 was used to first generate a new cell line with a stable Syndecan-1 knock down (KdS1), and second to further decidualize the cells with progesterone. As a replacement for the ethically inapplicable embryo all cells were treated with the embryonic factors and secretion products interleukin-1β, interferon-γ, tumor necrosis factor-α, transforming growth factor-β1 and anti-Fas antibody to mimic the embryo contact. Detection of apoptosis was verified via Caspase ELISAs, PARP cleavage and Annexin V staining. Apoptosis-related proteins were investigated via antibody arrays and underlying signaling pathways were analyzed by Western blot. Non-decidualized endometrial stromal cells showed a resistance towards apoptosis which was rescinded by decidualization and Syndecan-1 knock down independent of decidualization. This was correlated with an altered expression of several pro- and anti-apoptotic proteins and connected to a higher activation of pro-survival Akt in non-differentiated St-T1 as an upstream mediator of apoptotis-related proteins. This study provides insight into the largely elusive process of implantation, proposing an important role for stromal cell apoptosis to successfully establish a pregnancy. The impact of Syndecan-1 in attenuating the apoptotic signal is particularly interesting in the light of an already described influence on pregnancy disorders and therefore might provide a useful clinical tool in the future to prevent pregnancy complications provoked by inadequate implantation.
Altered small‐world brain functional networks in children with attention‐deficit/hyperactivity disorder

In this study, we investigated the changes in topological architectures of brain functional networks in attention‐deficit/hyperactivity disorder (ADHD). Functional magnetic resonance images (fMRI) were obtained from 19 children with ADHD and 20 healthy controls during resting state. Brain functional networks were constructed by thresholding the correlation matrix between 90 cortical and subcortical regions and further analyzed by applying graph theoretical approaches. Experimental results showed that, although brain networks of both groups exhibited economical small‐world topology, altered functional networks were demonstrated in the brain of ADHD when compared with the normal controls. In particular, increased local efficiencies combined with a decreasing tendency in global efficiencies found in ADHD suggested a disorder‐related shift of the topology toward regular networks. Additionally, significant alterations in nodal efficiency were also found in ADHD, involving prefrontal, temporal, and occipital cortex regions, which were compatible with previous ADHD studies. The present study provided the first evidence for brain dysfunction in ADHD from the viewpoint of global organization of brain functional networks by using resting‐state fMRI. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Ecological correlates of population genetic structure: a comparative approach using a vertebrate metacommunity

Identifying ecological factors associated with population genetic differentiation is important for understanding microevolutionary processes and guiding the management of threatened populations. We identified ecological correlates of several population genetic parameters for three interacting species (two garter snakes and an anuran) that occupy a common landscape. Using multiple regression analysis, we found that species interactions were more important in explaining variation in population genetic parameters than habitat and nearest-neighbour characteristics. Effective population size was best explained by census size, while migration was associated with differences in species abundance. In contrast, genetic distance was poorly explained by the ecological correlates that we tested, but geographical distance was prominent in models for all species. We found substantially different population dynamics for the prey species relative to the two predators, characterized by larger effective sizes, lower gene flow and a state of migration-drift equilibrium. We also identified an escarpment formed by a series of block faults that serves as a barrier to dispersal for the predators. Our results suggest that successful landscape-level management should incorporate genetic and ecological data for all relevant species, because even closely associated species can exhibit very different population genetic dynamics on the same landscape.
Ensemble Sparse Models for Image Analysis

Sparse representations with learned dictionaries have been successful in several image analysis applications. In this paper, we propose and analyze the framework of ensemble sparse models, and demonstrate their utility in image restoration and unsupervised clustering. The proposed ensemble model approximates the data as a linear combination of approximations from multiple \textit{weak} sparse models. Theoretical analysis of the ensemble model reveals that even in the worst-case, the ensemble can perform better than any of its constituent individual models. The dictionaries corresponding to the individual sparse models are obtained using either random example selection or boosted approaches. Boosted approaches learn one dictionary per round such that the dictionary learned in a particular round is optimized for the training examples having high reconstruction error in the previous round. Results with compressed recovery show that the ensemble representations lead to a better performance compared to using a single dictionary obtained with the conventional alternating minimization approach. The proposed ensemble models are also used for single image superresolution, and we show that they perform comparably to the recent approaches. In unsupervised clustering, experiments show that the proposed model performs better than baseline approaches in several standard datasets.
Emergency Reversal of Anticoagulation After Intracerebral Hemorrhage

Background and Purpose Although intracerebral hemorrhage is one of the most serious complications during oral anticoagulant therapy, there are no guidelines on emergency treatment with respect to reversal of anticoagulation effect in these patients. Methods We retrospectively compared laboratory data and clinical features in 17 cases of anticoagulantrelated intracerebral hemorrhage treated with prothrombin complex concentrate (n=10) or freshfrozen plasma (n=7). Results In the group of patients treated with prothrombin complex concentrate, the mean prothrombin time decreased from 2.83 to 1.22 International Normalized Ratio within 4.8 hours, compared with a decrease from 2.97 to 1.74 within 7.3 hours in those given fresh frozen plasma (i.e., four to five times more rapidly after treatment with prothrombin complex concentrate) (p< 0.001). Symptoms and signs of intracerebral hemorrhage, measured on an eight-graded Reaction Level Scale, progressed on average 0.2 grades in patients given prothrombin complex concentrate compared with 1.9 grades in those given fresh-frozen plasma (p<0.05). In patients with prothrombin values above 1.46, clinical progression within 12 hours occurred in five of six cases. Conclusions Treatment with prothrombin complex concentrate reverses anticoagulation more rapidly than fresh-frozen plasma, which might be of importance for the prevention of further bleeding.
Plexin-D1 Is a Novel Regulator of Germinal Centers and Humoral Immune Responses

Long-lived humoral immune responses depend upon the generation of memory B cells and long-lived plasma cells during the germinal center (GC) reaction. These memory compartments, characterized by class-switched IgG and high-affinity Abs, are the basis for successful vaccination. We report that a new member of the plexin family of molecules, plexin-D1, controls the GC reaction and is required for secondary humoral immune responses. Plexin-D1 was not required for B cell maturation, marginal zone precursor development, dark and light zone formation, Igλ+ and Igκ+ B cell skewing, B1/B2 development, and the initial extrafollicular response. Plexin-D1 expression was increased following B cell activation, and PlxnD1−/− mice exhibited defective GC reactions during T-dependent immune activation. PlxnD1−/− B cells showed a defect in migration toward the GC chemokines, CXCL12, CXCL13, and CCL19. Accordingly, PlxnD1−/− mice exhibited defective production of IgG1 and IgG2b, but not IgG3 serum Ab, accompanied by reductions in long-lived bone marrow plasmacytes and recall humoral memory responses. These data show a new role for immune plexins in the GC reaction and generation of immunologic memory.
Development of a Multi-Channel Piezoelectric Acoustic Sensor Based on an Artificial Basilar Membrane

In this research, we have developed a multi-channel piezoelectric acoustic sensor (McPAS) that mimics the function of the natural basilar membrane capable of separating incoming acoustic signals mechanically by their frequency and generating corresponding electrical signals. The McPAS operates without an external energy source and signal processing unit with a vibrating piezoelectric thin film membrane. The shape of the vibrating membrane was chosen to be trapezoidal such that different locations of membrane have different local resonance frequencies. The length of the membrane is 28 mm and the width of the membrane varies from 1 mm to 8 mm. Multiphysics finite element analysis (FEA) was carried out to predict and design the mechanical behaviors and piezoelectric response of the McPAS model. The designed McPAS was fabricated with a MEMS fabrication process based on the simulated results. The fabricated device was tested with a mouth simulator to measure its mechanical and piezoelectrical frequency response with a laser Doppler vibrometer and acoustic signal analyzer. The experimental results show that the as fabricated McPAS can successfully separate incoming acoustic signals within the 2.5 kHz–13.5 kHz range and the maximum electrical signal output upon acoustic signal input of 94 dBSPL was 6.33 mVpp. The performance of the fabricated McPAS coincided well with the designed parameters.
Das Gruppenprogramm «Depression bewältigen» und seine Varianten – eine aktualisierte Metaanalyse

The Coping with Depression Course and Its Variants – an Updated Meta-Analysis Background: The Coping with Depression Course is a psychoeducational group program for the treatment and prevention of unipolar depression. During the last years, variants of the program have been developed for different settings. Material and Methods: The present metaanalysis summarizes existing efficacy studies on the program. A total of 24 German and English studies with more than 1,000 clients were included. Effects are mainly presented as pre-post improvement effect sizes. Results: With regard to symptomatic improvement, a large effect resulted for clients within the clinical range of depression at pretest (ES = 1.45) while, expectedly, that for subclinical samples was lower (ES = 0.65). Less than 30% of improvement variance was attributable to placebo effects. Among the clinically depressed samples, self-referred clients displayed larger improvement effects than studyreferred clients. Treatment effects were stable at least over a medium-term post-intervention period. Discussion: Requirements for more and methodologically sound studies on the program and its variants in different settings are underscored, which should allow for further outcome criteria, comparisons with other active treatments, and health economic aspects of such interventions.
The effects of protein degradability and food intake on milk yield and composition in cows in early lactation

1. In two experiments measurements were made of food intake, live-weight change, milk yield and milk composition in early lactation when dairy cows were given diets containing varying proportions of protein as fish meal (low rumen degradability) or as groundnut meal (high rumen degradability). In a preliminary trial measurements were also made with cows given supplements of either fish meal or barley and fed at a restricted level of feeding. 2. When metabolizable energy (ME) intake exceeded 160 MJ/d there was no evidence of responses to changes in protein degradability, but at ME intakes below 135 MJ/d increases in the supply of undegradable protein led to increases in fat-corrected milk yield, protein content and live-weight loss. 3. The interaction between energy intake and protein degradability is unexpected because net protein:net energy requirement increases as milk yield increases, but may be explained in terms of differential effects of changing rumen outflow rates on degradabilities.
Six Key Factors for Changing Preservice Teachers' Attitudes/Beliefs about Diversity

In this article the author postulates there are six key factors associated with changing preservice teachers' attitudes toward and beliefs about diversity-their dispositions, which include openness, self-awarenesss/self-reflectiveness, and commitment to social justice; and their experiences, which include intercultural, educational, and support group experiences. The author discusses each factor in turn and explains how research on the effectiveness of multicultural teacher education courses and experiences offers evidence of the great importance of each of these six factors.
Functional β-Adrenoceptors Are Important for Early Muscle Regeneration in Mice through Effects on Myoblast Proliferation and Differentiation

Muscles can be injured in different ways and the trauma and subsequent loss of function and physical capacity can impact significantly on the lives of patients through physical impairments and compromised quality of life. The relative success of muscle repair after injury will largely determine the extent of functional recovery. Unfortunately, regenerative processes are often slow and incomplete, and so developing novel strategies to enhance muscle regeneration is important. While the capacity to enhance muscle repair by stimulating β2-adrenoceptors (β-ARs) using β2-AR agonists (β2-agonists) has been demonstrated previously, the exact role β-ARs play in regulating the regenerative process remains unclear. To investigate β-AR-mediated signaling in muscle regeneration after myotoxic damage, we examined the regenerative capacity of tibialis anterior and extensor digitorum longus muscles from mice lacking either β1-AR (β1-KO) and/or β2-ARs (β2-KO), testing the hypothesis that muscles from mice lacking the β2-AR would exhibit impaired functional regeneration after damage compared with muscles from β1-KO or β1/β2-AR null (β1/β2-KO) KO mice. At 7 days post-injury, regenerating muscles from β1/β2-KO mice produced less force than those of controls but muscles from β1-KO or β2-KO mice did not exhibit any delay in functional restoration. Compared with controls, β1/β2-KO mice exhibited an enhanced inflammatory response to injury, which delayed early muscle regeneration, but an enhanced myoblast proliferation later during regeneration ensured a similar functional recovery (to controls) by 14 days post-injury. This apparent redundancy in the β-AR signaling pathway was unexpected and may have important implications for manipulating β-AR signaling to improve the rate, extent and efficacy of muscle regeneration to enhance functional recovery after injury.
Writing Performance

Preparing a written outline during prewriting and composing a rough rather than a polished first draft are cognitive strategies that may lessen a writer's work load. The present laboratory and field research examined whether these strategies enhance writing performance. In an experiment, I manipulated the use of these strategies by college students in a letter writing task. The students' writing process, efficiency, and quality were examined. The results showed that preparing a written outline, compared with not doing so, increased the time spent translating ideas into text, improved the quality of letters, and failed to enhance overall efficiency. The use of rough versus polished drafts affected when the students reviewed their work, as expected, but had no influence on quality or efficiency. A survey of science and engineering faculty revealed that the frequency of using written outlines correlated positively with writing productivity, whereas use of polished drafts was uncorrelated with productivity.
MRI using radiofrequency magnetic field phase gradients

Conventionally, MR images are formed by applying gradients to the main static magnetic field (B0). However, the B0 gradient equipment is expensive, power‐hungry, complex, and noisy and can induce eddy currents in nearby conducting structures, including the patient. Here, we describe a new silent, B0 gradient‐free MRI principle, Transmit Array Spatial Encoding (TRASE), based on phase gradients of the radio‐frequency (RF) field. RF phase gradients offer a new method of k‐space traversal. Echo trains using at least two different RF phase gradients allow spin phase to accumulate, causing k‐space traversal. Two such RF fields provide one‐dimensional imaging and three are sufficient for two‐dimensional imaging. Since TRASE is a k‐space method, analogues of many conventional pulse sequences are possible. Experimental results demonstrate one‐dimensional and two‐dimensional RF MRI and slice selection using a single‐channel, transmit/receive, 0.2 T, permanent magnet, human MR system. The experimentally demonstrated spatial resolution is much higher than that provided by RF receive coil array sensitivity encoding alone but lower than generally achievable with B0 gradients. Potential applications are those in which one or more of the features of simplified equipment, lower costs, silent MRI, or the different physics of the image formation process are particularly advantageous. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.
Techno-economic Analysis of Software Defined Networking as Architecture for the Virtualization of a Mobile Network

Worldwide mobile network operators have to spend billions to upgrade their own network to the latest standards for wireless communication of high-speed data for mobile phones (e.g. Long Term Evolution, LTE). This is in contrast with the decline in average revenue per user and threatens: (1) their profitability and (2) the fast adaptation of new standards. Investigating new mechanisms that can decrease the capital expenditures (capex) and operational expenditures (opex) of a mobile network is therefore essential. Enabling multiple mobile network operators on a common infrastructure is one such mechanism. Software defined networks can overcome this problem and a solution based on exploring OpenFlow (OF) as architecture for mobile network virtualization has been proposed. We investigate two network scenarios based on this OF solution in a techno-economic analysis: (scenario 1) software-defined, non-shared networks and (scenario 2) virtualized, shared networks and compare it against the current situation. By doing so, this paper provides insights on the relative cost savings that a mobile network operator can reach through Software Defined Networking (SDN) and network sharing. The techno-economic analysis indicates that SDN and virtualization of the first aggregation stage and second aggregation stage network infrastructure leads to substantial capex cost reductions for the mobile network operator. As a consequence, mobile network infrastructure virtualization through the use of OpenFlow could be one of the problem solvers to tackle the issue of rising costs and decreasing profitability. Still, we did not take into account the direct effect on operational expenditures and the indirect effect that network sharing can adversely affect the ability of the operators to differentiate themselves.
Effect of Online Reviews on Consumer Purchase Behavior

In order to understand the effect of online reviews on consumer purchase behavior, more than 400 Taobao shops’ online reviews are collected. Based on S-O-R model (Stimulus-Organism-Response Model), this paper studies the influence on consumer purchase behavior according to online reviews of experience goods from a new perspective of consumer learning. Using SPSS 19.0 software for data analysis and assumptions, statistical results show that the positive reviews, describing rating, picture reviews, appended reviews and cumulative reviews have an effect on consumer purchase behavior. The moderate reviews, negative reviews, logistics rating and service rating are not significant in the results. Finally, this paper puts forward suggestions and summary.