Miracle-dz/UniFAR-FTUs huggingface dataset:
Alcohol and PRAS40 knockdown decrease mTOR activity and protein synthesis via AMPK signaling and changes in mTORC1 interaction

The mTORC1 protein kinase complex consists of mTOR, raptor, mLST8/GβL and PRAS40. Previously, we reported that mTOR plays an important role in regulating protein synthesis in response to alcohol (EtOH). However, the mechanisms by which EtOH regulates mTORC1 activity have not been established. Here, we investigated the effect of EtOH on the phosphorylation and interaction of components of mTORC1 in C2C12 myocytes. We also examined the specific role that PRAS40 plays in this process. Incubation of myocytes with EtOH (100 mM, 24 h) increased raptor and PRAS40 phosphorylation. Likewise, there were increased levels of the PRAS40 upstream regulators Akt and IRS‐1. EtOH also caused changes in mTORC1 protein–protein interactions. EtOH enhanced the binding of raptor and PRAS40 with mTOR. These alterations occurred in concert with increased binding of 14‐3‐3 to raptor, while the PRAS40 and 14‐3‐3 interaction was not affected. The shRNA knockdown (KD) of PRAS40 decreased protein synthesis similarly to EtOH. PRAS40 KD increased raptor phosphorylation and its association with 14‐3‐3, whereas decreased GβL–mTOR binding. The effects of EtOH and PRAS40 KD were mediated by AMPK. Both factors increased in vitro AMPK activity towards the substrate raptor. In addition, KD enhanced the activity of AMPK towards TSC2. Collectively, our results indicate that EtOH stabilizes the association of raptor, PRAS40, and GβL with mTOR, while likewise increasing the interaction of raptor with 14‐3‐3. These data suggest a possible mechanism for the inhibitory effects of EtOH on mTOR kinase activity and protein synthesis in myocytes. J. Cell. Biochem. 109: 1172–1184, 2010. © 2010 Wiley‐Liss, Inc.
A Comparison of Methods for Incorporating Spatial Dependence in Predictive Vegetation Models : A Mojave Desert Case Study

In this study, presence/absence models of eleven vegetation alliances in a portion of the Mojave Desert (California, USA) were developed using generalized linear models (GLM) and classification tree (CT) models, and two different methods for explicitly incorporating spatial dependence. In the first method, spatial dependence was included as a model term, along with environmental variables, and predictions were generated. In the second method, the residuals from the models using environmental variables were added to the model predictions. Accuracy was assessed with relative-operator characteristic (ROC) plots, using a portion of the sample data not used for model development. Spatial predictions of alliance presence/absence were compared among all twelve of the models. In general, incorporating spatial dependence improved the classification accuracy of most of the models. Models for more common alliances showed a greater increase in accuracy, while models for rare alliances were less consistent. This was most likely related to the relative of data on ‘presence’ observations for rare alliances. The residual interpolation method had more consistently positive results in terms of increased accuracy than the method of including spatial dependence as a predictor variable. One problem associated with the latter method is that the resulting models may become less generalizable, as they rely too heavily on presence data rather than environmental correlates. Additionally, the spatial patterning of the dependence variables, particularly the overly smooth kriged surface, can result in ecologically unrealistic predictions.
Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph‐positive acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 study

Dasatinib 70 mg twice daily is indicated for Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL) intolerant or resistant to imatinib. In patients with chronic‐phase chronic myelogenous leukemia, once‐daily dosing has similar efficacy with improved safety, compared with twice‐daily dosing. A phase 3 study (n = 611) assessed the efficacy and safety of dasatinib 140 mg once daily versus 70 mg twice‐daily in patients with advanced phase chronic myelogenous leukemia or Ph+ ALL resistant or intolerant to imatinib. Here, results from the Ph+ ALL subset (n = 84) with a 2‐year follow‐up are reported. Patients were randomly assigned to receive dasatinib either 140 mg once daily (n = 40) or 70 mg twice daily (n = 44). The rate of confirmed major hematologic response with once‐daily dosing (38%) was similar to that with twice‐daily dosing (32%). The rate of major cytogenetic response with once‐daily dosing (70%) was higher than that with twice‐daily dosing (52%). Compared with the twice‐daily schedule, the once‐daily schedule had longer progression‐free survival (median, 3.0 months versus 4.0 months, respectively) and shorter overall survival (median, 9.1 months versus 6.5 months, respectively). Overall safety profiles were similar between two groups, with nonhematologic adverse events being mostly grade 1 or 2. Pleural effusion was less frequent with once‐daily dosing than with twice‐daily dosing (all grades, 18% versus 32%). Notably, none of the differences between the two schedules was statistically significant. Compared with the 70 mg twice daily, dasatinib 140 mg once daily had similar overall efficacy and safety in patients with imatinib‐resistant or intolerant Ph+ ALL. (clinicaltrials.gov identifier: NCT00123487). Am. J. Hematol. 2010. © 2009 Wiley‐Liss, Inc.
Macroprudential policy transmission and interaction with fiscal and monetary policy in an emerging economy: a DSGE model for Brazil

ABSTRACT We investigate the transmission of macroprudential (MaP) instruments in a dynamic stochastic general equilibrium model where foreign capital flows interact with financial frictions and banks are exposed to different sources of credit default risk. The model is estimated for Brazil with Bayesian techniques. We compute optimal combinations of simple MaP, fiscal and monetary policy rules that can react to the business and/or the financial cycle. We find that the gains from implementing a cyclical fiscal policy are only significant if MaP policy countercyclically reacts to the financial cycle. Optimal fiscal policy is countercyclical in the business cycle.
Helical structure and stability in human apolipoprotein A-I by hydrogen exchange and mass spectrometry

Apolipoprotein A-I (apoA-I) stabilizes anti-atherogenic high density lipoprotein particles (HDL) in the circulation and governs their biogenesis, metabolism, and functional interactions. To decipher these important structure–function relationships, it will be necessary to understand the structure, stability, and plasticity of the apoA-I molecule. Biophysical studies show that lipid-free apoA-I contains a large amount of α-helical structure but the location of this structure and its properties are not established. We used hydrogen-deuterium exchange coupled with a fragmentation-separation method and mass spectrometric analysis to study human lipid-free apoA-I in its physiologically pertinent monomeric form. The acquisition of ≈100 overlapping peptide fragments that redundantly cover the 243-residue apoA-I polypeptide made it possible to define the positions and stabilities of helical segments and to draw inferences about their interactions and dynamic properties. Residues 7–44, 54–65, 70–78, 81–115, and 147–178 form α-helices, accounting for a helical content of 48 ± 3%, in agreement with circular dichroism measurements (49%). At 3 to 5 kcal/mol in free energy of stabilization, the helices are far more stable than could be achieved in isolation, indicating mutually stabilizing helix bundle interactions. However the helical structure is dynamic, unfolding and refolding in seconds, allowing facile apoA-I reorganization during HDL particle formation and remodeling.
Induction of Keratinocyte Migration via Transactivation of the Epidermal Growth Factor Receptor by the Antimicrobial Peptide LL-371

The closure of skin wounds is essential for resistance against microbial pathogens, and keratinocyte migration is an important step in skin wound healing. Cathelicidin hCAP18/LL-37 is an innate antimicrobial peptide that is expressed in the skin and acts to eliminate microbial pathogens. Because hCAP18/LL-37 is up-regulated at skin wound sites, we hypothesized that LL-37 induces keratinocyte migration. In this study, we found that 1 μg/ml LL-37 induced the maximum level of keratinocyte migration in the Boyden chamber assay. In addition, LL-37 phosphorylated the epidermal growth factor receptor (EGFR) after 10 min, which suggests that LL-37-induced keratinocyte migration occurs via EGFR transactivation. To test this assumption, we used inhibitors that block the sequential steps of EGFR transactivation, such as OSU8-1, CRM197, anti-EGFR no. 225 Ab, and AG1478. All of these inhibitors completely blocked LL-37-induced keratinocyte migration, which indicates that migration occurs via HB-EGF-mediated EGFR transactivation. Furthermore, CRM197, anti-EGFR no. 225, and AG1478 blocked the LL-37-induced phosphorylation of STAT3, and transfection with a dominant-negative mutant of STAT3 abolished LL-37-induced keratinocyte migration, indicating the involvement of the STAT3 pathway downstream of EGFR transactivation. Finally, we tested whether the suppressor of cytokine signaling (SOCS)/cytokine-inducible Src homology 2-containing protein (CIS) family of negative regulators of STAT3 regulates LL-37-induced keratinocyte migration. Transfection with SOCS1/Jak2 binding protein or SOCS3/CIS3 almost completely abolished LL-37-induced keratinocyte migration. In conclusion, LL-37 induces keratinocyte migration via heparin-binding-EGF-mediated transactivation of EGFR, and SOCS1/Jak 2 binding and SOCS3/CIS3 negatively regulate this migration. The results of this study suggest that LL-37 closes skin wounds by the induction of keratinocyte migration.
Power and Maximum Strength Relationships During Performance of Dynamic and Static Weighted Jumps

The purpose of this study was to investigate the relationship of the 1 repetition maximum (1RM) squat to power output during countermovement and static weighted vertical squat jumps. The training experience of subjects (N = 22, 87.0 ± 15.3 kg, 14.1 ± 7.1% fat, 22.2 ± 3.8 years) ranged from 7 weeks to 15+ years. Based on the 1RM squat, subjects were further divided into the 5 strongest and 5 weakest subjects (p ≤ 0.05). Squat jumps were performed with a counter-movement or statically at 2 different sessions spaced 1 week apart. Jumps were performed with weights ranging from 10 to 100% of the 1RM squat. A maximum effort was made for each trial; subjects performed jumps (feet left the floor) with weights up to approximately 90% of 1RM. Squat-jump power was determined using the V-scope 120. Results indicate strong correlations (r = 0.77–0.94) between the 1RM squat and both countermovement and static jump power up to 90% of 1RM. The highest power outputs for both jump conditions occurred at 10% of the 1RM and decreased as the relative intensity increased. Comparisons of weak and strong subjects indicate that as maximum strength increases the percentage of 1RM at which peak power occurs also increases (40 vs. 10% of 1RM). From a practical aspect, to improve jumping power output, these results suggest that improving maximum strength should be a primary component of training programs and that strength training should shift from lighter (10% 1RM) to heavier (40% 1RM) loads.
An improved Kalman filter algorithm base on quaternion correlation in object tracking

In this paper, we proposed an improved Kalman filter algorithm based on quaternion correlation of color image. Kalman filter is used to predict the object motion direction and define the searching window. In the searching window, the correlation of object and the window image is calculated to get the accurate position of the object. When the object is covered partly, we can get good result, too. Experiments results showed that the accuracy of our algorithm is higher than mean-shift algorithm.
Evolution in the management of Hirschsprung's disease in the UK and Ireland: a national survey of practice revisited.

INTRODUCTION The management of Hirschsprung's disease continues to evolve. This questionnaire survey aimed to determine current surgical management strategies for Hirschsprung's disease in Britain. SUBJECTS AND METHODS The survey was sent electronically to all British paediatric surgeons. Initial questions explored individual experience and regional service provision. Additional questions, reserved for surgeons who perform definitive Hirschsprung's disease surgery, addressed specific clinical scenarios. RESULTS Surveys were sent to 142 surgeons yielding 85 responses. After exclusions, 64 surveys from 21 centres were analysed. Forty-seven respondents worked in centres with designated 'Hirschsprung's disease surgeons'. Forty respondents perform definitive Hirschsprung's disease surgery. In a well neonate with left-sided Hirschsprung's disease, 34 of 40 surgeons favour primary pull-through following bowel decompression with rectal washouts; 35 of 40 surgeons aim to perform definitive surgery at less than 3 months of age, with 17 favouring laparoscopic-assisted Soave-Boley and 15 favouring an open Duhamel pull-through. Of the 40 surgeons, 36 use a staged approach to right-sided/total colonic Hirschsprung's disease with 23 favouring a Duhamel or Long Duhamel pull-through. CONCLUSIONS The primary pull-through, using an open Duhamel or laparoscopic-assisted Soave-Boley technique, during the first 3 months of life, has become the operative strategy of choice in rectosigmoid Hirschsprung's disease in Britain. Marked variation in practice remains for right-sided Hirschsprung's disease.
Second price all-pay auctions, how much money do players get or lose?

The paper studies second price all-pay auctions - wars of attrition - in a new way, based on class room experiments and Kosfeld, Droste and Voorneveld’s (2002) best reply matching equilibrium. Two players fight over a prize of value V, have a budget M, submit bids lower or equal to M; both pay the lowest bid and the prize goes to the highest bidder. The behaviour probability distributions in the class room experiments are strikingly different from the mixed Nash equilibrium. They fit with best reply matching or generalized best reply matching, an ordinal logic according to which, if bid A is the best response to bid B, and if B is played with probability p, then A is also played with probability p. In the mixed Nash equilibrium, the expected payoff is never negative and close to 0. In the best reply and generalized best reply matching equilibria, players may lose money, up to 1/12th of the budget when M is large in comparison to V, but they can also get a lot of money, especially if V is large. The study leads to examine possible bifurcations in the bidding behaviour and gives some insights into how to regulate games to avoid pathological gambling with a huge waste of money.
Widespread and frequent horizontal transfers of transposable elements in plants

Vertical, transgenerational transmission of genetic material occurs through reproduction of living organisms. In addition to vertical inheritance, horizontal gene transfer between reproductively isolated species has recently been shown to be an important, if not dominant, mechanism in the evolution of prokaryotic genomes. In contrast, only a few horizontal transfer (HT) events have been characterized so far in eukaryotes and mainly concern transposable elements (TEs). Whether these are frequent and have a significant impact on genome evolution remains largely unknown. We performed a computational search for highly conserved LTR retrotransposons among 40 sequenced eukaryotic genomes representing the major plant families. We found that 26 genomes (65%) harbor at least one case of horizontal TE transfer (HTT). These transfers concern species as distantly related as palm and grapevine, tomato and bean, or poplar and peach. In total, we identified 32 cases of HTTs, which could translate into more than 2 million among the 13,551 monocot and dicot genera. Moreover, we show that these TEs have remained functional after their transfer, occasionally causing a transpositional burst. This suggests that plants can frequently exchange genetic material through horizontal transfers and that this mechanism may be important in TE-driven genome evolution.
RF Performance Potential of Array-Based Carbon-Nanotube Transistors—Part II: Extrinsic Results

A comprehensive study, which is presented in two parts, is performed to assess the radio-frequency (RF) performance potential of array-based carbon-nanotube field-effect transistors. In Part II, which is presented in this paper, the infrastructure from Part I is utilized to examine more advanced aspects of the RF characteristics. The subversive effects of the extrinsic (parasitic) resistances and capacitances are added to an array-based structure, and the behaviors of key RF figures of merit, such as the extrinsic unity-current-gain frequency fT, the attainable power gain, and the unity-power-gain frequency fmax, are examined versus tube pitch and gate-finger layout. The results are compared with those of state-of-the-art high-frequency transistors and to the benchmark determined by the next generation of RF CMOS-as defined by the International Technology Roadmap for Semiconductors for the year 2015-and they provide an indication of the potential advantages and disadvantages of array-based nanotube transistors.
A quantitative approach to distinguishing older adults with insomnia from good sleeper controls.

STUDY OBJECTIVE Establishing quantitative criteria to distinguish individuals with and without insomnia is important for clinical and research applications, but consensus has not yet been reached for specific values. The purpose of this study was to identify the optimal quantitative thresholds for actigraphy and sleep diary that differentiate older adults (> 60 years) with insomnia from good sleeper controls. METHODS A total of 119 participants (79 insomnia [35% male], 40 control [31.7% male]; mean age = 71.7 [7.2] years) completed at least 7 nights of sleep diary and actigraphy. Receiver operating characteristic curve analyses and the Youden index were used to identify optimal threshold values. Outcomes for each measurement method included sleep onset latency (SOL), wake time after sleep onset (WASO), sleep efficiency (SE), and total sleep time (TST). RESULTS Sleep diary measures produced areas under the curves (AUC) in the high range (0.84-0.97), whereas actigraphy performed poorly at discriminating the two groups (AUC 0.58-0.61). The Youden index identified SOL = 18 minutes, WASO = 21 minutes, SE = 92%, and TST = 388 minutes as the sleep diary measures that yielded the highest sensitivity and specificity values for insomnia-control discrimination. Accounting for hypnotic medication and sleep apnea use did not change the findings. CONCLUSION Sleep diary parameters discriminated individuals with insomnia from good sleepers more accurately than actigraphy. These quantitative criteria are similar to those reported by other investigators using different methods and samples, including younger adults. The results suggest that the sleep diary, an inexpensive self-report sleep measure, may be used in clinical and research settings to help distinguish older adults with and without insomnia.
Positive coeliac serology in irritable bowel syndrome patients with normal duodenal biopsies: Video capsule endoscopy findings and HLA-DQ typing may affect clinical management.

OBJECTIVES To investigate a group of IBS patients (Rome criteria) with positive coeliac serology (EMA, TTG, IgG or IgA AGA) and normal small bowel biopsies. Video capsule endoscopy (VCE) findings of the small bowell were compared with DQ-typing. METHODS Twenty-two patients with chronic abdominal pain (with or without diarrhea) and at least one positive result of any of the coeliac serological markers (AGA, TTG, EMA) and normal duodenal biopsy were enrolled and underwent VCE. Twelve healthy volunteers with VCE served as control group. Coeliac related HLA DQ2 or DQ8 markers were determined. RESULTS 12/ 22 (55%) patients had small bowel abnormalities with VCE. No mucosal abnormalities were recognized in the control group (p = 0.002). Inflammatory changes were classified as moderate or pronounced. Eight patients (36%) had moderate changes and four patients (18%) demonstrated pronounced changes. Only 6 of the 21 IBS patients were positive for DQ2 and/or DQ8. CONCLUSIONS The patients in this study fulfilled the diagnostic Rome criteria for Irritable Bowel Syndrome. We suggest that patients with positive coeliac serology and normal duodenal biopsies should undergo HLA typing. In patients positive for DQ2 and/or DQ8, a VCE should be performed. Patients with mucosal abnormalities compatible with CD should be considered as a group distinct from IBS patients and could be tested with gluten challenge or treated with a gluten free diet.
bcl-2 acts early to restrict Semliki Forest virus replication and delays virus-induced programmed cell death

As characterized by morphological assessment and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, Semliki Forest virus (SFV) infection of rat prostatic adenocarcinoma cells triggers an apoptotic cell response. Cell death proceeded more rapidly following infection with the neurovirulent L10 strain of SFV than with the avirulent A7 strain. Overexpression of the antiapoptotic proto-oncogene bcl-2 allowed survival of cultures infected with either strain of virus. bcl-2 overexpression drastically reduced the numbers of productively infected cells within the cultures. In situ hybridization for viral message-sense RNA coupled with immunostaining for viral protein indicated that bcl-2 functions at an early stage of the virus life cycle, at entry, pretranscriptional events or at transcription, to inhibit virus replication. Double-immunofluorescent labeling for bcl-2 and viral glycoproteins revealed double-positive cells, demonstrating that with time, this early block in replication can be overcome. These productively infected bcl-2-expressing cells do, with time, undergo apoptosis. As a result of changing the balance between cell death and cell division by restricting productive virus replication and delaying virus-induced cell death, bcl-2 expression led to the establishment of chronically infected cell lines which could be passaged.
Hypothalamic Pituitary Adrenal Axis and Immune Responses to Endotoxin in Rats with Chronic Adjuvant-Induced Arthritis

We investigated the effect of immune challenge with LPS in both control rats and rats with adjuvant-induced arthritis (AA). Fourteen day-AA rats showed the expected activation of the hypothalamic-pituitary adrenal axis associated with increases in vasopressin mRNA and paradoxical decreases in corticotropin-releasing hormone (CRH) mRNA in parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). However, following LPS there was an increase in both CRH and vasopressin mRNA in the PVN. Neither control rats nor rats with AA had measurable plasma levels of IL-6, but plasma levels of IL-1beta were 2.7-fold higher in AA animals. Following LPS injection both IL-1beta and IL-6 increased more markedly in AA than in control rats. Neither controls nor AA rats expressed IL-1beta or IL-6 mRNA in the brain. However, following LPS these were induced in the subfornical organ, choroid plexus, and median eminence of both groups of animals. The areas expressing IL-1b mRNA were larger in the AA animals and exhibited a punctate pattern throughout the brain parenchyma and PVN. These data reveal an increased peripheral and central immunological response to LPS during the chronic inflammatory process of AA, providing a mechanism through which inflammatory disease can influence the response to a novel immunological challenge.