Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-34a repression of SIRT1 regulates apoptosis

MicroRNA 34a (miR-34a) is a tumor suppressor gene, but how it regulates cell proliferation is not completely understood. We now show that the microRNA miR-34a regulates silent information regulator 1 (SIRT1) expression. MiR-34a inhibits SIRT1 expression through a miR-34a-binding site within the 3′ UTR of SIRT1. MiR-34 inhibition of SIRT1 leads to an increase in acetylated p53 and expression of p21 and PUMA, transcriptional targets of p53 that regulate the cell cycle and apoptosis, respectively. Furthermore, miR-34 suppression of SIRT1 ultimately leads to apoptosis in WT human colon cancer cells but not in human colon cancer cells lacking p53. Finally, miR-34a itself is a transcriptional target of p53, suggesting a positive feedback loop between p53 and miR-34a. Thus, miR-34a functions as a tumor suppressor, in part, through a SIRT1-p53 pathway.
Localization Based on Social Big Data Analysis in the Vehicular Networks

Location-based services, especially for vehicular localization, are an indispensable component of most technologies and applications related to the vehicular networks. However, because of the randomness of the vehicle movement and the complexity of a driving environment, attempts to develop an effective localization solution face certain difficulties. In this paper, an overlapping and hierarchical social clustering model (OHSC) is first designed to classify the vehicles into different social clusters by exploring the social relationship between them. By using the results of the OHSC model, we propose a social-based localization algorithm (SBL) that use location prediction to assist in global localization in the vehicular networks. The experiment results validate the performance of the OHSC model and show that the presented SBL algorithm demonstrates superior localization performance compared with the existing methods.
Gliomas induce and exploit microglial MT 1-MMP expression for tumor expansion

aCellular Neuroscience, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany; bDepartment of Neurosurgery, Helios Clinics, 13125 Berlin, Germany; cDepartments of Neurosurgery and fNeuropathology and eCecilie Vogt Clinic for Neurology, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany; dLaboratory of Transcription Regulation, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland; gDepartment of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit, VU University Medical Center, 1081 BT Amsterdam, The Netherlands; and hCraniofacial Skeletal Diseases Branch, Matrix Metalloproteinase Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
EFFECTS OF INDIVIDUAL HETEROGENEITY IN ESTIMATING THE PERSISTENCE OF SMALL POPULATIONS

ABSTRACT. Population viability models are commonly used to estimate the probability of persistence of small, threatened, or endangered populations. Demographic, temporal, spatial, and individual heterogeneity are important factors affecting the probability of persistence of small populations. Because stochastic process are intractable analytically (Lud‐wig [1996]), computer simulation models are often used for estimating population viability via numerical techniques. Although demographic, spatial, and temporal stochasticity have been incorporated into some population viability models, individual heterogeneity has not been included. In this paper we include individual heterogeneity in a simulation model and examine probabilities of population persistence at different levels of heterogeneity and population size. Individual heterogeneity may increase the probability of persistence of small populations. The mechanism for the extension in persistence may be explained by natural selection. Genotypes persisting through a decline may be those that survive better under the conditions causing the decline. These individuals that survive and reproduce in the face of adverse conditions may extend the probability that a small population persists.
Current Account Sustainability: the case of Bosnia and Herzegovina

This research investigates whether the persistent current account deficit in Bosnia and Herzegovina (BH) is sustainable. Initially current account sustainability is investigated by using the concept of a stationary condition and the mean reversion proposition. It is argued that stationarity of the current account presents a minimum requirement for current account sustainability assessment based on less strict intertemporal solvency conditions. It was found that four out of the five Western Balkan countries investigated have a stationary current account to GDP ratio and therefore met this minimum requirement for sustainability. In order to develop an empirical model to assess current account sustainability in BH, next the Fundamental Equilibrium Exchange Rate is estimated. The conclusion drawn from this analysis was that BH‟s high and persistent current account deficit was not caused by exchange rate misalignment, thus there is no need to adjust the peg. The main reason behind the BH current account deficit is its trade deficit. In the absence of previous analyses of trade deficit sustainability in the WB the next question assessed was whether forming an free trade agreement is a helpful policy for BH utilising an ex post empirical analysis. The analysis of the new Central European Free Trade Agreement concentrates upon three effects: on trade flows using gravity equations; on Bosnia and Herzegovina‟s trade potential and on future deficit sustainability in BH. It was found that although BH trade flows were affected by the CEFTA agreement, the net effect was to contribute to a further widening of the trade deficit in BH. Given the finding that BH‟s current account deficit cannot be attributed to (real) exchange rate misalignment the main conclusion is that current account sustainability analysis must be based on understanding the reasons why BH has a persistent trade deficit. The main reason behind BH current account deficit is its trade deficit. The main factor underlying trade deficit in BH is strong demand for imported goods and also BH‟s supply side weaknesses. Policy-makers need to create an environment for the private sector to develop. Hence both micro and macroeconomic conditions would have to be considered by BH policy-makers in order for this country to improve its export competitiveness and its trade position, which could reduce high BH current account deficit.
The Making of Might-Have-Beens

Counterfactual thoughts are based on the assumption that one situation could result in multiple possible outcomes. This assumption underlies most theories of free will and contradicts deterministic views that there is only one possible outcome of any situation. Three studies tested the hypothesis that stronger belief in free will would lead to more counterfactual thinking. Experimental manipulations (Studies 1-2) and a measure (Studies 3-4) of belief in free will were linked to increased counterfactual thinking in response to autobiographical (Studies 1, 3, and 4) and hypothetical (Study 2) events. Belief in free will also predicted the kind of counterfactuals generated. Belief in free will was associated with an increase in the generation of self and upward counterfactuals, which have been shown to be particularly useful for learning. These findings fit the view that belief in free will is promoted by societies because it facilitates learning and culturally valued change.
Circuit projection from suprachiasmatic nucleus to ventral tegmental area: a novel circadian output pathway

The suprachiasmatic nucleus (SCN) is a circadian pacemaker that synchronizes a number of vital processes. Although a great deal of research has focused on input pathways to SCN and on the central clock itself, relatively little is known about SCN output signaling pathways. The ventral tegmental area (VTA) has been extensively studied for its influence in motivated learning and, recently, for a potential role in arousal and sleep–wake regulation. Here we present data that SCN indirectly projects to VTA via the medial preoptic nucleus (MPON). Microinjection of the retrograde, transynaptic tracer pseudorabies virus (PRV) in rat VTA consistently labeled SCN neurons at time points indicative of an indirect circuit projection. To specify intermediate relay nuclei between SCN and VTA, putative relays were lesioned 1 week prior to PRV injections in VTA. Unilateral lesions of MPON reduced PRV labeling in SCN by 81.6% in the ipsilateral hemisphere and 75.8% in the contralateral hemisphere. Bilateral lesions of the caudal–dorsal lateral septum, another putative relay nucleus and dorsal injection control, did not significantly reduce PRV labeling in the SCN. Single‐unit extracellular recordings under halothane anesthesia revealed a novel population of VTA neurons that selectively fired during the active circadian phase. These results show that SCN provides an indirect circuit pathway to VTA via MPON, and that VTA neurons exhibit a circadian rhythm in their impulse activity. This pathway may function in the circadian regulation of numerous behavioral processes including arousal and motivation.
Mitogenicity of bacterial endotoxins: characterization of the mitogenic principle.

Endotoxins from smooth strains of Salmonella typhimurium and from rough variants of Ra, Rc and Re chemotype were mitogenic for mouse spleen cells. Haptenic polysaccharides and native protoplasmic polysaccharides possessed very little mitogenicity. Lipid A was strongly mitogenic. Mild alkaline hydrolysis of complete endotoxin or lipid A, a procedure which cleaves off ester-linked fatty acids, caused a substantial loss of mitogenic activity. These data indicate that endotoxin acts as a nonspecific or general mitogen and that the mitogenic response is not mediated by immunologic mechanisms.
Rhizonin, the First Mycotoxin Isolated from the Zygomycota, Is Not a Fungal Metabolite but Is Produced by Bacterial Endosymbionts

ABSTRACT Rhizonin is a hepatotoxic cyclopeptide isolated from cultures of a fungal Rhizopus microsporus strain that grew on moldy ground nuts in Mozambique. Reinvestigation of this fungal strain by a series of experiments unequivocally revealed that this “first mycotoxin from lower fungi” is actually not produced by the fungus. PCR experiments and phylogenetic studies based on 16S rRNA gene sequences revealed that the fungus is associated with bacteria belonging to the genus Burkholderia. By transmission electron microscopy, the bacteria were localized within the fungal cytosol. Toxin production and the presence of the endosymbionts were correlated by curing the fungus with an antibiotic, yielding a nonproducing, symbiont-free phenotype. The final evidence for a bacterial biogenesis of the toxin was obtained by the successful fermentation of the endosymbiotic bacteria in pure culture and isolation of rhizonin A from the broth. This finding is of particular interest since Rhizopus microsporus and related Rhizopus species are frequently used in food preparations such as tempeh and sufu.
Vhs2 is a novel regulator of septin dynamics in budding yeast

In budding yeast, septins are assembled into structures that undergo dramatic changes during the cell cycle. The molecular mechanisms that drive these remodelings are not fully uncovered. In this study, we describe a characterization of Vhs2, a nonessential protein that revealed to be a new player in septin dynamics. In particular, we report that Vhs2 is important to maintain the stability of the double septin ring structure until telophase. In addition, we show that Vhs2 undergoes multiple phosphorylations during the cell cycle, being phosphorylated during S phase until nuclear division and dephosphorylated just before cell division. Importantly we report that cyclin-dependent protein kinase Cdk1 and protein phosphatase Cdc14 control these Vhs2 post-translational modifications. These results reveal that Vhs2 is a novel Cdc14 substrate that is involved in the control of septin organization.
G9a/GLP Histone Lysine Dimethyltransferase Complex Activity in the Hippocampus and the Entorhinal Cortex Is Required for Gene Activation and Silencing during Memory Consolidation

Learning triggers alterations in gene transcription in brain regions such as the hippocampus and the entorhinal cortex (EC) that are necessary for long-term memory (LTM) formation. Here, we identify an essential role for the G9a/G9a-like protein (GLP) lysine dimethyltransferase complex and the histone H3 lysine 9 dimethylation (H3K9me2) marks it catalyzes, in the transcriptional regulation of genes in area CA1 of the rat hippocampus and the EC during memory consolidation. Contextual fear learning increased global levels of H3K9me2 in area CA1 and the EC, with observable changes at the Zif268, DNMT3a, BDNF exon IV, and cFOS gene promoters, which occurred in concert with mRNA expression. Inhibition of G9a/GLP in the EC, but not in the hippocampus, enhanced contextual fear conditioning relative to control animals. The inhibition of G9a/GLP in the EC induced several histone modifications that include not only methylation but also acetylation. Surprisingly, we found that downregulation of G9a/GLP activity in the EC enhanced H3K9me2 in area CA1, resulting in transcriptional silencing of the non-memory permissive gene COMT in the hippocampus. In addition, synaptic plasticity studies at two distinct EC–CA1 cellular pathways revealed that G9a/GLP activity is critical for hippocampus-dependent long-term potentiation initiated in the EC via the perforant pathway, but not the temporoammonic pathway. Together, these data demonstrate that G9a/GLP differentially regulates gene transcription in the hippocampus and the EC during memory consolidation. Furthermore, these findings support the possibility of a role for G9a/GLP in the regulation of cellular and molecular cross talk between these two brain regions during LTM formation.
Stress at Work: Do Managers Really Count the Costs?

Organizations are being forced to contend with an increasingly diverse range of influential factors which have implications for their efficiency and effectiveness. Such factors are likely to create a cumulative spiral of pressures for organization members and render them susceptible to the adverse effects of stress. Increased prevalence of work stress among employees, coupled with its harmful effects for the operation of companies, prompted an investigation of managerial attitudes to stress at work in the clothing industry. Structured interviews were carried out with managers from 44 companies. Of the respondents 70.5 per cent believed that employees in their company experienced stress at work. Many identified a range of causes and effects, and 81.4 per cent acknowledged that stress is a problem for individuals and organizations. However, few companies had any mechanisms for identifying and helping stressed employees. Highlights a need for companies to take cognizance of the costs of stress within organiz.
Novel delay-dependent synchronization criteria for chaotic Lur'e Systems

This paper studies the synchronization problem for a class of chaotic Lur'e systems using a time-delay feedback control. By dividing the delay interval into multiple segments, some proper Lyapunov-Krasovskii functionals with different weighting matrices corresponding to different segments are constructed. Based on new Lyapunov-Krasovskii functionals and linear matrix inequality technique, some new delay-dependent synchronization criteria are derived. Moreover, delayed feedback controllers are established under which the chaotic master and slave systems are synchronized with a guaranteed H∞ performance. Finally, two numerical simulations are given to validate the effectiveness and feasibility of the obtained results.
Analysis of genome instability biomarkers in children with non-syndromic orofacial clefts

The non-syndromic cleft lip and/or palate (NSCL/P) is a common birth defect caused by a combination of genetic and environmental factors. The possible role of genome instability on NSCL/P patient needs more investigation, since DNA metabolism is an essential cellular function to keep cells with normal genotypes and gene expression patterns according to tissue specificities, which is critical during embryo development because it requires sensitive regulation of cell proliferation, apoptosis and differentiation. Thus, genome stability is ultimately essential to maintain a healthy life. The aim of this study was to assess the frequency of genome instability biomarkers and their relationship with NSCL/P. Cytokinesis-block micronucleus assay was performed to estimate the biomarkers frequency and gene expression was analyzed by the transcriptogram in order to further explore the role of genome instability and other biological processes in this birth defect. The NSCL/P patients had higher baseline frequency of micronucleus, nuclear buds and nucleoplasmic bridges (P < 0.001) than the control group. Moreover, new nuclear morphologies (fused, circular and horseshoe) was detected in the patients' cells analyzed, possibly indicating that chronic folic acid deficiency is interfering in their genome instability. Children with clefts had 2.3 times more risk to have high micronuclei frequency (P = 0.043) according to binary logistic regression. The high genomic instability in children with oral clefts suggests that misrepaired double strand breaks in DNA that create micronuclei representing a significant factor in NSCL/P development. This study was published in 52nd EUROTOX Abstract Book.
A novel planar level chip interconnection for unpackaged MMICs in the millimeter wave frequency range

This paper presents a novel planar interconnection technology for unpackaged monolithic microwave integrated circuits (MMICs), which work in the millimeter wave (mmw) frequency range. Compared to standard wire bonding, the new technique provides considerable advantages with regard to the electrical characteristics and manufacturing processes. The manufacturing process for a module containing surface mounted devices (SMD) and unpackaged MMICs is described. In order to determine the electrical behavior, a model of a single interconnection is developed using a full wave field simulation and compared to a model of a wire bond. Finally, the insertion losses are determined by measuring the output power of an active frequency doubler, which is assembled using both technologies. Because of the availability of commercial MMICs an operating frequency of 77 GHz is considered.
Why Do Firms Announce Open Market Repurchase Programs

Empirically, a price increase accompanies the announcement of an open-market stock repurchase program, even though the announcement is not a commitment. In fact, for many announced programs no shares are ever actually repurchased. This article explores this puzzle. In the single-firm-type version of the model, the option that a firm grants itself by announcing a program does not generate announcement returns. In equilibrium, long-run gains from the informed trading that the option creates are offset by short-run costs from the market's accounting for this adverse selection. Based on this trade-off, I construct a signaling (two-type) model that can deliver announcement returns. In the separating equilibrium, good firms do not incur any cost when they announce programs. Their gains from informed trading in the long run offset the cost of announcement incurred in the short run. Mimicry is costly, because a bad firm's long-run gains from informed trading cannot compensate for the short-run cost of announcing. Copyright 2005, Oxford University Press.
Deficits, delays, and distractions: An evaluation of symbolic play and memory in children with autism

Two experiments were conducted to evaluate symbolic-deficit and memory-deficit hypotheses to account for the cognitive problems seen in children with autism. Experiment 1 tested imitation, in immediate and deferred conditions, of familiar actions with different sets of objects representing the developmental progression from functional to symbolic play. The results showed that the autism group and both their receptive language and nonverbal IQ-matched controls imitated familiar actions with realistic objects (evidence for functional play) and placeholder objects (evidence for symbolic play) after delays ranging from 24 hr to 3 weeks. Experiment 2 tested familiar three-step event sequences in which a placeholder object was substituted for the second step in half the events. The results showed that the autism group remembered as many of the actions with the placeholder objects as their language-matched controls and as many correctly ordered sequences, a finding that supports a symbolic-delay (rather than deficit) hypothesis. These results were obtained in highly structured test situations and sharply contrast with the impairments seen in children with autism who are observed in naturalistic settings. Two interpretations of these findings are offered. First, structured test settings minimize distractions that typically occur in naturalistic settings that may interfere or disrupt symbolic play in children with autism. Second, the results are consistent with an executive function deficit in that the autistic group demonstrated more knowledge in the test settings than they demonstrate spontaneously in naturalistic ones.
Ultracold photoassociative ionization collisions in an atomic beam: Optical field intensity and polarization dependence of the rate constant.

We report here measurements of two-body photoassociative ionization collisions between sodium atoms within an ultranarrow velocity class selected from a well-collimated, thermal atomic beam. Doppler-shifted excitation of the Na(3[ital s] [sup 2][ital S][sub 1/2];[ital F]=1)[r arrow]Na(5[ital p] [sup 2][ital P][sub 3/2]) transition at 285 nm by a single-mode laser defines the narrow velocity class that subsequently populates the [ital F]=2 hyperfine level of the Na ground state by optical pumping. Probe laser beam excitation tuned near the Na(3[ital s] [sup 2][ital S][sub 1/2];[ital F]=2)[r arrow]Na(3[ital p] [sup 2][ital P][sub 3/2];[ital F]=3) transition produced photoassociative ionization with an average collision energy [ital E][sub [ital K]] corresponding to a temperature of 5.3 mK ([ital E][sub [ital K]]=3/2[ital kT]). We determine the rate constant for the process as a function of probe beam intensity and polarization.