Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Disputed Mutations in the rpoB Gene in Interpretation of Automated Liquid MGIT Culture Results for Rifampin Susceptibility Testing of Mycobacterium tuberculosis

ABSTRACT Low-level rifampin resistance associated with specific rpoB mutations (referred as “disputed”) in Mycobacterium tuberculosis is easily missed by some phenotypic methods. To understand the mechanism by which some mutations are systematically missed by MGIT phenotypic testing, we performed an in silico analysis of their effect on the structural interaction between the RpoB protein and rifampin. We also characterized 24 representative clinical isolates by determining MICs on 7H10 agar and testing them by an extended MGIT protocol. We analyzed 2,097 line probe assays, and 156 (7.4%) cases showed a hybridization pattern referred to here as “no wild type + no mutation. ” Isolates harboring “disputed” mutations (L430P, D435Y, H445C/L/N/S, and L452P) tested susceptible in MGIT, with prevalence ranging from 15 to 57% (overall, 16 out of 55 isolates [29%]). Our in silico analysis did not highlight any difference between “disputed” and “undisputed” substitutions, indicating that all rpoB missense mutations affect the rifampin binding site. MIC testing showed that “undisputed” mutations are associated with higher MIC values (≥20 mg/liter) compared to “disputed” mutations (4 to >20 mg/liter). Whereas “undisputed” mutations didn't show any delay (Δ) in time to positivity of the test tube compared to the control tube on extended MGIT protocol, “disputed” mutations showed a mean Δ of 7.2 days (95% confidence interval [CI], 4.2 to 10.2 days; P < 0.05), providing evidence that mutations conferring low-level resistance are associated with a delay in growth on MGIT. Considering the proved relevance of L430P, D435Y, H445C/L/N, and L452P mutations in determining clinical resistance, genotypic drug susceptibility testing (DST) should be used to replace phenotypic results (MGIT) when such mutations are found.
Reconstructing surfaces of particle-based fluids using anisotropic kernels

In this article we present a novel surface reconstruction method for particle-based fluid simulators such as Smoothed Particle Hydrodynamics. In particle-based simulations, fluid surfaces are usually defined as a level set of an implicit function. We formulate the implicit function as a sum of anisotropic smoothing kernels, and the direction of anisotropy at a particle is determined by performing Principal Component Analysis (PCA) over the neighboring particles. In addition, we perform a smoothing step that repositions the centers of these smoothing kernels. Since these anisotropic smoothing kernels capture the local particle distributions more accurately, our method has advantages over existing methods in representing smooth surfaces, thin streams, and sharp features of fluids. Our method is fast, easy to implement, and our results demonstrate a significant improvement in the quality of reconstructed surfaces as compared to existing methods.
Label-Free FimH Protein Interaction Analysis Using Silicon Nanoribbon BioFETs

The detection of biomarkers at very low concentration and low cost is increasingly important for clinical diagnosis. Moreover, monitoring affinities for receptor-antagonist interactions by time-resolved measurements is crucial for drug discovery and development. Biosensors based on ion-sensitive field-effect transistors (BioFETs) are promising candidates for being integrated into CMOS structures and cost-effective production. The detection of DNA and proteins with silicon nanowires has been successfully demonstrated using high affinity systems such as the biotin–streptavidin interaction. Here, we show the time-resolved label-free detection of the interaction of the bacterial FimH lectin with an immobilized mannose ligand on gold-coated silicon nanoribbon BioFETs. By comparing our results with a commercial state of the art surface plasmon resonance system, additional surface effects become visible when using this charge based detection method. Furthermore, we demonstrate the effect of sensor area on signal.
Probabilistic one class learning for automatic detection of multiple sclerosis lesions

This paper presents an automatic algorithm for the detection of multiple sclerosis lesions (MSL) from multi-sequence magnetic resonance imaging (MRI). We build a probabilistic classifier that can recognize MSL as a novel class, trained only on Normal Appearing Brain Tissues (NABT). Patch based intensity information of MRI images is used to train a classifier at the voxel level. The classifier is in turn used to compute a probability characterizing the likelihood of each voxel to be a lesion. This probability is then used to identify a lesion voxel based on simple Otsu thresholding. The proposed framework is evaluated on 16 patients and our analysis reveals that our approach is well suited for MSL detection and outperforms other benchmark approaches.
An Initial Investigation of the Neural Correlates of Word Processing in Preschoolers With Specific Language Impairment.

Purpose Previous behavioral studies have found deficits in lexical-semantic abilities in children with specific language impairment (SLI), including reduced depth and breadth of word knowledge. This study explored the neural correlates of early emerging familiar word processing in preschoolers with SLI and typical development. Method Fifteen preschoolers with typical development and 15 preschoolers with SLI were presented with pictures followed after a brief delay by an auditory label that did or did not match. Event-related brain potentials were time locked to the onset of the auditory labels. Children provided verbal judgments of whether the label matched the picture. Results There were no group differences in the accuracy of identifying when pictures and labels matched or mismatched. Event-related brain potential data revealed that mismatch trials elicited a robust N400 in both groups, with no group differences in mean amplitude or peak latency. However, the typically developing group demonstrated a more robust late positive component, elicited by mismatch trials. Conclusions These initial findings indicate that lexical-semantic access of early acquired words, indexed by the N400, does not differ between preschoolers with SLI and typical development when highly familiar words are presented in isolation. However, the typically developing group demonstrated a more mature profile of postlexical reanalysis and integration, indexed by an emerging late positive component. The findings lay the necessary groundwork for better understanding processing of newly learned words in children with SLI.
Feasibility of vocal emotion conversion on modulation spectrogram for simulated cochlear implants

Cochlear implant (CI) listeners were found to have great difficulty with vocal emotion recognition because of the limited spectral cues provided by CI devices. Previous studies have shown that the modulation spectral features of temporal envelopes may be important cues for vocal emotion recognition of noise-vocoded speech (NVS) as simulated CIs. In this paper, the feasibility of vocal emotion conversion on a modulation spectrogram for simulated CIs for correctly recognizing vocal emotion is confirmed. A method based on a linear prediction scheme is proposed to modify the modulation spectrogram and its features of neutral speech to match that of emotional speech. The logic of this approach is that if vocal emotion perception of NVS is based on the modulation spectral features, NVS with similar modulation spectral features of emotional speech will be recognized as the same emotion. As a result, it was found that the modulation spectrogram of neutral speech can be successfully converted to that of emotional speech. The results of the evaluation experiment showed the feasibility of vocal emotion conversion on the modulation spectrogram for simulated CIs. The vocal emotion enhancement on the modulation spectrogram was also further discussed.
A new method for the high-precision assessment of tumor changes in response to treatment

Motivation: Imaging demonstrates that preclinical and human tumors are heterogeneous, i.e. a single tumor can exhibit multiple regions that behave differently during both development and also in response to treatment. The large variations observed in control group, tumors can obscure detection of significant therapeutic effects due to the ambiguity in attributing causes of change. This can hinder development of effective therapies due to limitations in experimental design rather than due to therapeutic failure. An improved method to model biological variation and heterogeneity in imaging signals is described. Specifically, linear Poisson modeling (LPM) evaluates changes in apparent diffusion co‐efficient between baseline and 72 h after radiotherapy, in two xenograft models of colorectal cancer. The statistical significance of measured changes is compared to those attainable using a conventional t‐test analysis on basic apparent diffusion co‐efficient distribution parameters. Results: When LPMs were applied to treated tumors, the LPMs detected highly significant changes. The analyses were significant for all tumors, equating to a gain in power of 4‐fold (i.e. equivalent to having a sample size 16 times larger), compared with the conventional approach. In contrast, highly significant changes are only detected at a cohort level using t‐tests, restricting their potential use within personalized medicine and increasing the number of animals required during testing. Furthermore, LPM enabled the relative volumes of responding and non‐responding tissue to be estimated for each xenograft model. Leave‐one‐out analysis of the treated xenografts provided quality control and identified potential outliers, raising confidence in LPM data at clinically relevant sample sizes. Availability and implementation: TINA Vision open source software is available from www.tina‐vision.net. Supplementary information: Supplementary data are available at Bioinformatics online.
IN-VIVO IMMUNOMODULATORY POTENTIAL OF STANDARDIZED PUERARIA TUBEROSA EXTRACT AND ITS ISOFLAVONOIDS

Objective: The present study was designed to investigate the immunomodulatory potential of Pueraria tuberosa tuber extract and isoflavones puerarin, daidzein and genistein in rats. Methods: The immunomodulatory potential of standardized P. tuberosa tuber extract (100-200 mg/kg; p.o.) and isoflavones puerarin (25-50 mg/kg; p.o.), daidzein (25-50 mg/kg; p.o.) and genistein (25-50 mg/kg; p.o.) was evaluated in swiss albino rats. Immunomodulatory potential was evaluated against sheep red blood cells (SRBCs) antigenic challenge using the models include total and differential leukocyte cell counts, nitrobluetetrazolium reduction test, haemagglutinin titre assay, neutrophil adhesion test, carbon clearance test and delayed type hypersensitivity reaction. The study was also constituted the active marker based RP-HPLC standardization of PTTE. Results: RP-HPLC analysis revealed those P. tuberosa tubers extract contains (w/w) puerarin (8.31% ± 0.06), daidzein (1.70% ± 0.04) and genistein (1.37% ± 0.02). Oral administration of the P. tuberosa extract, puerarin and daidzein dose dependently increased total leukocyte cell count, monocyte and lymphocyte counts, nitroblue-tetrazolium reduction, haemagglutinin titre and phagocytic index whereas suppressed delayed type hypersensitivity response in their specified concentration range in SRBC immunized rats. The P. tuberosa extract was also enhanced the neutrophil adhesion, while puerarin and daidzein had no effect on the neutrophil adhesion. Genistein dose dependently suppressed all the above parameters. Results suggest that the P. tuberosa extract augmented some innate as well as humoral immune responses against SRBC challenged in rats. Conclusion: P. tuberosa holds a promising therapeutic potential as an immunomodulator and the effects mostly due to the effects of isoflavones puerarin, daidzein and genistein.
Intimate blending of binary polymer systems from their common cyclodextrin inclusion compounds

A procedure for the formation of intimate blends of three binary polymer systems polycarbonate (PC)/poly(methyl methacrylate) (PMMA), PC/poly(vinyl acetate) (PVAc) and PMMA/PVAc is described. PC/PMMA, PC/PVAc, and PMMA/PVAc pairs were included in γ-cyclodextrin (γ-CD) channels and were then simultaneously coalesced from their common γ-CD inclusion compounds (ICs) to obtain intimately mixed blends. The formation of ICs between polymer pairs and γ-CD were confirmed by wide-angle X-ray diffraction (WAXD), fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). It was observed [solution 1H nuclear magnetic resonance (NMR)] that the ratios of polymers in coalesced PC/PMMA and PC/PVAc binary blends are significantly different than the starting ratios, and PC was found to be preferentially included in γ-CD channels when compared with PMMA or PVAc. Physical mixtures of polymer pairs were also prepared by coprecipitation and solution casting methods for comparison. DSC, solid-state 1H NMR, thermogravimetric analysis (TGA), and direct insertion probe pyrolysis mass spectrometry (DIP-MS) data indicated that the PC/PMMA, PC/PVAc, and PMMA/PVAc binary polymer blends were homogeneously mixed when they were coalesced from their ICs. A single, common glass transition temperature (Tg) recorded by DSC heating scans strongly suggested the presence of a homogeneous amorphous phase in the coalesced binary polymer blends, which is retained after thermal cycling to 270 °C. The physical mixture samples showed two distinct Tgs and 1H T1ρ values for the polymer components, which indicated phase-separated blends with domain sizes above 5 nm, while the coalesced blends exhibited uniform 1H spin-lattice relaxation values, indicating intimate blending in the coalesced samples. The TGA results of coalesced and physical binary blends of PC/PMMA and PC/PVAc reveal that in the presence of PC, the thermal stability of both PMMA and PVAc increases. Yet, the presence of PMMA and PVAc decreases the thermal stability of PC itself. DIP-MS observations suggested that the degradation mechanisms of the polymers changed in the coalesced blends, which was attributed to the presence of molecular interactions between the well-mixed polymer components in the coalesced samples. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2578–2593, 2005
Privacy implications of geosocial proximity

Geosocial networks, social networks integrating their users' location, meet an undeniable success. While traditional social networks are already subject to privacy breaches, the addition of location make such breaches to pile up. However, a not obvious question is : does this combination create a new type breaches which were not previously conceivable by the sole use of social networks or location information? We address this matter in two experiments. A first one which takes geosocial network users' profiles and classify them depending on whether their friends live globally close to or far from them. We find that 70 % of users in our Foursquare dataset have their friends living relatively close to them. The second experiment that we led use the check-ins of Gowalla and Brightkite users to discover their social graphs. The check-ins model the users' movements then we assume that users whose modellings are sufficiently similar are friends. This assumption comes from the fact that one often makes new friends in the places that he likes and where he spends a long time. Our partial findings seems to indicate that we are able to discover a half of a user'ssocial graph in average. Thus, we attempt a beginning of answer saying that geosocial networks actually allow new types of attacks against their users' privacy.
PGC1β Organizes the Osteoclast Cytoskeleton by Mitochondrial Biogenesis and Activation

Osteoclasts are mitochondria‐rich cells, but the role of these energy‐producing organelles in bone resorption is poorly defined. To this end, we conditionally deleted the mitochondria‐inducing co‐activator, PGC1β, in myeloid lineage cells to generate PGC1βLysM mice. In contrast to previous reports, PGC1β‐deficient macrophages differentiate normally into osteoclasts albeit with impaired resorptive function due to cytoskeletal disorganization. Consequently, bone mass of PGC1βLysM mice is double that of wild type. Mitochondrial biogenesis and function are diminished in PGC1βLysM osteoclasts. All abnormalities are normalized by PGC1β transduction. Furthermore, OXPHOS inhibitors reproduce the phenotype of PGC1β deletion. PGC1β's organization of the osteoclast cytoskeleton is mediated by expression of GIT1, which also promotes mitochondrial biogenesis. Thus, osteoclast mitochondria regulate the cell's resorptive activity by promoting cytoskeletal organization. © 2018 American Society for Bone and Mineral Research.
Properties of Concrete using Tanjung Bin Power Plant Coal Bottom Ash and Fly Ash

Coal combustion by-products (CCPs) have been around since man understood that burning coal generates electricity, and its utilization in concrete production for nearly a century. The concept of sustainable development only reawaken our consciousness to the huge amount of CCPs around us and the need for proper reutilization than the current method of disposal which has severe consequences both to man and the environment. This paper presents the result of utilization of waste from thermal power plants to improve some engineering properties of concrete. Coal bottom ash (CBA) and fly ash were utilized in partial replacement for fine aggregates and cement respectively. The results of compressive strength at 7, 28, 56 & 90 days curing are presented because of the pozzolanic reaction. Other properties investigated include physical properties, fresh concrete properties and density. The results showed that for a grade 35 concrete with a combination of CBA and fly ash can produce 28 day strength above 30 MPa.
Ten years of biosimilars in Europe: development and evolution of the regulatory pathways

A biosimilar is defined by the European Medicines Agency as a biological medicine that is similar to another biological medicine that has already been authorized for use. A science-based regulatory framework to ensure high-quality biosimilars has been established in Europe since 2005 and is monitored and updated on an ongoing basis. The guiding principle of a biosimilar development program is to establish similarity between the biosimilar and the reference medicine by the best possible means, ensuring that the previously proven safety and efficacy of the reference medicinal product also applies to the biosimilar. Development of a biosimilar is underpinned by state-of-the-art analytical techniques to characterize both reference medicines and biosimilars. The extent and nature of the nonclinical in vivo studies and clinical studies to be performed depend on the level of evidence obtained in the previous step(s), including the robustness of the physicochemical, biological, and nonclinical in vitro data. Extrapolation is an important element of the biosimilarity concept. When biosimilar comparability has been demonstrated in one indication, extrapolation of the data package to other indications of the reference medicine could be acceptable, but needs to be scientifically justified and considered in light of the demonstrated level of sameness by all analytical, nonclinical, and clinical data. The credibility of the scientific basis behind the biosimilar concept, and quality of regulatory decision-making, is demonstrated by the successful approval and clinical use of 20 biosimilar medicines since 2006 when Omnitrope® was the first biosimilar to be approved. The regulatory environment for biosimilars continues to evolve, both in recognition of advances in technology/analytical methods and the availability of new targets for biosimilar development.
Experiments on a grid layer prototype for shared data programming model

In the grid context, there is little support for programming paradigms such as shared data or associative programming. We have previously proposed an original idea to attack shared data programming on the grid by making use of both relaxed consistency models and user specified type consistency in an object oriented model. In this paper we present the experimental results of GUN, a lightweight Java prototype implementation of our shared data programming model. In order to assess GUN's performance, some generic experiments are designed. First, GUN's correctness has been proved in a real grid deployment where a limited number of nodes were available. In order to observe GUN's scalability with an increasing number of nodes, experiments have been conducted in a simulated large scale grid environment. The conducted experiments have shown a good scalability of GUN, as well as promising results in terms of response times and usability.
Barriers to Appropriate Technology Growth in Sustainable Development

Given the urgency of development problems world-wide, as well as the opportunities of open source appropriate technology (OSAT) to help expedite sustainable development goals, a better understanding of the barriers limiting the scaling of OSAT is needed. In this study, key organizations and researchers working in the field of appropriate technology (AT) were interviewed to identify barriers to OSAT. The data was analyzed via pattern coding and content analysis. Results reveal that among the most pressing problems for those working in the field of AT were the need for better communication and collaboration between the agencies and communities to share the knowledge and resources, and to work in partnership. Specific barriers include: i) AT seen as inferior or “poor person's” technology, ii) technical transferability and robustness of AT, iii) insufficient funding, iv) weak institutional support, and v) the challenges of distance and time in tackling rural poverty. Finally, future work is outlined to better understand and overcome these barriers.
Effect of Traditional Treatment of Diabetes Mellitus with Xanthosoma sagittifolium on the Male Reproductive System of Alloxan-Induced Diabetic Wistar Rats

Abstract Introduction The management of diabetes mellitus (DM) targets glycemic control as well as prevention or reversal of other complications associated with the metabolic disorder. One of such complications is the infertility which has been traced to oxidative stress and DNA damage caused by DM. Subjects and methods In this study, experimentally-induced diabetic male Wistar rats were fed with Xanthosoma sagittifolium (cocoyam) for 14 days and its effect on sperm morphology and characteristics, as well as histology of the testes were assessed. X. sagittifolium corm feed (Xs) were reconstituted with commercial rat feed to contain 25, 50, 75 or 100% X. sagittifolium on a weight/weight basis. Result One primary and 7 secondary cell abnormalities were observed with overall increased total abnormal sperm cells in the diabetic rats. Sperm cell motility was significantly (p<0.05) reduced in all diabetic rats, but diabetic rats fed with Xs showed increased motility and liveability. Sperm volume was unchanged, but the depressed sperm count in the untreated diabetic rats was increased in Xs-fed rats. Histology of Xs-fed diabetic rats showed reduction in seminiferous tubule diameter and luminal diameter which was significantly enlarged in untreated diabetic rats. Conclusion X. sagittifolium significantly (p<0.05) prevented further deterioration of sperm cell quality and reversed cell apoptosis as presented by increased sperm motility, liveability and count. In the overall, the chances of fertilization by sperm cells from diabetic patients will be increased as well as achievement of good glycemic control and prevention of further damage by the disease condition.