E-MSD: an integrated data resource for bioinformatics.

PubMed

Golovin, A; Oldfield, T J; Tate, J G; Velankar, S; Barton, G J; Boutselakis, H; Dimitropoulos, D; Fillon, J; Hussain, A; Ionides, J M C; John, M; Keller, P A; Krissinel, E; McNeil, P; Naim, A; Newman, R; Pajon, A; Pineda, J; Rachedi, A; Copeland, J; Sitnov, A; Sobhany, S; Suarez-Uruena, A; Swaminathan, G J; Tagari, M; Tromm, S; Vranken, W; Henrick, K

2004-01-01

The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the Protein Data Bank (PDB) and to work towards the integration of various bioinformatics data resources. We have implemented a simple form-based interface that allows users to query the MSD directly. The MSD 'atlas pages' show all of the information in the MSD for a particular PDB entry. The group has designed new search interfaces aimed at specific areas of interest, such as the environment of ligands and the secondary structures of proteins. We have also implemented a novel search interface that begins to integrate separate MSD search services in a single graphical tool. We have worked closely with collaborators to build a new visualization tool that can present both structure and sequence data in a unified interface, and this data viewer is now used throughout the MSD services for the visualization and presentation of search results. Examples showcasing the functionality and power of these tools are available from tutorial webpages (http://www. ebi.ac.uk/msd-srv/docs/roadshow_tutorial/).

E-MSD: an integrated data resource for bioinformatics

PubMed Central

Golovin, A.; Oldfield, T. J.; Tate, J. G.; Velankar, S.; Barton, G. J.; Boutselakis, H.; Dimitropoulos, D.; Fillon, J.; Hussain, A.; Ionides, J. M. C.; John, M.; Keller, P. A.; Krissinel, E.; McNeil, P.; Naim, A.; Newman, R.; Pajon, A.; Pineda, J.; Rachedi, A.; Copeland, J.; Sitnov, A.; Sobhany, S.; Suarez-Uruena, A.; Swaminathan, G. J.; Tagari, M.; Tromm, S.; Vranken, W.; Henrick, K.

2004-01-01

The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the Protein Data Bank (PDB) and to work towards the integration of various bioinformatics data resources. We have implemented a simple form-based interface that allows users to query the MSD directly. The MSD ‘atlas pages’ show all of the information in the MSD for a particular PDB entry. The group has designed new search interfaces aimed at specific areas of interest, such as the environment of ligands and the secondary structures of proteins. We have also implemented a novel search interface that begins to integrate separate MSD search services in a single graphical tool. We have worked closely with collaborators to build a new visualization tool that can present both structure and sequence data in a unified interface, and this data viewer is now used throughout the MSD services for the visualization and presentation of search results. Examples showcasing the functionality and power of these tools are available from tutorial webpages (http://www.ebi.ac.uk/msd-srv/docs/roadshow_tutorial/). PMID:14681397

Effects of Mentoring Speed Dating as an Innovative Matching Tool in Undergraduate Medical Education: A Mixed Methods Study.

PubMed

Guse, Jennifer; Schweigert, Eva; Kulms, Gerhild; Heinen, Ines; Martens, Claudia; Guse, Andreas H

2016-01-01

Choosing the right mentor is crucial for effective mentorship. Yet, many medical students have difficulties finding a suitable mentor. Thus we developed mentoring speed dating (MSD) as a promising matching tool to connect students and faculty mentors successfully. The purpose of this study was to explore mentees' and mentors' experience with MSD and investigate the impact of MSD on the perceived mentorship quality and continuance of the mentoring relationship. The authors completed a mixed methods study at the University Medical Center Hamburg-Eppendorf, Germany, between June 2011 and March 2014. They conducted four focus groups with mentees and mentors who participated in a mentoring speed dating event and analyzed transcripts using conventional content analysis with inductive categorizing. In addition, three mentoring cohorts (two matched via MSD, one matched via conventional online profiles) were surveyed on mentorship satisfaction and the 1-year continuance of their mentorship was monitored. Fifteen mentees and fifteen mentors participated in the focus groups. The authors identified several themes such as short and long term benefits of MSD and fulfillment of expectations. Benefits included finding out about the personal connection, matching expectations, providing an efficient overview of candidates. The survey was completed by 93 students (n = 29 without MSD; n = 64 with MSD). Independent t-tests and multivariate analysis of variance were used to analyze the impact of MSD on student's mentorship satisfaction. There were significant differences in responses to the items "Commitment of mentor" (p = .019) and "Constructive feedback" (p = .038) among the students who attended MSD and the students without MSD. After one year far more mentoring relationships existed among those mentees who participated in MSD in comparison to the "no MSD group". MSD is a valuable matching tool with beneficial effects on the mentorship quality. It enhances essential factors in the mentoring relationship such as commitment and satisfaction.

Effects of Mentoring Speed Dating as an Innovative Matching Tool in Undergraduate Medical Education: A Mixed Methods Study

PubMed Central

Guse, Jennifer; Schweigert, Eva; Kulms, Gerhild; Heinen, Ines; Martens, Claudia; Guse, Andreas H.

2016-01-01

Objectives Choosing the right mentor is crucial for effective mentorship. Yet, many medical students have difficulties finding a suitable mentor. Thus we developed mentoring speed dating (MSD) as a promising matching tool to connect students and faculty mentors successfully. The purpose of this study was to explore mentees’ and mentors’ experience with MSD and investigate the impact of MSD on the perceived mentorship quality and continuance of the mentoring relationship. Methods The authors completed a mixed methods study at the University Medical Center Hamburg-Eppendorf, Germany, between June 2011 and March 2014. They conducted four focus groups with mentees and mentors who participated in a mentoring speed dating event and analyzed transcripts using conventional content analysis with inductive categorizing. In addition, three mentoring cohorts (two matched via MSD, one matched via conventional online profiles) were surveyed on mentorship satisfaction and the 1-year continuance of their mentorship was monitored. Fifteen mentees and fifteen mentors participated in the focus groups. The authors identified several themes such as short and long term benefits of MSD and fulfillment of expectations. Benefits included finding out about the personal connection, matching expectations, providing an efficient overview of candidates. The survey was completed by 93 students (n = 29 without MSD; n = 64 with MSD). Independent t-tests and multivariate analysis of variance were used to analyze the impact of MSD on student’s mentorship satisfaction. Results There were significant differences in responses to the items “Commitment of mentor” (p = .019) and “Constructive feedback” (p = .038) among the students who attended MSD and the students without MSD. After one year far more mentoring relationships existed among those mentees who participated in MSD in comparison to the “no MSD group”. Conclusion MSD is a valuable matching tool with beneficial effects on the mentorship quality. It enhances essential factors in the mentoring relationship such as commitment and satisfaction. PMID:26859845

Front view of the Orbiter Discovery from an elevated platform ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Front view of the Orbiter Discovery from an elevated platform in the Vehicle Assembly Building at NASA's Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Association of TNF-α polymorphism rs1800629 with multisomatoform disorder in a group of German patients and healthy controls: an explorative study.

PubMed

Harms, Katharina C; Kapitza, Karl P; Pahl, Lisa; Tran, Anh-Thu; Volkmann, Lilly; Buers, Dennis; Karst, Matthias; Stuhrmann, Manfred; Bernateck, Michael

2013-02-01

The etiology of multisomatoform disorder (MSD) is still largely unknown, but genetic factors seem to have an influence on pathogenesis. Pain is a major symptom of MSD and polymorphisms of different proinflammatory cytokines have been found associated with pain in former studies. Therefore, we presumed that cytokine polymorphisms could also be associated with MSD. Groups of 148 MSD patients with pain as the leading clinical symptom and 149 age and gender matched healthy controls participated in this study. Nine cytokine polymorphisms were genotyped and statistically analyzed for associations with MSD. Allelic and genotypic associations were found for rs16944 (interleukin 1β), rs1800629 (tumor necrosis factor) and rs909253 (lymphotoxin α). After correcting for multiple testing, the association of rs1800629 with MSD remained significant. The rare A-allele was correlated with MSD (p=0.007). Since the common G-allele of rs1800629 (TNFα) occurs much more often in the control group than in the MSD group it is assumed to be protective. Being carrier of the A-allele seems to be a risk factor for MSD. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Withdrawal of an advertising campaign to promote the quadrivalent human papilloma virus vaccine in Spain].

PubMed

Martín-Llaguno, Marta; Alvarez-Dardet, Carlos

2010-01-01

The inclusion of the quadrivalent human papilloma virus (HPV) vaccine in the schedule of the Spanish National Health System sparked the debate over Gardasil, which was presented to the public as a "vaccine against cervical cancer". In this context, Sanofi Pasteur MSD was sued for misleading advertising in the campaign "cuentaselo.org". Although the complaint was not admitted, the lawsuit triggered five changes in the ownership of the web domain which, although backed by scientific societies, was not supported by law. Because of the violation of the Law of the Society of Information Services, and prompted by the suspicion that the pharmaceutical company was behind these changes (as it could not advertise the product), the platform for the moratorium on the HPV vaccine filed a complaint against the Spanish Society of Gynecology and Obstetrics (whose logo appeared on the webpage) for breaching the code of advertising self-regulation. Sanofi Pasteur MSD, the advertiser which was not mentioned, "accepted the complaint and removed the webpage", thus corroborating its involvement. Copyright 2009 SESPAS. Published by Elsevier Espana. All rights reserved.

Underreporting of musculoskeletal disorders in 10 regions in France in 2009.

PubMed

Rivière, Stéphanie; Penven, Emmanuelle; Cadéac-Birman, Hélène; Roquelaure, Yves; Valenty, Madeleine

2014-10-01

Underreporting of occupational diseases (OD) has been quantified, in particular in the United States, but little information is available in other countries. The aim of this study was to evaluate underreporting of musculoskeletal disorders (MSD) in France in 2009. We calculated an indicator that approximated the underreporting rate of MSD in 10 regions of France. Two databases were used: data on OD compensated by insurance funding and data from the surveillance program for uncompensated work-related diseases. Analyses were performed for carpal tunnel syndrome (CTS) and elbow, shoulder, and lumbar spine MSD. The underreporting rate was estimated at 59% (range 52-64%) for CTS, 73% (range 67-79%) for elbow MSD, 69% (range 63-74%) for shoulder MSD, and 63% (range 50-76%) for lumbar spine MSD. This study revealed that MSD are substantially underreported in France, as in the United States, despite the differences in workers' compensation systems. © 2014 Wiley Periodicals, Inc.

E-MSD: an integrated data resource for bioinformatics.

PubMed

Velankar, S; McNeil, P; Mittard-Runte, V; Suarez, A; Barrell, D; Apweiler, R; Henrick, K

2005-01-01

The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the worldwide Protein Data Bank (wwPDB) and to work towards the integration of various bioinformatics data resources. One of the major obstacles to the improved integration of structural databases such as MSD and sequence databases like UniProt is the absence of up to date and well-maintained mapping between corresponding entries. We have worked closely with the UniProt group at the EBI to clean up the taxonomy and sequence cross-reference information in the MSD and UniProt databases. This information is vital for the reliable integration of the sequence family databases such as Pfam and Interpro with the structure-oriented databases of SCOP and CATH. This information has been made available to the eFamily group (http://www.efamily.org.uk/) and now forms the basis of the regular interchange of information between the member databases (MSD, UniProt, Pfam, Interpro, SCOP and CATH). This exchange of annotation information has enriched the structural information in the MSD database with annotation from wider sequence-oriented resources. This work was carried out under the 'Structure Integration with Function, Taxonomy and Sequences (SIFTS)' initiative (http://www.ebi.ac.uk/msd-srv/docs/sifts) in the MSD group.

Does age matter in predicting musculoskeletal disorder risk? An analysis of workplace predictors over 4 years.

PubMed

Oakman, Jodi; Neupane, Subas; Nygård, Clas-Håkan

2016-10-01

Musculoskeletal disorders (MSDs) are a major workplace issue. With increasing pressure to extend working lives, predictors of MSD risk across all age groups require accurate identification to inform risk reduction strategies. In 2005 and 2009, a survey was conducted in a Finnish food processing company (N = 734). Data on workplace physical and psychosocial hazards, work ability, job satisfaction and lifestyle-related variables were collected, and MSD risk was measured through assessment of work-related strain in four body areas. Predictors of MSD risk across three age groups (20-35, 36-49, 50+) were assessed with linear regression analysis. Physical hazards and MSD risk were related differently for each age group. The relationship between psychosocial hazards and MSD risk was less clear. For younger workers, physical hazards were not associated with MSD risk. In contrast, for those aged 36-49, repetitive movements (B = 1.76, p < 0.001) and awkward postures (B = 1.30, p = 0.02) were associated with increased MSD risk. For older workers, environmental hazards were positively associated with MSD risk (B = 0.37, p = 0.04). Predictors of MSD risk changed differently for each age group during 4 years of follow-up. For younger workers, change in environment and repetitive movements, for middle age team support and for older workers change in awkward posture were significant predictors of MSD risk. These results support the need for workplace-specific hazard surveillance data. This will ensure that all contributing factors to MSD risk can be accurately identified and controlled independent of age.

A research framework for the development and implementation of interventions preventing work-related musculoskeletal disorders.

PubMed

van der Beek, Allard J; Dennerlein, Jack T; Huysmans, Maaike A; Mathiassen, Svend Erik; Burdorf, Alex; van Mechelen, Willem; van Dieën, Jaap H; Frings-Dresen, Monique Hw; Holtermann, Andreas; Janwantanakul, Prawit; van der Molen, Henk F; Rempel, David; Straker, Leon; Walker-Bone, Karen; Coenen, Pieter

2017-11-01

Objectives Work-related musculoskeletal disorders (MSD) are highly prevalent and put a large burden on (working) society. Primary prevention of work-related MSD focuses often on physical risk factors (such as manual lifting and awkward postures) but has not been too successful in reducing the MSD burden. This may partly be caused by insufficient knowledge of etiological mechanisms and/or a lack of adequately feasible interventions (theory failure and program failure, respectively), possibly due to limited integration of research disciplines. A research framework could link research disciplines thereby strengthening the development and implementation of preventive interventions. Our objective was to define and describe such a framework for multi-disciplinary research on work-related MSD prevention. Methods We described a framework for MSD prevention research, partly based on frameworks from other research fields (ie, sports injury prevention and public health). Results The framework is composed of a repeated sequence of six steps comprising the assessment of (i) incidence and severity of MSD, (ii) risk factors for MSD, and (iii) underlying mechanisms; and the (iv) development, (v) evaluation, and (vi) implementation of preventive intervention(s). Conclusions In the present framework for optimal work-related MSD prevention, research disciplines are linked. This framework can thereby help to improve theories and strengthen the development and implementation of prevention strategies for work-related MSD.

E-MSD: an integrated data resource for bioinformatics

PubMed Central

Velankar, S.; McNeil, P.; Mittard-Runte, V.; Suarez, A.; Barrell, D.; Apweiler, R.; Henrick, K.

2005-01-01

The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the worldwide Protein Data Bank (wwPDB) and to work towards the integration of various bioinformatics data resources. One of the major obstacles to the improved integration of structural databases such as MSD and sequence databases like UniProt is the absence of up to date and well-maintained mapping between corresponding entries. We have worked closely with the UniProt group at the EBI to clean up the taxonomy and sequence cross-reference information in the MSD and UniProt databases. This information is vital for the reliable integration of the sequence family databases such as Pfam and Interpro with the structure-oriented databases of SCOP and CATH. This information has been made available to the eFamily group (http://www.efamily.org.uk/) and now forms the basis of the regular interchange of information between the member databases (MSD, UniProt, Pfam, Interpro, SCOP and CATH). This exchange of annotation information has enriched the structural information in the MSD database with annotation from wider sequence-oriented resources. This work was carried out under the ‘Structure Integration with Function, Taxonomy and Sequences (SIFTS)’ initiative (http://www.ebi.ac.uk/msd-srv/docs/sifts) in the MSD group. PMID:15608192

Benefits from Funding the MSD Engineering List: A Fiscal Year 1999 Case Study

DTIC Science & Technology

2004-03-01

BENEFITS FROM FUNDING THE MSD ENGINEERING LIST: A FISCAL YEAR 1999 CASE STUDY THESIS...States Government. AFIT/GLM/ENS/04-03 BENEFITS FROM FUNDING THE MSD ENGINEERING LIST: A FISCAL YEAR 1999 CASE STUDY...ENS/04-03 BENEFITS FROM FUNDING THE MSD ENGINEERING LIST: A FISCAL YEAR 1999 CASE STUDY David L. Gehrich, BS Captain, USAF

Musculoskeletal disorders and stress among footwear industry workers.

PubMed

de Almeida, Larissa Brentini; Vieira, Edgar Ramos; Zaia, José Eduardo; de Oliveira Santos, Branca Maria; Lourenço, Américo Riccardi Vaccari; Quemelo, Paulo Roberto Veiga

2017-01-01

Manufacturing footwear requires intense manual labor and high repetitions with low variability in function that may lead to musculoskeletal disorders (MSD) symptoms and psychological stress. To evaluate a potential association between musculoskeletal disorders (MSD) and perceived stress among footwear industry workers. The Nordic General Questionnaire (NGQ) and the Perceived Stress Scale (PSS-10) were completed by 357 footwear industry workers. The association between MSD and perceived stress was evaluated using the Chi-Square test and Odds Ratios along with their 95% Confidence Interval (95% CI) were calculated. The twelve-month prevalence of MSD symptoms among the respondents was 66% (n = 236) and the symptoms were significantly associated with perceived stress (p = 0.002, OR: 10, 95% CI: 1.7 to 60.6). The seven-day prevalence of MSD symptoms was 33% and the symptoms were also significantly associated with perceived stress (p = 0.001, OR: 2.7, 95% CI:0.8 to 9.3). The association between perceived stress and MSD symptoms indicates a strong association between MSD symptoms and perceived stress levels. Considering that these problems are important determinants of worker's health, a combined approach to reduce both stress and MSD symptoms is necessary for prevention and health promotion in the footwear industry.

Msd1/SSX2IP-dependent microtubule anchorage ensures spindle orientation and primary cilia formation

PubMed Central

Hori, Akiko; Ikebe, Chiho; Tada, Masazumi; Toda, Takashi

2014-01-01

Anchoring microtubules to the centrosome is critical for cell geometry and polarity, yet the molecular mechanism remains unknown. Here we show that the conserved human Msd1/SSX2IP is required for microtubule anchoring. hMsd1/SSX2IP is delivered to the centrosome in a centriolar satellite-dependent manner and binds the microtubule-nucleator γ-tubulin complex. hMsd1/SSX2IP depletion leads to disorganised interphase microtubules and misoriented mitotic spindles with reduced length and intensity. Furthermore, hMsd1/SSX2IP is essential for ciliogenesis, and during zebrafish embryogenesis, knockdown of its orthologue results in ciliary defects and disturbs left-right asymmetry. We propose that the Msd1 family comprises conserved microtubule-anchoring proteins. PMID:24397932

17 CFR 249.1100 - Form MSD, application for registration as a municipal securities dealer pursuant to rule 15Ba2-1...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form MSD, application for... of Municipal Securities Dealers § 249.1100 Form MSD, application for registration as a municipal... Exchange Act of 1934 (the “Act”), or to amend such application. Note: Copies of Form MSD have been filed...

Haploidentical and Matched Sibling Donor Hematopoietic Cell Transplantation for Patients with HLA-Homozygous Haplotypes.

PubMed

Kanda, Junya; Ikegame, Kazuhiro; Fuji, Shigeo; Kurokawa, Mineo; Kanamori, Heiwa; Fukuda, Takahiro; Ohashi, Kazuteru; Ishikawa, Jun; Ogawa, Hiroyasu; Inoue, Masami; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

2016-11-01

More than 1% of the Japanese population has HLA-homozygous haplotypes. For patients with such haplotypes, HLA-haploidentical family members who have no HLA mismatch in the graft-versus-host direction are readily available donor candidates for hematopoietic cell transplantation (HCT). In this study, the outcomes of patients with homozygous HLA-A, -B, and -DRB1 antigens who received HCT without T cell depletion from a haploidentical related donor with mismatches in the host-versus-graft direction only (hetero-to-homo, n = 78) or from an HLA-matched sibling donor (MSD) (MSD-homo, n = 153) were compared with those in patients with heterozygous haplotypes who received HCT from an MSD (MSD-hetero, n = 7242). Transplant outcomes in the hetero-to-homo group were similar to those in the MSD-hetero group regarding neutrophil engraftment, grades III to IV acute graft-versus-host disease (aGVHD), nonrelapse mortality (NRM), relapse, and overall survival. On the other hand, the incidences of severe aGVHD and NRM in the MSD-homo group were significantly lower than those in the MSD-hetero group (grades III to IV aGVHD: aHR .50, P = .034; NRM: aHR .48, P = .004). In conclusion, patients with HLA-homozygous haplotypes achieved lower GVHD and NRM rates for MSD transplantation than those with HLA-heterozygous haplotypes. When an MSD or an appropriate alternative donor is not available for patients with HLA-homozygous haplotypes who need immediate transplantation, transplantation from a haploidentical donor without T cell depletion is a viable option, given the comparable transplant outcomes for hetero-to-homo HCT and MSD-hetero HCT. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Mapping Global Potential Risk of Mango Sudden Decline Disease Caused by Ceratocystis fimbriata.

PubMed

Galdino, Tarcísio Visintin da Silva; Kumar, Sunil; Oliveira, Leonardo S S; Alfenas, Acelino C; Neven, Lisa G; Al-Sadi, Abdullah M; Picanço, Marcelo C

2016-01-01

The Mango Sudden Decline (MSD), also referred to as Mango Wilt, is an important disease of mango in Brazil, Oman and Pakistan. This fungus is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Stebbing), by infected plant material, and the infested soils where it is able to survive for long periods. The best way to avoid losses due to MSD is to prevent its establishment in mango production areas. Our objectives in this study were to: (1) predict the global potential distribution of MSD, (2) identify the mango growing areas that are under potential risk of MSD establishment, and (3) identify climatic factors associated with MSD distribution. Occurrence records were collected from Brazil, Oman and Pakistan where the disease is currently known to occur in mango. We used the correlative maximum entropy based model (MaxEnt) algorithm to assess the global potential distribution of MSD. The MaxEnt model predicted suitable areas in countries where the disease does not already occur in mango, but where mango is grown. Among these areas are the largest mango producers in the world including India, China, Thailand, Indonesia, and Mexico. The mean annual temperature, precipitation of coldest quarter, precipitation seasonality, and precipitation of driest month variables contributed most to the potential distribution of MSD disease. The mango bark beetle vector is known to occur beyond the locations where MSD currently exists and where the model predicted suitable areas, thus showing a high likelihood for disease establishment in areas predicted by our model. Our study is the first to map the potential risk of MSD establishment on a global scale. This information can be used in designing strategies to prevent introduction and establishment of MSD disease, and in preparation of efficient pest risk assessments and monitoring programs.

Mapping Global Potential Risk of Mango Sudden Decline Disease Caused by Ceratocystis fimbriata

PubMed Central

Oliveira, Leonardo S. S.; Alfenas, Acelino C.; Neven, Lisa G.; Al-Sadi, Abdullah M.

2016-01-01

The Mango Sudden Decline (MSD), also referred to as Mango Wilt, is an important disease of mango in Brazil, Oman and Pakistan. This fungus is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Stebbing), by infected plant material, and the infested soils where it is able to survive for long periods. The best way to avoid losses due to MSD is to prevent its establishment in mango production areas. Our objectives in this study were to: (1) predict the global potential distribution of MSD, (2) identify the mango growing areas that are under potential risk of MSD establishment, and (3) identify climatic factors associated with MSD distribution. Occurrence records were collected from Brazil, Oman and Pakistan where the disease is currently known to occur in mango. We used the correlative maximum entropy based model (MaxEnt) algorithm to assess the global potential distribution of MSD. The MaxEnt model predicted suitable areas in countries where the disease does not already occur in mango, but where mango is grown. Among these areas are the largest mango producers in the world including India, China, Thailand, Indonesia, and Mexico. The mean annual temperature, precipitation of coldest quarter, precipitation seasonality, and precipitation of driest month variables contributed most to the potential distribution of MSD disease. The mango bark beetle vector is known to occur beyond the locations where MSD currently exists and where the model predicted suitable areas, thus showing a high likelihood for disease establishment in areas predicted by our model. Our study is the first to map the potential risk of MSD establishment on a global scale. This information can be used in designing strategies to prevent introduction and establishment of MSD disease, and in preparation of efficient pest risk assessments and monitoring programs. PMID:27415625

A systematic review of musculoskeletal disorders among school teachers

PubMed Central

2011-01-01

Background Musculoskeletal disorders (MSD) represent one of the most common and most expensive occupational health problems in both developed and developing countries. School teachers represent an occupational group among which there appears to be a high prevalence of MSD. Given that causes of MSD have been described as multi-factorial and prevalence rates vary between body sites and location of study, the objective of this systematic review was to investigate the prevalence and risk factors for MSD among teaching staff. Methods The study involved an extensive search of MEDLINE and EMBASE databases in 2011. All studies which reported on the prevalence and/or risk factors for MSD in the teaching profession were initially selected for inclusion. Reference lists of articles identified in the original search were then examined for additional publications. Of the 80 articles initially located, a final group of 33 met the inclusion criteria and were examined in detail. Results This review suggests that the prevalence of self-reported MSD among school teachers ranges between 39% and 95%. The most prevalent body sites appear to be the back, neck and upper limbs. Nursery school teachers appear to be more likely to report suffering from low back pain. Factors such as gender, age, length of employment and awkward posture have been associated with higher MSD prevalence rates. Conclusion Overall, this study suggests that school teachers are at a high risk of MSD. Further research, preferably longitudinal, is required to more thoroughly investigate the issue of MSD among teachers, with a greater emphasis on the possible wider use of ergonomic principles. This would represent a major step forward in the prevention of MSD among teachers, especially if easy to implement control measures could be recommended. PMID:22087739

Mass spectrometry-based biomarker discovery: toward a global proteome index of individuality.

PubMed

Hawkridge, Adam M; Muddiman, David C

2009-01-01

Biomarker discovery and proteomics have become synonymous with mass spectrometry in recent years. Although this conflation is an injustice to the many essential biomolecular techniques widely used in biomarker-discovery platforms, it underscores the power and potential of contemporary mass spectrometry. Numerous novel and powerful technologies have been developed around mass spectrometry, proteomics, and biomarker discovery over the past 20 years to globally study complex proteomes (e.g., plasma). However, very few large-scale longitudinal studies have been carried out using these platforms to establish the analytical variability relative to true biological variability. The purpose of this review is not to cover exhaustively the applications of mass spectrometry to biomarker discovery, but rather to discuss the analytical methods and strategies that have been developed for mass spectrometry-based biomarker-discovery platforms and to place them in the context of the many challenges and opportunities yet to be addressed.

The symmetric MSD encoder for one-step adder of ternary optical computer

NASA Astrophysics Data System (ADS)

Kai, Song; LiPing, Yan

2016-08-01

The symmetric Modified Signed-Digit (MSD) encoding is important for achieving the one-step MSD adder of Ternary Optical Computer (TOC). The paper described the symmetric MSD encoding algorithm in detail, and developed its truth table which has nine rows and nine columns. According to the truth table, the state table was developed, and the optical-path structure and circuit-implementation scheme of the symmetric MSD encoder (SME) for one-step adder of TOC were proposed. Finally, a series of experiments were designed and performed. The observed results of the experiments showed that the scheme to implement SME was correct, feasible and efficient.

Current DOT research on the effect of multiple site damage on structural integrity

NASA Technical Reports Server (NTRS)

Tong, P.; Arin, Kemal; Jeong, David Y.; Greif, R.; Brewer, John C.; Bobo, Stephan N.; Sampath, Sam N.

1992-01-01

Multiple site damage (MSD) is a type of cracking that may be found in aging airplanes and which may adversely affect their continuing airworthiness. The Volpe National Transportation Systems Center has supported the Federal Aviation Administration Technical Center on structural integrity research for the past two and half years. The work has focused on understanding the behavior of MSD, detection of MSD during airframe inspection, and the avoidance of MSD in future designs. These three elements of the MSD problem are addressed and a summary of the completed work, the current status, and requirements for future research is provided.

Real-Time Discovery Services over Large, Heterogeneous and Complex Healthcare Datasets Using Schema-Less, Column-Oriented Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Begoli, Edmon; Dunning, Ted; Charlie, Frasure

We present a service platform for schema-leess exploration of data and discovery of patient-related statistics from healthcare data sets. The architecture of this platform is motivated by the need for fast, schema-less, and flexible approaches to SQL-based exploration and discovery of information embedded in the common, heterogeneously structured healthcare data sets and supporting components (electronic health records, practice management systems, etc.) The motivating use cases described in the paper are clinical trials candidate discovery, and a treatment effectiveness analysis. Following the use cases, we discuss the key features and software architecture of the platform, the underlying core components (Apache Parquet,more » Drill, the web services server), and the runtime profiles and performance characteristics of the platform. We conclude by showing dramatic speedup with some approaches, and the performance tradeoffs and limitations of others.« less

Berkeley Lab - Materials Sciences Division

Science.gov Websites

MSD Support Human Resources Facilities & Space Planning Procurement and Property Proposals & ; Finance Templates Travel One-Stop Acknowledging MSD Support Human Resources Facilities & Space Operations For information regarding Human Resources, procedures for acknowledging MSD support, division

The role of HIV infection in the etiology and epidemiology of diarrheal disease among children aged 0-59 months in Manhiça district, Rural Mozambique.

PubMed

Acácio, Sozinho; Nhampossa, Tacilta; Quintó, Llorenç; Vubil, Delfino; Sacoor, Charfudin; Kotloff, Karen; Farag, Tamer; Dilruba, Nasrin; Macete, Eusebio; Levine, Myron M; Alonso, Pedro; Mandomando, Inácio; Bassat, Quique

2018-05-28

Diarrhea is an important health problem among HIV-infected patients. This study evaluates the role of HIV on the epidemiology, etiology and severity of diarrheal disease among children. The Global Enteric Multicenter Study enrolled children with moderate-to-severe (MSD) and less severe (LSD) diarrhea between December 2007 and November 2012. One to three controls for MSD cases and one per LSD case were enrolled and matched by age, sex and neighborhood. All children were tested for HIV. Clinical, anthropometric data and stools were collected. A follow-up was performed at 60 days. 214 MSD cases and 418 controls, together with 349 LSD cases and 214 controls were tested. HIV prevalence among MSD cases was 25% (4% for matched controls) and 6% among LSD cases (6% among matched controls). HIV-infected children were more likely to have MSD (OR=5.6, p< 0.0001). Mortality rates were higher among HIV-infected children compared with uninfected (34 vs. 5 per 1000 children-weeks at risk; p=0.0039). Cryptosporidium, Giardia, EAEC (aatA only) were more prevalent among HIV-infected MSD-cases than uninfected ones. HIV is an important risk factor for MSD. The high mortality rate implies that children with MSD should be screened for HIV and managed accordingly. Copyright © 2018. Published by Elsevier Ltd.

Prevalence and Risk Factors Associated with Musculoskeletal Discomfort in Spay and Neuter Veterinarians.

PubMed

White, Sara C

2013-02-04

A cross-sectional study to investigate musculoskeletal discomfort (MSD) surveyed 219 veterinarians who currently or previously perform spays and neuters at least 4 hours per week. Participants were asked about the presence and severity of hand and body MSD during the previous month, whether MSD interfered with work or daily activities, whether they attributed their MSD to their spay/neuter work, and whether MSD had ever necessitated absence from work. The period prevalence of MSD was 99.1%, with 76.7% experiencing hand or wrist pain and 98.2% experiencing body pain. Hand discomfort was most commonly reported in the right thumb and/or thumb base (49.8%) and the right wrist (37.9%). Body discomfort was most commonly reported in the lower back (76.7%), shoulders (72.6%), and neck (71.7%). Increasing career length, increasing weekly hours in surgery and decreasing job satisfaction were the work-related factors with the greatest relative contribution accounting for variation in hand pain severity and total pain. Although 94.4% of respondents felt that posture during surgery is important, only 30.6% had received any instruction in posture and positioning for surgery. Future interventions should aim to optimize surgical efficiency, surgeon work schedules, and working environment. Analysis and intervention studies are required to determine further causes of MSD in these veterinarians and develop interventions to prevent MSD.

Conceptualization of the Sexual Response Models in Men: Are there Differences Between Sexually Functional and Dysfunctional Men?

PubMed

Connaughton, Catherine; McCabe, Marita; Karantzas, Gery

2016-03-01

Research to validate models of sexual response empirically in men with and without sexual dysfunction (MSD), as currently defined, is limited. To explore the extent to which the traditional linear or the Basson circular model best represents male sexual response for men with MSD and sexually functional men. In total, 573 men completed an online questionnaire to assess sexual function and aspects of the models of sexual response. In total, 42.2% of men (242) were sexually functional, and 57.8% (331) had at least one MSD. Models were built and tested using bootstrapping and structural equation modeling. Fit of models for men with and without MSD. The linear model and the initial circular model were a poor fit for men with and without MSD. A modified version of the circular model demonstrated adequate fit for the two groups and showed important interactions between psychological factors and sexual response for men with and without MSD. Male sexual response was not represented by the linear model for men with or without MSD, excluding possible healthy responsive desire. The circular model provided a better fit for the two groups of men but demonstrated that the relations between psychological factors and phases of sexual response were different for men with and without MSD as currently defined. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Pain-related musculoskeletal disorders, psychological comorbidity, and the relationship with physical and mental well-being in Gulf War veterans.

PubMed

Kelsall, Helen Louise; McKenzie, Dean Philip; Forbes, Andrew Benjamin; Roberts, Minainyo Helen; Urquhart, Donna Michelle; Sim, Malcolm Ross

2014-04-01

Occupational activities such as lifting loads, working in constrained spaces, and training increase the risk of pain-related musculoskeletal disorders (MSDs) in military veterans. Few studies have investigated MSD and psychological disorder in veterans, and previous studies had limitations. This cross-sectional study compared pain-related MSD and psychological comorbidity and well-being between 1381 male Australian 1990-1991 Gulf War veterans (veterans) and a military comparison group (n=1377, of whom 39.6% were serving and 32.7% had previously deployed). At a medical assessment, 2000-2002, reported doctor-diagnosed arthritis or rheumatism, back or neck problems, joint problems, and soft tissue disorders were rated by medical practitioners as nonmedical, unlikely, possible, or probable diagnoses. Only probable MSDs were analysed. Psychological disorders in the past 12 months were measured using the Composite International Diagnostic Interview. The Short-Form Health Survey (SF-12) assessed 4-week physical and mental well-being. Almost one-quarter of veterans (24.5%) and the comparison group (22.4%) reported an MSD. Having any or specific MSD was associated with depression and posttraumatic stress disorder (PTSD), but not alcohol disorders. Physical and mental well-being was poorer in those with an MSD compared to those without, in both study groups (eg, veterans with any MSD, difference in SF-12 physical component summary scale medians = -10.49: 95% confidence interval -12.40, -8.57), and in those with MSD and psychological comorbidity compared with MSD alone. Comorbidity of any MSD and psychological disorder was more common in veterans, but MSDs were associated with depression, PTSD, and poorer well-being in both groups. Psychological comorbidity needs consideration in MSD management. Longitudinal studies are needed to assess directionality and causality. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Evaluation of monoclonal antibody-based sandwich direct ELISA (MSD-ELISA) for antigen detection of foot-and-mouth disease virus using clinical samples.

PubMed

Morioka, Kazuki; Fukai, Katsuhiko; Sakamoto, Kenichi; Yoshida, Kazuo; Kanno, Toru

2014-01-01

A monoclonal antibody-based sandwich direct ELISA (MSD-ELISA) method was previously developed for foot-and-mouth disease (FMD) viral antigen detection. Here we evaluated the sensitivity and specificity of two FMD viral antigen detection MSD-ELISAs and compared them with conventional indirect sandwich (IS)-ELISA. The MSD-ELISAs were able to detect the antigen in saliva samples of experimentally-infected pigs for a longer term compared to the IS-ELISA. We also used 178 RT-PCR-positive field samples from cattle and pigs affected by the 2010 type-O FMD outbreak in Japan, and we found that the sensitivities of both MSD-ELISAs were about 7 times higher than that of the IS-ELISA against each sample (P<0.01). In terms of the FMD-positive farm detection rate, the sensitivities of the MSD-ELISAs were about 6 times higher than that of the IS-ELISA against each farm (P<0.01). Although it is necessary to conduct further validation study using the other virus strains, MSD-ELISAs could be appropriate as a method to replace IS-ELISA for FMD antigen detection.

An approach to the optical MSD adder

NASA Astrophysics Data System (ADS)

Takahashi, Hideya; Matsushita, Kenji; Shimizu, Eiji

1990-07-01

The intrinsic parallelism of optical elements for computation is presently taken fuller advantage of than heretofore possible through an optical implementation of the modified signed digit (MSD) number system, which yields carry-free addition and subtraction. In the present optical implementation of the MSD system, optical phase data are used to preclude negative value representation. Attention is given to an MSD adder array for addition operations on two n-digit trinary numbers; the output is composed of n + 1 trinary digits.

Physiotherapy in Primary Care Triage - the effects on utilization of medical services at primary health care clinics by patients and sub-groups of patients with musculoskeletal disorders: a case-control study.

PubMed

Bornhöft, Lena; Larsson, Maria E H; Thorn, Jörgen

2015-01-01

Primary Care Triage is a patient sorting system used in some primary health care clinics (PHCCs) in Sweden where patients with musculoskeletal disorders (MSD) are triaged directly to physiotherapists. The purpose of this study was to investigate whether sorting/triaging patients seeking a PHCC for MSD directly to physiotherapists affects their utilization of medical services at the clinic for the MSD and to determine whether the effects of the triaging system vary for different sub-groups of patients. A retrospective case-control study design was used at two PHCCs. At the intervention clinic, 656 patients with MSD were initially triaged to physiotherapists. At the control clinic, 1673 patients were initially assessed by general practitioners (GPs). The main outcome measures were the number of patients continuing to visit GPs after the initial assessment, the number of patients receiving referrals to specialists/external examinations, doctors' notes for sick-leave or prescriptions for analgesics during one year, all for the original MSD. Significantly fewer patients triaged to physiotherapists required multiple GP visits for the MSD or received MSD-related referrals to specialists/external examinations, sick-leave recommendations or prescriptions during the following year compared to the GP-assessed group. This applies to all sub-groups except for the group with lower extremity disorders, which did not reach significance for either multiple GP visits or sick-leave recommendations. The reduced utilization of medical services by patients with MSD who were triaged to physiotherapists at a PHCC is likely due to altered management of MSD with initial assessment by physiotherapists.

A Perspective on Implementing a Quantitative Systems Pharmacology Platform for Drug Discovery and the Advancement of Personalized Medicine

PubMed Central

Stern, Andrew M.; Schurdak, Mark E.; Bahar, Ivet; Berg, Jeremy M.; Taylor, D. Lansing

2016-01-01

Drug candidates exhibiting well-defined pharmacokinetic and pharmacodynamic profiles that are otherwise safe often fail to demonstrate proof-of-concept in phase II and III trials. Innovation in drug discovery and development has been identified as a critical need for improving the efficiency of drug discovery, especially through collaborations between academia, government agencies, and industry. To address the innovation challenge, we describe a comprehensive, unbiased, integrated, and iterative quantitative systems pharmacology (QSP)–driven drug discovery and development strategy and platform that we have implemented at the University of Pittsburgh Drug Discovery Institute. Intrinsic to QSP is its integrated use of multiscale experimental and computational methods to identify mechanisms of disease progression and to test predicted therapeutic strategies likely to achieve clinical validation for appropriate subpopulations of patients. The QSP platform can address biological heterogeneity and anticipate the evolution of resistance mechanisms, which are major challenges for drug development. The implementation of this platform is dedicated to gaining an understanding of mechanism(s) of disease progression to enable the identification of novel therapeutic strategies as well as repurposing drugs. The QSP platform will help promote the paradigm shift from reactive population-based medicine to proactive personalized medicine by focusing on the patient as the starting and the end point. PMID:26962875

Longitudinal relationship of work hours, mandatory overtime, and on-call to musculoskeletal problems in nurses.

PubMed

Trinkoff, Alison M; Le, Rong; Geiger-Brown, Jeanne; Lipscomb, Jane; Lang, Gary

2006-11-01

Nurses are at very high risk for work-related musculoskeletal injury/disorders (MSD) with low back pain/injury being the most frequently occurring MSD. Nurses are also likely to work extended schedules (long hours, on-call, mandatory overtime, working on days off). The purpose of this study was to examine the relationship of extended work schedules in nurses to MSD. Using a longitudinal, three wave survey of 2,617 registered nurses, Wave 1 work schedule data were related to neck, shoulder, and back (MSD) cases occurring in Waves 2 or 3. Schedule characteristics increasing MSD risk included 13+ hour/days, off-shifts, weekend work, work during time off (while sick, on days off, without breaks), and overtime/on-call. These increases in risk were not explained by psychological demands, but were largely explained by physical demands. Adverse schedules are significantly related to nurse MSD. Healthier schedules, less overtime, and reducing work on days off would minimize risk and recovery time. Copyright (c) 2006 Wiley-Liss, Inc.

Cell and small animal models for phenotypic drug discovery.

PubMed

Szabo, Mihaly; Svensson Akusjärvi, Sara; Saxena, Ankur; Liu, Jianping; Chandrasekar, Gayathri; Kitambi, Satish S

2017-01-01

The phenotype-based drug discovery (PDD) approach is re-emerging as an alternative platform for drug discovery. This review provides an overview of the various model systems and technical advances in imaging and image analyses that strengthen the PDD platform. In PDD screens, compounds of therapeutic value are identified based on the phenotypic perturbations produced irrespective of target(s) or mechanism of action. In this article, examples of phenotypic changes that can be detected and quantified with relative ease in a cell-based setup are discussed. In addition, a higher order of PDD screening setup using small animal models is also explored. As PDD screens integrate physiology and multiple signaling mechanisms during the screening process, the identified hits have higher biomedical applicability. Taken together, this review highlights the advantages gained by adopting a PDD approach in drug discovery. Such a PDD platform can complement target-based systems that are currently in practice to accelerate drug discovery.

Construction of small plasmid vectors for use in genetic improvement of the extremely acidophilic Acidithiobacillus caldus.

PubMed

Meng, Jianzhou; Wang, Huiyan; Liu, Xiangmei; Lin, Jianqun; Pang, Xin; Lin, Jianqiang

2013-10-01

The genetic improvement of biomining bacteria including Acidithiobacillus caldus could facilitate the bioleaching process of sulfur-containing minerals. However, the available vectors for use in A. caldus are very scanty and limited to relatively large broad-host-range IncQ plasmids. In this study, a set of small, mobilizable plasmid vectors (pBBR1MCS-6, pMSD1 and pMSD2) were constructed based on plasmid pBBR1MCS-2, which does not belong to the IncQ, IncW, or IncP groups. The function of the tac promoter on 5.8-kb pMSD2 was determined by inserting a kanamycin-resistant reporter gene. The resulting recombinant pMSD2-Km was successfully transferred by conjugation into A. caldus MTH-04 with transfer frequency of 1.38±0.64×10(-5). The stability and plasmid copy number of pMSD2-Km in A. caldus MTH-04 were 75±2.7% and 5-6 copies per cell, respectively. By inserting an arsABC operon into pMSD2, an arsenic-resistant recombinant pMSD2-As was constructed and transferred into A. caldus MTH-04 by conjugation. The arsenic tolerance of A. caldus MTH-04 containing pMSD2-As was obviously increased up to 45mM of NaAsO2. These vectors could be applied in genetic improvement of A. caldus as well as other bioleaching bacteria. Copyright © 2013 Elsevier GmbH. All rights reserved.

Fast processing of digital imaging and communications in medicine (DICOM) metadata using multiseries DICOM format.

PubMed

Ismail, Mahmoud; Philbin, James

2015-04-01

The digital imaging and communications in medicine (DICOM) information model combines pixel data and its metadata in a single object. There are user scenarios that only need metadata manipulation, such as deidentification and study migration. Most picture archiving and communication system use a database to store and update the metadata rather than updating the raw DICOM files themselves. The multiseries DICOM (MSD) format separates metadata from pixel data and eliminates duplicate attributes. This work promotes storing DICOM studies in MSD format to reduce the metadata processing time. A set of experiments are performed that update the metadata of a set of DICOM studies for deidentification and migration. The studies are stored in both the traditional single frame DICOM (SFD) format and the MSD format. The results show that it is faster to update studies' metadata in MSD format than in SFD format because the bulk data is separated in MSD and is not retrieved from the storage system. In addition, it is space efficient to store the deidentified studies in MSD format as it shares the same bulk data object with the original study. In summary, separation of metadata from pixel data using the MSD format provides fast metadata access and speeds up applications that process only the metadata.

Fast processing of digital imaging and communications in medicine (DICOM) metadata using multiseries DICOM format

PubMed Central

Ismail, Mahmoud; Philbin, James

2015-01-01

Abstract. The digital imaging and communications in medicine (DICOM) information model combines pixel data and its metadata in a single object. There are user scenarios that only need metadata manipulation, such as deidentification and study migration. Most picture archiving and communication system use a database to store and update the metadata rather than updating the raw DICOM files themselves. The multiseries DICOM (MSD) format separates metadata from pixel data and eliminates duplicate attributes. This work promotes storing DICOM studies in MSD format to reduce the metadata processing time. A set of experiments are performed that update the metadata of a set of DICOM studies for deidentification and migration. The studies are stored in both the traditional single frame DICOM (SFD) format and the MSD format. The results show that it is faster to update studies’ metadata in MSD format than in SFD format because the bulk data is separated in MSD and is not retrieved from the storage system. In addition, it is space efficient to store the deidentified studies in MSD format as it shares the same bulk data object with the original study. In summary, separation of metadata from pixel data using the MSD format provides fast metadata access and speeds up applications that process only the metadata. PMID:26158117

The Msd1–Wdr8–Pkl1 complex anchors microtubule minus ends to fission yeast spindle pole bodies

PubMed Central

Yukawa, Masashi; Ikebe, Chiho

2015-01-01

The minus ends of spindle microtubules are anchored to a microtubule-organizing center. The conserved Msd1/SSX2IP proteins are localized to the spindle pole body (SPB) and the centrosome in fission yeast and humans, respectively, and play a critical role in microtubule anchoring. In this paper, we show that fission yeast Msd1 forms a ternary complex with another conserved protein, Wdr8, and the minus end–directed Pkl1/kinesin-14. Individual deletion mutants displayed the identical spindle-protrusion phenotypes. Msd1 and Wdr8 were delivered by Pkl1 to mitotic SPBs, where Pkl1 was tethered through Msd1–Wdr8. The spindle-anchoring defect imposed by msd1/wdr8/pkl1 deletions was suppressed by a mutation of the plus end–directed Cut7/kinesin-5, which was shown to be mutual. Intriguingly, Pkl1 motor activity was not required for its anchoring role once targeted to the SPB. Therefore, spindle anchoring through Msd1–Wdr8–Pkl1 is crucial for balancing the Cut7/kinesin-5–mediated outward force at the SPB. Our analysis provides mechanistic insight into the spatiotemporal regulation of two opposing kinesins to ensure mitotic spindle bipolarity. PMID:25987607

A novel tamponade agent for management of post partum hemorrhage: adaptation of the Xstat mini-sponge applicator for obstetric use.

PubMed

Rodriguez, Maria I; Jensen, Jeffrey T; Gregory, Kenton; Bullard, Mary; Longo, Paul; Heidel, Jerry; Edelman, Alison

2017-06-13

Although uterine tamponade is an effective treatment for postpartum hemorrhage (PPH), current methods have key limitations in their use, particularly in low resource settings. The XStat™ Mini Sponge Dressing (MSD) is approved for the management of non-compressible wounds in the battlefield/trauma setting. The MSD applies highly compressed medical sponges capable of stopping high-flow arterial bleeding within seconds. The objective of our study was to adopt the MSD for use in managing PPH. We performed desktop testing using a uterine model with pressure sensors to compare key design elements of the obstetrical prototype MSD (fundal pressure achieved, reduction in fluid loss, time to deploy, and time to remove) with alternativetechniques (uterine packing, balloon tamponade). To evaluate safety, we delivered the fetus of pregnant ewes by cesarean section and used the prototype to deliver the MSD into one uterine horn, and closed the hysterotomy. We followed the clinical recovery of animals (n = 3) over 24 h, and then removed the reproductive tract for histologic evaluation. To evaluate late effects, we surgically removed the MSDs after 24 h, and followed the clinical recovery of animals (n = 6) for an additional seven days before tissue removal. The obstetrical prototype has a long tapered delivery system designed to be deployed during vaginal examination, and administers three times the volume of the approved MSD trauma bandage. The MSD are deployed within a mesh bag to facilitate removal by vaginaltraction. On desktop testing, the MSD resulted in the highest average fundal pressure (113 mmHg), followed by the MSD bag device (85.8 mmHg), gauze packing (15.5 mmHg), and the uterine balloon (8.2 mmHg). The MSD bag test group achieved the largest fluid flow reduction of -74%, followed by gauze packing (-55%), MSD (-35%), and uterine balloon (-19%). Animal testing demonstrated good uterine fill with no evidence of adverse clinical recovery, uterine trauma or infection at 24 h, or up to 7 days following device removal. We adapted a highly effective trauma dressing and applicator for use in the treatment of severe PPH. Preliminary desktop and animal testing provide a basis for initial clinical trials in women.

Integration of lyoplate based flow cytometry and computational analysis for standardized immunological biomarker discovery.

PubMed

Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R; Nestle, Frank O

2013-01-01

Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases.

Integration of Lyoplate Based Flow Cytometry and Computational Analysis for Standardized Immunological Biomarker Discovery

PubMed Central

Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A. Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R.; Nestle, Frank O.

2013-01-01

Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases. PMID:23843942

Fatigue analysis of multiple site damage at a row of holes in a wide panel

NASA Technical Reports Server (NTRS)

Buhler, Kimberley; Grandt, Alten F., Jr.; Moukawsher, E. J.

1994-01-01

This paper is concerned with predicting the fatigue life of unstiffened panels which contain multiple site damage (MSD). The initial damage consists of through-the-thickness cracks emanating from a row of holes in the center of a finite width panel. A fracture mechanics analysis has been developed to predict the growth, interaction, and coalescence of the various cracks which propagate in the panel. A strain-life analysis incorporating Neuber's rule for notches, and Miner's rule for cumulative damage, is also employed to predict crack initiation for holes without initial cracking. This analysis is compared with the results of a series of fatigue tests on 2024-T3 aluminum panels, and is shown to do an excellent job of predicting the influence of MSD on the fatigue life of nine inch wide specimens. Having established confidence in the ability to analyze the influence of MSD on fatigue life, a parametric study is conducted to examine the influence of various MSD scenarios in an unstiffened panel. The numerical study considered 135 cases in all, with the parametric variables being the applied cyclic stress level, the lead crack geometry, and the number and location of MSD cracks. The numerical analysis provides details for the manner in which lead cracks and MSD cracks grow and coalesce leading to final failure. The results indicate that MSD located adjacent to lead cracks is the most damaging configuration, while for cases without lead cracks, MSD clusters which are not separated by uncracked holes are most damaging.

Biomarkers of systemic inflammation in farmers with musculoskeletal disorders; a plasma proteomic study.

PubMed

Ghafouri, Bijar; Carlsson, Anders; Holmberg, Sara; Thelin, Anders; Tagesson, Christer

2016-05-10

Farmers have an increased risk for musculoskeletal disorders (MSD) such as osteoarthritis of the hip, low back pain, and neck and upper limb complaints. The underlying mechanisms are not fully understood. Work-related exposures and inflammatory responses might be involved. Our objective was to identify plasma proteins that differentiated farmers with MSD from rural referents. Plasma samples from 13 farmers with MSD and rural referents were included in the investigation. Gel based proteomics was used for protein analysis and proteins that differed significantly between the groups were identified by mass spectrometry. In total, 15 proteins differed significantly between the groups. The levels of leucine-rich alpha-2-glycoprotein, haptoglobin, complement factor B, serotransferrin, one isoform of kininogen, one isoform of alpha-1-antitrypsin, and two isoforms of hemopexin were higher in farmers with MSD than in referents. On the other hand, the levels of alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, vitamin D- binding protein, apolipoprotein A1, antithrombin, one isoform of kininogen, and one isoform of alpha-1-antitrypsin were lower in farmers than in referents. Many of the identified proteins are known to be involved in inflammation. Farmers with MSD had altered plasma levels of protein biomarkers compared to the referents, indicating that farmers with MSD may be subject to a more systemic inflammation. It is possible that the identified differences of proteins may give clues to the biochemical changes occurring during the development and progression of MSD in farmers, and that one or several of these protein biomarkers might eventually be used to identify and prevent work-related MSD.

Expert ratings of job demand and job control as predictors of injury and musculoskeletal disorder risk in a manufacturing cohort

PubMed Central

Cantley, Linda F; Tessier-Sherman, Baylah; Slade, Martin D; Galusha, Deron; Cullen, Mark R

2016-01-01

Objective To examine associations between workplace injury and musculoskeletal disorder (MSD) risk and expert ratings of job-level psychosocial demand and job control, adjusting for job-level physical demand. Methods Among a cohort of 9260 aluminium manufacturing workers in jobs for which expert ratings of job-level physical and psychological demand and control were obtained during the 2 years following rating obtainment, multivariate mixed effects models were used to estimate relative risk (RR) of minor injury and minor MSD, serious injury and MSD, minor MSD only and serious MSD only by tertile of demand and control, adjusting for physical demand as well as other recognised risk factors. Results Compared with workers in jobs rated as having low psychological demand, workers in jobs with high psychological demand had 49% greater risk of serious injury and serious MSD requiring medical treatment, work restrictions or lost work time (RR=1.49; 95% CI 1.10 to 2.01). Workers in jobs rated as having low control displayed increased risk for minor injury and minor MSD (RR=1.45; 95% CI 1.12 to 1.87) compared with those in jobs rated as having high control. Conclusions Using expert ratings of job-level exposures, this study provides evidence that psychological job demand and job control contribute independently to injury and MSD risk in a blue-collar manufacturing cohort, and emphasises the importance of monitoring psychosocial workplace exposures in addition to physical workplace exposures to promote worker health and safety. PMID:26163544

Canaries in the Coal Mine: Perceptions of Threat and Media System Dependency Relations.

ERIC Educational Resources Information Center

Loges, William E.

1994-01-01

Investigates whether the intensity and scope of media system dependency (MSD) relations are positively related to perceptions of threats in the environment. Finds that higher perceptions of threat are associated with more intense MSD relations; threat perceptions are strong predictors of the intensity of MSD relations when demographic variables…

18 CFR 1304.101 - Nonnavigable houseboats.

Code of Federal Regulations, 2010 CFR

2010-04-01

... follows with a properly installed and operating Marine Sanitation Device (MSD) or Sewage Holding Tank and... or Type II MSD. (2) Nonnavigable houseboats moored in: “No Discharge Lakes” must be equipped with... equipped with a Type I or Type II MSD, it must be secured to prevent discharge into the lake. (d) Approved...

12 CFR 10.2 - Filing requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

....2 Filing requirements. (a) A national bank shall use Form MSD-4 (Uniform Application for Municipal... § 10.1(b). A national bank receiving a completed MSD-4 form from a person identified in § 10.1(b) must... securities principal or a municipal securities representative. (b) A national bank must submit Form MSD-5...

Advanced Visualization and Interactive Display Rapid Innovation and Discovery Evaluation Research (VISRIDER) Program Task 6: Point Cloud Visualization Techniques for Desktop and Web Platforms

DTIC Science & Technology

2017-04-01

ADVANCED VISUALIZATION AND INTERACTIVE DISPLAY RAPID INNOVATION AND DISCOVERY EVALUATION RESEARCH (VISRIDER) PROGRAM TASK 6: POINT CLOUD...To) OCT 2013 – SEP 2014 4. TITLE AND SUBTITLE ADVANCED VISUALIZATION AND INTERACTIVE DISPLAY RAPID INNOVATION AND DISCOVERY EVALUATION RESEARCH...various point cloud visualization techniques for viewing large scale LiDAR datasets. Evaluate their potential use for thick client desktop platforms

A Perspective on Implementing a Quantitative Systems Pharmacology Platform for Drug Discovery and the Advancement of Personalized Medicine.

PubMed

Stern, Andrew M; Schurdak, Mark E; Bahar, Ivet; Berg, Jeremy M; Taylor, D Lansing

2016-07-01

Drug candidates exhibiting well-defined pharmacokinetic and pharmacodynamic profiles that are otherwise safe often fail to demonstrate proof-of-concept in phase II and III trials. Innovation in drug discovery and development has been identified as a critical need for improving the efficiency of drug discovery, especially through collaborations between academia, government agencies, and industry. To address the innovation challenge, we describe a comprehensive, unbiased, integrated, and iterative quantitative systems pharmacology (QSP)-driven drug discovery and development strategy and platform that we have implemented at the University of Pittsburgh Drug Discovery Institute. Intrinsic to QSP is its integrated use of multiscale experimental and computational methods to identify mechanisms of disease progression and to test predicted therapeutic strategies likely to achieve clinical validation for appropriate subpopulations of patients. The QSP platform can address biological heterogeneity and anticipate the evolution of resistance mechanisms, which are major challenges for drug development. The implementation of this platform is dedicated to gaining an understanding of mechanism(s) of disease progression to enable the identification of novel therapeutic strategies as well as repurposing drugs. The QSP platform will help promote the paradigm shift from reactive population-based medicine to proactive personalized medicine by focusing on the patient as the starting and the end point. © 2016 Society for Laboratory Automation and Screening.

Cultural meanings of musculoskeletal diseases in Chile's Mapuche Population.

PubMed

Alarcon, Ana M; Vidal, Aldo; Castro, Marcela

2013-10-01

Eight out of 10 Mapuche indigenous women have a musculoskeletal disorder (MSD) and do not seek early medical aid. To study both the cultural meanings and implications of MSD from the Mapuche worldview. Ethnographic study carried out from 2008 to 2011 on indigenous reserves in southern Chile. Sixty-four Mapuches participated in comprehensive interviews, which were transcribed and analyzed by the research team. Five cultural domains: (a) foro kutran/bone disease is the general denomination of MSD; (b) Re-Rume Kutran/progressive and incurable course, refers to the course of the disease; (c) Kalül fücha mawiza/body is an old tree, describes internal manifestations such as worn bones, dry body, weak blood, and spiritual weakness; (d) witrür tripai foro/deformation is the external manifestation of MSD; and (e) Reñma ka lof kutran/family and community suffering refers to the impact of MSD. The explanation of MSD is consistent with the integrated body-nature-spirit worldview of the Mapuche. To provide cultural nursing health care so that patients receive prompt diagnosis and care.

Low back pain and widespread pain predict sickness absence among industrial workers

PubMed Central

Morken, Tone; Riise, Trond; Moen, Bente; Hauge, Signe HV; Holien, Solrun; Langedrag, Anne; Pedersen, Svein; Saue, Inger Lise L; Seljebø, Guri M; Thoppil, Varughese

2003-01-01

Background The prevalence of musculoskeletal disorders (MSD) in the aluminium industry is high, and there is a considerable work-related fraction. More knowledge about the predictors of sickness absence from MSD in this industry will be valuable in determining strategies for prevention. The aim of this study was to analyse the relative impact of body parts, psychosocial and individual factors as predictors for short- and long-term sickness absence from MSD among industrial workers. Methods A follow-up study was conducted among all the workers at eight aluminium plants in Norway. A questionnaire was completed by 5654 workers at baseline in 1998. A total of 3320 of these participated in the follow-up study in 2000. Cox regression analysis was applied to investigate the relative impact of MSD in various parts of the body and of psychosocial and individual factors reported in 1998 on short-term and long-term sickness absence from MSD reported in 2000. Results MSD accounted for 45% of all working days lost the year prior to follow-up in 2000. Blue-collar workers had significantly higher risk than white-collar workers for both short- and long-term sickness absence from MSD (long-term sickness absence: RR = 3.04, 95% CI 2.08–4.45). Widespread and low back pain in 1998 significantly predicted both short- and long-term sickness absence in 2000. In addition, shoulder pain predicted long-term sickness absence. Low social support predicted short-term sickness absence (RR = 1.28, 95% CI 1.11–1.49). Conclusions Reducing sickness absence from MSD among industrial workers requires focusing on the working conditions of blue-collar workers and risk factors for low back pain and widespread pain. Increasing social support in the work environment may have effects in reducing short-term sickness absence from MSD. PMID:12956891

Correctors of the Major Cystic Fibrosis Mutant Interact through Membrane-Spanning Domains.

PubMed

Laselva, Onofrio; Molinski, Steven; Casavola, Valeria; Bear, Christine E

2018-06-01

The most common cystic fibrosis causing mutation is deletion of phenylalanine at position 508 (F508del), a mutation that leads to protein misassembly with defective processing. Small molecule corrector compounds: VX-809 or Corr-4a (C4) partially restores processing of the major mutant. These two prototypical corrector compounds cause an additive effect on F508del/cystic fibrosis transmembrane conductance regulator (CFTR) processing, and hence were proposed to act through distinct mechanisms: VX-809 stabilizing the first membrane-spanning domain (MSD) 1, and C4 acting on the second half of the molecule [consisting of MSD2 and/or nucleotide binding domain (NBD) 2]. We confirmed the effect of VX-809 in enhancing the stability of MSD1 and showed that it also allosterically modulates MSD2 when coexpressed with MSD1. We showed for the first time that C4 stabilizes the second half of the CFTR protein through its action on MSD2. Given the allosteric effect of VX-809 on MSD2, we were prompted to test the hypothesis that the two correctors interact in the full-length mutant protein. We did see evidence supporting their interaction in the full-length F508del-CFTR protein bearing secondary mutations targeting domain:domain interfaces. Disruption of the MSD1:F508del-NBD1 interaction (R170G) prevented correction by both compounds, pointing to the importance of this interface in processing. On the other hand, stabilization of the MSD2:F508del-NBD1 interface (by introducing R1070W) led to a synergistic effect of the compound combination on the total abundance of both the immature and mature forms of the protein. Together, these findings suggest that the two correctors interact in stabilizing the complex of MSDs in F508del-CFTR. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Effects of modified Sanhuang decoction () enema on serum tumor necrosis factor-α and colonic mucosa interleukin-1β, interleukin-6 levels in ulcerative colitis rats.

PubMed

Wang, Shuai; Zhou, Tao; Zhai, Jun-Peng; Wang, Li-Hua; Chen, Jing

2014-11-01

To investigate the effects of Modified Sanhuang Decoction (, MSD) enema on the serum tumor necrosis factor alpha (TNF-α) and colonic mucosa interleukin-1β (IL-1β), interleukin-6 (IL-6) levels in experimental ulcerative colitis (UC) rats. Forty-five male Wistar rats were randomly divided into 4 groups: normal group (n=12), model group (n=11), salazosulfapyridine (SASP) group (n=11) and MSD group (n=11). The UC model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Rats in the normal group and model group were clystered with 0.9% normal saline, while in the SASP group and MSD group were clystered with SASP and MSD enema, respectively. After drug administration (10 mL/kg body weight, for 7 days), colonic gross changes and colonic mucosa histology were observed, serum TNF-α and colonic mucosa IL-1β, IL-6 levels were tested by enzyme linked immunosorbent assay and radioimmunoassay, respectively. As compared with the normal group, the experimental UC rats, the colonic mucosal damage index scores (CMDIs), histopathological scores (HS) and the serum TNF-α and colonic mucosa IL-1β, IL-6 levels significantly increased (P<0.05 or P<0.01). In the MSD and SASP groups, the ulcer area significantly reduced, and edema disappeared. The CMDIs, HS, the serum TNF-α and colonic mucosa IL-1β, IL-6 levels in the MSD and SASP groups significantly decreased (P<0.05 or P<0.01) compared with the model group. The CMDIs in the MSD group were lower than that in the SASP group (P<0.05), but there were no significant differences in HS, serum TNF-α or colonic mucosa IL-1β, IL-6 levels between the MSD and SASP groups. MSD enema can improve colonic mucosa impairment and decrease serum TNF-α and colonic mucosa IL-1β, IL-6 levels in experimental UC.

Association between pain catastrophising and musculoskeletal disorders is modified by past injuries in Malaysian military recruits.

PubMed

Mohd Din, F H; Rampal, Sanjay; Muslan, M A; Hoe, Victor C W

2016-07-01

Pain catastrophising is defined as exaggerated negative thoughts, which can occur during an actual or anticipated painful experience, such as musculoskeletal injuries (MSI) or disorders (MSD). The aims of this study are to examine the association between pain catastrophising and MSI and MSD in Malaysian Army male recruits, and evaluate the effects of past injury. A cohort of 611 male Malaysian Army recruits were recruited and followed up at 3 and 6 months. Pain catastrophising, MSD, sociodemographic and work factors were measured using a self-administered questionnaire, and MSI incidence was retrieved from the medical records. Multivariable fixed effects regression was used to model the cumulative incidence of MSD and MSI. Approximately 12% of the recruits were diagnosed with incident MSI and 80% reported incident MSD. Higher pain catastrophising at baseline was associated with higher 6 month MSD risk (adjusted OR (aOR) 1.6 per 1 SD increase of Pain Catastrophising Scale (PCS) scores; 95% CI 1.2 to 2.0), and longitudinally associated with MSD incidence (aOR 1.2, 95% CI 1.1 to 1.4). Pain catastrophising was not associated with MSI incidence (aOR 1.0, 95% CI 0.8 to 1.3). The association between pain catastrophising and self-reported MSD was stronger among recruits with self-reported past injury (p for interaction <0.001). Pain catastrophising was able to predict symptomatic MSD, and not physician-diagnosed MSI, and these findings are directly related to individual health beliefs. Pain catastrophising has a greater influence on how military recruits perceived their musculoskeletal conditions during training, and efforts to reduce pain catastrophising may be beneficial. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Work-life conflict and musculoskeletal disorders: a cross-sectional study of an unexplored association

PubMed Central

2011-01-01

Background The health consequences of work-family or rather work-life conflict (WLC) have been studied by numerous researchers. The work-related causes of musculoskeletal disorders (MSD) are also well explored. And stress (at work) has been found to be a consequence of WLC as well as a cause of MSD. But very little is known about a potential association between WLC and MSD and the possible mediating role of stress in this relationship. Methods Survey data collected in 2007 among the workforces of four large companies in Switzerland were used for this study. The study population covered 6091 employees. As the exposure variable and hypothesized risk factor for MSD, WLC was measured by using a 10-item scale based on an established 18-item scale on work-family conflict. The outcome variables used as indicators of MSD were (low) back pain and neck/shoulder pain. Stress as the assumed intervening variable was assessed by a validated single-item measure of general stress perception. Correlation coefficients (r), standardized regression coefficients (β) and multiple adjusted odds ratios (OR) were calculated as measures of association. Results WLC was found to be quite strongly associated with MSD (β = .21). This association turned out to be substantially confounded by physical strain at work, workload and job autonomy and was considerably reduced but far from being completely eliminated after adjusting for general stress as another identified risk factor of MSD and a proven strong correlate of WLC (r = .44). A significant and relevant association still remained (β = .10) after having controlled for all considered covariates. This association could be fully attributed to only one direction of WLC, namely the work-to-life conflict. In subsequent analyses, a clear gradient between this WLC direction and both types of MSD was found, and proved to be consistent for both men and women. Employees who were most exposed to such work-to-life conflict were also most at risk and showed a fivefold higher prevalence rate (19%-42%) and also an up to sixfold increased relative risk (OR = 3.8-6.3) of suffering greatly from these types of MSD compared with the least exposed reference group showing very low WLC in this direction. Including stress in the regression models again reduced the strength of the association significantly (OR = 1.9-4.1), giving an indication for a possible indirect effect of WLC on MSD mediated by stress. Conclusion Future research and workplace interventions for the prevention of MSD need to consider WLC as an important stressor, and the MSD risk factor identified in this study. PMID:21410950

Work-life conflict and musculoskeletal disorders: a cross-sectional study of an unexplored association.

PubMed

Hämmig, Oliver; Knecht, Michaela; Läubli, Thomas; Bauer, Georg F

2011-03-16

The health consequences of work-family or rather work-life conflict (WLC) have been studied by numerous researchers. The work-related causes of musculoskeletal disorders (MSD) are also well explored. And stress (at work) has been found to be a consequence of WLC as well as a cause of MSD. But very little is known about a potential association between WLC and MSD and the possible mediating role of stress in this relationship. Survey data collected in 2007 among the workforces of four large companies in Switzerland were used for this study. The study population covered 6091 employees. As the exposure variable and hypothesized risk factor for MSD, WLC was measured by using a 10-item scale based on an established 18-item scale on work-family conflict. The outcome variables used as indicators of MSD were (low) back pain and neck/shoulder pain. Stress as the assumed intervening variable was assessed by a validated single-item measure of general stress perception. Correlation coefficients (r), standardized regression coefficients (β) and multiple adjusted odds ratios (OR) were calculated as measures of association. WLC was found to be quite strongly associated with MSD (β=.21). This association turned out to be substantially confounded by physical strain at work, workload and job autonomy and was considerably reduced but far from being completely eliminated after adjusting for general stress as another identified risk factor of MSD and a proven strong correlate of WLC (r=.44). A significant and relevant association still remained (β=.10) after having controlled for all considered covariates. This association could be fully attributed to only one direction of WLC, namely the work-to-life conflict. In subsequent analyses, a clear gradient between this WLC direction and both types of MSD was found, and proved to be consistent for both men and women. Employees who were most exposed to such work-to-life conflict were also most at risk and showed a fivefold higher prevalence rate (19%-42%) and also an up to sixfold increased relative risk (OR = 3.8-6.3) of suffering greatly from these types of MSD compared with the least exposed reference group showing very low WLC in this direction. Including stress in the regression models again reduced the strength of the association significantly (OR=1.9-4.1), giving an indication for a possible indirect effect of WLC on MSD mediated by stress. Future research and workplace interventions for the prevention of MSD need to consider WLC as an important stressor, and the MSD risk factor identified in this study. © 2011 Hämmig et al; licensee BioMed Central Ltd.

Advances in microfluidics for drug discovery.

PubMed

Lombardi, Dario; Dittrich, Petra S

2010-11-01

Microfluidics is considered as an enabling technology for the development of unconventional and innovative methods in the drug discovery process. The concept of micrometer-sized reaction systems in the form of continuous flow reactors, microdroplets or microchambers is intriguing, and the versatility of the technology perfectly fits with the requirements of drug synthesis, drug screening and drug testing. In this review article, we introduce key microfluidic approaches to the drug discovery process, highlighting the latest and promising achievements in this field, mainly from the years 2007 - 2010. Despite high expectations of microfluidic approaches to several stages of the drug discovery process, up to now microfluidic technology has not been able to significantly replace conventional drug discovery platforms. Our aim is to identify bottlenecks that have impeded the transfer of microfluidics into routine platforms for drug discovery and show some recent solutions to overcome these hurdles. Although most microfluidic approaches are still applied only for proof-of-concept studies, thanks to creative microfluidic research in the past years unprecedented novel capabilities of microdevices could be demonstrated, and general applicable, robust and reliable microfluidic platforms seem to be within reach.

An implementation evaluation of a qualitative culture assessment tool.

PubMed

Tappin, D C; Bentley, T A; Ashby, L E

2015-03-01

Safety culture has been identified as a critical element of healthy and safe workplaces and as such warrants the attention of ergonomists involved in occupational health and safety (OHS). This study sought to evaluate a tool for assessing organisational safety culture as it impacts a common OHS problem: musculoskeletal disorders (MSD). The level of advancement across nine cultural aspects was assessed in two implementation site organisations. These organisations, in residential healthcare and timber processing, enabled evaluation of the tool in contrasting settings, with reported MSD rates also high in both sectors. Interviews were conducted with 39 managers and workers across the two organisations. Interview responses and company documentation were compared by two researchers to the descriptor items for each MSD culture aspect. An assignment of the level of advancement, using a five stage framework, was made for each aspect. The tool was readily adapted to each implementation site context and provided sufficient evidence to assess their levels of advancement. Assessments for most MSD culture aspects were in the mid to upper levels of advancement, although the levels differed within each organisation, indicating that different aspects of MSD culture, as with safety culture, develop at a different pace within organisations. Areas for MSD culture improvement were identified for each organisation. Reflections are made on the use and merits of the tool by ergonomists for addressing MSD risk. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

75 FR 53987 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-02

..., Washington, DC 20549-0213. Extension: Rule 15Ba2-1 and Form MSD; SEC File No. 270-0088; OMB Control No. 3235... by a bank municipal securities dealer must be filed on Form MSD (17 CFR 249.1100). The Commission uses the information contained in Form MSD to determine whether bank municipal securities dealers meet...

Sexual dysfunction among Chinese married men aged 30-60 years: a population-based study in Hong Kong.

PubMed

Zhang, Huiping; Yip, Andrew W C; Fan, Susan; Yip, Paul S F

2013-02-01

To estimate the prevalence of, and risk factors associated with, sexual dysfunction among Hong Kong Chinese married men aged 30-60 years. The present study was a part of the Ninth Knowledge, Attitude, and Practice survey conducted in 2007 by the Family Planning Association of Hong Kong. The data set consisted of 728 face-to-face interviews with Hong Kong Chinese married men aged 30-60 years living in the community. The classification of sexual dysfunction in the "Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition" was used to measure male sexual dysfunction (MSD). Regarding MSD prevalence, approximately 15% of men reported ≥ 1 form of MSD, with a lack of sexual interest, erectile dysfunction, and premature ejaculation present in 11.1%, 4.3%, and 4.7%, respectively. Multivariate analysis showed that age (odds ratio 2.39), employment status (odds ratio 3.62), having a wife who sought medical help for sexual problems (odds ratio 4.47), liberal attitudes toward female sexual initiation (odds ratio 2.07), and marital dissatisfaction (odds ratio 2.35) were all statistically significant risk factors for MSD and its specific components among the sample. However, having traditional attitudes toward female sexual refusal was a protective factor for MSD (odds ratio 0.51) and lack of sexual interest (odds ratio 0.51). The prevalence of MSD was low among young and middle-age married men in Hong Kong. Factors contributing to the risk of MSD spanned the domains of socioeconomic status, attitudes toward sex, and relationship factors. These findings suggest future directions for public health policies and the delivery of services that address the prevention and treatment of MSD. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictors of musculoskeletal discomfort: A cross-cultural comparison between Malaysian and Australian office workers.

PubMed

Maakip, Ismail; Keegel, Tessa; Oakman, Jodi

2017-04-01

Prevalence and predictors associated with musculoskeletal disorders (MSDs) vary considerably between countries. It is plausible that socio-cultural contexts may contribute to these differences. We conducted a cross-sectional survey with 1184 Malaysian and Australian office workers with the aim to examine predictors associated with MSD discomfort. The 6-month period prevalence of self-reported MSD discomfort for Malaysian office workers was 92.8% and 71.2% among Australian workers. In Malaysia, a model regressing level of musculoskeletal discomfort against possible risk factors was significant overall (F [6, 370] = 17.35; p < 0.001) and explained 22% (r = 0.46) of its variance. MSD discomfort was significantly associated with predictors that included gender (β = 14), physical (β = 0.38) and psychosocial hazards (β = -0.10), and work-life balance (β = -0.13). In Australia, the regression model is also significant (F [6, 539] = 16.47; p < 0.001) with the model explaining 15.5% (r = 0.39) of the variance in MSD discomfort. Predictors such as gender (β = 0.14), physical (β = 24) and psychosocial hazards (β = -0.17), were associated with MSD discomfort in Australian office workers. Predictors associated with MSD discomfort were similar, but their relative importance differed. Work-life balance was significantly associated with increased MSD discomfort for the Malaysian population only. Design and implementation of MSD risk management needs to take into account the work practices and culture of the target population. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Expert ratings of job demand and job control as predictors of injury and musculoskeletal disorder risk in a manufacturing cohort.

PubMed

Cantley, Linda F; Tessier-Sherman, Baylah; Slade, Martin D; Galusha, Deron; Cullen, Mark R

2016-04-01

To examine associations between workplace injury and musculoskeletal disorder (MSD) risk and expert ratings of job-level psychosocial demand and job control, adjusting for job-level physical demand. Among a cohort of 9260 aluminium manufacturing workers in jobs for which expert ratings of job-level physical and psychological demand and control were obtained during the 2 years following rating obtainment, multivariate mixed effects models were used to estimate relative risk (RR) of minor injury and minor MSD, serious injury and MSD, minor MSD only and serious MSD only by tertile of demand and control, adjusting for physical demand as well as other recognised risk factors. Compared with workers in jobs rated as having low psychological demand, workers in jobs with high psychological demand had 49% greater risk of serious injury and serious MSD requiring medical treatment, work restrictions or lost work time (RR=1.49; 95% CI 1.10 to 2.01). Workers in jobs rated as having low control displayed increased risk for minor injury and minor MSD (RR=1.45; 95% CI 1.12 to 1.87) compared with those in jobs rated as having high control. Using expert ratings of job-level exposures, this study provides evidence that psychological job demand and job control contribute independently to injury and MSD risk in a blue-collar manufacturing cohort, and emphasises the importance of monitoring psychosocial workplace exposures in addition to physical workplace exposures to promote worker health and safety. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Effect of Multiple Sulfatase Deficiency (MSD) on Dental Development: Can We Use the Teeth as an Early Diagnostic Tool?

PubMed

Zilberman, Uri; Bibi, Haim

2016-01-01

Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of metabolism due to reduced catalytic activity of the different sulfatase. Affected individuals show neurologic deterioration with mental retardation, skeletal anomalies, organomegaly, and skin changes as in X-linked ichthyosis. The only organ that was not examined in MSD patients is the dentition. To evaluate the effect of the metabolic error on dental development in a patient with the intermediate severe late-infantile form of MSD (S155P). Histological and chemical study were performed on three deciduous and five permanent teeth from MSD patient and pair-matched normal patients. Tooth germ size and enamel thickness were reduced in both deciduous and permanent MSD teeth, and the scalloping feature of the DEJ was missing in MSD teeth causing enamel to break off from the dentin. The mineral components in the enamel and dentin were different. The metabolic error insults the teeth in the stage of organogenesis in both the deciduous and permanent dentition. The end result is teeth with very sharp cusp tips, thin hypomineralized enamel, and exposed dentin due to the break off of enamel. These findings are different from all other types of MPS syndromes.Clinically the phenotype of intermediate severe late-infantile form of MSD appeared during the third year of life. In children of parents that are carriers, we can diagnose the disease as early as birth using X-ray radiograph of the anterior upper region or as early as 6-8 months when the first deciduous tooth erupt and consider very early treatment to ameliorate the symptoms.

Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.

PubMed

Aiba, Toshiki; Saito, Toshiyuki; Hayashi, Akiko; Sato, Shinji; Yunokawa, Harunobu; Maruyama, Toru; Fujibuchi, Wataru; Kurita, Hisaka; Tohyama, Chiharu; Ohsako, Seiichiroh

2017-03-09

It has been pointed out that environmental factors or chemicals can cause diseases that are developmental in origin. To detect abnormal epigenetic alterations in DNA methylation, convenient and cost-effective methods are required for such research, in which multiple samples are processed simultaneously. We here present methylated site display (MSD), a unique technique for the preparation of DNA libraries. By combining it with amplified fragment length polymorphism (AFLP) analysis, we developed a new method, MSD-AFLP. Methylated site display libraries consist of only DNAs derived from DNA fragments that are CpG methylated at the 5' end in the original genomic DNA sample. To test the effectiveness of this method, CpG methylation levels in liver, kidney, and hippocampal tissues of mice were compared to examine if MSD-AFLP can detect subtle differences in the levels of tissue-specific differentially methylated CpGs. As a result, many CpG sites suspected to be tissue-specific differentially methylated were detected. Nucleotide sequences adjacent to these methyl-CpG sites were identified and we determined the methylation level by methylation-sensitive restriction endonuclease (MSRE)-PCR analysis to confirm the accuracy of AFLP analysis. The differences of the methylation level among tissues were almost identical among these methods. By MSD-AFLP analysis, we detected many CpGs showing less than 5% statistically significant tissue-specific difference and less than 10% degree of variability. Additionally, MSD-AFLP analysis could be used to identify CpG methylation sites in other organisms including humans. MSD-AFLP analysis can potentially be used to measure slight changes in CpG methylation level. Regarding the remarkable precision, sensitivity, and throughput of MSD-AFLP analysis studies, this method will be advantageous in a variety of epigenetics-based research.

Matched sibling versus matched unrelated allogeneic hematopoietic stem cell transplantation in children with severe acquired aplastic anemia: experience of the polish pediatric group for hematopoietic stem cell transplantation.

PubMed

Szpecht, Dawid; Gorczyńska, Ewa; Kałwak, Krzysztof; Owoc-Lempach, Joanna; Choma, Marta; Styczyński, Jan; Goździk, Jolanta; Dłużniewska, Agnieszka; Wysocki, Mariusz; Kowalczyk, Jerzy R; Chybicka, Alicja; Pieczonka, Anna; Wachowiak, Jacek

2012-06-01

In the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelated donor (MUD) between 2000 and 2009 were evaluated. Engraftment was achieved in 45 (93.75 %) patients after MSD-hematopoietic stem cell transplantation (HSCT) and in 33 (86.8 %) after MUD-HSCT. Transplant-related mortality rate after MSD-HSCT was 8 %, while 37 % after MUD-HSCT. After MSD-HSCT 44 (91.7 %) patients are alive for 1-216 months (median: 85 months), while after MUD-HSCT 24 (63.2 %) patients for 1-84 months (median: 16 months). The 5-year probability of event-free survival after MSD-HSCT and MUD-HSCT was 87 and 53 %, respectively, while 5 years of overall survival was 91 and 64 %, respectively. It was concluded that MSD-HSCT as the first line treatment for children with SAA is a safe therapeutic approach with a low rate of treatment failures and excellent outcome. Results of MUD-HSCT in pediatric patients with SAA who failed to respond to immunosuppressive therapy are still inferior than those of MSD-HSCT. Treatment failures of MUD-HSCT are mainly related to infectious complications and graft failure. It seems, however, that HLA-matching of unrelated donors at allelic level along with early MUD-HSCT after FCA (FLUDA, low-dose cyclophosphamide, and anti-thymocyte globulin) conditioning, perhaps using lower Thymoglobulin dose could enable further improvement of long-term results in children with SAA who lack MSD.

Prevalence of musculoskeletal disorders among school teachers from urban and rural areas in Chuquisaca, Bolivia: a cross-sectional study.

PubMed

Solis-Soto, María Teresa; Schön, Anabel; Solis-Soto, Angel; Parra, Manuel; Radon, Katja

2017-10-27

Musculoskeletal disorders (MSD) are important health problems in working populations. The study aimed to determine the prevalence of MSD among school teachers from urban and rural areas in Chuquisaca, Bolivia. A cross-sectional study was conducted in 60 randomly selected schools. In total, 1062 teachers were invited to participate (response 58%). The Spanish version of the Standardized Nordic questionnaire was used assessing the 12-months and 7-days prevalence of MSD as well as the 12-months prevalence of work limiting pain. Prevalence were calculated for the different parts of the body; as summary measures, MSD in any part of the body and in ≥3 parts of the body were assessed. Crude and adjusted odds ratios with 95% confidence intervals were calculated using logistic regression models adjusting for age, sex, teaching level and school type. Prevalence of MSD in any part of the body was 86% during the last 12 months, 63% during the last 7 days and 15% for work limiting pain. MSD was most common in the neck (12-months prevalence 47%) and least common in the wrist/hands (26%). In the adjusted model, teachers working in rural areas presented significantly higher odds than teachers from urban schools for work-limiting pain during the last 12-months considering any part of the body (aOR 2.2; 95% CI 1.1-4.1), and for ≥3 parts of the body (aOR 3.7; 95% CI 1.3-10.6). The prevalence of MSD is high in School teachers, even more in teachers working in rural areas. It is needed to identify risk factors for MSD in teachers in order to propose appropriate strategies to control and reduce it.

The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hori, Akiko; Morand, Agathe; Ikebe, Chiho

2015-12-04

The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, asmore » one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation. - Highlights: • Human Wdr8 is a centrosomal protein enriched in the proximal end of the centriole. • Wdr8 and hMsd1/SSX2IP form a complex conserved in fungi. • Depletion of Wdr8 results in shorter, tilted spindle microtubules. • Depletion phenotypes of Wdr8 are very similar to those of hMsd1/SSX2IP knockdown.« less

Work disability benefits due to musculoskeletal disorders among Brazilian private sector workers.

PubMed

Vieira, E R; Albuquerque-Oliveira, P R; Barbosa-Branco, A

2011-05-14

To evaluate the prevalence and characteristics of disability benefits due to musculoskeletal disorders (MSD) granted to Brazilian private sector workers. This was a population-based epidemiological study of MSD-related benefits among registered private sector workers (n=32 959 329). The prevalence (benefits/10 000 workers/year) of work disability benefits was calculated by gender, age, state, Human Development Index (HDI), economic activity, MSD type and work-relatedness. The prevalence of MSD-related benefits in Brazil among registered private sector workers in 2008 was 93.6/10 000 workers. The prevalence increased with age, and was higher for women (112.2) than for men (88.1), although the former had shorter benefit duration. The gender-adjusted prevalence by state varied from 16.6 to 90.3 for non-work-related, and from 7.8 to 59.6 for work-related benefits. The Brazilian states with a high-very high HDI had the highest prevalence. The top four most common types of MSD-related benefits were due to back pain, intervertebral disc disorders, sinovitis/tenosynovitis and shoulder disorders. MSD is a frequent cause of work disability in Brazil. There were differences in prevalence among economic activities and between states grouped by HDI. This study demonstrates that further evaluation of the contributing factors associated with MSD-related disability benefits is required. Factors that should be considered include production processes, political organisation, socioeconomic and educational characteristics, the compensation and recording systems, and employee-employer power relationships. These factors may play an important role in the prevalence of MSD-related disability benefits, especially in countries with large socioeconomic iniquities such as Brazil.

Interleukin-18 and CD30 serum levels in patients with moderate-severe depression.

PubMed Central

Merendino, Rosaria Alba; Di Rosa, Antonio Enrico; Di Pasquale, Giuseppe; Minciullo, Paola Lucia; Mangraviti, Carmela; Costantino, Antonella; Ruello, Antonella; Gangemi, Sebastiano

2002-01-01

Interleukin-18 (IL-18), a pro-inflammatory cytokine that plays an important role in the T-cell-helper type 1 response, is a new member of the family of cytokines produced in the brain. CD30 is a marker of T-cell-helper type 2 lymphocytes. We evaluated IL-18 and CD30 serum levels in 10 patients affected by moderate-severe depression (MSD). We demonstrated for the first time that serum IL-18 levels of MSD patients were significantly higher than those of healthy donors. On the contrary, no significant difference was found between serum CD30 levels of MSD patients compared with those of healthy donors. These data strengthen the hypothesis that MSD disease is associated with an inflammatory response, mainly T-cell-helper type 1, and suggest an important role for IL-18 in the pathophysiology of MSD. PMID:12396479

The integration between Business Model Canvas and Manufacturing System Design

NASA Astrophysics Data System (ADS)

Prasetyawan, Y.; Maulida, N.; Lutvitasari, M. R.

2018-04-01

Business Model Canvas (BMC) is an increasingly popular business design tool especially for a start-up business and new business player. In general, BMC seeks a balance between effective working patterns with suppliers, good relation with customers and ability to understand and manage internal resources. This balance will expedite the implementation of Manufacturing System Design (MSD). The existing use of BMC and MSD is frequently applied separately at various business levels. BMC business plan is primarily to have engagement with customers and explore potential revenue to increase profits, while MSD primarily aims to meet production targets with available resources. The purpose of this research is to provide a roadmap to align BMC and MSD. A series of simple mathematical (modified) and integration models are created to connect BMC and MSD. Several results in various industries (new, developed and mature) are presented and used as examples of implementation.

Prevention of MSD within OHSMS/IMS: a systematic review of risk assessment strategies.

PubMed

Yazdani, Amin; Wells, Richard

2012-01-01

The purpose of this systematic review was to identify and summarize the research evidence on prevention of Musculoskeletal Disorders (MSD) within Occupational Health and Safety Management Systems (OHSMS) and Integrated Management Systems (IMS). Databases in business, management, engineering and health and safety were systematically searched and relevant publications were synthesized. The number of papers that could address the research questions was small. However, the review revealed that many of the techniques to address MSD hazards require substantial background knowledge and training. This may limit employees' involvement in the technical aspects of the risk assessment process. Also these techniques did not usually fit into techniques used by companies to address other risk factors within their management systems. This could result in MSD prevention becoming a separate issue that cannot be managed with company-wide tools. In addition, this review also suggested that there is a research gap concerning the MSD prevention within companies' management systems.

MetaCoMET: a web platform for discovery and visualization of the core microbiome

USDA-ARS?s Scientific Manuscript database

A key component of the analysis of microbiome datasets is the identification of OTUs shared between multiple experimental conditions, commonly referred to as the core microbiome. Results: We present a web platform named MetaCoMET that enables the discovery and visualization of the core microbiome an...

HEx: A heterologous expression platform for the discovery of fungal natural products

PubMed Central

Schlecht, Ulrich; Horecka, Joe; Lin, Hsiao-Ching; Naughton, Brian; Miranda, Molly; Li, Yong Fuga; Hennessy, James R.; Vandova, Gergana A.; Steinmetz, Lars M.; Sattely, Elizabeth; Khosla, Chaitan; Hillenmeyer, Maureen E.

2018-01-01

For decades, fungi have been a source of U.S. Food and Drug Administration–approved natural products such as penicillin, cyclosporine, and the statins. Recent breakthroughs in DNA sequencing suggest that millions of fungal species exist on Earth, with each genome encoding pathways capable of generating as many as dozens of natural products. However, the majority of encoded molecules are difficult or impossible to access because the organisms are uncultivable or the genes are transcriptionally silent. To overcome this bottleneck in natural product discovery, we developed the HEx (Heterologous EXpression) synthetic biology platform for rapid, scalable expression of fungal biosynthetic genes and their encoded metabolites in Saccharomyces cerevisiae. We applied this platform to 41 fungal biosynthetic gene clusters from diverse fungal species from around the world, 22 of which produced detectable compounds. These included novel compounds with unexpected biosynthetic origins, particularly from poorly studied species. This result establishes the HEx platform for rapid discovery of natural products from any fungal species, even those that are uncultivable, and opens the door to discovery of the next generation of natural products. PMID:29651464

Discovery and bio-optimization of human antibody therapeutics using the XenoMouse® transgenic mouse platform.

PubMed

Foltz, Ian N; Gunasekaran, Kannan; King, Chadwick T

2016-03-01

Since the late 1990s, the use of transgenic animal platforms has transformed the discovery of fully human therapeutic monoclonal antibodies. The first approved therapy derived from a transgenic platform--the epidermal growth factor receptor antagonist panitumumab to treat advanced colorectal cancer--was developed using XenoMouse(®) technology. Since its approval in 2006, the science of discovering and developing therapeutic monoclonal antibodies derived from the XenoMouse(®) platform has advanced considerably. The emerging array of antibody therapeutics developed using transgenic technologies is expected to include antibodies and antibody fragments with novel mechanisms of action and extreme potencies. In addition to these impressive functional properties, these antibodies will be designed to have superior biophysical properties that enable highly efficient large-scale manufacturing methods. Achieving these new heights in antibody drug discovery will ultimately bring better medicines to patients. Here, we review best practices for the discovery and bio-optimization of monoclonal antibodies that fit functional design goals and meet high manufacturing standards. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

78 FR 36605 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-18

..., Washington, DC 20549-0213. Extension: Rule 15Ba2-1 and Form MSD. SEC File No. 270-0088, OMB Control No. 3235... existing collection of information provided for in Rule 15Ba2-1 (17 CFR 240.15Ba2-1) and Form MSD (17 CFR... registration with the Commission by a bank municipal securities dealer must be filed on Form MSD. The...

75 FR 35853 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-23

..., Washington, DC 20549-0213. Extension: Rule 15Ba2-1 and Form MSD; SEC File No. 270-0088; OMB Control No. 3235... collection of information provided for in Rule 15Ba2-1 (17 CFR 240.15Ba2-1) and Form MSD (17 CFR 249.1100... bank municipal securities dealer must be filed on Form MSD. The Commission uses the information...

Toe thumb: a musculoskeletal disorder related to transesophageal echocardiography.

PubMed

Tewari, Prabhat; Raju, P S N; Neema, P K

2014-01-01

The musculoskeletal disorders (MSD) are common in healthcare providers and those who are doing sonography are also affected. There are reports of MSD in healthcare providers who do transthoracic echocardiography. Transesophageal echocardiography (TEE) is being regularly used in peri-operative setting. We describe MSD of hand in a cardiovascular and thoracic anesthesiologist who has been performing TEE scanning for 10% of his work-time in operating room and critical care area for the last 8 years. As the role of TEE is increasing and many doctors are doing it on a routine basis, the knowledge of association of MSD with TEE and measures to prevent it is important.

Characterization of single-file diffusion in one-dimensional dusty plasma

NASA Astrophysics Data System (ADS)

Theisen, W. L.; Sheridan, T. E.

2010-11-01

Single-file diffusion occurs in one-dimensional systems when particles cannot pass each other and the mean-squared displacement (msd) of these particles increases with time t. Diffusive processes that follow Ficks law predict that the msd increases as t, however, single-file diffusion is sub-Fickean meaning that the msd is predicted to increase as t^1/2. One-dimensional dusty plasma rings have been created under strongly coupled, over-damped conditions. Particle position data from these rings will be analyzed to determine the scaling of the msd with time. Results will be compared with predictions of single-file diffusion theory.

Accuracy of a disability instrument to identify workers likely to develop upper extremity musculoskeletal disorders.

PubMed

Stover, Bert; Silverstein, Barbara; Wickizer, Thomas; Martin, Diane P; Kaufman, Joel

2007-06-01

Work related upper extremity musculoskeletal disorders (MSD) result in substantial disability, and expense. Identifying workers or jobs with high risk can trigger intervention before workers are injured or the condition worsens. We investigated a disability instrument, the QuickDASH, as a workplace screening tool to identify workers at high risk of developing upper extremity MSDs. Subjects included workers reporting recurring upper extremity MSD symptoms in the past 7 days (n = 559). The QuickDASH was reasonably accurate at baseline with sensitivity of 73% for MSD diagnosis, and 96% for symptom severity. Specificity was 56% for diagnosis, and 53% for symptom severity. At 1-year follow-up sensitivity and specificity for MSD diagnosis was 72% and 54%, respectively, as predicted by the baseline QuickDASH score. For symptom severity, sensitivity and specificity were 86% and 52%. An a priori target sensitivity of 70% and specificity of 50% was met by symptom severity, work pace and quality, and MSD diagnosis. The QuickDASH may be useful for identifying jobs or workers with increased risk for upper extremity MSDs. It may provide an efficient health surveillance screening tool useful for targeting early workplace intervention for prevention of upper extremity MSD problems.

The neuroprotective effect of modified "Shengyu" decoction is mediated through an anti-inflammatory mechanism in the rat after traumatic brain injury.

PubMed

Zhao, Guang-Wei; Wang, Yong; Li, Yong-Cai; Jiang, Zheng-Lin; Sun, Li; Xi, Xin; He, Peng; Wang, Guo-Hua; Xu, Shi-Hui; Ma, Dong-Ming; Ke, Kai-Fu

2014-01-01

"Shengyu" decoction, a traditional Chinese medicine, has been used to treat diseases with deficit in "qi" and "blood" induced frequently by profound loss of blood or by long sores with heavy pus, in which a potential anti-inflammatory effect is implied. The modified "Shengyu" decoction (MSD) used in the present study was designed on the basis of the "Shengyu" decoction, additional four herbs were added in. Many ingredients in these herbs have been demonstrated to be anti-inflammatory and thus MSD may be used for the treatment of traumatic brain injury (TBI). To evaluate the neuroprotective effect and the underlying mechanisms of MSD on the rat brain after TBI. TBI was induced in the right cerebral cortex of male adult rats using Feeney's weight-drop method. The rats were administered a gavage of MSD (0.5, 1.0 or 2.0 ml/200 g) 6h after TBI. The neurological functions, brain water content, contusion volume, and neuron loss were determined. The levels of TNF-α, IL-1β, IL-6, and IL-10 and the number of GFAP- and Iba1-positive cells in the brain ipsilateral to TBI were also measured. Moreover, the influence of MSD on these variables was observed at the same time. The neurological deficits, brain water content, and neuron loss were significantly reduced after 1.0 or 2.0 ml/200 g of MSD treatment but not after 0.5 ml/200 g. In addition, treatment with MSD (1.0 ml/200 g) significantly increased the level of IL-10 and reduced the level of TNF-α and IL-1β and the number of GFAP- and Iba1-positive cells after TBI. However, the contusion volume of brain tissue and the expression of IL-6 were not significantly changed. MSD may be a potential therapeutic for the treatment of TBI because MSD alleviated secondary brain injury induced by TBI. In addition, MSD inhibited the inflammatory response through reducing the expression of inflammatory cytokines and the activation of microglial cells and astrocytes in the brain tissue of rats after TBI. Therefore, a potential anti-inflammatory mechanism of the "Shengyu" decoction was confirmed, which may be one of the main reasons of "Shengyu" decoction used to treat diseases with obvious inflammatory responses. © 2013 Elsevier Ireland Ltd. All rights reserved.

BioGraph: unsupervised biomedical knowledge discovery via automated hypothesis generation

PubMed Central

2011-01-01

We present BioGraph, a data integration and data mining platform for the exploration and discovery of biomedical information. The platform offers prioritizations of putative disease genes, supported by functional hypotheses. We show that BioGraph can retrospectively confirm recently discovered disease genes and identify potential susceptibility genes, outperforming existing technologies, without requiring prior domain knowledge. Additionally, BioGraph allows for generic biomedical applications beyond gene discovery. BioGraph is accessible at http://www.biograph.be. PMID:21696594

E-MSD: improving data deposition and structure quality.

PubMed

Tagari, M; Tate, J; Swaminathan, G J; Newman, R; Naim, A; Vranken, W; Kapopoulou, A; Hussain, A; Fillon, J; Henrick, K; Velankar, S

2006-01-01

The Macromolecular Structure Database (MSD) (http://www.ebi.ac.uk/msd/) [H. Boutselakis, D. Dimitropoulos, J. Fillon, A. Golovin, K. Henrick, A. Hussain, J. Ionides, M. John, P. A. Keller, E. Krissinel et al. (2003) E-MSD: the European Bioinformatics Institute Macromolecular Structure Database. Nucleic Acids Res., 31, 458-462.] group is one of the three partners in the worldwide Protein DataBank (wwPDB), the consortium entrusted with the collation, maintenance and distribution of the global repository of macromolecular structure data [H. Berman, K. Henrick and H. Nakamura (2003) Announcing the worldwide Protein Data Bank. Nature Struct. Biol., 10, 980.]. Since its inception, the MSD group has worked with partners around the world to improve the quality of PDB data, through a clean up programme that addresses inconsistencies and inaccuracies in the legacy archive. The improvements in data quality in the legacy archive have been achieved largely through the creation of a unified data archive, in the form of a relational database that stores all of the data in the wwPDB. The three partners are working towards improving the tools and methods for the deposition of new data by the community at large. The implementation of the MSD database, together with the parallel development of improved tools and methodologies for data harvesting, validation and archival, has lead to significant improvements in the quality of data that enters the archive. Through this and related projects in the NMR and EM realms the MSD continues to improve the quality of publicly available structural data.

The Effects of Modified Simiao Decoction in the Treatment of Gouty Arthritis: A Systematic Review and Meta-Analysis

PubMed Central

Huang, Ying; Wen, Cai-Yu-Zhu; Zhang, Jun-Jun; Xing, Guo-Lan; Chen, Zhe

2017-01-01

The modified Simiao decoctions (MSD) have been wildly applied in the treatment of gouty arthritis in China. However, the evidence needs to be evaluated by a systematic review and meta-analysis. After filtering, twenty-four randomised, controlled trials (RCTs) comparing the effects of MSD and anti-inflammation medications and/or urate-lowering therapies in patients with gouty arthritis were included. In comparison with anti-inflammation medications, urate-lowering therapies, or coadministration of anti-inflammation medications and urate-lowering therapies, MSD monotherapy significantly lowered serum uric acid (p < 0.00001, mean difference = −90.62, and 95% CI [−128.38, −52.86]; p < 0.00001, mean difference = −91.43, and 95% CI [−122.38, −60.49]; p = 0.02, mean difference = −40.30, and 95% CI [−74.24, −6.36], resp.). Compared with anti-inflammation medications and/or urate-lowering therapies, MSD monotherapy significantly decreased ESR (p < 0.00001; mean difference = −8.11; 95% CI [−12.53, −3.69]) and CRP (p = 0.03; mean difference = −3.21; 95% CI [−6.07, −0.36]). Additionally, the adverse effects (AEs) of MSD were fewer (p < 0.00001; OR = 0.08; 95% CI [0.05, 0.16]). MSD are effective in the treatment of gouty arthritis through anti-inflammation and lowering urate. However, the efficacy of MSD should be estimated with more RCTs. PMID:28373889

Prevalence, diagnostics and management of musculoskeletal disorders in primary health care in Sweden – an investigation of 2000 randomly selected patient records

PubMed Central

Fahlström, Martin; Djupsjöbacka, Mats

2016-01-01

Abstract Rationale, aims and objectives The aims of this study is to investigate the prevalence of patients seeking care due to different musculoskeletal disorders (MSDs) at primary health care centres (PHCs), to chart different factors such as symptoms, diagnosis and actions prescribed for patients that visited the PHCs due to MSD and to make comparisons regarding differences due to gender, age and rural or urban PHC. Methods Patient records (2000) for patients in working age were randomly selected equally distributed on one rural and one urban PHC. A 3‐year period was reviewed retrospectively. For all patient records' background data, cause to the visit and diagnosis were registered. For visits due to MSD, type and location of symptoms and actions to resolve the patients problems were registered. Data was analysed using cross tabulation, multidimensional chi‐squared. Results The prevalence of MSD was high; almost 60% of all patients were seeking care due to MSD. Upper and lower limb problems were most common. Symptoms were most prevalent in the young and middle age groups. The patients got a variety of different diagnoses, and between 13 and 35% of the patients did not receive a MSD diagnose despite having MSD symptoms. There was a great variation in how the cases were handled. Conclusions The present study points out some weaknesses regarding diagnostics and management of MSD in primary care. PMID:27538347

Prevalence, diagnostics and management of musculoskeletal disorders in primary health care in Sweden - an investigation of 2000 randomly selected patient records.

PubMed

Wiitavaara, Birgitta; Fahlström, Martin; Djupsjöbacka, Mats

2017-04-01

The aims of this study is to investigate the prevalence of patients seeking care due to different musculoskeletal disorders (MSDs) at primary health care centres (PHCs), to chart different factors such as symptoms, diagnosis and actions prescribed for patients that visited the PHCs due to MSD and to make comparisons regarding differences due to gender, age and rural or urban PHC. Patient records (2000) for patients in working age were randomly selected equally distributed on one rural and one urban PHC. A 3-year period was reviewed retrospectively. For all patient records' background data, cause to the visit and diagnosis were registered. For visits due to MSD, type and location of symptoms and actions to resolve the patients problems were registered. Data was analysed using cross tabulation, multidimensional chi-squared. The prevalence of MSD was high; almost 60% of all patients were seeking care due to MSD. Upper and lower limb problems were most common. Symptoms were most prevalent in the young and middle age groups. The patients got a variety of different diagnoses, and between 13 and 35% of the patients did not receive a MSD diagnose despite having MSD symptoms. There was a great variation in how the cases were handled. The present study points out some weaknesses regarding diagnostics and management of MSD in primary care. © 2016 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

Organs-on-a-chip for drug discovery.

PubMed

Selimović, Seila; Dokmeci, Mehmet R; Khademhosseini, Ali

2013-10-01

The current drug discovery process is arduous and costly, and a majority of the drug candidates entering clinical trials fail to make it to the marketplace. The standard static well culture approaches, although useful, do not fully capture the intricate in vivo environment. By merging the advances in microfluidics with microfabrication technologies, novel platforms are being introduced that lead to the creation of organ functions on a single chip. Within these platforms, microengineering enables precise control over the cellular microenvironment, whereas microfluidics provides an ability to perfuse the constructs on a chip and to connect individual sections with each other. This approach results in microsystems that may better represent the in vivo environment. These organ-on-a-chip platforms can be utilized for developing disease models as well as for conducting drug testing studies. In this article, we highlight several key developments in these microscale platforms for drug discovery applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Haploidentical Transplantation Without In Vitro T-Cell Depletion Results in Outcomes Equivalent to Those of Contemporaneous Matched Sibling and Unrelated Donor Transplantation for Acute Leukemia.

PubMed

Yu, Sijian; Fan, Qian; Sun, Jing; Fan, Zhiping; Zhang, Yu; Jiang, Qianli; Huang, Fen; Xuan, Li; Dai, Min; Zhou, Hongsheng; Liu, Hui; Liu, Qi-Fa

2016-03-01

The aim of the study is to determine whether HLA-haploidentical-related donor (HRD) transplant can achieve equivalent outcomes and have stronger GVL compared to HLA-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants. A total of 355 consecutive patients with acute leukemia undergoing allogeneic transplant at our single institute between March 2008 and March 2014 were enrolled in this retrospective investigation. Of the 355 patients, 96 cases received HRD, 153 MSD, and 106 MUD transplants. HRD transplant was associated with higher incidences of grade II to IV aGVHD (40.6%) compared with MSD (23.5%, P = 0.002) and MUD transplants (34.0%, P = 0.049), whereas incidences of grade III to IV aGVHD (11.4%, 7.8%, 10.5%, respectively; P = 0.590) and cGVHD (29.5%, 24.0%, 29.5%, respectively; P = 0.538) did not differ among 3 groups. Five-year relapse rates were 19.2%, 26.8%, and 23.0% in 3 groups, respectively (P = 0.419). However, of 206 high-risk patients, the relapse rate in HRD transplant was lower than in MSD transplant (23.8% vs 41.9%, P = 0.026). Multivariate analysis showed that HRD had beneficial impact on relapse (for MSD: P = 0.006). Five-year transplant-related mortality was lower in MSD transplant compared with those in HRD (17.3% vs 26.4%, P = 0.041) and MUD transplants (17.3% vs 24.1%, P = 0.037). Five-year overall survival were 60.4%, 64.6%, and 61.0%, respectively, in HRD, MSD, and MUD groups (P = 0.371); 5-year disease-free survival were 59.6%, 58.8%, and 54.9%, respectively (P = 0.423). Our results suggest that HRD transplant results in outcomes equivalent to MSD and MUD transplants. HRD might carry a superior GVL effect compared to MSD for high-risk patients.

Radiological analysis of minimal safe distance and optimal screw angle to avoid facet violation in open-door laminoplasty using precontoured plate.

PubMed

Min, Woo-Kie; Seo, Il; Na, Sang-Bong; Choi, Young-Seo; Choi, Ji-Yeon

2017-01-01

This study aimed to present radiologic analysis of minimal safe distance (MSD) and optimal screw angle (OSA) that enables to fix screws in a lateral mass safely without facet joint violation in open-door laminoplasty using a plate. A retrospective analysis was made of 22 patients (male: 17; female: 5), average age 62 years. Seventy-nine lateral mass screws were fixed among a total of 158 screws. MSD that doesn't allow 5-mm screws to violate a facet joint was measured for C3-C7 and a comparative analysis was performed. If the MSD is not secured, the OSA to be given to the cephalad direction is calculated to avoid violation of the facet joint. The screws violating inferior facet joints accounted for 34.1% of the screws fixed in inferior lateral mass. Joint surface to distal mini-screw distances were 3.18 ± 1.46 mm and 4.75 ± 1.71 mm in groups of facet joint violation and non-facet violation (FV), respectively ( p = 0.001). When 5-mm screws were inserted into a lateral mass, MSD was 4.39 ± 0.83 mm. The average MSD of C3, C4, and C5 was 4.05 ± 0.78 mm, 4.10 ± 0.70 mm, and 4.26 ± 0.74 mm, respectively. There was no significant differences among levels ( p > 0.05). The average MSD of C6 and C7 was 4.92 ± 0.81 mm and 4.80 ± 0.96 mm, respectively, showing significant differences from those of C3, C4, and C5 ( p < 0.05). If 6 mm of the MSD isn't secured, OSA showed in the cephalad direction of 11.5° for 5 mm and 22° for 4 mm approximately. We suggest that mini-screw on lateral mass can be fixed safely without FV, if they are fixed at MSD of 6 mm from a joint surface. Facet joint violation doesn't occur if an OSA is given in the cephalad direction in case of not enough MSD for mini-screws.

Improvement in the neural stem cell proliferation in rats treated with modified "Shengyu" decoction may contribute to the neurorestoration.

PubMed

Chen, Miao-Miao; Zhao, Guang-Wei; He, Peng; Jiang, Zheng-Lin; Xi, Xin; Xu, Shi-Hui; Ma, Dong-Ming; Wang, Yong; Li, Yong-Cai; Wang, Guo-Hua

2015-05-13

"Shengyu" decoction, a traditional Chinese medicine, has been used to treat diseases with deficit in "qi" and "blood". The modified "Shengyu" decoction (MSD) used in the present study was designed to treat traumatic brain injury (TBI) on the basis of the "Shengyu" decoction, in which additional four herbs were added. Many ingredients in these herbs have been demonstrated to be effective for the treatment of brain injury. The present study was performed to evaluate the neurorestorative effect and the underlying mechanisms of MSD on the rat brain after a TBI. TBI was induced in the right cerebral cortex of adult rats using Feeney's weight-drop method. Intragastrical administration of MSD (1.0 ml/200 g) was begun 6h after TBI. The neurological functions and neuronal loss in the cortex and hippocampus were determined. The levels of nerve growth-related factors GDNF, NGF, NCAM, TN-C, and Nogo-A and the number of GFAP(+)/GDNF(+), BrdU(+)/nestin(+), BrdU(+)/NeuN(+) immunoreactive cells in the brain ipsilateral to TBI were also measured. Moreover, the influences of MSD on these variables were observed at the same time. We found that treatment with MSD in TBI rats ameliorated the neurological functions and alleviated neuronal loss. MSD treatment elevated the expression of GDNF, NGF, NCAM, and TN-C, and inhibited the expression of Nogo-A. Moreover, MSD treatment increased the number of GFAP(+)/GDNF(+), BrdU(+)/nestin(+), and BrdU(+)/NeuN(+) immunoreactive cells in the cortex and hippocampus. The present results suggest that MSD treatment in TBI rats could improve the proliferation of neural stem/progenitor cells and differentiation into neurons, which may facilitate neural regeneration and tissue repair and thus contribute to the recovery of neurological functions. These effects of modified "Shengyu" decoction may provide a foundation for the use of MSD as a prescription of medicinal herbs in the traditional medicine to treat brain injuries in order to improve the neurorestoration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Anomalous diffusion of a probe in a bath of active granular chains

NASA Astrophysics Data System (ADS)

Jerez, Michael Jade Y.; Confesor, Mark Nolan P.; Carpio-Bernido, M. Victoria; Bernido, Christopher C.

2017-08-01

We investigate the dynamics of a passive probe particle in a bath of active granular chains (AGC). The bath and the probe are enclosed in an experimental compartment with a sinusoidal boundary to prevent AGC congestion along the boundary while connected to an electrodynamic shaker. Single AGC trajectory analysis reveals a persistent type of motion compared to a purely Brownian motion as seen in its mean squared displacement (MSD). It was found that at small concentration, Φ ≤ 0.44, the MSD exhibits two dynamical regimes characterized by two different scaling exponents. For small time scales, the dynamics is superdiffusive (1.32-1.63) with the MSD scaling exponent increasing monotonically with increasing AGC concentration. On the other hand, at long time, we recover the Brownian dynamics regime, MSD = DΔt, where the mobility D ∝ Φ. We quantify the probe dynamics at short time scale by modeling it as a fractional Brownian motion. The analytical form of the MSD agrees with experimental results.

Evaluation of Seismic Performance and Effectiveness of Multiple Slim-Type Damper System for Seismic Response Control of Building Structures

PubMed Central

Kim, David; Sung, Eun Hee; Park, Kwan-Soon; Park, Jaegyun

2014-01-01

This paper presents the evaluation of seismic performance and cost-effectiveness of a multiple slim-type damper system developed for the vibration control of earthquake excited buildings. The multiple slim-type damper (MSD) that consists of several small slim-type dampers and linkage units can control damping capacity easily by changing the number of small dampers. To evaluate the performance of the MSD, dynamic loading tests are performed with three slim-type dampers manufactured at a real scale. Numerical simulations are also carried out by nonlinear time history analysis with a ten-story earthquake excited building structure. The seismic performance and cost-effectiveness of the MSD system are investigated according to the various installation configurations of the MSD system. From the results of numerical simulation and cost-effectiveness evaluation, it is shown that combinations of the MSD systems can effectively improve the seismic performance of earthquake excited building structures. PMID:25301387

Residues in the membrane-spanning domain core modulate conformation and fusogenicity of the HIV-1 envelope glycoprotein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shang Liang; Hunter, Eric, E-mail: eric.hunter2@emory.ed

2010-09-01

The membrane-spanning domain (MSD) of human immunodeficiency virus type I (HIV-1) envelope glycoprotein (Env) is critical for its biological activity. Initial studies have defined an almost invariant 'core' structure in the MSD and demonstrated that it is crucial for anchoring Env in the membrane and virus entry. We show here that amino acid substitutions in the MSD 'core' do not influence specific virus-cell attachment, nor CD4 receptor and CXCR4 coreceptor recognition by Env. However, substitutions within the MSD 'core' delayed the kinetics and reduced the efficiency of cell-cell fusion mediated by Env. Although we observed no evidence that membrane fusionmore » mediated by the MSD core mutants was arrested at a hemifusion stage, impaired Env fusogenicity was correlated with minor conformational changes in the V2, C1, and C5 regions in gp120 and the immunodominant loop in gp41. These changes could delay initiation of the conformational changes required in the fusion process.« less

Multitask saliency detection model for synthetic aperture radar (SAR) image and its application in SAR and optical image fusion

NASA Astrophysics Data System (ADS)

Liu, Chunhui; Zhang, Duona; Zhao, Xintao

2018-03-01

Saliency detection in synthetic aperture radar (SAR) images is a difficult problem. This paper proposed a multitask saliency detection (MSD) model for the saliency detection task of SAR images. We extract four features of the SAR image, which include the intensity, orientation, uniqueness, and global contrast, as the input of the MSD model. The saliency map is generated by the multitask sparsity pursuit, which integrates the multiple features collaboratively. Detection of different scale features is also taken into consideration. Subjective and objective evaluation of the MSD model verifies its effectiveness. Based on the saliency maps obtained by the MSD model, we apply the saliency map of the SAR image to the SAR and color optical image fusion. The experimental results of real data show that the saliency map obtained by the MSD model helps to improve the fusion effect, and the salient areas in the SAR image can be highlighted in the fusion results.

AGOR 28: SIO Shipyard Representative Bi-Weekly Progress Report

DTIC Science & Technology

2015-10-23

constant tension operation. These items will be rechecked next week. 3 • Red Fox MSD – Tested and Commissioned by vendor...No operational issues, however both overboarding pumps had cracked housings. Vendor suspects factory defect and is replace with new. MSD ...593-001-3 MSD System Operational Test 10/6 422-001-3 Navigation Signal & Search Light Demonstration 10/9. 573-001-2 125% & 100 % Portable Crane 10/12

The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation

PubMed Central

Hori, Akiko; Morand, Agathe; Ikebe, Chiho; Frith, David; Snijders, Ambrosius P.; Toda, Takashi

2015-01-01

The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, as one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation. PMID:26545777

VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1

PubMed Central

Ren, Hong Yu; Grove, Diane E.; De La Rosa, Oxana; Houck, Scott A.; Sopha, Pattarawut; Van Goor, Fredrick; Hoffman, Beth J.; Cyr, Douglas M.

2013-01-01

Cystic fibrosis (CF) is a fatal genetic disorder associated with defective hydration of lung airways due to the loss of chloride transport through the CF transmembrane conductance regulator protein (CFTR). CFTR contains two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory domain, and its channel assembly requires multiple interdomain contacts. The most common CF-causing mutation, F508del, occurs in NBD1 and results in misfolding and premature degradation of F508del-CFTR. VX-809 is an investigational CFTR corrector that partially restores CFTR function in people who are homozygous for F508del-CFTR. To identify the folding defect(s) in F508del-CFTR that must be repaired to treat CF, we explored the mechanism of VX-809 action. VX-809 stabilized an N-terminal domain in CFTR that contains only MSD1 and efficaciously restored function to CFTR forms that have missense mutations in MSD1. The action of VX-809 on MSD1 appears to suppress folding defects in F508del-CFTR by enhancing interactions among the NBD1, MSD1, and MSD2 domains. The ability of VX-809 to correct F508del-CFTR is enhanced when combined with mutations that improve F508del-NBD1 interaction with MSD2. These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR. PMID:23924900

VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1.

PubMed

Ren, Hong Yu; Grove, Diane E; De La Rosa, Oxana; Houck, Scott A; Sopha, Pattarawut; Van Goor, Fredrick; Hoffman, Beth J; Cyr, Douglas M

2013-10-01

Cystic fibrosis (CF) is a fatal genetic disorder associated with defective hydration of lung airways due to the loss of chloride transport through the CF transmembrane conductance regulator protein (CFTR). CFTR contains two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory domain, and its channel assembly requires multiple interdomain contacts. The most common CF-causing mutation, F508del, occurs in NBD1 and results in misfolding and premature degradation of F508del-CFTR. VX-809 is an investigational CFTR corrector that partially restores CFTR function in people who are homozygous for F508del-CFTR. To identify the folding defect(s) in F508del-CFTR that must be repaired to treat CF, we explored the mechanism of VX-809 action. VX-809 stabilized an N-terminal domain in CFTR that contains only MSD1 and efficaciously restored function to CFTR forms that have missense mutations in MSD1. The action of VX-809 on MSD1 appears to suppress folding defects in F508del-CFTR by enhancing interactions among the NBD1, MSD1, and MSD2 domains. The ability of VX-809 to correct F508del-CFTR is enhanced when combined with mutations that improve F508del-NBD1 interaction with MSD2. These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR.

Neural, Hormonal, and Cognitive Correlates of Metabolic Dysfunction and Emotional Reactivity.

PubMed

Wolf, Tovah; Tsenkova, Vera; Ryff, Carol D; Davidson, Richard J; Willette, Auriel A

2018-06-01

Prediabetes and type 2 diabetes (i.e., hyperglycemia) are characterized by insulin resistance. These problems with energy metabolism may exacerbate emotional reactivity to negatively valenced stimuli and related phenomena such as predisposition toward negative affect, as well as cognitive deficits. Higher emotional reactivity is seen with hyperglycemia and insulin resistance. However, it is largely unknown how metabolic dysfunction correlates with related neural, hormonal, and cognitive outcomes. Among 331 adults from the Midlife in the United States study, eye-blink response (EBR) we cross sectionally examined to gauge reactivity to negative, positive, or neutrally valenced pictures from international affect picture system stimuli proximal to an acoustic startle probe. Increased EBR to negative stimuli was considered an index of stress reactivity. Frontal alpha asymmetry, a biomarker of negative affect predisposition, was determined using resting electroencephalography. Baseline urinary cortisol output was collected. Cognitive performance was gauged using the Brief Test of Adult Cognition by telephone. Fasting glucose and insulin characterized hyperglycemia or the homeostatic model assessment of insulin resistance. Higher homeostatic model assessment of insulin resistance corresponded to an increased startle response, measured by EBR magnitude, for negative versus positive stimuli (R = 0.218, F(1,457) = 5.48, p = .020, euglycemia: M(SD) = .092(.776), hyperglycemia: M(SD) = .120(.881)). Participants with hyperglycemia versus euglycemia showed greater right frontal alpha asymmetry (F(1,307) = 6.62, p = .011, euglycemia: M(SD) = .018(.167), hyperglycemia: M(SD) = -.029(.160)), and worse Brief Test of Adult Cognition by telephone arithmetic performance (F(1,284) = 4.25, p = .040, euglycemia: M(SD) = 2.390(1.526), hyperglycemia: M(SD) = 1.920(1.462)). Baseline urinary cortisol (log10 μg/12 hours) was also dysregulated in individuals with hyperglycemia (F(1,324) = 5.09, p = .025, euglycemia: M(SD) = 1.052 ± .332, hyperglycemia: M(SD) = .961 (.362)). These results suggest that dysmetabolism is associated with increased emotional reactivity, predisposition toward negative affect, and specific cognitive deficits.

Prevalence and Risk Factors Associated with Musculoskeletal Discomfort in Spay and Neuter Veterinarians

PubMed Central

White, Sara C.

2013-01-01

Simple Summary This study examined musculoskeletal pain and discomfort in spay and neuter veterinarians using an internet-based questionnaire. Hand pain was most common in the right thumb and wrist, and body pain was most common in the lower back, shoulders, and neck. Several work-related risk factors for discomfort were discovered, including long career in spay and neuter, increasing weekly hours in surgery, and decreasing job satisfaction. Although most respondents felt posture during surgery was important, few spay and neuter veterinarians have received any instruction in posture or ergonomics in surgery. Abstract A cross-sectional study to investigate musculoskeletal discomfort (MSD) surveyed 219 veterinarians who currently or previously perform spays and neuters at least 4 hours per week. Participants were asked about the presence and severity of hand and body MSD during the previous month, whether MSD interfered with work or daily activities, whether they attributed their MSD to their spay/neuter work, and whether MSD had ever necessitated absence from work. The period prevalence of MSD was 99.1%, with 76.7% experiencing hand or wrist pain and 98.2% experiencing body pain. Hand discomfort was most commonly reported in the right thumb and/or thumb base (49.8%) and the right wrist (37.9%). Body discomfort was most commonly reported in the lower back (76.7%), shoulders (72.6%), and neck (71.7%). Increasing career length, increasing weekly hours in surgery and decreasing job satisfaction were the work-related factors with the greatest relative contribution accounting for variation in hand pain severity and total pain. Although 94.4% of respondents felt that posture during surgery is important, only 30.6% had received any instruction in posture and positioning for surgery. Future interventions should aim to optimize surgical efficiency, surgeon work schedules, and working environment. Analysis and intervention studies are required to determine further causes of MSD in these veterinarians and develop interventions to prevent MSD. PMID:26487311

Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis.

PubMed

Ghosh, Nilanjan; Karmali, Reem; Rocha, Vanderson; Ahn, Kwang Woo; DiGilio, Alyssa; Hari, Parameswaran N; Bachanova, Veronika; Bacher, Ulrike; Dahi, Parastoo; de Lima, Marcos; D'Souza, Anita; Fenske, Timothy S; Ganguly, Siddhartha; Kharfan-Dabaja, Mohamed A; Prestidge, Tim D; Savani, Bipin N; Smith, Sonali M; Sureda, Anna M; Waller, Edmund K; Jaglowski, Samantha; Herrera, Alex F; Armand, Philippe; Salit, Rachel B; Wagner-Johnston, Nina D; Fuchs, Ephraim; Bolaños-Meade, Javier; Hamadani, Mehdi

2016-09-10

Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD. © 2016 by American Society of Clinical Oncology.

Mortality with musculoskeletal disorders as underlying cause in Sweden 1997-2013: a time trend aggregate level study.

PubMed

Kiadaliri, Aliasghar A; Englund, Martin

2016-04-14

The aim was to assess time trend of mortality with musculoskeletal disorders (MSD) as underlying cause of death in Sweden from 1997 to 2013. We obtained data on MSD as underlying cause of death across age and sex groups from the National Board of Health and Welfare's Cause of Death Register. Age-standardized mortality rates per million population for all MSD, its six major subgroups, and all other ICD-10 (International Classification of Disease) chapters were calculated. We computed the average annual percent change (AAPC) in the mortality rates across age/sex groups using joinpoint regression analysis by fitting a regression line to the natural logarithm of the age-standardized mortality rates and calendar year as a predictor. There were a total of 7 976 deaths (0.5% of all causes deaths) with MSD as the underlying cause of death (32.5% of these deaths caused by rheumatoid arthritis [RA]). The overall age-standardized mortality rates (95% CI) were 16.0 (15.4 to 16.7) and 24.9 (24.1 to 25.7) per million among men and women, respectively (women/men rate ratio 1.55; 95%CI 1.47 to 1.63). On average, mortality rate declined by 2.3% per year and only circulatory system mortality had a more favourable decline than mortality with MSD as underlying cause. Among MSD the highest decline was observed in RA (3.7% per year) during study period. Across age groups, while there were generally stable or declining trends, spondylopathies and osteoporosis mortality among people ≥ 75 years increased by 2 and 1.5% per year, respectively. In overall, mortality with MSD as underlying cause has declined in Sweden over last two decades, with the highest decline for RA. However, there are variations across MSD subgroups which warrants further investigations.

Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis

PubMed Central

Ghosh, Nilanjan; Karmali, Reem; Rocha, Vanderson; Ahn, Kwang Woo; DiGilio, Alyssa; Hari, Parameswaran N.; Bachanova, Veronika; Bacher, Ulrike; Dahi, Parastoo; de Lima, Marcos; D’Souza, Anita; Fenske, Timothy S.; Ganguly, Siddhartha; Kharfan-Dabaja, Mohamed A.; Prestidge, Tim D.; Savani, Bipin N.; Smith, Sonali M.; Sureda, Anna M.; Waller, Edmund K.; Jaglowski, Samantha; Herrera, Alex F.; Armand, Philippe; Salit, Rachel B.; Wagner-Johnston, Nina D.; Fuchs, Ephraim; Bolaños-Meade, Javier

2016-01-01

Purpose Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor–based GVHD prophylaxis. Results Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD. PMID:27269951

Seeking Insights About Cycling Mood Disorders via Anonymized Search Logs

PubMed Central

White, Ryen W; Horvitz, Eric

2014-01-01

Background Mood disorders affect a significant portion of the general population. Cycling mood disorders are characterized by intermittent episodes (or events) of the disease. Objective Using anonymized Web search logs, we identify a population of people with significant interest in mood stabilizing drugs (MSD) and seek evidence of mood swings in this population. Methods We extracted queries to the Microsoft Bing search engine made by 20,046 Web searchers over six months, separately explored searcher demographics using data from a large external panel of users, and sought supporting information from people with mood disorders via a survey. We analyzed changes in information needs over time relative to searches on MSD. Results Queries for MSD focused on side effects and their relation to the disease. We found evidence of significant changes in search behavior and interests coinciding with days that MSD queries are made. These include large increases (>100%) in the access of nutrition information, commercial information, and adult materials. A survey of patients diagnosed with mood disorders provided evidence that repeated queries on MSD may come with exacerbations of mood disorder. A classifier predicting the occurrence of such queries one day before they are observed obtains strong performance (AUC=0.78). Conclusions Observed patterns in search behavior align with known behaviors and those highlighted by survey respondents. These observations suggest that searchers showing intensive interest in MSD may be patients who have been prescribed these drugs. Given behavioral dynamics, we surmise that the days on which MSD queries are made may coincide with commencement of mania or depression. Although we do not have data on mood changes and whether users have been diagnosed with bipolar illness, we see evidence of cycling in people who show interest in MSD and further show that we can predict impending shifts in behavior and interest. PMID:24568936

Open discovery: An integrated live Linux platform of Bioinformatics tools.

PubMed

Vetrivel, Umashankar; Pilla, Kalabharath

2008-01-01

Historically, live linux distributions for Bioinformatics have paved way for portability of Bioinformatics workbench in a platform independent manner. Moreover, most of the existing live Linux distributions limit their usage to sequence analysis and basic molecular visualization programs and are devoid of data persistence. Hence, open discovery - a live linux distribution has been developed with the capability to perform complex tasks like molecular modeling, docking and molecular dynamics in a swift manner. Furthermore, it is also equipped with complete sequence analysis environment and is capable of running windows executable programs in Linux environment. Open discovery portrays the advanced customizable configuration of fedora, with data persistency accessible via USB drive or DVD. The Open Discovery is distributed free under Academic Free License (AFL) and can be downloaded from http://www.OpenDiscovery.org.in.

The Emory Chemical Biology Discovery Center: leveraging academic innovation to advance novel targets through HTS and beyond.

PubMed

Johns, Margaret A; Meyerkord-Belton, Cheryl L; Du, Yuhong; Fu, Haian

2014-03-01

The Emory Chemical Biology Discovery Center (ECBDC) aims to accelerate high throughput biology and translation of biomedical research discoveries into therapeutic targets and future medicines by providing high throughput research platforms to scientific collaborators worldwide. ECBDC research is focused at the interface of chemistry and biology, seeking to fundamentally advance understanding of disease-related biology with its HTS/HCS platforms and chemical tools, ultimately supporting drug discovery. Established HTS/HCS capabilities, university setting, and expertise in diverse assay formats, including protein-protein interaction interrogation, have enabled the ECBDC to contribute to national chemical biology efforts, empower translational research, and serve as a training ground for young scientists. With these resources, the ECBDC is poised to leverage academic innovation to advance biology and therapeutic discovery.

Design and implementation of the one-step MSD adder of optical computer.

PubMed

Song, Kai; Yan, Liping

2012-03-01

On the basis of the symmetric encoding algorithm for the modified signed-digit (MSD), a 7*7 truth table that can be realized with optical methods was developed. And based on the truth table, the optical path structures and circuit implementations of the one-step MSD adder of ternary optical computer (TOC) were designed. Experiments show that the scheme is correct, feasible, and efficient. © 2012 Optical Society of America

Magnetic field line random walk in two-dimensional dynamical turbulence

NASA Astrophysics Data System (ADS)

Wang, J. F.; Qin, G.; Ma, Q. M.; Song, T.; Yuan, S. B.

2017-08-01

The field line random walk (FLRW) of magnetic turbulence is one of the important topics in plasma physics and astrophysics. In this article, by using the field line tracing method, the mean square displacement (MSD) of FLRW is calculated on all possible length scales for pure two-dimensional turbulence with the damping dynamical model. We demonstrate that in order to describe FLRW with the damping dynamical model, a new dimensionless quantity R is needed to be introduced. On different length scales, dimensionless MSD shows different relationships with the dimensionless quantity R. Although the temporal effect affects the MSD of FLRW and even changes regimes of FLRW, it does not affect the relationship between the dimensionless MSD and dimensionless quantity R on all possible length scales.

Common mental and musculoskeletal disorders as predictors of disability retirement among Finns.

PubMed

Kaila-Kangas, Leena; Haukka, Eija; Miranda, Helena; Kivekäs, Teija; Ahola, Kirsi; Luukkonen, Ritva; Shiri, Rahman; Kääriä, Sanna; Heliövaara, Markku; Leino-Arjas, Päivi

2014-08-01

The contribution of common mental disorders (CMD) co-occurring with chronic musculoskeletal disorders (MSD) to disability retirement is not known. A nationally representative sample (the Health 2000 survey) comprised 3943 occupationally active Finns aged 30-63. MSD and other chronic disorders were assessed by a physician in a standardized clinical examination, and CMD using the Composite International Diagnostic Interview. Disability pension data for 2000-2011 was retrieved from national pension records. Cox regression was used with censoring for death and pension other than that for disability. Covariate information was based on an interview. The baseline prevalence of CMD was 9.4% and of MSD 31.1%. CMD co-occurred with MSD in 3.3% of participants. The risks inflicted by CMD and MSD were additive. Thirty-eight per cent of the co-morbid subjects, 18% of those with CMD and 19% of those with MSD retired prematurely during the average follow-up of 8.6 years. Compared with those with neither type of disorder, the hazard ratio (HR) for disability pension was 2.4 (95% CI 1.7-2.7) for CMD only, 2.2 (1.8-2.7) for MSD only, and 4.1 (2.9-5.7) for the occurrence of both, allowing for age, gender, other chronic disorders, working conditions, and socio-economic and lifestyle factors. No synergistic or antagonistic interactive effects were observed. The determinants were measured only once and we had no information on incident disorders during the follow-up. It is important to identify subjects with both mental and musculoskeletal complaints in order to efficiently support their work ability. Copyright © 2014 Elsevier B.V. All rights reserved.

Aging underdamped scaled Brownian motion: Ensemble- and time-averaged particle displacements, nonergodicity, and the failure of the overdamping approximation.

PubMed

Safdari, Hadiseh; Cherstvy, Andrey G; Chechkin, Aleksei V; Bodrova, Anna; Metzler, Ralf

2017-01-01

We investigate both analytically and by computer simulations the ensemble- and time-averaged, nonergodic, and aging properties of massive particles diffusing in a medium with a time dependent diffusivity. We call this stochastic diffusion process the (aging) underdamped scaled Brownian motion (UDSBM). We demonstrate how the mean squared displacement (MSD) and the time-averaged MSD of UDSBM are affected by the inertial term in the Langevin equation, both at short, intermediate, and even long diffusion times. In particular, we quantify the ballistic regime for the MSD and the time-averaged MSD as well as the spread of individual time-averaged MSD trajectories. One of the main effects we observe is that, both for the MSD and the time-averaged MSD, for superdiffusive UDSBM the ballistic regime is much shorter than for ordinary Brownian motion. In contrast, for subdiffusive UDSBM, the ballistic region extends to much longer diffusion times. Therefore, particular care needs to be taken under what conditions the overdamped limit indeed provides a correct description, even in the long time limit. We also analyze to what extent ergodicity in the Boltzmann-Khinchin sense in this nonstationary system is broken, both for subdiffusive and superdiffusive UDSBM. Finally, the limiting case of ultraslow UDSBM is considered, with a mixed logarithmic and power-law dependence of the ensemble- and time-averaged MSDs of the particles. In the limit of strong aging, remarkably, the ordinary UDSBM and the ultraslow UDSBM behave similarly in the short time ballistic limit. The approaches developed here open ways for considering other stochastic processes under physically important conditions when a finite particle mass and aging in the system cannot be neglected.

Aging underdamped scaled Brownian motion: Ensemble- and time-averaged particle displacements, nonergodicity, and the failure of the overdamping approximation

NASA Astrophysics Data System (ADS)

Safdari, Hadiseh; Cherstvy, Andrey G.; Chechkin, Aleksei V.; Bodrova, Anna; Metzler, Ralf

2017-01-01

We investigate both analytically and by computer simulations the ensemble- and time-averaged, nonergodic, and aging properties of massive particles diffusing in a medium with a time dependent diffusivity. We call this stochastic diffusion process the (aging) underdamped scaled Brownian motion (UDSBM). We demonstrate how the mean squared displacement (MSD) and the time-averaged MSD of UDSBM are affected by the inertial term in the Langevin equation, both at short, intermediate, and even long diffusion times. In particular, we quantify the ballistic regime for the MSD and the time-averaged MSD as well as the spread of individual time-averaged MSD trajectories. One of the main effects we observe is that, both for the MSD and the time-averaged MSD, for superdiffusive UDSBM the ballistic regime is much shorter than for ordinary Brownian motion. In contrast, for subdiffusive UDSBM, the ballistic region extends to much longer diffusion times. Therefore, particular care needs to be taken under what conditions the overdamped limit indeed provides a correct description, even in the long time limit. We also analyze to what extent ergodicity in the Boltzmann-Khinchin sense in this nonstationary system is broken, both for subdiffusive and superdiffusive UDSBM. Finally, the limiting case of ultraslow UDSBM is considered, with a mixed logarithmic and power-law dependence of the ensemble- and time-averaged MSDs of the particles. In the limit of strong aging, remarkably, the ordinary UDSBM and the ultraslow UDSBM behave similarly in the short time ballistic limit. The approaches developed here open ways for considering other stochastic processes under physically important conditions when a finite particle mass and aging in the system cannot be neglected.

Depression and anxiety in multisomatoform disorder: prevalence and clinical predictors in primary care.

PubMed

Muller, Jacqueline E; Wentzel, Ignatius; Nel, Daniel G; Stein, Dan J

2008-06-01

Multisomatoform disorder (MSD) is characterised by > or = 3 medically inexplicable, troublesome physical symptoms, together with a > or = 2-year history of somatisation. The aim of this study was to evaluate the prevalence of depressive and anxiety disorders in a South African sample MSD, and to compare demographic and clinical outcomes in those patients with and without co-morbidity. Fifty-one adult outpatients with MSD were recruited from primary care clinics in the Cape Town metropolitan area. Participants were assessed for the presence of co-morbid depressive and anxiety disorders using the Mini Neuropsychiatric Interview-Plus (MINI-Plus). Outcomes included somatic symptom severity, disability, reported sick days and health care visits, pain experience, patient satisfaction with health services, and clinician-experienced difficulty. A current co-morbid depressive disorder was present in 29.4% (N = 15) of patients, and a current co-morbid anxiety disorder in 52.9% (N = 27). MSD patients with a co-morbid depressive disorder (current or lifetime) had significantly higher physical symptom counts, greater functional impairment, higher unemployment rates, more clinician-reported difficulties, and more dissatisfaction with health care services than those without the disorder. A larger number of co-morbid disorders was associated with greater overall disability. High rates of co-morbid depressive and anxiety disorders were present in a South African sample of primary care patients with MSD. Not all patients had co-morbidity, which is consistent with the view that MSD should be viewed as an independent disorder. However, co-morbid depressive disorders were associated with increased symptom severity and functional impairment, consistent with previous reports from developing countries, emphasising the importance of comorbidity in MSD.

Stone heterogeneity index on single-energy noncontrast computed tomography can be a positive predictor of urinary stone composition

PubMed Central

Lee, Jong Soo; Cho, Kang Su; Lee, Seung Hwan; Yoon, Young Eun; Kang, Dong Hyuk; Jeong, Won Sik; Jung, Hae Do; Kwon, Jong Kyou

2018-01-01

The aim of this study was to investigate the correlation between stone composition and single-energy noncontrast computed tomography (NCCT) parameters, including stone heterogeneity index (SHI) and mean stone density (MSD), in patients with urinary calculi. We retrospectively reviewed medical records of 255 patients who underwent operations or procedures for urinary stones or had spontaneous stone passage between December 2014 and October 2015. Among these, 214 patients with urinary calculi who underwent NCCT and stone composition analyses were included in the study. Maximal stone length (MSL), mean stone density (MSD), and stone heterogeneity index (SHI) were determined on pretreatment NCCT. The mean MSD (454.68±177.80 HU) and SHI (115.82±96.31 HU) of uric acid stones were lower than those of all other types. Based on post hoc tests, MSD was lower for uric acid stones than for the other types (vs. CaOx: P<0.001; vs. infection stones: P<0.001). SHI was lower for uric acid stones than for the other types (vs. CaOx: P<0.001; vs. infection stones: P<0.001) Receiver operating characteristic curves of uric acid stones for MSD and SHI demonstrated that SHI (cut-off value: 140.4 HU) was superior to MSD (cut-off value: 572.3 HU) in predicting uric acid stones (P<0.001). PMID:29649219

Phenotypic dysregulation of microglial activation in young offspring rats with maternal sleep deprivation-induced cognitive impairment

PubMed Central

Zhao, Qiuying; Xie, Xiaofang; Fan, Yonghua; Zhang, Jinqiang; Jiang, Wei; Wu, Xiaohui; Yan, Shuo; Chen, Yubo; Peng, Cheng; You, Zili

2015-01-01

Despite the potential adverse effects of maternal sleep deprivation (MSD) on physiological and behavioral aspects of offspring, the mechanisms remain poorly understood. The present study was intended to investigate the roles of microglia on neurodevelopment and cognition in young offspring rats with prenatal sleep deprivation. Pregnant Wistar rats received 72 h sleep deprivation in the last trimester of gestation, and their prepuberty male offspring were given the intraperitoneal injection with or without minocycline. The results showed the number of Iba1+ microglia increased, that of hippocampal neurogenesis decreased, and the hippocampus-dependent spatial learning and memory were impaired in MSD offspring. The classical microglial activation markers (M1 phenotype) IL-1β, IL-6, TNF-α, CD68 and iNOS were increased, while the alternative microglial activation markers (M2 phenotype) Arg1, Ym1, IL-4, IL-10 and CD206 were reduced in hippocampus of MSD offspring. After minocycline administration, the MSD offspring showed improvement in MWM behaviors and increase in BrdU+/DCX+ cells. Minocycline reduced Iba1+ cells, suppressed the production of pro-inflammatory molecules, and reversed the reduction of M2 microglial markers in the MSD prepuberty offspring. These results indicate that dysregulation in microglial pro- and anti-inflammatory activation is involved in MSD-induced inhibition of neurogenesis and impairment of spatial learning and memory. PMID:25830666

Musculoskeletal disorders in shipyard industry: prevalence, health care use, and absenteeism.

PubMed

Alexopoulos, Evangelos C; Tanagra, Dimitra; Konstantinou, Eleni; Burdorf, Alex

2006-11-24

It is unclear whether the well-known risk factors for the occurrence of musculoskeletal disorders (MSD) also play an important role in the determining consequences of MSD in terms of sickness absence and health care use. A cross-sectional study was conducted among 853 shipyard employees. Data were collected by questionnaire on physical and psychosocial workload, need for recovery, perceived general health, occurrence of musculoskeletal complaints, and health care use during the past year. Retrospective data on absenteeism were also available from the company register. In total, 37%, 22%, and 15% of employees reported complaints of low back, shoulder/neck, and hand/wrist during the past 12 months, respectively. Among all employees with at least one MSD, 27% visited a physician at least once and 20% took at least one period of sick leave. Various individual and work-related factors were associated with the occurrence of MSD. Health care use and absenteeism were strongest influenced by chronicity of musculoskeletal complaints and comorbidity with other musculoskeletal complaints and, to a lesser extent, by work-related factors. In programmes aimed at preventing the unfavourable consequences of MSD in terms of sickness absence and health care use it is important to identify the (individual) factors that determine the development of chronicity of complaints. These factors may differ from the well-know risk factors for the occurrence of MSD that are targeted in primary prevention.

Sub-Fickean Diffusion in a One-Dimensional Plasma Ring

NASA Astrophysics Data System (ADS)

Theisen, W. L.

2013-12-01

A one-dimensional dusty plasma ring is formed in a strongly-coupled complex plasma. The dust particles in the ring can be characterized as a one-dimensional system where the particles cannot pass each other. The particles perform random walks due to thermal motions. This single-file self diffusion is characterized by the mean-squared displacement (msd) of the individual particles which increases with time t. Diffusive processes that follow Ficks law predict that the msd increases as t, however, single-file diffusion is sub-Fickean meaning that the msd is predicted to increase as t^(1/2). Particle position data from the dusty plasma ring is analyzed to determine the scaling of the msd with time. Results are compared with predictions of single-file diffusion theory.

Open discovery: An integrated live Linux platform of Bioinformatics tools

PubMed Central

Vetrivel, Umashankar; Pilla, Kalabharath

2008-01-01

Historically, live linux distributions for Bioinformatics have paved way for portability of Bioinformatics workbench in a platform independent manner. Moreover, most of the existing live Linux distributions limit their usage to sequence analysis and basic molecular visualization programs and are devoid of data persistence. Hence, open discovery ‐ a live linux distribution has been developed with the capability to perform complex tasks like molecular modeling, docking and molecular dynamics in a swift manner. Furthermore, it is also equipped with complete sequence analysis environment and is capable of running windows executable programs in Linux environment. Open discovery portrays the advanced customizable configuration of fedora, with data persistency accessible via USB drive or DVD. Availability The Open Discovery is distributed free under Academic Free License (AFL) and can be downloaded from http://www.OpenDiscovery.org.in PMID:19238235

Oblique view of the Orbiter Discovery from an elevated platform ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Oblique view of the Orbiter Discovery from an elevated platform in the Vehicle Assembly Building at NASA's Kennedy Space Center. Note the Forward Reaction Control System (RCS) Module from the forward section and the Orbiter Maneuvering System (OMS)/RCS pods from the aft section have been removed. Ground support equipment called Strongbacks are attached to the payload bay doors and the Flight Deck windows have been covered by ground support equipment. Also note the scale figure standing by the Orbiter. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Evaporation Rates of Chemical Warfare Agents Using 5-CM Wind Tunnels I. CASARM Sulfur Mustard (HD) from Glass

DTIC Science & Technology

2008-10-01

Blank CONTENTS 1. INTRODUCTION 9 2. EXPERIMENTAL PROCEDURES 9 2.1 Wind Tunnel 9 2.2 Agent 10 2.3 Gas Chromatography /Mass Spectrometry Detection 10...protective equipment. 2.3 Gas Chromatography /Mass Spectrometry Detection (GC/MSD) The GC/MSD analysis of the thermal desorption tubes was performed on a...coupled to thermal desorption tubes that were analyzed using gas chromatography /mass spectrometry detection (GC/MSD). Differences between the tunnels

HLA-Matched Sibling versus Unrelated versus Haploidentical Related Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients Aged Over 60 Years with Acute Myeloid Leukemia: A Single-Center Donor Comparison.

PubMed

Devillier, Raynier; Legrand, Faezeh; Rey, Jérôme; Castagna, Luca; Fürst, Sabine; Granata, Angela; Charbonnier, Aude; Harbi, Samia; d'Incan, Evelyne; Pagliardini, Thomas; Faucher, Catherine; Lemarie, Claude; Saillard, Colombe; Calmels, Boris; Mohty, Bilal; Maisano, Valerio; Weiller, Pierre-Jean; Chabannon, Christian; Vey, Norbert; Blaise, Didier

2018-02-12

Haploidentical related donor (HRD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) was developed as a valid option for the treatment of acute myeloid leukemia (AML) in the absence of a matched donor. However, many investigators are reluctant to consider the use of this alternative in elderly patients, anticipating high morbidity. Here, we report a single-center comparison of HRD versus matched sibling donor (MSD) and unrelated donor (UD) allo-HSCT for patients with AML aged ≥60 years. Ninety-four patients (MSD: n = 31; UD: n = 30; HRD: n = 33) were analyzed. The median age was 65 (range, 60 to 73) years. We observed a higher cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) after UD allo-HSCT (MSD versus UD versus HRD: 3% versus 33% versus 6%, respectively; P = .006). Two-year cumulative incidence of moderate or severe chronic GVHD was 17%, 27%, and 16% in the MSD, UD, and HRD groups, respectively (P = .487). No difference was observed in the 2-year cumulative incidence of relapse or nonrelapse mortality (NRM) (relapse: MSD versus UD versus HRD: 32% versus 25% versus 25%, respectively; P = .411; NRM: MSD versus UD versus HRD: 19% versus 27% versus 24%, respectively; P = .709). At 2 years, progression-free survival, overall survival, and GVHD- and relapse-free survival were 48%, 50%, and 39%, respectively, in the MSD group; 48%, 51%, and 23%, respectively, in the UD group; and 50%, 52%, and 32%, respectively, in the HRD group, without statistically significant differences between the groups. We conclude that HRD allo-HSCT is highly feasible and no less efficient than MSD or UD allo-HSCT in patients with AML aged ≥60 years. Thus, the absence of a HLA-identical donor should not limit the consideration of allo-HSCT for the treatment of AML. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Measurement error of mean sac diameter and crown-rump length among pregnant women at Mulago hospital, Uganda.

PubMed

Ali, Sam; Byanyima, Rosemary Kusaba; Ononge, Sam; Ictho, Jerry; Nyamwiza, Jean; Loro, Emmanuel Lako Ernesto; Mukisa, John; Musewa, Angella; Nalutaaya, Annet; Ssenyonga, Ronald; Kawooya, Ismael; Temper, Benjamin; Katamba, Achilles; Kalyango, Joan; Karamagi, Charles

2018-05-04

Ultrasonography is essential in the prenatal diagnosis and care for the pregnant mothers. However, the measurements obtained often contain a small percentage of unavoidable error that may have serious clinical implications if substantial. We therefore evaluated the level of intra and inter-observer error in measuring mean sac diameter (MSD) and crown-rump length (CRL) in women between 6 and 10 weeks' gestation at Mulago hospital. This was a cross-sectional study conducted from January to March 2016. We enrolled 56 women with an intrauterine single viable embryo. The women were scanned using a transvaginal (TVS) technique by two observers who were blinded of each other's measurements. Each observer measured the CRL twice and the MSD once for each woman. Intra-class correlation coefficients (ICCs), 95% limits of agreement (LOA) and technical error of measurement (TEM) were used for analysis. Intra-observer ICCs for CRL measurements were 0.995 and 0.993 while inter-observer ICCs were 0.988 for CRL and 0.955 for MSD measurements. Intra-observer 95% LOA for CRL were ± 2.04 mm and ± 1.66 mm. Inter-observer LOA were ± 2.35 mm for CRL and ± 4.87 mm for MSD. The intra-observer relative TEM for CRL were 4.62% and 3.70% whereas inter-observer relative TEM were 5.88% and 5.93% for CRL and MSD respectively. Intra- and inter-observer error of CRL and MSD measurements among pregnant women at Mulago hospital were acceptable. This implies that at Mulago hospital, the error in pregnancy dating is within acceptable margins of ±3 days in first trimester, and the CRL and MSD cut offs of ≥7 mm and ≥ 25 mm respectively are fit for diagnosis of miscarriage on TVS. These findings should be extrapolated to the whole country with caution. Sonographers can achieve acceptable and comparable diagnostic accuracy levels of MSD and CLR measurements with proper training and adherence to practice guidelines.

Is neuroplasticity in the central nervous system the missing link to our understanding of chronic musculoskeletal disorders?

PubMed

Pelletier, René; Higgins, Johanne; Bourbonnais, Daniel

2015-02-12

Musculoskeletal rehabilitative care and research have traditionally been guided by a structural pathology paradigm and directed their resources towards the structural, functional, and biological abnormalities located locally within the musculoskeletal system to understand and treat Musculoskeletal Disorders (MSD). However the structural pathology model does not adequately explain many of the clinical and experimental findings in subjects with chronic MSD and, more importantly, treatment guided by this paradigm fails to effectively treat many of these conditions. Increasing evidence reveals structural and functional changes within the Central Nervous System (CNS) of people with chronic MSD that appear to play a prominent role in the pathophysiology of these disorders. These neuroplastic changes are reflective of adaptive neurophysiological processes occurring as the result of altered afferent stimuli including nociceptive and neuropathic transmission to spinal, subcortical and cortical areas with MSD that are initially beneficial but may persist in a chronic state, may be part and parcel in the pathophysiology of the condition and the development and maintenance of chronic signs and symptoms. Neuroplastic changes within different areas of the CNS may help to explain the transition from acute to chronic conditions, sensory-motor findings, perceptual disturbances, why some individuals continue to experience pain when no structural cause can be discerned, and why some fail to respond to conservative interventions in subjects with chronic MSD. We argue that a change in paradigm is necessary that integrates CNS changes associated with chronic MSD and that these findings are highly relevant for the design and implementation of rehabilitative interventions for this population. Recent findings suggest that a change in model and approach is required in the rehabilitation of chronic MSD that integrate the findings of neuroplastic changes across the CNS and are targeted by rehabilitative interventions. Effects of current interventions may be mediated through peripheral and central changes but may not specifically address all underlying neuroplastic changes in the CNS potentially associated with chronic MSD. Novel approaches to address these neuroplastic changes show promise and require further investigation to improve efficacy of currents approaches.

Orbiter processing facility service platform failure and redesign

NASA Technical Reports Server (NTRS)

Harris, Jesse L.

1988-01-01

In a high bay of the Orbiter Processing Facility (OPF) at the Kennedy Space Center, technicians were preparing the space shuttle orbiter Discovery for rollout to the Vehicle Assembly Building (VAB). A service platform, commonly referred to as an OPF Bucket, was being retracted when it suddenly fell, striking a technician and impacting Discovery's payload bay door. A critical component in the OPF Bucket hoist system had failed, allowing the platform to fall. The incident was thoroughly investigated by both NASA and Lockheed, revealing many design deficiencies within the system. The deficiencies and the design changes made to correct them are reviewed.

A Collaborative Web-Based Architecture For Sharing ToxCast Data

EPA Science Inventory

Collaborative Drug Discovery (CDD) has created a scalable platform that combines traditional drug discovery informatics with Web2.0 features. Traditional drug discovery capabilities include substructure, similarity searching and export to excel or sdf formats. Web2.0 features inc...

Berkeley Lab - Materials Sciences Division

Science.gov Websites

Berkeley Lab Berkeley Lab A-Z Index Phone Book Jobs Search DOE Search MSD Go MSD - Materials Investigators Division Staff Facilities and Centers Staff Jobs Safety Personnel Resources Committees In Case of

Prevention of musculoskeletal disorders within management systems: A scoping review of practices, approaches, and techniques.

PubMed

Yazdani, Amin; Neumann, W Patrick; Imbeau, Daniel; Bigelow, Philip; Pagell, Mark; Wells, Richard

2015-11-01

The purpose of this study was to identify and summarize the current research evidence on approaches to preventing musculoskeletal disorders (MSD) within Occupational Health and Safety Management Systems (OHSMS). Databases in business, engineering, and health and safety were searched and 718 potentially relevant publications were identified and examined for their relevance. Twenty-one papers met the selection criteria and were subjected to thematic analysis. There was very little literature describing the integration of MSD risk assessment and prevention into management systems. This lack of information may isolate MSD prevention, leading to difficulties in preventing these disorders at an organizational level. The findings of this review argue for further research to integrate MSD prevention into management systems and to evaluate the effectiveness of the approach. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Examining the interaction of force and repetition on musculoskeletal disorder risk: a systematic literature review.

PubMed

Gallagher, Sean; Heberger, John R

2013-02-01

Our aims were (a) to perform a systematic literature review of epidemiological studies that examined the interaction of force and repetition with respect to musculoskeletal disorder (MSD) risk, (b) to assess the relationship of force and repetition in fatigue failure studies of musculoskeletal tissues, and (c) to synthesize these findings. Many epidemiological studies have examined the effects of force and repetition on MSD risk; however, relatively few have examined the interaction between these risk factors. In a literature search, we identified 12 studies that allowed evaluation of a force-repetition interaction with respect to MSD risk. Identified studies were subjected to a methodological quality assessment and critical review. We evaluated laboratory studies of fatigue failure to examine tissue failure responses to force and repetition. Of the 12 epidemiological studies that tested a Force x Repetition interaction, 10 reported evidence of interaction. Based on these results, the suggestion is made that force and repetition may be interdependent in terms of their influence on MSD risk. Fatigue failure studies of musculoskeletal tissues show a pattern of failure that mirrors the MSD risk observed in epidemiological studies. Evidence suggests that there may be interdependence between force and repetition with respect to MSD risk. Repetition seems to result in modest increases in risk for low-force tasks but rapid increases in risk for high-force tasks. This interaction may be representative of a fatigue failure process in affected tissues.

Sanitation and Hygiene-Specific Risk Factors for Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study, 2007-2011: Case-Control Study.

PubMed

Baker, Kelly K; O'Reilly, Ciara E; Levine, Myron M; Kotloff, Karen L; Nataro, James P; Ayers, Tracy L; Farag, Tamer H; Nasrin, Dilruba; Blackwelder, William C; Wu, Yukun; Alonso, Pedro L; Breiman, Robert F; Omore, Richard; Faruque, Abu S G; Das, Sumon Kumar; Ahmed, Shahnawaz; Saha, Debasish; Sow, Samba O; Sur, Dipika; Zaidi, Anita K M; Quadri, Fahreen; Mintz, Eric D

2016-05-01

Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged <5 y old experiencing MSD and for 12,390 asymptomatic age, gender, and neighborhood-matched controls. An MSD case was defined as a child with a diarrheal illness <7 d duration comprising ≥3 loose stools in 24 h and ≥1 of the following: sunken eyes, skin tenting, dysentery, intravenous (IV) rehydration, or hospitalization. Site-specific conditional logistic regression models were used to explore the association between sanitation and hygiene exposures and MSD. Most households at six sites (>93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1-2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved.

A probabilistic fatigue analysis of multiple site damage

NASA Technical Reports Server (NTRS)

Rohrbaugh, S. M.; Ruff, D.; Hillberry, B. M.; Mccabe, G.; Grandt, A. F., Jr.

1994-01-01

The variability in initial crack size and fatigue crack growth is incorporated in a probabilistic model that is used to predict the fatigue lives for unstiffened aluminum alloy panels containing multiple site damage (MSD). The uncertainty of the damage in the MSD panel is represented by a distribution of fatigue crack lengths that are analytically derived from equivalent initial flaw sizes. The variability in fatigue crack growth rate is characterized by stochastic descriptions of crack growth parameters for a modified Paris crack growth law. A Monte-Carlo simulation explicitly describes the MSD panel by randomly selecting values from the stochastic variables and then grows the MSD cracks with a deterministic fatigue model until the panel fails. Different simulations investigate the influences of the fatigue variability on the distributions of remaining fatigue lives. Six cases that consider fixed and variable conditions of initial crack size and fatigue crack growth rate are examined. The crack size distribution exhibited a dominant effect on the remaining fatigue life distribution, and the variable crack growth rate exhibited a lesser effect on the distribution. In addition, the probabilistic model predicted that only a small percentage of the life remains after a lead crack develops in the MSD panel.

Computational comparison of quantum-mechanical models for multistep direct reactions

NASA Astrophysics Data System (ADS)

Koning, A. J.; Akkermans, J. M.

1993-02-01

We have carried out a computational comparison of all existing quantum-mechanical models for multistep direct (MSD) reactions. The various MSD models, including the so-called Feshbach-Kerman-Koonin, Tamura-Udagawa-Lenske and Nishioka-Yoshida-Weidenmüller models, have been implemented in a single computer system. All model calculations thus use the same set of parameters and the same numerical techniques; only one adjustable parameter is employed. The computational results have been compared with experimental energy spectra and angular distributions for several nuclear reactions, namely, 90Zr(p,p') at 80 MeV, 209Bi(p,p') at 62 MeV, and 93Nb(n,n') at 25.7 MeV. In addition, the results have been compared with the Kalbach systematics and with semiclassical exciton model calculations. All quantum MSD models provide a good fit to the experimental data. In addition, they reproduce the systematics very well and are clearly better than semiclassical model calculations. We furthermore show that the calculated predictions do not differ very strongly between the various quantum MSD models, leading to the conclusion that the simplest MSD model (the Feshbach-Kerman-Koonin model) is adequate for the analysis of experimental data.

Gestational sac and embryonic growth are not useful as criteria to define miscarriage: a multicenter observational study.

PubMed

Abdallah, Y; Daemen, A; Guha, S; Syed, S; Naji, O; Pexsters, A; Kirk, E; Stalder, C; Gould, D; Ahmed, S; Bottomley, C; Timmerman, D; Bourne, T

2011-11-01

We studied changes in mean gestational sac diameter (MSD) and embryonic crown-rump length (CRL) in intrauterine pregnancies of uncertain viability (IPUVs). We aimed to establish cut-off values for MSD and CRL growth that could be definitively associated with either viability or miscarriage, and to establish the relationship between growth in MSD and appearance of embryonic structures in the gestational sac. One thousand and sixty consecutive IPUVs were recruited prospectively from four London University hospitals: 462 with no yolk sac or embryo, 419 with a yolk sac but no embryo, and 179 with an embryo but no heartbeat visible. IPUV was defined as an empty gestational sac with or without a yolk sac but no embryo seen with MSD < 20 or < 30 mm (depending on center) or an embryo with no heartbeat and CRL < 6 mm or < 8 mm (depending on center). Scans were repeated 7-14 days later. The endpoint was viability at first-trimester screening ultrasonography between 11 and 14 weeks. Change in MSD and CRL between the first and second scans of each pregnancy was compared with respect to viability and appearance of embryonic structures using the two-sample t-test. The study included 359 pregnancies in which a gestational sac with or without embryo was identified at the follow-up scan 7-14 days later. Of these, 192 were viable and 167 non-viable at the 11-14-week scan. MSD growth was significantly higher in viable than non-viable pregnancies (mean 1.003 vs. 0.503 mm/day; P < 0.001, 95% CI of difference 0.403-0.596). A difference in CRL growth was found between the two groups (mean 0.673 vs. 0.148 mm/day; P < 0.001, 95% CI of difference 0.345-0.703). MSD growth of 0.6 mm/day was associated with a specificity for diagnosing miscarriage of 90.1%, a sensitivity of 61.7% and 19 false-positive test results. A cut-off of CRL growth rate of 0.2 mm/day gave a sensitivity of 76.3% and there were no false-positive test results for miscarriage. On repeat scan the failure of either a yolk sac or embryo to be visualized was always associated with miscarriage. There is an overlap in MSD growth rates between viable and non-viable IPUV. No cut-off exists for MSD growth below which a viable pregnancy could be safely excluded. A cut-off value for CRL growth of 0.2 mm/day was always associated with miscarriage. These data suggest that criteria to diagnose miscarriage based on growth in MSD and CRL are potentially unsafe. However, finding an empty gestational sac on two scans more than 7 days apart is highly likely to indicate miscarriage, irrespective of growth. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Self-Reported Musculoskeletal Disorders of the Distal Upper Extremities and the Neck in German Veterinarians: A Cross-Sectional Study

PubMed Central

Kozak, Agnessa; Schedlbauer, Grita; Peters, Claudia; Nienhaus, Albert

2014-01-01

Background Veterinary work is a physically demanding profession and entails the risk of injuries and diseases of the musculoskeletal system, particularly in the upper body. The prevalence of musculoskeletal disorders (MSD), the consequences and work-related accidents in German veterinarians were investigated. Work-related and individual factors associated with MSD of upper extremities and the neck were analyzed. Methods In 2011, a self-reporting Standardized Nordic Questionnaire was mailed to registered veterinarians in seven federal medical associations in Germany. A total of 3174 (38.4%) veterinarians responded. Logistic regression analysis was used to determine the association between risk factors and MSD-related impairment of daily activities. Results MSD in the neck (66.6%) and shoulder (60.5%) were more prevalent than in the hand (34.5%) or elbow (24.5%). Normal activities were affected in 28.7% (neck), 29.5% (shoulder), 19.4% (hand) and 14% (elbow) of the respondents. MSD in the upper body occurred significantly more often in large animal practitioners. Accidents that resulted in MSD were most frequently reported in the hand/wrist (14.3%) or in the shoulder (10.8%). The majority of all accidents in the distal upper extremities were caused by animals than by other factors (19% vs. 9.2%). For each area of the body, a specific set of individual and work-related factors contributed significantly to severe MSD: Older age, gender, previous injuries, BMI, practice type, veterinary procedures such as dentistry, rectal procedures and obstetric procedures as well as high demands and personal burnout. Conclusion From the perspective of occupational health and safety, it seems to be necessary to improve accident prevention and to optimize the ergonomics of specific tasks. Our data suggest the need for target group-specific preventive measures that also focus on the psychological factors at work. PMID:24586718

The Prevalence of and Risk Factors Associated with Musculoskeletal Disorders among Sonographers in Central China: A Cross-Sectional Study

PubMed Central

Feng, Qingmin; Liu, Shenglin; Yang, Lei; Xie, Mingxing

2016-01-01

Objective Studies from industrialized countries show that musculoskeletal disorders (MSD) occur commonly in sonographers. However, little is known about sonographers in China, where the awareness of ergonomics and MSD, workload, and available equipment/facilities may differ. We aimed to investigate the prevalence of MSD and associated risk factors in sonographers in central China. Methods A cross-sectional survey was conducted with 381 sonographers from 14 randomly selected tertiary hospitals in Hubei province, central China. Musculoskeletal symptoms (using the Nordic Questionnaire) and risk factors (mostly derived from the Health Benefit Trust survey instrument and the Dutch Musculoskeletal Questionnaire) were recorded. Multivariate logistic regression was used to quantify associations between risk factors and MSD. Results The 12-month period prevalence of MSD was 98.3%, being highest in the neck (93.5%) and shoulder (92.2%), followed by the lower back (83.2%), wrist/hand, upper back, and elbow. Factors contributing to neck pain were psychological fatigue, shoulder abduction and trunk bend-and-twist posture. Height-adjustable tables and chairs were protective factors. Shoulder pain was associated with female sex, health status, mental stress, shoulder abduction, and trunk bend-and-twist posture. Height-adjustable chairs and the awareness of adjusting the workstation before scanning were protective factors. Elbow pain was associated with health status and height-adjustable tables. Wrist/hand pain was associated with female sex, bending the wrist, and working with obese patients. Upper back pain was associated with shoulder abduction, height-adjustable chairs, and device location. Lower back pain was associated with the number of scans performed per day, awkward postures, bending the trunk, twisting or bending the neck forward, and using a footrest. Conclusions This study suggests a high prevalence of MSD in sonographers in central China. Hence, it is necessary to improve the awareness of MSD by training, and the ergonomics of their current work environment by addressing physical workload, and psychological and equipment/facility-related factors. PMID:27695095

Modified-Signed-Digit Optical Computing Using Fan-Out

NASA Technical Reports Server (NTRS)

Liu, Hua-Kuang; Zhou, Shaomin; Yeh, Pochi

1996-01-01

Experimental optical computing system containing optical fan-out elements implements modified signed-digit (MSD) arithmetic and logic. In comparison with previous optical implementations of MSD arithmetic, this one characterized by larger throughput, greater flexibility, and simpler optics.

Dissolution comparisons using a Multivariate Statistical Distance (MSD) test and a comparison of various approaches for calculating the measurements of dissolution profile comparison.

PubMed

Cardot, J-M; Roudier, B; Schütz, H

2017-07-01

The f 2 test is generally used for comparing dissolution profiles. In cases of high variability, the f 2 test is not applicable, and the Multivariate Statistical Distance (MSD) test is frequently proposed as an alternative by the FDA and EMA. The guidelines provide only general recommendations. MSD tests can be performed either on raw data with or without time as a variable or on parameters of models. In addition, data can be limited-as in the case of the f 2 test-to dissolutions of up to 85% or to all available data. In the context of the present paper, the recommended calculation included all raw dissolution data up to the first point greater than 85% as a variable-without the various times as parameters. The proposed MSD overcomes several drawbacks found in other methods.

Job Hazard Analyses for Musculoskeletal Disorder Risk Factors in Pressing Operations of Dry-cleaning Establishments.

PubMed

Park, Jung-Keun

2016-12-01

Job hazard analyses were conducted to assess exposure to musculoskeletal disorder (MSD) risk factors in seven workers of three dry-cleaning establishments. In accordance with the Washington State Ergonomics Rule, the analyses were performed in two separate steps: (1) observation and checklist approaches were made to identify a "caution zone job" in the seven workers' pressing operations across the three shops; and (2) detailed posture and motion analyses were undertaken to determine a "MSD hazard" in one worker's operation using a video technique. One "caution zone job" was identified and it was the pressing operation job in which five physical risk factors were found in the pressing operations. The detailed analyses confirmed that one "MSD hazard", i.e., awkward posture in shoulders, was prevalent in the pressing operations of the three dry-cleaning facilities. It would be desirable to reduce MSD risk factors including awkward shoulder posture in the dry-cleaning industry.

Anti-inflammatory activity of cannabinoid receptor 2 ligands in primary hPDL fibroblasts.

PubMed

Abidi, Ammaar H; Presley, Chaela S; Dabbous, Mustafa; Tipton, David A; Mustafa, Suni M; Moore, Bob M

2018-03-01

Approximately 65 million adults in the US have periodontitis, causing tooth loss and decreased quality of life. Cannabinoids modulate immune responses, and endocannabinoids are prevalent during oral cavity inflammation. Targets for intervention in periodontal inflammation are cannabinoid type 1 and 2 receptors (CB1R, CB2R), particularly CB2R because its levels increase during inflammation. We previously demonstrated that SMM-189 (CB2R inverse agonist) decreased pro-inflammatory cytokine production in primary microglial cells. The hypothesis of this study was that cannabinoids anandamide (AEA), HU-308 (CB2R selective agonist), and SMM-189 decrease pro-inflammatory IL-6 and MCP-1 production by primary human periodontal ligament fibroblasts (hPDLFs) stimulated with P. gingivalis LPS, TNF-α, or IL-1β. Cytotoxic effects of cannabinoid compounds (10 -4 -10 -6.5  M), LPS (1-1000 ng/ml), TNFα (10 ng/ml) and IL-1β (1 ng/ml) were assessed by measuring effects on cellular dehydrogenase activity. IL-6 and MCP-1 production were measured using Mesoscale Discovery (MSD) Human Pro-Inflammatory IL-6 and MSD Human Chemokine MCP-1 kits and analyzed using MSD Sector 2400 machine. EC 50 values for AEA, SMM-189, and HU-308 were 16 μM, 13 μM, and 7.3 μM respectively. LPS (1 μg/ml), TNF-α (10 ng/ml), and IL-1β (1 ng/ml) increased IL-6 and MCP-1 production, which were inhibited by AEA, SMM-189, and HU-308. AEA alone significantly increased IL-6, but not MCP-1 levels, but the other cannabinoids alone had no effect. The effective inhibition of LPS, TNF-α, IL-1β stimulated IL-6 and MCP-1 production by CB2R ligands in hPDLFs suggests that targeting the endocannabinoid system may lead to development of novel drugs for periodontal therapy, aiding strategies to improve oral health. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Prevalence of Musculoskeletal Disorder and Association with Productivity Loss: A Preliminary Study among Labour Intensive Manual Harvesting Activities in Oil Palm Plantation

PubMed Central

NG, Yee Guan; TAMRIN, Shamsul Bahri Mohd; YIK, Wai Mun; YUSOFF, Irwan Syah Mohd; MORI, Ippei

2013-01-01

Production agriculture such as harvesting in oil palm plantation has been frequently associated with MSD and significant loss of productivities. This study tends to evaluate from the viewpoint of health, the association between self-reported prevalence of musculoskeletal disorders and productivities; the impact of musculoskeletal disorders on productivity. A cross-sectional study was conducted among 143 harvesters in oil palm plantation. A general questionnaire was used to collect socio-demographic background data while Nordic Musculoskeletal Questionnaire was used to determine the prevalence of MSD. Expressed in 4 different indicators; daily harvesting quantity, efficiency score, sick leave and presenteeism, the productivity data were analysed for association. There is significant association between reported acute prevalence of MSD (within 7 d) and productivity loss in terms of presenteeism (χ2=5.088; p<0.05) as well as quantity of daily harvest (χ2=7.406; p<0.01). Logistic regression adjusted for age, BMI and smoking indicate that harvesters with MSD (past seven days) were more likely to be engaged in presenteeism (OR=2.87 95% CI=1.34, 6.14) and had lower daily productivity (OR=2.09 95% CI=1.02, 4.29) compared to harvesters without MSD (past 7 d). This study reveals that oil palm harvesters suffering acute MSD (for the past week) were likely to be still present to work and produce half lesser than their healthy counterparts. Thus, further study with comprehensive surveillance strategy is essential in order to determine the urgency or need of appropriate intervention. PMID:24292878

Investigation on musculoskeletal discomfort and ergonomics risk factors among production team members at an automotive component assembly plant

NASA Astrophysics Data System (ADS)

Aziz, Fazilah Abdul; Ghazalli, Zakri; Zuki Mohamed, Nik Mohd; Isfar, Amri

2017-10-01

Musculoskeletal discomfort (MSD) is very common condition in automotive industry. MSD is affecting the worker’s health, well-being and lower down the productivity. Therefore, the main objective of this study was to identify the prevalence of MSD and ergonomics risk factors among the production team members at a selected automotive component manufacturer in Malaysia. MSD data were collected by conducting structure interview with all participants by referring to the Cornell Musculoskeletal Disorder Questionnaire (CMDQ). Those production team members who achieved a total discomfort score for all body regions more than 100 was selected for job task assessment. The physical exposure risk factors of work related musculoskeletal disorders (WMSD) has evaluated by using Quick Exposure Check (QEC) techniques. The results of the study identified the severe MSD associated with production assembly team members. It is expected that the prevalence of MSD for those production assembly team members was lower back (75.4%), upper back (63.2%), right shoulder (61.4%), and right wrist (60%). The QEC analysis discovered that about 70% of job tasks had very high risks for neck posture and 60% had high risks for the back (in moving condition) and shoulder/arm postures. There were 80% of respondents have produced a high score for exposure risk to vibration. As a conclusion, the main implication of the current study is that special attention should be paid to the physical and psychosocial aspects in production team members with musculoskeletal discomfort to improve their safety, health, and well-being, maintain work ability and productivity.

[Musculoskeletal disorders and temporary disability. Characteristics and duration. Catalonia, 2007-2010].

PubMed

Manent Bistué, Ignasi; Ramada Rodilla, José Mª; Serra Pujadas, Consol

Musculoskeletal disorders (MSD) are the leading cause of sickness absence (SA) in Spain and the second in Catalonia. A greater knowledge of this field could allow the refocusing of social protection policies and interventions to reduce their frequency and duration. The objective of the study was to describe the characteristics and duration of SA due to MSD in Catalonia between 2007 and 2010. The study population included all incident SA episodes due to MSD during the period 2007-2010, registered in the Institut Català d'AvaluacionsMèdiques (ICAM) database.We selected the 10 most frequentMSD (824.646 episodes) and extracted 607.732 (74%) SA episodes. We calculated the median duration of SA and analyzed the differences with Mann-Whitney U or Kruskal-Wallis tests, and studied the differences with a post-hoc test. We also conducted a survival analysis using Kaplan-Meier curves. The most frequent MSD were low back pain and neck pain. Median duration was greater for gonarthrosis and calcific tendonitis of the shoulder. The median duration of SA episodes was greater when pain was due to an organic disorder, in women (Z=51770950,5; p<0,001), increased with age (K=17335,72; p<0,001), and was longer in self-employed workers (Z=20965263,1; p<0.001) and in those working in agriculture and livestock (K=736,822; p<0,001). This study shows that the median duration of SA caused by MSD is influenced by the diagnosis, sex, age, type of work and type of social protection. Copyright belongs to the Societat Catalana de Salut Laboral.

Identifying the most successful dose (MSD) in dose-finding studies in cancer.

PubMed

Zohar, Sarah; O'Quigley, John

2006-01-01

For a dose finding study in cancer, the most successful dose (MSD), among a group of available doses, is that dose at which the overall success rate is the highest. This rate is the product of the rate of seeing non-toxicities together with the rate of tumor response. A successful dose finding trial in this context is one where we manage to identify the MSD in an efficient manner. In practice we may also need to consider algorithms for identifying the MSD which can incorporate certain restrictions, the most common restriction maintaining the estimated toxicity rate alone below some maximum rate. In this case the MSD may correspond to a different level than that for the unconstrained MSD and, in providing a final recommendation, it is important to underline that it is subject to the given constraint. We work with the approach described in O'Quigley et al. [Biometrics 2001; 57(4):1018-1029]. The focus of that work was dose finding in HIV where both information on toxicity and efficacy were almost immediately available. Recent cancer studies are beginning to fall under this same heading where, as before, toxicity can be quickly evaluated and, in addition, we can rely on biological markers or other measures of tumor response. Mindful of the particular context of cancer, our purpose here is to consider the methodology developed by O'Quigley et al. and its practical implementation. We also carry out a study on the doubly under-parameterized model, developed by O'Quigley et al. but not

The prevalence of musculoskeletal disorder and association with productivity loss: a preliminary study among labour intensive manual harvesting activities in oil palm plantation.

PubMed

Ng, Yee Guan; Tamrin, Shamsul Bahri Mohd; Yik, Wai Mun; Yusoff, Irwan Syah Mohd; Mori, Ippei

2014-01-01

Production agriculture such as harvesting in oil palm plantation has been frequently associated with MSD and significant loss of productivities. This study tends to evaluate from the viewpoint of health, the association between self-reported prevalence of musculoskeletal disorders and productivities; the impact of musculoskeletal disorders on productivity. A cross-sectional study was conducted among 143 harvesters in oil palm plantation. A general questionnaire was used to collect socio-demographic background data while Nordic Musculoskeletal Questionnaire was used to determine the prevalence of MSD. Expressed in 4 different indicators; daily harvesting quantity, efficiency score, sick leave and presenteeism, the productivity data were analysed for association. There is significant association between reported acute prevalence of MSD (within 7 d) and productivity loss in terms of presenteeism (χ(2)=5.088; p<0.05) as well as quantity of daily harvest (χ(2)=7.406; p<0.01). Logistic regression adjusted for age, BMI and smoking indicate that harvesters with MSD (past seven days) were more likely to be engaged in presenteeism (OR=2.87 95% CI=1.34, 6.14) and had lower daily productivity (OR=2.09 95% CI=1.02, 4.29) compared to harvesters without MSD (past 7 d). This study reveals that oil palm harvesters suffering acute MSD (for the past week) were likely to be still present to work and produce half lesser than their healthy counterparts. Thus, further study with comprehensive surveillance strategy is essential in order to determine the urgency or need of appropriate intervention.

Looking for new biomarkers of skin wound vitality with a cytokine-based multiplex assay: preliminary study.

PubMed

Peyron, Pierre-Antoine; Baccino, Éric; Nagot, Nicolas; Lehmann, Sylvain; Delaby, Constance

2017-02-01

Determination of skin wound vitality is an important issue in forensic practice. No reliable biomarker currently exists. Quantification of inflammatory cytokines in injured skin with MSD ® technology is an innovative and promising approach. This preliminary study aims to develop a protocol for the preparation and the analysis of skin samples. Samples from ante mortem wounds, post mortem wounds, and intact skin ("control samples") were taken from corpses at the autopsy. After an optimization of the pre-analytical protocol had been performed in terms of skin homogeneisation and proteic extraction, the concentration of TNF-α was measured in each sample with the MSD ® approach. Then five other cytokines of interest (IL-1β, IL-6, IL-10, IL-12p70 and IFN-γ) were simultaneously quantified with a MSD ® multiplex assay. The optimal pre-analytical conditions consist in a proteic extraction from a 6 mm diameter skin sample, in a PBS buffer with triton 0,05%. Our results show the linearity and the reproductibility of the TNF-α quantification with MSD ® , and an inter- and intra-individual variability of the concentrations of proteins. The MSD ® multiplex assay is likely to detect differential skin concentrations for each cytokine of interest. This preliminary study was used to develop and optimize the pre-analytical and analytical conditions of the MSD ® method using injured and healthy skin samples, for the purpose of looking for and identifying the cytokine, or the set of cytokines, that may be biomarkers of skin wound vitality.

Is complementary and alternative medicine effective in job satisfaction among dentists with musculoskeletal disorders? A cross sectional study.

PubMed

Gupta, Devanand; Bhaskar, Dara John; Gupta, Rajendra Kumar; Jain, Ankita; Yadav, Priyanka; Dalai, Deepak Ranjan; Singh, Rajeshwar; Singh, Nisha; Chaudhary, Varunjeet; Singh, Ankit; Yadav, Ankit; Karim, Bushra

2014-01-01

Musculoskeletal disorders have serious impact on the profession of dentistry. There is common occurrence of pain due to incorrect posture in dental professionals. Complementary and alternative medicine (CAM) therapies may cast a new light on preventing and intercepting musculoskeletal disorders (MSD). An epidemiological study was conducted in an effort to contribute to the prevention of musculoskeletal disorders in dentistry. The purpose of this study was to determine the prevalence of MSD at dentists using CAM as a treatment and preventive modality for MSD and to compare job/career satisfaction between dentists who use CAM and conventional therapy (CT). Dentists registered in Uttrakhand state, India, under the Dental Council of India and registered members of the Indian Dental Association, Uttrakhand branch (N = 1496) were surveyed. Statistical analysis was conducted using SPSS 17. A response rate of 84% (N = 1257) was obtained, revealing that 90% (N = 1131) had the problem of MSD. Seventy three percentage (N = 826) of dentists with MSD reported the use of CAM and CT. Complementary and alternative medicine users reported greater overall health (72.7% vs. 51%, p < 0.001), job satisfaction (61.2% vs. 35%, p < 0.001) and work efficiency compared to CT users. Complementary and alternative medicine therapies may improve quality of life, reduce work interruption and enhance job satisfaction for dentists who suffers from MSD. Through the course of their studies, dentists should be equipped with knowledge on ergonomics and CAM therapies, such as yoga and others, to help them prevent musculoskeletal disorders more effectively.

Berkeley Lab - Materials Sciences Division

Science.gov Websites

MSD Support Human Resources Facilities & Space Planning Procurement and Property Proposals & ; Finance Templates Travel One-Stop Acknowledging MSD Support Human Resources Facilities & Space Planning Procurement and Property Proposals & Finance Templates Travel Human Resources General

Back and neck pain disability and upper limb symptoms of home healthcare workers: A case-control study from Northern Italy.

PubMed

Riccò, Matteo; Pezzetti, Federica; Signorelli, Carlo

2017-03-30

Work-related musculoskeletal disorders (MSD) are quite frequent in healthcare workers (HCWs), but data about MSD in home-based healthcare workers (HHWs) are lacking. In this study we describe the prevalence of MSD among Italian HHWs. A case-control study was carried out among 300 random-selected female HCWs, the sample comprising 100 HHWs, 100 HCWs with a low exposure to patient handling (MAPO - Movimentazione e Assistenza Pazienti Ospedalizzati - Movement and Assistance of Hospital Patients index 0-5) and 100 HCWs with high exposure to patient handling (MAPO index ≥ 5.01). As a negative control group, 200 visual display unit workers were also randomly selected. Musculoskeletal disorder cases were collected using a standardized case definition. A multivariate logistic regression analysis was performed comparing the MSD prevalence in the 4 groups. The overall prevalence of MSD was 17% in the reference group and 28.3% for HCWs. HHWs and HCWs with MAPO index ≥ 5.01 had similar prevalence of neck pain (9% and 11%, respectively), whereas lumbosacral pain prevalence was higher in the HHWs group (31%), with similar results in residential HCWs groups (21% in MAPO index 0-5 group and 25% in MAPO index ≥ 5.01 group). HCWs of group MAPO index ≥ 5.01 and HHWs showed the higher prevalence of upper limb complaints, with a prevalence of 20% and 10%, respectively. In multivariate regression analysis, prevalence of MSD complaints was quite similar in HHWs (adjusted odds ratio (OR_adj) = 2.335, 95% confidence interval (CI): 1.318-4.138) and in HCWs of the group MAPO ≥ 5.01 (OR_adj = 2.729, 95% CI: 1.552-4.797). The prevalence of MSD in the examined HCWs was relatively high, with HHWs appearing as a particularly high-risk group for lumbosacral back pain. In higher exposed HCWs, upper-limb symptoms were particularly frequent, probably reflecting the different tasks required to manage residential and homebased patients. In conclusion, this study reaffirms the high prevalence of MSD in HHWs, seemly similar to high-risk residential groups. Int J Occup Med Environ Health 2017;30(2):291-304. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

78 FR 41803 - Notice of Lodging of Proposed Amendment to Consent Decree Under the Clean Water Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-11

... original 2012 consent decree, the Metropolitan St. Louis Sewer District (``MSD'') agreed to undertake... specific combined sewer overflow control measures. MSD still is in the process of complying with the 2012...

Modified signed-digit trinary addition using synthetic wavelet filter

NASA Astrophysics Data System (ADS)

Iftekharuddin, K. M.; Razzaque, M. A.

2000-09-01

The modified signed-digit (MSD) number system has been a topic of interest as it allows for parallel carry-free addition of two numbers for digital optical computing. In this paper, harmonic wavelet joint transform (HWJT)-based correlation technique is introduced for optical implementation of MSD trinary adder implementation. The realization of the carry-propagation-free addition of MSD trinary numerals is demonstrated using synthetic HWJT correlator model. It is also shown that the proposed synthetic wavelet filter-based correlator shows high performance in logic processing. Simulation results are presented to validate the performance of the proposed technique.

Service user and family member perspectives on services for mental health, substance use/addiction, and violence: a qualitative study of their goals, experiences and recommendations.

PubMed

Haskell, Rebecca; Graham, Kathryn; Bernards, Sharon; Flynn, Andrea; Wells, Samantha

2016-01-01

Mental health and substance use disorders (MSD) are significant public health concerns that often co-occur with violence. To improve services that address MSD and violence [MSD(V)], it is critical to understand the perspectives of those most affected, people who have sought help for MSD(V) (i.e., "service users"), especially those with co-occurring issues, as well as their family members. We conducted structured interviews with 73 service users and 41 family members of service users in two Ontario communities (one urban, one rural) regarding their goals related to help-seeking, positive and negative experiences, and recommendations for improving systems of care. Overall, participants expressed a need for services that: (1) are respectful, nonjudgmental, and supportive, help service users to feel more 'normal' and include education to reduce stigma; (2) are accessible, varied and publicly funded, thereby meeting individual needs and addressing equity concerns at a systems level; and (3) are coordinated, holistic and inclusive of family members who often support service users. The findings provide a rich understanding of how service users and their families perceive services for MSD(V) issues and identify key ways to better meet their needs.

Fracture analysis of stiffened panels under biaxial loading with widespread cracking

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.; Dawicke, D. S.

1995-01-01

An elastic-plastic finite-element analysis with a critical crack-tip-opening angle (CTOA) fracture criterion was used to model stable crack growth and fracture of 2024-T3 aluminum alloy (bare and clad) panels for several thicknesses. The panels had either single or multiple-site damage (MSD) cracks subjected to uniaxial or biaxial loading. Analyses were also conducted on cracked stiffened panels with single or MSD cracks. The critical CTOA value for each thickness was determined by matching the failure load on a middle-crack tension specimen. Comparisons were made between the critical angles determined from the finite-element analyses and those measured with photographic methods. Predicted load-against-crack extension and failure loads for panels under biaxial loading, panels with MSD cracks, and panels with various number of stiffeners were compared with test data, whenever possible. The predicted results agreed well with the test data even for large-scale plastic deformations. The analyses were also able to predict stable tearing behavior of a large lead crack in the presence of MSD cracks. The analyses were then used to study the influence of stiffeners on residual strength in the presence of widespread fatigue cracking. Small MSD cracks were found to greatly reduce the residual strength for large lead cracks even for stiffened panels.

Fracture analysis of stiffened panels under biaxial loading with widespread cracking

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.

1995-01-01

An elastic-plastic finite-element analysis with a critical crack-tip opening angle (CTOA) fracture criterion was used to model stable crack growth and fracture of 2024-T3 aluminum alloy (bare and clad) panels for several thicknesses. The panels had either single or multiple-site damage (MSD) cracks subjected to uniaxial or biaxial loading. Analyses were also conducted on cracked stiffened panels with single or MSD cracks. The critical CTOA value for each thickness was determined by matching the failure load on a middle-crack tension specimen. Comparisons were made between the critical angles determined from the finite-element analyses and those measured with photographic methods. Predicted load-against-crack extension and failure loads for panels under biaxial loading, panels with MSD cracks, and panels with various numbers of stiffeners were compared with test data whenever possible. The predicted results agreed well with the test data even for large-scale plastic deformations. The analyses were also able to predict stable tearing behavior of a large lead crack in the presence of MSD cracks. The analyses were then used to study the influence of stiffeners on residual strength in the presence of widespread fatigue cracking. Small MSD cracks were found to greatly reduce the residual strength for large lead cracks even for stiffened panels.

Scientific workflows as productivity tools for drug discovery.

PubMed

Shon, John; Ohkawa, Hitomi; Hammer, Juergen

2008-05-01

Large pharmaceutical companies annually invest tens to hundreds of millions of US dollars in research informatics to support their early drug discovery processes. Traditionally, most of these investments are designed to increase the efficiency of drug discovery. The introduction of do-it-yourself scientific workflow platforms has enabled research informatics organizations to shift their efforts toward scientific innovation, ultimately resulting in a possible increase in return on their investments. Unlike the handling of most scientific data and application integration approaches, researchers apply scientific workflows to in silico experimentation and exploration, leading to scientific discoveries that lie beyond automation and integration. This review highlights some key requirements for scientific workflow environments in the pharmaceutical industry that are necessary for increasing research productivity. Examples of the application of scientific workflows in research and a summary of recent platform advances are also provided.

A laboratory study of multiple site damage in fuselage lap splices

DOT National Transportation Integrated Search

1993-12-01

This report details an experimental study that was conducted to explore the causes of : fuselage lap splice multiple site damage (MSD), which has been observed in several : aging aircraft. MSD was partially responsible for the 1988 Aloha Airlines acc...

Musculoskeletal disorders among nursing staff: a comparison of five hospitals in Uganda

PubMed Central

Munabi, Ian Guyton; Buwembo, William; Kitara, David Lagoro; Ochieng, Joseph; Nabirye, Rose Chalo; Mwaka, Erisa Sabakaki

2014-01-01

Introduction Low and middle income countries have severe nursing staff shortages which is associated with risk of poor quality of patient care and increased patient exposure to adverse events. This is accompanied with increased risk of musculoskeletal disorders to the nursing staff. This paper sets out to identify and compare factors associated with musculoskeletal disorders among nursing staff in 5 different hospitals in Uganda. Methods This was a cross sectional study on nurses from 5 different hospitals in Uganda. The study used a 12 month recall of reported Musculoskeletal disorders (MSD) among nurses. Ethical approval was obtained. Logistic regression analysis and ANOVA were used. The level of significance was set at 0.05 for all statistical tests. Results There were 755 respondents of whom 433 (58.4%) were nurses. The prevalence of MSD at anybody site was 80.8%. There were significant differences in reported MSD among nursing staff across different hospital settings which were worse in the public hospitals as compared to the private and private not for profit hospitals (p <0.001). Age (adjusted OR 1.03, 95% CI 1.01-1.06), self reported poor general health status (adj OR 4.5, 95% CI 2.8-7.24) and stress as suggested by waking up tired in the morning (adj OR 3.4, 95% CI 2.17-5.32) were significant associated factors for MSD in this population. Conclusiom Reported MSD among nursing staff across 5 different hospitals is worse in public as compared to private hospitals. Age, self reported poor general health status and stress were important factors for MSD in this population. PMID:25018829

Relationship between fumonisin contamination of feed and mystery swine disease. A case-control study.

PubMed

Bane, D P; Neumann, E J; Hall, W F; Harlin, K S; Slife, R L

1992-02-01

Fumonisin is a recently identified mycotoxin that has been shown to be the cause of pulmonary edema disease in swine and leukoencephalomalacia in horses. Mystery Swine Disease (MSD), is an economically devastating disease complex of unknown etiology that has been reported to have occurred in several swine producing states since 1988. To determine the relationship between MSD and fumonisin, a case-control study was carried out in Illinois in mid-1990. Feed samples collected from 12 case and 9 control farms were analyzed for fumonisin. Sera from swine on all farms was screened for titers against encephalomyocarditis (EMC) virus and concentrations of alpha-1 acid glycoprotein (an acute phase reactive protein). Fumonisin concentrations greater than or equal to 20 ppm were found on 1 control farm (1/9) and 8 case farms (8/12). Titers against EMC virus (greater than or equal to 1:16) were found on 5 control farms (5/9) and on 6 case farms (6/12). Farms with greater than or equal to 20 ppm fumonisin in the feed were at significantly increased risk (OR = 11.2, Fisher's exact test p = 0.037) for MSD. Furthermore, the pi2 test for trend was (p = 0.017), meaning that as the level of fumonisin in the feed increased, the risk of MSD also increased. The presence of EMC virus titers in the sow herd was not a significant risk for MSD (OR = 1.25, Fisher's exact test p = 0.75). Alpha-1 acid glycoprotein concentrations obtained from a 2-week old nursing pigs differed significantly (p = 0.0005) between MSD case and control herds.

Evaluation of self-reported work ability and usefulness of interventions among sick-listed patients.

PubMed

Wåhlin, Charlotte; Ekberg, Kerstin; Persson, Jan; Bernfort, Lars; Öberg, Birgitta

2013-03-01

To describe the types of intervention offered, to investigate the relationship between the type of intervention given, patient-reported usefulness of interventions and the effect on self-reported work ability in a cohort of sick-listed patients with musculoskeletal disorders (MSD) or mental disorders (MD). A prospective cohort study was performed including 810 newly sick-listed patients (MSD 62 % and MD 38 %). The baseline questionnaire included sociodemographic characteristics and measures of work ability. The 3-month follow-up questionnaire included measures of work ability, type of intervention received, and judgment of usefulness. Twenty-five percent received medical intervention modalities (MI) only, 45 % received a combination of medical and rehabilitative intervention modalities (CRI) and 31 % received work-related interventions combined with medical or rehabilitative intervention modalities (WI). Behavioural treatments were more common for patients with MD compared with MSD and exercise therapy were more common for patients with MSD. The most prevalent workplace interventions were adjustment of work tasks or the work environment. Among patients with MD, WI was found to be useful and improved work ability significantly more compared with only MI or CRI. For patients with MSD, no significant differences in improved work ability were found between interventions. Patients with MD who received a combination of work-related and clinical interventions reported best usefulness and best improvement in work ability. There was no difference in improvements in work ability between rehabilitation methods in the MSD group. There seems to be a gap between scientific evidence and praxis behaviour in the rehabilitation process. Unimodal rehabilitation was widely applied in the early rehabilitation process, a multimodal treatment approach was rare and only one-third received work-related interventions. It remains a challenge to understand who needs what type of intervention.

Effectiveness of participatory training for prevention of musculoskeletal disorders: a randomized controlled trial.

PubMed

Yu, Wenzhou; Yu, Ignatius T S; Wang, Xiaorong; Li, Zhimin; Wan, Sabrina; Qiu, Hong; Lin, Hui; Xie, Shaohua; Sun, Trevor

2013-05-01

Health and safety training program has been applied to prevent work-related musculoskeletal disorders (MSDs) in workplace. We evaluated the effectiveness of participatory training and didactic training programs on MSD prevention among frontline workers in Shenzhen, China. The authors randomly assigned 918 workers from intervention factories to receive participatory training (intervention group), and 907 workers from intervention factories and 1,654 workers from control factories to receive didactic training (control_1 group, control_2 group, respectively) from June 1, 2008 to November 30, 2009. Participants were asked to report experience of ache, pain or discomfort in 10 body parts at baseline and 1 year after training. Data were analyzed to compare the MSD prevalence 1 year before and 1 year after training in different groups from 2009 to 2010. The follow-up rate was 61 % (2,120/3,479) at 1 year after training. In the year after training, there were no statistically significant changes in the proportion of workers who reported MSD in any body part. MSD prevalence rates in the intervention group reduced from 16.8 to 9.9 % for lower extremities (χ(2) = 13.102, p < 0.001) and from 12.9 to 8.3 % (χ(2) = 9.433, p = 0.002) for wrist and finger at 1 year after training. However, the rates did not change significantly for upper back, lower back, neck, shoulder and elbow in the intervention group and for all 10 body parts in two control groups. Overall, the training programs did not seem to prevent the occurrence of MSD among frontline workers. However, participatory training might be effective to reduce MSD in the lower extremities and wrist and finger.

Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure.

PubMed

Smith, Sonali M; Godfrey, James; Ahn, Kwang Woo; DiGilio, Alyssa; Ahmed, Sairah; Agrawal, Vaibhav; Bachanova, Veronika; Bacher, Ulrike; Bashey, Asad; Bolaños-Meade, Javier; Cairo, Mitchell; Chen, Andy; Chhabra, Saurabh; Copelan, Edward; Dahi, Parastoo B; Aljurf, Mahmoud; Farooq, Umar; Ganguly, Siddhartha; Hertzberg, Mark; Holmberg, Leona; Inwards, David; Kanate, Abraham S; Karmali, Reem; Kenkre, Vaishalee P; Kharfan-Dabaja, Mohamed A; Klein, Andreas; Lazarus, Hillard M; Mei, Matthew; Mussetti, Alberto; Nishihori, Taiga; Ramakrishnan Geethakumari, Praveen; Saad, Ayman; Savani, Bipin N; Schouten, Harry C; Shah, Nirav; Urbano-Ispizua, Alvaro; Vij, Ravi; Vose, Julie; Sureda, Anna; Hamadani, Mehdi

2018-06-15

Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated. This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM). Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P < .0001). The 5-year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P < .0001). Patients with high-risk FL, as defined by ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. © 2018 American Cancer Society. © 2018 American Cancer Society.

Alessandra Lanzara

Science.gov Websites

Berkeley Lab Berkeley Lab A-Z Index Phone Book Jobs Search DOE Search MSD Go MSD - Materials Investigators Division Staff Facilities and Centers Staff Jobs Safety Personnel Resources Committees In Case of ; Finance Templates Travel One-Stop Investigators Division Staff Facilities and Centers Staff Jobs

ENHANCING TEST SENSITIVITY IN TOXICITY TESTING BY USING A STATISTICAL PERFORMANCE STANDARD

EPA Science Inventory

Previous reports have shown that within-test sensitivity can vary markedly among laboratories. Experts have advocated an empirical approach to controlling test variability based on the MSD, control means, and other test acceptability criteria. (The MSD represents the smallest dif...

36 CFR 3.13 - What conditions apply to the use of Marine Sanitation Devices (MSD)?

Code of Federal Regulations, 2013 CFR

2013-07-01

... the door to the space enclosing the toilets with a padlock or door handle key lock. (c) The... fresh water that is equipped with toilet facilities and/or a MSD that is capable of discharge, must lock...

36 CFR 3.13 - What conditions apply to the use of Marine Sanitation Devices (MSD)?

Code of Federal Regulations, 2012 CFR

2012-07-01

... the door to the space enclosing the toilets with a padlock or door handle key lock. (c) The... fresh water that is equipped with toilet facilities and/or a MSD that is capable of discharge, must lock...

36 CFR 3.13 - What conditions apply to the use of Marine Sanitation Devices (MSD)?

Code of Federal Regulations, 2014 CFR

2014-07-01

... the door to the space enclosing the toilets with a padlock or door handle key lock. (c) The... fresh water that is equipped with toilet facilities and/or a MSD that is capable of discharge, must lock...

Atomic mean-square displacement of a solid: A Green's-function approach

NASA Astrophysics Data System (ADS)

Shukla, R. C.; Hübschle, Hermann

1989-07-01

We have presented a Green's-function method of calculating the atomic mean-square displacement (MSD) of a solid. The method effectively sums a class of all anharmonic contributions to the MSD. From the point of view of perturbation theory (PT) our expression for MSD includes the lowest-order (λ2) PT contributions (cubic and quartic) with correct numerical coefficients. The numerical results obtained by this method in the high-temperature limit for a fcc nearest-neighbor Lennard-Jones-solid model are in excellent agreement with the Monte Carlo (MC) method for the same model over the entire temperature range of the solid. Highly accurate results for the order-λ2 PT contributions to MSD are obtained by eliminating the uncertainty in the convergence of the cubic contributions in the earlier work of Heiser, Shukla, and Cowly and they are now in much better agreement with the MC results but still inferior to the Green's-function method at the highest temperature.

Cardiovascular Organ-on-a-Chip Platforms for Drug Discovery and Development

PubMed Central

Ribas, João; Sadeghi, Hossein; Manbachi, Amir; Leijten, Jeroen; Brinegar, Katelyn; Zhang, Yu Shrike; Ferreira, Lino

2016-01-01

Abstract Cardiovascular diseases are prevalent worldwide and are the most frequent causes of death in the United States. Although spending in drug discovery/development has increased, the amount of drug approvals has seen a progressive decline. Particularly, adverse side effects to the heart and general vasculature have become common causes for preclinical project closures, and preclinical models do not fully recapitulate human in vivo dynamics. Recently, organs-on-a-chip technologies have been proposed to mimic the dynamic conditions of the cardiovascular system—in particular, heart and general vasculature. These systems pay particular attention to mimicking structural organization, shear stress, transmural pressure, mechanical stretching, and electrical stimulation. Heart- and vasculature-on-a-chip platforms have been successfully generated to study a variety of physiological phenomena, model diseases, and probe the effects of drugs. Here, we review and discuss recent breakthroughs in the development of cardiovascular organs-on-a-chip platforms, and their current and future applications in the area of drug discovery and development. PMID:28971113

Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study.

PubMed

Conan, Anne; O'Reilly, Ciara E; Ogola, Eric; Ochieng, J Benjamin; Blackstock, Anna J; Omore, Richard; Ochieng, Linus; Moke, Fenny; Parsons, Michele B; Xiao, Lihua; Roellig, Dawn; Farag, Tamer H; Nataro, James P; Kotloff, Karen L; Levine, Myron M; Mintz, Eric D; Breiman, Robert F; Cleaveland, Sarah; Knobel, Darryn L

2017-08-01

Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children's homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08-0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02-0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0-1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5-37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2-12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents.

Return-to-work for multiple jobholders with a work-related musculoskeletal disorder: A population-based, matched cohort in British Columbia.

PubMed

Maas, Esther T; Koehoorn, Mieke; McLeod, Christopher B

2018-01-01

Multiple jobholders (MJHs) have a higher risk of injury compared to single jobholders (SJHs), but it is unknown if return-to-work (RTW) after a work injury is affected by multiple jobholding. This study examined the association between multiple versus single jobholding and time to RTW for workers with a work-related musculoskeletal disorder (MSD). We used administrative workers' compensation data to identify injured workers with an accepted MSD lost-time claim between 2010-2014 in British Columbia, Canada (n = 125,639 SJHs and 9,029 MJHs). The outcome was days until RTW during twelve months after the first day of time-loss. The MJH and SJH cohorts were balanced using coarsened exact matching that yielded a final matched cohort of 8,389 MJHs and 8,389 SJHs. The outcome was estimated with Cox regression, using piecewise models, and the hazard ratios were stratified by type of MSD, a serious injury indicator, gender, weekly workdays preceding MSD, and wage categories. MJHs were less likely to RTW compared to SJHs within the first six months after the first time-loss day, with greater and longer lasting effects for males, workers with a serious injury, and a higher wage. No difference between MJHs and SJHs was found for workers who had a six- or seven-day work week preceding MSD, for workers with dislocations, and for workers who were still off work after six months. Overall, MJHs with a workweek of maximum five days are disadvantaged compared to SJHs in terms of RTW following a work-related MSD within the first six months after the first time-loss day. This difference might be caused by more precarious job contracts for MJHs that challenges RTW because of lack of support for modified work, higher workload, and reduced likelihood that MJHs file a workers' compensation claim. Despite adjusting for type of MSD, severity of injury and occupation, the differences persisted for the vast majority of the study sample.

Return-to-work for multiple jobholders with a work-related musculoskeletal disorder: A population-based, matched cohort in British Columbia

PubMed Central

Koehoorn, Mieke; McLeod, Christopher B.

2018-01-01

Introduction Multiple jobholders (MJHs) have a higher risk of injury compared to single jobholders (SJHs), but it is unknown if return-to-work (RTW) after a work injury is affected by multiple jobholding. This study examined the association between multiple versus single jobholding and time to RTW for workers with a work-related musculoskeletal disorder (MSD). Methods We used administrative workers’ compensation data to identify injured workers with an accepted MSD lost-time claim between 2010–2014 in British Columbia, Canada (n = 125,639 SJHs and 9,029 MJHs). The outcome was days until RTW during twelve months after the first day of time-loss. The MJH and SJH cohorts were balanced using coarsened exact matching that yielded a final matched cohort of 8,389 MJHs and 8,389 SJHs. The outcome was estimated with Cox regression, using piecewise models, and the hazard ratios were stratified by type of MSD, a serious injury indicator, gender, weekly workdays preceding MSD, and wage categories. Results MJHs were less likely to RTW compared to SJHs within the first six months after the first time-loss day, with greater and longer lasting effects for males, workers with a serious injury, and a higher wage. No difference between MJHs and SJHs was found for workers who had a six- or seven-day work week preceding MSD, for workers with dislocations, and for workers who were still off work after six months. Conclusions Overall, MJHs with a workweek of maximum five days are disadvantaged compared to SJHs in terms of RTW following a work-related MSD within the first six months after the first time-loss day. This difference might be caused by more precarious job contracts for MJHs that challenges RTW because of lack of support for modified work, higher workload, and reduced likelihood that MJHs file a workers’ compensation claim. Despite adjusting for type of MSD, severity of injury and occupation, the differences persisted for the vast majority of the study sample. PMID:29614128

Overview of a multi-stakeholder dialogue around Shared Services for Health: the Digital Health Opportunity in Bangladesh.

PubMed

Ashraf, Sania; Moore, Carolyn; Gupta, Vaibhav; Chowdhury, Anir; Azad, Abul K; Singh, Neelu; Hagan, David; Labrique, Alain B

2015-12-09

National level policymaking and implementation includes multiple stakeholders with varied interests and priorities. Multi-stakeholder dialogues (MSDs) can facilitate consensus building through collective identification of challenges, recognition of shared goals and interests, and creation of solution pathways. This can shape joint planning and implementation for long-term efficiency in health and other sectors. Scaling up the effective use of information and communication technologies (ICTs) requires cohesive strategic planning towards a shared goal. In Bangladesh, the government and partners convened an MSD in March 2015 to increase stakeholder engagement in policymaking and implementation of a national ICT or electronic or mobile health (eHealth or mHealth) strategy, which seeks to incorporate ICTs into the national health system, aligning with the Digital Bangladesh Vision 2021. Relevant stakeholders were identified and key priorities and challenges were mapped through key informant interviews. An MSD was conducted with key stakeholders in Dhaka, Bangladesh. The MSD included presentations, group option generation, agreement and prioritization of barriers to scaling up ICTs. The MSD approach to building consensus on key priorities highlights the value of dialogue and collaboration with relevant stakeholders to encourage country ownership of nationwide efforts such as ICT scale-up. This MSD showed the dynamic context in which stakeholders operate, including those from academia, donors and foundations, healthcare professionals, associations, multilateral organizations, non-governmental organizations, partner countries and the private sector. Through this MSD, participants improved understanding of each other's contributions and interests, identified existing relationships, and agreed on policy and implementation gaps that needed to be filled. Collaboration among stakeholders in ICT efforts and research can promote a cohesive approach to scaling up, as well as improve policymaking by integrating interests and feedback of different key cross sectoral actors. MSDs can align stakeholders to identify challenges and solution pathways, and lead to coordinated action and accountability for resources and results. In addition, the MSD template and approach has been useful to guide ICT scale up in Bangladesh and could be replicated in other contexts to facilitate multi-constituency, multi-sector collaboration.

Tracer particles in two-dimensional elastic networks diffuse logarithmically slow

NASA Astrophysics Data System (ADS)

Lizana, Ludvig; Ambjörnsson, Tobias; Lomholt, Michael A.

2017-01-01

Several experiments on tagged molecules or particles in living systems suggest that they move anomalously slow—their mean squared displacement (MSD) increase slower than linearly with time. Leading models aimed at understanding these experiments predict that the MSD grows as a power law with a growth exponent that is smaller than unity. However, in some experiments the growth is so slow (fitted exponent  ˜0.1-0.2) that they hint towards other mechanisms at play. In this paper, we theoretically demonstrate how in-plane collective modes excited by thermal fluctuations in a two dimensional membrane lead to logarithmic time dependence for the the tracer particle’s MSD.

A Common Platform for Antibiotic Dereplication and Adjuvant Discovery.

PubMed

Cox, Georgina; Sieron, Arthur; King, Andrew M; De Pascale, Gianfranco; Pawlowski, Andrew C; Koteva, Kalinka; Wright, Gerard D

2017-01-19

Solving the antibiotic resistance crisis requires the discovery of new antimicrobial drugs and the preservation of existing ones. The discovery of inhibitors of antibiotic resistance, antibiotic adjuvants, is a proven example of the latter. A major difficulty in identifying new antibiotics is the frequent rediscovery of known compounds, necessitating laborious "dereplication" to identify novel chemical entities. We have developed an antibiotic resistance platform (ARP) that can be used for both the identification of antibiotic adjuvants and for antibiotic dereplication. The ARP is a cell-based array of mechanistically distinct individual resistance elements in an identical genetic background. In dereplication mode, we demonstrate the rapid identification, and thus discrimination, of common antibiotics. In adjuvant discovery mode, we show that the ARP can be harnessed in screens to identify inhibitors of resistance. The ARP is therefore a powerful tool that has broad application in confronting the resistance crisis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Case Study: Installation and Monitoring of Green Infrastructure Stormwater Controls in Louisville, Kentucky

EPA Science Inventory

In 2005, the Louisville and Jefferson County Metropolitan Sewer District (MSD) entered into a Consent Decree with the U.S. Environmental Protection Agency (EPA), Kentucky Department for Environmental Protection, and the U.S. Department of Justice. In 2009, MSD submitted the Inte...

Estimating the returns to United Kingdom publicly funded musculoskeletal disease research in terms of net value of improved health outcomes.

PubMed

Glover, Matthew; Montague, Erin; Pollitt, Alexandra; Guthrie, Susan; Hanney, Stephen; Buxton, Martin; Grant, Jonathan

2018-01-10

Building on an approach applied to cardiovascular and cancer research, we estimated the economic returns from United Kingdom public- and charitable-funded musculoskeletal disease (MSD) research that arise from the net value of the improved health outcomes in the United Kingdom. To calculate the economic returns from MSD-related research in the United Kingdom, we estimated (1) the public and charitable expenditure on MSD-related research in the United Kingdom between 1970 and 2013; (2) the net monetary benefit (NMB), derived from the health benefit in quality adjusted life years (QALYs) valued in monetary terms (using a base-case value of a QALY of £25,000) minus the cost of delivering that benefit, for a prioritised list of interventions from 1994 to 2013; (3) the proportion of NMB attributable to United Kingdom research; and (4) the elapsed time between research funding and health gain. The data collected from these four key elements were used to estimate the internal rate of return (IRR) from MSD-related research investments on health benefits. We analysed the uncertainties in the IRR estimate using a one-way sensitivity analysis. Expressed in 2013 prices, total expenditure on MSD-related research from 1970 to 2013 was £3.5 billion, and for the period used to estimate the rate of return, 1978-1997, was £1.4 billion. Over the period 1994-2013 the key interventions analysed produced 871,000 QALYs with a NMB of £16 billion, allowing for the net NHS costs resulting from them and valuing a QALY at £25,000. The proportion of benefit attributable to United Kingdom research was 30% and the elapsed time between funding and impact of MSD treatments was 16 years. Our best estimate of the IRR from MSD-related research was 7%, which is similar to the 9% for CVD and 10% for cancer research. Our estimate of the IRR from the net health gain to public and charitable funding of MSD-related research in the United Kingdom is substantial, and justifies the research investments made between 1978 and 1997. We also demonstrated the applicability of the approach previously used in assessing the returns from cardiovascular and cancer research. Inevitably, with a study of this kind, there are a number of important assumptions and caveats that we highlight, and these can inform future research.

Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study.

PubMed

Ruggeri, Annalisa; Battipaglia, Giorgia; Labopin, Myriam; Ehninger, Gerhard; Beelen, Dietrich; Tischer, Johanna; Ganser, Arnold; Schwerdtfeger, Rainer; Glass, Bertram; Finke, Jurgen; Michallet, Mauricette; Stelljes, Matthias; Jindra, Pavel; Arnold, Renate; Kröger, Nicolaus; Mohty, Mohamad; Nagler, Arnon

2016-09-17

Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated. We analyzed 1554 adults with AML transplanted from MSD (n = 961) or UD (n = 593, HLA-matched 10/10, n = 481; 9/10, n = 112). Compared to MSD, UD recipients were older (49 vs 52 years, p = 0.001), transplanted more recently (2009 vs 2006, p = 0.001), and with a longer interval to transplant (10 vs 9 months, p = 0.001). Conditioning regimen was more frequently myeloablative for patients transplanted with a MSD (61 vs 46 %, p = 0.001). Median follow-up was 28 (range 3-157) months. Cumulative incidence (CI) of neutrophil engraftment (p = 0.07), grades II-IV acute GVHD (p = 0.11), chronic GVHD (p = 0.9), and non-relapse mortality (NRM, p = 0.24) was not different according to the type of donor. At 2 years, CI of relapse (relapse incidence (RI)) was 57 vs 49 % (p = 0.001). Leukemia-free survival (LFS) at 2 years was 21 vs 26 % (p = 0.001), and overall survival (OS) was 26 vs 33 % (p = 0.004) for MSD vs UD, respectively. Chronic GVHD as time-dependent variable was associated with lower RI (HR 0.78, p = 0.05), higher NRM (HR 1.71, p = 0.001), and higher OS (HR 0.69, p = 0.001). According to HLA match, RI was 57 vs 50 vs 45 %, (p = 0.001) NRM was 23 vs 23 vs 29 % (p = 0.26), and LFS at 2 years was 21 vs 27 vs 25 % (p = 0.003) for MSD, 10/10, and 9/10 UD, respectively. In multivariate analysis adjusted for differences between the two groups, UD was associated with lower RI (HR 0.76, p = 0.001) and higher LFS (HR 0.83, p = 0.001) compared to MSD. Interval between diagnosis and transplant was the other factor associated with better outcomes (RI (HR 0.62, p < 0.001) and LFS (HR 0.67, p < 0.001)). Transplantation using UD was associated with better LFS and lower RI compared to MSD for high-risk patients with AML transplanted in first relapse.

Comparable Outcomes after HLA-Matched Sibling and Alternative Donor Hematopoietic Cell Transplantation for Children with Fanconi Anemia and Severe Aplastic Anemia.

PubMed

Ebens, Christen L; DeFor, Todd E; Tryon, Rebecca; Wagner, John E; MacMillan, Margaret L

2018-04-01

Fanconi anemia (FA)-associated severe aplastic anemia (SAA) requires allogeneic hematopoietic cell transplantation (HCT) for cure. With the evolution of conditioning regimens over time, outcomes of alternative donor HCT (AD-HCT) have improved dramatically. We compared outcomes of HLA-matched sibling donor HCT (MSD-HCT; n = 17) and AD-HCT (n = 57) performed for FA-associated SAA at a single institution between 2001 and 2016. Overall survival at 5 years was 94% for MSD-HCT versus 86% for AD-HCT, neutrophil engraftment was 100% versus 95%, platelet recovery was 100% versus 89%, grade II-IV acute graft-versus-host disease (GVHD) was 6% versus 12%, grade III-IV acute GVHD was 6% versus 4%, and chronic GVHD was 0 versus 7%, with no statistically significant differences by type of transplant. The use of UCB was associated with decreased rates of neutrophil recovery in AD-HCT and platelet recovery in both MSD-HCT and AD-HCT. A trend toward a higher serious infection density before day +100 post-HCT was observed in AD-HCT compared with MSD-HCT (P = .02). These data demonstrate that AD-HCT should be considered at the same time as MSD-HCT for patients with FA-associated SAA. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Is there a stronger graft-versus-leukemia effect using HLA-haploidentical donors compared with HLA-identical siblings?

PubMed

Ringdén, O; Labopin, M; Ciceri, F; Velardi, A; Bacigalupo, A; Arcese, W; Ghavamzadeh, A; Hamladji, R M; Schmid, C; Nagler, A; Mohty, M

2016-02-01

Haploidentical hematopoietic stem cell transplants (HSCTs) are increasingly used, but it is unknown whether they have a stronger graft-versus-leukemia (GVL) effect. We analyzed 10 679 acute leukemia patients who underwent HSCT from an HLA-matched sibling donor (MSD, n=9815) or a haploidentical donor (⩾2 HLA-antigen disparity, n=864) between 2007 and 2012, reported to the European Group for Blood and Marrow Transplantation. In a Cox regression model, acute and chronic graft-versus-host disease (GVHD) was added as time-dependent variables. There was no difference in probability of relapse between recipients of haploidentical and MSD grafts. Factors of importance for relapse after T-cell-replete grafts included remission status at HSCT, Karnofsky score ⩽80, acute GVHD of grade II or higher and chronic GVHD (P<10(-5)). Patients with post-transplant cyclophosphamide (n=194) had similar outcome as other T-cell-replete haploidentical transplants (n=369). Non-relapse mortality was significantly higher in the haploidentical group compared with that in MSD patients (P<10(-5)). Leukemia-free survival was superior in the MSD patients receiving T-cell-replete (P<10(-5)) or T-cell-depleted grafts (P=0.0006). The risk of relapse was the same in acute leukemia patients who received haploidentical donor grafts as in those given MSD transplants, suggesting a similar GVL effect.

Effects of Modified Simiao Decoction on IL-1 β and TNF α Secretion in Monocytic THP-1 Cells with Monosodium Urate Crystals-Induced Inflammation.

PubMed

Liu, Ya-Fei; Tu, Sheng-Hao; Chen, Zhe; Wang, Yu; Hu, Yong-Hong; Dong, Hui

2014-01-01

Simiao pill, a Chinese herbal formula containing four herbs, has been used in the treatment of gouty arthritis for many years. The aim of this study was to explore the effects of modified Simiao decoction (MSD) on IL-1 β and TNF α secretion in monocytic THP-1 cells with monosodium urate (MSU) crystals-induced inflammation. The MSU crystals-induced inflammation model in THP-1 cells was successfully established by the stimulation of phorbol 12-myristate 13-acetate (PMA) and MSU crystals. Then, the MSD-derived serum or control serum extracted from rat was administered to different treatment groups. The morphology of MSU crystals and THP-1 cells was observed. IL-1 β and TNF α protein expression in supernatant of THP-1 cells were determined by ELISA. Our data demonstrated that MSU crystals induced time-dependent increase of IL-1 β and TNF α . Moreover, MSD significantly decreased IL-1 β release in THP-1 cells with MSU crystals-induced inflammation. These results suggest that MSD is promising in the treatment of MSU crystals-induced inflammation in THP-1 cells. MSD may act as an anti-IL-1 agent in treating gout. The underlying mechanism may be related to NALP3 inflammasome which needs to be validated in future studies.

Effects of Modified Simiao Decoction on IL-1β and TNFα Secretion in Monocytic THP-1 Cells with Monosodium Urate Crystals-Induced Inflammation

PubMed Central

Liu, Ya-Fei; Tu, Sheng-Hao; Chen, Zhe; Wang, Yu; Hu, Yong-Hong; Dong, Hui

2014-01-01

Simiao pill, a Chinese herbal formula containing four herbs, has been used in the treatment of gouty arthritis for many years. The aim of this study was to explore the effects of modified Simiao decoction (MSD) on IL-1β and TNFα secretion in monocytic THP-1 cells with monosodium urate (MSU) crystals-induced inflammation. The MSU crystals-induced inflammation model in THP-1 cells was successfully established by the stimulation of phorbol 12-myristate 13-acetate (PMA) and MSU crystals. Then, the MSD-derived serum or control serum extracted from rat was administered to different treatment groups. The morphology of MSU crystals and THP-1 cells was observed. IL-1β and TNFα protein expression in supernatant of THP-1 cells were determined by ELISA. Our data demonstrated that MSU crystals induced time-dependent increase of IL-1β and TNFα. Moreover, MSD significantly decreased IL-1β release in THP-1 cells with MSU crystals-induced inflammation. These results suggest that MSD is promising in the treatment of MSU crystals-induced inflammation in THP-1 cells. MSD may act as an anti-IL-1 agent in treating gout. The underlying mechanism may be related to NALP3 inflammasome which needs to be validated in future studies. PMID:24999366

Transport Properties of Ibuprofen Encapsulated in Cyclodextrin Nanosponge Hydrogels: A Proton HR-MAS NMR Spectroscopy Study.

PubMed

Ferro, Monica; Castiglione, Franca; Punta, Carlo; Melone, Lucio; Panzeri, Walter; Rossi, Barbara; Trotta, Francesco; Mele, Andrea

2016-08-15

The chemical cross-linking of β-cyclodextrin (β-CD) with ethylenediaminetetraacetic dianhydride (EDTA) led to branched polymers referred to as cyclodextrin nanosponges (CDNSEDTA). Two different preparations are described with 1:4 and 1:8 CD-EDTA molar ratios. The corresponding cross-linked polymers were contacted with 0.27 M aqueous solution of ibuprofen sodium salt (IP) leading to homogeneous, colorless, drug loaded hydrogels. The systems were characterized by high resolution magic angle spinning (HR-MAS) NMR spectroscopy. Pulsed field gradient spin echo (PGSE) NMR spectroscopy was used to determine the mean square displacement (MSD) of IP inside the polymeric gel at different observation times td. The data were further processed in order to study the time dependence of MSD: MSD = f(td). The proposed methodology is useful to characterize the different diffusion regimes that, in principle, the solute may experience inside the hydrogel, namely normal or anomalous diffusion. The full protocols including the polymer preparation and purification, the obtainment of drug-loaded hydrogels, the NMR sample preparation, the measurement of MSD by HR-MAS NMR spectroscopy and the final data processing to achieve the time dependence of MSD are here reported and discussed. The presented experiments represent a paradigmatic case and the data are discussed in terms of innovative approach to the characterization of the transport properties of an encapsulated guest within a polymeric host of potential application for drug delivery.

Studying the association between musculoskeletal disorders, quality of life and mental health. A primary care pilot study in rural Crete, Greece

PubMed Central

2009-01-01

Background The burden of musculoskeletal disorders (MSD) on the general health and well-being of the population has been documented in various studies. The objective of this study was to explore the association between MSD and the quality of life and mental health of patients and to discuss issues concerning care seeking patterns in rural Greece. Methods Patients registered at one rural Primary Care Centre (PCC) in Crete were invited to complete the Nordic Musculoskeletal Questionnaire (NMQ) for the analysis of musculoskeletal symptoms, together with validated instruments for measuring health related quality of life (SF-36) and mental distress (GHQ-28). Results The prevalence rate of MSD was found to be 71.2%, with low back and knee pain being the most common symptoms. Most conditions significantly impaired the quality of life, especially the physical dimensions of SF-36. Depression was strongly correlated to most MSD (p < 0.001). Multiple logistic analyses revealed that patients who consulted the PCC due to MSD were likely to have more mental distress or impaired physical functioning compared to those who did not. Conclusion Musculoskeletal disorders were common in patients attending the rural PCC of this study and were associated with a poor quality of life and mental distress that affected their consultation behaviour. PMID:19930570

Synthetic biology platform technologies for antimicrobial applications.

PubMed

Braff, Dana; Shis, David; Collins, James J

2016-10-01

The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the multi-seeded (msd) mutant of sorghum for ethanol production

USDA-ARS?s Scientific Manuscript database

Grain sorghum [Sorghum bicolor (L.) Moench], a cost effective crop in semiarid regions, is an underestimated supplement to corn in starch based ethanol production. Twenty three multi-seeded (msd) mutant sorghums and one wild type sorghum BTx623 were evaluated for ethanol production and effect of che...

17 CFR 240.15Ba2-1 - Application for registration of municipal securities dealers which are banks or separately...

Code of Federal Regulations, 2010 CFR

2010-04-01

... Board), shall be filed with the Commission on Form MSD (§ 249.950 of this chapter), in accordance with... inaccurate for any reason, applicant shall promptly file an amendment on Form MSD (§ 249.950 of this chapter...

Characterization of a multi-seeded (msd) mutant of sorghum that displays significant enhancement in seed number

USDA-ARS?s Scientific Manuscript database

Sorghum (Sorghum bicolor L. Moench) cultivars and germplasm display branched inflorescence or panicle, characterized by spikelets composed of a single sessile, fertile floret that develop into viable seed and one or two adjacent sterile pedicellate florets (Monoseeded [MSD] trait). Based on total nu...

Case Study: Installation and Monitoring of Green Infrastructure Stormwater Controls in Louisville, Kentucky (Abstract)

EPA Science Inventory

In 2005, the Louisville and Jefferson County Metropolitan Sewer District (MSD) entered into a Consent Decree with the U.S. Environmental Protection Agency (EPA), Kentucky Dept. of Environmental Protection, and the U.S. Department of Justice. In 2009, the MSD submitted the Integr...

Case Study: Installation and Monitoring of Green Infrastructure Stormwater Controls in Louisville, Kentucky - slides

EPA Science Inventory

In 2005, the Louisville and Jefferson County Metropolitan Sewer District (MSD) entered into a Consent Decree with the U.S. Environmental Protection Agency (EPA), Kentucky Department for Environmental Protection, and the U.S. Department of Justice. MSD committed to monitor the pe...

18 CFR 1304.401 - Marine sanitation devices.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 2 2012-04-01 2012-04-01 false Marine sanitation... Miscellaneous § 1304.401 Marine sanitation devices. No person operating a commercial boat dock permitted under... equipped with a marine sanitation device (MSD) unless such MSD is in compliance with all applicable...

18 CFR 1304.401 - Marine sanitation devices.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Marine sanitation... Miscellaneous § 1304.401 Marine sanitation devices. No person operating a commercial boat dock permitted under... equipped with a marine sanitation device (MSD) unless such MSD is in compliance with all applicable...

18 CFR 1304.401 - Marine sanitation devices.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 2 2013-04-01 2012-04-01 true Marine sanitation... Miscellaneous § 1304.401 Marine sanitation devices. No person operating a commercial boat dock permitted under... equipped with a marine sanitation device (MSD) unless such MSD is in compliance with all applicable...

18 CFR 1304.401 - Marine sanitation devices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 2 2014-04-01 2014-04-01 false Marine sanitation... Miscellaneous § 1304.401 Marine sanitation devices. No person operating a commercial boat dock permitted under... equipped with a marine sanitation device (MSD) unless such MSD is in compliance with all applicable...

18 CFR 1304.401 - Marine sanitation devices.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Marine sanitation... Miscellaneous § 1304.401 Marine sanitation devices. No person operating a commercial boat dock permitted under... equipped with a marine sanitation device (MSD) unless such MSD is in compliance with all applicable...

Berkeley Lab - Materials Sciences Division

Science.gov Websites

Computational Study of Excited-State Phenomena in Energy Materials Center for X-ray Optics MSD Facilities Ion Excited-State Phenomena in Energy Materials Center for X-ray Optics MSD Facilities Ion Beam Analysis Behavior of Lithium Metal across a Rigid Block Copolymer Electrolyte Membrane. Journal of the

A multiplexed analysis approach identifies new association of inflammatory proteins in patients with overactive bladder

PubMed Central

Ma, Emily; Vetter, Joel; Bliss, Laura; Lai, H. Henry; Mysorekar, Indira U.

2016-01-01

Overactive bladder (OAB) is a common debilitating bladder condition with unknown etiology and limited diagnostic modalities. Here, we explored a novel high-throughput and unbiased multiplex approach with cellular and molecular components in a well-characterized patient cohort to identify biomarkers that could be reliably used to distinguish OAB from controls or provide insights into underlying etiology. As a secondary analysis, we determined whether this method could discriminate between OAB and other chronic bladder conditions. We analyzed plasma samples from healthy volunteers (n = 19) and patients diagnosed with OAB, interstitial cystitis/bladder pain syndrome (IC/BPS), or urinary tract infections (UTI; n = 51) for proinflammatory, chemokine, cytokine, angiogenesis, and vascular injury factors using Meso Scale Discovery (MSD) analysis and urinary cytological analysis. Wilcoxon rank-sum tests were used to perform univariate and multivariate comparisons between patient groups (controls, OAB, IC/BPS, and UTI). Multivariate logistic regression models were fit for each MSD analyte on 1) OAB patients and controls, 2) OAB and IC/BPS patients, and 3) OAB and UTI patients. Age, race, and sex were included as independent variables in all multivariate analysis. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic potential of a given analyte. Our findings demonstrate that five analytes, i.e., interleukin 4, TNF-α, macrophage inflammatory protein-1β, serum amyloid A, and Tie2 can reliably differentiate OAB relative to controls and can be used to distinguish OAB from the other conditions. Together, our pilot study suggests a molecular imbalance in inflammatory proteins may contribute to OAB pathogenesis. PMID:27029431

Discovery of FDA-Approved Drugs that Promote Retinal Cell Survival or Regeneration

DTIC Science & Technology

2015-10-01

1 AD______________ AWARD NUMBER: W81XWH-14-1-0407 TITLE:Discovery of FDA-Approved Drugs that Promote Retinal Cell Survival or Regeneration...SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0407Discovery of FDA-Approved Drugs that Promote Retinal Cell Survival or Regeneration 5c...vivo drug discovery platform named Automated Reporter Quantification in vivo (ARQiv). ARQiv quantifies reporter activity in transgenic zebrafish at

KSC-98pc1180

NASA Image and Video Library

1998-09-28

KENNEDY SPACE CENTER, FLA. -- At left, the payload canister for Space Shuttle Discovery is lifted from its canister movement vehicle to the top of the Rotating Service Structure on Launch Pad 39-B. Discovery (right), sitting atop the Mobile Launch Platform and next to the Fixed Service Structure, is scheduled for launch on Oct. 29, 1998, for the STS-95 mission. That mission includes the International Extreme Ultraviolet Hitchhiker (IEH-3), the Hubble Space Telescope Orbital Systems Test Platform, the Spartan solar-observing deployable spacecraft, and the SPACEHAB single module with experiments on space flight and the aging process

Detail view looking aft along the starboard side of the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Detail view looking aft along the starboard side of the Orbiter Discovery where the forward section meets the mid-fuselage. Note the head of the jack stand and its mechanism to connect to the one of the forward hoist attach points of the orbiter. Also note the support structure of the service platforms. This view was taken from the service platform in the Orbiter Processing Facility at Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Next-generation sequencing in clinical virology: Discovery of new viruses.

PubMed

Datta, Sibnarayan; Budhauliya, Raghvendra; Das, Bidisha; Chatterjee, Soumya; Vanlalhmuaka; Veer, Vijay

2015-08-12

Viruses are a cause of significant health problem worldwide, especially in the developing nations. Due to different anthropological activities, human populations are exposed to different viral pathogens, many of which emerge as outbreaks. In such situations, discovery of novel viruses is utmost important for deciding prevention and treatment strategies. Since last century, a number of different virus discovery methods, based on cell culture inoculation, sequence-independent PCR have been used for identification of a variety of viruses. However, the recent emergence and commercial availability of next-generation sequencers (NGS) has entirely changed the field of virus discovery. These massively parallel sequencing platforms can sequence a mixture of genetic materials from a very heterogeneous mix, with high sensitivity. Moreover, these platforms work in a sequence-independent manner, making them ideal tools for virus discovery. However, for their application in clinics, sample preparation or enrichment is necessary to detect low abundance virus populations. A number of techniques have also been developed for enrichment or viral nucleic acids. In this manuscript, we review the evolution of sequencing; NGS technologies available today as well as widely used virus enrichment technologies. We also discuss the challenges associated with their applications in the clinical virus discovery.

Advances in fragment-based drug discovery platforms.

PubMed

Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

2009-11-01

Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

Potential of multiseeded mutant (msd) to boost sorghum grain yield

USDA-ARS?s Scientific Manuscript database

Seed number per plant is an important determinant of the grain yield in cereal and other crops. We have isolated a class of multiseeded (msd) sorghum (Sorghum bicolor L. Moench) mutants that are capable of producing three times the seed number and twice the seed weight per panicle as compared with t...

Classification of Professional Values Based on Motivational Content: An Exploratory Study on Italian Adolescents

ERIC Educational Resources Information Center

Pallini, Susanna; Bove, Giuseppe; Laghi, Fiorenzo

2011-01-01

This study applies a multidimensional scaling (MSD) technique to investigate the structural validity of the Work Values Inventory for Adolescents with a sample of Italian students. The MSD results indicated the presence of two underlying orthogonal dimensions: individuality versus sociality and conservation versus exploration. Implications for…

Mainstream Teachers' Experiences of Communicating with Students with Multiple and Severe Disabilities

ERIC Educational Resources Information Center

De Bortoli, Tania; Balandin, Susan; Foreman, Phil; Arthur-Kelly, Michael; Mathisen, Bernice

2012-01-01

The aim of this study was to explore regular teachers' perceptions and experiences of supports and obstacles to communicative interactions for students with multiple and severe disabilities (MSD). Five teachers of students with MSD participated in two in-depth interviews. Interview transcripts were analysed using content analysis. Transcripts were…

Hand, Foot, and Mouth Disease Preliminarily Diagnosed as Hypochondriasis.

ERIC Educational Resources Information Center

Davidson, Michael Jay; And Others

1990-01-01

A case in which a dental student with hand, foot, and mouth disease was told he had "medical student disease" (MSD), or hypochondriasis, is related; literature pertaining to the occurrence and treatment of MSD is reviewed, and the importance of care in approaches to both students and patients are discussed. (MSE)

Berkeley Lab - Materials Sciences Division

Science.gov Websites

Synthesis Condensed Matter and Materials Physics Scattering and Instrumentation Science Centers Center for materials and phenomena at multiple time and length scales. Through our core programs and research centers Berkeley Lab Berkeley Lab A-Z Index Phone Book Jobs Search DOE Search MSD Go MSD - Materials

The application of an industry level participatory ergonomics approach in developing MSD interventions.

PubMed

Tappin, D C; Vitalis, A; Bentley, T A

2016-01-01

Participatory ergonomics projects are traditionally applied within one organisation. In this study, a participative approach was applied across the New Zealand meat processing industry, involving multiple organisations and geographical regions. The purpose was to develop interventions to reduce musculoskeletal disorder (MSD) risk. This paper considers the value of an industry level participatory ergonomics approach in achieving this. The main rationale for a participative approach included the need for industry credibility, and to generate MSD interventions that address industry level MSD risk factors. An industry key stakeholder group became the primary vehicle for formal participation. The study resulted in an intervention plan that included the wider work system and industry practices. These interventions were championed across the industry by the key stakeholder group and have extended beyond the life of the study. While this approach helped to meet the study aim, the existence of an industry-supported key stakeholder group and a mandate for the initiative are important prerequisites for success. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

On decoding of multi-level MPSK modulation codes

NASA Technical Reports Server (NTRS)

Lin, Shu; Gupta, Alok Kumar

1990-01-01

The decoding problem of multi-level block modulation codes is investigated. The hardware design of soft-decision Viterbi decoder for some short length 8-PSK block modulation codes is presented. An effective way to reduce the hardware complexity of the decoder by reducing the branch metric and path metric, using a non-uniform floating-point to integer mapping scheme, is proposed and discussed. The simulation results of the design are presented. The multi-stage decoding (MSD) of multi-level modulation codes is also investigated. The cases of soft-decision and hard-decision MSD are considered and their performance are evaluated for several codes of different lengths and different minimum squared Euclidean distances. It is shown that the soft-decision MSD reduces the decoding complexity drastically and it is suboptimum. The hard-decision MSD further simplifies the decoding while still maintaining a reasonable coding gain over the uncoded system, if the component codes are chosen properly. Finally, some basic 3-level 8-PSK modulation codes using BCH codes as component codes are constructed and their coding gains are found for hard decision multistage decoding.

Prevalence and predictors for musculoskeletal discomfort in Malaysian office workers: Investigating explanatory factors for a developing country.

PubMed

Maakip, Ismail; Keegel, Tessa; Oakman, Jodi

2016-03-01

Musculoskeletal disorders (MSDs) are a major occupational health issue for workers in developed and developing countries, including Malaysia. Most research related to MSDs has been undertaken in developed countries; given the different regulatory and cultural practices it is plausible that contributions of hazard and risk factors may be different. A population of Malaysian public service office workers were surveyed (N = 417, 65.5% response rate) to determine prevalence and associated predictors of MSD discomfort. The 6-month period prevalence of MSD discomfort was 92.8% (95%CI = 90.2-95.2%). Akaike's Information Criterion (AIC) analyses was used to compare a range of models and determine a model of best fit. Contributions associated with MSD discomfort in the final model consisted of physical demands (61%), workload (14%), gender (13%), work-home balance (9%) and psychosocial factors (3%). Factors associated with MSD discomfort were similar in developed and developing countries but the relative contribution of factors was different, providing insight into future development of risk management strategies. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Inflammation reduces physiological tissue tolerance in the development of work-related musculoskeletal disorders.

PubMed

Barr, Ann E; Barbe, Mary F

2004-02-01

Work-related musculoskeletal disorders (MSDs) cause substantial worker discomfort, disability and loss of productivity. Due to the difficulty in analyzing the tissues of patients in the early stages of work-related MSD, there is controversy concerning the pathomechanisms of the development of these disorders. The pathophysiology of work-related MSD can be studied more easily in animal models. The purpose of this review is to relate theories of the development of tissue injury due to repeated motion to findings of recent investigations in animals that address the role of the inflammatory response in propagating tissue injury and contributing to chronic or recurring tissue injury. These tissue effects are related to behavioral indicators of discomfort and movement dysfunction with the aim of clarifying key time points for specific intervention approaches. The results from animal models of MSD are discussed in the light of findings in patients, whose tissues are examined at a much later phase of MSD development. Finally, a conceptual model of the potentially negative impact of inflammation on tissue tolerance is proposed along with suggestions for future research directions.

Transgenic mouse strains as platforms for the successful discovery and development of human therapeutic monoclonal antibodies.

PubMed

Green, Larry L

2014-03-01

Transgenic mice have yielded seven of the ten currently-approved human antibody drugs, making them the most successful platform for the discovery of fully human antibody therapeutics. The use of the in vivo immune system helps drive this success by taking advantage of the natural selection process that produces antibodies with desirable characteristics. Appropriately genetically-engineered mice act as robust engines for the generation of diverse repertoires of affinity- matured fully human variable regions with intrinsic properties necessary for successful antibody drug development including high potency, specificity, manufacturability, solubility and low risk of immunogenicity. A broad range of mAb drug targets are addressable in these mice, comprising both secreted and transmembrane targets, including membrane multi-spanning targets, as well as human target antigens that share high sequence identity with their mouse orthologue. Transgenic mice can routinely yield antibodies with sub-nanomolar binding affinity for their antigen, with lead candidate mAbs frequently possessing affinities for binding to their target of less than 100 picomolar, without requiring any ex vivo affinity optimization. While the originator transgenic mice platforms are no longer broadly available, a new generation of transgenic platforms is in development for discovery of the next wave of human therapeutic antibodies.

Transvaginal ultrasound in threatened abortions with empty gestational sacs.

PubMed

Tongsong, T; Wanapirak, C; Srisomboon, J; Sirichotiyakul, S; Polsrisuthikul, T; Pongsatha, S

1994-09-01

To determine whether transvaginal ultrasound criteria alone can distinguish viable from non-viable gestational sacs at a single examination. A prospective descriptive study was undertaken and analysis performed on 211 pregnancies complicated by threatened abortion and empty gestation sacs diagnosed by transvaginal ultrasound. The main outcome measure was the final diagnosis of viable or non-viable gestation on subsequent transvaginal sonography. The study shows that a single transvaginal ultrasound examination is useful in differentiating viable from non-viable gestation sacs. The mean sac diameter (MSD) was found to be the most useful criterion for determining non-viability. An MSD of > or = 17 mm that lacked an embryo and an MSD of > or = 13 mm without visible yolk sac were reliable predictors of non-viable gestation sacs at a single examination with 100% specificity and 100% positive predictive value. An MSD > or = 13 mm without visible yolk sac was the most sensitive criterion. Using MSD criteria, 73% of non-viable gestations could be reliably identified without any false-positive diagnoses. Deformed shape, low position and thin decidual reaction are strong indicators of non-viable gestations but are not 100% accurate. There is still a significant proportion of empty sacs, where no accurate distinction between viable and non-viable can be made according to one criterion at a single examination and in these cases serial examinations should be carried out before any active management is advocated. In most cases, transvaginal sonographic criteria alone can distinguish viable from non-viable empty gestational sacs at a single examination.

Musculoskeletal disorders and skin disease among workers in a Japanese CD manufacturing plant.

PubMed

Smith, Derek Richard; Takeda, Yasuhisa; Mizutani, Takashi; Yamagata, Zentaro

2002-12-01

We investigated the prevalence of musculoskeletal disorders (MSD) and skin disease within a Japanese compact disk (CD) manufacturing plant. For this study, a stratified cross-section of workers completed self-reported questionnaires distributed over a 6-month time period. Low back pain (LBP) was the most commonly reported category (affecting 20.1%), followed by MSD of the shoulder (15.4%), neck (10.1%) and head (5.4%). Dermatitis was the most frequent skin disease (affecting 8.1%), followed by eczema (3.4%), acne (3.4%) and xerosis (2.7%). The odds of suffering neck MSD was 10.8 times higher among staff who sat in a chair all day (95% CI 1.8-112.8, P < 0.05). Standing all day was also a risk factor for this condition (OR 8.2, 95% CI 1.2-81.7, P < 0.05). Female gender increased the risk of shoulder MSD 4.3 fold (95% CI 1.4-13.7, P < 0.05), as did alcohol consumption (OR 3.3, 95% CI 1.1-11.9, P < 0.05). The odds of suffering any skin disease were significantly enhanced by working longer than 12 months in one's current job (OR 10.7, 95% CI 1.5-7.3, P < 0.05) and having a history of atopic disease (OR 7.2, 95% CI 2.6-21.4, P < 0.001). Overall, the staff within our study reported generally lower levels of MSD and skin disease than in previous investigations of other workplaces.

Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency.

PubMed

Dvorak, Christopher C; Hassan, Amel; Slatter, Mary A; Hönig, Manfred; Lankester, Arjan C; Buckley, Rebecca H; Pulsipher, Michael A; Davis, Jeffrey H; Güngör, Tayfun; Gabriel, Melissa; Bleesing, Jacob H; Bunin, Nancy; Sedlacek, Petr; Connelly, James A; Crawford, David F; Notarangelo, Luigi D; Pai, Sung-Yun; Hassid, Jake; Veys, Paul; Gennery, Andrew R; Cowan, Morton J

2014-10-01

Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy. We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs. We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66). Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001). Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Meta Salud Diabetes study protocol: a cluster-randomised trial to reduce cardiovascular risk among a diabetic population of Mexico

PubMed Central

Cornejo Vucovich, Elsa; Ingram, Maia; Valenica, Celina; Castro Vasquez, Maria del Carmen; Gonzalez-Fagoaga, Eduardo; Geurnsey de Zapien, Jill

2018-01-01

Introduction Northern Mexico has among the highest rates of cardiovascular disease (CVD) and diabetes in the world. This research addresses core gaps in implementation science to develop, test and scale-up CVD risk-reduction interventions in diabetics through a national primary care health system. Methods and analysis The Meta Salud Diabetes (MSD) research project is a parallel two-arm cluster-randomised clinical behavioural trial based in 22 (n=22) health centres in Sonora, Mexico. MSD aims to evaluate the effectiveness of the MSD intervention for the secondary prevention of CVD risk factors among a diabetic population (n=320) compared with the study control of usual care. The MSD intervention consists of 2-hour class sessions delivered over a 13-week period providing educational information to encourage sustainable behavioural change to prevent disease complications including the adoption of physical activity. MSD is delivered within the context of Mexico’s national primary care health centre system by health professionals, including nurses, physicians and community health workers via existing social support groups for individuals diagnosed with chronic disease. Mixed models are used to estimate the effect of MSD by comparing cardiovascular risk, as measured by the Framingham Risk Score, between the trial arms. Secondary outcomes include hypertension, behavioural risk factors and psychosocial factors. Ethics and dissemination This work is supported by the National Institutes of Health, National Heart Lung and Blood Institute (1R01HL125996-01) and approved by the University of Arizona Research Institutional Review Board (Protocol 1508040144) and the Research Bioethics Committee at the University of Sonora. The first Internal Review Board approval date was 31 August 2015 with five subsequent approved amendments. This article refers to protocol V.0.2, dated 30 January 2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences and will be shared through meetings with health systems officials. Trial registration number NCT0280469; Pre-results. PMID:29530914

Quantitative PCR for detection of Shigella improves ascertainment of Shigella burden in children with moderate-to-severe diarrhea in low-income countries.

PubMed

Lindsay, Brianna; Ochieng, John B; Ikumapayi, Usman N; Toure, Aliou; Ahmed, Dilruba; Li, Shan; Panchalingam, Sandra; Levine, Myron M; Kotloff, Karen; Rasko, David A; Morris, Carolyn R; Juma, Jane; Fields, Barry S; Dione, Michel; Malle, Dramane; Becker, Stephen M; Houpt, Eric R; Nataro, James P; Sommerfelt, Halvor; Pop, Mihai; Oundo, Joe; Antonio, Martin; Hossain, Anowar; Tamboura, Boubou; Stine, O Colin

2013-06-01

Estimates of the prevalence of Shigella spp. are limited by the suboptimal sensitivity of current diagnostic and surveillance methods. We used a quantitative PCR (qPCR) assay to detect Shigella in the stool samples of 3,533 children aged <59 months from the Gambia, Mali, Kenya, and Bangladesh, with or without moderate-to-severe diarrhea (MSD). We compared the results from conventional culture to those from qPCR for the Shigella ipaH gene. Using MSD as the reference standard, we determined the optimal cutpoint to be 2.9 × 10(4) ipaH copies per 100 ng of stool DNA for set 1 (n = 877). One hundred fifty-eight (18%) specimens yielded >2.9 × 10(4) ipaH copies. Ninety (10%) specimens were positive by traditional culture for Shigella. Individuals with ≥ 2.9 × 10(4) ipaH copies have 5.6-times-higher odds of having diarrhea than those with <2.9 × 10(4) ipaH copies (95% confidence interval, 3.7 to 8.5; P < 0.0001). Nearly identical results were found using an independent set of samples. qPCR detected 155 additional MSD cases with high copy numbers of ipaH, a 90% increase from the 172 cases detected by culture in both samples. Among a subset (n = 2,874) comprising MSD cases and their age-, gender-, and location-matched controls, the fraction of MSD cases that were attributable to Shigella infection increased from 9.6% (n = 129) for culture to 17.6% (n = 262) for qPCR when employing our cutpoint. We suggest that qPCR with a cutpoint of approximately 1.4 × 10(4) ipaH copies be the new reference standard for the detection and diagnosis of shigellosis in children in low-income countries. The acceptance of this new standard would substantially increase the fraction of MSD cases that are attributable to Shigella.

Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

PubMed

Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

2016-02-01

ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International Society on Thrombosis and Haemostasis.

Development of Transcriptomics-based Biomarkers for Selected Endocrine Disrupting Chemicals in Zebrafish (Danio rerio)

EPA Science Inventory

Genome-wide transcriptional profiling by microarrays provides a powerful platform for gene expression-based biomarker discovery. After their wide acceptance in human disease diagnosis, prognosis, and drug discovery, these gene signatures are increasingly being adopted for environ...

Development of transcriptomics-based biomarkers for selected endocrine disrupting chemicals in zebrafish (Danio rerio)

EPA Science Inventory

Genome-wide transcriptional profiling by microarrays provides a powerful platform for gene expression-based biomarker discovery. After their wide acceptance in human disease diagnosis, prognosis, and drug discovery, these gene signatures are increasingly being adopted for environ...

Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study

PubMed Central

Conan, Anne; O’Reilly, Ciara E.; Ogola, Eric; Ochieng, J. Benjamin; Blackstock, Anna J.; Omore, Richard; Ochieng, Linus; Moke, Fenny; Parsons, Michele B.; Xiao, Lihua; Roellig, Dawn; Farag, Tamer H.; Nataro, James P.; Kotloff, Karen L.; Levine, Myron M.; Mintz, Eric D.; Breiman, Robert F.; Cleaveland, Sarah

2017-01-01

Background Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. Methodology/Principal findings We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children’s homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08–0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02–0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0–1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5–37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2–12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Conclusions and significance Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents. PMID:28783751

Physician practicing preferences for conventional or homeopathic medicines in elderly subjects with musculoskeletal disorders in the EPI3-MSD cohort

PubMed Central

Danno, Karine; Joubert, Clementine; Duru, Gerard; Vetel, Jean-Marie

2014-01-01

Background Musculoskeletal pain is common in elderly persons. Analgesic use is high in the elderly and may involve unacceptable risk in individuals with chronic pain. Our aim was to compare the socio-demographic characteristics of elderly subjects with musculoskeletal disorders (MSD) and to assess medication use and clinical evolution of musculoskeletal pain according to physician prescribing preference: homeopathy (Ho) group, conventional medicine (CM) group, or mixed prescription (MX) group. Methods The EPI3 study was a 1 year observational survey carried out among general practitioners in France between March 2007 and July 2008. This sub-analysis was carried out on elderly subjects aged ≥70 years from the original EPI3 cohort. Socio-demographic data were collected at inclusion using a self-administered patient questionnaire and medical data were recorded for each patient. Quality of life was measured using the Short Form-12 questionnaire. Patients completed a structured telephone interview on their functional status (evaluated with the QuickDash questionnaire, EIFEL scale or Lequesne index) within 72 hours of inclusion. This telephone interview was repeated at 1, 3, and 12 months. Drug exposure was also assessed during these interviews. Results 146 patients (mean age ± standard deviation: 75.8±4.8 years) were analyzed (80.1% female, 74.7% MSD of the spine or lower limbs, 64.4% chronic MSD). Patients in the CM and MX groups were 3.7 times or 2.5 times more likely (odds ratio [OR] =3.71, 95% confidence interval [CI]: 1.12–12.30; OR =2.52, 95% CI: 1.05–6.05; respectively) to have used non-steroidal anti-inflammatory drugs (NSAIDs) than those in the Ho group. In contrast, analgesic use was comparable in the three groups (OR =1.06 [CM versus Ho], 95% CI: 0.09–12.11; OR =0.34 [MX versus Ho], 95% CI: 0.07–1.57). Overall functional score evolution was similar in the three groups over time (P=0.16). Conclusion NSAID use was significantly higher in elderly MSD patients consulting a conventional practice general practitioner. In contrast, analgesic use and MSD evolution were similar in the three groups. Consulting a homeopathic physician for MSD management does not appear to represent a loss of therapeutic opportunity, and decreases the use of NSAIDs. PMID:25298739

Physician practicing preferences for conventional or homeopathic medicines in elderly subjects with musculoskeletal disorders in the EPI3-MSD cohort.

PubMed

Danno, Karine; Joubert, Clementine; Duru, Gerard; Vetel, Jean-Marie

2014-01-01

Musculoskeletal pain is common in elderly persons. Analgesic use is high in the elderly and may involve unacceptable risk in individuals with chronic pain. Our aim was to compare the socio-demographic characteristics of elderly subjects with musculoskeletal disorders (MSD) and to assess medication use and clinical evolution of musculoskeletal pain according to physician prescribing preference: homeopathy (Ho) group, conventional medicine (CM) group, or mixed prescription (MX) group. The EPI3 study was a 1 year observational survey carried out among general practitioners in France between March 2007 and July 2008. This sub-analysis was carried out on elderly subjects aged ≥70 years from the original EPI3 cohort. Socio-demographic data were collected at inclusion using a self-administered patient questionnaire and medical data were recorded for each patient. Quality of life was measured using the Short Form-12 questionnaire. Patients completed a structured telephone interview on their functional status (evaluated with the QuickDash questionnaire, EIFEL scale or Lequesne index) within 72 hours of inclusion. This telephone interview was repeated at 1, 3, and 12 months. Drug exposure was also assessed during these interviews. 146 patients (mean age ± standard deviation: 75.8±4.8 years) were analyzed (80.1% female, 74.7% MSD of the spine or lower limbs, 64.4% chronic MSD). Patients in the CM and MX groups were 3.7 times or 2.5 times more likely (odds ratio [OR] =3.71, 95% confidence interval [CI]: 1.12-12.30; OR =2.52, 95% CI: 1.05-6.05; respectively) to have used non-steroidal anti-inflammatory drugs (NSAIDs) than those in the Ho group. In contrast, analgesic use was comparable in the three groups (OR =1.06 [CM versus Ho], 95% CI: 0.09-12.11; OR =0.34 [MX versus Ho], 95% CI: 0.07-1.57). Overall functional score evolution was similar in the three groups over time (P=0.16). NSAID use was significantly higher in elderly MSD patients consulting a conventional practice general practitioner. In contrast, analgesic use and MSD evolution were similar in the three groups. Consulting a homeopathic physician for MSD management does not appear to represent a loss of therapeutic opportunity, and decreases the use of NSAIDs.

Musculoskeletal disorder risk factors among nursing professionals in low resource settings: a cross-sectional study in Uganda.

PubMed

Munabi, Ian G; Buwembo, William; Kitara, David L; Ochieng, Joseph; Mwaka, Erisa S

2014-02-24

Musculoskeletal disorders (MSD) constitute one of the main occupational hazards among health care workers. However, few epidemiological studies on work related MSD among nursing professionals have been carried out in Africa. The purpose of this study was to assess the work related musculoskeletal disorders and associated risk factors among nursing professionals in Uganda. This was a cross-sectional study of MSD among 880 nursing professionals from five selected hospitals in Uganda. Data was collected using a questionnaire adapted from the Dutch Musculoskeletal and Nordic Musculoskeletal questionnaires. Descriptive (mean, standard deviation and percentages) and inferential (Chi square test and logistic regression analysis) statistics were used to analyse data. Alpha level was set at p < 0.05. A total of 741 completed questionnaires were analysed (response rate 85.4%). The average age of the respondents was 35.4 (SD 10.7) years and a majority were female (85.7%). The average working hours per week was 43.7 (SD 18.9 hours). The 12-month period-prevalence of MSD at anybody site was 80.8%. The most common site of MSD was the lower back (61.9%). Significant risk factors for reported MSD included often working in a slightly bent posture (adjOR 2.25, 95% CI 1.20-4.26), often working in a slightly twisted posture for long (adjOR 1.97, 95% CI 1.03-3.77), mental exhaustion (adjOR 2.05, 95% CI 1.17-3.5), being absent from the work station for more than 6 months due to illness or an accident (adjO|R, 4.35, 95% CI 1.44-13.08) and feeling rested after a break (adjOR 2.09, 95% CI 1.16-3.76). Musculoskeletal disorders affect more than 80% of nursing professionals in Uganda with the most commonly, affected site being the lower back. Significant risk factors for MSD include; being absent from the work station for more than 6 months due to illness or an accident, working in awkward postures, pushing/pulling of heavy loads and mental exhaustion. There is a need for greater advocacy, better working conditions and adoption of strategies to reduce occupational injuries.

Tissue constructs: platforms for basic research and drug discovery.

PubMed

Elson, Elliot L; Genin, Guy M

2016-02-06

The functions, form and mechanical properties of cells are inextricably linked to their extracellular environment. Cells from solid tissues change fundamentally when, isolated from this environment, they are cultured on rigid two-dimensional substrata. These changes limit the significance of mechanical measurements on cells in two-dimensional culture and motivate the development of constructs with cells embedded in three-dimensional matrices that mimic the natural tissue. While measurements of cell mechanics are difficult in natural tissues, they have proven effective in engineered tissue constructs, especially constructs that emphasize specific cell types and their functions, e.g. engineered heart tissues. Tissue constructs developed as models of disease also have been useful as platforms for drug discovery. Underlying the use of tissue constructs as platforms for basic research and drug discovery is integration of multiscale biomaterials measurement and computational modelling to dissect the distinguishable mechanical responses separately of cells and extracellular matrix from measurements on tissue constructs and to quantify the effects of drug treatment on these responses. These methods and their application are the main subjects of this review.

Institutional profile: the national Swedish academic drug discovery & development platform at SciLifeLab

PubMed Central

Arvidsson, Per I; Sandberg, Kristian; Sakariassen, Kjell S

2017-01-01

The Science for Life Laboratory Drug Discovery and Development Platform (SciLifeLab DDD) was established in Stockholm and Uppsala, Sweden, in 2014. It is one of ten platforms of the Swedish national SciLifeLab which support projects run by Swedish academic researchers with large-scale technologies for molecular biosciences with a focus on health and environment. SciLifeLab was created by the coordinated effort of four universities in Stockholm and Uppsala: Stockholm University, Karolinska Institutet, KTH Royal Institute of Technology and Uppsala University, and has recently expanded to other Swedish university locations. The primary goal of the SciLifeLab DDD is to support selected academic discovery and development research projects with tools and resources to discover novel lead therapeutics, either molecules or human antibodies. Intellectual property developed with the help of SciLifeLab DDD is wholly owned by the academic research group. The bulk of SciLifeLab DDD's research and service activities are funded from the Swedish state, with only consumables paid by the academic research group through individual grants. PMID:28670468

Tissue constructs: platforms for basic research and drug discovery

PubMed Central

Elson, Elliot L.; Genin, Guy M.

2016-01-01

The functions, form and mechanical properties of cells are inextricably linked to their extracellular environment. Cells from solid tissues change fundamentally when, isolated from this environment, they are cultured on rigid two-dimensional substrata. These changes limit the significance of mechanical measurements on cells in two-dimensional culture and motivate the development of constructs with cells embedded in three-dimensional matrices that mimic the natural tissue. While measurements of cell mechanics are difficult in natural tissues, they have proven effective in engineered tissue constructs, especially constructs that emphasize specific cell types and their functions, e.g. engineered heart tissues. Tissue constructs developed as models of disease also have been useful as platforms for drug discovery. Underlying the use of tissue constructs as platforms for basic research and drug discovery is integration of multiscale biomaterials measurement and computational modelling to dissect the distinguishable mechanical responses separately of cells and extracellular matrix from measurements on tissue constructs and to quantify the effects of drug treatment on these responses. These methods and their application are the main subjects of this review. PMID:26855763

Institutional profile: the national Swedish academic drug discovery & development platform at SciLifeLab.

PubMed

Arvidsson, Per I; Sandberg, Kristian; Sakariassen, Kjell S

2017-06-01

The Science for Life Laboratory Drug Discovery and Development Platform (SciLifeLab DDD) was established in Stockholm and Uppsala, Sweden, in 2014. It is one of ten platforms of the Swedish national SciLifeLab which support projects run by Swedish academic researchers with large-scale technologies for molecular biosciences with a focus on health and environment. SciLifeLab was created by the coordinated effort of four universities in Stockholm and Uppsala: Stockholm University, Karolinska Institutet, KTH Royal Institute of Technology and Uppsala University, and has recently expanded to other Swedish university locations. The primary goal of the SciLifeLab DDD is to support selected academic discovery and development research projects with tools and resources to discover novel lead therapeutics, either molecules or human antibodies. Intellectual property developed with the help of SciLifeLab DDD is wholly owned by the academic research group. The bulk of SciLifeLab DDD's research and service activities are funded from the Swedish state, with only consumables paid by the academic research group through individual grants.

Port side view of the Orbiter Discovery from an elevated ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Port side view of the Orbiter Discovery from an elevated platform in the Vehicle Assembly Building at NASA's Kennedy Space Center. Note the ground support hardware known as Strongbacks attached to the payload bay doors, the crew access hatch below the name Discovery on the forward section of the Orbiter and the removed Orbiter Maneuvering System/Reaction Control System pod from the aft (tai) section. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

MODEL SCHOOL DIVISION--A REPORT OF THE BOARD OF EDUCATION, JUNE, 1967.

ERIC Educational Resources Information Center

HANSEN, CARL F.; NICKENS, NORMAN W.

DESCRIBED IN THIS REPORT IS THE MODEL SCHOOL DIVISION (MSD) WHICH SERVES THE INNER-CITY PUBLIC SCHOOLS OF WASHINGTON, D.C. FUNCTIONING AS A SEMI-AUTONOMOUS UNIT WITHIN THE SCHOOL SYSTEM, MSD HAS AS ITS BASIC OBJECTIVES IMPROVING EDUCATIONAL QUALITY, SERVING THE SPECIAL EDUCATIONAL NEEDS OF THE COMMUNITY, STIMULATING SCHOOL-COMMUNITY INVOLVEMENT,…

An Evaluation of a Summer Reading Institute, 1968.

ERIC Educational Resources Information Center

Rosenfeld, Michael

This document describes part of the evaluation of a six-week reading institute for 69 K-3 teachers from the Raymond School, Model School Division (MSD), Washington, D.C. and thereby provides an evaluation model for schools to use in their own inservice training programs. Two evaluation instruments developed by an MSD innovation team in cooperation…

76 FR 78253 - New York State Prohibition of Discharges of Vessel Sewage; Final Affirmative Determination

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

... holding tank, to a municipal wastewater treatment plant or to an on-site septic system. With 37 pumpouts... and install holding tanks for effluent. Such retrofitting is complicated due to the extremely limited... Sanitation Device (MSD) can be converted to a Type III MSD, commonly called a holding tank, which can be...

Wavepacket dynamics in one-dimensional system with long-range correlated disorder

NASA Astrophysics Data System (ADS)

Yamada, Hiroaki S.

2018-03-01

We numerically investigate dynamical property in the one-dimensional tight-binding model with long-range correlated disorder having power spectrum 1 /fα (α: spectrum exponent) generated by Fourier filtering method. For relatively small α <αc (=2) time-dependence of mean square displacement (MSD) of the initially localized wavepacket shows ballistic spread and localizes as time elapses. It is shown that α-dependence of the dynamical localization length determined by the MSD exhibits a simple scaling law in the localization regime for the relatively weak disorder strength W. Furthermore, scaled MSD by the dynamical localization length almost obeys an universal function from the ballistic to the localization regime in the various combinations of the parameters α and W.

A fracture criterion for widespread cracking in thin-sheet aluminum alloys

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.; Dawicke, D. S.; Sutton, M. A.; Bigelow, C. A.

1993-01-01

An elastic-plastic finite-element analysis was used with a critical crack-tip-opening angle (CTOA) fracture criterion to model stable crack growth in thin-sheet 2024-T3 aluminum alloy panels with single and multiple-site damage (MSD) cracks. Comparisons were made between critical angles determined from the analyses and those measured with photographic methods. Calculated load against crack extension and load against crack-tip displacement on single crack specimens agreed well with test data even for large-scale plastic deformations. The analyses were also able to predict the stable tearing behavior of large lead cracks in the presence of stably tearing MSD cracks. Small MSD cracks significantly reduced the residual strength for large lead cracks.

Preliminary investigation of single-file diffusion in complex plasma rings

NASA Astrophysics Data System (ADS)

Theisen, W. L.; Sheridan, T. E.

2010-04-01

Particles in one-dimensional (1D) systems cannot pass each other. However, it is still possible to define a diffusion process where the mean-squared displacement (msd) of an ensemble of particles in a 1D chain increases with time t. This process is called single-file diffusion. In contrast to diffusive processes that follow Fick's law, msdt, single-file diffusion is sub-Fickean and the msd is predicted to increase as t^1/2. We have recently created 1D dusty (complex) plasma rings in the DONUT (Dusty ONU experimenT) apparatus. Particle position data from these rings will be analyzed to determine the scaling of the msd with time and results will be compared with predictions of single-file diffusion theory.

High-throughput platform assay technology for the discovery of pre-microrna-selective small molecule probes.

PubMed

Lorenz, Daniel A; Song, James M; Garner, Amanda L

2015-01-21

MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.

Biomarker discovery for colon cancer using a 761 gene RT-PCR assay.

PubMed

Clark-Langone, Kim M; Wu, Jenny Y; Sangli, Chithra; Chen, Angela; Snable, James L; Nguyen, Anhthu; Hackett, James R; Baker, Joffre; Yothers, Greg; Kim, Chungyeul; Cronin, Maureen T

2007-08-15

Reverse transcription PCR (RT-PCR) is widely recognized to be the gold standard method for quantifying gene expression. Studies using RT-PCR technology as a discovery tool have historically been limited to relatively small gene sets compared to other gene expression platforms such as microarrays. We have recently shown that TaqMan RT-PCR can be scaled up to profile expression for 192 genes in fixed paraffin-embedded (FPE) clinical study tumor specimens. This technology has also been used to develop and commercialize a widely used clinical test for breast cancer prognosis and prediction, the Onco typeDX assay. A similar need exists in colon cancer for a test that provides information on the likelihood of disease recurrence in colon cancer (prognosis) and the likelihood of tumor response to standard chemotherapy regimens (prediction). We have now scaled our RT-PCR assay to efficiently screen 761 biomarkers across hundreds of patient samples and applied this process to biomarker discovery in colon cancer. This screening strategy remains attractive due to the inherent advantages of maintaining platform consistency from discovery through clinical application. RNA was extracted from formalin fixed paraffin embedded (FPE) tissue, as old as 28 years, from 354 patients enrolled in NSABP C-01 and C-02 colon cancer studies. Multiplexed reverse transcription reactions were performed using a gene specific primer pool containing 761 unique primers. PCR was performed as independent TaqMan reactions for each candidate gene. Hierarchal clustering demonstrates that genes expected to co-express form obvious, distinct and in certain cases very tightly correlated clusters, validating the reliability of this technical approach to biomarker discovery. We have developed a high throughput, quantitatively precise multi-analyte gene expression platform for biomarker discovery that approaches low density DNA arrays in numbers of genes analyzed while maintaining the high specificity, sensitivity and reproducibility that are characteristics of RT-PCR. Biomarkers discovered using this approach can be transferred to a clinical reference laboratory setting without having to re-validate the assay on a second technology platform.

STS-29 Discovery, Orbiter Vehicle (OV) 103, roll out to KSC LC Pad 39B

NASA Technical Reports Server (NTRS)

1989-01-01

In the early morning hours, STS-29 Discovery, Orbiter Vehicle (OV) 103, mated to the external tank (ET) and solid rocket boosters (SRBs) is rolled out to Kennedy Space Center (KSC) Launch Complex (LC) Pad 39B atop the mobile launcher platform. Trees, shrubs, and a light mist surround the mobile launcher platform as it makes its way to LC Pad 39B. OV-103 will fly on Mission STS-29 scheduled for launch in mid-March. View provided by KSC with alternate KSC number KSC-89PC-50.

STS-95 Space Shuttle Discovery rollout to Launch Pad 39B

NASA Technical Reports Server (NTRS)

1998-01-01

Perched on the Mobile Launch Platform, in the early morning hours Space Shuttle Discovery approaches Launch Complex Pad 39B after a 6-hour, 4.2-mile trip from the Vehicle Assembly Building. At the launch pad, the orbiter, external tank and solid rocket boosters will undergo final preparations for the launch, scheduled to lift off Oct. 29. The mission includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

Computational drug discovery

PubMed Central

Ou-Yang, Si-sheng; Lu, Jun-yan; Kong, Xiang-qian; Liang, Zhong-jie; Luo, Cheng; Jiang, Hualiang

2012-01-01

Computational drug discovery is an effective strategy for accelerating and economizing drug discovery and development process. Because of the dramatic increase in the availability of biological macromolecule and small molecule information, the applicability of computational drug discovery has been extended and broadly applied to nearly every stage in the drug discovery and development workflow, including target identification and validation, lead discovery and optimization and preclinical tests. Over the past decades, computational drug discovery methods such as molecular docking, pharmacophore modeling and mapping, de novo design, molecular similarity calculation and sequence-based virtual screening have been greatly improved. In this review, we present an overview of these important computational methods, platforms and successful applications in this field. PMID:22922346

System Architecture Development for Energy and Water Infrastructure Data Management and Geovisual Analytics

NASA Astrophysics Data System (ADS)

Berres, A.; Karthik, R.; Nugent, P.; Sorokine, A.; Myers, A.; Pang, H.

2017-12-01

Building an integrated data infrastructure that can meet the needs of a sustainable energy-water resource management requires a robust data management and geovisual analytics platform, capable of cross-domain scientific discovery and knowledge generation. Such a platform can facilitate the investigation of diverse complex research and policy questions for emerging priorities in Energy-Water Nexus (EWN) science areas. Using advanced data analytics, machine learning techniques, multi-dimensional statistical tools, and interactive geovisualization components, such a multi-layered federated platform is being developed, the Energy-Water Nexus Knowledge Discovery Framework (EWN-KDF). This platform utilizes several enterprise-grade software design concepts and standards such as extensible service-oriented architecture, open standard protocols, event-driven programming model, enterprise service bus, and adaptive user interfaces to provide a strategic value to the integrative computational and data infrastructure. EWN-KDF is built on the Compute and Data Environment for Science (CADES) environment in Oak Ridge National Laboratory (ORNL).

Technical issues in the conduct of large space platform experiments in plasma physics and geoplasma sciences

NASA Technical Reports Server (NTRS)

Szuszczewicz, Edward P.

1986-01-01

Large, permanently-manned space platforms can provide exciting opportunities for discoveries in basic plasma and geoplasma sciences. The potential for these discoveries will depend very critically on the properties of the platform, its subsystems, and their abilities to fulfill a spectrum of scientific requirements. With this in mind, the planning of space station research initiatives and the development of attendant platform engineering should allow for the identification of critical science and technology issues that must be clarified far in advance of space station program implementation. An attempt is made to contribute to that process, with a perspective that looks to the development of the space station as a permanently-manned Spaceborne Ionospheric Weather Station. The development of this concept requires a synergism of science and technology which leads to several critical design issues. To explore the identification of these issues, the development of the concept of an Ionospheric Weather Station will necessarily touch upon a number of diverse areas. These areas are discussed.

The ergonomics body posture on repetitive and heavy lifting activities of workers in aerospace manufacturing warehouse

NASA Astrophysics Data System (ADS)

Kamat, S. R.; Zula, N. E. N. Md; Rayme, N. S.; Shamsuddin, S.; Husain, K.

2017-06-01

Warehouse is an important entity in manufacturing organizations. It usually involves working activities that relate ergonomics risk factors including repetitive and heavy lifting activities. Aerospace manufacturing workers are prone of having musculoskeletal disorder (MSD) problems because of the manual handling activities. From the questionnaires is states that the workers may have experience discomforts experience during manual handling work. Thus, the objectives of this study are; to investigate the body posture and analyze the level of discomfort for body posture of the workers while performing the repetitive and heavy lifting activities that cause MSD problems and to suggest proper body posture and alternatives to reduce the MSD related problems. Methodology of this study involves interviews, questionnaires distribution, anthropometry measurements, RULA (Right Upper Limb Assessment) assessment sheet and CATIA V5 RULA analysis, NIOSH lifting index (LI) and recommended weight limit (RWL). Ten workers are selected for pilot study and as for anthropometry measurement all workers in the warehouse department were involved. From the first pilot study, the RULA assessment score in CATIA V5 shows the highest score which is 7 for all postures and results after improvement of working posture is very low hence, detecting weight of the material handling is not in recommendation. To reduce the risk of MSD through the improvisation of working posture, the weight limit is also calculated in order to have a RWL for each worker. Therefore, proposing a guideline for the aerospace workers involved with repetitive movement and excessive lifting will help in reducing the risk of getting MSD.

Cellular responses to the expression of unstable secretory proteins in the filamentous fungus Aspergillus oryzae.

PubMed

Yokota, Jun-Ichi; Shiro, Daisuke; Tanaka, Mizuki; Onozaki, Yasumichi; Mizutani, Osamu; Kakizono, Dararat; Ichinose, Sakurako; Shintani, Tomoko; Gomi, Katsuya; Shintani, Takahiro

2017-03-01

Filamentous fungi are often used as cell factories for recombinant protein production because of their ability to secrete large quantities of hydrolytic enzymes. However, even using strong transcriptional promoters, yields of nonfungal proteins are generally much lower than those of fungal proteins. Recent analyses revealed that expression of certain nonfungal secretory proteins induced the unfolded protein response (UPR), suggesting that they are recognized as proteins with folding defects in filamentous fungi. More recently, however, even highly expressed endogenous secretory proteins were found to evoke the UPR. These findings raise the question of whether the unfolded or misfolded state of proteins is selectively recognized by quality control mechanisms in filamentous fungi. In this study, a fungal secretory protein (1,2-α-D-mannosidase; MsdS) with a mutation that decreases its thermostability was expressed at different levels in Aspergillus oryzae. We found that, at moderate expression levels, wild-type MsdS was secreted to the medium, while the mutant was not. In the strain with a deletion for the hrdA gene, which is involved in the endoplasmic reticulum-associated degradation pathway, mutant MsdS had specifically increased levels in the intracellular fraction but was not secreted. When overexpressed, the mutant protein was secreted to the medium to a similar extent as the wild-type protein; however, the mutant underwent hyperglycosylation and induced the UPR. Deletion of α-amylase (the most abundant secretory protein in A. oryzae) alleviated the UPR induction by mutant MsdS overexpression. These findings suggest that misfolded MsdS and unfolded species of α-amylase might act synergistically for UPR induction.

The contribution of major diagnostic causes to socioeconomic differences in disability retirement.

PubMed

Polvinen, Anu; Laaksonen, Mikko; Gould, Raija; Lahelma, Eero; Martikainen, Pekka

2014-07-01

The aim of this study was twofold: to investigate socioeconomic differences in disability retirement (DR) due to major diseases and find out which diseases contribute most to the overall socioeconomic differences in DR. The data were longitudinal register-based (10% sample of Finns) from Statistics Finland. These data included 258 428 participants aged 35-64 years during the follow-up. The participants were employed or unemployed before the follow-up period 1997-2010. Of all participants, 14 303 men and 13 188 women ended up in DR during the follow-up. Socioeconomic status was categorized into upper- and lower-class non-manual employees, manual workers, and self-employed persons. Cox models were used to estimate hazard ratios for DR due to different diseases. Compared to upper-class non-manual employees, DR was especially high for manual workers whose retirement diagnoses included psychoactive substance use, musculoskeletal diseases (MSD), or cardiovascular diseases. Socioeconomic differences in DR were stronger for younger age groups and men versus women. For females and males, the largest part of the excess DR among manual workers compared to upper-class non-manual employees was due to MSD. In the age group 54-64 years, the contribution of MSD to the total excess was >50% among male manual workers and 75% among female manual workers. Excess DR due to mental disorders concerned only 35-54-year-old manual workers (among 23% men and 26% women). The contribution of MSD to the total excess DR among lower socioeconomic groups was large. Prevention of MSD among manual workers would likely reduce socioeconomic differences in DR.

A descriptive study of U.S. OSHA penalties and inspection frequency for musculoskeletal disorders in the workplace.

PubMed

Courtney, T K; Clancy, E A

1998-08-01

Information on the frequency and cost of OSHA enforcement penalties for musculoskeletal disorders (MSD) in the literature is limited. Such information would be of value to organizations in estimating the likelihood and financial impact of enforcement activity in their operations. This descriptive study utilized data from federal Occupational Safety and Health Administration (OSHA) inspections to examine the distribution of penalty costs arising from inspections with MSD-related citations from January 1985 to June 1994 and to estimate the probability of OSHA inspection in general and OSHA citation for MSD hazards from October 1985 to September 1993. The mean and median values of proposed penalties were $47,707 and $3600 respectively. A substantial influence of 1991 changes to the penalty structure was noted with decreasing mean and increasing median penalty values. Penalty values increased with establishment size and were higher for unplanned than for planned inspections. The probability of a federal OSHA inspection for any establishment ranged from 1:50 in 1986 to 1:100 in 1993 whereas the estimated probability of an inspection with MSD-related citations ranged from 1:167,000 in 1996 to as much as 1:38,000 during the peak of enforcement activity in 1990. The probability of an inspection with MSD citations for the largest establishments during the period was more than 1000 times greater than that for the smallest. The results of this study may be utilized by organizations seeking to demonstrate the advantages of reducing musculoskeletal morbidity in the workplace.

Comparison of Musculoskeletal Disorder Health Claims Between Construction Floor Layers and a General Working Population

PubMed Central

Dale, Ann Marie; Ryan, Daniel; Welch, Laura; Olsen, Margaret A.; Buchholz, Bryan; Evanoff, Bradley

2014-01-01

Objectives Compare rates of medical insurance claims for musculoskeletal disorders (MSD) between workers in a construction trade and a general worker population to determine if higher physical exposures in construction lead to higher rates of claims on personal medical insurance. Methods Health insurance claims between 2006 and 2010 from floor layers were frequency matched by age, gender, eligibility time, and geographic location to claims from insured workers in general industry obtained from MarketScan. We extracted MSD claims and dates of service from six regions of the body: neck, low back, knee, lower extremity, shoulder, and distal arm, and evaluated differences in claim rates. Results Fifty-one percent of floor layers (n=1,475) experienced musculoskeletal claims compared to 39% of MarketScan members (p<0.001). Claim rates were higher for floor layers across all body regions with nearly double the rate ratios for the knee and neck regions (RR: 2.10 and 2.07). The excess risk was greatest for the neck and low back regions; younger workers had disproportionately higher rates in the knee, neck, low back, and distal arm. A larger proportion of floor layers (22%) filed MSD claims in more than one body region compared to general workers (10%; p<0.001). Conclusions Floor layers have markedly higher rates of MSD claims compared to a general worker population, suggesting shifting of medical costs for work-related MSD to personal health insurance. The occurrence of disorders in multiple body regions and among the youngest workers highlights the need for improved work methods and tools for construction workers. PMID:25224720

KSC-2009-2938

NASA Image and Video Library

2009-05-05

CAPE CANAVERAL, Fla. – In the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, technicians place equipment in the Resupply Stowage Platform, or RSP, to be installed in the multi-purpose logistics module Leonardo. The module is part of the payload for space shuttle Discovery's STS-128 mission. Discovery will carry science and storage racks to the International Space Station . Launch of Discovery is targeted for Aug. 6. Photo credit: NASA/Kim Shiflett

Payload canister for Discovery is lifted in place for transfer

NASA Technical Reports Server (NTRS)

1998-01-01

At left, the payload canister for Space Shuttle Discovery is lifted from its canister movement vehicle to the top of the Rotating Service Structure on Launch Pad 39-B. Discovery (right), sitting atop the Mobile Launch Platform and next to the Fixed Service Structure (FSS), is scheduled for launch on Oct. 29, 1998, for the STS-95 mission. That mission includes the International Extreme Ultraviolet Hitchhiker (IEH-3), the Hubble Space Telescope Orbital Systems Test Platform, the Spartan solar- observing deployable spacecraft, and the SPACEHAB single module with experiments on space flight and the aging process. At the top of the FSS can be seen the 80-foot lightning mast . The 4- foot-high lightning rod on top helps prevent lightning current from passing directly through the Space Shuttle and the structures on the pad.

An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products.

PubMed

Johnston, Chad W; Skinnider, Michael A; Wyatt, Morgan A; Li, Xiang; Ranieri, Michael R M; Yang, Lian; Zechel, David L; Ma, Bin; Magarvey, Nathan A

2015-09-28

Bacterial natural products are a diverse and valuable group of small molecules, and genome sequencing indicates that the vast majority remain undiscovered. The prediction of natural product structures from biosynthetic assembly lines can facilitate their discovery, but highly automated, accurate, and integrated systems are required to mine the broad spectrum of sequenced bacterial genomes. Here we present a genome-guided natural products discovery tool to automatically predict, combinatorialize and identify polyketides and nonribosomal peptides from biosynthetic assembly lines using LC-MS/MS data of crude extracts in a high-throughput manner. We detail the directed identification and isolation of six genetically predicted polyketides and nonribosomal peptides using our Genome-to-Natural Products platform. This highly automated, user-friendly programme provides a means of realizing the potential of genetically encoded natural products.

Annotation-based genome-wide SNP discovery in the large and complex Aegilops tauschii genome using next-generation sequencing without a reference genome sequence

PubMed Central

2011-01-01

Background Many plants have large and complex genomes with an abundance of repeated sequences. Many plants are also polyploid. Both of these attributes typify the genome architecture in the tribe Triticeae, whose members include economically important wheat, rye and barley. Large genome sizes, an abundance of repeated sequences, and polyploidy present challenges to genome-wide SNP discovery using next-generation sequencing (NGS) of total genomic DNA by making alignment and clustering of short reads generated by the NGS platforms difficult, particularly in the absence of a reference genome sequence. Results An annotation-based, genome-wide SNP discovery pipeline is reported using NGS data for large and complex genomes without a reference genome sequence. Roche 454 shotgun reads with low genome coverage of one genotype are annotated in order to distinguish single-copy sequences and repeat junctions from repetitive sequences and sequences shared by paralogous genes. Multiple genome equivalents of shotgun reads of another genotype generated with SOLiD or Solexa are then mapped to the annotated Roche 454 reads to identify putative SNPs. A pipeline program package, AGSNP, was developed and used for genome-wide SNP discovery in Aegilops tauschii-the diploid source of the wheat D genome, and with a genome size of 4.02 Gb, of which 90% is repetitive sequences. Genomic DNA of Ae. tauschii accession AL8/78 was sequenced with the Roche 454 NGS platform. Genomic DNA and cDNA of Ae. tauschii accession AS75 was sequenced primarily with SOLiD, although some Solexa and Roche 454 genomic sequences were also generated. A total of 195,631 putative SNPs were discovered in gene sequences, 155,580 putative SNPs were discovered in uncharacterized single-copy regions, and another 145,907 putative SNPs were discovered in repeat junctions. These SNPs were dispersed across the entire Ae. tauschii genome. To assess the false positive SNP discovery rate, DNA containing putative SNPs was amplified by PCR from AL8/78 and AS75 and resequenced with the ABI 3730 xl. In a sample of 302 randomly selected putative SNPs, 84.0% in gene regions, 88.0% in repeat junctions, and 81.3% in uncharacterized regions were validated. Conclusion An annotation-based genome-wide SNP discovery pipeline for NGS platforms was developed. The pipeline is suitable for SNP discovery in genomic libraries of complex genomes and does not require a reference genome sequence. The pipeline is applicable to all current NGS platforms, provided that at least one such platform generates relatively long reads. The pipeline package, AGSNP, and the discovered 497,118 Ae. tauschii SNPs can be accessed at (http://avena.pw.usda.gov/wheatD/agsnp.shtml). PMID:21266061

Developing a Satellite Educational Program for Deaf and Hard of Hearing Students Residing in a Rural Setting.

ERIC Educational Resources Information Center

Witt, Sheree; Howell, Ruth

The Allegany County School System and the Maryland School for the Deaf (MSD) have collaborated to develop a satellite program that brings MSD educational services to hard-of-hearing and deaf elementary students in rural western Maryland. In the past 5 years, the number of hearing-impaired preschoolers in Allegany and Garrett Counties increased…

Five Essential Features of Quality Educational Programs for Students with Moderate and Severe Intellectual Disability: A Guide for Administrators

ERIC Educational Resources Information Center

Pennington, Robert; Courtade, Ginevra; Jones Ault, Melinda; Delano, Monica

2016-01-01

Despite encouraging changes in the expectations of programming for persons with moderate to severe intellectual disability (MSD), data suggest that programs for these individuals are still lacking in several critical areas. Building administrators play a key role in promoting high quality programs for students with MSD within local schools but may…

36 CFR 3.13 - What conditions apply to the use of Marine Sanitation Devices (MSD)?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false What conditions apply to the use of Marine Sanitation Devices (MSD)? 3.13 Section 3.13 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR BOATING AND WATER USE ACTIVITIES § 3.13 What conditions apply...

36 CFR 3.13 - What conditions apply to the use of Marine Sanitation Devices (MSD)?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false What conditions apply to the use of Marine Sanitation Devices (MSD)? 3.13 Section 3.13 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR BOATING AND WATER USE ACTIVITIES § 3.13 What conditions apply...

Examination of postures and frequency of musculoskeletal disorders among manual workers in Calcutta, India.

PubMed

Sarkar, Krishnendu; Dev, Samrat; Das, Tamal; Chakrabarty, Sabarni; Gangopadhyay, Somnath

2016-04-01

Manual material handling (MMH) activities require workers to adopt various awkward postures leading to the development of musculoskeletal disorders (MSD). To investigate the postures adopted during heavy load handling and the frequency of MSDs among MMH workers in Calcutta, India. We conducted a cross-sectional study with 100 MMH workers. MSD frequency was assessed via the Standardized Nordic Questionnaire. The Ovako Working Posture Assessment System (OWAS) was used to analyze working posture. We used logistic regression to predict MSD risk factors. Ninety five percent of workers reported a MSD in at least one body part in the past 12 months. According to OWAS results, 83% of the analysed work postures require immediate corrective measures for worker safety. The most harmful posture was carrying a heavy load overhead. Carrying more than 120 kg increased the odds of low back and neck pain by 4.527 and 4.555, respectively. This sample had a high frequency of reported MSDs, likely attributed to physiologically strenuous occupational activities repeated on average of 30-40 times daily. Ergonomic interventions, such as the use of handcarts, and occupational training are urgently needed.

Cooperative unfolding of distinctive mechanoreceptor domains transduces force into signals

PubMed Central

Ju, Lining; Chen, Yunfeng; Xue, Lingzhou; Du, Xiaoping; Zhu, Cheng

2016-01-01

How cells sense their mechanical environment and transduce forces into biochemical signals is a crucial yet unresolved question in mechanobiology. Platelets use receptor glycoprotein Ib (GPIb), specifically its α subunit (GPIbα), to signal as they tether and translocate on von Willebrand factor (VWF) of injured arterial surfaces against blood flow. Force elicits catch bonds to slow VWF–GPIbα dissociation and unfolds the GPIbα leucine-rich repeat domain (LRRD) and juxtamembrane mechanosensitive domain (MSD). How these mechanical processes trigger biochemical signals remains unknown. Here we analyze these extracellular events and the resulting intracellular Ca2+ on a single platelet in real time, revealing that LRRD unfolding intensifies Ca2+ signal whereas MSD unfolding affects the type of Ca2+ signal. Therefore, LRRD and MSD are analog and digital force transducers, respectively. The >30 nm macroglycopeptide separating the two domains transmits force on the VWF–GPIbα bond (whose lifetime is prolonged by LRRD unfolding) to the MSD to enhance its unfolding, resulting in unfolding cooperativity at an optimal force. These elements may provide design principles for a generic mechanosensory protein machine. DOI: http://dx.doi.org/10.7554/eLife.15447.001 PMID:27434669

Interannual Variability of the Bimodal Distribution of Summertime Rainfall Over Central America and Tropical Storm Activity in the Far-Eastern Pacific

NASA Technical Reports Server (NTRS)

Curtis, Scott; Starr, David OC. (Technical Monitor)

2002-01-01

The summer climate of southern Mexico and Central America is characterized by a mid summer drought (MSD), where rainfall is reduced by 40% in July as compared to June and September. A mid-summer reduction in the climatological number of eastern Pacific tropical cyclones has also been noted. Little is understood about the climatology and interannual variability of these minima. The present study uses a novel approach to quantify the bimodal distribution of summertime rainfall for the globe and finds that this feature of the annual cycle is most extreme over Pan America and adjacent oceans. One dominant interannual signal in this region occurs the summer before a strong winter El Nino/Southern Oscillation ENSO. Before El Nino events the region is dry, the MSD is strong and centered over the ocean, and the mid-summer minimum in tropical cyclone frequency is most pronounced. This is significantly different from Neutral cases (non-El Nino and non-La Nina) when the MSD is weak and positioned over the land bridge. The MSD is highly variable for La Nina years, and there is not an obvious mid-summer minimum in the number of tropical cyclones.

Mitochondrial fluctuations as a measure of active biomechanical properties of mammalian cells

NASA Astrophysics Data System (ADS)

Xu, Wenlong; Alizadeh, Elaheh; Castle, Jordan; Prasad, Ashok

A single-cell assay of mechanical properties would give significant insights into cellular processes. Force spectrum microscopy is one such technique, which involves both active and passive particle tracking microrheology on the same cells. Since active microrheology requires expensive instruments, it is of great interest to develop simpler alternatives. Here we study an alternative using endogenous mitochondrial fluctuations, rather than fluorescent beads, in particle tracking microrheology. Mitochondria of the C3H-10T1/2 cell line are labeled and tracked using confocal microscopy, their mean square displacement (MSD) measured, and mechanical parameters calculated. Active fluctuations are distinguished from passive fluctuations by treatment with ATP synthesis inhibitors. We find that the MSD of mitochondria resembles that of particles in viscoelastic media. However, comparisons of MSD between controls and cells disrupted in the actin or microtubule network showed surprisingly small effects, while ATP-depleted cells showed significantly decreased MSD, and characteristics of thermally driven fluctuations. Both active and ATP-depleted parameters showed heterogeneity among cells and between cell lines. This method is potentially very useful due to its simplicity. We gratefully acknowledge support from NSF CAREER Grant PHY-1151454 awarded to Ashok Prasad.

Musculoskeletal disorder risk as a function of vehicle rotation angle during assembly tasks.

PubMed

Ferguson, Sue A; Marras, Williams S; Gary Allread, W; Knapik, Gregory G; Vandlen, Kimberly A; Splittstoesser, Riley E; Yang, Gang

2011-07-01

Musculoskeletal disorders (MSD) are costly and common problem in automotive manufacturing. The research goal was to quantify MSD exposure as a function of vehicle rotation angle and region during assembly tasks. The study was conducted at the Center for Occupational Health in Automotive Manufacturing (COHAM) Laboratory. Twelve subjects participated in the study. The vehicle was divided into seven regions, (3 interior, 2 underbody and 2 engine regions) representative of work areas during assembly. Three vehicle rotation angles were examined for each region. The standard horizontal assembly condition (0° rotation) was the reference frame. Exposure was assessed on the spine loads and posture, shoulder posture and muscle activity, neck posture and muscle activity as well as wrist posture. In all regions, rotating the vehicle reduced musculoskeletal exposure. In five of the seven regions 45° of vehicle rotation represented the position that reduced MSD exposure most. Two of the seven regions indicated 90° of vehicle rotation had the greatest impact for reducing MSD exposure. This study demonstrated that vehicle rotation shows promise for reducing exposure to risk factors for MDS during automobile assembly tasks. Copyright © 2010 Elsevier Ltd and The Ergonomics Society. All rights reserved.

KENNEDY SPACE CENTER, FLA. - This bird's-eye view of a high bay in the Orbiter Processing Facility (OPF) shows the open payload bay of Space Shuttle Discovery surrounded by the standard platforms and equipment required to process a Space Shuttle orbiter. The high bay is 197 feet (60 meters) long, 150 feet (46 meters) wide, 95 feet (29 meters) high, and encompasses a 29,000-square-foot (2,694-meter) area. The 30-ton (27-metric-ton) bridge crane (yellow device, right) has a hook height of approximately 66 feet (20 meters). Platforms, a main access bridge, and two rolling bridges with trucks provide access to various parts of the orbiter. In addition to routine servicing and checkout, the inspections and modifications made to enhance Discovery's performance and upgrade its systems were performed in the OPF during its recently completed Orbiter Major Modification (OMM) period.

NASA Image and Video Library

2003-09-02

KENNEDY SPACE CENTER, FLA. - This bird's-eye view of a high bay in the Orbiter Processing Facility (OPF) shows the open payload bay of Space Shuttle Discovery surrounded by the standard platforms and equipment required to process a Space Shuttle orbiter. The high bay is 197 feet (60 meters) long, 150 feet (46 meters) wide, 95 feet (29 meters) high, and encompasses a 29,000-square-foot (2,694-meter) area. The 30-ton (27-metric-ton) bridge crane (yellow device, right) has a hook height of approximately 66 feet (20 meters). Platforms, a main access bridge, and two rolling bridges with trucks provide access to various parts of the orbiter. In addition to routine servicing and checkout, the inspections and modifications made to enhance Discovery's performance and upgrade its systems were performed in the OPF during its recently completed Orbiter Major Modification (OMM) period.

Integrated Platform for Expedited Synthesis–Purification–Testing of Small Molecule Libraries

PubMed Central

2017-01-01

The productivity of medicinal chemistry programs can be significantly increased through the introduction of automation, leading to shortened discovery cycle times. Herein, we describe a platform that consolidates synthesis, purification, quantitation, dissolution, and testing of small molecule libraries. The system was validated through the synthesis and testing of two libraries of binders of polycomb protein EED, and excellent correlation of obtained data with results generated through conventional approaches was observed. The fully automated and integrated platform enables batch-supported compound synthesis based on a broad array of chemical transformations with testing in a variety of biochemical assay formats. A library turnaround time of between 24 and 36 h was achieved, and notably, each library synthesis produces sufficient amounts of compounds for further evaluation in secondary assays thereby contributing significantly to the shortening of medicinal chemistry discovery cycles. PMID:28435537

Network-based drug discovery by integrating systems biology and computational technologies

PubMed Central

Leung, Elaine L.; Cao, Zhi-Wei; Jiang, Zhi-Hong; Zhou, Hua

2013-01-01

Network-based intervention has been a trend of curing systemic diseases, but it relies on regimen optimization and valid multi-target actions of the drugs. The complex multi-component nature of medicinal herbs may serve as valuable resources for network-based multi-target drug discovery due to its potential treatment effects by synergy. Recently, robustness of multiple systems biology platforms shows powerful to uncover molecular mechanisms and connections between the drugs and their targeting dynamic network. However, optimization methods of drug combination are insufficient, owning to lacking of tighter integration across multiple ‘-omics’ databases. The newly developed algorithm- or network-based computational models can tightly integrate ‘-omics’ databases and optimize combinational regimens of drug development, which encourage using medicinal herbs to develop into new wave of network-based multi-target drugs. However, challenges on further integration across the databases of medicinal herbs with multiple system biology platforms for multi-target drug optimization remain to the uncertain reliability of individual data sets, width and depth and degree of standardization of herbal medicine. Standardization of the methodology and terminology of multiple system biology and herbal database would facilitate the integration. Enhance public accessible databases and the number of research using system biology platform on herbal medicine would be helpful. Further integration across various ‘-omics’ platforms and computational tools would accelerate development of network-based drug discovery and network medicine. PMID:22877768

Aging ballistic Lévy walks

NASA Astrophysics Data System (ADS)

Magdziarz, Marcin; Zorawik, Tomasz

2017-02-01

Aging can be observed for numerous physical systems. In such systems statistical properties [like probability distribution, mean square displacement (MSD), first-passage time] depend on a time span ta between the initialization and the beginning of observations. In this paper we study aging properties of ballistic Lévy walks and two closely related jump models: wait-first and jump-first. We calculate explicitly their probability distributions and MSDs. It turns out that despite similarities these models react very differently to the delay ta. Aging weakly affects the shape of probability density function and MSD of standard Lévy walks. For the jump models the shape of the probability density function is changed drastically. Moreover for the wait-first jump model we observe a different behavior of MSD when ta≪t and ta≫t .

[Between mind and body. Psychologicall methods for patients with musculoskeletal pain].

PubMed

Jabłońska-Brzozowska, Judyta

According to the currently prevailing trends in medicine in restoring the psychosomatic unity of human, it is important to ask the question about the function and role of psychology in the rehabilitation of patients with chronic musculoskeletal disorder, MSD. In this article authors present the theoretical basis of psychical and body rehabilitation of patients with MSD. In the first part of this article, problem of the prevalence of MSD in population, its biological, psychological and social components and its impact on the economy of the country, have been discussed. Secondly, there was a focus on the mental representation of the body and its role as a psychophysical integrating unit. The following sections discuss therapeutic methods, like cognitive-behavioral therapy and chosen body work methods as complex rehabilitation of patients with musculoskeletal pain.

Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation

PubMed Central

Kourtesi, Christina; Ball, Anthony R; Huang, Ying-Ying; Jachak, Sanjay M; Vera, D Mariano A; Khondkar, Proma; Gibbons, Simon; Hamblin, Michael R; Tegos, George P

2013-01-01

Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches. PMID:23569468

The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS).

PubMed

Sow, Samba O; Muhsen, Khitam; Nasrin, Dilruba; Blackwelder, William C; Wu, Yukun; Farag, Tamer H; Panchalingam, Sandra; Sur, Dipika; Zaidi, Anita K M; Faruque, Abu S G; Saha, Debasish; Adegbola, Richard; Alonso, Pedro L; Breiman, Robert F; Bassat, Quique; Tamboura, Boubou; Sanogo, Doh; Onwuchekwa, Uma; Manna, Byomkesh; Ramamurthy, Thandavarayan; Kanungo, Suman; Ahmed, Shahnawaz; Qureshi, Shahida; Quadri, Farheen; Hossain, Anowar; Das, Sumon K; Antonio, Martin; Hossain, M Jahangir; Mandomando, Inacio; Nhampossa, Tacilta; Acácio, Sozinho; Omore, Richard; Oundo, Joseph O; Ochieng, John B; Mintz, Eric D; O'Reilly, Ciara E; Berkeley, Lynette Y; Livio, Sofie; Tennant, Sharon M; Sommerfelt, Halvor; Nataro, James P; Ziv-Baran, Tomer; Robins-Browne, Roy M; Mishcherkin, Vladimir; Zhang, Jixian; Liu, Jie; Houpt, Eric R; Kotloff, Karen L; Levine, Myron M

2016-05-01

The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27-4.67) and 3.18 (95% CI, 1.85-4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73-2.08) and 1.36 (95% CI, 0.66-2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33-5.01) and 4.88 (95% CI, 0.82-8.92) in infants and 4.04 (95% CI, 0.56-7.51) and 4.71 (95% CI, 0.24-9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies.

The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS)

PubMed Central

Nasrin, Dilruba; Blackwelder, William C.; Wu, Yukun; Farag, Tamer H.; Panchalingam, Sandra; Sur, Dipika; Zaidi, Anita K. M.; Faruque, Abu S. G.; Saha, Debasish; Adegbola, Richard; Alonso, Pedro L.; Breiman, Robert F.; Bassat, Quique; Tamboura, Boubou; Sanogo, Doh; Onwuchekwa, Uma; Manna, Byomkesh; Ramamurthy, Thandavarayan; Kanungo, Suman; Ahmed, Shahnawaz; Qureshi, Shahida; Quadri, Farheen; Hossain, Anowar; Das, Sumon K.; Antonio, Martin; Hossain, M. Jahangir; Mandomando, Inacio; Nhampossa, Tacilta; Acácio, Sozinho; Omore, Richard; Oundo, Joseph O.; Ochieng, John B.; Mintz, Eric D.; O’Reilly, Ciara E.; Berkeley, Lynette Y.; Livio, Sofie; Tennant, Sharon M.; Sommerfelt, Halvor; Nataro, James P.; Ziv-Baran, Tomer; Robins-Browne, Roy M.; Mishcherkin, Vladimir; Zhang, Jixian; Liu, Jie; Houpt, Eric R.; Kotloff, Karen L.; Levine, Myron M.

2016-01-01

Background The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. Methods Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. Findings Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27–4.67) and 3.18 (95% CI, 1.85–4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73–2.08) and 1.36 (95% CI, 0.66–2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33–5.01) and 4.88 (95% CI, 0.82–8.92) in infants and 4.04 (95% CI, 0.56–7.51) and 4.71 (95% CI, 0.24–9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. Conclusions The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies. PMID:27219054

ATOM - Accelerating therapeutics through opportunities in medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mcmahon, Benjamin Hamilton; Dotson, Paul Jeffrey

Create a new paradigm of drug discovery that would reduce the time from an identified drug target to clinical candidate from the current ~6 years to just 12 months. ATOM will develop, test, and validate a multidisciplinary approach to drug discovery in which modern science, technology and engineering, supercomputing, simulations, data science, and artificial intelligence are highly integrated into a single drug-discovery platform that can ultimately be shared with the drug development community at-large.

Development of an Automated Microfluidic Reaction Platform for Multidimensional Screening: Reaction Discovery Employing Bicyclo[3.2.1]octanoid Scaffolds

PubMed Central

Goodell, John R.; McMullen, Jonathan P.; Zaborenko, Nikolay; Maloney, Jason R.; Ho, Chuan-Xing; Jensen, Klavs F.; Porco, John A.

2010-01-01

An automated, silicon-based microreactor system has been developed for rapid, low-volume, multidimensional reaction screening. Use of the microfluidic platform to identify transformations of densely functionalized bicyclo[3.2.1]octanoid scaffolds will be described. PMID:20560568

The Relationship between Mean Square Differences and Standard Error of Measurement: Comment on Barchard (2012)

ERIC Educational Resources Information Center

Pan, Tianshu; Yin, Yue

2012-01-01

In the discussion of mean square difference (MSD) and standard error of measurement (SEM), Barchard (2012) concluded that the MSD between 2 sets of test scores is greater than 2(SEM)[superscript 2] and SEM underestimates the score difference between 2 tests when the 2 tests are not parallel. This conclusion has limitations for 2 reasons. First,…

Berkeley Lab - Materials Sciences Division

Science.gov Websites

Berkeley Lab Berkeley Lab A-Z Index Phone Book Jobs Search DOE Search MSD Go MSD - Materials Investigators Ager, Joel W » Alivisatos, A Paul » Altman, Ehud » Analytis, James » Anderson, Christopher  , Naomi » Gullikson, Eric M » Harris, Stephen J » Hasan, M. Zahid » Hellman, Frances » Helms, Brett A

SLAC Phone Directory: Search Form

Science.gov Websites

Facilities LCLS Hard X-Ray LCLS IT & Networking LCLS IT Photon Systems LCLS Instrumentation Dev LCLS Delivery Dept LCLS Science Research & DevDiv LCLS Soft X-Ray LCLS Technical Support LCLS User Beam Line Ops Sup SSRL MSD Hard X-rays SSRL MSD Soft X-rays SSRL MSDBeam Line Elec SSRL MSDBeam Line

St. Francis Rain Garden Water Quality Sampling Interim Data Report; Total Nitrogen, Total Phosphorus, Sediments or Solids, and E. Coli for the period April to June, 2014

EPA Science Inventory

This interim data reported is being provided per request to the Metropolitan Sewer District (MSD) to provide summary statistics on a limited set of water quality parameters as measured at the St. Francis Rain Garden site in the Lick Run Valley as it pertains to MSD's Project Grou...

Meta Salud Diabetes study protocol: a cluster-randomised trial to reduce cardiovascular risk among a diabetic population of Mexico.

PubMed

Sabo, Samantha; Denman Champion, Catalina; Bell, Melanie L; Cornejo Vucovich, Elsa; Ingram, Maia; Valenica, Celina; Castro Vasquez, Maria Del Carmen; Gonzalez-Fagoaga, Eduardo; Geurnsey de Zapien, Jill; Rosales, Cecilia B

2018-03-12

Northern Mexico has among the highest rates of cardiovascular disease (CVD) and diabetes in the world. This research addresses core gaps in implementation science to develop, test and scale-up CVD risk-reduction interventions in diabetics through a national primary care health system. The Meta Salud Diabetes (MSD) research project is a parallel two-arm cluster-randomised clinical behavioural trial based in 22 (n=22) health centres in Sonora, Mexico. MSD aims to evaluate the effectiveness of the MSD intervention for the secondary prevention of CVD risk factors among a diabetic population (n=320) compared with the study control of usual care. The MSD intervention consists of 2-hour class sessions delivered over a 13-week period providing educational information to encourage sustainable behavioural change to prevent disease complications including the adoption of physical activity. MSD is delivered within the context of Mexico's national primary care health centre system by health professionals, including nurses, physicians and community health workers via existing social support groups for individuals diagnosed with chronic disease. Mixed models are used to estimate the effect of MSD by comparing cardiovascular risk, as measured by the Framingham Risk Score, between the trial arms. Secondary outcomes include hypertension, behavioural risk factors and psychosocial factors. This work is supported by the National Institutes of Health, National Heart Lung and Blood Institute (1R01HL125996-01) and approved by the University of Arizona Research Institutional Review Board (Protocol 1508040144) and the Research Bioethics Committee at the University of Sonora. The first Internal Review Board approval date was 31 August 2015 with five subsequent approved amendments. This article refers to protocol V.0.2, dated 30 January 2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences and will be shared through meetings with health systems officials. NCT0280469; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[A comparative study of unrelated donor and matched-sibling donor allogeneic hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia].

PubMed

Zhou, J; Fu, Y W; Liang, L J; Wang, Q; Han, L J; Zu, Y L; Zhang, Yanli; Zhu, X H; Yu, F K; Fang, B J; Wei, X D; Song, Y P

2016-12-01

Objective: To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT) for children and adolescents with severe aplastic anemia (SAA). Methods: Clinical data of 34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015. According to the source of donor, the patients were divided into matched sibling donor allo-HSCT group (MSD group) and unrelated donor group (URD group). The clinical outcome of SAA children and adolescents receiving URD allo-HSCT was assessed, and patients in MSD allo-HSCT group were enrolled as control at the same period. Results: The rate of hematopoietic reconstitution, the time of neutrophil and platelet engraftment, incidence of chimerism and graft rejection between two groups were not statistically different.The incidence of acute graft-versus-host disease (GVHD) in URD group was significantly higher than that in MSD group [42.9%(6/14) vs 10.5%(2/19), P =0.047]. The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD in URD were higher than those in MSD group [21.4%(3/14) vs 5.3%(1/19), P =0.288; 35.7%(5/14) vs 5.3%(1/19), P =0.062, respectively], yet without significant difference between two groups. Other transplant-related complications including pulmonary complications, hemorrhagic cystitis, incidence of EBV and CMV reactivation and venous occlusive disease were comparable with two regimens. Estimated 5-years overall survival (OS) rate and disease free survival (DFS) rate were not statistically significant between URD group and MSD group [(84.4±6.6)% vs (89.4±7.1)%, (82.5±5.4)% vs (82.1±4.3)%; P =0.766, P =0.884, respectively]. Conclusions: By multivariate analysis, the outcome of URD allo-HSCT in SAA children and adolescent is similar to MSD allo-HSCT. It could be an alternative option as the first-line treatment for SAA children and adolescents without HLA matched sibling donors.

Molecular and structural characteristics of multidrug resistance-associated protein 7 in Chinese liver fluke Clonorchis sinensis.

PubMed

Dai, Fuhong; Yoo, Won Gi; Lee, Ji-Yun; Lu, Yanyan; Pak, Jhang Ho; Sohn, Woon-Mok; Hong, Sung-Jong

2017-03-01

Multidrug resistance-associated protein 7 (MRP7, ABCC10) is a C subfamily member of the ATP-binding cassette (ABC) superfamily. MRP7 is a lipophilic anion transporter that pumps endogenous and xenobiotic substrates from the cytoplasm to the extracellular milieu. Here, we cloned and characterized CsMRP7 as a novel ABC transporter from the Chinese liver fluke, Clonorchis sinensis. Full-length cDNA of CsMRP7 was 5174 nt, encoded 1636 amino acids (aa), and harbored a 147-bp 5'-untranslated region (5'-UTR) and 116-bp 3'-UTR. Phylogenetic analysis confirmed that CsMRP7 was closer to the ABCC subfamily than the ABCB subfamily. Tertiary structures of the N-terminal region (1-322 aa) and core region (323-1621 aa) of CsMRP7 were generated by homology modeling using glucagon receptor (PDB ID: 5ee7_A) and P-glycoprotein (PDB ID: 4f4c_A) as templates, respectively. CsMRP7 nucleotide-binding domain 2 (NBD2) was conserved more than NBD1, which was the sites of ATP binding and hydrolysis. Like typical long MRPs, CsMRP7 has an additional membrane-spanning domain 0 (MSD0) and cytoplasmic loop, along with a common structural fold consisting of MSD1-NBD1-MSD2-NBD2 as a single polypeptide assembly. MSD0, MSD1, and MSD2 consisted of TM1-7, TM8-13, and TM14-19, respectively. The CsMRP7 transcript was more abundant in the metacercariae than in the adult worms. Truncated NBD1 (39 kDa) and NBD2 (44 kDa) were produced in bacteria and mouse immune sera were raised. CsMRP7 was localized in the apical side of the intestinal epithelium, sperm in the testes and seminal receptacle, receptacle membrane, and mesenchymal tissue around intestine in the adult worm. These results provide molecular information and insights into structural and functional characteristics of CsMRP7 and homologs of flukes.

Development of the chronic obstructive pulmonary disease morning symptom diary (COPD-MSD).

PubMed

Globe, Gary; Currie, Brooke; Leidy, Nancy Kline; Jones, Paul; Mannino, David; Martinez, Fernando; Klekotka, Paul; O'Quinn, Sean; Karlsson, Niklas; Wiklund, Ingela

2016-07-16

The morning tends to be the most difficult time of day for many patients with chronic obstructive pulmonary disease (COPD) when symptoms can limit one's ability to perform even simple activities. Morning symptoms have been linked to higher levels of work absenteeism, thereby increasing the already substantial economic burden associated with COPD. A validated patient-reported outcome (PRO) instrument designed to capture morning symptoms will allow for a more comprehensive approach to the evaluation of treatment benefit in COPD clinical trials. A qualitative interview study was conducted among a sample of symptomatic adults with COPD. Concept elicitation interviews (n = 35) were conducted to identify COPD morning symptoms, followed by cognitive interviews (n = 21) to ensure patient comprehension of the items, instructions and response options of the draft COPD Morning Symptom Diary (COPD-MSD). All interview transcript data were coded using ATLAS.ti software for content analysis. Mean age of the concept elicitation and cognitive interview sample was 65.0 years (±7.5) and 62.3 years (±8.3), respectively. The study sample represented the full range of COPD severity (Global Initiative for Chronic Lung Disease [GOLD] classifications I-IV) and included a mix of racial backgrounds, employment status and educational achievement. During the concept elicitation interviews, the three most frequently reported morning symptoms were shortness of breath (n = 35/35; 100 %), phlegm/mucus (n = 31/35; 88.6 %), and cough (n = 30/35; 85.7 %). A group of clinical and instrument development experts convened to review the concept elicitation data and develop the initial 32-item draft COPD-MSD. Cognitive interviews indicated subjects found the draft COPD-MSD to be comprehensive, clear, and easy to understand. The COPD-MSD underwent minor editorial revisions and streamlining based on cognitive interviews and input from the experts to yield the final 19-item daily diary. This study supports the content validity of the new COPD-MSD and positions the diary for quantitative psychometric testing.

Observed soil temperature trends associated with climate change in the Tibetan Plateau, 1960-2014

NASA Astrophysics Data System (ADS)

Fang, Xuewei; Luo, Siqiong; Lyu, Shihua

2018-01-01

Soil temperature, an important indicator of climate change, has rarely explored due to scarce observations, especially in the Tibetan Plateau (TP) area. In this study, changes observed in five meteorological variables obtained from the TP between 1960 and 2014 were investigated using two non-parametric methods, the modified Mann-Kendall test and Sen's slope estimator method. Analysis of annual series from 1960 to 2014 has shown that surface (0 cm), shallow (5-20 cm), deep (40-320 cm) soil temperatures (ST), mean air temperature (AT), and precipitation (P) increased with rates of 0.47 °C/decade, 0.36 °C/decade, 0.36 °C/decade, 0.35 °C/decade, and 7.36 mm/decade, respectively, while maximum frozen soil depth (MFD) as well as snow cover depth (MSD) decreased with rates of 5.58 and 0.07 cm/decade. Trends were significant at 99 or 95% confidence level for the variables, with the exception of P and MSD. More impressive rate of the ST at each level than the AT indicates the clear response of soil to climate warming on a regional scale. Monthly changes observed in surface ST in the past decades were consistent with those of AT, indicating a central place of AT in the soil warming. In addition, with the exception of MFD, regional scale increasing trend of P as well as the decreasing MSD also shed light on the mechanisms driving soil trends. Significant negative-dominated correlation coefficients (α = 0.05) between ST and MSD indicate the decreasing MSD trends in TP were attributable to increasing ST, especially in surface layer. Owing to the frozen ground, the relationship between ST and P is complicated in the area. Higher P also induced higher ST, while the inhibition of freeze and thaw process on the ST in summer. With the increasing AT, P accompanied with the decreasing MFD, MSD should be the major factors induced the conspicuous soil warming of the TP in the past decades.

Comparison of 3 kidney injury multiplex panels in rats.

PubMed

John-Baptiste, Annette; Vitsky, Allison; Sace, Frederick; Zong, Qing; Ko, Mira; Yafawi, Rolla; Liu, Ling

2012-01-01

Kidney injury biomarkers have been utilized by pharmaceutical companies as a means to assess the potential of candidate drugs to induce nephrotoxicity. Multiple platforms and assay methods exist, but the comparison of these methods has not been described. Millipore's Kidney Toxicity panel, EMD/Novagen's Widescreen Kidney Toxicity panel, and Meso Scales Kidney Injury panel were selected based on published information. Kidney injury molecule 1, cystatin C, clusterin, and osteopontin were the 4 biomarkers common among all kits tested and the focus of this study. Rats were treated with a low and high dose of para-aminophenol, a known nephrotoxicant, and urine samples were collected and analyzed on the Bio-Plex 200 or MSD's Sector Imager 6000, according to manufacturers specifications. Comparatively, of the 3 kits, Millipore was the most consistent in detecting elevations of 3 out of the 4 biomarkers at both dose levels and indicated time points.

Clinical analysis of genome next-generation sequencing data using the Omicia platform

PubMed Central

Coonrod, Emily M; Margraf, Rebecca L; Russell, Archie; Voelkerding, Karl V; Reese, Martin G

2013-01-01

Aims Next-generation sequencing is being implemented in the clinical laboratory environment for the purposes of candidate causal variant discovery in patients affected with a variety of genetic disorders. The successful implementation of this technology for diagnosing genetic disorders requires a rapid, user-friendly method to annotate variants and generate short lists of clinically relevant variants of interest. This report describes Omicia’s Opal platform, a new software tool designed for variant discovery and interpretation in a clinical laboratory environment. The software allows clinical scientists to process, analyze, interpret and report on personal genome files. Materials & Methods To demonstrate the software, the authors describe the interactive use of the system for the rapid discovery of disease-causing variants using three cases. Results & Conclusion Here, the authors show the features of the Opal system and their use in uncovering variants of clinical significance. PMID:23895124

Stem cells: a model for screening, discovery and development of drugs.

PubMed

Kitambi, Satish Srinivas; Chandrasekar, Gayathri

2011-01-01

The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficacy studies using stem cells offers a reliable platform for the drug discovery process. Advances made in the generation of induced pluripotent stem cells from normal or diseased tissue serves as a platform to perform drug screens aimed at developing cell-based therapies against conditions like Parkinson's disease and diabetes. This review discusses the application of stem cells and cancer stem cells in drug screening and their role in complementing, reducing, and replacing animal testing. In addition to this, target identification and major advances in the field of personalized medicine using induced pluripotent cells are also discussed.

The STS-93 external tank and booster stack sits at the Mobile Launcher Platform park site

NASA Technical Reports Server (NTRS)

1999-01-01

The STS-93 stack of solid rocket boosters and external tank sits at the Mobile Launcher Platform park site waiting for lightning shield wires to be installed on the Vehicle Assembly Building (VAB) in the background. The stack is being temporarily stored outside the VAB while Space Shuttle Discovery undergoes repair to hail damage in High Bay 1. Discovery was rolled back from Pad 39B to the VAB for repairs because access to all of the damaged areas was not possible at the pad. The STS-93 stack will be moved under the wires at the VAB for protection until Discovery returns to the pad, later this week. The scheduled date for launch of mission STS-96 is no earlier than May 27. STS-93 is targeted for launch on July 22, carrying the Chandra X-ray Observatory.

A Road Map for Precision Medicine in the Epilepsies

PubMed Central

2015-01-01

Summary Technological advances have paved the way for accelerated genomic discovery and are bringing precision medicine clearly into view. Epilepsy research in particular is well-suited to serve as a model for the development and deployment of targeted therapeutics in precision medicine because of the rapidly expanding genetic knowledge base in epilepsy, the availability of good in vitro and in vivo model systems to efficiently study the biological consequences of genetic mutations, the ability to turn these models into effective drug screening platforms, and the establishment of collaborative research groups. Moving forward, it is critical that we strengthen these collaborations, particularly through integrated research platforms to provide robust analyses both for accurate personal genome analysis and gene and drug discovery. Similarly, the implementation of clinical trial networks will allow the expansion of patient sample populations with genetically defined epilepsy so that drug discovery can be translated into clinical practice. PMID:26416172

Impact of physician preferences for homeopathic or conventional medicines on patients with musculoskeletal disorders: results from the EPI3-MSD cohort.

PubMed

Rossignol, Michel; Begaud, Bernard; Engel, Pierre; Avouac, Bernard; Lert, France; Rouillon, Frederic; Bénichou, Jacques; Massol, Jacques; Duru, Gerard; Magnier, Anne-Marie; Guillemot, Didier; Grimaldi-Bensouda, Lamiae; Abenhaim, Lucien

2012-10-01

The objective of this study was to assess the effect of physician practicing preferences (PPP) in primary care for homeopathy (Ho), CAM (Complementary and alternative medicines) with conventional medicine (Mx) or exclusively conventional medicine (CM) on patients with musculoskeletal disorders (MSDs), with reference to clinical progression, drug consumption, side effects and loss of therapeutic opportunity. The EPI3-MSD study was a nationwide observational cohort of a representative sample of general practitioners (GP) and their patients in France. Recruitment of GP was stratified by PPP, which was self-declared. Diagnoses and comorbidities were recorded by GP at inclusion. Patients completed a standardized telephone interview at inclusion, one, three and twelve months, including MSD-functional scales and medication consumption. 1153 MSD patients were included in the three PPP groups. Patients did not differ between groups except for chronicity of MSDs (>12 weeks), which was higher in the Ho group (62.1%) than in the CM (48.6%) and Mx groups (50.3%). The twelve-month development of specific functional scores was identical across the three groups after controlling for baseline score (p > 0.05). After adjusting for propensity scores, NSAID use over 12 months was almost half in the Ho group (OR, 0.54; 95%CI, 0.38-0.78) as compared to the CM group; no difference was found in the Mx group (OR, 0.81; 95% CI: 0.59-1.15). MSD patients seen by homeopathic physicians showed a similar clinical progression when less exposed to NSAID in comparison to patients seen in CM practice, with fewer NSAID-related adverse events and no loss of therapeutic opportunity. Copyright © 2012 John Wiley & Sons, Ltd.

Relationship of Musculoskeletal Disorder Pain to Patterns of Clinical Care in California Dental Hygienists.

PubMed

Humann, Pamela; Rowe, Dorothy J

2015-10-01

To relate self-reported levels of musculoskeletal disorder (MSD) pain and patterns of clinical care among members of the California Dental Hygienists' Association (CDHA), using a web-based survey. The 24-item survey consisted of questions on patterns of clinical care, health habits, experience with MSD pain and demographic information. Recruitment information, including survey link and consent form, was emailed to the CDHA for distribution to its members. Descriptive analysis and cross tabulations were conducted using the online software program Qualtrics™. A Chi-square test determined statistical significant differences between the responses of the no/mild pain and moderate/severe pain groups. The response rate was 19% (500/2,700). Ninety-six percent of all respondents reported some level of MSD pain, causing nearly 25% of the respondents to miss work. Respondents, who reported moderate/severe pain, treated more patients per day (p=0.007) and on average treated greater numbers of moderate to heavy calculus patients (p=0.017) than those respondents reporting no/mild pain. Forty percent of the respondents in the moderate/severe group treated more than 8 patients per day. A higher percentage of respondents (p=0.000) in the moderate/severe pain group than in the no/mild group reported using proper posture less than 50% of treatment time. Using proper posture more than 50% of treatment time was more frequent in respondents who had practiced more than (p=0.012), compared with less than, 5 years. Workload and ergonomics are related to MSD pain. Educational programs need to emphasize the importance of these factors in the development and reduction of MSD pain. Copyright © 2015 The American Dental Hygienists’ Association.

Health care seeking for Childhood Diarrhea in Developing Countries: Evidence from Seven Sites in Africa and Asia

PubMed Central

Nasrin, Dilruba; Wu, Yukun; Blackwelder, William C.; Farag, Tamer H.; Saha, Debasish; Sow, Samba O.; Alonso, Pedro L.; Breiman, Robert F.; Sur, Dipika; Faruque, Abu S. G.; Zaidi, Anita K. M.; Biswas, Kousick; Van Eijk, Anna Maria; Walker, Damian G.; Levine, Myron M.; Kotloff, Karen L.

2013-01-01

We performed serial Health Care Utilization and Attitudes Surveys (HUASs) among caretakers of children ages 0–59 months randomly selected from demographically defined populations participating in the Global Enteric Multicenter Study (GEMS), a case-control study of moderate-to-severe diarrhea (MSD) in seven developing countries. The surveys aimed to estimate the proportion of children with MSD who would present to sentinel health centers (SHCs) where GEMS case recruitment would occur and provide a basis for adjusting disease incidence rates to include cases not seen at the SHCs. The proportion of children at each site reported to have had an incident episode of MSD during the 7 days preceding the survey ranged from 0.7% to 4.4% for infants (0–11 months of age), from 0.4% to 4.7% for toddlers (12–23 months of age), and from 0.3% to 2.4% for preschoolers (24–59 months of age). The proportion of MSD episodes at each site taken to an SHC within 7 days of diarrhea onset was 15–56%, 17–64%, and 7–33% in the three age strata, respectively. High cost of care and insufficient knowledge about danger signs were associated with lack of any care-seeking outside the home. Most children were not offered recommended fluids and continuing feeds at home. We have shown the utility of serial HUASs as a tool for optimizing operational and methodological issues related to the performance of a large case-control study and deriving population-based incidence rates of MSD. Moreover, the surveys suggest key targets for educational interventions that might improve the outcome of diarrheal diseases in low-resource settings. PMID:23629939

Main clinical, therapeutic and technical factors related to patient's maximum skin dose in interventional cardiology procedures

PubMed Central

Journy, N; Sinno-Tellier, S; Maccia, C; Le Tertre, A; Pirard, P; Pagès, P; Eilstein, D; Donadieu, J; Bar, O

2012-01-01

Objective The study aimed to characterise the factors related to the X-ray dose delivered to the patient's skin during interventional cardiology procedures. Methods We studied 177 coronary angiographies (CAs) and/or percutaneous transluminal coronary angioplasties (PTCAs) carried out in a French clinic on the same radiography table. The clinical and therapeutic characteristics, and the technical parameters of the procedures, were collected. The dose area product (DAP) and the maximum skin dose (MSD) were measured by an ionisation chamber (Diamentor; Philips, Amsterdam, The Netherlands) and radiosensitive film (Gafchromic; International Specialty Products Advanced Materials Group, Wayne, NJ). Multivariate analyses were used to assess the effects of the factors of interest on dose. Results The mean MSD and DAP were respectively 389 mGy and 65 Gy cm−2 for CAs, and 916 mGy and 69 Gy cm−2 for PTCAs. For 8% of the procedures, the MSD exceeded 2 Gy. Although a linear relationship between the MSD and the DAP was observed for CAs (r=0.93), a simple extrapolation of such a model to PTCAs would lead to an inadequate assessment of the risk, especially for the highest dose values. For PTCAs, the body mass index, the therapeutic complexity, the fluoroscopy time and the number of cine frames were independent explanatory factors of the MSD, whoever the practitioner was. Moreover, the effect of technical factors such as collimation, cinematography settings and X-ray tube orientations on the DAP was shown. Conclusion Optimising the technical options for interventional procedures and training staff on radiation protection might notably reduce the dose and ultimately avoid patient skin lesions. PMID:22457404

Climate Change and the Central American Mid-summer Drought - The Importance of Changing Precipitation Patterns for Food and Water Security

NASA Astrophysics Data System (ADS)

Maurer, E. P.; Stewart, I. T.; Sundstrom, W.; Bacon, C. M.

2016-12-01

In addition to periodic long-term drought, much of Central America experiences a rainy season with two peaks separated by a dry period of weeks to over a month in duration, termed the mid-summer drought (MSD). Food and water security for smallholder farmers in the region hinge on accommodating this phenomenon, anticipating its arrival and estimating its duration. Model output from 1980 through the late 21st century projects changes in precipitation amount, variability, and timing, with potential to affect regional food production. Using surveys of farmer experiences in conjunction with gridded daily precipitation for a historic period on multiple scales, and with projections through the 21st century, we characterize the MSD across much of Central America using four measures: onset date, duration, intensity, and minimum, and test for significant changes. Our findings indicate that the most significant changes are for the duration, which, by the end of the century, is projected to increase by an average of over a week, and the MSD minimum precipitation, which is projected to decline by an average of over 26%, with statistically significant changes for most of Nicaragua, Honduras, El Salvador, and Guatemala (assuming a higher emissions pathway through the 21st century). These changes toward a longer and drier MSD have important implications for food and water security for vulnerable communities through the region. We find that for the four metrics the changes in interannual variability are small compared to historical variability, and are generally statistically insignificant. New farmer survey results are compared to findings from our climate analysis for the historic period, are used to interpret what MSD characteristics are of greatest interest locally, and are used for the development of adaptation strategies.

Comparison of musculoskeletal disorder health claims between construction floor layers and a general working population.

PubMed

Dale, Ann Marie; Ryan, Daniel; Welch, Laura; Olsen, Margaret A; Buchholz, Bryan; Evanoff, Bradley

2015-01-01

Compare rates of medical insurance claims for musculoskeletal disorders (MSD) between workers in a construction trade and a general worker population to determine if higher physical exposures in construction lead to higher rates of claims on personal medical insurance. Health insurance claims between 2006 and 2010 from floor layers were frequency matched by age, gender, eligibility time and geographic location to claims from insured workers in general industry obtained from MarketScan. We extracted MSD claims and dates of service from six regions of the body: neck, low back, knee, lower extremity, shoulder and distal arm, and evaluated differences in claim rates. Fifty-one per cent of floor layers (n=1475) experienced musculoskeletal claims compared with 39% of MarketScan members (p<0.001). Claim rates were higher for floor layers across all body regions with nearly double the rate ratios for the knee and neck regions (RR 2.10 and 2.07). The excess risk was greatest for the neck and low back regions; younger workers had disproportionately higher rates in the knee, neck, low back and distal arm. A larger proportion of floor layers (22%) filed MSD claims in more than one body region compared with general workers (10%; p<0.001). Floor layers have markedly higher rates of MSD claims compared with a general worker population, suggesting a shifting of medical costs for work-related MSD to personal health insurance. The occurrence of disorders in multiple body regions and among the youngest workers highlights the need for improved work methods and tools for construction workers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Danish Observational Study of Eldercare work and musculoskeletal disorderS (DOSES): a prospective study at 20 nursing homes in Denmark

PubMed Central

Karstad, Kristina; Jørgensen, Anette F B; Greiner, Birgit A; Burdorf, Alex; Søgaard, Karen; Rugulies, Reiner; Holtermann, Andreas

2018-01-01

Purpose Musculoskeletal disorders (MSDs), sickness absence and premature retirement are highly prevalent among eldercare workers. We conducted a prospective observational workplace study with the main purpose to investigate longitudinal associations between physical and psychosocial working conditions and occurrence of MSD and its consequences (pain-related interference with daily work activities and sickness absence) among Danish eldercare workers. Participants At 20 Danish nursing homes, a total of 941 eldercare workers employed in day and evening shifts were invited to the study. Of those, 553 participated in the baseline measurements, and 441 completed the total period of 12 months follow-up. Findings to date Data were collected from September 2013 to January 2016. Physical and psychosocial working conditions were assessed with multiple methods (observations, accelerometer measurements and work schedules), and multiple levels of information (nursing home, ward, resident and eldercare worker) were incorporated in the data collection. MSD and the consequences hereof were assessed monthly during a 1-year follow-up. Study participants and non-participants were comparable on most of the 27 sociodemographic, health and working condition characteristics at baseline. The exceptions were higher neck–shoulder pain intensity, less sickness absence, more exposure to negative behaviour from residents and a higher percentage of working day shifts and fewer evening shifts among participants compared with non-participants. Future plans The first publications will report on the associations of physical and psychosocial working conditions with occurrence of MSD and its consequences. In addition, the cohort gives the opportunity to investigate the importance of organisational, management and team factors for distribution of physical work demands and development of MSD among the workers. This will provide important knowledge for future workplace interventions to reduce MSD and sickness absence. PMID:29490965

Allowing for MSD prevention during facilities planning for a public service: an a posteriori analysis of 10 library design projects.

PubMed

Bellemare, Marie; Trudel, Louis; Ledoux, Elise; Montreuil, Sylvie; Marier, Micheline; Laberge, Marie; Vincent, Patrick

2006-01-01

Research was conducted to identify an ergonomics-based intervention model designed to factor in musculoskeletal disorder (MSD) prevention when library projects are being designed. The first stage of the research involved an a posteriori analysis of 10 recent redesign projects. The purpose of the analysis was to document perceptions about the attention given to MSD prevention measures over the course of a project on the part of 2 categories of employees: librarians responsible for such projects and personnel working in the libraries before and after changes. Subjects were interviewed in focus groups. Outcomes of the analysis can guide our ergonomic assessment of current situations and contribute to a better understanding of the way inclusion or improvement of prevention measures can support the workplace design process.

The EGS Data Collaboration Platform: Enabling Scientific Discovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weers, Jonathan D; Johnston, Henry; Huggins, Jay V

Collaboration in the digital age has been stifled in recent years. Reasonable responses to legitimate security concerns have created a virtual landscape of silos and fortified castles incapable of sharing information efficiently. This trend is unfortunately opposed to the geothermal scientific community's migration toward larger, more collaborative projects. To facilitate efficient sharing of information between team members from multiple national labs, universities, and private organizations, the 'EGS Collab' team has developed a universally accessible, secure data collaboration platform and has fully integrated it with the U.S. Department of Energy's (DOE) Geothermal Data Repository (GDR) and the National Geothermal Data Systemmore » (NGDS). This paper will explore some of the challenges of collaboration in the modern digital age, highlight strategies for active data management, and discuss the integration of the EGS Collab data management platform with the GDR to enable scientific discovery through the timely dissemination of information.« less

Observed Changes in the Alertness and Communicative Involvement of Students with Multiple and Severe Disability Following In-Class Mentor Modelling for Staff in Segregated and General Education Classrooms

ERIC Educational Resources Information Center

Foreman, P.; Arthur-Kelly, M.; Bennett, D.; Neilands, J.; Colyvas, K.

2014-01-01

Background: The improvement of engagement and involvement in communicative and socially centred exchanges for individuals with multiple and severe disability (MSD) presents complex and urgent challenges to educators. This paper reports the findings of an intervention study designed to enhance the interactive skills of students with MSD using an…

Automatic Data Processing Equipment (ADPE) acquisition plan for the medical sciences

NASA Technical Reports Server (NTRS)

1979-01-01

An effective mechanism for meeting the SLSD/MSD data handling/processing requirements for Shuttle is discussed. The ability to meet these requirements depends upon the availability of a general purpose high speed digital computer system. This system is expected to implement those data base management and processing functions required across all SLSD/MSD programs during training, laboratory operations/analysis, simulations, mission operations, and post mission analysis/reporting.

The National Shipbuilding Research Program: Producibility Cost Reductions through Alternative Materials and Processes

DTIC Science & Technology

1999-03-01

steel; -60F - 250 F; nonflammable acrylic mod- ified methyl - methacrylate Hernon MI React 761; Act 63 two component unprimed steel/primed/ painted trowel... MSD ) of the University of Michigan Transportation Institute (UMTRI), the Shipyards Division of Avondale Industries, and Damilic Corporation, to...classification society requirements. This research was conducted by the research team of the Marine Systems Division ( MSD ) of the University of Michigan

A prospective registration study to determine feasibility of hematopoietic SCT in adults with acute leukemia: planning, expectations and reality.

PubMed

Labopin, M; Gorin, N-C; Polge, E; Socié, G; Gurman, G; Gluckman, E; Jindra, P; Poiré, X; Schäfer-Eckart, K; Ruutu, T; Milone, G; Arcese, W; Mohty, M; Rocha, V

2014-03-01

For adults with acute leukemia, it is important to know whether the therapeutic schemes initially planned were actually implemented. The European Group for Blood and Marrow transplantation Acute Leukemia Working Party prospectively followed 695 consecutive patients who were registered at the time of HLA typing. Of 304 patients with an available matched sibling donor (MSD), SCT was planned in 264, chemotherapy in 33 and autografting in 7. For the rest, an unrelated donor (UD) search was initiated in 198. Among these, 117 were transplanted, 114 received chemotherapy and 77 underwent autografting. Probabilities of receiving a planned treatment were 60 and 65% at 1 and 2 years, respectively. Patients scheduled to receive MSD SCT had an 82% probability, whereas those scheduled to undergo UD SCT had a 57% probability, of receiving their transplant at 1 year. The only factor associated with a lower probability of MSD SCT in first remission was delayed HLA typing (HR=0.82; P=0.03). One year after enrollment, 40% of patients did not follow their initial treatment plan. Because OS was 50% only at 3 years and only 57% of the patients without a MSD underwent SCT, this suggests room for improvement in outcomes for adults with acute leukemia.

Work–Life Imbalance and Musculoskeletal Disorders among South Korean Workers

PubMed Central

Kim, Young-Mee

2017-01-01

Employed workers often have family responsibilities such as childcare or homemaking. This dual burden may increase work-related health problems, particularly if there are conflicts between work and family responsibilities. This study assessed whether difficulty in work–life balance is associated with musculoskeletal disorders (MSD) among Korean employees. Data from the population-based Korean Working Conditions Survey of 2011, including 28,640 male and 21,392 female workers, were used. Men and women were analyzed separately to investigate gender differences. MSD were defined as pain in the back, neck, shoulder, or extremities during the past year. Self-assessed difficulty in work–life balance was defined as a work–life conflict (WLC). Adjustments for physical factors, as well as other occupational and socio-demographic variables, were made using multiple logistic regression analysis. Interaction terms including WLCs and key covariates were also incorporated. WLC was significantly associated with increased frequency of MSD in both men (OR: 1.49) and women (OR: 1.50). There were significant interaction effects between WLC and some key covariates (job stress for men and job stress, work hours, physical demand, and frequent overtime work for women). We suggest that having the flexibility to coordinate work and family life is important to prevent MSD among employees. PMID:29104228

Multistate approaches in computational protein design

PubMed Central

Davey, James A; Chica, Roberto A

2012-01-01

Computational protein design (CPD) is a useful tool for protein engineers. It has been successfully applied towards the creation of proteins with increased thermostability, improved binding affinity, novel enzymatic activity, and altered ligand specificity. Traditionally, CPD calculations search and rank sequences using a single fixed protein backbone template in an approach referred to as single-state design (SSD). While SSD has enjoyed considerable success, certain design objectives require the explicit consideration of multiple conformational and/or chemical states. Cases where a “multistate” approach may be advantageous over the SSD approach include designing conformational changes into proteins, using native ensembles to mimic backbone flexibility, and designing ligand or oligomeric association specificities. These design objectives can be efficiently tackled using multistate design (MSD), an emerging methodology in CPD that considers any number of protein conformational or chemical states as inputs instead of a single protein backbone template, as in SSD. In this review article, recent examples of the successful design of a desired property into proteins using MSD are described. These studies employing MSD are divided into two categories—those that utilized multiple conformational states, and those that utilized multiple chemical states. In addition, the scoring of competing states during negative design is discussed as a current challenge for MSD. PMID:22811394

A non-local structural derivative model for characterization of ultraslow diffusion in dense colloids

NASA Astrophysics Data System (ADS)

Liang, Yingjie; Chen, Wen

2018-03-01

Ultraslow diffusion has been observed in numerous complicated systems. Its mean squared displacement (MSD) is not a power law function of time, but instead a logarithmic function, and in some cases grows even more slowly than the logarithmic rate. The distributed-order fractional diffusion equation model simply does not work for the general ultraslow diffusion. Recent study has used the local structural derivative to describe ultraslow diffusion dynamics by using the inverse Mittag-Leffler function as the structural function, in which the MSD is a function of inverse Mittag-Leffler function. In this study, a new stretched logarithmic diffusion law and its underlying non-local structural derivative diffusion model are proposed to characterize the ultraslow diffusion in aging dense colloidal glass at both the short and long waiting times. It is observed that the aging dynamics of dense colloids is a class of the stretched logarithmic ultraslow diffusion processes. Compared with the power, the logarithmic, and the inverse Mittag-Leffler diffusion laws, the stretched logarithmic diffusion law has better precision in fitting the MSD of the colloidal particles at high densities. The corresponding non-local structural derivative diffusion equation manifests clear physical mechanism, and its structural function is equivalent to the first-order derivative of the MSD.

Assembly and misassembly of cystic fibrosis transmembrane conductance regulator: folding defects caused by deletion of F508 occur before and after the calnexin-dependent association of membrane spanning domain (MSD) 1 and MSD2.

PubMed

Rosser, Meredith F N; Grove, Diane E; Chen, Liling; Cyr, Douglas M

2008-11-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is a polytopic membrane protein that functions as a Cl(-) channel and consists of two membrane spanning domains (MSDs), two cytosolic nucleotide binding domains (NBDs), and a cytosolic regulatory domain. Cytosolic 70-kDa heat shock protein (Hsp70), and endoplasmic reticulum-localized calnexin are chaperones that facilitate CFTR biogenesis. Hsp70 functions in both the cotranslational folding and posttranslational degradation of CFTR. Yet, the mechanism for calnexin action in folding and quality control of CFTR is not clear. Investigation of this question revealed that calnexin is not essential for CFTR or CFTRDeltaF508 degradation. We identified a dependence on calnexin for proper assembly of CFTR's membrane spanning domains. Interestingly, efficient folding of NBD2 was also found to be dependent upon calnexin binding to CFTR. Furthermore, we identified folding defects caused by deletion of F508 that occurred before and after the calnexin-dependent association of MSD1 and MSD2. Early folding defects are evident upon translation of the NBD1 and R-domain and are sensed by the RMA-1 ubiquitin ligase complex.

Work-Life Imbalance and Musculoskeletal Disorders among South Korean Workers.

PubMed

Kim, Young-Mee; Cho, Sung-Il

2017-11-01

Employed workers often have family responsibilities such as childcare or homemaking. This dual burden may increase work-related health problems, particularly if there are conflicts between work and family responsibilities. This study assessed whether difficulty in work-life balance is associated with musculoskeletal disorders (MSD) among Korean employees. Data from the population-based Korean Working Conditions Survey of 2011, including 28,640 male and 21,392 female workers, were used. Men and women were analyzed separately to investigate gender differences. MSD were defined as pain in the back, neck, shoulder, or extremities during the past year. Self-assessed difficulty in work-life balance was defined as a work-life conflict (WLC). Adjustments for physical factors, as well as other occupational and socio-demographic variables, were made using multiple logistic regression analysis. Interaction terms including WLCs and key covariates were also incorporated. WLC was significantly associated with increased frequency of MSD in both men (OR: 1.49) and women (OR: 1.50). There were significant interaction effects between WLC and some key covariates (job stress for men and job stress, work hours, physical demand, and frequent overtime work for women). We suggest that having the flexibility to coordinate work and family life is important to prevent MSD among employees.

Multiscale Modelling of Relationships between Protein Classes and Drug Behavior Across all Diseases Using the CANDO Platform

PubMed Central

Samudrala, Ram

2015-01-01

We have examined the effect of eight different protein classes (channels, GPCRs, kinases, ligases, nuclear receptors, proteases, phosphatases, transporters) on the benchmarking performance of the CANDO drug discovery and repurposing platform (http://protinfo.org/cando). The first version of the CANDO platform utilizes a matrix of predicted interactions between 48278 proteins and 3733 human ingestible compounds (including FDA approved drugs and supplements) that map to 2030 indications/diseases using a hierarchical chem and bio-informatic fragment based docking with dynamics protocol (> one billion predicted interactions considered). The platform uses similarity of compound-proteome interaction signatures as indicative of similar functional behavior and benchmarking accuracy is calculated across 1439 indications/diseases with more than one approved drug. The CANDO platform yields a significant correlation (0.99, p-value < 0.0001) between the number of proteins considered and benchmarking accuracy obtained indicating the importance of multitargeting for drug discovery. Average benchmarking accuracies range from 6.2 % to 7.6 % for the eight classes when the top 10 ranked compounds are considered, in contrast to a range of 5.5 % to 11.7 % obtained for the comparison/control sets consisting of 10, 100, 1000, and 10000 single best performing proteins. These results are generally two orders of magnitude better than the average accuracy of 0.2% obtained when randomly generated (fully scrambled) matrices are used. Different indications perform well when different classes are used but the best accuracies (up to 11.7% for the top 10 ranked compounds) are achieved when a combination of classes are used containing the broadest distribution of protein folds. Our results illustrate the utility of the CANDO approach and the consideration of different protein classes for devising indication specific protocols for drug repurposing as well as drug discovery. PMID:25694071

Targeted proteomics guided by label-free global proteome analysis in saliva reveal transition signatures from health to periodontal disease.

PubMed

Bostanci, Nagihan; Selevsek, Nathalie; Wolski, Witold; Grossmann, Jonas; Bao, Kai; Wahlander, Asa; Trachsel, Christian; Schlapbach, Ralph; Özturk, Veli Özgen; Afacan, Beral; Emingil, Gulnur; Belibasakis, Georgios N

2018-04-02

Periodontal diseases are among the most prevalent worldwide, but largely silent, chronic diseases. They affect the tooth-supporting tissues with multiple ramifications on life quality. Their early diagnosis is still challenging, due to lack of appropriate molecular diagnostic methods. Saliva offers a non-invasively collectable reservoir of clinically relevant biomarkers, which, if utilized efficiently, could facilitate early diagnosis and monitoring of ongoing disease. Despite several novel protein markers being recently enlisted by discovery proteomics, their routine diagnostic application is hampered by the lack of validation platforms that allow for rapid, accurate and simultaneous quantification of multiple proteins in large cohorts. We carried out a pipeline of two proteomic platforms; firstly, we applied open ended label-free quantitative (LFQ) proteomics for discovery in saliva (n=67, health, gingivitis, and periodontitis), followed by selected-reaction monitoring (SRM)-targeted proteomics for validation in an independent cohort (n=82). The LFQ platform led to the discovery of 119 proteins with at least two-fold significant difference between health and disease. The 65 proteins chosen for the subsequent SRM platform included 50 related proteins derived from the significantly enriched processes of the LFQ data, 11 from literature-mining, and four house-keeping ones. Among those, 60 were reproducibly quantifiable proteins (92% success rate), represented by a total of 143 peptides. Machine-learning modeling led to a narrowed-down panel of five proteins of high predictive value for periodontal diseases (higher in disease: Matrix metalloproteinase-9, Ras-related protein-1, Actin-related protein 2/3 complex subunit 5; lower in disease: Clusterin, Deleted in Malignant Brain Tumors 1), with maximum area under the receiver operating curve >0.97. This panel enriches the pool of credible clinical biomarker candidates for diagnostic assay development. Yet, the quantum leap brought in periodontal diagnostics by this study lies in the introduction of the well established discovery-through-verification pipeline for periodontal biomarker discovery and validation in further periodontal patient cohorts. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

3D cell culture systems--towards primary drug discovery platforms: an interview with Heinz Ruffner (Novartis) and Jan Lichtenberg (InSphero).

PubMed

Ruffner, Heinz; Lichtenberg, Jan

2012-07-01

Advanced cell culture systems for regenerative medicine, drug efficacy and toxicity testing, enabling technologies to create and analyze 3D cell culture systems were the topics of the 3D cell culture meeting taking place in March 14-16, 2012 at the Technopark in Zurich, Switzerland. At this meeting Biotechnology Journal had the pleasure to talk to Dr. Heinz Ruffner, Novartis AG, and Dr. Jan Lichtenberg, co-founder and CEO of InSphero AG, about challenges and perspectives in using 3D cell culture systems as primary drug discovery platforms. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Variable-order fractional MSD function to describe the evolution of protein lateral diffusion ability in cell membranes

NASA Astrophysics Data System (ADS)

Yin, Deshun; Qu, Pengfei

2018-02-01

Protein lateral diffusion is considered anomalous in the plasma membrane. And this diffusion is related to membrane microstructure. In order to better describe the property of protein lateral diffusion and find out the inner relationship between protein lateral diffusion and membrane microstructure, this article applies variable-order fractional mean square displacement (f-MSD) function for characterizing the anomalous diffusion. It is found that the variable order can reflect the evolution of diffusion ability. The results of numerical simulation demonstrate variable-order f-MSD function can predict the tendency of anomalous diffusion during the process of confined diffusion. It is also noted that protein lateral diffusion ability during the processes of confined and hop diffusion can be split into three parts. In addition, the comparative analyses reveal that the variable order is related to the confinement-domain size and microstructure of compartment boundary too.

Molecular dynamics simulations of aggregation of copper nanoparticles with different heating rates

NASA Astrophysics Data System (ADS)

Li, Qibin; Wang, Meng; Liang, Yunpei; Lin, Liyang; Fu, Tao; Wei, Peitang; Peng, Tiefeng

2017-06-01

Molecular dynamics simulations were employed to investigate the heating rates' effect on aggregation of two copper nanoparticles. The aggregation can be distinguished into three distinct regimes by the contacting and melting of nanoparticles. The nanoparticles contacting at a lower temperature during the sintering with lower heating rate, meanwhile, some temporary stacking fault exists at the contacting neck. The aggregation properties of the system, i.e. neck diameter, shrinkage ratio, potential energy, mean square displacement (MSD) and relative gyration radius, experience drastic changes due to the free surface annihilation. After the nanoparticles coalesced for a stable period, the shrinkage ratio, MSD, relative gyration radius and neck diameter of the system are dramatically changed during the melting process. It is shown that the shrinkage ratio and MSD have relative larger increasing ratio for a lower heating rate. While the evolution of the relative gyration radius and neck diameter is only sensitive to the temperature.

Musculoskeletal disorder costs and medical claim filing in the US retail trade sector.

PubMed

Bhattacharya, Anasua; Leigh, J Paul

2011-01-01

The average costs of Musculoskeletal Disorder (MSD) and odds ratios for filing medical claims related to MSD were examined. The medical claims were identified by ICD 9 codes for four US Census regions within retail trade. Large private firms' medical claims data from Thomson Reuters Inc. MarketScan databases for the years 2003 through 2006 were used. Average costs were highest for claims related to lumbar region (ICD 9 Code: 724.02) and number of claims were largest for low back syndrome (ICD 9 Code: 724.2). Whereas the odds of filing an MSD claim did not vary greatly over time, average costs declined over time. The odds of filing claims rose with age and were higher for females and southerners than men and non-southerners. Total estimated national medical costs for MSDs within retail trade were $389 million (2007 USD).

Demonstration of an optoelectronic interconnect architecture for a parallel modified signed-digit adder and subtracter

NASA Astrophysics Data System (ADS)

Sun, Degui; Wang, Na-Xin; He, Li-Ming; Weng, Zhao-Heng; Wang, Daheng; Chen, Ray T.

1996-06-01

A space-position-logic-encoding scheme is proposed and demonstrated. This encoding scheme not only makes the best use of the convenience of binary logic operation, but is also suitable for the trinary property of modified signed- digit (MSD) numbers. Based on the space-position-logic-encoding scheme, a fully parallel modified signed-digit adder and subtractor is built using optoelectronic switch technologies in conjunction with fiber-multistage 3D optoelectronic interconnects. Thus an effective combination of a parallel algorithm and a parallel architecture is implemented. In addition, the performance of the optoelectronic switches used in this system is experimentally studied and verified. Both the 3-bit experimental model and the experimental results of a parallel addition and a parallel subtraction are provided and discussed. Finally, the speed ratio between the MSD adder and binary adders is discussed and the advantage of the MSD in operating speed is demonstrated.

Kinetics of proton migration in liquid water.

PubMed

Chen, Hanning; Voth, Gregory A; Agmon, Noam

2010-01-14

We have utilized multistate empirical valence bond (MS-EVB3) simulations of protonated liquid water to calculate the relative mean-square displacement (MSD) and the history-independent time correlation function, c(t), of the hydrated proton center of excess charge (CEC) with respect to the water molecule on which it has initially resided. The MSD is nonlinear for the first 15 ps, suggesting that the relative diffusion coefficient increases from a small value, D(0), at short separations to its larger bulk value, D(infinity), at large separations. With the ensuing distance-dependent diffusion coefficient, D(r), the time dependence of both the MSD and c(t) agrees quantitatively with the solution of a diffusion equation for reversible geminate recombination. This suggests that the relative motion of the CEC is not independent from the nearby water molecules, in agreement with theoretical and experimental observations that large water clusters participate in the mechanism of proton mobility.

Posturedontics: How does dentistry fit you?

PubMed

Jodalli, Praveen S; Kurana, Suchi; Shameema; Ragher, Mallikarjuna; Khed, Jaishree; Prabhu, Vishnu

2015-08-01

Dentists are at high risk for musculoskeletal disorders (MSD's) due to their work. MSD's is an umbrella term for number of injuries affecting different parts of the body, including joints, muscles, tendons, nerves that can arise from sudden exertion or making the same motions repeatedly. These injuries can develop over time and can lead to long-term disability. Dental professional often develop musculoskeletal problems due to bad working habits, uncomfortable physical posture causing unnecessary musculoskeletal loading, discomfort and fatigue. Ergonomic principles when it is applied, it will help to reduce stress and eliminate many potential injuries and disorders associated with the overuse of muscles, bad posture, and repeated tasks. This can be accomplished by using a proper dental chair, lighting and the selection of ergonomically-friendly equipment to fit the dental professionals physical capabilities and limitations. This review addresses about the basics of ergonomics, positioning, viewing, handling, and prevention of MSD's.

Posturedontics: How does dentistry fit you?

PubMed Central

Jodalli, Praveen S.; Kurana, Suchi; Shameema; Ragher, Mallikarjuna; Khed, Jaishree; Prabhu, Vishnu

2015-01-01

Dentists are at high risk for musculoskeletal disorders (MSD's) due to their work. MSD's is an umbrella term for number of injuries affecting different parts of the body, including joints, muscles, tendons, nerves that can arise from sudden exertion or making the same motions repeatedly. These injuries can develop over time and can lead to long-term disability. Dental professional often develop musculoskeletal problems due to bad working habits, uncomfortable physical posture causing unnecessary musculoskeletal loading, discomfort and fatigue. Ergonomic principles when it is applied, it will help to reduce stress and eliminate many potential injuries and disorders associated with the overuse of muscles, bad posture, and repeated tasks. This can be accomplished by using a proper dental chair, lighting and the selection of ergonomically-friendly equipment to fit the dental professionals physical capabilities and limitations. This review addresses about the basics of ergonomics, positioning, viewing, handling, and prevention of MSD's. PMID:26538885

Closeup view of the aft fuselage of the Orbiter Discovery ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Close-up view of the aft fuselage of the Orbiter Discovery on the starboard side looking forward. This view is of the attach surface for the Orbiter Maneuvering System/Reaction Control System (OMS/RCS) Pod. The OMS/RCS pods are removed for processing and reconditioning at another facility. This view was taken from a service platform in the Orbiter Processing Facility at Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Discovery touches down after successful mission STS-95

NASA Technical Reports Server (NTRS)

1998-01-01

Orbiter Discovery smokes its tires as it touches down on runway 33 at the Shuttle Landing Facility. Discovery returns to Earth with its crew of seven after a successful mission STS-95 lasting nearly nine days and 3.6 million miles. The mission included research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

Discovery touches down after successful mission STS-95

NASA Technical Reports Server (NTRS)

1998-01-01

Orbiter Discovery startles a great white egret next to runway 33 as it touches down at the Shuttle Landing Facility. Discovery returns to Earth with its crew of seven after a successful mission STS-95 lasting nearly nine days and 3.6 million miles. The mission included research payloads such as the Spartan solar- observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

Development of a robust flow cytometry-based pharmacodynamic assay to detect phospho-protein signals for phosphatidylinositol 3-kinase inhibitors in multiple myeloma.

PubMed

Li, Congfen; Takahashi, Chikara; Zhang, Liangxuan; Huseni, Mahrukh; Stankovich, Basha; Mashhedi, Haider; Lee, Joanna; French, Dorothy; Anderson, Jeff Eastham; Kim, Doris; Howell, Kathy; Brauer, Matthew J; Kowanetz, Marcin; Yan, Yibing; Humke, Eric; Ebens, Allen; Hampton, Garret; Lackner, Mark R; Hegde, Priti; Jia, Shidong

2013-03-23

The phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in multiple myeloma (MM), a blood cancer associated with uncontrolled proliferation of bone marrow plasma cells. This study aimed to develop a robust clinical pharmacodynamic (PD) assay to measure the on-target PD effects of the selective PI3K inhibitor GDC-0941 in MM patients. We conducted an in vitro drug wash-out study to evaluate the feasibility of biochemical approaches in measuring the phosphorylation of S6 ribosomal protein (S6), one of the commonly used PD markers for PI3K pathway inhibition. We then developed a 7-color phospho-specific flow cytometry assay, or phospho flow assay, to measure the phosphorylation state of intracellular S6 in bone marrow aspirate (BMA) and peripheral blood (PB). Integrated mean fluorescence intensity (iMFI) was used to calculate fold changes of phosphorylation. Assay sensitivity was evaluated by comparing phospho flow with Meso Scale Discovery (MSD) and immunohistochemistry (IHC) assays. Finally, a sample handling method was developed to maintain the integrity of phospho signal during sample shipping and storage to ensure clinical application. The phospho flow assay provided single-cell PD monitoring of S6 phosphorylation in tumor and surrogate cells using fixed BMA and PB, assessing pathway modulation in response to GDC-0941 with sensitivity similar to that of MSD assay. The one-shot sample fixation and handling protocol herein demonstrated exceptional preservation of protein phosphorylation. In contrast, the IHC assay was less sensitive in terms of signal quantification while the biochemical approach (MSD) was less suitable to assess PD activities due to the undesirable impact associated with cell isolation on the protein phosphorylation in tumor cells. We developed a robust PD biomarker assay for the clinical evaluation of PI3K inhibitors in MM, allowing one to decipher the PD response in a relevant cell population. To our knowledge, this is the first report of an easily implemented clinical PD assay that incorporates an unbiased one-shot sample handling protocol, all (staining)-in-one (tube) phospho flow staining protocol, and an integrated modified data analysis for PD monitoring of kinase inhibitors in relevant cell populations in BMA and PB. The methods described here ensure a real-time, reliable and reproducible PD readout, which can provide information for dose selection as well as help to identify optimal combinations of targeted agents in early clinical trials.

Development of a robust flow cytometry-based pharmacodynamic assay to detect phospho-protein signals for phosphatidylinositol 3-kinase inhibitors in multiple myeloma

PubMed Central

2013-01-01

Background The phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in multiple myeloma (MM), a blood cancer associated with uncontrolled proliferation of bone marrow plasma cells. This study aimed to develop a robust clinical pharmacodynamic (PD) assay to measure the on-target PD effects of the selective PI3K inhibitor GDC-0941 in MM patients. Methods We conducted an in vitro drug wash-out study to evaluate the feasibility of biochemical approaches in measuring the phosphorylation of S6 ribosomal protein (S6), one of the commonly used PD markers for PI3K pathway inhibition. We then developed a 7-color phospho-specific flow cytometry assay, or phospho flow assay, to measure the phosphorylation state of intracellular S6 in bone marrow aspirate (BMA) and peripheral blood (PB). Integrated mean fluorescence intensity (iMFI) was used to calculate fold changes of phosphorylation. Assay sensitivity was evaluated by comparing phospho flow with Meso Scale Discovery (MSD) and immunohistochemistry (IHC) assays. Finally, a sample handling method was developed to maintain the integrity of phospho signal during sample shipping and storage to ensure clinical application. Results The phospho flow assay provided single-cell PD monitoring of S6 phosphorylation in tumor and surrogate cells using fixed BMA and PB, assessing pathway modulation in response to GDC-0941 with sensitivity similar to that of MSD assay. The one-shot sample fixation and handling protocol herein demonstrated exceptional preservation of protein phosphorylation. In contrast, the IHC assay was less sensitive in terms of signal quantification while the biochemical approach (MSD) was less suitable to assess PD activities due to the undesirable impact associated with cell isolation on the protein phosphorylation in tumor cells. Conclusions We developed a robust PD biomarker assay for the clinical evaluation of PI3K inhibitors in MM, allowing one to decipher the PD response in a relevant cell population. To our knowledge, this is the first report of an easily implemented clinical PD assay that incorporates an unbiased one-shot sample handling protocol, all (staining)-in-one (tube) phospho flow staining protocol, and an integrated modified data analysis for PD monitoring of kinase inhibitors in relevant cell populations in BMA and PB. The methods described here ensure a real-time, reliable and reproducible PD readout, which can provide information for dose selection as well as help to identify optimal combinations of targeted agents in early clinical trials. PMID:23522020

Games as a Platform for Student Participation in Authentic Scientific Research

ERIC Educational Resources Information Center

Magnussen, Rikke; Hansen, Sidse Damgaard; Planke, Tilo; Sherson, Jacob Friis

2014-01-01

This paper presents results from the design and testing of an educational version of Quantum Moves, a Scientific Discovery Game that allows players to help solve authentic scientific challenges in the effort to develop a quantum computer. The primary aim of developing a game-based platform for student-research collaboration is to investigate if…

Enhancing Mobility: Integrating New Services into Your Library's Mobile Platform to Increase Traffic

ERIC Educational Resources Information Center

Felts, John W., Jr.

2014-01-01

Kimbel Library launched its mobile environment and ran it in full production for several months yet usage patterns were quite low and flat. The library only saw a substantial increase in usage when new, value-added services were integrated into this platform. Upon implementing and integrating discovery services, chat and SMS capabilities, and…

The role of transients in the Mid Summer Drought over the Tropical Americas

NASA Astrophysics Data System (ADS)

Herrera, E.; Magaña Rueda, V.; Caetano, E.

2013-05-01

The Mid Summer Drought (MSD) has raised the interested of those interested in regional climate dynamics since it appears to be a unique characteristic of the tropical Americas climate. The MSD corresponds to a relative minimum in summer precipitation between July and August in the Mesoamerican region. Several theories have been posed to explain its origin including the annual cycle march of the ITCZ, a teleconnection from the Asian monsoon region, or an air sea interaction process that relates the warm pools over the eastern Pacific and the Caribbean Sea. However, none of them has addressed the various characteristics of the MSD described by Magaña et al (1999) and Magaña and Caetano (2005). In the present paper, the role of the transient mean flow interaction over the Caribbean Sea is explored. The Caribbean Low Level Jet (CLLJ) and the transients interact in such a way that the CLLJ reaches maximum intensity when the MSD occurs. This is a period of minimum Perturbation Kinetic Energy in the region, suggesting that a CLLJ stronger than approximately 15 m/s tends to inhibit the amplification of eddies. Transients are crucial dynamic elements to produce precipitation over the Mexico and Central American region. Over the eastern Pacific warm pool, tropical convection and sea surface temperature are related by a sort of Clausius Clapeyron exponential equation. However, there are two branches for the relationship, one for the first maximum in tropical convection during June, and a second one during September, with a relative minimum corresponding to the MSD in July - August. The most interesting aspect of such patterns is that while the June exponential curves occurs at SST larger than 28°C, the curve corresponding to September takes place at lower SSTs, suggesting that transient activity in this period is necessary to enhance tropical convective activity during the latter part of the summer rains in the region. This is exactly the period when PKE increases over the Intra Americas Seas and the eastern tropical Pacific. A more comprehensive qualitative model is proposed to connect the various dynamical elements in the region that result in the MSD. This new model presents a more complicated picture of the regional climate dynamics than various theories have proposed.

Influence of age, body weight and body condition score before mating start date on the pubertal rate of maiden Holstein-Friesian heifers and implications for subsequent cow performance and profitability.

PubMed

Archbold, H; Shalloo, L; Kennedy, E; Pierce, K M; Buckley, F

2012-07-01

The aim of this study was to assess the influence of age, body weight (BW) and body condition score (BCS) of maiden Holstein-Friesian heifers before mating start date (MSD) on the rate of puberty, subsequent production and longevity and their implications with regard to farm profitability. Data were available on 871 Holstein-Friesian heifers from 48 herds. BW was recorded electronically and BCS was recorded by a single operator on a scale of 1 to 5. Heifer age was calculated as the number of days from birth to the day of visit. All of the independent variables of interest were grouped into three or four categories. Three age categories (thirtiles), four BW categories (quartiles) and four BCS categories (≤ 2.75, 3.00, 3.25 and ≥ 3.50) were formed. Heifers with an identifiable corpus lutuem (CL) in the presence or absence of large follicles and peri-ovulatory signs and with a plasma progesterone (P4) concentration ≥ 1 ng/ml were classified as pubertal. In addition, heifers without an identifiable CL in the presence or absence of large follicles and peri-ovulatory signs but with a P4 concentration ≥ 1 ng/ml were also classified as pubertal. Age, BW and BCS at MSD were all found to be significantly associated with pubertal rate (P < 0.05). Age was shown to have no practical implications on subsequent cow performance. BW at MSD was favourably associated with subsequent calving date (P < 0.05), subsequent cow BW (P < 0.001) and potential (305 days) milk fat plus protein yield (P < 0.001). BCS at MSD was found to be favourably associated with milk fat plus protein yield potential (P < 0.05) and BCS (P < 0.001) during lactation. The economic analysis undertaken indicated that larger, well-grown heifers will be more profitable because of superior production potential, all else being equal. However, because of the finding of poorer reproductive efficiency in heifers grown to more than 343 kg at MSD, heifers at ∼330 kg at MSD are deemed optimal. This will correspond to mature cow BW of ∼550 kg.

Fatigue damage assessment of high-usage in-service aircraft fuselage structure

NASA Astrophysics Data System (ADS)

Mosinyi, Bao Rasebolai

As the commercial and military aircraft fleets continue to age, there is a growing concern that multiple-site damage (MSD) can compromise structural integrity. Multiple site damage is the simultaneous occurrence of many small cracks at independent structural locations, and is the natural result of fatigue, corrosion, fretting and other possible damage mechanisms. These MSD cracks may linkup and form a fatigue lead crack of critical length. The presence of MSD also reduces the structure's ability to withstand longer cracks. The objective of the current study is to assess, both experimentally and analytically, MSD formation and growth in the lap joint of curved panels removed from a retired aircraft. A Boeing 727-232 airplane owned and operated by Delta Air Lines, and retired at its design service goal, was selected for the study. Two panels removed from the left-hand side of the fuselage crown, near stringer 4L, were subjected to extended fatigue testing using the Full-Scale Aircraft Structural Test Evaluation and Research (FASTER) facility located at the Federal Aviation Administration (FAA) William J. Hughes Technical Center. The state of MSD was continuously assessed using several nondestructive inspection (NDI) methods. Damage to the load attachment points of the first panel resulted in termination of the fatigue test at 43,500 fatigue cycles, before cracks had developed in the lap joint. The fatigue test for the second panel was initially conducted under simulated in-service loading conditions for 120,000 cycles, and no cracks were detected in the skin of the panel test section. Artificial damage was then introduced into the panel at selected rivets in the critical (lower) rivet row, and the fatigue loads were increased. Visually detectable crack growth from the artificial notches was first seen after 133,000 cycles. The resulting lead crack grew along the lower rivet row, eventually forming an 11.8" long unstable crack after 141,771 cycles, at which point the test was terminated. Posttest fractograpic examinations of the crack surfaces were conducted, revealing the presence of subsurface MSD at the critical rivet row of the lap joint. Special attention was also given to the stringer clips that attach the fuselage frames to the stringers, since they also experienced cracking during the fatigue tests. The performance of the different conventional and emerging NDI methods was also assessed, and some of the emerging NDI methods were quite effective in detecting and measuring the length of subsurface cracks. Delta Air Lines conducted a separate destructive investigation on the state of damage along the right-hand side of the fuselage, near stringer 4R. A comparison of these two studies showed that the lap joint on the left hand-side of the aircraft, along stringer 4L, had better fatigue life than the one on the opposite side, along stringer 4R. The cause of the difference in fatigue life was investigated by close examination of the rivet installation qualities, and was found to be a result of better rivet installation along the lap joint at stringer 4L. Finite element models for both the skin and substructures of the panels were developed and geometrically nonlinear finite element analyses were conducted to verify the loading conditions and to determine near-field parameters governing MSD initiation and growth. Fatigue crack growth predictions based on the NASGRO equation were in good agreement with the experimental crack growth data for through-the-thickness cracks. For subsurface cracks, simulation of crack growth was found to correlate better with fractography data when an empirical crack growth model was used. The results of the study contribute to the understanding of the initiation and growth of MSD in the inner skin layer of a lap joint, and provide valuable data for the evaluation and validation of analytical methodologies to predict MSD initiation and growth and a better understanding on the effect of manufacturing quality on damage accumulation along the lap joint.

In Conversation with Jim Schuck: Nano-optics

ScienceCinema

Jim Schuck and Alice Egan

2017-12-09

Sponsored by Berkeley Lab's Materials Sciences Division (MSD), "In Conversation with" is a next generation science seminar series. Host Alice Egan is the assistant to MSD Director Miquel Salmeron. Alice conducts a fun and informative interview, touching on the lives and work of the guest. The first In Conversation With took place July 9 with Jim Schuck, a staff scientist in the Molecular Foundry's Imaging and Manipulation Facility as our first guest. He discussed the world of Nano-optics.

In Conversation with Jim Schuck: Nano-optics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jim Schuck and Alice Egan

Sponsored by Berkeley Lab's Materials Sciences Division (MSD), "In Conversation with" is a next generation science seminar series. Host Alice Egan is the assistant to MSD Director Miquel Salmeron. Alice conducts a fun and informative interview, touching on the lives and work of the guest. The first In Conversation With took place July 9 with Jim Schuck, a staff scientist in the Molecular Foundry's Imaging and Manipulation Facility as our first guest. He discussed the world of Nano-optics.

Communication: Distinguishing between short-time non-Fickian diffusion and long-time Fickian diffusion for a random walk on a crowded lattice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellery, Adam J.; Simpson, Matthew J.; Baker, Ruth E.

2016-05-07

The motion of cells and molecules through biological environments is often hindered by the presence of other cells and molecules. A common approach to modeling this kind of hindered transport is to examine the mean squared displacement (MSD) of a motile tracer particle in a lattice-based stochastic random walk in which some lattice sites are occupied by obstacles. Unfortunately, stochastic models can be computationally expensive to analyze because we must average over a large ensemble of identically prepared realizations to obtain meaningful results. To overcome this limitation we describe an exact method for analyzing a lattice-based model of the motionmore » of an agent moving through a crowded environment. Using our approach we calculate the exact MSD of the motile agent. Our analysis confirms the existence of a transition period where, at first, the MSD does not follow a power law with time. However, after a sufficiently long period of time, the MSD increases in proportion to time. This latter phase corresponds to Fickian diffusion with a reduced diffusivity owing to the presence of the obstacles. Our main result is to provide a mathematically motivated, reproducible, and objective estimate of the amount of time required for the transport to become Fickian. Our new method to calculate this crossover time does not rely on stochastic simulations.« less

Efficacy of a Combined Intracerebral and Systemic Gene Delivery Approach for the Treatment of a Severe Lysosomal Storage Disorder

PubMed Central

Spampanato, Carmine; De Leonibus, Elvira; Dama, Paola; Gargiulo, Annagiusi; Fraldi, Alessandro; Sorrentino, Nicolina Cristina; Russo, Fabio; Nusco, Edoardo; Auricchio, Alberto; Surace, Enrico M; Ballabio, Andrea

2011-01-01

Multiple sulfatase deficiency (MSD), a severe autosomal recessive disease is caused by mutations in the sulfatase modifying factor 1 gene (Sumf1). We have previously shown that in the Sumf1 knockout mouse model (Sumf1−/−) sulfatase activities are completely absent and, similarly to MSD patients, this mouse model displays growth retardation and early mortality. The severity of the phenotype makes MSD unsuitable to be treated by enzyme replacement or bone marrow transplantation, hence the importance of testing the efficacy of novel treatment strategies. Here we show that recombinant adeno-associated virus serotype 9 (rAAV9) vector injected into the cerebral ventricles of neonatal mice resulted in efficient and widespread transduction of the brain parenchyma. In addition, we compared a combined, intracerebral ventricles and systemic, administration of an rAAV9 vector encoding SUMF1 gene to the single administrations—either directly in brain, or systemic alone —in MSD mice. The combined treatment resulted in the global activation of sulfatases, near-complete clearance of glycosaminoglycans (GAGs) and decrease of inflammation in both the central nervous system (CNS) and visceral organs. Furthermore, behavioral abilities were improved by the combined treatment. These results underscore that the “combined” mode of rAAV9 vector administration is an efficient option for the treatment of severe whole-body disorders. PMID:21326216

Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly

PubMed Central

Hori, Akiko; Peddie, Christopher J.; Collinson, Lucy M.; Toda, Takashi

2015-01-01

Centriolar satellites are numerous electron-dense granules dispersed around the centrosome. Mutations in their components are linked to various human diseases, but their molecular roles remain elusive. In particular, the significance of spatial communication between centriolar satellites and the centrosome is unknown. hMsd1/SSX2IP localizes to both the centrosome and centriolar satellites and is required for tethering microtubules to the centrosome. Here we show that hMsd1/SSX2IP-mediated microtubule anchoring is essential for proper centriole assembly and duplication. On hMsd1/SSX2IP knockdown, the centriolar satellites become stuck at the microtubule minus end near the centrosome. Intriguingly, these satellites contain many proteins that normally localize to the centrosome. Of importance, microtubule structures, albeit not being anchored properly, are still required for the emergence of abnormal satellites, as complete microtubule depolymerization results in the disappearance of these aggregates from the vicinity of the centrosome. We highlighted, using superresolution and electron microscopy, that under these conditions, centriole structures are faulty. Remarkably, these cells are insensitive to Plk4 overproduction–induced ectopic centriole formation, yet they accelerate centrosome reduplication upon hydroxyurea arrest. Finally, the appearance of satellite aggregates is cancer cell specific. Together our findings provide novel insights into the mechanism of centriole assembly and microtubule anchoring. PMID:25833712

Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy children

PubMed Central

McWilliam, Stephen J; Antoine, Daniel J; Sabbisetti, Venkata; Pearce, Robin E; Jorgensen, Andrea L; Lin, Yvonne; Leeder, J Steven; Bonventre, Joseph V; Smyth, Rosalind L; Pirmohamed, Munir

2014-01-01

Aim The aim of this study was to establish reference intervals in healthy children for two novel urinary biomarkers of acute kidney injury, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Materials & Methods Urinary biomarkers were determined in samples from children in the UK (n = 120) and the USA (n = 171) using both Meso Scale Discovery (MSD) and Luminex-based analytical approaches. Results 95% reference intervals for each biomarker in each cohort are presented and stratified by sex or ethnicity where necessary, and age-related variability is explored using quantile regression. We identified consistently higher NGAL concentrations in females than males (p < 0.0001), and lower KIM-1 concentrations in African–Americans than Caucasians (p = 0.02). KIM-1 demonstrated diurnal variation, with higher concentrations in the morning (p < 0.001). Conclusion This is the first report of reference intervals for KIM-1 and NGAL using two analytical methods in a healthy pediatric population in both UK and US-based populations. PMID:24661102

A platform for the discovery of new macrolide antibiotics

NASA Astrophysics Data System (ADS)

Seiple, Ian B.; Zhang, Ziyang; Jakubec, Pavol; Langlois-Mercier, Audrey; Wright, Peter M.; Hog, Daniel T.; Yabu, Kazuo; Allu, Senkara Rao; Fukuzaki, Takehiro; Carlsen, Peter N.; Kitamura, Yoshiaki; Zhou, Xiang; Condakes, Matthew L.; Szczypiński, Filip T.; Green, William D.; Myers, Andrew G.

2016-05-01

The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture.

Developing the Biomolecular Screening Facility at the EPFL into the Chemical Biology Screening Platform for Switzerland.

PubMed

Turcatti, Gerardo

2014-05-01

The Biomolecular Screening Facility (BSF) is a multidisciplinary laboratory created in 2006 at the Ecole Polytechnique Federale de Lausanne (EPFL) to perform medium and high throughput screening in life sciences-related projects. The BSF was conceived and developed to meet the needs of a wide range of researchers, without privileging a particular biological discipline or therapeutic area. The facility has the necessary infrastructure, multidisciplinary expertise and flexibility to perform large screening programs using small interfering RNAs (siRNAs) and chemical collections in the areas of chemical biology, systems biology and drug discovery. In the framework of the National Centres of Competence in Research (NCCR) Chemical Biology, the BSF is hosting 'ACCESS', the Academic Chemical Screening Platform of Switzerland that provides the scientific community with chemical diversity, screening facilities and know-how in chemical genetics. In addition, the BSF started its own applied research axes that are driven by innovation in thematic areas related to preclinical drug discovery and discovery of bioactive probes.

Rush-hour aromatic and chlorinated hydrocarbons in selected subway stations of Shanghai, China.

PubMed

Zhang, Yanli; Li, Chunlei; Wang, Xinming; Guo, Hai; Feng, Yanli; Chen, Jianmin

2012-01-01

Air samples were collected simultaneously at platform, mezzanine and outdoor in five typical stations of subway system in Shanghai, China using stainless steel canisters and analyzed by gas chromatography-mass selective detector (GC-MSD) after cryogenic preconcentration. Benzene, toluene, ethylbenzene and xylenes (BTEX) at the platforms and mezzanines inside the stations averaged (10.3 +/- 2.1), (38.7 +/- 9.0), (19.4 +/- 10.1) and (30.0 +/- 11.1) microg/m3, respectively; while trichloroethylene (TrCE), tetrachloroethylene (TeCE) and para-dichlorobenzene (pDCB), vinyl chloride and carbon tetrachloride were the most abundant chlorinated hydrocarbons inside the stations with average levels of (3.6 +/- 1.3), (1.3 +/- 0.5), (4.1 +/- 1.1), (2.2 +/- 1.1) and (1.2 +/- 0.3) microg/m3, respectively. Mean levels of major aromatic and chlorinated hydrocarbons were higher indoor (platforms and mezzanines) than outdoor with average indoor/outdoor (I/O) ratios of 1.1-9.5, whereas no significant indoor/outdoor differences were found except for benzene and TrCE. The highly significant mutual correlations (p < 0.01) for BTEX between indoor and outdoor and their significant correlation (p < 0.05) with methyl tert-butyl ether (MTBE), a marker of traffic-related emission without other indoor and outdoor sources, indicated that BTEX were introduced into the subway stations from indoor/outdoor air exchange and traffic emission should be their dominant source. TrCE and pDCB were mainly from indoor emission and TeCE might have both indoor emission sources and contribution from outdoor air, especially in the mezzanines.

Preliminary AMS Study in Cretaceous Igneous Rocks of Valle Chico Complex, Uruguay: Statistical Determination of Magnetic Susceptibility

NASA Astrophysics Data System (ADS)

Barcelona, H.; Mena, M.; Sanchez-Bettucci, L.

2009-05-01

The Valle Chico Complex, at southeast Uruguay, is related Paraná-Etendeka Province. The study involved basaltic lavas, quarz-syenites, and rhyolitic and trachytic dikes. Samples were taken from 18 sites and the AMS of 250 specimens was analyzed. The AMS is modeled by a second order tensor K and it graphical representation is a symmetric ellipsoid. The axes relations determine parameters which describe different properties like shape, lineation, and foliation, degree of anisotropy and bulk magnetic susceptibility. Under this perspective, one lava, dike, or igneous body can be considered a mosaic of magnetic susceptibility domains (MSD). The DSM is an area with specific degree of homogeneity in the distribution of parameters values and cinematic conditions. An average tensor would weigh only one MSD, but if the site is a mosaic, subsets of specimens with similar parameters can be created. Hypothesis tests can be used to establish parameter similarities. It would be suitable considered as a MSD the subsets with statistically significant differences in at least one of its means parameters, and therefore, be treated independently. Once defined the MSDs the tensor analysis continues. The basalt-andesitic lavas present MSD with an NNW magnetic foliation, dipping 10. The K1 are sub-horizontal, oriented E-W and reprsent the magmatic flow direction. The quartz-syenites show a variable magnetic fabric or prolate ellipsoids mayor axes dispose parallel to the flow direction (10 to the SSE). Deformed syenites show N300/11 magnetic foliation, consistent with the trend of fractures. The K1 is subvertical. The MSD defined in rhyolitic dikes have magnetic foliations consistent with the structural trend. The trachytic dikes show an important indetermination in the magnetic response. However, a 62/N90 magnetic lineation was defined. The MSDs obtained are consistent with the geological structures and contribute to the knowledge of the tectonic, magmatic and kinematic events.

SU-E-J-129: Atlas Development for Cardiac Automatic Contouring Using Multi-Atlas Segmentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, R; Yang, J; Pan, T

Purpose: To develop a set of atlases for automatic contouring of cardiac structures to determine heart radiation dose and the associated toxicity. Methods: Six thoracic cancer patients with both contrast and non-contrast CT images were acquired for this study. Eight radiation oncologists manually and independently delineated cardiac contours on the non-contrast CT by referring to the fused contrast CT and following the RTOG 1106 atlas contouring guideline. Fifteen regions of interest (ROIs) were delineated, including heart, four chambers, four coronary arteries, pulmonary artery and vein, inferior and superior vena cava, and ascending and descending aorta. Individual expert contours were fusedmore » using the simultaneous truth and performance level estimation (STAPLE) algorithm for each ROI and each patient. The fused contours became atlases for an in-house multi-atlas segmentation. Using leave-one-out test, we generated auto-segmented contours for each ROI and each patient. The auto-segmented contours were compared with the fused contours using the Dice similarity coefficient (DSC) and the mean surface distance (MSD). Results: Inter-observer variability was not obvious for heart, chambers, and aorta but was large for other structures that were not clearly distinguishable on CT image. The average DSC between individual expert contours and the fused contours were less than 50% for coronary arteries and pulmonary vein, and the average MSD were greater than 4.0 mm. The largest MSD of expert contours deviating from the fused contours was 2.5 cm. The mean DSC and MSD of auto-segmented contours were within one standard deviation of expert contouring variability except the right coronary artery. The coronary arteries, vena cava, and pulmonary vein had DSC<70% and MSD>3.0 mm. Conclusion: A set of cardiac atlases was created for cardiac automatic contouring, the accuracy of which was comparable to the variability in expert contouring. However, substantial modification may need for auto-segmented contours of indistinguishable small structures.« less

Process evaluation of knowledge transfer across industries: Leveraging Coca-Cola's supply chain expertise for medicine availability in Tanzania.

PubMed

Linnander, Erika; Yuan, Christina T; Ahmed, Shirin; Cherlin, Emily; Talbert-Slagle, Kristina; Curry, Leslie A

2017-01-01

Persistent gaps in the availability of essential medicines have slowed the achievement of global health targets. Despite the supply chain knowledge and expertise that ministries of health might glean from other industries, limited empirical research has examined the process of knowledge transfer from other industries into global public health. We examined a partnership designed to improve the availability of medical supplies in Tanzania by transferring knowledge from The Coca-Cola system to Tanzania's Medical Stores Department (MSD). We conducted a process evaluation including in-depth interviews with 70 participants between July 2011 and May 2014, corresponding to each phase of the partnership, with focus on challenges and strategies to address them, as well as benefits perceived by partners. Partners faced challenges in (1) identifying relevant knowledge to transfer, (2) translating operational solutions from Coca-Cola to MSD, and (3) maintaining momentum between project phases. Strategies to respond to these challenges emerged through real-time problem solving and included (1) leveraging the receptivity of MSD leadership, (2) engaging a boundary spanner to identify knowledge to transfer, (3) promoting local recognition of commonalities across industries, (4) engaging external technical experts to manage translation activities, (5) developing tools with visible benefits for MSD, (6) investing in local relationships, and (7) providing time and space for the partnership model to evolve. Benefits of the partnership perceived by MSD staff included enhanced collaboration and communication, more proactive orientations in managing operations, and greater attention to performance management. Benefits perceived by Coca-Cola staff included strengthened knowledge transfer capability and enhanced job satisfaction. Linking theoretical constructs with practical experiences from the field, we highlight the challenges, emergent strategies, and perceived benefits of a partnership across industry boundaries that may be useful to others seeking to promote the transfer of knowledge to improve global health.

Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT.

PubMed

Dufour, Carlo; Veys, Paul; Carraro, Elisa; Bhatnagar, Neha; Pillon, Marta; Wynn, Rob; Gibson, Brenda; Vora, Ajay J; Steward, Colin G; Ewins, Anna M; Hough, Rachael E; de la Fuente, Josu; Velangi, Mark; Amrolia, Persis J; Skinner, Roderick; Bacigalupo, Andrea; Risitano, Antonio M; Socie, Gerard; Peffault de Latour, Regis; Passweg, Jakob; Rovo, Alicia; Tichelli, André; Schrezenmeier, Hubert; Hochsmann, Britta; Bader, Peter; van Biezen, Anja; Aljurf, Mahmoud D; Kulasekararaj, Austin; Marsh, Judith C; Samarasinghe, Sujith

2015-11-01

We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (P = 0·02).The 2-year event-free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0·02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD. © 2015 John Wiley & Sons Ltd.

Process evaluation of knowledge transfer across industries: Leveraging Coca-Cola’s supply chain expertise for medicine availability in Tanzania

PubMed Central

Yuan, Christina T.; Ahmed, Shirin; Cherlin, Emily; Talbert-Slagle, Kristina; Curry, Leslie A.

2017-01-01

Persistent gaps in the availability of essential medicines have slowed the achievement of global health targets. Despite the supply chain knowledge and expertise that ministries of health might glean from other industries, limited empirical research has examined the process of knowledge transfer from other industries into global public health. We examined a partnership designed to improve the availability of medical supplies in Tanzania by transferring knowledge from The Coca-Cola system to Tanzania’s Medical Stores Department (MSD). We conducted a process evaluation including in-depth interviews with 70 participants between July 2011 and May 2014, corresponding to each phase of the partnership, with focus on challenges and strategies to address them, as well as benefits perceived by partners. Partners faced challenges in (1) identifying relevant knowledge to transfer, (2) translating operational solutions from Coca-Cola to MSD, and (3) maintaining momentum between project phases. Strategies to respond to these challenges emerged through real-time problem solving and included (1) leveraging the receptivity of MSD leadership, (2) engaging a boundary spanner to identify knowledge to transfer, (3) promoting local recognition of commonalities across industries, (4) engaging external technical experts to manage translation activities, (5) developing tools with visible benefits for MSD, (6) investing in local relationships, and (7) providing time and space for the partnership model to evolve. Benefits of the partnership perceived by MSD staff included enhanced collaboration and communication, more proactive orientations in managing operations, and greater attention to performance management. Benefits perceived by Coca-Cola staff included strengthened knowledge transfer capability and enhanced job satisfaction. Linking theoretical constructs with practical experiences from the field, we highlight the challenges, emergent strategies, and perceived benefits of a partnership across industry boundaries that may be useful to others seeking to promote the transfer of knowledge to improve global health. PMID:29121051

Automatic and integrated micro-enzyme assay (AIμEA) platform for highly sensitive thrombin analysis via an engineered fluorescence protein-functionalized monolithic capillary column.

PubMed

Lin, Lihua; Liu, Shengquan; Nie, Zhou; Chen, Yingzhuang; Lei, Chunyang; Wang, Zhen; Yin, Chao; Hu, Huiping; Huang, Yan; Yao, Shouzhuo

2015-04-21

Nowadays, large-scale screening for enzyme discovery, engineering, and drug discovery processes require simple, fast, and sensitive enzyme activity assay platforms with high integration and potential for high-throughput detection. Herein, a novel automatic and integrated micro-enzyme assay (AIμEA) platform was proposed based on a unique microreaction system fabricated by a engineered green fluorescence protein (GFP)-functionalized monolithic capillary column, with thrombin as an example. The recombinant GFP probe was rationally engineered to possess a His-tag and a substrate sequence of thrombin, which enable it to be immobilized on the monolith via metal affinity binding, and to be released after thrombin digestion. Combined with capillary electrophoresis-laser-induced fluorescence (CE-LIF), all the procedures, including thrombin injection, online enzymatic digestion in the microreaction system, and label-free detection of the released GFP, were integrated in a single electrophoretic process. By taking advantage of the ultrahigh loading capacity of the AIμEA platform and the CE automatic programming setup, one microreaction column was sufficient for many times digestion without replacement. The novel microreaction system showed significantly enhanced catalytic efficiency, about 30 fold higher than that of the equivalent bulk reaction. Accordingly, the AIμEA platform was highly sensitive with a limit of detection down to 1 pM of thrombin. Moreover, the AIμEA platform was robust and reliable to detect thrombin in human serum samples and its inhibition by hirudin. Hence, this AIμEA platform exhibits great potential for high-throughput analysis in future biological application, disease diagnostics, and drug screening.

All the World's a Stage: Facilitating Discovery Science and Improved Cancer Care through the Global Alliance for Genomics and Health.

PubMed

Lawler, Mark; Siu, Lillian L; Rehm, Heidi L; Chanock, Stephen J; Alterovitz, Gil; Burn, John; Calvo, Fabien; Lacombe, Denis; Teh, Bin Tean; North, Kathryn N; Sawyers, Charles L

2015-11-01

The recent explosion of genetic and clinical data generated from tumor genome analysis presents an unparalleled opportunity to enhance our understanding of cancer, but this opportunity is compromised by the reluctance of many in the scientific community to share datasets and the lack of interoperability between different data platforms. The Global Alliance for Genomics and Health is addressing these barriers and challenges through a cooperative framework that encourages "team science" and responsible data sharing, complemented by the development of a series of application program interfaces that link different data platforms, thus breaking down traditional silos and liberating the data to enable new discoveries and ultimately benefit patients. ©2015 American Association for Cancer Research.

Toxic Substances Registry System. Index of Material Safety Data Sheets

NASA Technical Reports Server (NTRS)

1994-01-01

The October 1994 revision of the KSC Toxic Substances Registry System (TSRS) Material Safety Data Sheets (MSD's) is presented. The listed MSD's which were submitted to the TSRS are maintained by the Base Operations Contractors of the Biomedical Operations and Research Office of KSC. The purpose of the index is to provide a means of accessing information on the hazards associated with the toxic and otherwise hazardous chemicals stored and used at KSC. Indices are provided for manufacturers, trademarks, and stock numbers.

Non-equilibrium Numerical Analysis of Microwave-supported Detonation Threshold Propagating through Diatomic Gas

NASA Astrophysics Data System (ADS)

Shiraishi, Hiroyuki

2015-09-01

Microwave-supported Detonation (MSD), one type of Microwave-supported Plasma (MSP), is considered as one of the most important phenomena because it can generate high pressure and high temperature for beam-powered space propulsion systems. In this study, I numerically simulate MSD waves propagating through a diatomic gas. In order to evaluate the threshold of beam intensity, I use the physical-fluid dynamics scheme, which has been developed for simulating unsteady and non-equilibrium LSD waves propagating through a hydrogen gas.

The Effect of a Third Generation Hemostatic Dressing in a Subclavian Artery and Vein Transection Porcine Model

DTIC Science & Technology

2014-04-01

The MSD is comprised of a syringe applicator filled with compressed chitosan coated sponges which are delivered into the wound at the site of the...transmitted effectively to the deep subclavian vessels to stop hemorrhage. As a result of their non-compressible nature and paucity of effective field...followed by three minutes of compression to the packed dressing. The mini- sponge dressing (MSD) is a novel product that utilizes compressed, chitosan

Quantitative structure-activity relationship: promising advances in drug discovery platforms.

PubMed

Wang, Tao; Wu, Mian-Bin; Lin, Jian-Ping; Yang, Li-Rong

2015-12-01

Quantitative structure-activity relationship (QSAR) modeling is one of the most popular computer-aided tools employed in medicinal chemistry for drug discovery and lead optimization. It is especially powerful in the absence of 3D structures of specific drug targets. QSAR methods have been shown to draw public attention since they were first introduced. In this review, the authors provide a brief discussion of the basic principles of QSAR, model development and model validation. They also highlight the current applications of QSAR in different fields, particularly in virtual screening, rational drug design and multi-target QSAR. Finally, in view of recent controversies, the authors detail the challenges faced by QSAR modeling and the relevant solutions. The aim of this review is to show how QSAR modeling can be applied in novel drug discovery, design and lead optimization. QSAR should intentionally be used as a powerful tool for fragment-based drug design platforms in the field of drug discovery and design. Although there have been an increasing number of experimentally determined protein structures in recent years, a great number of protein structures cannot be easily obtained (i.e., membrane transport proteins and G-protein coupled receptors). Fragment-based drug discovery, such as QSAR, could be applied further and have a significant role in dealing with these problems. Moreover, along with the development of computer software and hardware, it is believed that QSAR will be increasingly important.

Utilizing Social Bookmarking Tag Space for Web Content Discovery: A Social Network Analysis Approach

ERIC Educational Resources Information Center

Wei, Wei

2010-01-01

Social bookmarking has gained popularity since the advent of Web 2.0. Keywords known as tags are created to annotate web content, and the resulting tag space composed of the tags, the resources, and the users arises as a new platform for web content discovery. Useful and interesting web resources can be located through searching and browsing based…

General view taken inside of an assembly bay of the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

General view taken inside of an assembly bay of the Vehicle Assembly Building at the Kennedy Space Center. This view shows the Orbiter Discovery being lowered into position in preparation for being mated to the External Tank/Solid Rocket Booster assembly on the Mobile Launch Platform. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

SSWAP: A Simple Semantic Web Architecture and Protocol for semantic web services

PubMed Central

Gessler, Damian DG; Schiltz, Gary S; May, Greg D; Avraham, Shulamit; Town, Christopher D; Grant, David; Nelson, Rex T

2009-01-01

Background SSWAP (Simple Semantic Web Architecture and Protocol; pronounced "swap") is an architecture, protocol, and platform for using reasoning to semantically integrate heterogeneous disparate data and services on the web. SSWAP was developed as a hybrid semantic web services technology to overcome limitations found in both pure web service technologies and pure semantic web technologies. Results There are currently over 2400 resources published in SSWAP. Approximately two dozen are custom-written services for QTL (Quantitative Trait Loci) and mapping data for legumes and grasses (grains). The remaining are wrappers to Nucleic Acids Research Database and Web Server entries. As an architecture, SSWAP establishes how clients (users of data, services, and ontologies), providers (suppliers of data, services, and ontologies), and discovery servers (semantic search engines) interact to allow for the description, querying, discovery, invocation, and response of semantic web services. As a protocol, SSWAP provides the vocabulary and semantics to allow clients, providers, and discovery servers to engage in semantic web services. The protocol is based on the W3C-sanctioned first-order description logic language OWL DL. As an open source platform, a discovery server running at (as in to "swap info") uses the description logic reasoner Pellet to integrate semantic resources. The platform hosts an interactive guide to the protocol at , developer tools at , and a portal to third-party ontologies at (a "swap meet"). Conclusion SSWAP addresses the three basic requirements of a semantic web services architecture (i.e., a common syntax, shared semantic, and semantic discovery) while addressing three technology limitations common in distributed service systems: i.e., i) the fatal mutability of traditional interfaces, ii) the rigidity and fragility of static subsumption hierarchies, and iii) the confounding of content, structure, and presentation. SSWAP is novel by establishing the concept of a canonical yet mutable OWL DL graph that allows data and service providers to describe their resources, to allow discovery servers to offer semantically rich search engines, to allow clients to discover and invoke those resources, and to allow providers to respond with semantically tagged data. SSWAP allows for a mix-and-match of terms from both new and legacy third-party ontologies in these graphs. PMID:19775460

Musculoskeletal disorders and associated healthcare costs among family members of injured workers.

PubMed

Asfaw, Abay; Pana-Cryan, Regina; Bushnell, Tim; Sauter, Steven

2015-11-01

Research has infrequently looked beyond the injured worker when gauging the burden of occupational injury. We explored the relationship between occupational injury and musculoskeletal disorders (MSDs) among family members of injured workers. We used 2005 and 2006 Truven Health Analytics databases, which contain information on workers' compensation and family healthcare claims. We used descriptive analyses, and negative binomial and two-part models. Family members of severely injured workers had a 15% increase in the total number of MSD outpatient claims and a 34% increase in the mean cost of MSD claims compared to family members of non-severely injured workers within 3 months after injury. Extrapolating cost results to the national level implies that severe occupational injury would be associated with between $29 and $33 million additional cost of family member outpatient MSD claims. Occupational injury can impose a formerly unrecognized health burden on family members of injured workers. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Langevin dynamics for ramified structures

NASA Astrophysics Data System (ADS)

Méndez, Vicenç; Iomin, Alexander; Horsthemke, Werner; Campos, Daniel

2017-06-01

We propose a generalized Langevin formalism to describe transport in combs and similar ramified structures. Our approach consists of a Langevin equation without drift for the motion along the backbone. The motion along the secondary branches may be described either by a Langevin equation or by other types of random processes. The mean square displacement (MSD) along the backbone characterizes the transport through the ramified structure. We derive a general analytical expression for this observable in terms of the probability distribution function of the motion along the secondary branches. We apply our result to various types of motion along the secondary branches of finite or infinite length, such as subdiffusion, superdiffusion, and Langevin dynamics with colored Gaussian noise and with non-Gaussian white noise. Monte Carlo simulations show excellent agreement with the analytical results. The MSD for the case of Gaussian noise is shown to be independent of the noise color. We conclude by generalizing our analytical expression for the MSD to the case where each secondary branch is n dimensional.

Musculoskeletal symptoms as related to ergonomic factors in Iranian hand-woven carpet industry and general guidelines for workstation design.

PubMed

Choobineh, Alireza; Lahmi, Mohammadali; Shahnavaz, Houshang; Jazani, Reza Khani; Hosseini, Mostafa

2004-01-01

Carpet weaving is a high risk occupation for developing musculoskeletal disorders (MSDs). The objectives of the present study, which was carried out in the Iranian hand-woven carpet industry, were determination of the prevalence of MSD symptoms, identification of major factors associated with MSD symptoms and development of guidelines for workstation design. 1,439 randomly selected weavers participated in this study. A questionnaire was used to collect data on MSD symptoms. The results revealed that the prevalence rates for symptoms in different body regions were high as compared to the general Iranian population (for neck, back and large joints, p <.0001). The results of multivariate analyses showed that major ergonomic factors associated with musculoskeletal symptoms were loom type, working posture, daily working time and seat type. Based on the results, some general guidelines for designing weaving workstations were developed. A prototype test showed that the new workstation was acceptable for subject tests and that it improved working posture.

Measuring a diffusion coefficient by single-particle tracking: statistical analysis of experimental mean squared displacement curves.

PubMed

Ernst, Dominique; Köhler, Jürgen

2013-01-21

We provide experimental results on the accuracy of diffusion coefficients obtained by a mean squared displacement (MSD) analysis of single-particle trajectories. We have recorded very long trajectories comprising more than 1.5 × 10(5) data points and decomposed these long trajectories into shorter segments providing us with ensembles of trajectories of variable lengths. This enabled a statistical analysis of the resulting MSD curves as a function of the lengths of the segments. We find that the relative error of the diffusion coefficient can be minimized by taking an optimum number of points into account for fitting the MSD curves, and that this optimum does not depend on the segment length. Yet, the magnitude of the relative error for the diffusion coefficient does, and achieving an accuracy in the order of 10% requires the recording of trajectories with about 1000 data points. Finally, we compare our results with theoretical predictions and find very good qualitative and quantitative agreement between experiment and theory.

A comment on the position dependent diffusion coefficient representation of structural heterogeneity

NASA Astrophysics Data System (ADS)

Wolfson, Molly; Liepold, Christopher; Lin, Binhua; Rice, Stuart A.

2018-05-01

Experimental studies of the variation of the mean square displacement (MSD) of a particle in a confined colloid suspension that exhibits density variations on the scale length of the particle diameter are not in agreement with the prediction that the spatial variation in MSD should mimic the spatial variation in density. The predicted behavior is derived from the expectation that the MSD of a particle depends on the system density and the assumption that the force acting on a particle is a point function of position. The experimental data are obtained from studies of the MSDs of particles in narrow ribbon channels and between narrowly spaced parallel plates and from new data, reported herein, of the radial and azimuthal MSDs of a colloid particle in a dense colloid suspension confined to a small circular cavity. In each of these geometries, a dense colloid suspension exhibits pronounced density oscillations with spacing of a particle diameter. We remove the discrepancy between prediction and experiment using the Fisher-Methfessel interpretation of how local equilibrium in an inhomogeneous system is maintained to argue that the force acting on a particle is delocalized over a volume with radius equal to a particle diameter. Our interpretation has relevance to the relationship between the scale of inhomogeneity and the utility of translation of the particle MSD into a position dependent diffusion coefficient and to the use of a spatially dependent diffusion coefficient to describe mass transport in a heterogeneous system.

Effect of systematic ergonomic hazard identification and control implementation on musculoskeletal disorder and injury risk.

PubMed

Cantley, Linda F; Taiwo, Oyebode A; Galusha, Deron; Barbour, Russell; Slade, Martin D; Tessier-Sherman, Baylah; Cullen, Mark R

2014-01-01

This study aimed to examine the effect of an ergonomic hazard control (HC) initiative, undertaken as part of a company ergonomics standard, on worker injury risk. Using the company's ergonomic hazards database to identify jobs with and without ergonomic HC implementation and linking to individual job and injury histories, injury risk among person-jobs with HC implementation (the HC group) was compared to those without HC (NoHC group) using random coefficient models. Further analysis of the HC group was conducted to determine the effect of additional ergonomic hazards controlled on injury risk. Among 123 jobs at 17 plant locations, 347 ergonomic hazards were quantitatively identified during the study period. HC were implemented for 204 quantified ergonomic hazards in 84 jobs, impacting 10 385 persons (12 967 person-jobs). No HC were implemented for quantified ergonomic hazards in the remaining 39 jobs affecting 4155 persons (5046 person-jobs). Adjusting for age, sex, plant origin, and year to control for any temporal trend in injury risk, the relative risk (RR) for musculoskeletal disorder (MSD) was 0.85 and the RR for any injury or MSD was 0.92 in the HC compared to NoHC group. Among the HC group, each ergonomic hazard controlled was associated with risk reduction for MSD and acute injury outcomes (RR 0.93). Systematic ergonomic HC through participatory ergonomics, as part of a mandatory company ergonomics standard, is associated with MSD and injury risk reduction among workers in jobs with HC implemented.

Association Between Shigella Infection and Diarrhea Varies Based on Location and Age of Children.

PubMed

Lindsay, Brianna; Saha, Debasish; Sanogo, Doh; Das, Sumon Kumar; Omore, Richard; Farag, Tamer H; Nasrin, Dilruba; Li, Shan; Panchalingam, Sandra; Levine, Myron M; Kotloff, Karen; Nataro, James P; Magder, Laurence; Hungerford, Laura; Faruque, A S G; Oundo, Joseph; Hossain, M Anowar; Adeyemi, Mitchell; Stine, Oscar Colin

2015-11-01

Molecular identification of the invasion plasmid antigen-H (ipaH) gene has been established as a useful detection mechanism for Shigella spp. The Global Enteric Multicenter Study (GEMS) identified the etiology and burden of moderate-to-severe diarrhea (MSD) in sub-Saharan Africa and south Asia using a case-control study and traditional culture techniques. Here, we used quantitative polymerase chain reaction (qPCR) to identify Shigella spp. in 2,611 stool specimens from GEMS and compared these results to those using culture. Demographic and nutritional characteristics were assessed as possible risk factors. The qPCR identified more cases of shigellosis than culture; however, the distribution of demographic characteristics was similar by both methods. In regression models adjusting for Shigella quantity, age, and site, children who were exclusively breast-fed had significantly lower odds of MSD compared with children who were not breast-fed (odds ratio [OR] = 0.47, 95% confidence interval (CI) = 0.28-0.81). The association between Shigella quantity and MSD increased with age, with a peak in children of 24-35 months of age (OR = 8.2, 95% CI = 4.3-15.7) and the relationship between Shigella quantity and disease was greatest in Bangladesh (OR = 13.2, 95% CI = 7.3-23.8). This study found that qPCR identified more cases of Shigella and age, site, and breast-feeding status were significant risk factors for MSD. © The American Society of Tropical Medicine and Hygiene.

Paleoecological reconstruction of hominin-bearing middle Pliocene localities at Woranso-Mille, Ethiopia.

PubMed

Curran, Sabrina C; Haile-Selassie, Yohannes

2016-07-01

Woranso-Mille is a paleoanthropological site in Ethiopia sampling an important and under-represented time period in human evolution (3.8-3.6 million years ago). Specimens of cf. Australopithecus anamensis, Australopithecus afarensis, and the recently named Australopithecus deyiremeda have been recovered from this site. Using multiple habitat proxies, this study provides a paleoecological reconstruction of two fossiliferous collection areas from Woranso-Mille, Aralee Issie (ARI) and Mesgid Dora (MSD). Previous reconstructions based on faunal assemblages have pointed, due to the presence of aepycerotins, alcelaphins, and proboscideans, to the existence of open habitats as well as more closed ones, based on the occurrence of cercopithecids, giraffids, and traglephins. Results from community structure analysis (proportions of locomotor and dietary adaptations) at ARI and MSD indicated a predominance of open habitats, such as shrublands. Mesowear analysis revealed that ungulates of all dietary types (grazers, leaf and fruit browsers, and mixed feeders) were present in nearly equal proportions. Ecomorphological analyses using linear measurements of the astragalus and phalanges indicated that bovids utilizing locomotor behaviors associated with all habitat types were present, though the intermediate-cover habitat bovids were best represented in the sample (Heavy cover at ARI and Light cover at MSD). Together, these results suggest that the ARI and MSD localities were heterogeneous habitats (mosaics), likely with densely vegetated areas along a paleo-river and more open regions (woodlands, grasslands) available away from the river. Copyright © 2016 Elsevier Ltd. All rights reserved.

How compatible are participatory ergonomics programs with occupational health and safety management systems?

PubMed

Yazdani, Amin; Neumann, W Patrick; Imbeau, Daniel; Bigelow, Philip; Pagell, Mark; Theberge, Nancy; Hilbrecht, Margo; Wells, Richard

2015-03-01

Musculoskeletal disorders (MSD) are a major cause of pain, disability, and costs. Prevention of MSD at work is frequently described in terms of implementing an ergonomics program, often a participatory ergonomics (PE) program. Most other workplace injury prevention activities take place under the umbrella of a formal or informal occupational health and safety management system (OHSMS). This study assesses the similarities and differences between OHSMS and PE as such knowledge could help improve MSD prevention activities. Methods Using the internationally recognized Occupational Health and Safety Assessment Series (OHSAS 18001), 21 OHSMS elements were extracted. In order to define PE operationally, we identified the 20 most frequently cited papers on PE and extracted content relevant to each of the OHSAS 18001 elements. The PE literature provided a substantial amount of detail on five elements: (i) hazard identification, risk assessment and determining controls; (ii) resources, roles, responsibility, accountability, and authority; (iii) competence, training and awareness; (iv) participation and consultation; and (v) performance measurement and monitoring. However, of the 21 OHSAS elements, the PE literature was silent on 8 and provided few details on 8 others. The PE literature did not speak to many elements described in OHSMS and even when it did, the language used was often different. This may negatively affect the effectiveness and sustainability of PE initiatives within organizations. It is expected that paying attention to the approaches and language used in management system frameworks could make prevention of MSD activities more effective and sustainable.

Informatics for neglected diseases collaborations.

PubMed

Bost, Frederic; Jacobs, Robert T; Kowalczyk, Paul

2010-05-01

Many different public and private organizations from across the globe are collaborating on neglected diseases drug-discovery and development projects with the aim of identifying a cure for tropical infectious diseases. These neglected diseases collaborations require a global, secure, multi-organization data-management solution, combined with a platform that facilitates communication and supports collaborative work. This review discusses the solutions offered by 'Software as a Service' (SaaS) web-based platforms, despite notable challenges, and the evolution of these platforms required to foster efficient virtual research efforts by geographically dispersed scientists.

ARQiv-HTS, a versatile whole-organism screening platform enabling in vivo drug discovery at high-throughput rates

PubMed Central

White, David T; Eroglu, Arife Unal; Wang, Guohua; Zhang, Liyun; Sengupta, Sumitra; Ding, Ding; Rajpurohit, Surendra K; Walker, Steven L; Ji, Hongkai; Qian, Jiang; Mumm, Jeff S

2017-01-01

The zebrafish has emerged as an important model for whole-organism small-molecule screening. However, most zebrafish-based chemical screens have achieved only mid-throughput rates. Here we describe a versatile whole-organism drug discovery platform that can achieve true high-throughput screening (HTS) capacities. This system combines our automated reporter quantification in vivo (ARQiv) system with customized robotics, and is termed ‘ARQiv-HTS’. We detail the process of establishing and implementing ARQiv-HTS: (i) assay design and optimization, (ii) calculation of sample size and hit criteria, (iii) large-scale egg production, (iv) automated compound titration, (v) dispensing of embryos into microtiter plates, and (vi) reporter quantification. We also outline what we see as best practice strategies for leveraging the power of ARQiv-HTS for zebrafish-based drug discovery, and address technical challenges of applying zebrafish to large-scale chemical screens. Finally, we provide a detailed protocol for a recently completed inaugural ARQiv-HTS effort, which involved the identification of compounds that elevate insulin reporter activity. Compounds that increased the number of insulin-producing pancreatic beta cells represent potential new therapeutics for diabetic patients. For this effort, individual screening sessions took 1 week to conclude, and sessions were performed iteratively approximately every other day to increase throughput. At the conclusion of the screen, more than a half million drug-treated larvae had been evaluated. Beyond this initial example, however, the ARQiv-HTS platform is adaptable to almost any reporter-based assay designed to evaluate the effects of chemical compounds in living small-animal models. ARQiv-HTS thus enables large-scale whole-organism drug discovery for a variety of model species and from numerous disease-oriented perspectives. PMID:27831568

STS-95 Space Shuttle Discovery rollout to Launch Pad 39B

NASA Technical Reports Server (NTRS)

1998-01-01

As daylight creeps over the horizon, STS-95 Space Shuttle Discovery, on the Mobile Launch Platform, arrives at Launch Complex Pad 39B after a 4.2-mile trip taking approximately 6 hours. At the left is the 'white room,' attached to the orbiter access arm. The white room is an environmental chamber that mates with the orbiter and holds six persons. At the launch pad, the orbiter, external tank and solid rocket boosters will undergo final preparations for the launch, scheduled to lift off Oct. 29. The mission includes research payloads such as the Spartan solar- observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

KENNEDY SPACE CENTER, FLA. - STS-114 Mission Specialist Soichi Noguchi looks at tile on the underside of the orbiter Discovery. Noguchi is with the Japanese Aerospace and Exploration Agency. He and other crew members are at KSC becoming familiar with Shuttle and mission equipment. The mission is Logistics Flight 1, which is scheduled to deliver supplies and equipment plus the external stowage platform to the International Space Station.

NASA Image and Video Library

2004-03-05

KENNEDY SPACE CENTER, FLA. - STS-114 Mission Specialist Soichi Noguchi looks at tile on the underside of the orbiter Discovery. Noguchi is with the Japanese Aerospace and Exploration Agency. He and other crew members are at KSC becoming familiar with Shuttle and mission equipment. The mission is Logistics Flight 1, which is scheduled to deliver supplies and equipment plus the external stowage platform to the International Space Station.

KSC-98pc1179

NASA Image and Video Library

1998-09-28

KENNEDY SPACE CENTER, FLA. -- At left, the payload canister for Space Shuttle Discovery is lifted from its canister movement vehicle to the top of the Rotating Service Structure on Launch Pad 39-B. Discovery (right), sitting atop the Mobile Launch Platform and next to the Fixed Service Structure (FSS), is scheduled for launch on Oct. 29, 1998, for the STS-95 mission. That mission includes the International Extreme Ultraviolet Hitchhiker (IEH-3), the Hubble Space Telescope Orbital Systems Test Platform, the Spartan solar-observing deployable spacecraft, and the SPACEHAB single module with experiments on space flight and the aging process. At the top of the FSS can be seen the 80-foot lightning mast . The 4-foot-high lightning rod on top helps prevent lightning current from passing directly through the Space Shuttle and the structures on the pad

Chemical screening platforms for autophagy drug discovery to identify therapeutic candidates for Huntington's disease and other neurodegenerative disorders.

PubMed

Sarkar, Sovan

2013-01-01

Autophagy is a cellular degradation process involved in the clearance of aggregate-prone proteins associated with neurodegenerative diseases. While the mTOR pathway has been known to be the major regulator of autophagy, recent advancements into the regulation of autophagy have identified mTOR-independent autophagy pathways that are amenable to chemical perturbations. Several chemical and genetic screens have been undertaken to identify small molecule and genetic regulators of autophagy, respectively. The small molecule autophagy enhancers offer great potential as therapeutic candidates not only for neurodegenerative diseases, but also for diverse human diseases where autophagy acts as a protective pathway. This review highlights the various chemical screening platforms for autophagy drug discovery pertinent for the treatment of neurodegenerative diseases.

Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

PubMed

Ioset, Jean-Robert; Chang, Shing

2011-09-01

The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

Detail View looking at the protected structure and landing gear ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Detail View looking at the protected structure and landing gear housing in the void created by the removal of the Forward Reaction Control System Module from the forward section of the Orbiter Discovery. This view was taken from the service platform in the Orbiter Processing Facility at Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Reducing the Bottleneck in Discovery of Novel Antibiotics.

PubMed

Jones, Marcus B; Nierman, William C; Shan, Yue; Frank, Bryan C; Spoering, Amy; Ling, Losee; Peoples, Aaron; Zullo, Ashley; Lewis, Kim; Nelson, Karen E

2017-04-01

Most antibiotics were discovered by screening soil actinomycetes, but the efficiency of the discovery platform collapsed in the 1960s. By now, more than 3000 antibiotics have been described and most of the current discovery effort is focused on the rediscovery of known compounds, making the approach impractical. The last marketed broad-spectrum antibiotics discovered were daptomycin, linezolid, and fidaxomicin. The current state of the art in the development of new anti-infectives is a non-existent pipeline in the absence of a discovery platform. This is particularly troubling given the emergence of pan-resistant pathogens. The current practice in dealing with the problem of the background of known compounds is to use chemical dereplication of extracts to assess the relative novelty of a compound it contains. Dereplication typically requires scale-up, extraction, and often fractionation before an accurate mass and structure can be produced by MS analysis in combination with 2D NMR. Here, we describe a transcriptome analysis approach using RNA sequencing (RNASeq) to identify promising novel antimicrobial compounds from microbial extracts. Our pipeline permits identification of antimicrobial compounds that produce distinct transcription profiles using unfractionated cell extracts. This efficient pipeline will eliminate the requirement for purification and structure determination of compounds from extracts and will facilitate high-throughput screen of cell extracts for identification of novel compounds.

GWATCH: a web platform for automated gene association discovery analysis.

PubMed

Svitin, Anton; Malov, Sergey; Cherkasov, Nikolay; Geerts, Paul; Rotkevich, Mikhail; Dobrynin, Pavel; Shevchenko, Andrey; Guan, Li; Troyer, Jennifer; Hendrickson, Sher; Dilks, Holli Hutcheson; Oleksyk, Taras K; Donfield, Sharyne; Gomperts, Edward; Jabs, Douglas A; Sezgin, Efe; Van Natta, Mark; Harrigan, P Richard; Brumme, Zabrina L; O'Brien, Stephen J

2014-01-01

As genome-wide sequence analyses for complex human disease determinants are expanding, it is increasingly necessary to develop strategies to promote discovery and validation of potential disease-gene associations. Here we present a dynamic web-based platform - GWATCH - that automates and facilitates four steps in genetic epidemiological discovery: 1) Rapid gene association search and discovery analysis of large genome-wide datasets; 2) Expanded visual display of gene associations for genome-wide variants (SNPs, indels, CNVs), including Manhattan plots, 2D and 3D snapshots of any gene region, and a dynamic genome browser illustrating gene association chromosomal regions; 3) Real-time validation/replication of candidate or putative genes suggested from other sources, limiting Bonferroni genome-wide association study (GWAS) penalties; 4) Open data release and sharing by eliminating privacy constraints (The National Human Genome Research Institute (NHGRI) Institutional Review Board (IRB), informed consent, The Health Insurance Portability and Accountability Act (HIPAA) of 1996 etc.) on unabridged results, which allows for open access comparative and meta-analysis. GWATCH is suitable for both GWAS and whole genome sequence association datasets. We illustrate the utility of GWATCH with three large genome-wide association studies for HIV-AIDS resistance genes screened in large multicenter cohorts; however, association datasets from any study can be uploaded and analyzed by GWATCH.

KSC-2009-4425

NASA Image and Video Library

2009-08-04

CAPE CANAVERAL, Fla. – Sitting on top of the mobile launcher platform, space shuttle Discovery straddles the flame trench, which channels the flames and smoke exhaust of the shuttle's solid rocket boosters away from the space shuttle during liftoff, on Launch Pad 39A at NASA's Kennedy Space Center in Florida. Traveling from the Vehicle Assembly Building, the shuttle took nearly 12 hours on the journey as technicians stopped several times to clear mud from the crawler's treads and bearings caused by the waterlogged crawlerway. First motion out of the VAB was at 2:07 a.m. EDT Aug. 4. Rollout was delayed approximately 2 hours due to lightning in the area. Discovery was secured, or "hard down" to Launch Pad 39A at 1:50 p.m. EDT. "Hard down" means that the mobile launcher platform, or MLP, is sitting on the pedestals on the pad, and the crawler has been jacked down, thus transferring the weight of the MLP from the crawler to the pad pedestals. Discovery's 13-day flight will deliver a new crew member and 33,000 pounds of equipment to the International Space Station. The equipment includes science and storage racks, a freezer to store research samples, a new sleeping compartment and the COLBERT treadmill. Launch of Discovery on its STS-128 mission is targeted for late August. Photo credit: NASA/Troy Cryder

Cost Effectiveness Study of Wastewater Management Systems for Selected U.S. Coast Guard Vessels. Volume V. Characteristics and Cost Estimates of Selected Marine Sanitary Devices

DTIC Science & Technology

1977-02-01

emissions to meet Applicable standards for () disposal Of oJ~l-cOntAminated residues At sAG (A) MSD) suhsystem tias no potential for prr’ducing ail...odoriferous compounds are oxidized to mainly carbon dioxide and water vapor. The vapor treatment section (VTS) consists mainly of 1-1/2 inch piping...materials in black water stream. 61 Ability of MSD secondary emissions to moot applicable standards for tile discharge of air pollutants (a) No

ARC - A source of multisensor satellite data for polar science

NASA Technical Reports Server (NTRS)

Van Woert, Michael L.; Whritner, Robert H.; Waliser, Duane E.; Bromwich, David H.; Comiso, J. C.

1992-01-01

The NSF's Antarctic Research Center (ARC) has been established to furnish real-time polar-orbiting satellite data in support of Antarctic field studies, as well as to maintain a multisensor satellite data (MSD) archive for retrospective data analysis. An account is presently given of the ways in which the complementary nature of an MSD set can deepen understanding of Antarctic physical processes. An active microwave SAR with 30-m resolution and a radar altimeter will be added to the ARC resources later in this decade, as will the Earth Observing System.

Teach-Discover-Treat (TDT): Collaborative Computational Drug Discovery for Neglected Diseases

PubMed Central

Jansen, Johanna M.; Cornell, Wendy; Tseng, Y. Jane; Amaro, Rommie E.

2012-01-01

Teach – Discover – Treat (TDT) is an initiative to promote the development and sharing of computational tools solicited through a competition with the aim to impact education and collaborative drug discovery for neglected diseases. Collaboration, multidisciplinary integration, and innovation are essential for successful drug discovery. This requires a workforce that is trained in state-of-the-art workflows and equipped with the ability to collaborate on platforms that are accessible and free. The TDT competition solicits high quality computational workflows for neglected disease targets, using freely available, open access tools. PMID:23085175

Bringing your tools to CyVerse Discovery Environment using Docker

PubMed Central

Devisetty, Upendra Kumar; Kennedy, Kathleen; Sarando, Paul; Merchant, Nirav; Lyons, Eric

2016-01-01

Docker has become a very popular container-based virtualization platform for software distribution that has revolutionized the way in which scientific software and software dependencies (software stacks) can be packaged, distributed, and deployed. Docker makes the complex and time-consuming installation procedures needed for scientific software a one-time process. Because it enables platform-independent installation, versioning of software environments, and easy redeployment and reproducibility, Docker is an ideal candidate for the deployment of identical software stacks on different compute environments such as XSEDE and Amazon AWS. CyVerse’s Discovery Environment also uses Docker for integrating its powerful, community-recommended software tools into CyVerse’s production environment for public use. This paper will help users bring their tools into CyVerse Discovery Environment (DE) which will not only allows users to integrate their tools with relative ease compared to the earlier method of tool deployment in DE but will also help users to share their apps with collaborators and release them for public use. PMID:27803802

Bringing your tools to CyVerse Discovery Environment using Docker.

PubMed

Devisetty, Upendra Kumar; Kennedy, Kathleen; Sarando, Paul; Merchant, Nirav; Lyons, Eric

2016-01-01

Docker has become a very popular container-based virtualization platform for software distribution that has revolutionized the way in which scientific software and software dependencies (software stacks) can be packaged, distributed, and deployed. Docker makes the complex and time-consuming installation procedures needed for scientific software a one-time process. Because it enables platform-independent installation, versioning of software environments, and easy redeployment and reproducibility, Docker is an ideal candidate for the deployment of identical software stacks on different compute environments such as XSEDE and Amazon AWS. CyVerse's Discovery Environment also uses Docker for integrating its powerful, community-recommended software tools into CyVerse's production environment for public use. This paper will help users bring their tools into CyVerse Discovery Environment (DE) which will not only allows users to integrate their tools with relative ease compared to the earlier method of tool deployment in DE but will also help users to share their apps with collaborators and release them for public use.

VOLTTRON™: An Agent Platform for Integrating Electric Vehicles and Smart Grid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haack, Jereme N.; Akyol, Bora A.; Tenney, Nathan D.

2013-12-06

The VOLTTRON™ platform provides a secure environment for the deployment of intelligent applications in the smart grid. VOLTTRON design is based on the needs of control applications running on small form factor devices, namely security and resource guarantees. Services such as resource discovery, secure agent mobility, and interacting with smart and legacy devices are provided by the platform to ease the development of control applications and accelerate their deployment. VOLTTRON platform has been demonstrated in several different domains that influenced and enhanced its capabilities. This paper will discuss the features of VOLTTRON and highlight its usage to coordinate electric vehiclemore » charging with home energy usage« less

Discovery of Regulators of Receptor Internalization with High-Throughput Flow Cytometry

PubMed Central

Tapia, Phillip H.; Fisher, Gregory W.; Simons, Peter C.; Strouse, J. Jacob; Foutz, Terry; Waggoner, Alan S.; Jarvik, Jonathan; Sklar, Larry A.

2012-01-01

We developed a platform combining fluorogen-activating protein (FAP) technology with high-throughput flow cytometry to detect real-time protein trafficking to and from the plasma membrane in living cells. The hybrid platform facilitates drug discovery for trafficking receptors such as G protein-coupled receptors and was validated with the β2-adrenergic receptor (β2AR) system. When a chemical library containing ∼1200 off-patent drugs was screened against cells expressing FAP-tagged β2ARs, all 33 known β2AR-active ligands in the library were successfully identified, together with a number of compounds that might regulate receptor internalization in a nontraditional manner. Results indicated that the platform identified ligands of target proteins regardless of the associated signaling pathway; therefore, this approach presents opportunities to search for biased receptor modulators and is suitable for screening of multiplexed targets for improved efficiency. The results revealed that ligands may be biased with respect to the rate or duration of receptor internalization and that receptor internalization may be independent of activation of the mitogen-activated protein kinase pathway. PMID:22767611

A novel in silico approach to drug discovery via computational intelligence.

PubMed

Hecht, David; Fogel, Gary B

2009-04-01

A computational intelligence drug discovery platform is introduced as an innovative technology designed to accelerate high-throughput drug screening for generalized protein-targeted drug discovery. This technology results in collections of novel small molecule compounds that bind to protein targets as well as details on predicted binding modes and molecular interactions. The approach was tested on dihydrofolate reductase (DHFR) for novel antimalarial drug discovery; however, the methods developed can be applied broadly in early stage drug discovery and development. For this purpose, an initial fragment library was defined, and an automated fragment assembly algorithm was generated. These were combined with a computational intelligence screening tool for prescreening of compounds relative to DHFR inhibition. The entire method was assayed relative to spaces of known DHFR inhibitors and with chemical feasibility in mind, leading to experimental validation in future studies.

Perceptions, attitudes and experiences of family caregivers of patients with musculoskeletal diseases: a qualitative approach.

PubMed

Alfaro, Noelia; Lázaro, Pablo; Gabriele, Giovanna; Garcia-Vicuña, Rosario; Jover, Juan Ángel; Sevilla, Jordi

2013-01-01

To determine the perceptions, attitudes and experiences among family caregivers of patients with musculoskeletal diseases (MSD). Descriptive, exploratory, qualitative study. Two discussion groups were organized with family caregivers of MSD patients, representing the caregiver profile: gender (men/women) and age (31-45 years/46-65 years); and patient profiles: MSD type (rheumatoid arthritis/ankylosing spondylitis), work status (yes or no for the variables housewife, at least 3 episodes of sick leave, patients who abandoned their work, and patients with permanent work disability). A content analysis based on the Grounded Theory was done to detect and explore emerging categories. The emerging dimensions were: alterations in daily life activities, need for caregiver support, physical and psychological impact on the caregiver, characteristics of the patient, and several aspects of care. Relevant experiences mentioned were: the diagnosis of a MSD changes the patient and their family members' life affecting work, financial, social, psychological and physical spheres, making it necessary help for basic activities of daily living. Early age at onset or severe MSDs require dedication and effort on the part of caregivers which increases with time. This leads to a great emotional overload on the caregivers, which may be modulated by the support they receive when providing care. The primary consequences for caregivers are loss of purchasing power, work problems, social isolation and emotional stress. Programs for effective at-home support need to be developed with streamlined administrative processes to quickly classify the level of disability and provide official assistance. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Prevalence of work-related musculoskeletal injuries among South Indian hand screen-printing workers.

PubMed

Shankar, S; Naveen Kumar, R; Mohankumar, P; Jayaraman, Srinivasan

2017-01-01

Hand screen-printing (HSP) plays a predominant role in textile industries in developing countries. Workers from HSP industry were mostly affected by musculoskeletal injury due to monotonous, and prolonged work nature and poor workplace environment. The present study aims to investigate the prevalence of work-related musculoskeletal disorder (MSD) symptoms and risk factors associated among the HSP industry workers. Cochran's sample size for categorical data was used to select 385 HSP workers of 1000 samples from various provinces of Tamil Nadu, INDIA. Modified Nordic based questionnaire was used to assess the musculoskeletal injuries and risk factors among HSP workers. The statistical analysis revealed that 62.5% workers are prone to MSD symptoms with lower back (75.1%), shoulder (66.2%), knees (58.7%), and ankle/feet (55.6%). Age, experience, marital status, stress in the job were the risk factors which significantly (p < 0.05) associated with the reported MSDs. Further, this study result infers that the subjects with higher age and experience are exposed higher levels of MSD prevalence of 85.5% and 92.0% respectively in past 12 months than other groups. Among the different work categories in HSP task, the workers reported with the maximum discomfort during printing work (63.1%) with Odds ratio as 10.38 and 95% CI is 6.18-17.4. than the material handling and drying task. Study results infer that HSP workers are prone to lower back and shoulder pain followed by knees and ankle feet regions. Socio-demographic factors, awkward posture and repetitive movements contribute to cause MSD among hand screen-printing workers.

Effect of systematic ergonomic hazard identification and control implementation on musculoskeletal disorder and injury risk

PubMed Central

Cantley, Linda F; Taiwo, Oyebode A; Galusha, Deron; Barbour, Russell; Slade, Martin D; Tessier-Sherman, Baylah; Cullen, Mark R

2014-01-01

Objectives This study aimed to examine the effect of an ergonomic hazard control (HC) initiative, undertaken as part of a company ergonomics standard, on worker injury risk. Methods Using the company's ergonomic hazards database to identify jobs with and without ergonomic HC implementation and linking to individual job and injury histories, injury risk among person-jobs with HC implementation (the HC group) was compared to those without HC (NoHC group) using random coefficient models. Further analysis of the HC group was conducted to determine the effect of additional ergonomic hazards controlled on injury risk. Results Among 123jobs at 17 plant locations, 347 ergonomic hazards were quantitatively identified during the study period. HC were implemented for 204 quantified ergonomic hazards in 84 jobs, impacting 10 385 persons (12 967 person-jobs). No HC were implemented for quantified ergonomic hazards in the remaining 39 jobs affecting 4155 persons (5046 person-jobs). Adjusting for age, sex, plant origin, and year to control for any temporal trend in injury risk, the relative risk (RR) for musculoskeletal disorder (MSD) was 0.85 and the RR for any injury or MSD was 0.92 in the HC compared to NoHC group. Among the HC group, each ergonomic hazard controlled was associated with risk reduction for MSD and acute injury outcomes (RR 0.93). Conclusion Systematic ergonomic HC through participatory ergonomics, as part of a mandatory company ergonomics standard, is associated with MSD and injury risk reduction among workers in jobs with HC implemented. PMID:24142048

Matched signal detection on graphs: Theory and application to brain imaging data classification.

PubMed

Hu, Chenhui; Sepulcre, Jorge; Johnson, Keith A; Fakhri, Georges E; Lu, Yue M; Li, Quanzheng

2016-01-15

Motivated by recent progress in signal processing on graphs, we have developed a matched signal detection (MSD) theory for signals with intrinsic structures described by weighted graphs. First, we regard graph Laplacian eigenvalues as frequencies of graph-signals and assume that the signal is in a subspace spanned by the first few graph Laplacian eigenvectors associated with lower eigenvalues. The conventional matched subspace detector can be applied to this case. Furthermore, we study signals that may not merely live in a subspace. Concretely, we consider signals with bounded variation on graphs and more general signals that are randomly drawn from a prior distribution. For bounded variation signals, the test is a weighted energy detector. For the random signals, the test statistic is the difference of signal variations on associated graphs, if a degenerate Gaussian distribution specified by the graph Laplacian is adopted. We evaluate the effectiveness of the MSD on graphs both with simulated and real data sets. Specifically, we apply MSD to the brain imaging data classification problem of Alzheimer's disease (AD) based on two independent data sets: 1) positron emission tomography data with Pittsburgh compound-B tracer of 30 AD and 40 normal control (NC) subjects, and 2) resting-state functional magnetic resonance imaging (R-fMRI) data of 30 early mild cognitive impairment and 20 NC subjects. Our results demonstrate that the MSD approach is able to outperform the traditional methods and help detect AD at an early stage, probably due to the success of exploiting the manifold structure of the data. Copyright © 2015. Published by Elsevier Inc.

Workstyle and Musculoskeletal Discomfort (MSD): Exploring the Influence of Work Culture in Malaysia.

PubMed

Maakip, Ismail; Keegel, Tessa; Oakman, Jodi

2015-12-01

Workstyle can be defined as an individual pattern of cognitions, behaviours and physiological reactivity that can occur while performing job tasks. Workstyle has been associated with the development of musculoskeletal disorders (MSDs) amongst office workers in developed countries. However, little is known about the contribution of workstyle on MSDs in developing countries such as Malaysia. The objective of this cross-sectional study was to examine the relationship between workstyle and musculoskeletal discomfort in a sample of office workers in Malaysia. Office workers (N = 417; response rate 65.5 %) from four organisations completed a survey measuring physical and psychosocial hazards, job satisfaction, work-life balance, workstyle, and MSD discomfort levels. Hierarchical regression analyses were undertaken to examine predictors associated with self-reported musculoskeletal discomfort, and more specifically the relationship between workstyle and MSD discomfort. Musculoskeletal discomfort was significantly associated with working through pain, mental health, physical demands, gender and work-life balance (R (2) = 50.2, adjusted R (2) = 0.48; F (13, 324) = 25.09, p = 0.001). Working through pain is the strongest risk factor associated with MSD discomfort (ß = 0.49, p = 0.001) compared to other potential risk factors. Working through pain is influenced by work, social culture and religious beliefs. Workplace MSDs interventions that focus on the impact of physical and psychosocial hazards with emphasis on addressing adverse workstyles should take into account aspects related to work and social culture of the target population. Changes are recommended at both employee and management levels such as better communications and understanding concerning workplace problems with regards to minimizing MSDs at work.

Role of Occupational Stress and Burnout in Prevalence of Musculoskeletal Disorders Among Embassy Personnel of Foreign Countries in Iran

PubMed Central

Aghilinejad, Mashaallah; Sadeghi, Zargham; Abdullah, Amer; Sarebanha, Shima; Bahrami-Ahmadi, Amir

2014-01-01

Background: Occupation is one of the major parts of our daily lives that might cause a great amount of stress. Stress and job burnout are linked together. The association between musculoskeletal disorders (MSD) and burnout syndrome as a psychosocial factor was investigated previously. Objectives: The aim of this study was to identify the role of occupational stress and burnout in musculoskeletal complaint among diplomatic employees of different embassies in Iran. Materials and Methods: In a cross-sectional study, we assessed 200 employees of the foreign countries embassies in Iran. The participants were selected randomly from all the embassy personnel. Study questionnaires were delivered to the participants and finally 161 questionnaires were returned to the researchers (response rate: 80.5%). An assessment of burnout and MSD were made using the Maslach Burnout Inventory (MBI) and Nordic questionnaires. The work place stress was measured by the work place stress questionnaire. Results: Mean occupational stress was significantly higher among embassy personnel with MSD than among the personnel without this syndrome during the preceding week (17.18 ± 3.42 and 16.06 ± 2.19, respectively; P = 0.02) and the preceding year (17.17 ± 3.11 and 16.74 ± 3.03, respectively; P < 0.01) to the study. Only smoking and occupational stress were identified as independent predictors of MSD among embassy personnel. Conclusions: It seems that association between musculoskeletal complaints and burnout syndrome was more complex than being attributed to only occupation stress. Further studies are recommended to determine other related factors to this association. PMID:25031868

[Hematopoietic Reconstitution and Prognosis of HLA Matched and Haploidentical Hematopoietic Stem Cell Transplantation Using Modified FC/ATG Conditioning for Treatment of Severe Aplastic Anemia].

PubMed

Wang, Li; Wu, Ya-Mei; Cao, Yong-Bin; Li, Xiao-Hong; Xu, Li-Xin; Wang, Hai-Tao; Gao, Ya-Hui; Wu, Xiao-Xiong

2016-12-01

To analyse the feasibility and compare differences between hematopoietic reconstitution and prognosis of patients with severe aplastic anemia(SAA) after matched sibling donor (MSD) or haploidentical family donor (HFD) hematopoietic stem cell transplantation (HSCT) using the modified FC/ATG conditioning. The clinical data of 56 patients with SAA who received HSCT in First Affiliated Hospital of Chinese PLA General Hospital from January 2011 to June 2016 were analyzed retrospectively. The hematopoietic reconstitution, graft verus host disease (GVHD), transplantation related toxicity (TRT) and prognosis after transplantation were compared. Furthermore, the modifed conditioning FC/ATG included low-dose cyclophosphamide (total dose 100 mg/kg), infustion of third-party donor-derived mesenchymal stem cells. All 56 patients with MSD-HSCT or HFD-HSCT achieved hematopoietic reconstitution. Among them, not only the recovery of neutrophils and platelets, but also the incidences of III-IV aGVHD, extensive cGVHD and TRT were not significantly different (the P value were 0.58, 0.61, 0.73, 0.73 and 0.67, respectively). After following-up for 32(2-66) months, 48 patients alive well, the 1-year overall survival rates were 86% in HFD-HSCT group and 89% in MSD-HSCT group, respectively (P=0.58). After HSCT using the modifed FC/ATG conditioning, patients with SAA achieved stable engraftment, low toxicity, mild GVHD and excellent outcomes. Furthermore, the HFD-HSCT achieved comparable outcomes to MSD-HSCT and may be served as an alternate therapy for patients with SAA.

Role of occupational stress and burnout in prevalence of musculoskeletal disorders among embassy personnel of foreign countries in iran.

PubMed

Aghilinejad, Mashaallah; Sadeghi, Zargham; Abdullah, Amer; Sarebanha, Shima; Bahrami-Ahmadi, Amir

2014-05-01

Occupation is one of the major parts of our daily lives that might cause a great amount of stress. Stress and job burnout are linked together. The association between musculoskeletal disorders (MSD) and burnout syndrome as a psychosocial factor was investigated previously. The aim of this study was to identify the role of occupational stress and burnout in musculoskeletal complaint among diplomatic employees of different embassies in Iran. In a cross-sectional study, we assessed 200 employees of the foreign countries embassies in Iran. The participants were selected randomly from all the embassy personnel. Study questionnaires were delivered to the participants and finally 161 questionnaires were returned to the researchers (response rate: 80.5%). An assessment of burnout and MSD were made using the Maslach Burnout Inventory (MBI) and Nordic questionnaires. The work place stress was measured by the work place stress questionnaire. Mean occupational stress was significantly higher among embassy personnel with MSD than among the personnel without this syndrome during the preceding week (17.18 ± 3.42 and 16.06 ± 2.19, respectively; P = 0.02) and the preceding year (17.17 ± 3.11 and 16.74 ± 3.03, respectively; P < 0.01) to the study. Only smoking and occupational stress were identified as independent predictors of MSD among embassy personnel. It seems that association between musculoskeletal complaints and burnout syndrome was more complex than being attributed to only occupation stress. Further studies are recommended to determine other related factors to this association.

Health-related effects of early part-time sick leave due to musculoskeletal disorders: a randomized controlled trial.

PubMed

Shiri, Rahman; Kausto, Johanna; Martimo, Kari-Pekka; Kaila-Kangas, Leena; Takala, Esa-Pekka; Viikari-Juntura, Eira

2013-01-01

Previously we reported that early part-time sick leave enhances return to work (RTW) among employees with musculoskeletal disorders (MSD). This paper assesses the health-related effects of this intervention. Patients aged 18-60 years who were unable to perform their regular work due to MSD were randomized to part- or full-time sick leave groups. In the former, workload was reduced by halving working time. Using validated questionnaires, we assessed pain intensity and interference with work and sleep, region-specific disability due to MSD, self-rated general health, health-related quality of life (measured via EuroQol), productivity loss, depression, and sleep disturbance at baseline, 1, 3, 8, 12, and 52 weeks. We analyzed the repeated measures data (171-356 observations) with the generalized estimating equation approach. The intervention (part-time sick leave) and control (full-time sick leave) groups did not differ with regard to pain intensity, pain interference with work and sleep, region-specific disability, productivity loss, depression, or sleep disturbance. The intervention group reported better self-rated general health (adjusted P=0.07) and health-related quality of life (adjusted P=0.02) than the control group. In subgroup analyses, the intervention was more effective among the patients whose current problem began occurring <6 weeks before baseline and those with ≤30% productivity loss at baseline. Our findings showed that part-time sick leave did not exacerbate pain-related symptoms and functional disability, but improved self-rated general health and health-related quality of life in the early stage of work disability due to MSD.

High-Throughput Nano-Biofilm Microarray for Antifungal Drug Discovery

DTIC Science & Technology

2013-06-25

High-Throughput Nano-Biofilm Microarray for Antifungal Drug Discovery Anand Srinivasan,a, c Kai P. Leung,d Jose L. Lopez-Ribot,b, c Anand K...Ramasubramaniana, c Departments of Biomedical Engineeringa and Biologyb and South Texas Center for Emerging Infectious Diseases, c The University of Texas at San...of the opportunistic fungal pathogen Candida albicans on a microarray platform. The mi- croarray consists of 1,200 individual cultures of 30 nl of C

Detail view of the forward section, port side, of the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Detail view of the forward section, port side, of the Orbiter Discovery from an elevated platform in the Vehicle Assembly Building at NASA's Kennedy Space Center. Note the removal of the Forward Reaction Control System Module from the nose section, the ground-support window covers and the strongback attached to the payload bay door. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Closeup view of a Space Shuttle Main Engine (SSME) installed ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Close-up view of a Space Shuttle Main Engine (SSME) installed in position number one on the Orbiter Discovery. A ground-support mobile platform is in place below the engine to assist in technicians with the installation of the engine. This Photograph was taken in the Orbiter Processing Facility at the Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Validation of Biomarker Proteins Using Reverse Capture Protein Microarrays.

PubMed

Jozwik, Catherine; Eidelman, Ofer; Starr, Joshua; Pollard, Harvey B; Srivastava, Meera

2017-01-01

Genomics has revolutionized large-scale and high-throughput sequencing and has led to the discovery of thousands of new proteins. Protein chip technology is emerging as a miniaturized and highly parallel platform that is suited to rapid, simultaneous screening of large numbers of proteins and the analysis of various protein-binding activities, enzyme substrate relationships, and posttranslational modifications. Specifically, reverse capture protein microarrays provide the most appropriate platform for identifying low-abundance, disease-specific biomarker proteins in a sea of high-abundance proteins from biological fluids such as blood, serum, plasma, saliva, urine, and cerebrospinal fluid as well as tissues and cells obtained by biopsy. Samples from hundreds of patients can be spotted in serial dilutions on many replicate glass slides. Each slide can then be probed with one specific antibody to the biomarker of interest. That antibody's titer can then be determined quantitatively for each patient, allowing for the statistical assessment and validation of the diagnostic or prognostic utility of that particular antigen. As the technology matures and the availability of validated, platform-compatible antibodies increases, the platform will move further into the desirable realm of discovery science for detecting and quantitating low-abundance signaling proteins. In this chapter, we describe methods for the successful application of the reverse capture protein microarray platform for which we have made substantial contributions to the development and application of this method, particularly in the use of body fluids other than serum/plasma.

Chromosomal locus tracking with proper accounting of static and dynamic errors

PubMed Central

Backlund, Mikael P.; Joyner, Ryan; Moerner, W. E.

2015-01-01

The mean-squared displacement (MSD) and velocity autocorrelation (VAC) of tracked single particles or molecules are ubiquitous metrics for extracting parameters that describe the object’s motion, but they are both corrupted by experimental errors that hinder the quantitative extraction of underlying parameters. For the simple case of pure Brownian motion, the effects of localization error due to photon statistics (“static error”) and motion blur due to finite exposure time (“dynamic error”) on the MSD and VAC are already routinely treated. However, particles moving through complex environments such as cells, nuclei, or polymers often exhibit anomalous diffusion, for which the effects of these errors are less often sufficiently treated. We present data from tracked chromosomal loci in yeast that demonstrate the necessity of properly accounting for both static and dynamic error in the context of an anomalous diffusion that is consistent with a fractional Brownian motion (FBM). We compare these data to analytical forms of the expected values of the MSD and VAC for a general FBM in the presence of these errors. PMID:26172745

Genetic variation in heat tolerance-related traits in a population of wheat multiple synthetic derivatives

PubMed Central

Elbashir, Awad A. E.; Gorafi, Yasir S. A.; Tahir, Izzat S. A.; Elhashimi, Ashraf. M. A.; Abdalla, Modather G. A.; Tsujimoto, Hisashi

2017-01-01

In wheat (Triticum aestivum L.) high temperature (≥30°C) during grain filling leads to considerable reduction in grain yield. We studied 400 multiple synthetic derivatives (MSD) lines to examine the genetic variability of heat stress–adaptive traits and to identify new sources of heat tolerance to be used in wheat breeding programs. The experiment was arranged in an augmented randomized complete block design in four environments in Sudan. A wide range of genetic variability was found in most of the traits in all environments. For all traits examined, we found MSD lines that showed better performance than their parent ‘Norin 61’ and two adapted Sudanese cultivars. Using the heat tolerance efficiency, we identified 13 highly heat-tolerant lines and several lines with intermediate heat tolerance and good yield potential. We also identified lines with alleles that can be used to increase wheat yield potential. Our study revealed that the use of the MSD population is an efficient way to explore the genetic variation in Ae. tauschii for wheat breeding and improvement. PMID:29398942

Isolating long-wavelength fluctuation from structural relaxation in two-dimensional glass: cage-relative displacement

NASA Astrophysics Data System (ADS)

Shiba, Hayato; Keim, Peter; Kawasaki, Takeshi

2018-03-01

It has recently been revealed that long-wavelength fluctuation exists in two-dimensional (2D) glassy systems, having the same origin as that given by the Mermin-Wagner theorem for 2D crystalline solids. In this paper, we discuss how to characterise quantitatively the long-wavelength fluctuation in a molecular dynamics simulation of a lightly supercooled liquid. We employ the cage-relative mean-square displacement (MSD), defined on relative displacement to its cage, to quantitatively separate the long-wavelength fluctuation from the original MSD. For increasing system size the amplitude of acoustic long wavelength fluctuations not only increases but shifts to later times causing a crossover with structural relaxation of caging particles. We further analyse the dynamic correlation length using the cage-relative quantities. It grows as the structural relaxation becomes slower with decreasing temperature, uncovering an overestimation by the four-point correlation function due to the long-wavelength fluctuation. These findings motivate the usage of cage-relative MSD as a starting point for analysis of 2D glassy dynamics.

Design and implementation of the modified signed digit multiplication routine on a ternary optical computer.

PubMed

Xu, Qun; Wang, Xianchao; Xu, Chao

2017-06-01

Multiplication with traditional electronic computers is faced with a low calculating accuracy and a long computation time delay. To overcome these problems, the modified signed digit (MSD) multiplication routine is established based on the MSD system and the carry-free adder. Also, its parallel algorithm and optimization techniques are studied in detail. With the help of a ternary optical computer's characteristics, the structured data processor is designed especially for the multiplication routine. Several ternary optical operators are constructed to perform M transformations and summations in parallel, which has accelerated the iterative process of multiplication. In particular, the routine allocates data bits of the ternary optical processor based on digits of multiplication input, so the accuracy of the calculation results can always satisfy the users. Finally, the routine is verified by simulation experiments, and the results are in full compliance with the expectations. Compared with an electronic computer, the MSD multiplication routine is not only good at dealing with large-value data and high-precision arithmetic, but also maintains lower power consumption and fewer calculating delays.

An open source platform for multi-scale spatially distributed simulations of microbial ecosystems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Segre, Daniel

2014-08-14

The goal of this project was to develop a tool for facilitating simulation, validation and discovery of multiscale dynamical processes in microbial ecosystems. This led to the development of an open-source software platform for Computation Of Microbial Ecosystems in Time and Space (COMETS). COMETS performs spatially distributed time-dependent flux balance based simulations of microbial metabolism. Our plan involved building the software platform itself, calibrating and testing it through comparison with experimental data, and integrating simulations and experiments to address important open questions on the evolution and dynamics of cross-feeding interactions between microbial species.

Remembering Professor Benito Casu (1927-2016).

PubMed

Torri, Giangiacomo; Cassinelli, Giuseppe

2018-01-31

Heparin and related drugs have contributed in so many different ways to the drug discovery process, and have provided a platform to understand the pathophysiology of vascular and inflammatory diseases for nearly 100 years.

KENNEDY SPACE CENTER, FLA. - STS-114 Commander Eileen Collins and Mission Specialists Charles Camarda and Soichi Noguchi sit outside the crew hatch on the orbiter Discovery. Noguchi is with the Japanese Aerospace and Exploration Agency. They and other crew members are at KSC becoming familiar with Shuttle and mission equipment. The mission is Logistics Flight 1, which is scheduled to deliver supplies and equipment plus the external stowage platform to the International Space Station.

NASA Image and Video Library

2004-03-05

KENNEDY SPACE CENTER, FLA. - STS-114 Commander Eileen Collins and Mission Specialists Charles Camarda and Soichi Noguchi sit outside the crew hatch on the orbiter Discovery. Noguchi is with the Japanese Aerospace and Exploration Agency. They and other crew members are at KSC becoming familiar with Shuttle and mission equipment. The mission is Logistics Flight 1, which is scheduled to deliver supplies and equipment plus the external stowage platform to the International Space Station.

PCM-SABRE: a platform for benchmarking and comparing outcome prediction methods in precision cancer medicine.

PubMed

Eyal-Altman, Noah; Last, Mark; Rubin, Eitan

2017-01-17

Numerous publications attempt to predict cancer survival outcome from gene expression data using machine-learning methods. A direct comparison of these works is challenging for the following reasons: (1) inconsistent measures used to evaluate the performance of different models, and (2) incomplete specification of critical stages in the process of knowledge discovery. There is a need for a platform that would allow researchers to replicate previous works and to test the impact of changes in the knowledge discovery process on the accuracy of the induced models. We developed the PCM-SABRE platform, which supports the entire knowledge discovery process for cancer outcome analysis. PCM-SABRE was developed using KNIME. By using PCM-SABRE to reproduce the results of previously published works on breast cancer survival, we define a baseline for evaluating future attempts to predict cancer outcome with machine learning. We used PCM-SABRE to replicate previous work that describe predictive models of breast cancer recurrence, and tested the performance of all possible combinations of feature selection methods and data mining algorithms that was used in either of the works. We reconstructed the work of Chou et al. observing similar trends - superior performance of Probabilistic Neural Network (PNN) and logistic regression (LR) algorithms and inconclusive impact of feature pre-selection with the decision tree algorithm on subsequent analysis. PCM-SABRE is a software tool that provides an intuitive environment for rapid development of predictive models in cancer precision medicine.

Analysis and prediction of Multiple-Site Damage (MSD) fatigue crack growth

NASA Technical Reports Server (NTRS)

Dawicke, D. S.; Newman, J. C., Jr.

1992-01-01

A technique was developed to calculate the stress intensity factor for multiple interacting cracks. The analysis was verified through comparison with accepted methods of calculating stress intensity factors. The technique was incorporated into a fatigue crack growth prediction model and used to predict the fatigue crack growth life for multiple-site damage (MSD). The analysis was verified through comparison with experiments conducted on uniaxially loaded flat panels with multiple cracks. Configuration with nearly equal and unequal crack distribution were examined. The fatigue crack growth predictions agreed within 20 percent of the experimental lives for all crack configurations considered.

SSWAP: A Simple Semantic Web Architecture and Protocol for semantic web services.

PubMed

Gessler, Damian D G; Schiltz, Gary S; May, Greg D; Avraham, Shulamit; Town, Christopher D; Grant, David; Nelson, Rex T

2009-09-23

SSWAP (Simple Semantic Web Architecture and Protocol; pronounced "swap") is an architecture, protocol, and platform for using reasoning to semantically integrate heterogeneous disparate data and services on the web. SSWAP was developed as a hybrid semantic web services technology to overcome limitations found in both pure web service technologies and pure semantic web technologies. There are currently over 2400 resources published in SSWAP. Approximately two dozen are custom-written services for QTL (Quantitative Trait Loci) and mapping data for legumes and grasses (grains). The remaining are wrappers to Nucleic Acids Research Database and Web Server entries. As an architecture, SSWAP establishes how clients (users of data, services, and ontologies), providers (suppliers of data, services, and ontologies), and discovery servers (semantic search engines) interact to allow for the description, querying, discovery, invocation, and response of semantic web services. As a protocol, SSWAP provides the vocabulary and semantics to allow clients, providers, and discovery servers to engage in semantic web services. The protocol is based on the W3C-sanctioned first-order description logic language OWL DL. As an open source platform, a discovery server running at http://sswap.info (as in to "swap info") uses the description logic reasoner Pellet to integrate semantic resources. The platform hosts an interactive guide to the protocol at http://sswap.info/protocol.jsp, developer tools at http://sswap.info/developer.jsp, and a portal to third-party ontologies at http://sswapmeet.sswap.info (a "swap meet"). SSWAP addresses the three basic requirements of a semantic web services architecture (i.e., a common syntax, shared semantic, and semantic discovery) while addressing three technology limitations common in distributed service systems: i.e., i) the fatal mutability of traditional interfaces, ii) the rigidity and fragility of static subsumption hierarchies, and iii) the confounding of content, structure, and presentation. SSWAP is novel by establishing the concept of a canonical yet mutable OWL DL graph that allows data and service providers to describe their resources, to allow discovery servers to offer semantically rich search engines, to allow clients to discover and invoke those resources, and to allow providers to respond with semantically tagged data. SSWAP allows for a mix-and-match of terms from both new and legacy third-party ontologies in these graphs.

KSC01padig075

NASA Image and Video Library

2001-02-12

KENNEDY SPACE CENTER, Fla. -- As Space Shuttle Discovery, on its Mobile Launcher Platform, nears Launch Pad 39B, fog rolls over the top of the external tank and solid rocket boosters. Discovery will be flying on mission STS-102 to the International Space Station. Its payload is the Multi-Purpose Logistics Module Leonardo, a “moving van,” to carry laboratory racks filled with equipment, experiments and supplies to and from the Space Station aboard the Space Shuttle. The flight will also carry the Expedition Two crew up to the Space Station, replacing Expedition One, who will return to Earth on Discovery. Launch is scheduled for March 8 at 6:45 a.m. EST

KSC-05PD-1077

NASA Technical Reports Server (NTRS)

2005-01-01

KENNEDY SPACE CENTER, FLA. At Launch Complex 39B, technicians construct a platform in Space Shuttle Discovery's payload bay to support an upcoming borescope inspection of the retract link assembly on the orbiter's main landing gear door. The inspection is a precautionary measure after a small crack was found in a retract link assembly on the right-hand main landing gear on orbiter Atlantis. An initial review of the closeout photos of the link assembly on Discovery did not reveal any cracks. Discovery is scheduled to return the Space Shuttle fleet to operational status on mission STS-114. This additional work does not impact the launch planning window of July 13-31.

Accelerating target discovery using pre-competitive open science-patients need faster innovation more than anyone else.

PubMed

Low, Eric; Bountra, Chas; Lee, Wen Hwa

2016-01-01

We are experiencing a new era enabled by unencumbered access to high quality data through the emergence of open science initiatives in the historically challenging area of early stage drug discovery. At the same time, many patient-centric organisations are taking matters into their own hands by participating in, enabling and funding research. Here we present the rationale behind the innovative partnership between the Structural Genomics Consortium (SGC)-an open, pre-competitive pre-clinical research consortium and the research-focused patient organisation Myeloma UK to create a new, comprehensive platform to accelerate the discovery and development of new treatments for multiple myeloma.

KSC-05PD-1080

NASA Technical Reports Server (NTRS)

2005-01-01

KENNEDY SPACE CENTER, FLA. At Launch Complex 39B, technicians construct a platform in Space Shuttle Discovery's payload bay to support an upcoming borescope inspection of the retract link assembly on the orbiter's main landing gear door. The inspection is a precautionary measure after a small crack was found in a retract link assembly on the right-hand main landing gear on orbiter Atlantis. An initial review of the closeout photos of the link assembly on Discovery did not reveal any cracks. Discovery is scheduled to return the Space Shuttle fleet to operational status on mission STS-114. This additional work does not impact the launch planning window of July 13-31.

KSC-05PD-1079

NASA Technical Reports Server (NTRS)

2005-01-01

KENNEDY SPACE CENTER, FLA. At Launch Complex 39B, technicians construct a platform in Space Shuttle Discovery's payload bay to support an upcoming borescope inspection of the retract link assembly on the orbiter's main landing gear door. The inspection is a precautionary measure after a small crack was found in a retract link assembly on the right-hand main landing gear on orbiter Atlantis. An initial review of the closeout photos of the link assembly on Discovery did not reveal any cracks. Discovery is scheduled to return the Space Shuttle fleet to operational status on mission STS-114. This additional work does not impact the launch planning window of July 13-31.

Closeup view of the reflective insulation protecting the Crew Compartment ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Close-up view of the reflective insulation protecting the Crew Compartment bulkhead, orbiter structure and landing gear housing in the void created by the removal of the Forward Reaction Control System Module from the forward section of the Orbiter Discovery. This image was taken from the service platform in the Orbiter Processing Facility at Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Patient-derived tumour xenografts for breast cancer drug discovery.

PubMed

Cassidy, John W; Batra, Ankita S; Greenwood, Wendy; Bruna, Alejandra

2016-12-01

Despite remarkable advances in our understanding of the drivers of human malignancies, new targeted therapies often fail to show sufficient efficacy in clinical trials. Indeed, the cost of bringing a new agent to market has risen substantially in the last several decades, in part fuelled by extensive reliance on preclinical models that fail to accurately reflect tumour heterogeneity. To halt unsustainable rates of attrition in the drug discovery process, we must develop a new generation of preclinical models capable of reflecting the heterogeneity of varying degrees of complexity found in human cancers. Patient-derived tumour xenograft (PDTX) models prevail as arguably the most powerful in this regard because they capture cancer's heterogeneous nature. Herein, we review current breast cancer models and their use in the drug discovery process, before discussing best practices for developing a highly annotated cohort of PDTX models. We describe the importance of extensive multidimensional molecular and functional characterisation of models and combination drug-drug screens to identify complex biomarkers of drug resistance and response. We reflect on our own experiences and propose the use of a cost-effective intermediate pharmacogenomic platform (the PDTX-PDTC platform) for breast cancer drug and biomarker discovery. We discuss the limitations and unanswered questions of PDTX models; yet, still strongly envision that their use in basic and translational research will dramatically change our understanding of breast cancer biology and how to more effectively treat it. © 2016 The authors.

Sea Level Rise Data Discovery

NASA Astrophysics Data System (ADS)

Quach, N.; Huang, T.; Boening, C.; Gill, K. M.

2016-12-01

Research related to sea level rise crosses multiple disciplines from sea ice to land hydrology. The NASA Sea Level Change Portal (SLCP) is a one-stop source for current sea level change information and data, including interactive tools for accessing and viewing regional data, a virtual dashboard of sea level indicators, and ongoing updates through a suite of editorial products that include content articles, graphics, videos, and animations. The architecture behind the SLCP makes it possible to integrate web content and data relevant to sea level change that are archived across various data centers as well as new data generated by sea level change principal investigators. The Extensible Data Gateway Environment (EDGE) is incorporated into the SLCP architecture to provide a unified platform for web content and science data discovery. EDGE is a data integration platform designed to facilitate high-performance geospatial data discovery and access with the ability to support multi-metadata standard specifications. EDGE has the capability to retrieve data from one or more sources and package the resulting sets into a single response to the requestor. With this unified endpoint, the Data Analysis Tool that is available on the SLCP can retrieve dataset and granule level metadata as well as perform geospatial search on the data. This talk focuses on the architecture that makes it possible to seamlessly integrate and enable discovery of disparate data relevant to sea level rise.

Towards microfluidic technology-based MALDI-MS platforms for drug discovery: a review.

PubMed

Winkle, Richard F; Nagy, Judit M; Cass, Anthony Eg; Sharma, Sanjiv

2008-11-01

Microfluidic methods have found applications in various disciplines. It has been predicted that the microfluidic technology would be useful in performing routine steps in drug discovery ranging from target identification to lead optimisation in which the number of compounds evaluated in this regard determines the success of combinatorial screening. The sheer size of the parameter space that can be explored often poses an enormous challenge. We set out to find how close we are towards the use of integrated matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) microfluidic systems for drug discovery. In this article we review the latest applications of microfluidic technology in the area of MALDI-MS and drug discovery. Our literature survey revealed microfluidic technologies-based approaches for various stages of drug discovery; however, they are in still in developmental stages. Furthermore, we speculate on how these technologies could be used in the future.

KSC-00pp1296

NASA Image and Video Library

2000-09-12

KENNEDY SPACE CENTER, Fla. -- The morning sun spotlights Launch Pad 39A and Space Shuttle Discovery atop the Mobile Launcher Platform. To its left is the Rotating Service Structure in its open position, at the top of the ramp that the Shuttle must negotiate on the crawler-transporter. Above Discovery looms the 80-foot fiberglass lightning mast. At the far left is the Vehicle Assembly Building, where a Space Shuttle begins its voyage to the pad. Discovery is scheduled to launch on mission STS-92 Oct. 5 at 9:30 p.m. EDT. Making the 100th Space Shuttle mission launched from Kennedy Space Center, Discovery will carry two pieces of hardware for the International Space Station, the Z1 truss, which is the cornerstone truss of the Station, and the third Pressurized Mating Adapter. Discovery also will be making its 28th flight into space, more than any of the other orbiters to date

KSC00pp1296

NASA Image and Video Library

2000-09-12

KENNEDY SPACE CENTER, Fla. -- The morning sun spotlights Launch Pad 39A and Space Shuttle Discovery atop the Mobile Launcher Platform. To its left is the Rotating Service Structure in its open position, at the top of the ramp that the Shuttle must negotiate on the crawler-transporter. Above Discovery looms the 80-foot fiberglass lightning mast. At the far left is the Vehicle Assembly Building, where a Space Shuttle begins its voyage to the pad. Discovery is scheduled to launch on mission STS-92 Oct. 5 at 9:30 p.m. EDT. Making the 100th Space Shuttle mission launched from Kennedy Space Center, Discovery will carry two pieces of hardware for the International Space Station, the Z1 truss, which is the cornerstone truss of the Station, and the third Pressurized Mating Adapter. Discovery also will be making its 28th flight into space, more than any of the other orbiters to date

KSC-05PD-1148

NASA Technical Reports Server (NTRS)

2005-01-01

KENNEDY SPACE CENTER, FLA. Dwarfing the accompanying vehicles, Space Shuttle Discovery, resting on the Mobile Launcher Platform atop the Crawler/Transporter, heads along the crawlerway to the Vehicle Assembly Building (VAB). Discovery is rolling back from Launch Pad 39B (in the background). Once inside the VAB, Discovery will be demated from its External Tank and lifted into the transfer aisle. On or about June 7, Discovery will be lifted and attached to its new tank and Solid Rocket Boosters, which are already in the VAB. Only the 15th rollback in Space Shuttle Program history, the 4.2-mile journey allows additional modifications to be made to the External Tank prior to a safe Return to Flight. Discovery is expected to be rolled back to the launch pad in mid-June for Return to Flight mission STS-114. The launch window extends from July 13 to July 31.

Novel algorithm and MATLAB-based program for automated power law analysis of single particle, time-dependent mean-square displacement

NASA Astrophysics Data System (ADS)

Umansky, Moti; Weihs, Daphne

2012-08-01

In many physical and biophysical studies, single-particle tracking is utilized to reveal interactions, diffusion coefficients, active modes of driving motion, dynamic local structure, micromechanics, and microrheology. The basic analysis applied to those data is to determine the time-dependent mean-square displacement (MSD) of particle trajectories and perform time- and ensemble-averaging of similar motions. The motion of particles typically exhibits time-dependent power-law scaling, and only trajectories with qualitatively and quantitatively comparable MSD should be ensembled. Ensemble averaging trajectories that arise from different mechanisms, e.g., actively driven and diffusive, is incorrect and can result inaccurate correlations between structure, mechanics, and activity. We have developed an algorithm to automatically and accurately determine power-law scaling of experimentally measured single-particle MSD. Trajectories can then categorized and grouped according to user defined cutoffs of time, amplitudes, scaling exponent values, or combinations. Power-law fits are then provided for each trajectory alongside categorized groups of trajectories, histograms of power laws, and the ensemble-averaged MSD of each group. The codes are designed to be easily incorporated into existing user codes. We expect that this algorithm and program will be invaluable to anyone performing single-particle tracking, be it in physical or biophysical systems. Catalogue identifier: AEMD_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEMD_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 25 892 No. of bytes in distributed program, including test data, etc.: 5 572 780 Distribution format: tar.gz Programming language: MATLAB (MathWorks Inc.) version 7.11 (2010b) or higher, program should also be backwards compatible. Symbolic Math Toolboxes (5.5) is required. The Curve Fitting Toolbox (3.0) is recommended. Computer: Tested on Windows only, yet should work on any computer running MATLAB. In Windows 7, should be used as administrator, if the user is not the administrator the program may not be able to save outputs and temporary outputs to all locations. Operating system: Any supporting MATLAB (MathWorks Inc.) v7.11 / 2010b or higher. Supplementary material: Sample output files (approx. 30 MBytes) are available. Classification: 12 External routines: Several MATLAB subfunctions (m-files), freely available on the web, were used as part of and included in, this code: count, NaN suite, parseArgs, roundsd, subaxis, wcov, wmean, and the executable pdfTK.exe. Nature of problem: In many physical and biophysical areas employing single-particle tracking, having the time-dependent power-laws governing the time-averaged meansquare displacement (MSD) of a single particle is crucial. Those power laws determine the mode-of-motion and hint at the underlying mechanisms driving motion. Accurate determination of the power laws that describe each trajectory will allow categorization into groups for further analysis of single trajectories or ensemble analysis, e.g. ensemble and time-averaged MSD. Solution method: The algorithm in the provided program automatically analyzes and fits time-dependent power laws to single particle trajectories, then group particles according to user defined cutoffs. It accepts time-dependent trajectories of several particles, each trajectory is run through the program, its time-averaged MSD is calculated, and power laws are determined in regions where the MSD is linear on a log-log scale. Our algorithm searches for high-curvature points in experimental data, here time-dependent MSD. Those serve as anchor points for determining the ranges of the power-law fits. Power-law scaling is then accurately determined and error estimations of the parameters and quality of fit are provided. After all single trajectory time-averaged MSDs are fit, we obtain cutoffs from the user to categorize and segment the power laws into groups; cutoff are either in exponents of the power laws, time of appearance of the fits, or both together. The trajectories are sorted according to the cutoffs and the time- and ensemble-averaged MSD of each group is provided, with histograms of the distributions of the exponents in each group. The program then allows the user to generate new trajectory files with trajectories segmented according to the determined groups, for any further required analysis. Additional comments: README file giving the names and a brief description of all the files that make-up the package and clear instructions on the installation and execution of the program is included in the distribution package. Running time: On an i5 Windows 7 machine with 4 GB RAM the automated parts of the run (excluding data loading and user input) take less than 45 minutes to analyze and save all stages for an 844 trajectory file, including optional PDF save. Trajectory length did not affect run time (tested up to 3600 frames/trajectory), which was on average 3.2±0.4 seconds per trajectory.

Mortality Surveillance for Infectious Diseases in the U.S. Department of Defense (1998-2013).

PubMed

Potter, Robert N; Tremaine, Ladd A; Gaydos, Joel C

2017-03-01

The Mortality Surveillance Division (MSD) of the U.S. Armed Forces Medical Examiner System was established in 1998 to improve surveillance for all military deaths although emphasizing deaths from infectious diseases. Establishment of the MSD was part of the 1997 Department of Defense initiative to improve surveillance and response for emerging infectious diseases. Before 1998, mortality surveillance was limited to compiling information from death certificates, a system that provided limited useful information and lacked the timeliness needed to take meaningful action to address emerging infectious disease threats. The MSD was tasked to quickly identify all infectious disease deaths and the infecting agents. The system developed by the MSD staff identified deaths in near real-time and immediately notified military Public Health authorities of situations that warranted an investigation. Autopsy, medical, and investigative reports were collected. Testing specimens for agent identification was encouraged. The data and information collected were archived in the MSD-developed Medical Mortality Registry (MMR), a database that included all active duty Service Member deaths and contained manner and cause of death with medical, demographic, circumstantial, and diagnostic information. The MMR was the only comprehensive, autopsy-based source for mortality information on active duty military deaths. During 1998-2013, 217 (1.3%) infectious disease deaths were identified among 16,192 noncombat deaths. Of the 217 deaths, 29.5% were classified as respiratory, 18.0% cardiac, 15.2% blood borne, 12.9% nervous system, and 12.4% sepsis. A pathogen was identified for 64.5%. Agents of military interest identified included Neisseria meningitidis, influenza viruses, adenoviruses, and malaria. Neisseria meningitidis was identified in 10 fatal cases; grouping of the agent was done for eight cases. Four were group B, two were C, and two were Y. All eight had been immunized with a quadrivalent meningococcal vaccine. The most commonly detected respiratory agent was influenza virus (nine deaths), three of which were the 2009 pandemic H1N1 influenza virus. Adenoviruses were identified as the infectious agents in a total of nine deaths. Two deaths resulted from Plasmodium falciparum malaria infections acquired in Africa during military deployments. An important but unexplained finding was that Black Service Members made up only16.3% of all military personnel but accounted for 28.6% of all infectious disease deaths. The time lag between death and notification of the MSD at the start of this surveillance program was 24 to 48 hours. The lag at the end of the reported surveillance period was 8 to 24 hours. The MSD surveillance system identified an agent in 140 of 217 (64.5%) uniformed deaths. In a similar program by the Centers for Disease Control and Prevention, in 122 cases with specimens, an agent could be identified in 34 (28%). MMR data and information provided strong support for re-establishing the military recruit adenovirus vaccination program, which ceased in 1999 and was finally re-established in 2011. MMR data and information also assisted in monitoring the military meningococcal vaccine program, helped to describe the virulence of circulating influenza viruses, and identified areas where deadly malaria infections were not being prevented. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Collaborative drug discovery for More Medicines for Tuberculosis (MM4TB)

PubMed Central

Ekins, Sean; Spektor, Anna Coulon; Clark, Alex M.; Dole, Krishna; Bunin, Barry A.

2016-01-01

Neglected disease drug discovery is generally poorly funded compared with major diseases and hence there is an increasing focus on collaboration and precompetitive efforts such as public–private partnerships (PPPs). The More Medicines for Tuberculosis (MM4TB) project is one such collaboration funded by the EU with the goal of discovering new drugs for tuberculosis. Collaborative Drug Discovery has provided a commercial web-based platform called CDD Vault which is a hosted collaborative solution for securely sharing diverse chemistry and biology data. Using CDD Vault alongside other commercial and free cheminformatics tools has enabled support of this and other large collaborative projects, aiding drug discovery efforts and fostering collaboration. We will describe CDD's efforts in assisting with the MM4TB project. PMID:27884746

Comparison of three gas chromatography methods for the determination of slip agents in polyethylene films.

PubMed

Garrido-López, Alvaro; Esquiu, Vanesa; Tena, María Teresa

2007-05-25

Polymers require the use of some slip agents, such as oleamide and erucamide, in order to reduce their friction coefficient and to make films easier to handle. In this communication, three analytical methods consisting in pressurized liquid extraction (PLE) and gas chromatography (GC) are used to determine oleamide and erucamide in polyethylene films. The sample was extracted with pure isopropanol (two times) at 105 degrees C for 16 min. Then, the liquid extract containing oleamide and erucamide was analyzed by GC and three different detection systems: flame ionization detector (FID), thermoionic selective detector (TSD) and ion-trap mass spectrometry detector (MSD). Oleamide and erucamide were separated using a 30 m x 0.25 mm (I.D.) 5% phenyl-95% dimethyl-polysiloxane capillary column in 12 min. The chromatographic methods were characterized and compared in terms of repeatability, linearity and sensitivity. The GC-FID and GC-TSD methods were linear up to about 60 microg ml(-1), whereas the linear range for the GC-MSD method was shorter, from 20.5 to 42 microg ml(-1). LODs identified with GC-MSD were two times higher than those identified with the other two methods. Repeatability values (expressed as relative standard deviation) of less than 2.5% were found for FID and TSD but they were above 10% for MSD. Finally, each method was applied to determine the content of erucamide and oleamide in several polyethylene films and the results obtained were compared with those obtained from the nitrogen content measured by pyrolysis and gas-phase chemiluminescence. No significant differences were observed between the results of the methods.

Haploidentical transplantation compared with matched sibling and unrelated donor transplantation for adults with standard-risk acute lymphoblastic leukaemia in first complete remission.

PubMed

Han, Li-Jie; Wang, Yu; Fan, Zhi-Ping; Huang, Fen; Zhou, Jian; Fu, Yue-Wen; Qu, Hong; Xuan, Li; Xu, Na; Ye, Jie-Yu; Bian, Zhi-Lei; Song, Yong-Ping; Huang, Xiao-Jun; Liu, Qi-Fa

2017-10-01

We retrospectively investigated outcomes of haploidentical donor (HID) transplant for adults with standard-risk acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) compared with human leucocyte antigen (HLA)-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants. A total of 348 adult patients were enrolled, including 127 HID, 144 MSD and 77 MUD recipients. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 39·5%, 24·0% and 40·3% for HID, MSD and MUD, respectively (P = 0·020). However, there was no difference in grade III-IV aGVHD (11·4%, 7·7%, 13·5%, respectively, P = 0·468). The 5-year cumulative transplant-related mortality was 16·4%, 11·6% and 19·6% (P = 0·162), the 5-year relapse rate post-transplantation was 14·8%, 21·1% and 16·7% (P = 0·231), the 5-year overall survival was 70·1%, 73·7% and 69·8% (P = 0·525), and the 5-year disease-free survival was 68·7%, 67·3% and 63·7%, respectively (P = 0·606). Furthermore, the 3-year GVHD-free, relapse-free survival was not different (50·8%, 54·9% and 52·2%, respectively, P = 0·847). Our results indicate that the outcomes of HID transplants are equivalent to those of MSD and MUD, and that HID transplantation is a valid alternative for standard-risk adults with ALL in CR1 who lack matched donors. © 2017 John Wiley & Sons Ltd.

Mediterranean-style diet reduces metabolic syndrome components in obese children and adolescents with obesity

PubMed Central

2014-01-01

Background The beneficial effects of the Mediterranean diet have been amply proven in adults with cardiovascular risk factors. The effects of this diet have not been extensively assessed in pediatric populations with obesity, insulin resistance (IR) and metabolic syndrome (MetS). The aim of this study was to assess the efficacy of the Mediterranean style diet (MSD) to decrease cardiovascular risk factors in children and adolescents with obesity. Methods Participants were randomly assigned to a MSD rich in polyunsaturated fatty acids, fiber, flavonoids and antioxidants (60% of energy from carbohydrate, 25% from fat, and 15% from protein, (n = 24); or a standard diet (55% of carbohydrate, 30% from fat and 15% from protein, (n = 25), the caloric ingest was individualized. At baseline and 16-week of intervention, the glucose, triglycerides (TG), total cholesterol (TC), HDL-C, LDL-C were measured as well as the body composition and anthropometric data. The diet compliance was determined by the 24-hour recalls. Paired Student’s t and Macnemar’s test were used to compare effects in biochemical, body composition, anthropometric, and dietary variables. Results The MSD group had a significantly decrease in BMI, lean mass, fat mass, glucose, TC, TG, HDL-C and LDL-C. (p < 0.05); the diet compliance increased consumption of omega 9 fatty acids, zinc, vitamin E, selenium, and decreased consumption of saturated fatty acids (p < 0.05). The standard diet group decrease in glucose levels and frequency of glucose >100 mg/dL (p < 0.05). Conclusion The MSD improves the BMI, glucose and lipid profile in children and adolescents with obesity and any MetS component. PMID:24997634

A promising biotechnical approach to pest management of Diabrotica virgifera virgifera in Illinois maize fields under kairomonal shielding with the new MSD technique.

PubMed

Hummel, H E; Shaw, J T; Hein, D F

2005-01-01

Environmentally compatible and sustainable plant protection requires novel approaches to pest management characterized by minimal emphasis on toxicants. Classical toxicants traditionally dominated economic entomology for half a century. But worldwide problems with environmental pollution and with increasing resistance levels in all major pesticide classes and in many key insect species including Diabrotica virgifera virgifera (D.v.v.) strongly advocate a rethinking and a change in management paradigms used. Soft, minimally invasive, biological, biotechnical and cultural approaches should replace hard pesticides which are in favor up to now. Fortunately, pheromones, kairomones, plant attractants, better traps, new plant varieties and cultural methods like crop rotation, in short more sophisticated methods are now available as pressure for finding and exploring novel strategies increases. Facing this situation, a new biotechnical approach of population reduction of D.v.v., called "MSD" technique, is introduced. MSD is characterized as an approach combining mass trapping, shielding and deflecting of adult insects along an invisible odor barrier of synthetic kairomone which diminishes the flux of insects across a high capacity trap line baited with kairomone, thus reducing both the population fluctuation and number and its reproductive success within the shielded area. In the case of D.v.v. in Zea mays fields, effects realized by the MSD technique have been measured simultaneously by a number of independent criteria during the summers of 2003 and 2004 at 2 different locations in Illinois maize fields of up to one half hectare size. Results observed are statistically significant and cannot be explained by mass trapping alone. There is also an additional shielding and deflection, in short "diversion" effect whose basic sensory and behavioral mechanisms call for future exploration.

Determination of patulin in fruit juices using HPLC-DAD and GC-MSD techniques.

PubMed

Moukas, Athanasios; Panagiotopoulou, Vasiliki; Markaki, Panagiota

2008-08-15

A high performance liquid chromatography with a diode-array detector (HPLC-DAD) and a gas chromatography with a mass spectrometer (GC-MSD) are described for the determination of patulin (PAT) in apple juice. The limits of detection (DL) and quantification (QL) for the HPLC-DAD and GC-MSD method were found to be (DL=0.23μgkg(-1) QL=1.2μgkg(-1)) and (DL=5.8μgkg(-1) and QL=13.8μgkg(-1)), respectively. The recovery factors for HPLC-DAD and GC-MSD were found to be 99.5% (RSD%=0.73) and 41% (RSD%=10.03), respectively. The HPLC-DAD method was used to determine the occurrence of PAT in 90 samples of fruit juices. Results revealed the presence of PAT in 100% of the samples examined. The mean values of PAT in concentrated fruit juices and in the commercial fruit juices collected from the Greek market were found to be 10.54μg PAT kg(-1) and 5.57μg PAT kg(-1) juice, respectively. The most contaminated samples were four concentrated juices ranging from 18.10μg PAT kg(-1) to 36.8μg PAT kg(-1) juice. The daily exposure to patulin for the consumers of all ages in Greece, is ranging from 0.008μg PAT kg(-1) bw to 0.1μg PAT kg(-1) bw if the daily intake of fruit juices is from 0.1 to 0.5kg. With the exception to the most contaminated sample, the daily exposure due to the samples examined, is below the provisional maximum tolerable daily intake for PAT (0.4μg PAT kg(-1) bw). Copyright © 2008 Elsevier Ltd. All rights reserved.

Integration of GC-MSD and ER-Calux® assay into a single protocol for determining steroid estrogens in environmental samples.

PubMed

Avberšek, Miha; Žegura, Bojana; Filipič, Metka; Heath, Ester

2011-11-01

There are many published studies that use either chemical or biological methods to investigate steroid estrogens in the aquatic environment, but rarer are those that combine both. In this study, gas chromatography with mass selective detection (GC-MSD) and the ER-Calux(®) estrogenicity assay were integrated into a single protocol for simultaneous determination of natural (estrone--E1, 17β-estradiol--E2, estriol--E3) and synthetic (17α-ethinylestradiol--EE2) steroid estrogens concentrations and the total estrogenic potential of environmental samples. For integration purposes, several solvents were investigated and the commonly used dimethyl sulphoxide (DMSO) in the ER-Calux(®) assay was replaced by ethyl acetate, which is more compatible with gas chromatography and enables the same sample to be analysed by both GC-MSD and the ER-Calux(®) assay. The integrated protocol was initially tested using a standard mixture of estrogens. The results for pure standards showed that the estrogenicity calculated on the basis of GC-MSD and the ER-Calux(®) assay exhibited good correlation (r(2)=0.96; α=0.94). The result remained the same when spiked waste water extracts were tested (r(2)=0.92, α=1.02). When applied to real waste water influent and effluent samples the results proved (r(2)=0.93; α=0.99) the applicability of the protocol. The main advantages of this newly developed protocol are simple sample handling for both methods, and reduced material consumption and labour. In addition, it can be applied as either a complete or sequential analysis where the ER-Calux(®) assay is used as a pre-screening method prior to the chemical analysis. Copyright © 2011 Elsevier B.V. All rights reserved.

Mediterranean-style diet reduces metabolic syndrome components in obese children and adolescents with obesity.

PubMed

Velázquez-López, Lubia; Santiago-Díaz, Gerardo; Nava-Hernández, Julia; Muñoz-Torres, Abril V; Medina-Bravo, Patricia; Torres-Tamayo, Margarita

2014-07-05

The beneficial effects of the Mediterranean diet have been amply proven in adults with cardiovascular risk factors. The effects of this diet have not been extensively assessed in pediatric populations with obesity, insulin resistance (IR) and metabolic syndrome (MetS). The aim of this study was to assess the efficacy of the Mediterranean style diet (MSD) to decrease cardiovascular risk factors in children and adolescents with obesity. Participants were randomly assigned to a MSD rich in polyunsaturated fatty acids, fiber, flavonoids and antioxidants (60% of energy from carbohydrate, 25% from fat, and 15% from protein, (n = 24); or a standard diet (55% of carbohydrate, 30% from fat and 15% from protein, (n = 25), the caloric ingest was individualized. At baseline and 16-week of intervention, the glucose, triglycerides (TG), total cholesterol (TC), HDL-C, LDL-C were measured as well as the body composition and anthropometric data. The diet compliance was determined by the 24-hour recalls.Paired Student's t and Macnemar's test were used to compare effects in biochemical, body composition, anthropometric, and dietary variables. The MSD group had a significantly decrease in BMI, lean mass, fat mass, glucose, TC, TG, HDL-C and LDL-C. (p < 0.05); the diet compliance increased consumption of omega 9 fatty acids, zinc, vitamin E, selenium, and decreased consumption of saturated fatty acids (p < 0.05). The standard diet group decrease in glucose levels and frequency of glucose >100 mg/dL (p < 0.05). The MSD improves the BMI, glucose and lipid profile in children and adolescents with obesity and any MetS component.

The Global Enteric Multicenter Study (GEMS) of Diarrheal Disease in Infants and Young Children in Developing Countries: Epidemiologic and Clinical Methods of the Case/Control Study

PubMed Central

Kotloff, Karen L.; Blackwelder, William C.; Nasrin, Dilruba; Nataro, James P.; Farag, Tamer H.; van Eijk, Annemieke; Adegbola, Richard A.; Alonso, Pedro L.; Breiman, Robert F.; Golam Faruque, Abu Syed; Saha, Debasish; Sow, Samba O.; Sur, Dipika; Zaidi, Anita K. M.; Biswas, Kousick; Panchalingam, Sandra; Clemens, John D.; Cohen, Dani; Glass, Roger I.; Mintz, Eric D.; Sommerfelt, Halvor; Levine, Myron M.

2012-01-01

Background. Diarrhea is a leading cause of illness and death among children aged <5 years in developing countries. This paper describes the clinical and epidemiological methods used to conduct the Global Enteric Multicenter Study (GEMS), a 3-year, prospective, age-stratified, case/control study to estimate the population-based burden, microbiologic etiology, and adverse clinical consequences of acute moderate-to-severe diarrhea (MSD) among a censused population of children aged 0–59 months seeking care at health centers in sub-Saharan Africa and South Asia. Methods. GEMS was conducted at 7 field sites, each serving a population whose demography and healthcare utilization practices for childhood diarrhea were documented. We aimed to enroll 220 MSD cases per year from selected health centers serving each site in each of 3 age strata (0–11, 12–23, and 24–59 months), along with 1–3 matched community controls. Cases and controls supplied clinical, epidemiologic, and anthropometric data at enrollment and again approximately 60 days later, and provided enrollment stool specimens for identification and characterization of potential diarrheal pathogens. Verbal autopsy was performed if a child died. Analytic strategies will calculate the fraction of MSD attributable to each pathogen and the incidence, financial costs, nutritional consequences, and case fatality overall and by pathogen. Conclusions. When completed, GEMS will provide estimates of the incidence, etiology, and outcomes of MSD among infants and young children in sub-Saharan Africa and South Asia. This information can guide development and implementation of public health interventions to diminish morbidity and mortality from diarrheal diseases. PMID:23169936

Ureteral stenting can be a negative predictor for successful outcome following shock wave lithotripsy in patients with ureteral stones.

PubMed

Kang, Dong Hyuk; Cho, Kang Su; Ham, Won Sik; Chung, Doo Yong; Kwon, Jong Kyou; Choi, Young Deuk; Lee, Joo Yong

2016-11-01

To evaluate ureteral stenting as a negative predictive factor influencing ureteral stone clearance and to estimate the probability of one-session success in shock wave lithotripsy (SWL) patients with a ureteral stone. We retrospectively reviewed the medical records of 1,651 patients who underwent their first SWL. Among these patients, 680 had a ureteral stone measuring 4-20 mm and were thus eligible for our study. The 57 patients who underwent ureteral stenting during SWL were identified. Maximal stone length (MSL), mean stone density (MSD), skin-to-stone distance (SSD), and stone heterogeneity index (SHI) were determined by pre-SWL noncontrast computed tomography. After propensity score matching, 399 patients were extracted from the total patient cohort. There were no significant differences between stenting and stentless groups after matching, except for a higher one-session success rate in the stentless group (78.6% vs. 49.1%, p=0.026). In multivariate analysis, shorter MSL, lower MSD, higher SHI, and absence of a stent were positive predictors for one-session success in patients who underwent SWL. Using cutoff values of MSL and MSD obtained from receiver operator curve analysis, in patients with a lower MSD (≤784 HU), the success rate was lower in those with a stent (61.1%) than in those without (83.5%) (p=0.001). However, in patients with a higher MSL (>10 mm), the success rate was lower in those with a stent (23.6%) than in those without (52.2%) (p=0.002). Ureteral stenting during SWL was a negative predictor of one-session success in patients with a ureteral stone.

Diffusing-wave spectroscopy in an inhomogeneous object: Local viscoelastic spectra from ultrasound-assisted measurement of correlation decay arising from the ultrasound focal volume

NASA Astrophysics Data System (ADS)

Chandran, R. Sriram; Sarkar, Saikat; Kanhirodan, Rajan; Roy, Debasish; Vasu, Ram Mohan

2014-07-01

We demonstrate diffusing-wave spectroscopy (DWS) in a localized region of a viscoelastically inhomogeneous object by measurement of the intensity autocorrelation [g2(τ)] that captures only the decay introduced by the temperature-induced Brownian motion in the region. The region is roughly specified by the focal volume of an ultrasound transducer which introduces region specific mechanical vibration owing to insonification. Essential characteristics of the localized non-Markovian dynamics are contained in the decay of the modulation depth [M(τ)], introduced by the ultrasound forcing in the focal volume selected, on g2(τ). The modulation depth M (τi) at any delay time τi can be measured by short-time Fourier transform of g2(τ) and measurement of the magnitude of the spectrum at the ultrasound drive frequency. By following the established theoretical framework of DWS, we are able to connect the decay in M (τ) to the mean-squared displacement (MSD) of scattering centers and the MSD to G*(ω), the complex viscoelastic spectrum. A two-region composite polyvinyl alcohol phantom with different viscoelastic properties is selected for demonstrating local DWS-based recovery of G*(ω) corresponding to these regions from the measured region specific M (τi)vsτi. The ultrasound-assisted measurement of MSD is verified by simulating, using a generalized Langevin equation (GLE), the dynamics of the particles in the region selected as well as by the usual DWS experiment without the ultrasound. It is shown that whereas the MSD obtained by solving the GLE without the ultrasound forcing agreed with its experimental counterpart covering small and large values of τ, the match was good only in the initial transients in regard to experimental measurements with ultrasound.

Statistics of actin-propelled trajectories in noisy environments

NASA Astrophysics Data System (ADS)

Wen, Fu-Lai; Chen, Hsuan-Yi; Leung, Kwan-tai

2016-06-01

Actin polymerization is ubiquitously utilized to power the locomotion of eukaryotic cells and pathogenic bacteria in living systems. Inevitably, actin polymerization and depolymerization proceed in a fluctuating environment that renders the locomotion stochastic. Previously, we have introduced a deterministic model that manages to reproduce actin-propelled trajectories in experiments, but not to address fluctuations around them. To remedy this, here we supplement the deterministic model with noise terms. It enables us to compute the effects of fluctuating actin density and forces on the trajectories. Specifically, the mean-squared displacement (MSD) of the trajectories is computed and found to show a super-ballistic scaling with an exponent 3 in the early stage, followed by a crossover to a normal, diffusive scaling of exponent 1 in the late stage. For open-end trajectories such as straights and S-shaped curves, the time of crossover matches the decay time of orientational order of the velocities along trajectories, suggesting that it is the spreading of velocities that leads to the crossover. We show that the super-ballistic scaling of MSD arises from the initial, linearly increasing correlation of velocities, before time translational symmetry is established. When the spreading of velocities reaches a steady state in the long-time limit, short-range correlation then yields a diffusive scaling in MSD. In contrast, close-loop trajectories like circles exhibit localized periodic motion, which inhibits spreading. The initial super-ballistic scaling of MSD arises from velocity correlation that both linearly increases and oscillates in time. Finally, we find that the above statistical features of the trajectories transcend the nature of noises, be it additive or multiplicative, and generalize to other self-propelled systems that are not necessarily actin based.

Calculating the number of shock waves, expulsion time, and optimum stone parameters based on noncontrast computerized tomography characteristics.

PubMed

Foda, Khaled; Abdeldaeim, Hussein; Youssif, Mohamed; Assem, Akram

2013-11-01

To define the parameters that accompanied a successful extracorporeal shock wave lithotripsy (ESWL), namely the number of shock waves (SWs), expulsion time (ET), mean stone density (MSD), and the skin-to-stone distance (SSD). A total of 368 patients diagnosed with renal calculi using noncontrast computerized tomography had their MSD, diameter, and SSD recorded. All patients were treated using a Siemens lithotripter. ESWL success meant a stone-free status or presence of residual fragments <3 mm, ET was the time in days for the successful clearance of stone fragments. Correlation was performed between the stone characteristics, number of SWs, and ET. Two multiple regression analysis models defined the number of SWs and ET. Two receiver operating characteristic curves plotted the best MSD cutoff value and optimum SSD for a successful ESWL. Three hundred one patients were ESWL successes. A significant positive correlation was elicited between number of SWs and stone diameter, density and SSD; between ET and stone diameter and density. Multiple regressions concluded 2 equations: Number of SWs = 265.108 + 5.103 x1 + 22.39 x2 + 10.931 x3 ET (days) = -10.85 + 0.031 x1 + 2.11 x2 x1 = stone density (Hounsfield unit [HUs]), x2 = stone diameter (mm), and x3 = SSD (mm). Receiver operating characteristic curves demonstrated a cutoff value of ≤ 934 HUs with 94.4% sensitivity and 66.7% specificity and P = .0211. The SSD curve showed that a distance ≤ 99 mm was 85.7% sensitive, 87.5% specific, P <.0001. Stone disintegration is not recommended if MSD is >934 HUs and SSD >99 mm. The required number of SWs and the expected ET can be anticipated. Copyright © 2013 Elsevier Inc. All rights reserved.

Stability and change of body mass index as a predictor of disability pension.

PubMed

Ropponen, Annina; Silventoinen, Karri; Koskenvuo, Markku; Svedberg, Pia; Kaprio, Jaakko

2016-06-01

To investigate whether stability or change in body mass index (BMI) predict disability pension (DP) due to musculoskeletal diagnosis (MSD) when controlling for familial confounding. Our study cohort consisted of 17,169 Finnish twins born before 1958. Data on BMI and multiple covariates from questionnaires in 1975 and 1981 were included and DPs were collected from the national pension registers until the end of 2004. Cox proportional hazards regression models with Hazard Ratios (HR) and 95% Confidence Intervals (CI) were used for statistical analyses. General DP was granted to 2853 individuals and DP due to MSD to 1143 individuals during the 23-year follow-up. A one-unit increase in BMI in both 1975 (HR 1.08, 95% CI 1.05, 1.10) and 1981 (HR 1.06, 95% CI 1.04, 1.07), as well as the stability of and change in BMI from 1975 to 1981 were all associated with an increased risk of DP. These associations held in the analyses controlling for multiple covariates (age, sex, socioeconomic status, education, marital status, leisure-time physical activity, and musculoskeletal pain), and mainly also familial confounding, that is, genetics and shared environment. HR for stable obesity was 2.28 (95% CI 1.69, 3.08) for DP due to MSD, and 1.91 (95% CI 1.56, 2.34) for general DP in the fully adjusted models. CONCLUSIONS BMI IS AN EARLY PREDICTOR OF GENERAL DP AND ALSO OF DP DUE TO MSD OWING TO THE INDEPENDENCY OF VARIOUS COVARIATES AND POTENTIALLY ALSO FAMILIAL CONFOUNDING, BMI MAY POSSIBLY HAVE A DIRECT EFFECT ON THE RISK OF DP. © 2016 the Nordic Societies of Public Health.

Localized Surface Plasmon Resonance as a Biosensing Platform for Developing Countries

PubMed Central

Hammond, Jules L.; Bhalla, Nikhil; Rafiee, Sarah D.; Estrela, Pedro

2014-01-01

The discovery of the phenomena known as localized surface plasmon resonance (LSPR) has provided the basis for many research areas, ranging from materials science to biosensing. LSPR has since been viewed as a transduction platform that could yield affordable, portable devices for a multitude of applications. This review aims to outline the potential applications within developing countries and the challenges that are likely to be faced before the technology can be effectively employed. PMID:25587417

Yeast as a tool to identify anti-aging compounds

PubMed Central

Zimmermann, Andreas; Hofer, Sebastian; Pendl, Tobias; Kainz, Katharina; Madeo, Frank; Carmona-Gutierrez, Didac

2018-01-01

Abstract In the search for interventions against aging and age-related diseases, biological screening platforms are indispensable tools to identify anti-aging compounds among large substance libraries. The budding yeast, Saccharomyces cerevisiae, has emerged as a powerful chemical and genetic screening platform, as it combines a rapid workflow with experimental amenability and the availability of a wide range of genetic mutant libraries. Given the amount of conserved genes and aging mechanisms between yeast and human, testing candidate anti-aging substances in yeast gene-deletion or overexpression collections, or de novo derived mutants, has proven highly successful in finding potential molecular targets. Yeast-based studies, for example, have led to the discovery of the polyphenol resveratrol and the natural polyamine spermidine as potential anti-aging agents. Here, we present strategies for pharmacological anti-aging screens in yeast, discuss common pitfalls and summarize studies that have used yeast for drug discovery and target identification. PMID:29905792

Microfluidics for cell-based high throughput screening platforms - A review.

PubMed

Du, Guansheng; Fang, Qun; den Toonder, Jaap M J

2016-01-15

In the last decades, the basic techniques of microfluidics for the study of cells such as cell culture, cell separation, and cell lysis, have been well developed. Based on cell handling techniques, microfluidics has been widely applied in the field of PCR (Polymerase Chain Reaction), immunoassays, organ-on-chip, stem cell research, and analysis and identification of circulating tumor cells. As a major step in drug discovery, high-throughput screening allows rapid analysis of thousands of chemical, biochemical, genetic or pharmacological tests in parallel. In this review, we summarize the application of microfluidics in cell-based high throughput screening. The screening methods mentioned in this paper include approaches using the perfusion flow mode, the droplet mode, and the microarray mode. We also discuss the future development of microfluidic based high throughput screening platform for drug discovery. Copyright © 2015 Elsevier B.V. All rights reserved.

Genomic prediction unifies animal and plant breeding programs to form platforms for biological discovery.

PubMed

Hickey, John M; Chiurugwi, Tinashe; Mackay, Ian; Powell, Wayne

2017-08-30

The rate of annual yield increases for major staple crops must more than double relative to current levels in order to feed a predicted global population of 9 billion by 2050. Controlled hybridization and selective breeding have been used for centuries to adapt plant and animal species for human use. However, achieving higher, sustainable rates of improvement in yields in various species will require renewed genetic interventions and dramatic improvement of agricultural practices. Genomic prediction of breeding values has the potential to improve selection, reduce costs and provide a platform that unifies breeding approaches, biological discovery, and tools and methods. Here we compare and contrast some animal and plant breeding approaches to make a case for bringing the two together through the application of genomic selection. We propose a strategy for the use of genomic selection as a unifying approach to deliver innovative 'step changes' in the rate of genetic gain at scale.

Synthetic biology approaches: Towards sustainable exploitation of marine bioactive molecules.

PubMed

Seghal Kiran, G; Ramasamy, Pasiyappazham; Sekar, Sivasankari; Ramu, Meenatchi; Hassan, Saqib; Ninawe, A S; Selvin, Joseph

2018-06-01

The discovery of genes responsible for the production of bioactive metabolites via metabolic pathways combined with the advances in synthetic biology tools, has allowed the establishment of numerous microbial cell factories, for instance the yeast cell factories, for the manufacture of highly useful metabolites from renewable biomass. Genome mining and metagenomics are two platforms provide base-line data for reconstruction of genomes and metabolomes which is based in the development of synthetic/semi-synthetic genomes for marine natural products discovery. Engineered biofilms are being innovated on synthetic biology platform using genetic circuits and cell signalling systems as represillators controlling biofilm formation. Recombineering is a process of homologous recombination mediated genetic engineering, includes insertion, deletion or modification of any sequence specifically. Although this discipline considered new to the scientific domain, this field has now developed as promising endeavor on the accomplishment of sustainable exploitation of marine natural products. Copyright © 2018 Elsevier B.V. All rights reserved.

RNA-Targeted Therapeutics.

PubMed

Crooke, Stanley T; Witztum, Joseph L; Bennett, C Frank; Baker, Brenda F

2018-04-03

RNA-targeted therapies represent a platform for drug discovery involving chemically modified oligonucleotides, a wide range of cellular RNAs, and a novel target-binding motif, Watson-Crick base pairing. Numerous hurdles considered by many to be impassable have been overcome. Today, four RNA-targeted therapies are approved for commercial use for indications as diverse as Spinal Muscular Atrophy (SMA) and reduction of low-density lipoprotein cholesterol (LDL-C) and by routes of administration including subcutaneous, intravitreal, and intrathecal delivery. The technology is efficient and supports approaching "undruggable" targets. Three additional agents are progressing through registration, and more are in clinical development, representing several chemical and structural classes. Moreover, progress in understanding the molecular mechanisms by which these drugs work has led to steadily better clinical performance and a wide range of mechanisms that may be exploited for therapeutic purposes. Here we summarize the progress, future challenges, and opportunities for this drug discovery platform. Copyright © 2018 Elsevier Inc. All rights reserved.

Discovery of a new type of topological Weyl fermion semimetal state in Mo xW 1-xTe 2

DOE PAGES

Belopolski, Ilya; Sanchez, Daniel S.; Ishida, Yukiaki; ...

2016-12-05

Here, the recent discovery of a Weyl semimetal in TaAs offers the first Weyl fermion observed in nature and dramatically broadens the classification of topological phases. However, in TaAs it has proven challenging to study the rich transport phenomena arising from emergent Weyl fermions. The series Mo xW 1-xTe 2 are inversion-breaking, layered, tunable semimetals already under study as a promising platform for new electronics and recently proposed to host Type II, or strongly Lorentz-violating, Weyl fermions. Here we report the discovery of a Weyl semimetal in Mo xW 1-xTe 2 at x=25%. We use pump-probe angle-resolved photoemission spectroscopy (pump-probemore » ARPES) to directly observe a topological Fermi arc above the Fermi level, demonstrating a Weyl semimetal. The excellent agreement with calculation suggests that Mo xW 1-xTe 2 is a Type II Weyl semimetal. We also find that certain Weyl points are at the Fermi level, making Mo xW 1-xTe 2 a promising platform for transport and optics experiments on Weyl semimetals.« less

Discovery of a new type of topological Weyl fermion semimetal state in Mo xW 1-xTe 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belopolski, Ilya; Sanchez, Daniel S.; Ishida, Yukiaki

Here, the recent discovery of a Weyl semimetal in TaAs offers the first Weyl fermion observed in nature and dramatically broadens the classification of topological phases. However, in TaAs it has proven challenging to study the rich transport phenomena arising from emergent Weyl fermions. The series Mo xW 1-xTe 2 are inversion-breaking, layered, tunable semimetals already under study as a promising platform for new electronics and recently proposed to host Type II, or strongly Lorentz-violating, Weyl fermions. Here we report the discovery of a Weyl semimetal in Mo xW 1-xTe 2 at x=25%. We use pump-probe angle-resolved photoemission spectroscopy (pump-probemore » ARPES) to directly observe a topological Fermi arc above the Fermi level, demonstrating a Weyl semimetal. The excellent agreement with calculation suggests that Mo xW 1-xTe 2 is a Type II Weyl semimetal. We also find that certain Weyl points are at the Fermi level, making Mo xW 1-xTe 2 a promising platform for transport and optics experiments on Weyl semimetals.« less

Novel drug discovery approaches for treating arenavirus infections.

PubMed

Pasquato, Antonella; Kunz, Stefan

2016-01-01

Arenaviruses are enveloped negative stranded viruses endemic in Africa, Europe and the Americas. Several arenaviruses cause severe viral hemorrhagic fever with high mortality in humans and pose serious public health threats. So far, there are no FDA-approved vaccines and therapeutic options are restricted to the off-label use of ribavirin. The major human pathogenic arenaviruses are classified as Category A agents and require biosafety level (BSL)-4 containment. Herein, the authors cover the recent progress in the development of BSL2 surrogate systems that recapitulate the entire or specific steps of the arenavirus life cycle and are serving as powerful platforms for drug discovery. Furthermore, they highlight the identification of selected novel drugs that target individual steps of arenavirus multiplication describing their discovery, their targets, and mode of action. The lack of effective drugs against arenaviruses is an unmatched challenge in current medical virology. Novel technologies have provided important insights into the basic biology of arenaviruses and the mechanisms underlying virus-host cell interaction. Significant progress of our understanding of how the virus invades the host cell paved the way to develop powerful novel screening platforms. Recent efforts have provided a range of promising drug candidates currently under evaluation for therapeutic intervention in vivo.

An optimized protocol for generation and analysis of Ion Proton sequencing reads for RNA-Seq.

PubMed

Yuan, Yongxian; Xu, Huaiqian; Leung, Ross Ka-Kit

2016-05-26

Previous studies compared running cost, time and other performance measures of popular sequencing platforms. However, comprehensive assessment of library construction and analysis protocols for Proton sequencing platform remains unexplored. Unlike Illumina sequencing platforms, Proton reads are heterogeneous in length and quality. When sequencing data from different platforms are combined, this can result in reads with various read length. Whether the performance of the commonly used software for handling such kind of data is satisfactory is unknown. By using universal human reference RNA as the initial material, RNaseIII and chemical fragmentation methods in library construction showed similar result in gene and junction discovery number and expression level estimated accuracy. In contrast, sequencing quality, read length and the choice of software affected mapping rate to a much larger extent. Unspliced aligner TMAP attained the highest mapping rate (97.27 % to genome, 86.46 % to transcriptome), though 47.83 % of mapped reads were clipped. Long reads could paradoxically reduce mapping in junctions. With reference annotation guide, the mapping rate of TopHat2 significantly increased from 75.79 to 92.09 %, especially for long (>150 bp) reads. Sailfish, a k-mer based gene expression quantifier attained highly consistent results with that of TaqMan array and highest sensitivity. We provided for the first time, the reference statistics of library preparation methods, gene detection and quantification and junction discovery for RNA-Seq by the Ion Proton platform. Chemical fragmentation performed equally well with the enzyme-based one. The optimal Ion Proton sequencing options and analysis software have been evaluated.

A base-modified PNA-graphene oxide platform as a turn-on fluorescence sensor for the detection of human telomeric repeats

NASA Astrophysics Data System (ADS)

Sabale, Pramod M.; George, Jerrin Thomas; Srivatsan, Seergazhi G.

2014-08-01

Given the biological and therapeutic significance of telomeres and other G-quadruplex forming sequences in human genome, it is highly desirable to develop simple methods to study these structures, which can also be implemented in screening formats for the discovery of G-quadruplex binders. The majority of telomere detection methods developed so far are laborious and use elaborate assay and instrumental setups, and hence, are not amenable to discovery platforms. Here, we describe the development of a simple homogeneous fluorescence turn-on method, which uses a unique combination of an environment-sensitive fluorescent nucleobase analogue, the superior base pairing property of PNA, and DNA-binding and fluorescence quenching properties of graphene oxide, to detect human telomeric DNA repeats of varying lengths. Our results demonstrate that this method, which does not involve a rigorous assay setup, would provide new opportunities to study G-quadruplex structures.Given the biological and therapeutic significance of telomeres and other G-quadruplex forming sequences in human genome, it is highly desirable to develop simple methods to study these structures, which can also be implemented in screening formats for the discovery of G-quadruplex binders. The majority of telomere detection methods developed so far are laborious and use elaborate assay and instrumental setups, and hence, are not amenable to discovery platforms. Here, we describe the development of a simple homogeneous fluorescence turn-on method, which uses a unique combination of an environment-sensitive fluorescent nucleobase analogue, the superior base pairing property of PNA, and DNA-binding and fluorescence quenching properties of graphene oxide, to detect human telomeric DNA repeats of varying lengths. Our results demonstrate that this method, which does not involve a rigorous assay setup, would provide new opportunities to study G-quadruplex structures. Electronic supplementary information (ESI) available. Figures, tables, experimental procedures and NMR spectra. See DOI: 10.1039/c4nr00878b

KSC-07pd2397

NASA Image and Video Library

2007-09-05

KENNEDY SPACE CENTER, FLA. -- In the Vehicle Assembly Building at NASA's Kennedy Space Center, the top of external tank No. 120 is seen as the tank is lowered between the solid rocket boosters for mating on the mobile launcher platform. The external tank-SRB stack is being prepared for the orbiter Discovery, which will be mated to the stack in the VAB in two weeks. Space Shuttle Discovery is targeted to launch Oct. 23 on mission STS-120 to the International Space Station. Photo credit: NASA/George Shelton

Closeup view of the reinforced carboncarbon nose of the Orbiter ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Close-up view of the reinforced carbon-carbon nose of the Orbiter Discovery from the service platform in the Orbiter Processing Facility at Kennedy Space Center. Note the clear protective shield around the nose cap, and the reflective insulation protecting the Crew Compartment bulkhead and orbiter structure in the void created by the removal of the Forward Reaction Control Module. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Innovations in Undergraduate Science Education: Going Viral.

PubMed

Hatfull, Graham F

2015-08-01

Bacteriophage discovery and genomics provides a powerful and effective platform for integrating missions in research and education. Implementation of the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) program facilitates a broad impact by including a diverse array of schools, faculty, and students. The program generates new insights into the diversity and evolution of the bacteriophage population and presents a model for introducing first-year undergraduate students to discovery-based research experiences. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

View looking aft along the starboard side of the midfuselage ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View looking aft along the starboard side of the mid-fuselage of the Orbiter Discovery. This view shows the wing profile as it intersects with the fuselage. Also note in the foreground the panels protecting the Reinforced Carbon-Carbon leading edge of the wing. This view was taken from the service platform in the Orbiter Processing Facility at Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Live Cell in Vitro and in Vivo Imaging Applications: Accelerating Drug Discovery

PubMed Central

Isherwood, Beverley; Timpson, Paul; McGhee, Ewan J; Anderson, Kurt I; Canel, Marta; Serrels, Alan; Brunton, Valerie G; Carragher, Neil O

2011-01-01

Dynamic regulation of specific molecular processes and cellular phenotypes in live cell systems reveal unique insights into cell fate and drug pharmacology that are not gained from traditional fixed endpoint assays. Recent advances in microscopic imaging platform technology combined with the development of novel optical biosensors and sophisticated image analysis solutions have increased the scope of live cell imaging applications in drug discovery. We highlight recent literature examples where live cell imaging has uncovered novel insight into biological mechanism or drug mode-of-action. We survey distinct types of optical biosensors and associated analytical methods for monitoring molecular dynamics, in vitro and in vivo. We describe the recent expansion of live cell imaging into automated target validation and drug screening activities through the development of dedicated brightfield and fluorescence kinetic imaging platforms. We provide specific examples of how temporal profiling of phenotypic response signatures using such kinetic imaging platforms can increase the value of in vitro high-content screening. Finally, we offer a prospective view of how further application and development of live cell imaging technology and reagents can accelerate preclinical lead optimization cycles and enhance the in vitro to in vivo translation of drug candidates. PMID:24310493

The Growth of Multi-Site Fatigue Damage in Fuselage Lap Joints

NASA Technical Reports Server (NTRS)

Piascik, Robert S.; Willard, Scott A.

1999-01-01

Destructive examinations were performed to document the progression of multi-site damage (MSD) in three lap joint panels that were removed from a full scale fuselage test article that was tested to 60,000 full pressurization cycles. Similar fatigue crack growth characteristics were observed for small cracks (50 microns to 10 mm) emanating from counter bore rivets, straight shank rivets, and 100 deg counter sink rivets. Good correlation of the fatigue crack growth data base obtained in this study and FASTRAN Code predictions show that the growth of MSD in the fuselage lap joint structure can be predicted by fracture mechanics based methods.

Thermodynamic properties of semiconductor compounds studied based on Debye-Waller factors

NASA Astrophysics Data System (ADS)

Van Hung, Nguyen; Toan, Nguyen Cong; Ba Duc, Nguyen; Vuong, Dinh Quoc

2015-08-01

Thermodynamic properties of semiconductor compounds have been studied based on Debye-Waller factors (DWFs) described by the mean square displacement (MSD) which has close relation with the mean square relative displacement (MSRD). Their analytical expressions have been derived based on the statistical moment method (SMM) and the empirical many-body Stillinger-Weber potentials. Numerical results for the MSDs of GaAs, GaP, InP, InSb, which have zinc-blende structure, are found to be in reasonable agreement with experiment and other theories. This paper shows that an elements value for MSD is dependent on the binary semiconductor compound within which it resides.

Automatic segmentation and classification of gestational sac based on mean sac diameter using medical ultrasound image

NASA Astrophysics Data System (ADS)

Khazendar, Shan; Farren, Jessica; Al-Assam, Hisham; Sayasneh, Ahmed; Du, Hongbo; Bourne, Tom; Jassim, Sabah A.

2014-05-01

Ultrasound is an effective multipurpose imaging modality that has been widely used for monitoring and diagnosing early pregnancy events. Technology developments coupled with wide public acceptance has made ultrasound an ideal tool for better understanding and diagnosing of early pregnancy. The first measurable signs of an early pregnancy are the geometric characteristics of the Gestational Sac (GS). Currently, the size of the GS is manually estimated from ultrasound images. The manual measurement involves multiple subjective decisions, in which dimensions are taken in three planes to establish what is known as Mean Sac Diameter (MSD). The manual measurement results in inter- and intra-observer variations, which may lead to difficulties in diagnosis. This paper proposes a fully automated diagnosis solution to accurately identify miscarriage cases in the first trimester of pregnancy based on automatic quantification of the MSD. Our study shows a strong positive correlation between the manual and the automatic MSD estimations. Our experimental results based on a dataset of 68 ultrasound images illustrate the effectiveness of the proposed scheme in identifying early miscarriage cases with classification accuracies comparable with those of domain experts using K nearest neighbor classifier on automatically estimated MSDs.

Distributional behavior of diffusion coefficients obtained by single trajectories in annealed transit time model

NASA Astrophysics Data System (ADS)

Akimoto, Takuma; Yamamoto, Eiji

2016-12-01

Local diffusion coefficients in disordered systems such as spin glass systems and living cells are highly heterogeneous and may change over time. Such a time-dependent and spatially heterogeneous environment results in irreproducibility of single-particle-tracking measurements. Irreproducibility of time-averaged observables has been theoretically studied in the context of weak ergodicity breaking in stochastic processes. Here, we provide rigorous descriptions of equilibrium and non-equilibrium diffusion processes for the annealed transit time model, which is a heterogeneous diffusion model in living cells. We give analytical solutions for the mean square displacement (MSD) and the relative standard deviation of the time-averaged MSD for equilibrium and non-equilibrium situations. We find that the time-averaged MSD grows linearly with time and that the time-averaged diffusion coefficients are intrinsically random (irreproducible) even in the long-time measurements in non-equilibrium situations. Furthermore, the distribution of the time-averaged diffusion coefficients converges to a universal distribution in the sense that it does not depend on initial conditions. Our findings pave the way for a theoretical understanding of distributional behavior of the time-averaged diffusion coefficients in disordered systems.

V-T theory for the self-intermediate scattering function in a monatomic liquid

NASA Astrophysics Data System (ADS)

Wallace, Duane C.; Chisolm, Eric D.; De Lorenzi-Venneri, Giulia

2017-02-01

In V-T theory the atomic motion is harmonic vibrations in a liquid-specific potential energy valley, plus transits, which move the system rapidly among the multitude of such valleys. In its first application to the self intermediate scattering function (SISF), V-T theory produced an accurate account of molecular dynamics (MD) data at all wave numbers q and time t. Recently, analysis of the mean square displacement (MSD) resolved a crossover behavior that was not observed in the SISF study. Our purpose here is to apply the more accurate MSD calibration to the SISF, and assess the results. We derive and discuss the theoretical equations for vibrational and transit contributions to the SISF. The time evolution is divided into three successive intervals: the vibrational interval when the vibrational contribution alone accurately accounts for the MD data; the crossover when the vibrational contribution saturates and the transit contribution becomes resolved; and the diffusive interval when the transit contribution alone accurately accounts for the MD data. The resulting theoretical error is extremely small at all q and t. V-T theory is compared to mode-coupling theories for the MSD and SISF, and to recent developments in Brownian motion experiments and theory.

Quality of Piped and Stored Water in Households with Children Under Five Years of Age Enrolled in the Mali Site of the Global Enteric Multi-Center Study (GEMS)

PubMed Central

Baker, Kelly K.; Sow, Samba O.; Kotloff, Karen L.; Nataro, James P.; Farag, Tamer H.; Tamboura, Boubou; Doumbia, Mama; Sanogo, Doh; Diarra, Drissa; O'Reilly, Ciara E.; Mintz, Eric; Panchalingam, Sandra; Wu, Yukun; Blackwelder, William C.; Levine, Myron M.

2013-01-01

Water, sanitation, and hygiene information was collected during a matched case-control study of moderate and severe diarrhea (MSD) among 4,096 children < 5 years of age in Bamako, Mali. Primary use of piped water (conditional odds ratio [cOR] = 0.45; 0.34–0.62), continuous water access (cOR = 0.30; 0.20–0.43), fetching water daily (cOR = 0.77; 0.63–0.96), and breastfeeding (cOR = 0.65; 0.49–0.88) significantly reduced the likelihood of MSD. Fetching water in > 30 minutes (cOR = 2.56; 1.55–4.23) was associated with MSD. Piped tap water and courier-delivered water contained high (> 2 mg/L) concentrations of free residual chlorine and no detectable Escherichia coli. However, many households stored water overnight, resulting in inadequate free residual chlorine (< 0.2 mg/L) for preventing microbial contamination. Coliforms and E. coli were detected in 48% and 8% of stored household water samples, respectively. Although most of Bamako's population enjoys access to an improved water source, water quality is often compromised during household storage. PMID:23836570

Atomic motion from the mean square displacement in a monatomic liquid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallace, Duane C.; De Lorenzi-Venneri, Giulia; Chisolm, Eric D.

V-T theory is constructed in the many-body Hamiltonian formulation, and is being developed as a novel approach to liquid dynamics theory. In this theory the liquid atomic motion consists of two contributions, normal mode vibrations in a single representative potential energy valley, and transits, which carry the system across boundaries between valleys. The mean square displacement time correlation function (the MSD) is a direct measure of the atomic motion, and our goal is to determine if the V-T formalism can produce a physically sensible account of this motion. We employ molecular dynamics (MD) data for a system representing liquid Na,more » and find the motion evolves in three successive time intervals: on the first 'vibrational' interval, the vibrational motion alone gives a highly accurate account of the MD data; on the second 'crossover' interval, the vibrational MSD saturates to a constant while the transit motion builds up from zero; on the third 'random walk' interval, the transit motion produces a purely diffusive random walk of the vibrational equilibrium positions. Furthermore, this motional evolution agrees with, and adds refinement to, the MSD atomic motion as described by current liquid dynamics theories.« less

Atomic motion from the mean square displacement in a monatomic liquid

DOE PAGES

Wallace, Duane C.; De Lorenzi-Venneri, Giulia; Chisolm, Eric D.

2016-04-08

V-T theory is constructed in the many-body Hamiltonian formulation, and is being developed as a novel approach to liquid dynamics theory. In this theory the liquid atomic motion consists of two contributions, normal mode vibrations in a single representative potential energy valley, and transits, which carry the system across boundaries between valleys. The mean square displacement time correlation function (the MSD) is a direct measure of the atomic motion, and our goal is to determine if the V-T formalism can produce a physically sensible account of this motion. We employ molecular dynamics (MD) data for a system representing liquid Na,more » and find the motion evolves in three successive time intervals: on the first 'vibrational' interval, the vibrational motion alone gives a highly accurate account of the MD data; on the second 'crossover' interval, the vibrational MSD saturates to a constant while the transit motion builds up from zero; on the third 'random walk' interval, the transit motion produces a purely diffusive random walk of the vibrational equilibrium positions. Furthermore, this motional evolution agrees with, and adds refinement to, the MSD atomic motion as described by current liquid dynamics theories.« less

Residual Strength Analyses of Riveted Lap-Splice Joints

NASA Technical Reports Server (NTRS)

Seshadri, B. R.; Newman, J. C., Jr.

2000-01-01

The objective of this paper was to analyze the crack-linkup behavior in riveted-stiffened lap-splice joint panels with small multiple-site damage (MSD) cracks at several adjacent rivet holes. Analyses are based on the STAGS (STructural Analysis of General Shells) code with the critical crack-tip-opening angle (CTOA) fracture criterion. To account for high constraint around a crack front, the "plane strain core" option in STAGS was used. The importance of modeling rivet flexibility with fastener elements that accurately model load transfer across the joint is discussed. Fastener holes are not modeled but rivet connectivity is accounted for by attaching rivets to the sheet on one side of the cracks that simulated both the rivet diameter and MSD cracks. Residual strength analyses made on 2024-T3 alloy (1.6-mm thick) riveted-lap-splice joints with a lead crack and various size MSD cracks were compared with test data from Boeing Airplane Company. Analyses were conducted for both restrained and unrestrained buckling conditions. Comparison of results from these analyses and results from lap-splice-joint test panels, which were partially restrained against buckling indicate that the test results were bounded by the failure loads predicted by the analyses with restrained and unrestrained conditions.

A multiple maximum scatter difference discriminant criterion for facial feature extraction.

PubMed

Song, Fengxi; Zhang, David; Mei, Dayong; Guo, Zhongwei

2007-12-01

Maximum scatter difference (MSD) discriminant criterion was a recently presented binary discriminant criterion for pattern classification that utilizes the generalized scatter difference rather than the generalized Rayleigh quotient as a class separability measure, thereby avoiding the singularity problem when addressing small-sample-size problems. MSD classifiers based on this criterion have been quite effective on face-recognition tasks, but as they are binary classifiers, they are not as efficient on large-scale classification tasks. To address the problem, this paper generalizes the classification-oriented binary criterion to its multiple counterpart--multiple MSD (MMSD) discriminant criterion for facial feature extraction. The MMSD feature-extraction method, which is based on this novel discriminant criterion, is a new subspace-based feature-extraction method. Unlike most other subspace-based feature-extraction methods, the MMSD computes its discriminant vectors from both the range of the between-class scatter matrix and the null space of the within-class scatter matrix. The MMSD is theoretically elegant and easy to calculate. Extensive experimental studies conducted on the benchmark database, FERET, show that the MMSD out-performs state-of-the-art facial feature-extraction methods such as null space method, direct linear discriminant analysis (LDA), eigenface, Fisherface, and complete LDA.

Pain, fatigue, function and participation among long-term manual wheelchair users partnered with a mobility service dog.

PubMed

Vincent, Claude; Gagnon, Dany H; Dumont, Frédéric

2017-11-20

To assess the effects of a mobility service dog (MSD) on pain, fatigue, wheelchair-related functional tasks, participation and satisfaction among manual wheelchair users over a nine-month period. A longitudinal study with repeated assessment times before and three, six and nine months after intervention was achieved. Intervention consisted in partnering each participant with a MSD. The setting is a well-established provincial service dog training school and participants homes. A convenience sample of 24 long-term manual wheelchair users with a spinal cord injury was involved. Outcome measures were: Wheelchair User's Shoulder Pain Index (WUSPI), Rate of Perceived Exertion (RPE), vitality scale from the SF-36, grip strength, Wheelchair Skills Test (WST), Canadian Occupational Performance Measure (COPM), Reintegration to Normal Living Index (RNLI), Life Space Assessment, Psychosocial Impact of Assistive Devices Scale (PIADS) and Quebec User Evaluation of Satisfaction with assistive Technology (QUEST 2.0). Shoulder and wrist pain as well as fatigue decreased significantly over time with the use of a MSD as evidenced by scores from WUSPI, RPE and SF-36 (feeling less worn out). Manual wheelchair propulsion skills (steep slopes, soft surfaces and thresholds) improved significantly over time as confirmed by the WST. Participation increased significantly over time as revealed by the COPM (for five occupations) and the RNLI (for five items). Satisfaction with the MSD was high over time (QUEST: nine items) and with a high positive psychosocial impact (PIADS: 10 items). MSD represents a valuable mobility assistive technology option for manual wheelchair users. IMPLICATIONS FOR REHABILITATION   For manual wheelchair users partenered with mobility service dog  • Shoulder pain and fatigue significantly decreased and continued to decrease between the third and sixth month and the ninth month.   • Performance with propelling the wheelchair up steep slopes increased from 41 to 88% and on soft surfaces increased from 53 to 100% after 3 months, respectively.   • Occupational performance satisfaction was significantly increased for mobility in relation with the transfers, navigating in a natural environment and picking up objects.   • High satisfaction towards psychosocial competency, psychosocial adequacy and self-esteem were reported at months three, six and nine.

Stability and change in health behaviours as predictors for disability pension: a prospective cohort study of Swedish twins

PubMed Central

2011-01-01

Background Stability or changes of health behaviours have not been studied in association with incidence of disability pension (DP). The aims were to (1) investigate if stability or changes in health behaviours predict DP due to musculoskeletal diagnosis (MSD), (2) to evaluate if an association exists for DP in general, and (3) after taking familial confounding into account. Methods The study sample was 16,713 like-sexed twin individuals born in Sweden between 1935-1958 (6195 complete twin pairs) who had participated in two surveys 25 years apart, were alive, and not pensioned at the time of the latest survey. Cox proportional hazards analysis was used to assess the associations (hazard ratios (HR) with 95% confidence intervals (CI)) between stability and change in health behaviours (physical activity, tobacco and alcohol use, body mass index (BMI)), and number of pain locations collected at two time points 25 years apart and the incidence of DP until 2008. Results During the follow-up, 1843 (11%) individuals were granted DP with 747 of these due to MSD. A higher proportion of women were granted DP than men. Increase in BMI and stable use of tobacco products were predictors for DP due to MSD (HR 1.21-1.48) and DP in general (HR 1.10-1.41). The stability in the frequency of physical activity and increased frequency of physical activity were protective factors for DP due to MSD only when accounting for familial confounding. However, the number of pain locations (stability, increase, or decrease) was the strongest predictor for future DP due to MSD (HR 3.69, CI 2.99-4.56) and DP in general (HR 2.15, CI 1.92-2.42). In discordant pair analysis, the HRs for pain were lower, indicating potential familial confounding. Conclusions Health behaviours in adulthood, including an increase in pain locations were associated with the incidence of DP. The association between physical activity and DP was especially related to adulthood choices or habits, i.e., the individual decision about frequency of exercising. Thus, it is important to e.g. increase public awareness of the potential beneficial effects of exercise throughout life to avoid permanent exclusion from the labour market for medical reasons. PMID:21880151

Stability and change in health behaviours as predictors for disability pension: a prospective cohort study of Swedish twins.

PubMed

Ropponen, Annina; Narusyte, Jurgita; Alexanderson, Kristina; Svedberg, Pia

2011-08-31

Stability or changes of health behaviours have not been studied in association with incidence of disability pension (DP). The aims were to (1) investigate if stability or changes in health behaviours predict DP due to musculoskeletal diagnosis (MSD), (2) to evaluate if an association exists for DP in general, and (3) after taking familial confounding into account. The study sample was 16,713 like-sexed twin individuals born in Sweden between 1935-1958 (6195 complete twin pairs) who had participated in two surveys 25 years apart, were alive, and not pensioned at the time of the latest survey. Cox proportional hazards analysis was used to assess the associations (hazard ratios (HR) with 95% confidence intervals (CI)) between stability and change in health behaviours (physical activity, tobacco and alcohol use, body mass index (BMI)), and number of pain locations collected at two time points 25 years apart and the incidence of DP until 2008. During the follow-up, 1843 (11%) individuals were granted DP with 747 of these due to MSD. A higher proportion of women were granted DP than men. Increase in BMI and stable use of tobacco products were predictors for DP due to MSD (HR 1.21-1.48) and DP in general (HR 1.10-1.41). The stability in the frequency of physical activity and increased frequency of physical activity were protective factors for DP due to MSD only when accounting for familial confounding. However, the number of pain locations (stability, increase, or decrease) was the strongest predictor for future DP due to MSD (HR 3.69, CI 2.99-4.56) and DP in general (HR 2.15, CI 1.92-2.42). In discordant pair analysis, the HRs for pain were lower, indicating potential familial confounding. Health behaviours in adulthood, including an increase in pain locations were associated with the incidence of DP. The association between physical activity and DP was especially related to adulthood choices or habits, i.e., the individual decision about frequency of exercising. Thus, it is important to e.g. increase public awareness of the potential beneficial effects of exercise throughout life to avoid permanent exclusion from the labour market for medical reasons.

Rembrandt: Helping Personalized Medicine Become a Reality Through Integrative Translational Research

PubMed Central

Madhavan, Subha; Zenklusen, Jean-Claude; Kotliarov, Yuri; Sahni, Himanso; Fine, Howard A.; Buetow, Kenneth

2009-01-01

Finding better therapies for the treatment of brain tumors is hampered by the lack of consistently obtained molecular data in a large sample set, and ability to integrate biomedical data from disparate sources enabling translation of therapies from bench to bedside. Hence, a critical factor in the advancement of biomedical research and clinical translation is the ease with which data can be integrated, redistributed and analyzed both within and across functional domains. Novel biomedical informatics infrastructure and tools are essential for developing individualized patient treatment based on the specific genomic signatures in each patient’s tumor. Here we present Rembrandt, Repository of Molecular BRAin Neoplasia DaTa, a cancer clinical genomics database and a web-based data mining and analysis platform aimed at facilitating discovery by connecting the dots between clinical information and genomic characterization data. To date, Rembrandt contains data generated through the Glioma Molecular Diagnostic Initiative from 874 glioma specimens comprising nearly 566 gene expression arrays, 834 copy number arrays and 13,472 clinical phenotype data points. Data can be queried and visualized for a selected gene across all data platforms or for multiple genes in a selected platform. Additionally, gene sets can be limited to clinically important annotations including secreted, kinase, membrane, and known gene-anomaly pairs to facilitate the discovery of novel biomarkers and therapeutic targets. We believe that REMBRANDT represents a prototype of how high throughput genomic and clinical data can be integrated in a way that will allow expeditious and efficient translation of laboratory discoveries to the clinic. PMID:19208739

NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds

PubMed Central

Yu, Jun-lan; Chen, Tian-tian; Zhou, Chen; Lian, Fu-lin; Tang, Xu-long; Wen, Yi; Shen, Jing-kang; Xu, Ye-chun; Xiong, Bing; Zhang, Nai-xia

2016-01-01

Aim: Fragment-based lead discovery (FBLD) is a complementary approach in drug research and development. In this study, we established an NMR-based FBLD platform that was used to screen novel scaffolds targeting human bromodomain of BRD4, and investigated the binding interactions between hit compounds and the target protein. Methods: 1D NMR techniques were primarily used to generate the fragment library and to screen compounds. The inhibitory activity of hits on the first bromodomain of BRD4 [BRD4(I)] was examined using fluorescence anisotropy binding assay. 2D NMR and X-ray crystallography were applied to characterize the binding interactions between hit compounds and the target protein. Results: An NMR-based fragment library containing 539 compounds was established, which were clustered into 56 groups (8–10 compounds in each group). Eight hits with new scaffolds were found to inhibit BRD4(I). Four out of the 8 hits (compounds 1, 2, 8 and 9) had IC50 values of 100–260 μmol/L, demonstrating their potential for further BRD4-targeted hit-to-lead optimization. Analysis of the binding interactions revealed that compounds 1 and 2 shared a common quinazolin core structure and bound to BRD4(I) in a non-acetylated lysine mimetic mode. Conclusion: An NMR-based platform for FBLD was established and used in discovery of BRD4-targeted compounds. Four potential hit-to-lead optimization candidates have been found, two of them bound to BRD4(I) in a non-acetylated lysine mimetic mode, being selective BRD4(I) inhibitors. PMID:27238211

KSC-05PD-0620

NASA Technical Reports Server (NTRS)

2005-01-01

KENNEDY SPACE CENTER, FLA. In the waning twilight, the service structures on Launch Pad 39B (left) and the Mobile Launcher Platform carrying Space Shuttle Discovery glow with lights. The Shuttle began rollout to the pad at 2:04 p.m. EDT from the Vehicle Assembly Building at NASAs Kennedy Space Center, marking a major milestone in the Space Shuttle Programs Return to Flight. Launch of Discovery on its Return to Flight mission, STS-114, is targeted for May 15 with a launch window that extends to June 3. During its 12-day mission, Discoverys seven-person crew will test new hardware and techniques to improve Shuttle safety, as well as deliver supplies to the International Space Station.

Three-Component Reaction Discovery Enabled by Mass Spectrometry of Self-Assembled Monolayers

PubMed Central

Montavon, Timothy J.; Li, Jing; Cabrera-Pardo, Jaime R.; Mrksich, Milan; Kozmin, Sergey A.

2011-01-01

Multi-component reactions have been extensively employed in many areas of organic chemistry. Despite significant progress, the discovery of such enabling transformations remains challenging. Here, we present the development of a parallel, label-free reaction-discovery platform, which can be used for identification of new multi-component transformations. Our approach is based on the parallel mass spectrometric screening of interfacial chemical reactions on arrays of self-assembled monolayers. This strategy enabled the identification of a simple organic phosphine that can catalyze a previously unknown condensation of siloxy alkynes, aldehydes and amines to produce 3-hydroxy amides with high efficiency and diastereoselectivity. The reaction was further optimized using solution phase methods. PMID:22169871

The Z1 truss is transported to Launch Pad 39A

NASA Technical Reports Server (NTRS)

2000-01-01

At Launch Pad 39A, the payload canister at left draws closer to the Rotating Service Structure where it will be lifted to the Payload Changeout Room. There its cargo, the Integrated Truss Structure Z1, will be removed and later transferred to Space Shuttle Discovery's payload bay. Discovery is at right, sitting atop the Mobile Launcher Platform. The Z1 truss is the first of 10 that will become the backbone of the International Space Station, eventually stretching the length of a football field. Along with its companion payload, the third Pressurized Mating Adapter, the Z1 is scheduled to be launched aboard Discovery Oct. 5 at 9:38 p.m. EDT.

Mass spectrometry-driven drug discovery for development of herbal medicine.

PubMed

Zhang, Aihua; Sun, Hui; Wang, Xijun

2018-05-01

Herbal medicine (HM) has made a major contribution to the drug discovery process with regard to identifying products compounds. Currently, more attention has been focused on drug discovery from natural compounds of HM. Despite the rapid advancement of modern analytical techniques, drug discovery is still a difficult and lengthy process. Fortunately, mass spectrometry (MS) can provide us with useful structural information for drug discovery, has been recognized as a sensitive, rapid, and high-throughput technology for advancing drug discovery from HM in the post-genomic era. It is essential to develop an efficient, high-quality, high-throughput screening method integrated with an MS platform for early screening of candidate drug molecules from natural products. We have developed a new chinmedomics strategy reliant on MS that is capable of capturing the candidate molecules, facilitating their identification of novel chemical structures in the early phase; chinmedomics-guided natural product discovery based on MS may provide an effective tool that addresses challenges in early screening of effective constituents of herbs against disease. This critical review covers the use of MS with related techniques and methodologies for natural product discovery, biomarker identification, and determination of mechanisms of action. It also highlights high-throughput chinmedomics screening methods suitable for lead compound discovery illustrated by recent successes. © 2016 Wiley Periodicals, Inc.

The Application of the Open Pharmacological Concepts Triple Store (Open PHACTS) to Support Drug Discovery Research

PubMed Central

Ratnam, Joseline; Zdrazil, Barbara; Digles, Daniela; Cuadrado-Rodriguez, Emiliano; Neefs, Jean-Marc; Tipney, Hannah; Siebes, Ronald; Waagmeester, Andra; Bradley, Glyn; Chau, Chau Han; Richter, Lars; Brea, Jose; Evelo, Chris T.; Jacoby, Edgar; Senger, Stefan; Loza, Maria Isabel; Ecker, Gerhard F.; Chichester, Christine

2014-01-01

Integration of open access, curated, high-quality information from multiple disciplines in the Life and Biomedical Sciences provides a holistic understanding of the domain. Additionally, the effective linking of diverse data sources can unearth hidden relationships and guide potential research strategies. However, given the lack of consistency between descriptors and identifiers used in different resources and the absence of a simple mechanism to link them, gathering and combining relevant, comprehensive information from diverse databases remains a challenge. The Open Pharmacological Concepts Triple Store (Open PHACTS) is an Innovative Medicines Initiative project that uses semantic web technology approaches to enable scientists to easily access and process data from multiple sources to solve real-world drug discovery problems. The project draws together sources of publicly-available pharmacological, physicochemical and biomolecular data, represents it in a stable infrastructure and provides well-defined information exploration and retrieval methods. Here, we highlight the utility of this platform in conjunction with workflow tools to solve pharmacological research questions that require interoperability between target, compound, and pathway data. Use cases presented herein cover 1) the comprehensive identification of chemical matter for a dopamine receptor drug discovery program 2) the identification of compounds active against all targets in the Epidermal growth factor receptor (ErbB) signaling pathway that have a relevance to disease and 3) the evaluation of established targets in the Vitamin D metabolism pathway to aid novel Vitamin D analogue design. The example workflows presented illustrate how the Open PHACTS Discovery Platform can be used to exploit existing knowledge and generate new hypotheses in the process of drug discovery. PMID:25522365

An ion channel library for drug discovery and safety screening on automated platforms.

PubMed

Wible, Barbara A; Kuryshev, Yuri A; Smith, Stephen S; Liu, Zhiqi; Brown, Arthur M

2008-12-01

Ion channels represent the third largest class of targets in drug discovery after G-protein coupled receptors and kinases. In spite of this ranking, ion channels continue to be under exploited as drug targets compared with the other two groups for several reasons. First, with 400 ion channel genes and an even greater number of functional channels due to mixing and matching of individual subunits, a systematic collection of ion channel-expressing cell lines for drug discovery and safety screening has not been available. Second, the lack of high-throughput functional assays for ion channels has limited their use as drug targets. Now that automated electrophysiology has come of age and provided the technology to assay ion channels at medium to high throughput, we have addressed the need for a library of ion channel cell lines by constructing the Ion Channel Panel (ChanTest Corp., Cleveland, OH). From 400 ion channel genes, a collection of 82 of the most relevant human ion channels for drug discovery, safety, and human disease has been assembled.Each channel has been stably overexpressed in human embryonic kidney 293 or Chinese hamster ovary cells. Cell lines have been selected and validated on automated electrophysiology systems to facilitate cost-effective screening for safe and selective compounds at earlier stages in the drug development process. The screening and validation processes as well as the relative advantages of different screening platforms are discussed.

The Benefits and Complexities of Operating Geographic Information Systems (GIS) in a High Performance Computing (HPC) Environment

NASA Astrophysics Data System (ADS)

Shute, J.; Carriere, L.; Duffy, D.; Hoy, E.; Peters, J.; Shen, Y.; Kirschbaum, D.

2017-12-01

The NASA Center for Climate Simulation (NCCS) at the Goddard Space Flight Center is building and maintaining an Enterprise GIS capability for its stakeholders, to include NASA scientists, industry partners, and the public. This platform is powered by three GIS subsystems operating in a highly-available, virtualized environment: 1) the Spatial Analytics Platform is the primary NCCS GIS and provides users discoverability of the vast DigitalGlobe/NGA raster assets within the NCCS environment; 2) the Disaster Mapping Platform provides mapping and analytics services to NASA's Disaster Response Group; and 3) the internal (Advanced Data Analytics Platform/ADAPT) enterprise GIS provides users with the full suite of Esri and open source GIS software applications and services. All systems benefit from NCCS's cutting edge infrastructure, to include an InfiniBand network for high speed data transfers; a mixed/heterogeneous environment featuring seamless sharing of information between Linux and Windows subsystems; and in-depth system monitoring and warning systems. Due to its co-location with the NCCS Discover High Performance Computing (HPC) environment and the Advanced Data Analytics Platform (ADAPT), the GIS platform has direct access to several large NCCS datasets including DigitalGlobe/NGA, Landsat, MERRA, and MERRA2. Additionally, the NCCS ArcGIS Desktop Windows virtual machines utilize existing NetCDF and OPeNDAP assets for visualization, modelling, and analysis - thus eliminating the need for data duplication. With the advent of this platform, Earth scientists have full access to vast data repositories and the industry-leading tools required for successful management and analysis of these multi-petabyte, global datasets. The full system architecture and integration with scientific datasets will be presented. Additionally, key applications and scientific analyses will be explained, to include the NASA Global Landslide Catalog (GLC) Reporter crowdsourcing application, the NASA GLC Viewer discovery and analysis tool, the DigitalGlobe/NGA Data Discovery Tool, the NASA Disaster Response Group Mapping Platform (https://maps.disasters.nasa.gov), and support for NASA's Arctic - Boreal Vulnerability Experiment (ABoVE).

Interspecies chimeras.

PubMed

Suchy, Fabian; Nakauchi, Hiromitsu

2018-05-30

By probing early embryogenesis and regeneration, interspecies chimeras provide a unique platform for discovery and clinical use. Although efficient generation of human:animal chimeric embryos remains elusive, recent advancements attempt to overcome incompatibilities in xenogeneic development and transplantation. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Combinatorial Platform for the Optimization of Peptidomimetic Methyl-Lysine Reader Antagonists

NASA Astrophysics Data System (ADS)

Barnash, Kimberly D.

Post-translational modification of histone N-terminal tails mediates chromatin compaction and, consequently, DNA replication, transcription, and repair. While numerous post-translational modifications decorate histone tails, lysine methylation is an abundant mark important for both gene activation and repression. Methyl-lysine (Kme) readers function through binding mono-, di-, or trimethyl-lysine. Chemical intervention of Kme readers faces numerous challenges due to the broad surface-groove interactions between readers and their cognate histone peptides; yet, the increasing interest in understanding chromatin-modifying complexes suggests tractable lead compounds for Kme readers are critical for elucidating the mechanisms of chromatin dysregulation in disease states and validating the druggability of these domains and complexes. The successful discovery of a peptide-derived chemical probe, UNC3866, for the Polycomb repressive complex 1 (PRC1) chromodomain Kme readers has proven the potential for selective peptidomimetic inhibition of reader function. Unfortunately, the systematic modification of peptides-to-peptidomimetics is a costly and inefficient strategy for target-class hit discovery against Kme readers. Through the exploration of biased chemical space via combinatorial on-bead libraries, we have developed two concurrent methodologies for Kme reader chemical probe discovery. We employ biased peptide combinatorial libraries as a hit discovery strategy with subsequent optimization via iterative targeted libraries. Peptide-to-peptidomimetic optimization through targeted library design was applied based on structure-guided library design around the interaction of the endogenous peptide ligand with three target Kme readers. Efforts targeting the WD40 reader EED led to the discovery of the 3-mer peptidomimetic ligand UNC5115 while combinatorial repurposing of UNC3866 for off-target chromodomains resulted in the discovery of UNC4991, a CDYL/2-selective ligand, and UNC4848, a MPP8 and CDYL/2 ligand. Ultimately, our efforts demonstrate the generalizability of a peptidomimetic combinatorial platform for the optimization of Kme reader ligands in a target class manner.

Anomalous Diffusion of Particles Dispersed in Xanthan Solutions Subjected to Shear Flow

NASA Astrophysics Data System (ADS)

Takikawa, Yoshinori; Yasuta, Muneharu; Fujii, Shuji; Orihara, Hiroshi; Tanaka, Yoshimi; Nishinari, Katsuyoshi

2018-05-01

Xanthan gum exhibits viscoelastic and shear-thinning properties. We investigate the Brownian motion of particles dispersed in xanthan gum solutions that are subjected to simple shear flow. The mean square displacements (MSDs) are obtained in both the flow and vorticity directions. In the absence of shear flow, subdiffusion is observed, MSD ∝ tα with α < 1, where t is time. In the presence of shear flow, however, the exponent α becomes larger together with the MSD itself in both the flow and vorticity directions. We show that the diffusion is enhanced by Taylor dispersion in the flow direction, whereas in the vorticity direction it is enhanced by nonthermal self-diffusion.

NASA airframe structural integrity program

NASA Technical Reports Server (NTRS)

Harris, Charles E.

1991-01-01

NASA has initiated a research program with the long-term objective of supporting the aerospace industry in addressing issues related to the aging commercial transport fleet. The interdisciplinary program combines advanced fatigue crack growth prediction methodology with innovative nondestructive examination technology with the focus on multi-site damage (MSD) at riveted connections. A fracture mechanics evaluation of the concept of pressure proof testing the fuselage to screen for MSD has been completed. Also, a successful laboratory demonstration of the ability of the thermal flux method to detect disbonds at riveted lap splice joints has been conducted. All long-term program elements have been initiated and the plans for the methodology verification program are being coordinated with the airframe manufacturers.

NASA airframe structural integrity program

NASA Technical Reports Server (NTRS)

Harris, Charles E.

1990-01-01

NASA initiated a research program with the long-term objective of supporting the aerospace industry in addressing issues related to the aging of the commercial transport fleet. The program combines advanced fatigue crack growth prediction methodology with innovative nondestructive examination technology with the focus on multi-stage damage (MSD) at rivited connections. A fracture mechanics evaluation of the concept of pressure proof testing the fuselage to screen for MSD was completed. A successful laboratory demonstration of the ability of the thermal flux method to detect disbonds at rivited lap splice joints was conducted. All long-term program elements were initiated, and the plans for the methodology verification program are being coordinated with the airframe manufacturers.

The Classes of Authoring Programs.

ERIC Educational Resources Information Center

Kozel, Kathy

1997-01-01

Provides an overview of developments in authoring tools and describes ways to categorize products by platform, type of end-product, sophistication of end-product, and authoring metaphor. Discusses products from AimTech, Allegiant, Allen Communication, Asymetrix, Corel, Discovery Systems International, Enigma, Harrow Media, Horizons, Innovus,…

Detail view of the aft section, port side, of the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Detail view of the aft section, port side, of the Orbiter Discovery from an elevated platform in the Vehicle Assembly Building at NASA's Kennedy Space Center. Note the removed Orbiter Maneuvering System/Reaction Control System pod from the base of the vertical stabilizer the strongback ground-support equipment attached to the payload bay door. This view is also a good view of the leading edge and top surface of the Orbiter wing. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Closeup detail of the jackstand head and the attach mechanism ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Close-up detail of the jack-stand head and the attach mechanism connection to the hoist attach point on the starboard forward fuselage of the Orbiter Discovery. Note the profile of the wing intersection with the fuselage and the payload bay door in an open position with the strongback support structure attached. This view was taken from a service platform in the Orbiter Processing Facility at Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

STS-56 Discovery, OV-103, lifts off from KSC LC Pad 39B into darkness

NASA Technical Reports Server (NTRS)

1993-01-01

STS-56 Discovery, Orbiter Vehicle (OV) 103, lifts off from Kennedy Space Center (KSC) Launch Complex (LC) Pad 39B into the early morning darkness at 1:29 am (Eastern Daylight Time (EDT)). OV-103, atop its external tank (ET) and flanked by solid rocket boosters (SRBs), rises above the mobile launcher platform. Exhaust plumes trail from the SRBs. The glow of the SRB / space shuttle main engine (SSME) firings illuminate the fixed service structure (FSS) tower. Trees are silhouetted against the launch fireworks in the foreground.

Computer-aided drug design at Boehringer Ingelheim

NASA Astrophysics Data System (ADS)

Muegge, Ingo; Bergner, Andreas; Kriegl, Jan M.

2017-03-01

Computer-Aided Drug Design (CADD) is an integral part of the drug discovery endeavor at Boehringer Ingelheim (BI). CADD contributes to the evaluation of new therapeutic concepts, identifies small molecule starting points for drug discovery, and develops strategies for optimizing hit and lead compounds. The CADD scientists at BI benefit from the global use and development of both software platforms and computational services. A number of computational techniques developed in-house have significantly changed the way early drug discovery is carried out at BI. In particular, virtual screening in vast chemical spaces, which can be accessed by combinatorial chemistry, has added a new option for the identification of hits in many projects. Recently, a new framework has been implemented allowing fast, interactive predictions of relevant on and off target endpoints and other optimization parameters. In addition to the introduction of this new framework at BI, CADD has been focusing on the enablement of medicinal chemists to independently perform an increasing amount of molecular modeling and design work. This is made possible through the deployment of MOE as a global modeling platform, allowing computational and medicinal chemists to freely share ideas and modeling results. Furthermore, a central communication layer called the computational chemistry framework provides broad access to predictive models and other computational services.

Accessing Nature’s diversity through metabolic engineering and synthetic biology

PubMed Central

King, Jason R.; Edgar, Steven; Qiao, Kangjian; Stephanopoulos, Gregory

2016-01-01

In this perspective, we highlight recent examples and trends in metabolic engineering and synthetic biology that demonstrate the synthetic potential of enzyme and pathway engineering for natural product discovery. In doing so, we introduce natural paradigms of secondary metabolism whereby simple carbon substrates are combined into complex molecules through “scaffold diversification”, and subsequent “derivatization” of these scaffolds is used to synthesize distinct complex natural products. We provide examples in which modern pathway engineering efforts including combinatorial biosynthesis and biological retrosynthesis can be coupled to directed enzyme evolution and rational enzyme engineering to allow access to the “privileged” chemical space of natural products in industry-proven microbes. Finally, we forecast the potential to produce natural product-like discovery platforms in biological systems that are amenable to single-step discovery, validation, and synthesis for streamlined discovery and production of biologically active agents. PMID:27081481

Changing the Scale and Efficiency of Chemical Warfare Countermeasure Discovery Using the Zebrafish

PubMed Central

Peterson, Randall T.; MacRae, Calum A.

2013-01-01

As the scope of potential chemical warfare agents grows rapidly and as the diversity of potential threat scenarios expands with non-state actors, so a need for innovative approaches to countermeasure development has emerged. In the last few years, the utility of the zebrafish as a model organism that is amenable to high-throughput screening has become apparent and this system has been applied to the unbiased discovery of chemical warfare countermeasures. This review summarizes the in vivo screening approach that has been pioneered in the countermeasure discovery arena, and highlights the successes to date as well as the potential challenges in moving the field forward. Importantly, the establishment of a zebrafish platform for countermeasure discovery would offer a rapid response system for the development of antidotes to the continuous stream of new potential chemical warfare agents. PMID:24273586

Detail view of the vertical stabilizer of the Orbiter Discovery ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Detail view of the vertical stabilizer of the Orbiter Discovery Discovery showing the thermal protection system components with the white Advanced Flexible Reusable Surface Insulation (AFSI) Blanket and the black High-temperature Reusable Surface Insulation (HRSI) tiles along the outer edges . The marks seen on the HRSI tiles are injection point marks and holes for the application of waterproofing material. This view also a good detailed view of the two-piece rudder which is used to control the yaw position of orbiter on approach and landing in earth's atmosphere and upon landing the two-piece rudder splays open to both sides of the stabilizer to act as an air brake to help slow the craft to a stop. This view was taken from a service platform in the Orbiter Processing Facility at Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

Plenario: An Open Data Discovery and Exploration Platform for Urban Science

DOE Office of Scientific and Technical Information (OSTI.GOV)

Catlett, Charlie; Malik, Tanu; Goldstein, Brett J.

2014-12-01

The past decade has seen the widespread release of open data concerning city services, conditions, and activities by government bodies and public institutions of all sizes. Hundreds of open data portals now host thousands of datasets of many different types. These new data sources represent enormous po- tential for improved understanding of urban dynamics and processes—and, ultimately, for more livable, efficient, and prosperous communities. However, those who seek to realize this potential quickly discover that discovering and applying those data relevant to any particular question can be extraordinarily dif- ficult, due to decentralized storage, heterogeneous formats, and poor documentation. Inmore » this context, we introduce Plenario, a platform designed to automating time-consuming tasks associated with the discovery, exploration, and application of open city data—and, in so doing, reduce barriers to data use for researchers, policymakers, service providers, journalists, and members of the general public. Key innovations include a geospatial data warehouse that allows data from many sources to be registered into a common spatial and temporal frame; simple and intuitive interfaces that permit rapid discovery and exploration of data subsets pertaining to a particular area and time, regardless of type and source; easy export of such data subsets for further analysis; a user-configurable data ingest framework for automated importing and periodic updating of new datasets into the data warehouse; cloud hosting for elastic scaling and rapid creation of new Plenario instances; and an open source implementation to enable community contributions. We describe here the architecture and implementation of the Plenario platform, discuss lessons learned from its use by several communities, and outline plans for future work.« less

Plenario: A Spatio-Temporal Platform for Discovery and Exploration of Urban Science Data

NASA Astrophysics Data System (ADS)

Engler, W. H.; Malik, T.; Catlett, C.; Foster, I.; Goldstein, B.

2015-12-01

The past decade has seen the widespread release of open data concerning city services, conditions, and activities by government bodies and public institutions of all sizes. Hundreds of open data portals now host thousands of datasets of many different types. These new data sources represent enormous potential for improved understanding of urban dynamics and processes—and, ultimately, for more livable, efficient, and prosperous communities. However, those who seek to realize this potential quickly discover that discovering and applying those data relevant to any particular question can be extraordinarily difficult, due to decentralized storage, heterogeneous formats, and poor documentation. In this context, we introduce Plenario, a platform designed to automating time-consuming tasks associated with the discovery, exploration, and application of open city data—and, in so doing, reduce barriers to data use for researchers, policymakers, service providers, journalists, and members of the general public. Key innovations include a geospatial data warehouse that allows data from many sources to be registered into a common spatial and temporal frame; simple and intuitive interfaces that permit rapid discovery and exploration of data subsets pertaining to a particular area and time, regardless of type and source; easy export of such data subsets for further analysis; a user-configurable data ingest framework for automated importing and periodic updating of new datasets into the data warehouse; cloud hosting for elastic scaling and rapid creation of new Plenario instances; and an open source implementation to enable community contributions. We describe here the architecture and implementation of the Plenario platform, discuss lessons learned from its use by several communities, and outline plans for future work.

Microbial Efflux Pump Inhibition: Tactics and Strategies

PubMed Central

Tegos, George P.; Haynes, Mark; Strouse, J. Jacob; Khan, Mohiuddin Md. T.; Bologa, Cristian G.; Oprea, Tudor I.; Sklar, Larry A.

2013-01-01

Traditional antimicrobials are increasingly suffering from the emergence of multidrug resistance among pathogenic microorganisms. To overcome these deficiencies, a range of novel approaches to control microbial infections are under investigation as potential alternative treatments. Multidrug efflux is a key target of these efforts. Efflux mechanisms are broadly recognized as major components of resistance to many classes of chemotherapeutic agents as well as antimicrobials. Efflux occurs due to the activity of membrane transporter proteins widely known as Multidrug Efflux Systems (MES). They are implicated in a variety of physiological roles other than efflux and identifying natural substrates and inhibitors is an active and expanding research discipline. One plausible alternative is the combination of conventional antimicrobial agents/antibiotics with small molecules that block MES known as multidrug efflux pump inhibitors (EPIs). An array of approaches in academic and industrial research settings, varying from high-throughput screening (HTS) ventures to bioassay guided purification and determination, have yielded a number of promising EPIs in a series of pathogenic systems. This synergistic discovery platform has been exploited in translational directions beyond the potentiation of conventional antimicrobial treatments. This venture attempts to highlight different tactical elements of this platform, identifying the need for highly informative and comprehensive EPI-discovery strategies. Advances in assay development genomics, proteomics as well as the accumulation of bioactivity and structural information regarding MES facilitates the basis for a new discovery era. This platform is expanding drastically. A combination of chemogenomics and chemoinformatics approaches will integrate data mining with virtual and physical HTS ventures and populate the chemical-biological interface with a plethora of novel chemotypes. This comprehensive step will expedite the preclinical development of lead EPIs. PMID:21470111

Data Mining and Knowledge Discovery tools for exploiting big Earth-Observation data

NASA Astrophysics Data System (ADS)

Espinoza Molina, D.; Datcu, M.

2015-04-01

The continuous increase in the size of the archives and in the variety and complexity of Earth-Observation (EO) sensors require new methodologies and tools that allow the end-user to access a large image repository, to extract and to infer knowledge about the patterns hidden in the images, to retrieve dynamically a collection of relevant images, and to support the creation of emerging applications (e.g.: change detection, global monitoring, disaster and risk management, image time series, etc.). In this context, we are concerned with providing a platform for data mining and knowledge discovery content from EO archives. The platform's goal is to implement a communication channel between Payload Ground Segments and the end-user who receives the content of the data coded in an understandable format associated with semantics that is ready for immediate exploitation. It will provide the user with automated tools to explore and understand the content of highly complex images archives. The challenge lies in the extraction of meaningful information and understanding observations of large extended areas, over long periods of time, with a broad variety of EO imaging sensors in synergy with other related measurements and data. The platform is composed of several components such as 1.) ingestion of EO images and related data providing basic features for image analysis, 2.) query engine based on metadata, semantics and image content, 3.) data mining and knowledge discovery tools for supporting the interpretation and understanding of image content, 4.) semantic definition of the image content via machine learning methods. All these components are integrated and supported by a relational database management system, ensuring the integrity and consistency of Terabytes of Earth Observation data.

Case study: impact of technology investment on lead discovery at Bristol-Myers Squibb, 1998-2006.

PubMed

Houston, John G; Banks, Martyn N; Binnie, Alastair; Brenner, Stephen; O'Connell, Jonathan; Petrillo, Edward W

2008-01-01

We review strategic approaches taken over an eight-year period at BMS to implement new high-throughput approaches to lead discovery. Investments in compound management infrastructure and chemistry library production capability allowed significant growth in the size, diversity and quality of the BMS compound collection. Screening platforms were upgraded with robust automated technology to support miniaturized assay formats, while workflows and information handling technologies were streamlined for improved performance. These technology changes drove the need for a supporting organization in which critical engineering, informatics and scientific skills were more strongly represented. Taken together, these investments led to significant improvements in speed and productivity as well a greater impact of screening campaigns on the initiation of new drug discovery programs.

KSC-05PD-0633

NASA Technical Reports Server (NTRS)

2005-01-01

KENNEDY SPACE CENTER, FLA. Space Shuttle Discovery lingers at the foot of Launch Pad 39B in the evening twilight. First motion from the Vehicle Assembly Building was at 2:04 p.m. EDT April 6, and the Shuttle was hard down on the pad at 1:16 a.m. EDT April 7. The Shuttle sits atop a Mobile Launcher Platform transported by a Crawler-Transporter underneath. Launch of Discovery on its Return to Flight mission, STS-114, is targeted for May 15 with a launch window that extends to June 3. During its 12-day mission, Discoverys seven-member crew will test new hardware and techniques to improve Shuttle safety, as well as deliver supplies to the International Space Station. Photo courtesy of Scott Andrews.

Detail view of the lower portion of the vertical stabilizer ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Detail view of the lower portion of the vertical stabilizer of the Orbiter Discovery. The section below the rudder, often referred to as the "stinger", is used to house the orbiter drag chute assembly. The system consisted of a mortar deployed pilot chute, the main drag chute, a controller assembly and an attach/jettison mechanism. This system was a modification to the original design of the Orbiter Discovery to safely reduce the roll to stop distance without adversely affecting the vehicle handling qualities. This view was taken from a service platform in the Orbiter Processing Facility at Kennedy Space Center. - Space Transportation System, Orbiter Discovery (OV-103), Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, Harris County, TX

The Z1 truss is transported to Launch Pad 39A

NASA Technical Reports Server (NTRS)

2000-01-01

At Launch Pad 39A, the payload canister with the Integrated Truss Structure Z1 inside arrives at the spot under the Rotating Service Structure where the canister can be lifted to the Payload Changeout Room. There the Z1 truss will be removed and later transferred to Space Shuttle Discovery's payload bay. Discovery is at right, sitting atop the Mobile Launcher Platform. The Z1 truss is the first of 10 that will become the backbone of the International Space Station, eventually stretching the length of a football field. Along with its companion payload, the third Pressurized Mating Adapter, the Z1 is scheduled to be launched aboard Discovery Oct. 5 at 9:38 p.m. EDT.

KSC-2010-4716

NASA Image and Video Library

2010-09-20

CAPE CANAVERAL, Fla. -- Bathed in bright xenon lights, space shuttle Discovery makes its nighttime trek, known as "rollout," from the Vehicle Assembly Building to Launch Pad 39A at NASA's Kennedy Space Center in Florida. It will take the shuttle, attached to its external fuel tank, twin solid rocket boosters and mobile launcher platform, about six hours to complete the move atop a crawler-transporter. Rollout sets the stage for Discovery's STS-133 crew to practice countdown and launch procedures during the Terminal Countdown Demonstration Test in mid-October. Targeted to liftoff Nov. 1, Discovery will take the Permanent Multipurpose Module (PMM) packed with supplies and critical spare parts, as well as Robonaut 2 (R2) to the International Space Station. Photo credit: NASA/Frankie Martin