Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic potential of NADPH oxidase 1/4 inhibitors

The NADPH oxidase (NOX) family of enzymes produces ROS as their sole function and is becoming recognized as key modulators of signal transduction pathways with a physiological role under acute stress and a pathological role after excessive activation under chronic stress. The seven isoforms differ in their regulation, tissue and subcellular localization and ROS products. The most studied are NOX1, 2 and 4. Genetic deletion of NOX1 and 4, in contrast to NOX2, has revealed no significant spontaneous pathologies and a pathogenic relevance of both NOX1 and 4 across multiple organs in a wide range of diseases and in particular inflammatory and fibrotic diseases. This has stimulated interest in NOX inhibitors for therapeutic application. GKT136901 and GKT137831 are two structurally related compounds demonstrating a preferential inhibition of NOX1 and 4 that have suitable properties for in vivo studies and have consequently been evaluated across a range of disease models and compared with gene deletion. In contrast to gene deletion, these inhibitors do not completely suppress ROS production, maintaining some basal level of ROS. Despite this and consistent with most gene deletion studies, these inhibitors are well tolerated and slow or prevent disease progression in a range of models of chronic inflammatory and fibrotic diseases by modulating common signal transduction pathways. Clinical trials in patients with GKT137831 have demonstrated excellent tolerability and reduction of various markers of chronic inflammation. NOX1/4 inhibition may provide a safe and effective therapeutic strategy for a range of inflammatory and fibrotic diseases.
Differential Response of Ventral Midbrain and Striatal Progenitor Cells to Lesions of the Nigrostriatal Dopaminergic Projection

In response to injury, progenitor cells in the adult brain can proliferate and generate new neurons and/or glia, which may then participate in injury-induced compensatory processes. In this study, we explore the ability of young adult mice to generate new cells in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions, which selectively kill nigrostriatal dopaminergic neurons. Using the thymidine analogue 5-bromo-2′-deoxyuridine (BrdU), we labeled dividing cells 3, 10, and 15 days after MPTP lesion. A robust proliferative response was seen specifically in the substantia nigra (SN) and the dorsal striatum 3 days postlesion; the response persisted 10–14 days. To explore the fate of proliferative cells, we administered BrdU 3 days postlesion and examined the phenotype of BrdU+ cells at various times thereafter, using double immunolabeling. In the striatum, nearly all newly-generated cells rapidly differentiated into GFAP+ astrocytes that participated in the injury-induced glial reaction. In the SN, however, reactive astroglia were not BrdU+. Some midbrain cells co-immunostained for BrdU and Mac-1, a microglial marker. However, most BrdU+ cells in the SN failed to express markers for microglia, astroglia, oligodendroglia, or neurons, suggesting that they may remain as uncommitted progenitors. Thus, progenitors in the vicinity of the degenerating dopaminergic cell bodies respond differently to lesion than progenitors in the vicinity of the degenerating axon terminal. Although the putative midbrain progenitors appear uncommitted 22 days after their birth, it is possible that they may adopt neural or glial fates if allowed to survive longer, or if exposed to exogenous factors.
[Determination of histamine].

Introduction of the radio-immunological technique (IMMUNOTECH, Marseille) for the measurement of histamine will in the future facilitate measurement of this mediator and this will be specially interesting during provocation tests for food and drug allergies and for histamine release in anaphylactic accidents caused by hymenoptera venom. The technique is more sensitive than that of the automated fluorimetric analysis.
Muscarinic Cholinergic Receptor Measurements with [18F]FP-TZTP: Control and Competition Studies

[18F]Fluoropropyl-TZTP (FP-TZTP) is a subtype-selective muscarinic cholinergic ligand with potential suitability for studying Alzheimer's disease. Positron emission tomography studies in isofluorane-anesthetized rhesus monkeys were performed to assess the in vivo behavior of this radiotracer. First, control studies (n = 11) were performed to characterize the tracer kinetics and to choose an appropriate model using a metabolite-corrected arterial input function. Second, preblocking studies (n = 4) with unlabeled FP-TZTP were used to measure nonspecific binding. Third, the sensitivity of [18F]FP-TZTP binding to changes in brain acetylcholine (ACh) was assessed by administering physostigmine, an acetylcholinesterase (AChE) inhibitor, by intravenous infusion (100 to 200 μg·kg−1·h−1) beginning 30 minutes before tracer injection (n = 7). Tracer uptake in the brain was rapid with K1 values of 0.4 to 0.6 mL·min−1·mL−1 in gray matter. A model with one tissue compartment was chosen because reliable parameter estimates could not be obtained with a more complex model. Volume of distribution (V) values, determined from functional images created by pixel-by-pixel fitting, were very similar in cortical regions, basal ganglia, and thalamus, but significantly lower (P < 0.01) in the cerebellum, consistent with the distribution of M2 cholinergic receptors. Preblocking studies with unlabeled FP-TZTP reduced V by 60% to 70% in cortical and subcortical regions. Physostigmine produced a 35% reduction in cortical specific binding (P < 0.05), consistent with increased ACh competition. The reduction in basal ganglia (12%) was significantly smaller (P < 0.05), consistent with its markedly higher AChE activity. These studies indicate that [18F]FP-TZTP should be useful for the in vivo measurement of muscarinic receptors with positron emission tomography.
Da panaforização à metaforização: o caso de uma pequena frase sem eira nem beira textual

Neste artigo, apoiados na Analise de Discurso de base enunciativa, mais especificamente em Maingueneau (2010, 2011a, 2011b e 2012), procuramos analisar a irrupcao, a retomada, a transformacao e a circulacao do enunciado de curta extensao “A esperanca venceu o medo”, dado a circular pelos mais diversos suportes midiaticos brasileiros a partir do segundo semestre de 2002. De forma nao tao exaustiva, estabelecemos como recorte temporal o periodo compreendido entre os anos de 2002 a 2012. Inicialmente, procuramos definir as caracteristicas linguisticas e discursivas da expressao enunciado de curta extensao, diferenciando-o, por exemplo, de outros como slogan, proverbios, maxima, formula. Num segundo momento, descrevemos as caracteristicas enunciativas desse fenomeno linguistico- discursivo. A seguir, discorremos sobre as caracteristicas linguistico-discursivas que favorecem a retomada, a transformacao e a circulacao do enunciado. Em conclusao, por um lado, comentamos acerca dos determinantes genericos e semioticos mobilizados pela midia na retomada, transformacao e circulacao do enunciado em questao e, por outro, discutimos os diferentes acontecimentos discursivos engendrados por tais retomadas e circulacao, entendendo o enunciado “A esperanca venceu o medo”, por conta nao so da sua ampla circulacao, mas pelo fato mesmo de designar ao longo de mais de uma decada, os mais diferentes acontecimentos discursivos, enquanto uma metaforizacao, que difere do conceito de panaforizacao, proposto por Maingueneau 2010.
Activity of Metal-Responsive Transcription Factor 1 by Toxic Heavy Metals and H2O2 In Vitro Is Modulated by Metallothionein

ABSTRACT Metallothioneins are small, cysteine-rich proteins that avidly bind heavy metals such as zinc, copper, and cadmium to reduce their concentration to a physiological or nontoxic level. Metallothionein gene transcription is induced by several stimuli, notably heavy metal load and oxidative stress. Transcriptional induction of metallothionein genes is mediated by the metal-responsive transcription factor 1 (MTF-1), an essential zinc finger protein that binds to specific DNA motifs termed metal-response elements. In cell-free DNA binding reactions with nuclear extracts, MTF-1 requires elevated zinc concentrations for efficient DNA binding but paradoxically is inactivated by other in vivo inducers such as cadmium, copper, and hydrogen peroxide. Here we have developed a cell-free, MTF-1-dependent transcription system which accurately reproduces the activation of metallothionein gene promoters not only by zinc but also by these other inducers. We found that while transcriptional induction by zinc can be achieved by elevated zinc concentration alone, induction by cadmium, copper, or H2O2 additionally requires the presence of zinc-saturated metallothionein. This is explained by the preferential binding of cadmium or copper to metallothionein or its oxidation by H2O2; the concomitant release of zinc in turn leads to the activation of transcription factor MTF-1. Conversely, thionein, the metal-free form of metallothionein, inhibits activation of MTF-1. The release of zinc from cellular components, including metallothioneins, and the sequestration of zinc by newly produced apometallothionein might be a basic mechanism to regulate MTF-1 activity upon cellular stress.
Inhibition of Novel Reassortant Avian Influenza H7N9 Virus Infection in vitro with Three Antiviral Drugs, Oseltamivir, Peramivir and Favipiravir

Background: A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from three patients and was identified as H7N9 in China. Antiviral agents are required to treat patients with avian influenza H7N9 virus infection. Methods: In this study, we assessed the antiviral potential of oseltamivir, peramivir, favipiravir (T-705), amantadine and rimantadine against novel reassortant avian-origin influenza H7N9 virus in vitro. Results: All three avian influenza H7N9 virus strains were sensitive to oseltamivir, peramivir and favipiravir (T-705), but resistant to amantadine and rimantadine. Conclusions: Our data show a pattern of antiviral sensitivity for this novel H7N9 strain of influenza that suggests the compounds oseltamivir, peramivir and favipiravir should be useful for therapy.
Surface and grain-boundary amorphization: Thermodynamic melting of coesite below the glass transition temperature.

Coesite, a high-pressure SiO{sub 2} polymorph, becomes amorphous during isothermal annealing below the glass transition temperature, {ital T}{sub {ital g}}, at one-bar pressure. Transmission electron microscopy was used to examine this fusion process (vitrification) below {ital T}{sub {ital g}}. The transformation is dominated by a heterogeneous nucleation-and-growth controlled process above the thermodynamic melting temperature, {ital T}{sub {ital m}} (875 K), but below {ital T}{sub {ital g}} (1480 K). Amorphous domains nucleate at free surfaces and grain boundaries, and the amorphous-crystalline interface propagates into the interior of the crystal. This {open_quote}{open_quote}interface-mediated{close_quote}{close_quote} amorphization (vitrification) is the same as {open_quote}{open_quote}interface-mediated{close_quote}{close_quote} melting, based on the thermodynamic, microstructural, and mechanistic aspects of the transformation. This amorphization process parallels electron-irradiation and pressure-induced amorphization in coesite. {copyright} {ital 1996 The American Physical Society. }
CMOS Solid-State Nanopore DNA System-Level Sequencing Techniques Enhancement

This paper presents system level CMOS solid-state nanopore techniques enhancement for speedup next generation molecular recording and high throughput channels. This discussion also considers optimum number of base-pair (bp) measurements through channel as an important role to enhance potential read accuracy. Effective power consumption estimation offered suitable range of multi-channel configuration. Nanopore bp extraction model in statistical method could contribute higher read accuracy with longer read-length (200 < read-length). Nanopore ionic current switching with Time Multiplexing (TM) based multichannel readout system contributed hardware savings.
Detecting Contradictions in News Quotations

Detecting contradicting statements is a fundamental and challenging natural language processing and machine learning task, with numerous applications in information extraction and retrieval. For instance, contradictions need to be recognized by question answering systems or multi-document summarization systems. In terms of machine learning, it requires the ability, through supervised learning, to accurately estimate and capture the subtle differences between contradictions and for instance, paraphrases. This M.Sc. dissertation provides a system capable of detecting contradictions from a pair of affirmations published across newspapers with both a F1-score and Accuracy of 71%. I propose to address this problem as a classification task using features based on those used for detecting paraphrases and recognizing textual entailment, alongside with numeric and string based features. Furthermore, this M.Sc. dissertation provides an assessment of what are the most informative features for detecting contradictions and infer if exists a correlation between detecting paraphrases and contradictions. Detectar afirmações contraditórias é uma tarefa fundamental e desafiadora da linguagem natural e de aprendizagem automática, com inúmeras aplicações na extração e recuperação de informação. Por exemplo, contradições precisam de ser reconhecidas por sistemas de questão-resposta ou sistemas de sumarização de vários documentos. Relativamente a aprendizagem automática, requer a capacidade, através de aprendizagem supervisionada, para estimar com precisão e capturar as diferenças entre contradições e, por exemplo, paráfrases. Esta dissertação de Mestrado proporciona um sistema capaz de detectar contradições a partir de um par de afirmações publicado através de jornais com ambos resultados de F1 e precisão de 71%. Proponho-me a abordar este problema como um tarefa de classificação usando recursos baseados na detecção de paráfrases e reconhecimento de vinculação textual, juntamente com recursos numéricos e de cadeias de caracteres. Além disso, esta dissertação de Mestrado fornece uma avaliação de quais são as caracteŕısticas mais informativas para detectar contradições e inferir se existe uma correlação entre a detecção de paráfrases e contradições.
Aortic isthmus Doppler velocimetry: role in assessment of preterm fetal growth restriction

Intrauterine fetal growth restriction (IUGR) is an important pregnancy complication associated with significant adverse clinical outcome, stillbirth, perinatal morbidity and cerebral palsy. To date, no uniformly accepted management protocol of Doppler surveillance that reduces mortality and cognitive morbidity has emerged. Aortic isthmus (AoI) evaluation has been proposed as a potential monitoring tool for IUGR fetuses. In this review, the current knowledge of the relationship between AoI Doppler velocimetry and preterm fetal growth restriction is reviewed. Relevant technical aspects and reproducibility data are reviewed as we discuss AoI Doppler and its place within the existing repertoire of Doppler assessments in placental insufficiency. The AoI is a link between the right and left ventricles which perfuse the lower and upper body, respectively. The clinical use of AoI waveforms for monitoring fetal deterioration in IUGR has been limited, but preliminary work suggests that abnormal AoI impedance indices are an intermediate step between placental insufficiency‐hypoxemia and cardiac decompensation. Further prospective studies correlating AoI indices with arterial and venous Doppler indices and perinatal outcome are required before encorporating this index into clinical practice. Copyright © 2010 John Wiley & Sons, Ltd.
Hierarchical mechanisms build the DNA-binding specificity of FUSE binding protein

The far upstream element (FUSE) binding protein (FBP), a single-stranded nucleic acid binding protein, is recruited to the c-myc promoter after melting of FUSE by transcriptionally generated dynamic supercoils. Via interactions with TFIIH and FBP-interacting repressor (FIR), FBP modulates c-myc transcription. Here, we investigate the contributions of FBP's 4 K Homology (KH) domains to sequence selectivity. EMSA and missing contact point analysis revealed that FBP contacts 4 separate patches spanning a large segment of FUSE. A SELEX procedure using paired KH-domains defined the preferred subsequences for each KH domain. Unexpectedly, there was also a strong selection for the noncontacted residues between these subsequences, showing that the contact points must be optimally presented in a backbone that minimizes secondary structure. Strategic mutation of contact points defined in this study disabled FUSE activity in vivo. Because the biological specificity of FBP is tuned at several layers: (i) accessibility of the site; (ii) supercoil-driven melting; (iii) presentation of unhindered bases for recognition; and (iv) modular interaction of KH-domains with cognate bases, the FBP-FIR system and sequence-specific, single-strand DNA binding proteins in general are likely to prove versatile tools for adjusting gene expression.
Gender differences in genetic linkage and association on 11p15 in obsessive–compulsive disorder families

Several clinical and genetic studies have reported gender differences in obsessive–compulsive disorder (OCD). Previously, we conducted a linkage genome scan using multipoint allele‐sharing methods to test for linkage in 219 families participating in the OCD Collaborative Genetics Study. When these families were stratified by proband's gender, suggestive linkage to chromosome 11p15 at marker D11S2362 (KACall = 2.92, P = 0.00012) was detected in families with male probands, but not in the ones with female probands. We have since conducted fine mapping with a denser microsatellite marker panel in the region of 11p15, and detected a significant linkage signal at D11S4146 (KACall = 5.08, P < 0.00001) in the families of male probands. Subsequently, 632 SNPs were genotyped spanning a 4.0 Mb region of the 1 LOD unit interval surrounding the linkage peak in the original families and an additional 165 families. Six SNPs were associated with OCD (P < 0.001): two SNPs were identified when all the families were included, and four SNPs only in male proband families. No SNP showed significant association with the OCD phenotype only in the families with a female proband. The results suggest a possible gender effect in the etiology of OCD. © 2008 Wiley‐Liss, Inc.
Optimized green operation of LTE networks in the presence of multiple electricity providers

Energy efficiency aspects in cellular networks can significantly contribute to the reduction of greenhouse gas emissions and help to save the environment. The base station (BS) sleeping strategy has become a well-known technique to achieve energy savings by switching off redundant BSs mainly for lightly loaded networks. Besides, introducing renewable energies as alternative power sources becomes a real challenge to network operators. In this paper, we propose a method that reduces the energy consumption of BSs by not only shutting down underutilized BSs but also by optimizing the amounts of energy procured from different retailers (Renewable energy and electricity retailers). We formulate an optimization problem that leads to the maximization of the profit of a Long-Term Evolution (LTE) cellular operator, and at the same time to the minimization of CO2 emissions in green wireless cellular networks without affecting the desired Quality of Service.
Expression-invariant face recognition using depth and intensity dual-tree complex wavelet transform features

Abstract. A new multimodal expression-invariant face recognition method is proposed by extracting features of rigid and semirigid regions of the face which are less affected by facial expressions. Dual-tree complex wavelet transform is applied in one decomposition level to extract the desired feature from range and intensity images by transforming the regions into eight subimages, consisting of six band-pass subimages to represent face details and two low-pass subimages to represent face approximates. The support vector machine has been used to classify both feature fusion and score fusion modes. To test the algorithm, BU-3DFE and FRGC v2.0 datasets have been selected. The BU-3DFE dataset was tested by low intensity versus high intensity and high intensity versus low intensity strategies using all expressions in both training and testing stages in different levels. Findings include the best rank-1 identification rate of 99.8% and verification rate of 100% at a 0.1% false acceptance rate. The FRGC v2.0 was tested by the neutral versus non-neutral strategy, which applies images without expression in training and with expression in the testing stage, thereby achieving the best rank-1 identification rate of 93.5% and verification rate of 97.4% at a 0.1% false acceptance rate.
Targeted imaging and proteomic analysis of tumor-associated glycans in living animals.

Although it has been well known that dynamic changes in glycosylation are associated with tumor progression, it remains challenging to selectively visualize the cancer glycome in vivo. Herein, a strategy for the targeted imaging of tumor-associated glycans by using ligand-targeted liposomes encapsulating azidosugars is described. The intravenously injected liposomal nanoparticles selectively bound to the cancer-cell-specific receptors and installed azides into the melanoma glycans in a xenograft mouse model in a tissue-specific manner. Subsequently, a copper-free click reaction was performed in vivo to chemoselectively conjugate the azides with a near-infrared fluorescent dye. The glycosylation dynamics during tumor growth were monitored by in vivo fluorescence imaging. Furthermore, the newly synthesized sialylated glycoproteins were enriched during tumor growth and identified by glycoproteomics. Compared with the labeling methods using free azidosugars, this method offers improved labeling efficiency and high specificity and should facilitate the elucidation of the functional role of glycans in cancer biology.
Multisystemic Therapy for Adolescents With Poorly Controlled Type 1 Diabetes

OBJECTIVE—The study aim was to determine if multisystemic therapy (MST), an intensive home-based psychotherapy, could reduce hospital admissions for diabetic ketoacidosis (DKA) in youth with poorly controlled type 1 diabetes over 24 months. Potential cost savings from reductions in admissions were also evaluated. RESEARCH DESIGN AND METHODS—A total of 127 youth were randomly assigned to MST or control groups and also received standard medical care. RESULTS—Youth who received MST had significantly fewer hospital admissions than control subjects (χ2 = 11.77, 4 d.f., n = 127; P = 0.019). MST-treated youth had significantly fewer admissions versus their baseline rate at 6-month (P = 0.004), 12-month (P = 0.021), 18-month (P = 0.046), and 24-month follow-up (P = 0.034). Cost to provide MST was 6,934 USD per youth; however, substantial cost offsets occurred from reductions in DKA admissions. CONCLUSIONS—The study demonstrates the value of intensive behavioral interventions for high-risk youth with diabetes for reducing one of the most serious consequences of medication noncompliance.