Miracle-dz/UniFAR-FTUs huggingface dataset:
p300-Mediated Tax Transactivation from Recombinant Chromatin: Histone Tail Deletion Mimics Coactivator Function

ABSTRACT Efficient transcription of the human T-cell leukemia virus type 1 (HTLV-1) genome requires Tax, a virally encoded oncogenic transcription factor, in complex with the cellular transcription factor CREB and the coactivators p300/CBP. To examine Tax transactivation in vitro, we used a chromatin assembly system that included recombinant core histones. The addition of Tax, CREB, and p300 to the HTLV-1 promoter assembled into chromatin activated transcription several hundredfold. Chromatin templates selectively lacking amino-terminal histone tails demonstrated enhanced transcriptional activation by Tax and CREB, with significantly reduced dependence on p300 and acetyl coenzyme A (acetyl-CoA). Interestingly, Tax/CREB activation from the tailless chromatin templates retained a substantial requirement for acetyl-CoA, indicating a role for acetyl-CoA beyond histone acetylation. These data indicate that during Tax transcriptional activation, the amino-terminal histone tails are the major targets of p300 and that tail deletion and acetylation are functionally equivalent.
Multiagent Bidirectionally-Coordinated Nets: Emergence of Human-level Coordination in Learning to Play StarCraft Combat Games

Many artificial intelligence (AI) applications often require multiple intelligent agents to work in a collaborative effort. Efficient learning for intra-agent communication and coordination is an indispensable step towards general AI. In this paper, we take StarCraft combat game as a case study, where the task is to coordinate multiple agents as a team to defeat their enemies. To maintain a scalable yet effective communication protocol, we introduce a Multiagent Bidirectionally-Coordinated Network (BiCNet ['bIknet]) with a vectorised extension of actor-critic formulation. We show that BiCNet can handle different types of combats with arbitrary numbers of AI agents for both sides. Our analysis demonstrates that without any supervisions such as human demonstrations or labelled data, BiCNet could learn various types of advanced coordination strategies that have been commonly used by experienced game players. In our experiments, we evaluate our approach against multiple baselines under different scenarios; it shows state-of-the-art performance, and possesses potential values for large-scale real-world applications.
Effects of carprofen, meloxicam and deracoxib on platelet function in dogs.

OBJECTIVE To determine effects of anti-inflammatory doses of COX-2 selective NSAIDs carprofen, meloxicam, and deracoxib on platelet function in dogs and urine 11-dehydro-thromboxane B2. STUDY DESIGN Randomized, blocked, crossover design with a 14-day washout period. ANIMALS Healthy intact female Walker Hounds aged 1-6 years and weighing 20.5-24.2 kg. METHODS Dogs were given NSAIDs for 7 days at recommended doses: carprofen (2.2 mg kg(-1), PO, every 12 hours), carprofen (4.4 mg kg(-1), PO, every 24 hours), meloxicam (0.2 mg kg(-1), PO, on the 1st day then 0.1 mg kg(-1), PO, every 24 hours), and deracoxib (2 mg kg(-1), PO, every 24 hours). Collagen/epinephrine and collagen/ADP PFA-100 cartridges were used to evaluate platelet function before and during and every other day after administration of each drug. Urine 11-dehydro-thromboxane B(2) was also measured before and during administration of each drug. RESULTS All NSAIDs significantly prolonged PFA-100 closure times when measured with collagen/epinephrine cartridges, but not with collagen/ADP cartridges. The average duration from drug cessation until return of closure times (collagen/epinephrine cartridges) to baseline values was 11.6, 10.6, 11 and 10.6 days for carprofen (2.2 mg kg(-1) every 12 hours), carprofen (4.4 mg kg(-1) every 24 hours), meloxicam and deracoxib, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of some COX-2 selective NSAIDs causes detectable alterations in platelet function in dogs. As in humans, PFA-100 collagen/ADP cartridges do not reliably detect COX-mediated platelet dysfunction in dogs. Individual assessment of platelet function is advised when administering these drugs prior to surgery, particularly in the presence of other risk factors for bleeding.
In vivo studies of altered expression patterns of p53 and proliferative control genes in chronic vitamin A deficiency and hypervitaminosis.

Several clinical trials have revealed that individuals who were given beta-carotene and vitamin A did not have a reduced risk of cancer compared to those given placebo; rather, vitamin A could actually have caused an adverse effect in the lungs of smokers [Omenn, G.S. , Goodman, G.E. , Thornquist, M.D., Balmes, J., Cullen, M.R. , Glass, A. , Keogh, J.P., Meyskens, F.L. , Valanis, B. , Williams, J.H. , Barnhart, S. & Hammar, S. N. Engl. J. Med (1996) 334, 1150-1155; Hennekens, C.H. , Buring, J.E. , Manson, J.E. , Stampfer, M. , Rosner, B. , Cook, N.R. , Belanger, C. , LaMotte, F. , Gaziano, J.M. , Ridker, P.M. , Willet, W. & Peto, R. (1996) N. Engl. J. Med. 334, 1145-1149]. Using differential display techniques, an initial survey using rats showed that liver RNA expression of c-H-Ras was decreased and p53 increased in rats with chronic vitamin A deficiency. These findings prompted us to evaluate the expression of c-Jun, p53 and p21WAF1/CIF1 (by RT-PCR) in liver and lung of rats. This study showed that c-Jun levels were lower and that p53 and p21WAF1/CIF1 levels were higher in chronic vitamin A deficiency. Vitamin A supplementation increased expression of c-Jun, while decreasing the expression of p53 and p21WAF1/CIF1. Western-blot analysis demonstrated that c-Jun and p53 showed a similar pattern to that found in the RT-PCR analyses. Binding of retinoic acid receptors (RAR) to the c-Jun promoter was decreased in chronic vitamin A deficiency when compared to control hepatocytes, but contrasting results were found with acute vitamin A supplementated cells. DNA fragmentation and cytochrome c release from mitochondria were analyzed and no changes were found. In lung, an increase in the expression of c-Jun produced a significant increase in cyclin D1 expression. These results may explain, at least in part, the conflicting results found in patients supplemented with vitamin A and illustrate that the changes are not restricted to lung. Furthermore, these results suggest that pharmacological vitamin A supplementation may increase the risk of adverse effects including the risk of oncogenesis.
Comprehensive Ultrasound Assessment of the Craniocervical Circulation in Transient Global Amnesia

Structural changes and metabolic stress have been reported on diffusion‐weighted magnetic resonance imaging in the cornu ammonis 1 area of the hippocampus in patients with transient global amnesia (TGA), but a consensus on pathogenesis is still lacking. The aim of our study was to perform a comprehensive ultrasound analysis of the cerebrovascular circulation in our population of patients with TGA.
Advances in Brief Isolation Based on L-Selectin Expression of Immune Effector T Cells Derived from Tumor-draining Lymph Nodes 1

The ability to generate a large number of tumor-reactive T lymphocytes is the most critical requirement for adoptive immunotherapy. Our labo ratory has previously demonstrated that cells from tumor-draining lymph nodes (l,Ns) are an excellent source of tumor-reactive T lymphocytes. After activation with anti-CI)3, these cells readily proliferate in low concentrations of interleukin 2 and acquire effector functions. The adop tive transfer of these cells is capable of mediating the regression of tumors established in the lung as well as in the brain. Here, we analyzed several adhesion molecules on the tumor-draining IN T cells and separated them based on i. -selectin expression. The homing receptor i. -selectin mediates adhesion to the luminal surface of specialized high endothelial venules, thus regulating lymphocyte recirculation through peripheral LNs. In response to progressive tumor growth, a small population of draining IN T cells down-regulated 1,-selectin and increased the expression of CD44 and lymphocyte function-associated antigen I. In adoptive immunotherapy, purified T cells with low i. -selectin d. -selectin~) expression consti tuted all the i/i vivo antitumor reactivity, whereas isolated high i. -selectin <i. -sclcctm+l cells were ineffective. Furthermore, reverse transcriptionPC'R analysis revealed that l. -selcctin" cells expressed interleukin 2, II N-y Â¡nidtumor necrosis factor a mKNA upon in vitro stimulation with specific tumor cells. These results suggest that highly potent immune T cells can be isolated based on their pattern of adhesion molecule expres sion. The ability of the immune effector cells to transcribe cytokine genes when stimulated with tumor cells provides a basis for identifying similar cells for adoptive immunotherapy of cancer in humans.
The role of the central flexible region on the aggregation and conformational properties of human ataxin‐3

Aggregation of human ataxin‐3 (AT3) into amyloid fibrils is responsible for spinocerebellar ataxia type 3. This protein consists of a folded N‐terminal domain (Josephin domain, residues 1–182), a central flexible region (residues 183–291), a poly‐glutamine sequence of variable length and a short C‐terminal flexible region. Very little is known about the influence of the central flexible region on the conformational and aggregation properties of this protein. The present study aimed to investigate the specific role of this portion of the protein (residues 183–291). Accordingly, protein fragments 1–182 (AT3/182) and 1–291 (AT3/291) were produced and compared by thioflavin‐T fluorescence, Fourier transform infrared spectroscopy, CD, intrinsic fluorescence and ESI‐MS. It is shown that the central flexible region enhances protein aggregation and can populate conformational states with different degrees of compactness. Both monomeric and dimeric partially‐folded forms are identified for both protein fragments under denaturing conditions. Partially‐folded monomers and dimers accumulate to a larger extent in AT3/291. These species represent good candidates for early intermediates of the aggregation process under the experimental conditions employed in the present study.
Depressive personality in nonclinical subjects.

OBJECTIVE This study explored the reliability and clinical correlates of the depressive personality in nonclinical subjects. In particular, the authors were interested in determining the relationship between depressive personality and mood disorders. METHOD The subjects were 185 college students who were selected by using a battery of screening inventories assessing a variety of psychopathological symptoms and traits. The subjects were given structured diagnostic interviews that included a section on depressive temperament. RESULTS There were significant relationships between depressive personality and lifetime. DSM-III diagnoses of major depression and dysthymia. However, the magnitude of the associations was modest, indicating that these are distinct, although overlapping constructs. In addition, the subjects with depressive personality (N = 36) had significantly greater impairment and a higher rate of mood disorders in their first-degree relatives than did the subjects without depressive personality (N = 149). Moreover, these results were evident even after the subjects with a lifetime history of mood disorder were excluded. CONCLUSIONS These data suggest that depressive personality is a clinically important condition that is not subsumed by existing mood disorders categories but can be viewed as falling within the affective spectrum.
Coprological Study on Helminth Fauna in Eurasian Lynx (Lynx lynx) From the Białowieża Primeval Forest in Eastern Poland

One hundred fecal samples were collected during research on Eurasian lynx ecology and food habits in the Polish part of the Białowieża Primeval Forest (BPF) from 2001 to 2006. Seventy-three percent of samples contained eggs or larvae of helminths. A total of 10 species of helminths was identified, including 3 Cestoda (Diphyllobothrium latum, Spirometra janickii, and unidentified species of Taeniidae), 1 Trematoda (Alaria alata), and 6 Nematoda (Aelurostrongylus abstrusus, Ancylostoma tubaeforme, Eucoleus aerophilus, Metastrongylus sp., Nematodirus sp., and Toxocara cati). Alaria alata has not been reported previously in lynx. A statistical comparison of the 2 techniques used to isolate eggs, i.e., flotation and sedimentation, indicates that sedimentation was more effective.
Efficacy of Colistin versus β-Lactams, Aminoglycosides, and Rifampin as Monotherapy in a Mouse Model of Pneumonia Caused by Multiresistant Acinetobacter baumannii

ABSTRACT The treatment of life-threatening infections due to carbapenem-resistant Acinetobacter baumannii has become a serious challenge for physicians worldwide. Often, only colistin shows in general good in vitro activity against these carbapenem-resistant strains, but its antibacterial efficacy in comparison with the antibiotics most used in clinical practice is not well known. We studied the efficacy of colistin versus those of imipenem, sulbactam, tobramycin, and rifampin in an experimental pneumonia model with immunocompetent mice. We used three strains of A. baumannii corresponding to the main clones (A, D, and E) involved in the outbreaks of our hospital, with different grades of resistance to imipenem (imipenem MICs of 1, 8, and 512 μg/ml, respectively) and to the other antibiotics. The MIC of colistin was 0.5 μg/ml for the three strains. Reduction of log10 CFU/g in lung bacterial counts, clearance of bacteremia, and survival versus results with controls were used as parameters of efficacy. Imipenem and sulbactam (Δlung counts: −5.38 and −4.64 log10 CFU/ml) showed the highest level of bactericidal efficacy in infections by susceptible and even intermediate strains. Tobramycin and rifampin (−4.16 and −5.15 log10 CFU/ml) provided good results against intermediate or moderately resistant strains, in agreement with killing curves and pharmacodynamics. On the contrary, colistin showed the weakest antibacterial effect among the antibiotics tested, both in killing curves and in the in vivo model (−2.39 log10 CFU/ml; P < 0.05). We conclude that colistin did not appear as a good option for treatment of patients with pneumonia due to carbapenem-resistant A. baumannii strains. Other alternatives, including combinations with rifampin, may offer better therapeutic profiles and thus should be studied.
Human Faecal Microbiota Develops the Ability to Degrade Type 3 Resistant Starch During Weaning

Background: Colonisation of the human colon starts immediately after birth. Bacterial composition is substantially influenced by the type of feeding. During weaning, microbiota diversifies considerably to finally approach the composition of that of adults. The aim of this study was to investigate the ability of colonic microbiota obtained from different age groups to ferment resistant starch (RS). Methods: Faecal samples of breast-fed and formula-fed infants, infants at weaning, adults and elderly subjects were used as inocula. Fermentation experiments were performed by applying a standardised in vitro batch method. Fermentability was established by measuring both metabolite production and substrate degradation. An RS type 3 (RS-3) was used as substrate; its behaviour was compared with that of lactulose (positive control), whereas inoculum without substrate was used as negative control. Results: Overall fermentation patterns clearly showed that the human microbiota of all age groups is able to degrade lactulose. In contrast, RS-3 was found resistant to the attack by microbiota of both breast-fed and formula-fed infants. Bacteria collected from infants at weaning were able to degrade RS-3 completely, but slower compared with adults. With increasing age, RS-3 fermentation was observed to be slightly retarded again. Conclusions: Human faecal microbiota of all age groups is able to ferment lactulose in vitro quickly and completely. The ability to degrade RS-3, however, is only established during weaning. Whether fermentation-related production of short-chain fatty acids from RS-3 and concurrent modifications of the microbiota can result in potential health benefits to the host at this stage of life needs to be elucidated.
Unbundling Democracy: Tilly Trumps Schumpeter

Much of the recent political economy and political science literature views democracy in one-dimensional terms, primarily in terms of political rights. This feature is particularly pronounced in the empirical literature, especially in the recent strand that seeks to identify the determinants of democracy. We expand on this view of democracy by incorporating the role of civil liberties, noting that these are conceptually at the core of modern democracy. We offer a conceptual framework that identifies five sources of potential differences in the evolution of political rights and civil liberties. We investigate the empirical evidence on this differential evolution using cross-national panel data based on the Freedom House measures of political rights and civil liberties. We show that civil liberties are more persistent than political rights in affecting subsequent outcomes and that this result is robust to the addition of covariates, estimation techniques, and variations in our sample. Moreover, we also show that while prior levels of civil liberties impact substantially and positively current levels of political rights, the reverse is not the case. We then consider how the unbundling of democracy relates to two important recent findings: Acemoglu et al’s (2008) conclusion that long-run income changes do not affect democracy in terms of political rights holds as well for civil liberties; Tsui’s (2011) conclusion that changes in oil discoveries affect democracy in terms of political rights negatively is consistent with our finding that total oil reserves affect democracy negatively, not only in terms of political rights but also in terms of civil liberties.
Does modafinil produce euphoria?

incorrectly concluded that our group’s research on modafinil fails to support the lack of euphoria. We recently reported that modafinil promoted abstinence in cocaine-dependent subjects (N=62) during an 8-week placebo-controlled trial (2). We assessed modafinil abuse/overuse by dispensing a 9-day supply of study medications each week and analyzing pill return rates in the modafinil (N=30) and placebo (N=32) groups. There were no significant differences between the modafiniltreated and placebo-treated groups on pill return rates (χ 2 = 0.01, df=1, p=0.93), and the Mann-Whitney test showed no differences between the groups (z=–0.14, p=0.99) on pill return rates. Cocaine-addicted patients are arguably the most likely to abuse any substance that produces stimulant-like euphoria and are therefore unlikely to return pills that actually produce euphoria. Rather than producing additive euphoria when mixed with cocaine, modafinil blunts cocaine-induced euphoria under controlled laboratory conditions (3, 4). Modafinil is a schedule IV medication under the Controlled Substances Act and is chemically unrelated to central stimulants. It binds the dopamine transporter with an affinity that is well below that of the unscheduled antidepressant bupropion, also listed as producing euphoria by the PDR. Other studies (5) have reported that modafinil did not produce amphetamine-like effects and was indistinguishable from caffeine; that, in comparison with methylphenidate and placebo, modafinil “is not an amphetamine-like agent,” (6) and that subjects with a history of heavy cocaine abuse could not discriminate the cocaine-like effects of modafinil under controlled conditions. Only one study reported that women with a history of cocaine dependence (N=12) could discriminate some amphetamine-like effects of modafinil (7). Based on these premarketing studies, the Food and Drug Administration/Drug Enforcement Administration did not schedule modafinil along with methylphenidate and other stimulants in schedule II but rather in the less restrictive schedule IV. Postmarketing surveillance and animal studies suggest that modafinil has little potential for abuse. We therefore believe that modafinil has not been convincingly reported to produce euphoria, and there has been no indication of excessive use or abuse in clinical trials among individuals with cocaine de
[The participation of patients with schizophrenia in psychoeducation--the analysis from the patients' perspective].

AIM The aim of this study was to find out what the patients opinion about psychoeducation in schizophrenia is. METHOD We examined 169 patients suffering from schizophrenia. They answered a questionnaire about demographic data, their opinion about participation in sessions, the motivation to psychoeducation and the themes of sessions. RESULTS . 84% of the patients declared that they like psychoeducation. The main reason for participation in psychoeducation was the willingness to get more information about the illness and prevent relapses. The most important therapist attributes are: high communication abilities and appropriate knowledge. CONCLUSIONS The patients want to get more information about the illness and obtain more knowledge how to cope with symptoms in order to improve the quality of their life. It is important for the therapists to create an emotional atmosphere which helps to understand each other. During the psychoeducation sessions the therapist should use more various means to get the patients involved in participation.
The effects of breath-holding on vocal fold adduction: implications for safe swallowing.

OBJECTIVE To determine the effects, if any, of 3 different breath-holding techniques on a person's ability to attain vocal fold closure (VFC) to successfully complete swallowing maneuvers. DESIGN Prospective, randomized study. SETTING Private practice. PATIENTS A total of 150 healthy volunteers recruited from private practice patients and community volunteers. Intervention Group 1 received the easy breath-hold instruction; group 2 received the inhale/easy breath-hold instruction; and group 3 received the hard breath-hold instruction. MAIN OUTCOME MEASURE Closure of true and false vocal folds following the breath-hold instruction. RESULTS In the easy breath-hold group, true VFC occurred in 82% of the subjects, and closure of both the true and false vocal folds occurred in 30%. In the inhale/easy breath-hold group, true VFC occurred in 62%, and closure of both folds occurred in 46%. In the hard breath-hold group, true VFC occurred in 86%, and closure of both folds occurred in 64%. The differences among the 3 groups were significant for true VFC (chi2=9.242; P=.01) and for closure of both folds (chi2=11.625; P=.003). CONCLUSIONS The hard breath-hold instruction was the most effective method to attain full laryngeal closure, and the inhale/easy breath-hold instruction was the least effective method to attain true VFC for safe swallowing.