Miracle-dz/UniFAR-FTUs huggingface dataset:
Boceprevir in genotype 1 chronic hepatitis C: first experiences in Serbia.

INTRODUCTION The triple therapy which consists of one of the protease inhibitor plus pegylated interferon and ribavirin (P/R) is the standard of care for the treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection both in treatment-naïve and experienced patients. OBJECTIVE The aim of this study was to analyze the efficacy and tolerability of this regime in hospital practice in Serbia. METHODS From July 2012 to October 2012, 20 previously treated patients with advanced fibrosis and HCV G1 infection were included in the triple antiviral regimen in six referral centers in Serbia. All patients were treated with response guide therapy (RGT) regime according to the boceprevir treatment protocol. During the 4-week lead-in period all patients received peginterferon plus ribavirin. After the lead-in pe- riod boceprevir was added in the dosage of 800 mg three times a day orally.The subsequent treatment varied according to virologic response and fibrosis. During the therapy HCV RNA level was measured at week 4, 8, 12, 24 of the treatment for the assessment of virologic response profile. All patients who completed therapy were assessed at the end of the treatment and at the end of an additional 24-week treatment-free period for a sustained virologic response (SVR). RESULTS The total of 20 patients with advanced fibrosis was treated. Among patients with an undetectable HCV RNA level at week 8 the rate of SVR was 100%. No patient with decrease in the HCV RNA level < 1 log 10 IU/ml at treatment week 4 achieved SVR. The overall rate of SVR was 55%. The safety profile of the treatment regimen was good. Anemia was reported in 25% of patients. There was no life-threatening treatment adverse event. CONCLUSION Boceprevir in combination with P/R achieved fairly good SVR rates in patients that were"most difficult to treat"who failed on dual therapy and was effective among patients with cirrhosis.
Low Resting Potential and Postnatal Upregulation of NMDA Receptors May Cause Cajal–Retzius Cell Death

Using in situ patch-clamp techniques in rat telencephalic slices, we have followed resting potential (RP) properties and the functional expression of NMDA receptors in neocortical Cajal–Retzius (CR) cells from embryonic day 18 to postnatal day 13, the time around which these cells normally disappear. We find that throughout their lives CR cells have a relatively depolarized RP (approximately −50 mV), which can be made more hyperpolarized (approximately −70 mV) by stimulation of the Na/K pump with intracellular ATP. The NMDA receptors of CR cells are subjected to intense postnatal upregulation, but their similar properties (EC50, Hill number, sensitivity to antagonists, conductance, and kinetics) throughout development suggest that their subunit composition remains relatively homogeneous. The low RP of CR cells is within a range that allows for the relief of NMDA channels from Mg2+ blockade. Our findings are consistent with the hypothesis that CR cells may degenerate and die subsequent to uncontrolled overload of intracellular Ca2+ via NMDA receptor activation by ambient glutamate. In support of this hypothesis we have obtained evidence showing the protection of CR cells viain vivo blockade of NMDA receptors with dizocilpine.
Comprehensive Genomic Analysis and Expression Profiling of the NOX Gene Families under Abiotic Stresses and Hormones in Plants

Plasma membrane NADPH oxidases (NOXs) are key producers of reactive oxygen species under both normal and stress conditions in plants and they form functional subfamilies. Studies of these subfamilies indicated that they show considerable evolutionary selection. We performed a comparative genomic analysis that identified 50 ferric reduction oxidases (FRO) and 77 NOX gene homologs from 20 species representing the eight major plant lineages within the supergroup Plantae: glaucophytes, rhodophytes, chlorophytes, bryophytes, lycophytes, gymnosperms, monocots, and eudicots. Phylogenetic and structural analysis classified these FRO and NOX genes into four well-conserved groups represented as NOX, FRO I, FRO II, and FRO III. Further analysis of NOXs of phylogenetic and exon/intron structures showed that single intron loss and gain had occurred, yielding the diversified gene structures during the evolution of NOXs family genes and which were classified into four conserved subfamilies which are represented as Sub.I, Sub.II, Sub.III, and Sub.IV. Additionally, both available global microarray data analysis and quantitative real-time PCR experiments revealed that the NOX genes in Arabidopsis and rice (Oryza sativa) have different expression patterns in different developmental stages, various abiotic stresses and hormone treatments. Finally, coexpression network analysis of NOX genes in Arabidopsis and rice revealed that NOXs have significantly correlated expression profiles with genes which are involved in plants metabolic and resistance progresses. All these results suggest that NOX family underscores the functional diversity and divergence in plants. This finding will facilitate further studies of the NOX family and provide valuable information for functional validation of this family in plants.
Extending Decidable Existential Rules by Joining Acyclicity and Guardedness

Existential rules, i.e. Datalog extended with existential quantifiers in rule heads, are currently studied under a variety of names such as Datalog+/-, ∀∃-rules, and tuple-generating dependencies. The renewed interest in this formalism is fuelled by a wealth of recently discovered language fragments for which query answering is decidable. This paper extends and consolidates two of the main approaches in this field - acyclicity and guardedness - by providing (1) complexity-preserving generalisations of weakly acyclic and weakly (frontier-) guarded rules, and (2) a novel formalism of glut-(frontier-) guarded rules that subsumes both. This builds on an insight that acyclicity can be used to extend any existential rule language while retaining decidability. Besides decidability, combined query complexities are established in all cases.
The SMOS Mission: New Tool for Monitoring Key Elements ofthe Global Water Cycle

It is now well understood that data on soil moisture and sea surface salinity (SSS) are required to improve meteorological and climate predictions. These two quantities are not yet available globally or with adequate temporal or spatial sampling. It is recognized that a spaceborne L-band radiometer with a suitable antenna is the most promising way of fulfilling this gap. With these scientific objectives and technical solution at the heart of a proposed mission concept the European Space Agency (ESA) selected the Soil Moisture and Ocean Salinity (SMOS) mission as its second Earth Explorer Opportunity Mission. The development of the SMOS mission was led by ESA in collaboration with the Centre National d'Etudes Spatiales (CNES) in France and the Centro para el Desarrollo Tecnologico Industrial (CDTI) in Spain. SMOS carries a single payload, an L-Band 2-D interferometric radiometer operating in the 1400-1427-MHz protected band . The instrument receives the radiation emitted from Earth's surface, which can then be related to the moisture content in the first few centimeters of soil over land, and to salinity in the surface waters of the oceans. SMOS will achieve an unprecedented maximum spatial resolution of 50 km at L-band over land (43 km on average over the field of view), providing multiangular dual polarized (or fully polarized) brightness temperatures over the globe. SMOS has a revisit time of less than 3 days so as to retrieve soil moisture and ocean salinity data, meeting the mission's science objectives. The caveat in relation to its sampling requirements is that SMOS will have a somewhat reduced sensitivity when compared to conventional radiometers. The SMOS satellite was launched successfully on November 2, 2009.
Targeting epigenetics for treatment of BRAF mutated metastatic melanoma with decitabine in combination with vemurafenib: A phase lb study

Introduction Epigenetic modifications play an important role in progression and development of resistance in V600EBRAF positive metastatic melanoma. Therefore, we hypothesized that the action of vemurafenib (BRAF inhibitor) can be made more effective by combining with low dose decitabine (a DNA methyltransferase inhibitor). The primary objective of this phase lb study was to determine the dose limiting toxicity and maximum tolerated dose of combination of subcutaneous decitabine with oral vemurafenib in patients with V600EBRAF positive metastatic melanoma with or without any prior treatment. Experimental Design The study employed 3+3 dose escalation combining subcutaneous decitabine at different doses and schedules (4 cohorts) with the standard oral dose of vemurafenib 960 mg twice daily. Preclinical assessment and further analysis were also performed in A375 melanoma cell line. Results Fourteen patients received study treatment. No dose limiting toxicity was encountered and maximum tolerated dose was not reached. Important toxicities included fatigue, increased creatinine, neutropenia, leucopenia, hypophosphatemia, rash and hyperuricemia. Three patients achieved complete response, three had partial response and five had stable disease. Preclinical assessment demonstrated action of the combination which delayed the development of acquired resistance and improved duration of treatment sensitivity. Conclusions The combination of oral vemurafenib with subcutaneous decitabine is safe and showed activity in V600EBRAF positive metastatic melanoma. Since most responses were seen in cohort 1, which utilized low-dose, long-term decitabine, future studies of this combination treatment should utilize longer duration of decitabine, at the lowest dose of 0.1 mg/kg.
Physical Properties of Carbon Nanotubes Ao Teng

Carbon nanotubes, as the prototypes of artificial one dimensional nano materials, have been intensely investigated since 1991. They originated from graphite sheets, but come along with some new physical properties due to quantum confinement. Soon after they were discovered, researchers realized their broad applications in prospect. In this paper, a brief introduction focusing on basic concepts and geometry of carbon nanotubes will be conducted, followed by a series of discussions on related electronic properties of carbon nanotubes, as well as other physical properties.
Double Dissociation of Stimulus-Value and Action-Value Learning in Humans with Orbitofrontal or Anterior Cingulate Cortex Damage

Adaptive decision making involves selecting the most valuable option, typically by taking an action. Such choices require value comparisons, but there is debate about whether these comparisons occur at the level of stimuli (goods-based) value, action-based value, or both. One view is that value processes occur in series, with stimulus value informing action value. However, lesion work in nonhuman primates suggests that these two kinds of choice are dissociable. Here, we examined action-value and stimulus-value learning in humans with focal frontal lobe damage. Orbitofrontal damage disrupted the ability to sustain the correct choice of stimulus, but not of action, after positive feedback, while damage centered on dorsal anterior cingulate cortex led to the opposite deficit. These findings argue that there are distinct, domain-specific mechanisms by which outcome value is applied to guide subsequent decisions, depending on whether the choice is between stimuli or between actions.
An experimental study of pulmonary damage associated with intravenous injection of halothane in dogs.

SUMMARY Halothane was injected intravenously into two groups of dogs and the effects on the lungs noted. The nine dogs of group I were unanaesthetized and received no ventilatory support following injection. The dogs were killed at varying time intervals after injection and the macroscopic and microscopic appearances were studied. In the six dogs of group II the chests were open and they were artificially ventilated with 30 per cent oxygen and 70 per cent nitrous oxide at the time of injection. Serial biopsies were taken. The predominant lesions produced were generalized oedema and patchy alveolar haemorrhages. These changes were more severe in dogs of group I. The aetiology is conjectural, possibly being due to direct capillary damage or to embolization. The danger of accidental intravenous injection of halothane, a not unknown occurrence, is stressed.
Does Menu Design Influence Retirement Investment Choices? Evidence from Italian Occupational Pension Funds

Previous research has demonstrated that consumers’ decisions regarding supplementary pensions could be affected by biases. Bernatzi and Thaler’s experiment demonstrated that menu design can influence pension fund enrollment decisions, in that participants appear to adopt a naïve heuristic, i.e., “extremeness aversion”. Using a database of 27 occupational pension funds from 2007 to 2011, representing 1,732,530 employees, this study asked whether menu design affected Italian workers’ choices regarding the supplementary pension system as a result of the new rules enacted by the regulator in 2007. Most enrolled workers opted for the median investment line. I discuss the possible relevance of this result to public policy, in particular the possibility of including these preferences in the regulations, with the aim of benefiting employees.
Human microRNA hsa-miR-125a-5p interferes with expression of hepatitis B virus surface antigen

MicroRNAs are small non-coding RNAs that modulate gene expression at post-transcriptional level, playing a crucial role in cell differentiation and development. Recently, some reports have shown that a limited number of mammalian microRNAs are also involved in anti-viral defense. In this study, the analysis of the hepatitis B virus (HBV) genome by the computer program MiRanda led to the identification of seven sites that are potential targets for human liver microRNAs. These sites were found to be clustered in a 995-bp segment within the viral polymerase ORF and the overlapping surface antigen ORF, and conserved among the most common HBV subtypes. The HBV genomic targets were then subjected to a validation test based on cultured hepatic cells (HepG2, HuH-7 and PLC/PRF/5) and luciferase reporter genes. In this test, one of the selected microRNAs, hsa-miR-125a-5p, was found to interact with the viral sequence and to suppress the reporter activity markedly. The microRNA was then shown to interfere with the viral translation, down-regulating the expression of the surface antigen. Overall, these results support the emerging concept that some mammalian microRNAs play a role in virus-host interaction. Furthermore, they provide the basis for the development of new strategies for anti-HBV intervention.
Microglia-Mediated Neuroinflammation and Neurotrophic Factor-Induced Protection in the MPTP Mouse Model of Parkinson’s Disease-Lessons from Transgenic Mice

Parkinson’s disease (PD) is a neurodegenerative disease characterised by histopathological and biochemical manifestations such as loss of midbrain dopaminergic (DA) neurons and decrease in dopamine levels accompanied by a concomitant neuroinflammatory response in the affected brain regions. Over the past decades, the use of toxin-based animal models has been crucial to elucidate disease pathophysiology, and to develop therapeutic approaches aimed to alleviate its motor symptoms. Analyses of transgenic mice deficient for cytokines, chemokine as well as neurotrophic factors and their respective receptors in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD have broadened the current knowledge of neuroinflammation and neurotrophic support. Here, we provide a comprehensive review that summarises the contribution of microglia-mediated neuroinflammation in MPTP-induced neurodegeneration. Moreover, we highlight the contribution of neurotrophic factors as endogenous and/or exogenous molecules to slow the progression of midbrain dopaminergic (mDA) neurons and further discuss the potential of combined therapeutic approaches employing neuroinflammation modifying agents and neurotrophic factors.
High-Frequency Rugose Exopolysaccharide Production by Vibrio cholerae

ABSTRACT Vibrio cholerae can shift to a “rugose” phenotype, thereby producing copious exopolysaccharide (EPS), which promotes its environmental survival and persistence. We report conditions that promote high-frequency rugose EPS production (HFRP), whereby cells switch at high frequency (up to 80%) to rugose EPS production. HFRP appeared to be more common in clinical strains, as HFRP was found in 6 of 19 clinical strains (32%) (including classical, El Tor, and non-O1 strains) but in only 1 of 16 environmental strains (6%). Differences were found between strains in rugose colony morphology, conditions promoting HFRP, the frequency of rugose-to-smooth (R-S) cell reversion, and biofilm formation. We propose that rugose EPS and HFRP provide an evolutionary and adaptive advantage to specific epidemic V. cholerae strains for increased persistence in the environment.
High speed in-vivo imaging of retinal hemodynamics in a rodent model of hypertension

The eye is the only organ through which microcirculation can be visualized non-invasively. This unique feature makes the eye and specifically retinal vasculature an excellent target area to monitor and study micro-vascular damage in systemic diseases. Dynamic (real-time) changes of retinal vessels have been shown to be more specific to the disease in comparison with static measurements. In this study we utilize high speed imaging (i.e. 125 fps) to study and derive dynamic changes of retinal vessels in a rat model of hypertension. A Eulerian video magnification algorithm was used to extract retinal arterial and venous pulse amplitude from five Spontaneously Hypertensive Rats (SHR) and five Wister Kyoto (WKY) rats were used as the control group. Results showed that retinal arterial diameter and pulse amplitude are significantly lower in the SHRs compared with WKYs. Dynamic biomarkers of retinal micro-vasculature may be used as a diagnostic tool for systemic diseases.
Robust control for nonlinear time-varying systems with application to a robotic manipulator

Sliding mode control methods have been used widely because they provide robustness against parameter variations and disturbances. This paper focuses on the problem of a robust output-sliding control design for a class of nonlinear time-varying systems. Output signals are used for the switching function definition. The control law formulation is emphasized. Input and output linearization is used. Output tracking can be achieved against a class of time-varying parameter variations and external disturbances. An application to a two-degree-of-freedom manipulator indicates that the proposed switching control law drives the system state trajectories onto the chosen sliding mode in finite time and the output tracking is guaranteed.
Towards generic low-power area-efficient standard cell based memory architectures

Digital IC designers often use SRAM macrocells to implement on-chip memory functionality. In this paper we argue that in several situations, standard cell based memories (SCMs) can have advantages over SRAM macrocells. Various ways to implement SCMs are presented and compared to each other for different CMOS technologies and standard cell libraries and to corresponding macrocells, aiming for finding the most adequate memory option for each application. The benefits and drawbacks of SCMs compared to macrocells are illustrated with the example of a low-power low-density parity check (LDPC) decoder.
Can we measure software testing effectiveness?

The paper examines the issues of measuring and comparing the effectiveness of testing criteria. It argues that measurement, in the usual sense, is generally not possible, but that comparison is. In particular, it argues that uniform relations that guarantee that one criterion is better at fault detection than another, according to certain types of well-understood probabilistic measures of effectiveness, are especially valuable. <<ETX>>
Gridding for Non-Cartesian k-space Sampling

Nearly all routine clinical imaging in MRI is based on Cartesian sampling (measuring Fourier data on a regularly spaced rectlinear grid). This is true despite a large body of work has illustrated the potential benefits of various non-Cartesian methods (radial, spiral, etc.) in a variety of applications. These can include scan efficiency (maximum kspace coverage per time), robustness against motion, the ability to minimize T2(*) decay in the center of k-space, and general flexibility in measurement strategies. There are various reasons for the nearly complete lack of non-Cartesian methods in routine practice, one of them being the fidelity and simplicity of reconstruction (the subject of this abstract).
Significance of c-MET overexpression in cytotoxic anticancer drug-resistant small-cell lung cancer cells

The c‐MET receptor tyrosine kinase is the receptor for hepatocyte growth factor. Recently, activation of the c‐MET/hepatocyte growth factor signaling pathway was associated with poor prognosis in various solid tumors and was one of the mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib. But the link between c‐MET activation and the cytotoxic anticancer drug has not been fully examined. Here, we found that the enhanced expression and activation of c‐MET in cytotoxic anticancer agent‐resistant small‐cell lung cancer cells. Downregulation of c‐MET expression by siRNA against the c‐MET gene or inhibition of c‐MET activation by SU11274, a c‐MET inhibitor, in the resistant cells altered resistance to the cytotoxic anticancer agent. These results indicated that c‐MET overexpression might play an important role in acquired resistance to cytotoxic anticancer drugs. Furthermore, the number of c‐MET gene loci was increased in the resistant cells compared to the parental cells. In conclusion, increased c‐Met expression through an increase in the number of c‐MET gene loci is one of the mechanisms of acquired resistance to cytotoxic anticancer drugs. Our results add a new strategy, the targeting of c‐MET, for overcoming resistance to cytotoxic agents in small‐cell lung cancer.
New thinking about postoperative hypoalbuminemia: a hypothesis of occult protein-losing enteropathy

Hypoalbuminemia is a common and vexing postoperative complication. In some case series, about 20% to 40% of patients sustained an acute, prolonged, and profound drop in serum albumin after elective surgery. 1 - 3 Acute hypoalbuminemia is sufficiently common in critical care as to be an established risk factor in the APACHE index. 4 Hypoalbuminemia can lead to delayed mobilization, inadequate vascular access and unnecessary doses of diuretics. Where does the albumin go?