Tuberculosis Contact Screening and Isoniazid Preventive Therapy in a South Indian District: Operational Issues for Programmatic Consideration

BACKGROUND: Under India's Revised National Tuberculosis Control Programme (RNTCP), all household contacts of sputum smear positive Pulmonary Tuberculosis (PTB) patients are screened for TB. In the absence of active TB disease, household contacts aged <6 years are eligible for Isoniazid Preventive Therapy (IPT) (5 milligrams/kilogram body weight/day) for 6 months. OBJECTIVES: To estimate the number of household contacts aged <6 years, of sputum smear positive PTB patients registered for treatment under RNTCP from April to June'2008 in Krishna District, to assess the extent to which they are screened for TB disease and in its absence initiated on IPT. METHODS: A cross sectional study was conducted. Households of all smear positive PTB cases (n = 848) registered for treatment from April to June'2008 were included. Data on the number of household contacts aged <6 years, the extent to which they were screened for TB disease, and the status of initiation of IPT, was collected. RESULTS: Households of 825 (97%) patients were visited, and 172 household contacts aged <6 years were identified. Of them, 116 (67%) were evaluated for TB disease; none were found to be TB diseased and 97 (84%) contacts were initiated on IPT and 19 (16%) contacts were not initiated on IPT due to shortage of INH tablets in peripheral health centers. The reasons for non-evaluation of the remaining eligible children (n = 56, 33%) include no home visit by the health staff in 25 contacts, home visit done but not evaluated in 31 contacts. House-hold contacts in rural areas were less likely to be evaluated and initiated on IPT [risk ratio 6.65 (95% CI; 3.06-14.42)]. CONCLUSION: Contact screening and IPT implementation under routine programmatic conditions is sub-optimal. There is an urgent need to sensitize all concerned programme staff on its importance and establishment of mechanisms for rigorous monitoring

Annotation of protein residues based on a literature analysis: cross-validation against UniProtKb

<p>Abstract</p> <p>Background</p> <p>A protein annotation database, such as the Universal Protein Resource knowledge base (UniProtKb), is a valuable resource for the validation and interpretation of predicted 3D structure patterns in proteins. Existing studies have focussed on point mutation extraction methods from biomedical literature which can be used to support the time consuming work of manual database curation. However, these methods were limited to point mutation extraction and do not extract features for the annotation of proteins at the residue level.</p> <p>Results</p> <p>This work introduces a system that identifies protein residues in MEDLINE abstracts and annotates them with features extracted from the context written in the surrounding text. MEDLINE abstract texts have been processed to identify protein mentions in combination with taxonomic species and protein residues (F1-measure 0.52). The identified protein-species-residue triplets have been validated and benchmarked against reference data resources (UniProtKb, average F1-measure of 0.54). Then, contextual features were extracted through shallow and deep parsing and the features have been classified into predefined categories (F1-measure ranges from 0.15 to 0.67). Furthermore, the feature sets have been aligned with annotation types in UniProtKb to assess the relevance of the annotations for ongoing curation projects. Altogether, the annotations have been assessed automatically and manually against reference data resources.</p> <p>Conclusion</p> <p>This work proposes a solution for the automatic extraction of functional annotation for protein residues from biomedical articles. The presented approach is an extension to other existing systems in that a wider range of residue entities are considered and that features of residues are extracted as annotations.</p

Optoelectronic characterization of CuInGa(S)2 thin films grown by spray pyrolysis for photovoltaic application

[EN] Copper-indium gallium disulfide (CIGS) is a good absorber for photovoltaic application. Thin films of CIGS were prepared by spray pyrolysis on glass substrates in the ambient atmosphere. The films were characterized by different techniques, such as structural, morphological, optical and electrical properties of CIGS films were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), spectrophotometer and Hall effect, respectively. After optimization, the deposited films structure, grain size, and crystallinity became more important with an increase of annealing time at 370 degrees C for 20 min. Transmission electron microscopy (TEM) analysis shows that the interface sheets are well crystallized and the inter planer distance are 0.25 nm, 0.28 nm, and 0.36 nm. The atomic force microscopy (AFM) observation shows that the grain size and roughness can be tolerated by optimizing the annealing time. The strong absorbance and low transmittance were observed for the prepared films with a suitable energy bandgap about 1.46 eV. The Hall effect measurement system examined that CIGS films exhibited optimal electrical properties, resistivity, carrier mobility, and carrier concentration which were determined to be 4.22 x 10(6) omega cm, 6.18 x 10(2) cm(2) V-1 S-1 and 4.22 x 10(6) cm(-3), respectively. The optoelectronic properties of CIGS material recommended being used for the photovoltaic application.Prof. Bouchaib HARTITI, The Senior Associate at ICTP, is very grateful to ICTP for permanent support. Prof. Mohamed Ebn Touhami, Director of the University Center for Analysis, Expertise, Transfer of Technology and Incubation, Kenitra, Morocco, is very grateful to CUA2TI for financial support. Thanks to Doctor Diogo M.F. Santos for the supervision of Amal Bouich's work during her research in CeFEMA research center. The authors also thank researchers from CeFEMA (IST-ULisboa, Portugal) and CUA2TI (FS-Kenitra Morocco) for their help.Bouich, A.; Hartiti, B.; Ullah, S.; Ullah, H.; Ebn Touhami, M.; Santos, DMF.; Marí, B. (2019). Optoelectronic characterization of CuInGa(S)2 thin films grown by spray pyrolysis for photovoltaic application. Applied Physics A. 125(8):1-9. https://doi.org/10.1007/s00339-019-2874-4S191258T. Feurer, P. Reinhard, E. Avancini, B. Bissig, J. Löckinger, P. Fuchs, S. Buecheler, Progress in thin film CIGS photovoltaics–Research and development, manufacturing, and applications. Prog. Photovolt. Res. Appl. 25(7), 645–667 (2017)A. Zegadi, M.A. Slifkin, M. Djamin, A.E. Hill, R.D. Tomlinson, A photoacoustic study of CuInxGa1− xSe2 alloys. Phys. Status Solidi (A) 133(2), 533–540 (1992)T.H. Sajeesh, A.R. Warrier, C.S. Kartha, K.P. Vijayakumar, Optimization of parameters of chemical spray pyrolysis technique to get n and p-type layers of SnS. Thin Solid Films 518(15), 4370–4374 (2010)J. Liu, D. Zhuang, H. Luan, M. Cao, M. Xie, X. Li, Preparation of Cu (In, Ga) Se2 thin film by sputtering from Cu (In, Ga) Se2 quaternary target. Progr. Nat. Sci. Mater. Int. 23(2), 133–138 (2013)M.I. Hossain, Fabrication and characterization of CIGS solar cells with In2 S3 buffer layer deposited by PVD technique. Chalcogenide Lett. 9(5), 185–191 (2012)M.A. Mughal, R. Engelken, R. Sharma, Progress in indium (III) sulfide (In2S3) buffer layer deposition techniques for CIS, CIGS, and CdTe-based thin film solar cells. Sol. Energy 120, 131–146 (2015)M. Powalla, M. Cemernjak, J. Eberhardt, F. Kessler, R. Kniese, H.D. Mohring, B. Dimmler, Large-area CIGS modules: Pilot line production and new developments. Sol. Energy Mater Sol. Cells 90(18–19), 3158–3164 (2006)M.E. Calixto, P.J. Sebastian, R.N. Bhattacharya, R. Noufi, Compositional and optoelectronic properties of CIS and CIGS thin films formed by electrodeposition. Sol. Energy Mater. Sol. Cells 59(1–2), 75–84 (1999)S. Jung, S. Ahn, J.H. Yun, J. Gwak, D. Kim, K. Yoon, Effects of Ga contents on properties of CIGS thin films and solar cells fabricated by co-evaporation technique. Curr. Appl. Phys. 10(4), 990–996 (2010)S. R. Ovshinsky, X. Deng, R. Young, U.S. Patent No. 5,231,047. Washington, DC: U.S. Patent and Trademark Office (1993).M. Kaelin, D. Rudmann, A.N. Tiwari, Low cost processing of CIGS thin film solar cells. Sol. Energy 77(6), 749–756 (2004)Fangdan Jiang, Jiayou Feng, Effect of temperature on selenization process of metallic Cu–In alloy precursors. Thin Solid Films 515(4), 1950–1955 (2006)S. Shirakata, Y. Kannaka, H. Hasegawa, T. Kariya, S. Isomura, Properties of Cu (In, Ga) Se2 thin films prepared by chemical spray pyrolysis. Jpn. J. Appl. Phys. 38(9R), 4997 (1999)Y.K. Kumar, G.S. Babu, P.U. Bhaskar, V.S. Raja, Effect of starting-solution pH on the growth of Cu2ZnSnS4 thin films deposited by spray pyrolysis. Phys. Status Solidi (A) 206(7), 1525–1530 (2009)M. Ajili, M. Castagné, N.K. Turki, Characteristics of CuIn1− xGaxS2 thin films synthesized by chemical spray pyrolysis. J. Lumin. 150, 1–7 (2014)B.J. Babu, S. Velumani, A. Kassiba, R. Asomoza, J.A. Chavez-Carvayar, J. Yi, Deposition and characterization of graded Cu (In1-xGax) Se2 thin films by spray pyrolysis. Mater. Chem. Phys. 162, 59–68 (2015)S.F. Varol, G. Babür, G. Çankaya, U. Kölemen, Synthesis of sol–gel derived nano-crystalline ZnO thin films as TCO window layer: effect of sol aging and boron. RSC Adv. 4(100), 56645–56653 (2014)J.A. Frantz, R.Y. Bekele, V.Q. Nguyen, J.S. Sanghera, A. Bruce, S.V. Frolov, I.D. Aggarwal, Cu (In, Ga) Se2 thin films and devices sputtered from a single target without additional selenization. Thin Solid Films 519(22), 7763–7765 (2011)C. Calderón, G. Gordillo, P. Bartolo-Pérez, F. Mesa, Effect of the deposition conditions on the optical, morphological and compositional properties of CuIn1− xGaxSe2 thin films prepared by a multistage process. Revista Mexicana de Física 53(7), 270–273 (2007)D. Schmid, M. Ruckh, F. Grunwald, H.W. Schock, Chalcopyrite/defect chalcopyrite heterojunctions on the basis of CuInSe2. J. Appl. Phys. 73(6), 2902–2909 (1993)U.C. Matur, S. Akyol, N. Baydoğan, H. Cimenoglu, The optical properties of CIGS thin films derived by sol-gel dip coating process at different withdrawal speed. Proc. Soc. Behav. Sci. 195, 1762–1767 (2015)A. Bouich, B. Hartiti, S. Ullah, M.E. Touhami, B. Mari, D.M.F. Santos, Investigation of the optical properties of CuIn (Se, S)2 thin films for photovoltaic application. Mater. Today Proc. 13, 663–669 (2019)K. Matsumura, T. Fujita, H. Itoh, D. Fujita, Characterization of carrier concentration in CIGS solar cells by scanning capacitance microscopy. Meas. Sci. Technol. 25(4), 044020 (2014)A. Bouich, B. Hartiti, S. Ullah, H. Ullah, M.E. Touhami, D.M.F. Santos, B. Mari, Experimental, theoretical, and numerical simulation of the performance of CuInxGa(1–x) S2 based solar cells. Optik 183, 137–147 (2019

Optimum design of reinforced concrete retaining walls with the flower pollination algorithm

The flower pollination algorithm (FPA) is anefficient metaheuristicoptimizationalgorithm mimickingthe pollinationprocessof flowering species. In this study, FPA is applied, for first time, to the optimum design of reinforced concrete (RC) cantilever retaining walls. It is foundthat FPA offers important savings with respect to conventional design approachesand that it outperformsgenetic algorithm (GA)andthe particle swarm optimization (PSO) algorithm in this designproblem.Furthermore, parameter tuning reveals that the best FPA performance is achieved for switch probability values ranging between 0.4 and 0.7, a population size of 20 individualsand aLévy flightstep sizescale factor of 0.5. Finally, parametric optimum designs show that theoptimumcost of RC retaining walls increases rapidly with the wallheight and smoothly with the magnitude of surcharge loadin

Bub3 Is a Spindle Assembly Checkpoint Protein Regulating Chromosome Segregation during Mouse Oocyte Meiosis

In mitosis, the spindle assembly checkpoint (SAC) prevents anaphase onset until all chromosomes have been attached to the spindle microtubules and aligned correctly at the equatorial metaphase plate. The major checkpoint proteins in mitosis consist of mitotic arrest-deficient (Mad)1–3, budding uninhibited by benzimidazole (Bub)1, Bub3, and monopolar spindle 1(Mps1). During meiosis, for the formation of a haploid gamete, two consecutive rounds of chromosome segregation occur with only one round of DNA replication. To pull homologous chromosomes to opposite spindle poles during meiosis I, both sister kinetochores of a homologue must face toward the same pole which is very different from mitosis and meiosis II. As a core member of checkpoint proteins, the individual role of Bub3 in mammalian oocyte meiosis is unclear. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of Bub3 in mouse oocyte meiosis. Our data showed that overexpressed Bub3 inhibited meiotic metaphase-anaphase transition by preventing homologous chromosome and sister chromatid segregations in meiosis I and II, respectively. Misaligned chromosomes, abnormal polar body and double polar bodies were observed in Bub3 knock-down oocytes, causing aneuploidy. Furthermore, through cold treatment combined with Bub3 overexpression, we found that overexpressed Bub3 affected the attachments of microtubules and kinetochores during metaphase-anaphase transition. We propose that as a member of SAC, Bub3 is required for regulation of both meiosis I and II, and is potentially involved in kinetochore-microtubule attachment in mammalian oocytes

Genomic prediction in CIMMYT maize and wheat breeding programs

Genomic selection (GS) has been implemented in animal and plant species, and is regarded as a useful tool for accelerating genetic gains. Varying levels of genomic prediction accuracy have been obtained in plants, depending on the prediction problem assessed and on several other factors, such as trait heritability, the relationship between the individuals to be predicted and those used to train the models for prediction, number of markers, sample size and genotype × environment interaction (GE). The main objective of this article is to describe the results of genomic prediction in International Maize and Wheat Improvement Center's (CIMMYT's) maize and wheat breeding programs, from the initial assessment of the predictive ability of different models using pedigree and marker information to the present, when methods for implementing GS in practical global maize and wheat breeding programs are being studied and investigated. Results show that pedigree (population structure) accounts for a sizeable proportion of the prediction accuracy when a global population is the prediction problem to be assessed. However, when the prediction uses unrelated populations to train the prediction equations, prediction accuracy becomes negligible. When genomic prediction includes modeling GE, an increase in prediction accuracy can be achieved by borrowing information from correlated environments. Several questions on how to incorporate GS into CIMMYT's maize and wheat programs remain unanswered and subject to further investigation, for example, prediction within and between related bi-parental crosses. Further research on the quantification of breeding value components for GS in plant breeding populations is required.J Crossa, P Pérez, J Hickey, J Burgueño, L Ornella, J Cerón-Rojas, X Zhang, S Dreisigacker, R Babu, Y Li, D Bonnett and K Mathew

The cardiac troponin C mutation Leu29Gln found in a patient with hypertrophic cardiomyopathy does not alter contractile parameters in skinned murine myocardium

The present study investigates the effects of the first mutation of troponin C (hcTnCL29Q) found in a patient with hypertrophic cardiomyopathy (HCM) on force–pCa relations and the interplay with phosphorylation of sarcomeric PKA substrates. In triton-skinned murine cardiac fibers, the endogenous mcTnC was extracted and the fibers were subsequently reconstituted with recombinant wild-type and mutant hcTnC. Force–pCa relations of preparations containing hcTnCL29Q or hcTnCWT were similar. Incubation of fibers reconstituted with the recombinant proteins with phosphatase to dephosphorylate sarcomeric PKA substrates induced an increase in Ca2+ sensitivity, slightly more pronounced (0.04 pCa units) in hcTnCL29Q-containing fibers. Incubation of the dephosphorylated fibers with PKA induced significant rightward shifts of force–pCa relations of similar magnitude with both, hcTnCL29Q and hcTnCWT. No significant effects of hcTnCL29Q on the velocity of unloaded shortening were observed. In conclusion, no major differences in contractile parameters of preparations containing hcTnCL29Q compared to hcTnCWT were observed. Therefore, it appears unlikely that hcTnCL29Q induces the development of HCM by affecting the regulation of Ca2+-activated force and interference with PKA-mediated modulation of the Ca2+ sensitivity of contraction

Built Shallow to Maintain Homeostasis and Persistent Infection: Insight into the Transcriptional Regulatory Network of the Gastric Human Pathogen Helicobacter pylori

Transcriptional regulatory networks (TRNs) transduce environmental signals into coordinated output expression of the genome. Accordingly, they are central for the adaptation of bacteria to their living environments and in host–pathogen interactions. Few attempts have been made to describe a TRN for a human pathogen, because even in model organisms, such as Escherichia coli, the analysis is hindered by the large number of transcription factors involved. In light of the paucity of regulators, the gastric human pathogen Helicobacter pylori represents a very appealing system for understanding how bacterial TRNs are wired up to support infection in the host. Herein, we review and analyze the available molecular and “-omic” data in a coherent ensemble, including protein–DNA and protein–protein interactions relevant for transcriptional control of pathogenic responses. The analysis covers ∼80% of the annotated H. pylori regulators, and provides to our knowledge the first in-depth description of a TRN for an important pathogen. The emerging picture indicates a shallow TRN, made of four main modules (origons) that process the physiological responses needed to colonize the gastric niche. Specific network motifs confer distinct transcriptional response dynamics to the TRN, while long regulatory cascades are absent. Rather than having a plethora of specialized regulators, the TRN of H. pylori appears to transduce separate environmental inputs by using different combinations of a small set of regulators

A systematic, large-scale comparison of transcription factor binding site models

Background The modelling of gene regulation is a major challenge in biomedical research. This process is dominated by transcription factors (TFs) and mutations in their binding sites (TFBSs) may cause the misregulation of genes, eventually leading to disease. The consequences of DNA variants on TF binding are modelled in silico using binding matrices, but it remains unclear whether these are capable of accurately representing in vivo binding. In this study, we present a systematic comparison of binding models for 82 human TFs from three freely available sources: JASPAR matrices, HT-SELEX-generated models and matrices derived from protein binding microarrays (PBMs). We determined their ability to detect experimentally verified “real” in vivo TFBSs derived from ENCODE ChIP-seq data. As negative controls we chose random downstream exonic sequences, which are unlikely to harbour TFBS. All models were assessed by receiver operating characteristics (ROC) analysis. Results While the area- under-curve was low for most of the tested models with only 47 % reaching a score of 0.7 or higher, we noticed strong differences between the various position-specific scoring matrices with JASPAR and HT-SELEX models showing higher success rates than PBM-derived models. In addition, we found that while TFBS sequences showed a higher degree of conservation than randomly chosen sequences, there was a high variability between individual TFBSs. Conclusions Our results show that only few of the matrix-based models used to predict potential TFBS are able to reliably detect experimentally confirmed TFBS. We compiled our findings in a freely accessible web application called ePOSSUM (http:/mutationtaster.charite.de/ePOSSUM/) which uses a Bayes classifier to assess the impact of genetic alterations on TF binding in user-defined sequences. Additionally, ePOSSUM provides information on the reliability of the prediction using our test set of experimentally confirmed binding sites