Miracle-dz/UniFAR-FTUs huggingface dataset:
Seeking Stable Clusters in the Blogosphere

The popularity of blogs has been increasing dramatically over the last couple of years. As topics evolve in the blogosphere, keywords align together and form the heart of various stories. Intuitively we expect that in certain contexts, when there is a lot of discussion on a specific topic or event, a set of keywords will be correlated: the keywords in the set will frequently appear together (pair-wise or in conjunction) forming a cluster. Note that such keyword clusters are temporal (associated with specific time periods) and transient. As topics recede, associated keyword clusters dissolve, because their keywords no longer appear frequently together. In this paper, we formalize this intuition and present efficient algorithms to identify keyword clusters in large collections of blog posts for specific temporal intervals. We then formalize problems related to the temporal properties of such clusters. In particular, we present efficient algorithms to identify clusters that persist over time. Given the vast amounts of data involved, we present algorithms that are fast (can efficiently process millions of blogs with multiple millions of posts) and take special care to make them efficiently realizable in secondary storage. Although we instantiate our techniques in the context of blogs, our methodology is generic enough to apply equally well to any temporally ordered text source. We present the results of an experimental study using both real and synthetic data sets, demonstrating the efficiency of our algorithms, both in terms of performance and in terms of the quality of the keyword clusters and associated temporal properties we identify.
Identification and characterization of coumestans as novel HCV NS5B polymerase inhibitors

The hepatitis C virus (HCV) NS5B is essential for viral RNA replication and is therefore a prime target for development of HCV replication inhibitors. Here, we report the identification of a new class of HCV NS5B inhibitors belonging to the coumestan family of phytoestrogens. Based on the in vitro NS5B RNA-dependent RNA polymerase (RdRp) inhibition in the low micromolar range by wedelolactone, a naturally occurring coumestan, we evaluated the anti-NS5B activity of four synthetic coumestan analogues bearing different patterns of substitutions in their A and D rings, and observed a good structure-activity correlation. Kinetic characterization of coumestans revealed a noncompetitive mode of inhibition with respect to nucleoside triphosphate (rNTP) substrate and a mixed mode of inhibition towards the nucleic acid template, with a major competitive component. The modified order of addition experiments with coumestans and nucleic acid substrates affected the potencies of the coumestan inhibitors. Coumestan interference at the step of NS5B–RNA binary complex formation was confirmed by cross-linking experiments. Molecular docking of coumestans within the allosteric site of NS5B yielded significant correlation between their calculated binding energies and IC50 values. Coumestans thus add to the diversifying pool of anti-NS5B agents and provide a novel scaffold for structural refinement and development of potent NS5B inhibitors.
High speed parallel processing of biomedical optics data with PC graphic hardware

In the field of biomedical optics, many approaches need to process tremendous data set using complicated algorithms, which cause heavy computation and limit their applications in the real-time conditions, such as clinical diagnoses and therapy. In this paper, we present and review several successful applications using GPU (graphic processing unit) to accelerate the processing of biomedical optics data including image processing, Monte Carlo simulation, image reconstruction and statistics analysis. It is shown that GPU are proved to obtain significant performance improvement in contrast with the traditional used methods based on CPU calculation.
Cardiovascular Patterning as Determined by Hemodynamic Forces and Blood Vessel Genetics

Background Vascular patterning depends on coordinated timing of arteriovenous specification of endothelial cells and the concomitant hemodynamic forces supplied by the onset of cardiac function. Using a combination of 3D imaging by OPT and embryo registration techniques, we sought to identify structural differences between three different mouse models of cardiovascular perturbation. Results Endoglin mutant mice shared a high degree of similarity to Mlc2a mutant mice, which have been shown to have a primary developmental heart defect causing secondary vessel remodeling failures. Dll4 mutant mice, which have well-characterized arterial blood vessel specification defects, showed distinct differences in vascular patterning when compared to the disruptions seen in Mlc2a -/- and Eng -/- models. While Mlc2a -/- and Eng -/- embryos exhibited significantly larger atria than wild-type, Dll4 -/- embryos had significantly smaller hearts than wild-type, but this quantitative volume decrease was not limited to the developing atrium. Dll4 -/- embryos also had atretic dorsal aortae and smaller trunks, suggesting that the cardiac abnormalities were secondary to primary arterial blood vessel specification defects. Conclusions The similarities in Eng -/- and Mlc2a -/- embryos suggest that Eng -/- mice may suffer from a primary heart developmental defect and secondary defects in vessel patterning, while defects in Dll4 -/- embryos are consistent with primary defects in vessel patterning.
The TrustNo 1 Cryptoprocessor Concept

Cryptoprocessors feature an on-chip block cipher hardware between the cache and the bus interface. Code and data are decrypted on-the-fly while being fetched from RAM and are encrypted while being written into RAM. Even someone with full physical access to the printed circuit board cannot observe the executed cleartext software and its data structures. Cryptoprocessors have been used for many years as microcontrollers in security sensitive applications like financial transaction terminals. This paper explores the hardware, firmware, operating system, and key management mechanisms necessary in order to apply the cryptoprocessor concept in multitasking operating system workstations.
The Gibbs Centroid Sampler

The Gibbs Centroid Sampler is a software package designed for locating conserved elements in biopolymer sequences. The Gibbs Centroid Sampler reports a centroid alignment, i.e. an alignment that has the minimum total distance to the set of samples chosen from the a posteriori probability distribution of transcription factor binding-site alignments. In so doing, it garners information from the full ensemble of solutions, rather than only the single most probable point that is the target of many motif-finding algorithms, including its predecessor, the Gibbs Recursive Sampler. Centroid estimators have been shown to yield substantial improvements, in both sensitivity and positive predictive values, to the prediction of RNA secondary structure and motif finding. The Gibbs Centroid Sampler, along with interactive tutorials, an online user manual, and information on downloading the software, is available at: http://bayesweb.wadsworth. org/gibbs/gibbs.html.
Software process simulation modeling: preliminary results from an updated systematic review

Software Process Simulation Modeling (SPSM) has raised research interest since 1980s. However, it is observed that SPSM studies published in the ICSSP community may have dropped in recent years. The objective of this research is to update the recent status of this area. We conducted a Systematic Literature Review (SLR) using the QGS-based search strategy. The review identified 74 primary studies in the past five years (2008-2012). This paper presents the preliminary results from this updated SLR by answering the first four research questions. Based on the findings from this updated review, it can be concluded that in terms of the number of SPSM studies found in the overall software engineering community, there is no significant change (drop) compared to the former review stage (1998-2007).
Occluding junction structure-function relationships in a cultured epithelial monolayer

Electrical circuit analysis was used to study the structural development of occluding junctions (OJs) in cultured monolayers composed to T84 cells. The magnitude of the increments in transepithelial resistance predicted by such analysis was compared with the magnitude of the measured increments in resistance. Confluent sheets of epithelial cells were formed after cells were plated at high density on collagen-coated filters. Using Claude's OJ strand count- resistance hypothesis (1978, J. Membr. Biol. 39:219-232), electrical circuit analysis of histograms describing OJ strand count distribution at different time points after plating predicted that junctional resistance should rise in a proportion of 1:21:50 from 18 h to 2 d to 5 d. This reasonably paralleled the degree of rise in transepithelial resistance over this period, which was 1:29:59. The ability to predict the observed resistance rise was eliminated if only mean strand counts were analyzed or if electrical circuit analysis of OJ strand counts were performed using an OJ strand count-resistance relationship substantially different from that proposed by Claude. Measurements of unidirectional fluxes of inulin, mannitol, and sodium indicated that restriction of transjunctional permeability accounted for the observed resistance rise, and that T84 junctional strands have finite permeability to molecules with radii less than or equal to 3.6 A but are essentially impermeable to molecules with radii greater than or equal to 15 A. The results suggest that general correlates between OJ structure and OJ ability to resist passive ion flow do exist in T84 monolayers. The study also suggests that such correlates can be obtained only if OJ structural data are analyzed as an electrical circuit composed of parallel resistors.
A Single-Inductor 0.35 µm CMOS Energy-Investing Piezoelectric Harvester

Although miniaturized piezoelectric transducers usually derive more power from motion than their electrostatic and electromagnetic counterparts, they still generate little power. The reason for this is that the electromechanical coupling factor is low, which means the damping force that tiny transducers impose on vibrations (when drawing power) is hardly noticeable. The single-inductor 0.35 μm CMOS piezoelectric harvester proposed in this paper counters this deficiency by investing energy from the battery into the transducer. The idea is to strengthen the electrostatic force against which vibrations work. This way, the circuit draws more power from the transducer, up to 79 μW from a 2.7 cm piezoelectric cantilever that is driven up to 0.25 m/s 2 . Of the 79 μW drawn at 0.25 m/s 2 when investing 91 nJ of battery energy, the system outputs 52 μW, which is 3.6 times more output power than the 14.5 μW that a full-wave bridge rectifier with zero-volt diodes at its maximum power point can deliver from the same source. With 630 nW lost to the controller, power-conversion efficiency peaks at 69% when the harvester outputs 46 μW of the 67 μW it draws from the transducer at 0.25 m/s 2 when investing 0.8 nJ of battery energy.
Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders

Beneficial effects of cannabidiol (CBD) have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood. Similar to clinical antidepressant or atypical antipsychotic drugs, recent findings clearly indicate that CBD, either acutely or repeatedly administered, induces plastic changes. For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia. More recently, it was found that CBD modulates cell fate regulatory pathways such as autophagy and others critical pathways for neuronal survival in neurodegenerative experimental models, suggesting the potential benefit of CBD treatment for psychiatric/cognitive symptoms associated with neurodegeneration. These changes and their possible association with CBD beneficial effects in psychiatric disorders are reviewed here.
Collegiate Student-Athlete Perceptions of the Impact of Concussion on Academic Performance

The purpose of this qualitative study was to indicate the experiences of collegiate student-athletes in meeting academic demands when experiencing prolonged recovery from concussion and if they perceive a need for academic accommodations. There is a gap in present concussion and an absence of studies that examine if academic accommodations are helpful during concussion recovery. The study was guided by 3 research questions focused on the return to learn during the recovery process. The study was limited to 9 student-athletes currently enrolled at three postsecondary institutions: Christian Brothers University, Rhodes College, and the University of Memphis. The study participants met pre-established criteria for the study, were recruited by their athletic trainer at their respective institution, and voluntarily participated in individual interviews with the researcher or co-interviewer. Through a phenomenological approach, individual interviews were conducted with the participants. Four themes were identified in the data: negative impact on academic performance, academic pressures, inequity of student-athlete treatment, and impact on concentration ability. Each study participant’s story was shared through the data analysis process, and significant statements from the interviews as related to the research questions were included in the data analysis section. Ultimately, the data suggested that future research continue to focus on how student-athletes' recovery from concussion impacts their return to learn process.
Dual Targeting of HER2-Positive Cancer with Trastuzumab Emtansine and Pertuzumab: Critical Role for Neuregulin Blockade in Antitumor Response to Combination Therapy

Purpose: Targeting HER2 with multiple HER2-directed therapies represents a promising area of treatment for HER2-positive cancers. We investigated combining the HER2-directed antibody–drug conjugate trastuzumab emtansine (T-DM1) with the HER2 dimerization inhibitor pertuzumab (Perjeta). Experimental Design: Drug combination studies with T-DM1 and pertuzumab were performed on cultured tumor cells and in mouse xenograft models of HER2-amplified cancer. In patients with HER2-positive locally advanced or metastatic breast cancer (mBC), T-DM1 was dose-escalated with a fixed standard pertuzumab dose in a 3+3 phase Ib/II study design. Results: Treatment of HER2-overexpressing tumor cells in vitro with T-DM1 plus pertuzumab resulted in synergistic inhibition of cell proliferation and induction of apoptotic cell death. The presence of the HER3 ligand, heregulin (NRG-1β), reduced the cytotoxic activity of T-DM1 in a subset of breast cancer lines; this effect was reversed by the addition of pertuzumab. Results from mouse xenograft models showed enhanced antitumor efficacy with T-DM1 and pertuzumab resulting from the unique antitumor activities of each agent. In patients with mBC previously treated with trastuzumab, lapatinib, and chemotherapy, T-DM1 could be dosed at the maximum tolerated dose (MTD; 3.6 mg/kg every 3 weeks) with standard dose pertuzumab. Adverse events were mostly grade 1 and 2, with indications of clinical activity. Conclusions: Dual targeting of HER2 with the combination of T-DM1 and pertuzumab in cell culture and mouse xenograft models resulted in enhanced antitumor activity. In patients, this combination showed an encouraging safety and tolerability profile with preliminary evidence of efficacy. Clin Cancer Res; 20(2); 456–68. ©2013 AACR.
Adding Value Every Sprint: A Case Study on Large-Scale Continuous Requirements Engineering

Agile development practices, such as continuous integration and continuous delivery, promise value through shorter time to market and increased exibility. While these practices have been widely adopted in small-scale, they have shown to be challenging to adopt in large-scale, system development. This is often due to a distance between customer and developer in large scale systems, and the need to break down value from the whole system into manageable parts. The notion of value is fundamental for agile methods, especially for practices such as continuous delivery to the customer. However, how value should be handled in development practices is not clearly understood. In this paper, we investigate how the notion of adding value in every sprint has been perceived in a large-scale system development. Based on an exploratory qualitative case study, the outcome shows that it is perceived beneficial by practitioners although it comes at a price and challenges exist.
REGIME MILITAR NO BRASIL: OS GRUPOS DE INTERESSES E A FORMULAÇÃO DA POLÍTICA EXTERNA Military regime in Brazil: interest groups and foreign policy formulation

Introducao Os estudos sobre a politica externa brasileira, nas ultimas decadas, tem se afastado progressivamente das analises centradas na figura do Estado como ator central na formulacao e execucao da politica externa. Assim, ampliou-se o escopo de analise, ao considerara interacao de fatores como a dimensao externa e a estrutura domestica e, no interior desta, os interesses dos participantes e as estrategias utilizadas no processo de formulacao e decisao em politica externa. Parte-se do pressuposto que a formulacao da politica externa nao e algo exclusivo do poder executivo e o Estado nao e impermeavel as pressoes domesticas. Nos regimes autoritarios, em geral, e no regime militar do Brasil (1964-1985), em particular, o processo de formulacao em politica externa se fez em circulos que restringiam a participacao ampla de setores da sociedade civil, do Legislativo, entre outros. No entanto, outros segmentos, como setores empresariais nacionais e internacionais, por exemplo, tiveram um relacionamento intenso com a burocracia estatal. Utilizando os canais de comunicacao informais, ocupando postos estrategicos nos conselhos e agencia estatais, estes setores interferiram e influenciaram no processo
Over‐Responsiveness and Greater Variability in Roughness Perception in Autism

Although sensory problems, including tactile hypersensitivity and hyposensitivity (DSM‐5) are commonly associated with autism, there is a dearth of systematic and rigorous research in this domain. Here, we report findings from a psychophysical experiment that explored differences in tactile perception between individuals with autism and typically developing control participants, who, using their index finger, rated a series of surfaces on the extent of their roughness. Each surface was rated multiple times and we calculated both the average rating and the variability across trials. Relative to controls, the individuals with autism perceived the surfaces as rougher overall and exhibited greater variability in their ratings across trials. These findings characterize altered tactile perception in autism and suggest that sensory problems in autism may be the product of overly responsive and variable sensory processing. Autism Res 2016, 9: 393–402. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Evidence for Immune Response, Axonal Dysfunction and Reduced Endocytosis in the Substantia Nigra in Early Stage Parkinson’s Disease

Subjects with incidental Lewy body disease (iLBD) may represent the premotor stage of Parkinson’s disease (PD). To elucidate molecular mechanisms underlying neuronal dysfunction and alpha-synuclein pathology in the premotor phase of PD, we investigated the transcriptome of the substantia nigra (SN) of well-characterized iLBD, PD donors and age-matched controls with Braak alpha-synuclein stage ranging from 0–6. In Braak alpha-synuclein stages 1 and 2, we observed deregulation of pathways linked to axonal degeneration, immune response and endocytosis, including axonal guidance signaling, mTOR signaling, EIF2 signaling and clathrin-mediated endocytosis in the SN. In Braak stages 3 and 4, we observed deregulation of pathways involved in protein translation and cell survival, including mTOR and EIF2 signaling. In Braak stages 5 and 6, we observed deregulation of dopaminergic signaling, axonal guidance signaling and thrombin signaling. Throughout the progression of PD pathology, we observed a deregulation of mTOR, EIF2 and regulation of eIF4 and p70S6K signaling in the SN. Our results indicate that molecular mechanisms related to axonal dysfunction, endocytosis and immune response are an early event in PD pathology, whereas mTOR and EIF2 signaling are impaired throughout disease progression. These pathways may hold the key to altering the disease progression in PD.
Mdm2 inhibition confers protection of p53-proficient cells from the cytotoxic effects of Wee1 inhibitors

Pharmacological inhibition of the cell cycle regulatory kinase Wee1 represents a promising strategy to eliminate cancer cells. Wee1 inhibitors cooperate with chemotherapeutics, e. g. nucleoside analogues, pushing malignant cells from S phase towards premature mitosis and death. However, considerable toxicities are observed in preclinical and clinical trials. A high proportion of tumor cells can be distinguished from all other cells of a patient's body by inactivating mutations in the tumor suppressor p53. Here we set out to develop an approach for the selective protection of p53-proficient cells against the cytotoxic effects of Wee1 inhibitors. We pretreated such cells with Nutlin-3a, a prototype inhibitor of the p53-antagonist Mdm2. The resulting transient cell cycle arrest effectively increased the survival of cells that were subsequently treated with combinations of the Wee1 inhibitor MK-1775 and/or the nucleoside analogue gemcitabine. In this constellation, Nutlin-3a reduced caspase activation and diminished the phosphorylation of Histone 2AX, an indicator of the DNA damage response. Both effects were strictly dependent on the presence of p53. Moreover, Nutlin pre-treatment reduced the fraction of cells that were undergoing premature mitosis in response to Wee1 inhibition. We conclude that the pre-activation of p53 through Mdm2 antagonists serves as a viable option to selectively protect p53-proficient cells against the cytotoxic effects of Wee1 inhibitors, especially when combined with a nucleoside analogue. Thus, Mdm2 antagonists might prove useful to avoid unwanted side effects of Wee1 inhibitors. On the other hand, when a tumor contains wild type p53, care should be taken not to induce its activity before applying Wee1 inhibitors.
The herpes simplex virus VP16-induced complex: mechanisms of combinatorial transcriptional regulation.

At any one time, a cell transcribes only a small subsetof all the genes in its genome. To provide specificity tothe regulation of transcription, each cell relies on the assembly of particular sets or combinations of transcriptionfactors on different promoters. Through such combinatorial mechanisms, individual transcription factors can acquire different activities depending on the presence or absence of other coregulators in the same cell, thus reducingthe total number of regulators needed to control cellulartranscription.