Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting Tuberculosis and Malaria through Inhibition of Enoyl Reductase

Tuberculosis and malaria together result in an estimated 5 million deaths annually. The spread of multidrug resistance in the most pathogenic causative agents, Mycobacterium tuberculosis and Plasmodium falciparum, underscores the need to identify active compounds with novel inhibitory properties. Although genetically unrelated, both organisms use a type II fatty-acid synthase system. Enoyl acyl carrier protein reductase (ENR), a key type II enzyme, has been repeatedly validated as an effective antimicrobial target. Using high throughput inhibitor screens with a combinatorial library, we have identified two novel classes of compounds with activity against the M. tuberculosis and P. falciparum enzyme (referred to as InhA and PfENR, respectively). The crystal structure of InhA complexed with NAD+ and one of the inhibitors was determined to elucidate the mode of binding. Structural analysis of InhA with the broad spectrum antimicrobial triclosan revealed a unique stoichiometry where the enzyme contained either a single triclosan molecule, in a configuration typical of other bacterial ENR:triclosan structures, or harbored two triclosan molecules bound to the active site. Significantly, these compounds do not require activation and are effective against wild-type and drug-resistant strains of M. tuberculosis and P. falciparum. Moreover, they provide broader chemical diversity and elucidate key elements of inhibitor binding to InhA for subsequent chemical optimization.
Anthraquinones Inhibit Tau Aggregation and Dissolve Alzheimer's Paired Helical Filaments in Vitro and in Cells*

The abnormal aggregation of tau protein into paired helical filaments (PHFs) is one of the hallmarks of Alzheimer's disease. Aggregation takes place in the cytoplasm and could therefore be cytotoxic for neurons. To find inhibitors of PHF aggregation we screened a library of 200,000 compounds. The hits found in the PHF inhibition assay were also tested for their ability to dissolve preformed PHFs. The results were obtained using a thioflavin S fluorescence assay for the detection and quantification of tau aggregation in solution, a tryptophan fluorescence assay using tryptophan-containing mutants of tau, and confirmed by a pelleting assay and electron microscopy of the products. Here we demonstrate the feasibility of the approach with several compounds from the family of anthraquinones, including emodin, daunorubicin, adriamycin, and others. They were able to inhibit PHF formation with IC50 values of 1–5 μm and to disassemble preformed PHFs at DC50 values of 2–4 μm. The compounds had a similar activity for PHFs made from different tau isoforms and constructs. The compounds did not interfere with the stabilization of microtubules by tau. Tau-inducible neuroblastoma cells showed the formation of tau aggregates and concomitant cytotoxicity, which could be prevented by inhibitors. Thus, small molecule inhibitors could provide a basis for the development of tools for the treatment of tau pathology in AD and other tauopathies.
High efficiency n-type solar cells with screen-printed boron emitters and ion-implanted back surface field

Formation of low-cost boron-doped emitters for mass production of n-type silicon solar cells is a major challenge in the PV industry. In this paper, we report on commercially viable screen printing technology to create boron emitters. A screen-printed boron emitter and phosphorus implanted back surface field were formed simultaneously by a co-annealing process. Front and back surfaces were passivated by chemically-grown oxide/PECVD silicon nitride stack. Front and back contacts were formed by traditional screen printing and firing processes with silver/aluminum grid on front and local silver contacts on the rear. This resulted in 19.3 % high efficient large are (239cm2) n-type solar cells with an open-circuit voltage Voc of 653 mV, short-circuit current density Jsc of 37.7 mA/cm2, and fill factor FF of 78.3 %. Co-diffusion and co-firing reduced the number of processing steps compared to the traditional technologies like BBr3 diffusion. Detailed cell analysis gave a bulk lifetime of over 1 ms, the emitter saturation current density J0e of 101 fA/cm2, and base saturation current density J0b of 259 fA/cm2 respectively. This demonstrates the potential of this novel technology for production of low-cost high-efficiency cells.
Sacral neuromodulation outcomes for the treatment of refractory idiopathic detrusor overactivity stratified by indication: Lack of anticholinergic efficacy versus intolerability.

INTRODUCTION Patients may fail oral overactive bladder therapies due to either poor drug efficacy or intolerability. We determined if the success of sacral neuromodulation varies if performed secondary to lack of anticholinergic efficacy versus drug intolerability. METHODS A retrospective review was performed on 152 patients undergoing staged sacral neuromodulation from 2004 to 2010 for refractory idiopathic detrusor overactivity with or without urge incontinence. Outcomes following sacral neuromodulation trials were compared based on the primary indication for anticholinergic failure: lack of drug efficacy versus intolerable side effects. RESULTS Overall, successful sacral neuromodulation trials were reported in 70% (106/152) of patients. Successful outcomes were noted in 70% (89/128) and 71% (17/24) of patients with poor anti-cholinergic efficacy and drug intolerability, respectively (p = NS). CONCLUSIONS We found no significant difference in outcome success in patients undergoing sacral neuromodulation trials for refractory detrusor overactivity due to lack of anticholinergic efficacy versus intolerability.
Risk of abrupt changes in the property rights protection

The aim of this paper is to develop method for evaluating the predictability of the institutional environment. It is based on standard time-series analysis and suggests two measures of predictability. This method is applied on development of property rights protection level which is approximatively described by index based on expert evaluation from International Country Risk Guide (ICRG). Obtained measures of predictability are tested using econometric model with cross-sectional data and recognized as a significant predictor of economic performance.
Data Cleaning Method Based on Time Series Similarity Measurement for Large-Scale Smart Grid Load Data

On account of the strong time series feature of smart grid load data, this paper presents a data cleaning method based on similarity measurement of time series, which detects the abnormal data of load data and fills the vacancy value. In this paper, an up-and-coming symbolic method symbolic aggregate approximation(SAX) is applied to the similarity study of 96-point load data. The Euclidean distance algorithm is used to measure the similarity of time series, and the load data are cleaned according to the fitted curves obtained by adjusting similar sequences weighted by similarity. The experimental results show that the method has adequate accuracy and low computational complexity.
An Examination of the Leadership Practices Related to School Culture and Organizational Learning in a Consolidated Grade 7-12 School

This study aims to characterize the leadership practices related to the promotion of organizational learning and a single school culture in an Ontario, public-funded consolidated grade 7 -12 school. The research adopts a qualitative single case study approach that uses semi-structured interviews with a variety of current and former leaders in the school board, field notes and archival and current board correspondence. A brief examination of literature on educational leadership, school culture, and organizational learning will provide the necessary conceptual framework to identify and understand the practices that sustained the consolidation of 7-8 grades from various local K-8 schools and one 9-12 school into a large 7-12 school. Eacott’s (2013) conceptualization of leadership as a social practice which takes into consideration the social context in which leadership practices emerge, aligns with the purpose of this study. It is the intent of this research project to provide rich descriptions of the leadership processes that have taken place during the consolidation process and to offer further recommendations for similar processes in grade 7 -12 schools across the province. Key terms: school culture, organizational learning, leadership, school consolidation RUNNING HEAD: LEADERSHIP PRACTICES IN A GRADE 7-12 SCHOOL ii
Evaluation of the Bactec MGIT 960 System in Combination with the MGIT TBc Identification Test for Detection of Mycobacterium tuberculosis Complex in Respiratory Specimens

ABSTRACT The sensitivity and specificity of the MGIT TBc identification (TBc ID) test for Mycobacterium tuberculosis complex (MTC) detection in positive Bactec MGIT cultures were 95.2% and 99.2%, respectively. When MTC-positive results obtained from two additional molecular methods were included, the sensitivity of the MGIT TBc ID test was 85.4%, while that of culture was 95.7%.
Mouse α1(I)‐collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast

Cell‐ and time‐specific gene inactivation should enhance our knowledge of bone biology. Implementation of this technique requires construction of transgenic mouse lines expressing Cre recombinase in osteoblasts, the bone forming cell. We tested several promoter fragments for their ability to drive efficient Cre expression in osteoblasts. In the first mouse transgenic line, the Cre gene was placed under the control of the 2.3‐kb proximal fragment of the α1(I)‐collagen promoter, which is expressed at high levels in osteoblasts throughout their differentiation. Transgenic mice expressing this transgene in bone were bred with the ROSA26 reporter (R26R) strain in which the ROSA26 locus is targeted with a conditional LacZ reporter cassette. In R26R mice, Cre expression and subsequent Cre‐mediated recombination lead to expression of the LacZ reporter gene, an event that can be monitored by LacZ staining. LacZ staining was detected in virtually all osteoblasts of α1(I)‐Cre;R26R mice indicating that homologous recombination occurred in these cells. No other cell type stained blue. In the second line studied, the 1.3‐kb fragment of osteocalcin gene 2 (OG2) promoter, which is active in differentiated osteoblasts, was used to drive Cre expression. OG2‐Cre mice expressed Cre specifically in bone. However, cross of OG2‐Cre mice with R26R mice did not lead to any detectable LacZ staining in osteoblasts. Lastly, we tested a more active artificial promoter derived from the OG2 promoter. The artificial OG2‐Cre transgene was expressed by reverse transcriptase‐polymerase chain reaction in cartilage and bone samples. After cross of the artificial OG2‐Cre mice with R26R mice, we detected a LacZ staining in articular chondrocytes but not in osteoblasts. Our data suggest that the only promoter able to drive Cre expression at a level sufficient to induce recombination in osteoblasts is the α1(I)‐collagen promoter. © 2002 Wiley‐Liss, Inc.
Microwave Characterization of Silicon Wafer Using Rectangular Dielectric Waveguide

A non-destructive and easy to use method is presented to characterize p-type and n-type silicon semiconductor wafers using a rectangular dielectric waveguide measurement (RDWG) system. The measurement system consists of a vector network analyzer (VNA), a pair of coaxial cable, coaxial to waveguide adapter and dielectric-filled standard gain horn antenna. In this method, the reflection and transmission coefficients, S11 and S21 were measured for silicon wafer sandwiched between the two Teflon, the dielectric that filled the standard gain horn antenna. It was observed that, the dielectric constant of the silicon wafers are relatively constant, varying slightly over the frequency range of 9 to 12 GHz. The loss factor, loss tangent and conductivity of the doped wafers are higher than the undoped type
PENGARUH FREE CASH FLOW, INVESTMENT OPPORTUNITY SET, DAN SALES GROWTH TERHADAP DIVIDEND POLICY PADA PERUSAHAAN MANUFAKTUR YANG TERDAFTAR DI BURSA EFEK INDONESIA

Abstrak Penelitian ini bertujuan untuk menguji secara empiris pengaruh free cash flow, investment opportunity set, dan sales growth terhadap dividend policy pada perusahaan manufaktur di BEI periode 2010-2013. Teknik analisis data yang digunakan adalah regresi linier berganda. Hasil dari penelitian ini menunjukkan bahwa investment opportunity set berpengaruh negatif dan signifikan terhadap dividend policy . Free cash flow dan s ales growth tidak berpengaruh terhadap dividend policy . Pengujian secara simultan ketiga variabel ini mempunyai pengaruh terhadap dividend policy . Kata Kunci : Free Cash Flow, Investment Opportunity Set, Sales Growth, dan Dividend Policy . Abstract This study was aim ed to investigate the effects of free cash flow, investment opportunity set, and sales growth to the dividend policy of the manufacture compan ies listed in BEI during 2010-2013. M ultiple regression was used to analyze the data . The result of this study showed that investment opportunity set h ad negative and significant effect to debt policy. Free cash flow and sales growth had un-significant effect to d ividend policy . The simultaneous testing showed that the three variables had influence t o debt policy .
Urban mobility and location-based social networks: social, economic and environmental incentives

Location-based social networks (LBSNs) have recently attracted the interest of millions of users who can now not only connect and interact with their friends - as it also happens in traditional online social networks - but can also voluntarily share their whereabouts in real time. A location database is the backbone of a location-based social network and includes fine-grained semantic information for real-world places. The footprints captured in a location database represent the human socioeconomic activities and urban mobility at scale. LBSNs bridge the gap between the online and offline physical world, providing an unprecedented opportunity for researchers to access information that will allow them to place and understand human movements in the contexts of urban, social and economic activities. In this dissertation, I design statistical analysis and modeling frameworks to examine how factors, including social interaction, economic incentives and local events, affect human movement across places in urban space. The dissertation first shows that people's visitation to local places exhibit significant levels of homophily, where peer influence can explain up to 40% of a geographically localized similarity between friends. We also find that the social selection mechanism is triggered by non-trivial similarity which is captured by places with specific network characteristics. Next, our quasi-experimental analysis reveals that online promotions in LBSNs are not as effective as anecdotal stories might suggest in attracting customers, and consequently in affecting the underlying city-dweller mobility. These results can have significant implications on advertisement strategies for local businesses. Finally, our developed framework is applied to assess the impact of local government decisions on urban mobility and economic activities, which can provide a blueprint for future educated policy making. The outcome of this dissertation is envisioned to help better understand human urban movements motivated by social, economic and external environmental factors and further foster applications in sociology, local economy and urban planning.
Physarum actin is phosphorylated as the actin‐fragmin complex at residues Thr203 and Thr202 by a specific 80 kDa kinase.

The Physarum EGTA‐resistant actin‐fragmin complex, previously named cap 42(a+b), is phosphorylated in the actin subunit by an endogenous kinase [Maruta and Isenberg (1983) J. Biol. Chem., 258, 10151–10158]. This kinase has been purified and characterized. It is an 80 kDa monomeric enzyme, unaffected by known kinase regulators. Staurosporine acts as a potent inhibitor. The actin‐fragmin complex is the preferred substrate. The phosphorylation is inhibited by micromolar Ca2+ concentrations, but only in the presence of additional actin. Polymerized actin (vertebrate muscle and non‐muscle isoforms) and actin complexes with various actin‐binding proteins are poorly phosphorylated. The heterotrimer consisting of two actins and one fragmin, which is formed from cap 42(a+b) and actin in the presence of micromolar concentrations of Ca2+, is also a poor substrate. From the other substrates tested, only histones were significantly phosphorylated, in particular histone H1. In the same manner, casein kinase I could also phosphorylate the actin‐fragmin complex. The major phosphorylation site in actin is Thr203. A second minor site is Thr202. These residues constitute one of the contact sites for DNase I [Kabsch et al. (1990) Nature, 347, 37–44] and are also part of one of the predicted actin‐actin contact sites in the F‐actin model [Holmes et al. (1990) Nature, 347, 44–49].
Metabolism of 8-aminoquinoline antimalarial agents.

Some of the most effective antimalarial agents are derivatives of 8-aminoquinoline. The metabolic products of many of these compounds appear to be toxic to the erythrocytes of certain human subjects, especially those deficient in glucose-6-phosphate dehydrogenase. Although a number of studies have been conducted over many years, the metabolism of most of these compounds has not been determined. These studies are reviewed.Adult dogs dosed with tritium-labelled primaquine were observed to excrete approximately 16% of the injected radioactivity in the urine within 8 hours. Organic extracts of the urine were fractionated by thin-layer chromatography and the metabolic pattern obtained. Some primaquine was excreted along with at least five metabolites including 5-hydroxy-6-methoxy-8-(4-amino-1-methylbutylamino)quinoline (5HPQ) and a small amount of 6-hydroxy-8-(4-amino-1-methylbutylamino)quinoline (6HPQ). The 5HPQ could form a quinoneimine-type compound which may be a methaemoglobin-forming compound. This and other metabolites isolated from urine were found to be active methaemoglobin formers in in vitro studies. In vitro metabolism of primaquine by mouse liver enzymes also produced compounds capable of methaemoglobin formation. One of these had a blue colour when exposed to alkaline conditions, air, and light, and mass spectral data and nuclear magnetic resonance analysis indicated a structure similar to a 5,6-dihydroxy derivative of primaquine. However, the chemical structure of the metabolite was not identified in these studies.
THE TEACHEX PROJECT – GUIDING ISRAEL HIGHER EDUCATION INSTITUTIONS TOWARDS TEACHING EXCELLENCE

This paper presents the TeachEx project http://www.teachex. eu/, an Israel Erasmus+ Capacity Building in Higher Education project. The project started in November 2015 and will end in October 2018. The aim of the project is to promote teaching excellence amongst Israeli Higher Education institutions. The project consortium is led by the Interdisciplinary Center (IDC) Herzliya, and includes the following Israeli Higher Education Institutions: Ben-Gurion University, Beit Berl College, Belazel Academy of Arts and Design Jerusalem, Gordon Academic College of Education, and the Oranim Academic College of Education. The consortium also includes the following European Universities and Higher Education Institutions and Organizations that act as consultants: University of Brighton, University of Jagiellonian, University College Cork, Glasgow Caledonian University, University of Groningen, University of Nicosia and European Association of Institutions in Higher Education (EURASHE). Finally, as student involvement is extremely important in improving teaching, the National Union of Israeli Students (NUIS) participate in the consortium, providing significant input to teaching excellence, especially as perceived by students. In order to aim at teaching excellence, the project has identified five thematic areas pertaining to teaching excellence. These thematic areas have been matched to five training/learning modules, namely: (i) Diversity and Accessible Instruction, (ii) Active/Reflective Teaching and Learning: Learning from Art and Design, (iii) Mobile Learning, (iv) Lecturer as a Producer, and (v) Problem/Project-based Learning (PBL). The five modules will be used as training material for faculty members in order to help them improve their teaching effectiveness so that they can aim at teaching excellence and will be available as open educational resources through the on-line web-based repository, available through the projects web-site. The modules will be delivered to the faculty members by other faculty members (hereafter referred to as the trainers) who will be trained by the module developers. The trainers are members of the Centres of Teaching Excellence (CTE), which have been established in the Israeli institutions as part of this project. The paper is organized as follows. Introduction briefly introduces some recent developments with regards policies and practices in teaching and learning excellence and sets the framework within this project was developed. Section 2 explains the project’s main aims and objectives. Section 3 presents the five modules that have been developed within the project and underpin the main aim of the project, namely training of faculty members in teaching excellence. It also discusses their interconnection and how they provide support for teaching excellence. Finally, Conclusions summarize our work and findings and report on our future actions.
Permanently Blocked Stem Cells Derived From Breast Cancer Cell Lines

Cancer stem cells (CSCs) are thought to be resistant to standard chemotherapeutic drugs and the inimical conditions of the tumor microenvironment. Obtaining CSCs in sufficient quantities and maintaining their undifferentiated state have been major hurdles to their further characterization and to the identification of new pharmaceuticals that preferentially target these cells. We describe here the tagging of CSC‐like populations from four human breast cancer cell lines with green fluorescent protein (GFP) under the control of the Oct3/4 stem cell‐specific promoter. As expected, GFP was expressed by the CSC‐enriched populations. However, an unanticipated result was that these cells remained blocked in a CSC‐like state and tended to be resistant to chemotherapeutic drugs as well as acidotic and hypoxic conditions. These CSC‐like cells possessed several other in vitro attributes of CSCs and were able to reproducibly generate tumors in immunocompromised mice from as few as 100 cells. Moreover, the tumors derived from these cells were comprised almost exclusively of pure CSCs. The ability of the Oct3/4 promoter to block CSC differentiation underscores its potential general utility for obtaining highly purified CSC populations, although the mechanism by which it does so remains undefined and subject to further study. Nonetheless, such stable cell lines should be extremely valuable tools for studying basic questions pertaining to CSC biology and for the initial identification of novel CSC‐specific chemotherapeutic agents, which can then be verified in primary CSCs. STEM Cells 2010;28:1008–1018