Miracle-dz/UniFAR-FTUs huggingface dataset:
SIRT1 as a potential therapeutic target for treatment of nonalcoholic fatty liver disease

Summary Sirtuins are members of the silent information regulator 2 (Sir2) family, a group of Class III histone/protein deacetylases. There are 7 different sirtuins in mammals (SIRT1-7), of which SIRT1 is the best known and most studied. SIRT1 is responsible for the regulation of protein activation by means of deacetylating a variety of proteins that play important roles in the pathophysiology of metabolic diseases. Recently, it has been shown that SIRT1 plays key roles in the regulation of lipid and glucose homeostasis, control of insulin secretion and sensitivity, antiinflammatory effects, control of oxidative stress and the improvements in endothelial function that result due to increased mitochondrial biogenesis and β-oxidation capacity. Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease, and it has been accepted as the hepatic component of metabolic syndrome. Recent studies have shown that SIRT expression in the liver is significantly decreased in an NAFLD model of rats fed a high-fat diet, and moderate SIRT1 overexpression protects mice from developing NAFLD. In addition to resveratrol, a natural SIRT1 activator, small-molecule pharmacologic SIRT1 activators have positive effects on metabolic diseases. These effects are particularly promising in the case of diabetes mellitus, for which phase studies are currently being performed. With this information, we hypothesized that the pharmacologic activation of SIRT1, which has been implicated in the pathogenesis of NAFLD, will be a potential therapeutic target for treating NAFLD. In this paper, we review the metabolic effects of SIRT1 and its association with the pathophysiology of NAFLD.
Managed moves: schools collaborating for collective gain

Government guidance in the United Kingdom encourages groups of schools to take collective responsibility for supporting and making provision for excluded pupils and those at risk of exclusion. Managed moves are one way that some schools and authorities are enacting such guidance. This article presents the results of an evaluation of one such scheme. The scheme, involving seven neighbouring secondary schools, was nearing its first year of completion. The article draws primarily on interview data with pupils, parents and school staff to describe a number of positive outcomes associated with the scheme and to explore how these were achieved. We found that while some of these could be attributed directly to the managed move, others arose from the more inclusive ethos and practices of particular schools. The concepts of tailored support, care and commitment emerged as strong themes that underpinned the various practical ways in which some schools in the cluster were able to re‐engage ‘at‐risk’ pupils. As managed moves become more widely practised it will be important to remember that it is how the move proceeds and develops rather than the move itself that will ultimately make the difference for troubled and troublesome pupils.
Retrospective Questions or a Diary Method? A Two-Level Multitrait-Multimethod Analysis

This study describes a comparison between retrospective questions and daily diaries inquiring about positive and negative support in spousal interactions. The design was a multitrait-multimethod matrix with trait factors of positive and negative support, and method factors of retrospective questions and daily asked questions. Five questions were used for positive support and 2 questions were used for negative support. The data were multilevel, with daily measurement occasions nested within subjects. In addition, the data were ordered categorically. The negative support events proved to be so rare that the original 4-point response scale had to be dichotomized. The resulting model could be estimated using M plus, but the model and data complexities set some limits to the analysis. The results showed that at the subject level both positive and negative support could be assessed with sufficient reliability and validity. At the daily measurements level, positive support showed significant but low reliability and validity, but negative support could not be assessed reliably. It was concluded that at the daily level both positive and negative support should be viewed as transient events that do not indicate an underlying latent variable, but that could be modeled as a formative construct.
Statistical perspectives: all together NOT

An editorial under the title Statistics: all together now, one step at a time appeared in this and other physiological journals earlier this year (Drummond et al., 2011) to announce a forthcoming series of 14 perspective articles on statistics. Two of the articles have now been published in six journals (Drummond and Vowler, 2011a; Drummond and Vowler, 2011b) and the third has started to appear (Drummond and Tom, 2011). The purpose of this letter is to identify what we consider to be substantial errors and omissions.
Four Global Trends: Rise and Limitations

The world seems to be rushing into the state of a global risk-society. Is the diagnosis correct? What are the causes and reasons of the current tensions? What are the prospects? Four global trends are assumed to penetrate the new constellations of cooperation and conflict. The spreading of instrumental activism has its roots in the `conquer and dominate' philosophy of modern industrialism. It is trapped by its own expansion. Individualization is embodied in major evolutionary achievements. It is simultaneously the source of cultural and institutional imbalances. Modernity is marked by an accelerated upgrading of organizational rationality. The process brings about organizational pathologies as well. We witness a fast value-normative universalization. It is paralleled by symbolic and institutional particularizations. Managing these four inherently controversial trends is the major challenge to continuing modernization.
On the Social Welfare of Mechanisms for Repeated Batch Matching

We study hybrid online-batch matching problems, where agents arrive continuously, but are only matched in periodic rounds, when many of them can be considered simultaneously. Agents not getting matched in a given round remain in the market for the next round. This setting models several scenarios of interest, including many job markets as well as kidney exchange mechanisms. We consider the social utility of two commonly used mechanisms for such markets: one that aims for stability in each round (greedy), and one that attempts to maximize social utility in each round (max-weight). Surprisingly, we find that in the long term, the social utility of the greedy mechanism can be higher than that of the max-weight mechanism. We hypothesize that this is because the greedy mechanism behaves similarly to a soft threshold mechanism, where all connections below a certain threshold are rejected by the participants in favor of waiting until the next round. Motivated by this observation, we propose a method to approximately calculate the optimal threshold for an individual agent to use based on characteristics of the other agents participating, and demonstrate experimentally that social utility is high when all agents use this strategy. Thresholding can also be applied by the mechanism itself to improve social welfare; we demonstrate this with an example on graphs that model pairwise kidney exchange.
Characterization of the acid stress response of Acidithiobacillus ferrooxidans ATCC 23270 based on the method of microarray

Bioleaching has become a research hotspot, as a simple and effective technology for metal extraction from low-grade ores. During the process of bioleaching, the chemoautotroph organisms play a key role. However, their growth and activity are greatly restrained by the stress brought by over acidic extracellular environment in industrial practice. This research effort focused on the transciptome profile discrepancies of the typical bioleaching species Acidithiobacillus ferrooxidans ATCC 23270 when challenged by a pH downshift to pH 1.2 using the method of microarray. A total of 1853 genes were found to be significantly affected under acid stress challenge for 1 hr, and the array data revealed that A. ferrooxidans ATCC 23270 actively responses to acid stress from several levels: cell envelope level, cytoplasm level and transcription level. One remarkable change is that the ion transporters and the synthesis of glutamine and polyamines were regulated in chemoautotrophic A. ferrooxidans ATCC 23270 under acid stress, while in contrast, typical heterotrophic bacteria Escherichia coli depended on up-regulation of ATP synthase F0F1 and glutamate decarboxylase system. More specifically, the alkaline substances generated by glnA, glnB, glnD, glnE etc. were functional in buffering the cytoplasm pH, and certain proton pumps such as cytoplasm protons plasma-membrane proton transport P-type ATPase played an important role in proton expulsion to keep cytoplasm pH in certain range. The new information provided in this study could lead to a better understanding of the acid resistance mechanisms exhibited by autotrophic acidophilic bacteria.
Referential management and activated memory in Korean discourse

L'article explore la relation entre la selection de la forme des expressions referentielles et le statut memoriel des referents. On demande a deux groupes de locuteurs coreens de produire un enonce narratif descriptif en meme temps qu'ils visualisent une sequence d'images. Les images sont presentees de maniere a pouvoir controler le statut de l'activation memorielle du referent
SiRNA‐targeted carboxypeptidase D inhibits hepatocellular carcinoma growth

Carboxypeptidase D (CPD), a membrane‐bound metallocarboxypeptidase that functions as a docking receptor for duck hepatitis B virus, is frequently overexpressed in human cancers. We have explored its expression pattern, clinical significance, and biological function of CPD in hepatocellular carcinoma (HCC). CPD expression was markedly elevated in HCCs relative to adjacent non‐tumor liver tissues, as determined by quantitative real‐time polymerase chain reaction and Western blot analysis. Immunohistochemistry showed that 164 of 400 (41%) HCCs had high expression of CPD. CPD overexpression was significantly associated with serum levels of hepatitis B surface antigen and hepatitis B e antigen, liver cirrhosis, pathological grade, and intrahepatic metastasis. Knockdown of endogenous CPD expression in Huh7 HCC cells by RNA interference reduced cell proliferation, blocked the cell cycle at G1 phase, and increased apoptosis. Many genes implicated in cell‐cycle regulation, including P21waf1, P27 Kip1, SKP2, and CDC2, were deregulated by CPD downregulation. Thus CPD is frequently upregulated in HCC, and targeting CPD inhibits HCC cell proliferation through induction of G1 cell‐cycle arrest and apoptosis, thereby providing a potential therapeutic target for this malignancy.
Combined eye-head gaze shifts in the primate. III. Contributions to the accuracy of gaze saccades.

1. The behavior of the combined eye-head gaze saccade mechanism was investigated in the rhesus monkey under both normal circumstances and in the presence of perturbations delivered to the head by a torque motor. Animals were trained to follow a target light that stepped at regular intervals through an angle of 68 degrees (+/- 34 degrees with respect to the midsagittal plane). Thus all primary saccades were center crossing. On randomly occurring trials the torque motor was pulsed so as to perturb the trajectory of the head, thus allowing us to assess both the functional state of the vestibuloocular reflex (VOR) and the effects of such perturbations on gaze saccade accuracy (gaze is defined as the sum of eye-in-head plus head-in-space, and a gaze saccade as a combined eye-head saccadic gaze shift). 2. Gaze shifts can be divided into two discrete sections: the portion during which the gaze angle is changing (the saccadic portion), and the portion during which the gaze is stationary but the head continues to move (the terminal head-movement portion). For the system to accurately acquire eccentric targets, at least two criteria must be met: 1) the saccadic portion must be accurate, and 2) the compensatory eye movement that occurs during the terminal head-movement portion must be equal and opposite to the head movement, thereby maintaining gaze stability. Perturbations delivered during the terminal head-movement portion of the gaze shift indicated that VOR was functioning normally, and thus we concluded that the compensatory eye movements that accompany head movements were vestibular in origin. 3. As reported previously, during the saccadic portion of large-amplitude gaze saccades, the VOR ceases to function. In spite of this observation, the accuracy of the gaze saccade is not affected by perturbations delivered to the head. Gaze accuracy is maintained both by changing the duration of the saccadic portion and by altering the head trajectory. 4. Because rhesus monkeys often make very rapid head movements (1,200 degrees/s), we wished to discover the velocity range over which the monkey VOR might be expected to operate. Accordingly, in a second series of experiments, VOR function was assessed during passive whole-body rotations with the head fixed. By the use of spring-assisted manual rotations, peak velocities up to 850 degrees/s were achieved. When VOR gain was measured during such rotations, it was found to be equal to 0.9 up to the maximum velocities used. (ABSTRACT TRUNCATED AT 400 WORDS)
What Can Be Learned from Informal Student Writings in a Science Context

This exploratory study analyzed four informal science-related writing tasks produced by 374 seventh-grade students (172 boys and 202 girls) from two schools with different socioeconomic populations. The study demonstrates that students' informal writing in science contexts can provide a rich source of information regarding students' cognitive and attitudinal engagement with science. Students' writing reflects the level at which students understand previously learned science-related ideas and gives insight into themes and issues they would be interested in learning. This study further demonstrates how students organize and personalize science knowledge acquired inside as well as outside of school when given novel and unconventional (informal) science-related tasks. The study also demonstrates that informal writing tasks encourage students to express opinions, values, and attitudes associated with science and science learning. Examples are provided of similarities and differences in students' writing preferences and in the quality of writing produced by boys and girls. Suggestions for further studies for teachers and researchers are discussed.
Inhibition of Translation Initiation by Protein 169: A Vaccinia Virus Strategy to Suppress Innate and Adaptive Immunity and Alter Virus Virulence

Vaccinia virus (VACV) is the prototypic orthopoxvirus and the vaccine used to eradicate smallpox. Here we show that VACV strain Western Reserve protein 169 is a cytoplasmic polypeptide expressed early during infection that is excluded from virus factories and inhibits the initiation of cap-dependent and cap-independent translation. Ectopic expression of protein 169 causes the accumulation of 80S ribosomes, a reduction of polysomes, and inhibition of protein expression deriving from activation of multiple innate immune signaling pathways. A virus lacking 169 (vΔ169) replicates and spreads normally in cell culture but is more virulent than parental and revertant control viruses in intranasal and intradermal murine models of infection. Intranasal infection by vΔ169 caused increased pro-inflammatory cytokines and chemokines, infiltration of pulmonary leukocytes, and lung weight. These alterations in innate immunity resulted in a stronger CD8+ T-cell memory response and better protection against virus challenge. This work illustrates how inhibition of host protein synthesis can be a strategy for virus suppression of innate and adaptive immunity.
The Identification of a Small Molecule Compound That Reduces HIV-1 Nef-Mediated Viral Infectivity Enhancement

Nef is a multifunctional HIV-1 protein that accelerates progression to AIDS, and enhances the infectivity of progeny viruses through a mechanism that is not yet understood. Here, we show that the small molecule compound 2c reduces Nef-mediated viral infectivity enhancement. When added to viral producer cells, 2c did not affect the efficiency of viral production itself. However, the infectivity of the viruses produced in the presence of 2c was significantly lower than that of control viruses. Importantly, an inhibitory effect was observed with Nef+ wild-type viruses, but not with viruses produced in the absence of Nef or in the presence of proline-rich PxxP motif-disrupted Nef, both of which displayed significantly reduced intrinsic infectivity. Meanwhile, the overexpression of the SH3 domain of the tyrosine kinase Hck, which binds to a PxxP motif in Nef, also reduced viral infectivity. Importantly, 2c inhibited Hck SH3-Nef binding, which was more marked when Nef was pre-incubated with 2c prior to its incubation with Hck, indicating that both Hck SH3 and 2c directly bind to Nef and that their binding sites overlap. These results imply that both 2c and the Hck SH3 domain inhibit the interaction of Nef with an unidentified host protein and thereby reduce Nef-mediated infectivity enhancement. The first inhibitory compound 2c is therefore a valuable chemical probe for revealing the underlying molecular mechanism by which Nef enhances the infectivity of HIV-1.
MCEIL: An Improved Scoring Function for Overlapping Community Detection using Seed Expansion Methods

Community detection is one of the most well known problems in complex network analysis. In real-world networks, communities often overlap. Various approaches have been proposed in the literature to detect overlapping communities in networks. Local Expansion and optimization approaches have gained popularity due to their scalability and robustness. In a method based on local expansion, the seeding strategy and scoring function employed are crucial to the performance of the algorithm.In this paper, a scoring function called CEIL score is used with ground-truth seeds in local expansion and optimization algorithm. Using CEIL score has significantly improved performance of the algorithms with respect to evaluation metrics NMI and F1 score. However, CEIL has lower coverage than conductance. An extension to CEIL score, called MCEIL score is proposed. Using MCEIL score returns communities with coverage as high as conductance, and NMI and F1 scores higher than conductance on different kinds of datasets.Experiments on datasets of different types with different seeding strategies show that the improvements in NMI and F1 score obtained by MCEIL score are substantial.
Quaternary Ammonium Compounds as Water Channel Blockers

Excessive water uptake through Aquaporins (AQP) can be life-threatening and reversible AQP inhibitors are needed. Here, we determined the specificity, potency, and binding site of tetraethylammonium (TEA) to block Aquaporin water permeability. Using oocytes, externally applied TEA blocked AQP1/AQP2/AQP4 with IC50 values of 1.4, 6.2, and 9.8 μm, respectively. Related tetraammonium compounds yielded some (propyl) or no (methyl, butyl, or pentyl) inhibition. TEA inhibition was lost upon a Tyr to Phe amino acid switch in the external water pore of AQP1/AQP2/AQP4, whereas the water permeability of AQP3 and AQP5, which lack a corresponding Tyr, was not blocked by TEA. Consistent with experimental data, multi-nanosecond molecular dynamics simulations showed one stable binding site for TEA, but not tetramethyl (TMA), in AQP1, resulting in a nearly 50% water permeability inhibition, which was reduced in AQP1-Y186F due to effects on the TEA inhibitory binding region. Moreover, in the simulation TEA interacted with charged residues in the C (Asp128) and E (Asp185) loop, and the A(Tyr37-Asn42-Thr44) loop of the neighboring monomer, but not directly with Tyr186. The loss of TEA inhibition in oocytes expressing properly folded AQP1-N42A or -T44A is in line with the computationally predicted binding mode. Our data reveal that the molecular interaction of TEA with AQP1 differs and is about 1000-fold more effective on AQPs than on potassium channels. Moreover, the observed experimental and simulated similarities open the way for rational design and virtual screening for AQP-specific inhibitors, with quaternary ammonium compounds in general, and TEA in particular as a lead compound.
Social Modulation of Stress Reactivity and Learning in Young Worker Honey Bees

Alarm pheromone and its major component isopentylacetate induce stress-like responses in forager honey bees, impairing their ability to associate odors with a food reward. We investigated whether isopentylacetate exposure decreases appetitive learning also in young worker bees. While isopentylacetate-induced learning deficits were observed in guards and foragers collected from a queen-right colony, learning impairments resulting from exposure to this pheromone could not be detected in bees cleaning cells. As cell cleaners are generally among the youngest workers in the colony, effects of isopentylacetate on learning behavior were examined further using bees of known age. Adult workers were maintained under laboratory conditions from the time of adult emergence. Fifty percent of the bees were exposed to queen mandibular pheromone during this period, whereas control bees were not exposed to this pheromone. Isopentylacetate-induced learning impairments were apparent in young (less than one week old) controls, but not in bees of the same age exposed to queen mandibular pheromone. This study reveals young worker bees can exhibit a stress-like response to alarm pheromone, but isopentylacetate-induced learning impairments in young bees are suppressed by queen mandibular pheromone. While isopentylacetate exposure reduced responses during associative learning (acquisition), it did not affect one-hour memory retrieval.
Modeling for Information Diffusion in Online Social Networks via Hydrodynamics

In recent years, online social networks have gained tremendous popularity because of the massive number of online users, the fast spread of information, and strong inter-personal influence. However, due to the high complexity of the user interaction and the real-time changing of the online social networks, it is still a big challenge to model the spreading process of the information delicately and, then, to predict the information diffusion precisely. In this paper, we exploit a hydrodynamic model to describe the spreading process of the information in online social networks. By using the proposed hydrodynamic information diffusion prediction model (hydro-IDP), we can describe the spreading process of the information on both temporal and spatial perspectives. It is also helpful in extracting the characteristics of information diffusion (e.g., the information popularity, the user influence, and the diffusivity of social platform). We also consider the superimposed effect of the information diffusion resulted from influential users in the model. The high accuracy of the model results has illustrated that our proposed Hydro-IDP model is competent to describe and predict the spreading process of information in online social networks.