Miracle-dz/UniFAR-FTUs huggingface dataset:
Unveiling Benznidazole's mechanism of action through overexpression of DNA repair proteins in Trypanosoma cruzi

Benznidazole (BZ) is the most commonly used drug for the treatment of Chagas disease. Although BZ is known to induce the formation of free radicals and electrophilic metabolites within the parasite Trypanosoma cruzi, its precise mechanisms of action are still elusive. Here, we analyzed the survival of T. cruzi exposed to BZ using genetically modified parasites overexpressing different DNA repair proteins. Our results indicate that BZ induces oxidation mainly in the nucleotide pool, as heterologous expression of the nucleotide pyrophosphohydrolase MutT (but not overexpression of the glycosylase TcOgg1) increased drug resistance in the parasite. In addition, electron microscopy indicated that BZ catalyzes the formation of double‐stranded breaks in the parasite, as its genomic DNA undergoes extensive heterochromatin unpacking following exposure to the drug. Furthermore, the overexpression of proteins involved in the recombination‐mediated DNA repair increased resistance to BZ, reinforcing the idea that the drug causes double‐stranded breaks. Our results also show that the overexpression of mitochondrial DNA repair proteins increase parasite survival upon BZ exposure, indicating that the drug induces lesions in the mitochondrial DNA as well. These findings suggest that BZ preferentially oxidizes the nucleotide pool, and the extensive incorporation of oxidized nucleotides during DNA replication leads to potentially lethal double‐stranded DNA breaks in T. cruzi DNA. Environ. Mol. Mutagen. 55:309–321, 2014. © 2013 Wiley Periodicals, Inc.
High‐frequency oscillations, extent of surgical resection, and surgical outcome in drug‐resistant focal epilepsy

Removal of areas generating high‐frequency oscillations (HFOs) recorded from the intracerebral electroencephalography (iEEG) of patients with medically intractable epilepsy has been found to be correlated with improved surgical outcome. However, whether differences exist according to the type of epilepsy is largely unknown. We performed a comparative assessment of the impact of removing HFO‐generating tissue on surgical outcome between temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). We also assessed the relationship between the extent of surgical resection and surgical outcome.
The free mobility of a parallel manipulator

Singularities of a manipulator have been addressed repeatedly. However, the singularities and the degree(s) of freedom, as a matter of fact, are two different aspects of the mobility of a manipulator. Consequently, this paper dedicates to discussing the mobility properties through mobility space, which synchronously define the type, number and direction characteristics of the independent motions that the manipulator should execute. The mobility space of a manipulator can be obtained with reciprocal screws of the manipulator via singular value decomposition, which instantaneously depicts the singularity and mobility problems of the manipulators. Application example demonstrates that this methodology can investigate the all-sided mobility properties of parallel manipulators.
Optimizing Locations for a Vehicle Sharing System

Car-sharing business provides members access to a fleet of shared-use vehicles in a network of locations on a short-term, as-needed basis. It allows individuals to gain the benefits of private vehicle use without the costs and responsibilities of ownership. The primary advantage of car sharing as opposed to the car rental business is that it provides flexibility of using the vehicles for shorter periods of time. Secondly if you are a registered customer of the company, the process of accessing and using the vehicle is quite simple, self-serving and hassle-free. One of the main problems faced by the car-sharing businesses is that of finding the best stations to place the facility. These locations should be chosen by attractiveness of various parameters such as the socio-demographic-economic profile of the population that resides or works at the location and accessibility of other forms of public transport in that location. However the presence of one or more stations in the vicinity and the type of vehicles placed in a station are also critical for decision-making. It must be noted that the attractiveness factor of a parameter would be shared between different stations if they are present in the sphere of influence of that parameter. This study analyzes the performance of an electric car sharing service across different stations in and around the city of Nice. This service is operated by a major public transport operator in France and commenced its operations in April 2011. The main measure of performance of the stations is the average number of rides (usages) per day. The objective of this study is two-fold one, to analyze the performance of the car-sharing service across all stations and estimate the key drivers of demand, and secondly, to use these drivers to identify future station locations, such that the overall system performance is maximized. The methodology used by us to optimize the station locations follows two steps. In the first step, we perform an extensive data analysis and determine all those factors that we expect to be driving the demand for the service and build a linear regression model with station performance as the dependent variable that is explained by a host of other independent variables, such as public transport ridership, share of car-users in the locality, share of high income / education groups in the locality population, population density and presence of other mobility generators such as hotels, colleges and commercial centers. In the second and final step, we use the attractiveness of the different localities to optimally locate the new stations for the service. The main trade-off decision made by the model involves locating more stations in highly attractive localities versus locating new stations in less attractive but untapped localities. We validated and reported our results on a set of new stations that were opened quite recently, after the commencement of our study.
Plant Ribosome-Inactivating Proteins: Progesses, Challenges and Biotechnological Applications (and a Few Digressions)

Plant ribosome-inactivating protein (RIP) toxins are EC3.2. 2.22 N-glycosidases, found among most plant species encoded as small gene families, distributed in several tissues being endowed with defensive functions against fungal or viral infections. The two main plant RIP classes include type I (monomeric) and type II (dimeric) as the prototype ricin holotoxin from Ricinus communis that is composed of a catalytic active A chain linked via a disulphide bridge to a B-lectin domain that mediates efficient endocytosis in eukaryotic cells. Plant RIPs can recognize a universally conserved stem-loop, known as the α-sarcin/ ricin loop or SRL structure in 23S/25S/28S rRNA. By depurinating a single adenine (A4324 in 28S rat rRNA), they can irreversibly arrest protein translation and trigger cell death in the intoxicated mammalian cell. Besides their useful application as potential weapons against infected/tumor cells, ricin was also used in bio-terroristic attacks and, as such, constitutes a major concern. In this review, we aim to summarize past studies and more recent progresses made studying plant RIPs and discuss successful approaches that might help overcoming some of the bottlenecks encountered during the development of their biomedical applications.
DNA methylation biomarkers of prostate cancer: Confirmation of candidates and evidence urine is the most sensitive body fluid for non‐invasive detection

A prostate cancer (PCa) biomarker with improved specificity relative to PSA is a public health priority. Hypermethylated DNA can be detected in body fluids from PCa patients and may be a useful biomarker, although clinical performance varies between studies. We investigated the performance of candidate PCa DNA methylation biomarkers identified through a genome‐wide search.
Internal and External Bitstream Relocation for Partial Dynamic Reconfiguration

The research described in this paper shows how the runtime relocation of a reconfigurable component can be obtained using a system component that is able to update the bitstream information, moving the reconfigurable module in the desired position. This scenario defines the so-called partial bitstream relocation activity. This paper proposes a relocation filter that can be implemented both as a hardware and a software component. The former is hosted in the static part of the reconfigurable architecture, while the latter is made to be run on the processor placed on the field-programmable gate array (FPGA). The proposed approach has also been validated over different FPGAs, i.e., Virtex II Pro, Virtex 4, and Virtex 5, proposing a runtime relocation support that can be customized to meet all the different constraints associated with these different target architectures.
Yeast DNA Polymerase ε Participates in Leading-Strand DNA Replication

Multiple DNA polymerases participate in replicating the leading and lagging strands of the eukaryotic nuclear genome. Although 50 years have passed since the first DNA polymerase was discovered, the identity of the major polymerase used for leading-strand replication is uncertain. We constructed a derivative of yeast DNA polymerase ϵ that retains high replication activity but has strongly reduced replication fidelity, particularly for thymine-deoxythymidine 5'-monophosphate (T-dTMP) but not adenine-deoxyadenosine 5'-monophosphate (A-dAMP) mismatches. Yeast strains with this DNA polymerase ϵ allele have elevated rates of T to A substitution mutations. The position and rate of these substitutions depend on the orientation of the mutational reporter and its location relative to origins of DNA replication and reveal a pattern indicating that DNA polymerase ϵ participates in leading-strand DNA replication.
Culture of Lymphocytes and Hemopoietic Cells in Serum-Free Medium

Freshly explanted lymphocytes and hemopoietic cells can grow and differentiate to terminally functioning cells in culture. Such cultures provide an opportunity to study, in cells not previously subjected to in vitro selection, such phenomena as induction of growth in physiologically resting cells, immune recognition, and the function of specific polypeptide factors and cell surface receptors. There are circumstances in which it would be desirable to perform these cultures in the absence of serum. One may wish to assay or study the function of added polypeptide factors that may already be present in serum in unknown concentrations. In other situations, the desired responses may be inhibited by substances in serum, or may be induced via mechanisms irrelevant to the one under study. Particularly significant in the case of immune responses are the antigens and antibodies contained in serum over which the experimenter has no control. In eliminating serum from the cultures to avoid interpretational difficulties, it is important not to introduce new ones. This could happen if responses in serum-free conditions were inferior to those obtainable with serum through failure to fulfill nutritive requirements of the cells. When the conditions described here were developed, emphasis was placed on achieving responses in serum-free cultures that were at least as good as those in conventional conditions. As it turned out, responses in serum-free cultures significantly surpassed those normally seen in conventional serum-containing media, particularly in lymphocyte cultures [Iscove and Melchers, 1978; Iscove et al., 1980; Schreier, 1981].
Text Segmentation by Language Using Minimum Description Length

The problem addressed in this paper is to segment a given multilingual document into segments for each language and then identify the language of each segment. The problem was motivated by an attempt to collect a large amount of linguistic data for non-major languages from the web. The problem is formulated in terms of obtaining the minimum description length of a text, and the proposed solution finds the segments and their languages through dynamic programming. Empirical results demonstrating the potential of this approach are presented for experiments using texts taken from the Universal Declaration of Human Rights and Wikipedia, covering more than 200 languages.
SeDiTeC-testing based on sequence diagrams

In this paper we present a concept for automated testing of object-oriented applications and a tool called SeDiTeC that implements these concepts for Java applications. SeDiTeC uses UML sequence diagrams, that are complemented by test case data sets consisting of parameters and return values for the method calls, as test specification and therefore can easily be integrated into the development process as soon as the design phase starts. SeDiTeC supports specification of several test case data sets for each sequence diagram as well as to combine several sequence diagrams to so-called combined sequence diagrams thus reducing the number of diagrams needed. For classes and their methods whose behavior is specified in sequence diagrams and the corresponding test case data sets SeDiTeC can automatically generate test stubs thus enabling testing right from the beginning of the implementation phase. Validation is not restricted to comparing the test case data sets with the observed data, but can also include validation of pre- and postconditions.
Spectral Characterization and Antibacterial Activity of Synthesis Graphene Oxide Nanosheets

Graphene based materials have wide potential applications in biology, biomedical, agriculture environmental and biotechnology. Graphene Oxide (GO) is one of those substances and has a promising material as antimicrobial agents. In this work, the GO nanosheets have been synthesized by novel, easy, and efficient technique is simplified Hummer's method. The spectral properties of the synthesis GO nanosheets were characterized by using Raman, FTIR, and UV-Vis techniques. The Raman spectroscopy has been used to measure number of layers (sheets), grain size, and to identify the ordered and disordered structure of GO nanosheets. Fourier Transform-Infrared spectroscopy (FTIR) has confirmed the presence of the oxygen containing functional groups of the GO nanosheets. The Ultraviolet-Visible (UV-Vis) absorption spectrum shows two peaks, one in the UV region and the other band in visible region. The purpose of this work is to inspect the antibacterial activities of GO nanosheets, which has been synthesized by this novel way (simplified Hummer's method). It was tested against two microorganisms, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as model of Gram-negative bacteria and Gram-positive bacteria, respectively. Bacteriological studies were achieved by minimum inhibitory concentration (MIC), and cell viability analysis. The MIC showed the lowest concentration inhibits the bacterial growth of GO nanosheets, which is observed for E. coli was 125 μg/ml and 62.5 μg/ml for S. aureus. The cell viability analysis measured by florescent microscope has been confirmed the damage, which has been occurred on bacterial nucleic acid for the two types of bacteria.
Depressive Symptoms in Low-Income, Urban Adolescents: Cognitive and Contextual Factors

This study examined the relationships among cognitive variables, family immigration history, negative life events, and depressive symptoms in a sample of 306 low-income, urban fifth- and sixth-grade children. Explanatory style and negative automatic thoughts were the cognitive variables examined. There were three key findings. First, children who were immigrants reported significantly more depressive symptoms, more negative life events, and more negative automatic thoughts than children who were not immigrants. Second, both explanatory style and negative automatic thoughts were significantly associated with depressive symptoms above and beyond the effects of child immigration history and negative life events. Finally, negative automatic thoughts mediated the relationship between child immigration history and depressive symptoms. We discuss the clinical and research implications of these findings.
Automated model-based spreadsheet debugging

Spreadsheets are interactive data organization and calculation programs that are developed in spreadsheet environments like Microsoft Excel or LibreOffice Calc. They are probably the most successful example of end-user developed software and are utilized in almost all branches and at all levels of companies. Although spreadsheets often support important decision making processes, they are, like all software, prone to error. In several cases, faults in spreadsheets have caused severe losses of money. Spreadsheet developers are usually not educated in the practices of software development. As they are thus not familiar with quality control methods like systematic testing or debugging, they have to be supported by the spreadsheet environment itself to search for faults in their calculations in order to ensure the correctness and a better overall quality of the developed spreadsheets. This thesis by publication introduces several approaches to locate faults in spreadsheets. The presented approaches are based on the principles of Model-Based Diagnosis (MBD), which is a technique to find the possible reasons why a system does not behave as expected. Several new algorithmic enhancements of the general MBD approach are combined in this thesis to allow spreadsheet users to debug their spreadsheets and to efficiently find the reason of the observed unexpected output values. In order to assure a seamless integration into the environment that is wellknown to the spreadsheet developers, the presented approaches are implemented as an extension for Microsoft Excel. The first part of the thesis outlines the different algorithmic approaches that are introduced in this thesis and summarizes the improvements that were achieved over the general MBD approach. In the second part, the appendix, a selection of the author’s publications are presented. These publications comprise (a) a survey of the research in the area of spreadsheet quality assurance, (b) a work describing
Termination and verification for ill-posed semidefinite programming problems

We investigate ill-posed semidefinite programming problems for which Slater’s constraint qualifications fail, and propose a new reliable termination criterium dealing with such problems. This criterium is scale-independent and provides verified forward error bounds for the true optimal value, where all rounding errors due to floating point arithmetic are taken into account. It is based on a boundedness qualification, which is satisfied for many problems. Numerical experiments, including combinatorial problems, are presented.
The Medieval Origins of the Concept of Hypertension

Despite the well-known history of hypertension research in the modern era, like many other cardiovascular concepts, main points in the medieval concept of this disease and its early management methods remain obscure. This article attempts to make a brief review on the medieval origin of the concept of this disease from the Hidayat of Al-Akhawayni (? -983 AD). This article has reviewed the chapter of "Fi al-Imtela0" (About the Fullness) from the Hidβyat al-Muta′allimin fi al-Tibb (The Students′ Handbook of Medicine) of Al-Akhawayni. The definition, symptoms and treatments presented for the Imtela are compared with the current knowledge on hypertension. Akhawayni believed that Imtela could result from the excessive amount of blood within the blood vessels. It can manifest with symptoms including the presence of a pulsus magnus, sleepiness, weakness, dyspnea, facial blushing, engorgement of the vessels, thick urine, vascular rupture, and hemorrhagic stroke. He also suggested some ways to manage al-Imtela′. These include recommendations of changes in lifestyle (staying away from anger and sexual intercourse) and dietary program for patients (avoiding the consumption of wine, meat, and pastries, reducing the volume of food in a meal, maintaining a low-energy diet and the dietary usage of spinach and vinegar). Al-Akhawayni′s description of "Imtela," despite of its numerous differences with current knowledge of hypertension, can be considered as medieval origin of the concept of hypertension.
Targeting TRP Channels For Novel Migraine Therapeutics

Migraine is increasingly understood to be a disorder of the brain. In susceptible individuals, a variety of “triggers” may influence altered central excitability, resulting in the activation and sensitization of trigeminal nociceptive afferents surrounding blood vessels (i.e., the trigeminovascular system), leading to migraine pain. Transient receptor potential (TRP) channels are expressed in a subset of dural afferents, including those containing calcitonin gene related peptide (CGRP). Activation of TRP channels promotes excitation of nociceptive afferent fibers and potentially lead to pain. In addition to pain, allodynia to mechanical and cold stimuli can result from sensitization of both peripheral afferents and of central pain pathways. TRP channels respond to a variety of endogenous conditions including chemical mediators and low pH. These channels can be activated by exogenous stimuli including a wide range of chemical and environmental irritants, some of which have been demonstrated to trigger migraine in humans. Activation of TRP channels can elicit CGRP release, and blocking the effects of CGRP through receptor antagonism or antibody strategies has been demonstrated to be effective in the treatment of migraine. Identification of approaches that can prevent activation of TRP channels provides an additional novel strategy for discovery of migraine therapeutics.
Astrometric accuracy of phase-referenced observations with the vlba and evn

Astrometric accuracy of complex modern VLBI arrays cannot be calculated analytically. We study the astrometric accuracy of phase-referenced VLBI observations for the VLBA, EVN and global VLBI array by simulating VLBI data for targets at declinations -25$^\circ$, 0$^\circ$, 25$^\circ$, 50$^\circ$, 75$^\circ$ and 85$^\circ$. The systematic error components considered in this study are calibrator position, station coordinate, Earth orientation and troposphere parameter uncertainties. We provide complete tables of the astrometric accuracies of these arrays for a source separation of 1$^\circ$ either along the right ascension axis or along the declination axis. Astrometric accuracy is 50microas at mid declination and is 300microas at low (-25$^\circ$) and high (85$^\circ$) declinations for the VLBA and EVN. In extending our simulations to source separations of 0.5$^\circ$ and 2$^\circ$, we establish the formula for the astrometric accuracy of the VLBA: Delta = (Delta_1$^\circ$-14)*d+ 14 (microas) where Delta_1$^\circ$ is the astrometric accuracy for a separation d=1$^\circ$ provided in our tables for various declinations and conditions of the wet troposphere. We argue that this formula is also valid for the astrometric accuracy of the EVN and global VLBI array.