Quantitative Proteomics Reveals the Regulatory Networks of Circular RNA CDR1as in Hepatocellular Carcinoma Cells.

PubMed

Yang, Xue; Xiong, Qian; Wu, Ying; Li, Siting; Ge, Feng

2017-10-06

Circular RNAs (circRNAs), a class of widespread endogenous RNAs, play crucial roles in diverse biological processes and are potential biomarkers in diverse human diseases and cancers. Cerebellar-degeneration-related protein 1 antisense RNA (CDR1as), an oncogenic circRNA, is involved in human tumorigenesis and is dysregulated in hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying CDR1as functions in HCC remain unclear. Here we explored the functions of CDR1as and searched for CDR1as-regulated proteins in HCC cells. A quantitative proteomics strategy was employed to globally identify CDR1as-regulated proteins in HCC cells. In total, we identified 330 differentially expressed proteins (DEPs) upon enhanced CDR1as expression in HepG2 cells, indicating that they could be proteins regulated by CDR1as. Bioinformatic analysis revealed that many DEPs were involved in cell proliferation and the cell cycle. Further functional studies of epidermal growth factor receptor (EGFR) found that CDR1as exerts its effects on cell proliferation at least in part through the regulation of EGFR expression. We further confirmed that CDR1as could inhibit the expression of microRNA-7 (miR-7). EGFR is a validated target of miR-7; therefore, CDR1as may exert its function by regulating EGFR expression via targeting miR-7 in HCC cells. Taken together, we revealed novel functions and underlying mechanisms of CDR1as in HCC cells. This study serves as the first proteome-wide analysis of a circRNA-regulated protein in cells and provides a reliable and highly efficient method for globally identifying circRNA-regulated proteins.

Awareness of disease in dementia: Development of a multidimensional rating scale.

PubMed

Dourado, Marcia; Marinho, Valeska; Soares, Cláudia; Engelhardt, Eliasz; Laks, Jerson

2007-01-01

To describe the development of the Assessment Scale of Psychosocial Impact of the Diagnosis of Dementia (ASPIDD), a multidimensional scale to evaluate awareness of disease in dementia. The development of this scale was conducted in four steps. In step one, questions were drawn up after a review of the literature. The second step involved the suggestions offered by a neurologist regarding the skills considered important for the scale. The third step involved the re-writing and review of the domains and questions in the scale followed by a semantic evaluation performed by two independent psychiatrists. Step four consisted of the preliminary study aimed at evaluating the applicability of the ASPIDD. In the semantic evaluation only minor changes were proposed. The preliminary sample had 52 patients, comprising 23 CDR 1 (male=9; female=14) and 29 CDR2 (male=13; female=16).Mean age of patients was 69.7±5.51(CDR1) and 73.6±9.4 (CDR2), and age at onset was 66.4±5.7 years (CDR1) and 68.3±9.3 year (CDR2).Mean schooling was 9.0±4.3 years (CDR1) and 8.8±4.4 years (CDR2). Mean MMSE was 21.0±3.3(CDR1) and 17.6±3.5(CDR2).Mean Cornell was 4.8±2.3(CDR1) and 4.2±1.9 (CDR2). The patient and caregiver dyads were aware of problems, mainly of those related to social, family and affective relations. The higher rates of discrepant responses were found on the awareness of cognitive deficits and changes in ADL. The ASPIDD is a multidimensional instrument to assess awareness of disease among AD patients.

Awareness of disease in dementia: Development of a multidimensional rating scale

PubMed Central

Dourado, Marcia; Marinho, Valeska; Soares, Cláudia; Engelhardt, Eliasz; Laks, Jerson

2007-01-01

Objective To describe the development of the Assessment Scale of Psychosocial Impact of the Diagnosis of Dementia (ASPIDD), a multidimensional scale to evaluate awareness of disease in dementia. Method The development of this scale was conducted in four steps. In step one, questions were drawn up after a review of the literature. The second step involved the suggestions offered by a neurologist regarding the skills considered important for the scale. The third step involved the re-writing and review of the domains and questions in the scale followed by a semantic evaluation performed by two independent psychiatrists. Step four consisted of the preliminary study aimed at evaluating the applicability of the ASPIDD. Results In the semantic evaluation only minor changes were proposed. The preliminary sample had 52 patients, comprising 23 CDR 1 (male=9; female=14) and 29 CDR2 (male=13; female=16).Mean age of patients was 69.7±5.51(CDR1) and 73.6±9.4 (CDR2), and age at onset was 66.4±5.7 years (CDR1) and 68.3±9.3 year (CDR2).Mean schooling was 9.0±4.3 years (CDR1) and 8.8±4.4 years (CDR2). Mean MMSE was 21.0±3.3(CDR1) and 17.6±3.5(CDR2).Mean Cornell was 4.8±2.3(CDR1) and 4.2±1.9 (CDR2). The patient and caregiver dyads were aware of problems, mainly of those related to social, family and affective relations. The higher rates of discrepant responses were found on the awareness of cognitive deficits and changes in ADL. Conclusion The ASPIDD is a multidimensional instrument to assess awareness of disease among AD patients. PMID:29213371

Between Scylla and Charybdis: Delayed mitigation narrows the passage between large-scale CDR and high costs

NASA Astrophysics Data System (ADS)

Strefler, Jessica; Bauer, Nico; Kriegler, Elmar; Popp, Alexander; Giannousakis, Anastasis; Edenhofer, Ottmar

2018-04-01

There are major concerns about the sustainability of large-scale deployment of carbon dioxide removal (CDR) technologies. It is therefore an urgent question to what extent CDR will be needed to implement the long term ambition of the Paris Agreement. Here we show that ambitious near term mitigation significantly decreases CDR requirements to keep the Paris climate targets within reach. Following the nationally determined contributions (NDCs) until 2030 makes 2 °C unachievable without CDR. Reducing 2030 emissions by 20% below NDC levels alleviates the trade-off between high transitional challenges and high CDR deployment. Nevertheless, transitional challenges increase significantly if CDR is constrained to less than 5 Gt CO2 a‑1 in any year. At least 8 Gt CO2 a‑1 CDR are necessary in the long term to achieve 1.5 °C and more than 15 Gt CO2 a‑1 to keep transitional challenges in bounds.

Development of exercise devices to minimize musculoskeletal and cardiovascular deconditioning in microgravity

NASA Technical Reports Server (NTRS)

Schwandt, Douglas F.; Whalen, Robert T.; Watenpaugh, Donald E.; Parazynski, Scott E.; Hargens, Alan R.

1991-01-01

The paper describes three exercise devices, developed at the NASA-Ames Research Center, for maintaining musculoskeletal and cardiovascular fitness in astronauts during extended space flights. These devices represent the following exercise concepts: (1) exercise against LBNP, (2) instrumented dynamic interlimb resistance, and (3) multiple resistive exercise. The three devices complement each other to provide the aerobic and strength training exercises for different situations. All three devices permit eccentric, concentric, and isometric contractions for a variety of exercises.

CAD/CAM (Computer-Aided Design/Computer-Aided Manufacturing) Highlights.

DTIC Science & Technology

1984-10-01

ATTN: AMCRE-C/Ms. Jean Lamb C dr, ATTN: ANCRM-P/Mr. Jerry Gibson Cdr, ATTN: AMCQA-E/Mr. Billings Cdr, ATTN: AMXAM-TL/Technical Library US Army...Sands Missile Range, ATTN: STEWS -TE-TL/Technical Library Cdr, US Military Academy, ATTN: LTC Lanse Leach - - . Cdr, Yuma Proving Grounds, ATTN

Structural classification of CDR-H3 revisited: a lesson in antibody modeling.

PubMed

Kuroda, Daisuke; Shirai, Hiroki; Kobori, Masato; Nakamura, Haruki

2008-11-15

Among the six complementarity-determining regions (CDRs) in the variable domains of an antibody, the third CDR of the heavy chain (CDR-H3), which lies in the center of the antigen-binding site, plays a particularly important role in antigen recognition. CDR-H3 shows significant variability in its length, sequence, and structure. Although difficult, model building of this segment is the most critical step in antibody modeling. Since our first proposal of the "H3-rules," which classify CDR-H3 structure based on amino acid sequence, the number of experimentally determined antibody structures has increased. Here, we revise these H3-rules and propose an improved classification scheme for CDR-H3 structure modeling. In addition, we determine the common features of CDR-H3 in antibody drugs as well as discuss the concept of "antibody druggability," which can be applied as an indicator of antibody evaluation during drug discovery.

Beyond CDR-grafting: Structure-guided humanization of framework and CDR regions of an anti-myostatin antibody.

PubMed

Apgar, James R; Mader, Michelle; Agostinelli, Rita; Benard, Susan; Bialek, Peter; Johnson, Mark; Gao, Yijie; Krebs, Mark; Owens, Jane; Parris, Kevin; St Andre, Michael; Svenson, Kris; Morris, Carl; Tchistiakova, Lioudmila

2016-10-01

Antibodies are an important class of biotherapeutics that offer specificity to their antigen, long half-life, effector function interaction and good manufacturability. The immunogenicity of non-human-derived antibodies, which can be a major limitation to development, has been partially overcome by humanization through complementarity-determining region (CDR) grafting onto human acceptor frameworks. The retention of foreign content in the CDR regions, however, is still a potential immunogenic liability. Here, we describe the humanization of an anti-myostatin antibody utilizing a 2-step process of traditional CDR-grafting onto a human acceptor framework, followed by a structure-guided approach to further reduce the murine content of CDR-grafted antibodies. To accomplish this, we solved the co-crystal structures of myostatin with the chimeric (Protein Databank (PDB) id 5F3B) and CDR-grafted anti-myostatin antibody (PDB id 5F3H), allowing us to computationally predict the structurally important CDR residues as well as those making significant contacts with the antigen. Structure-based rational design enabled further germlining of the CDR-grafted antibody, reducing the murine content of the antibody without affecting antigen binding. The overall "humanness" was increased for both the light and heavy chain variable regions.

Beyond CDR-grafting: Structure-guided humanization of framework and CDR regions of an anti-myostatin antibody

PubMed Central

Apgar, James R.; Mader, Michelle; Agostinelli, Rita; Benard, Susan; Bialek, Peter; Johnson, Mark; Gao, Yijie; Krebs, Mark; Owens, Jane; Parris, Kevin; St. Andre, Michael; Svenson, Kris; Morris, Carl; Tchistiakova, Lioudmila

2016-01-01

ABSTRACT Antibodies are an important class of biotherapeutics that offer specificity to their antigen, long half-life, effector function interaction and good manufacturability. The immunogenicity of non-human-derived antibodies, which can be a major limitation to development, has been partially overcome by humanization through complementarity-determining region (CDR) grafting onto human acceptor frameworks. The retention of foreign content in the CDR regions, however, is still a potential immunogenic liability. Here, we describe the humanization of an anti-myostatin antibody utilizing a 2-step process of traditional CDR-grafting onto a human acceptor framework, followed by a structure-guided approach to further reduce the murine content of CDR-grafted antibodies. To accomplish this, we solved the co-crystal structures of myostatin with the chimeric (Protein Databank (PDB) id 5F3B) and CDR-grafted anti-myostatin antibody (PDB id 5F3H), allowing us to computationally predict the structurally important CDR residues as well as those making significant contacts with the antigen. Structure-based rational design enabled further germlining of the CDR-grafted antibody, reducing the murine content of the antibody without affecting antigen binding. The overall “humanness” was increased for both the light and heavy chain variable regions. PMID:27625211

Overexpression of pigeonpea stress-induced cold and drought regulatory gene (CcCDR) confers drought, salt, and cold tolerance in Arabidopsis

PubMed Central

Tamirisa, Srinath; Vudem, Dashavantha Reddy; Khareedu, Venkateswara Rao

2014-01-01

A potent cold and drought regulatory protein-encoding gene (CcCDR) was isolated from the subtractive cDNA library of pigeonpea plants subjected to drought stress. CcCDR was induced by different abiotic stress conditions in pigeonpea. Overexpression of CcCDR in Arabidopsis thaliana imparted enhanced tolerance against major abiotic stresses, namely drought, salinity, and low temperature, as evidenced by increased biomass, root length, and chlorophyll content. Transgenic plants also showed increased levels of antioxidant enzymes, proline, and reducing sugars under stress conditions. Furthermore, CcCDR-transgenic plants showed enhanced relative water content, osmotic potential, and cell membrane stability, as well as hypersensitivity to abscisic acid (ABA) as compared with control plants. Localization studies confirmed that CcCDR could enter the nucleus, as revealed by intense fluorescence, indicating its possible interaction with various nuclear proteins. Microarray analysis revealed that 1780 genes were up-regulated in CcCDR-transgenics compared with wild-type plants. Real-time PCR analysis on selected stress-responsive genes, involved in ABA-dependent and -independent signalling networks, revealed higher expression levels in transgenic plants, suggesting that CcCDR acts upstream of these genes. The overall results demonstrate the explicit role of CcCDR in conferring multiple abiotic stress tolerance at the whole-plant level. The multifunctional CcCDR seems promising as a prime candidate gene for enhancing abiotic stress tolerance in diverse plants. PMID:24868035

33 Years of Near-Global Daily Precipitation from Multisatellite Observations and its Application to Drought Monitoring

NASA Astrophysics Data System (ADS)

Ashouri, H.; Hsu, K.; Sorooshian, S.; Braithwaite, D.; Knapp, K. R.; Cecil, L. D.

2013-12-01

PERSIANN Climate Data Record (PERSIANN-CDR) is a new retrospective satellite-based precipitation data set that is constructed for long-term hydrological and climate studies. The PERSIANN-CDR is a near-global (60°S-60°N) long-term (1980-2012), multi-satellite, high-resolution precipitation product that provides rain rate estimates at 0.25° and daily spatiotemporal resolution. PERSIANN-CDR is aimed at addressing the need for a consistent, long-term, high resolution precipitation data set for studying the spatial and temporal variations and changes of precipitation patterns, particularly in a scale relevant to climate extremes at the global scale. PERSIANN-CDR is generated from the PERSIANN algorithm using GridSat-B1 infrared data from the International Satellite Cloud Climatology Project (ISCCP). PERSIANN-CDR is adjusted using the Global Precipitation Climatology Project (GPCP) monthly precipitation to maintain consistency of two data sets at 2.5° monthly scale throughout the entire reconstruction period. PERSIANN-CDR daily precipitation data demonstrates considerable consistency with both GPCP monthly and GPCP 1DD precipitation products. Verification studies over Hurricane Katrina show that PERSIANN-CDR has a good agreement with NCEP Stage IV radar data, noting that PERSIANN-CDR has better spatial coverage. In addition, the Probability Density Function (PDF) of PERSIANN-CDR over the contiguous United States was compared with the PDFs extracted from CPC gauge data and the TMPA precipitation product. The experiment also shows good agreement of the PDF of PERSIANN-CDR with the PDFs of TMPA and CPC gauge data. The application of PERSIANN-CDR in regional and global drought monitoring is investigated. Consisting of more than three decades of high-resolution precipitation data, PERSIANN-CDR makes us capable of long-term assessment of droughts at a higher resolution (0.25°) than previously possible. The results will be presented at the meeting.

The effect of parental factors in children with large cup-to-disc ratios.

PubMed

Park, Hae-Young Lopilly; Ha, Min Ji; Shin, Sun Young

2017-01-01

To investigate large cup-to-disc ratios (CDR) in children and to determine the relationship between parental CDR and clinical characteristics associated with glaucoma. Two hundred thirty six children aged 6 to 12 years with CDR ≥ 0.6 were enrolled in this study. Subjects were classified into two groups based on parental CDR: disc suspect children with disc suspect (CDR ≥0.6) parents and disc suspect children without disc suspect parents. Ocular variables were compared between the two groups. Of the 236 disc suspect children, 100 (42.4%) had at least one disc suspect parent. Intraocular pressure (IOP) was higher in disc suspect children with disc suspect parents (16.52±2.66 mmHg) than in disc suspect children without disc suspect parents (14.38±2.30 mmHg, p = 0.023). In the group with disc suspect parents, vertical CDR significantly correlated with IOP (R = -0.325, p = 0.001), average retinal nerve fiber layer (RNFL) thickness (R = -0.319, p = 0.001), rim area (R = -0.740, p = 0.001), and cup volume (R = 0.499, p = 0.001). However, spherical equivalent (R = 0.333, p = 0.001), AL (R = -0.223, p = 0.009), and disc area (R = 0.325, p = 0.001) significantly correlated with vertical CDR in disc suspect children without disc suspect parents, in contrast to those with disc suspect parents. Larger vertical CDR was associated with the presence of disc suspect parents (p = 0.001), larger disc area (p = 0.001), thinner rim area (p = 0.001), larger average CDR (p = 0.001), and larger cup volume (p = 0.021). Family history of large CDR was a significant factor associated with large vertical CDR in children. In children with disc suspect parents, there were significant correlations between IOP and average RNFL thickness and vertical CDR.

Pseudomonas aeruginosa uses a cyclic-di-GMP-regulated adhesin to reinforce the biofilm extracellular matrix

PubMed Central

Borlee, Bradley R; Goldman, Aaron D; Murakami, Keiji; Samudrala, Ram; Wozniak, Daniel J; Parsek, Matthew R

2010-01-01

Pseudomonas aeruginosa, the principal pathogen of cystic fibrosis patients, forms antibiotic-resistant biofilms promoting chronic colonization of the airways. The extracellular (EPS) matrix is a crucial component of biofilms that provides the community multiple benefits. Recent work suggests that the secondary messenger, cyclic-di-GMP, promotes biofilm formation. An analysis of factors specifically expressed in P. aeruginosa under conditions of elevated c-di-GMP, revealed functions involved in the production and maintenance of the biofilm extracellular matrix. We have characterized one of these components, encoded by the PA4625 gene, as a putative adhesin and designated it cdrA. CdrA shares structural similarities to extracellular adhesins that belong to two-partner secretion systems. The cdrA gene is in a two gene operon that also encodes a putative outer membrane transporter, CdrB. The cdrA gene encodes a 220 KDa protein that is predicted to be rod-shaped protein harbouring a β-helix structural motif. Western analysis indicates that the CdrA is produced as a 220 kDa proprotein and processed to 150 kDa before secretion into the extracellular medium. We demonstrated that cdrAB expression is minimal in liquid culture, but is elevated in biofilm cultures. CdrAB expression was found to promote biofilm formation and auto-aggregation in liquid culture. Aggregation mediated by CdrA is dependent on the Psl polysaccharide and can be disrupted by adding mannose, a key structural component of Psl. Immunoprecipitation of Psl present in culture supernatants resulted in co-immunoprecipitation of CdrA, providing additional evidence that CdrA directly binds to Psl. A mutation in cdrA caused a decrease in biofilm biomass and resulted in the formation of biofilms exhibiting decreased structural integrity. Psl-specific lectin staining suggests that CdrA either cross-links Psl polysaccharide polymers and/or tethers Psl to the cells, resulting in increased biofilm structural stability. Thus, this study identifies a key protein structural component of the P. aeruginosa EPS matrix. PMID:20088866

In vitro biomechanical comparison after fixed- and mobile-core artificial cervical disc replacement versus fusion

PubMed Central

Lou, Jigang; Li, Yuanchao; Wang, Beiyu; Meng, Yang; Wu, Tingkui; Liu, Hao

2017-01-01

Abstract In vitro biomechanical analysis after cervical disc replacement (CDR) with a novel artificial disc prosthesis (mobile core) was conducted and compared with the intact model, simulated fusion, and CDR with a fixed-core prosthesis. The purpose of this experimental study was to analyze the biomechanical changes after CDR with a novel prosthesis and the differences between fixed- and mobile-core prostheses. Six human cadaveric C2–C7 specimens were biomechanically tested sequentially in 4 different spinal models: intact specimens, simulated fusion, CDR with a fixed-core prosthesis (Discover, DePuy), and CDR with a mobile-core prosthesis (Pretic-I, Trauson). Moments up to 2 Nm with a 75 N follower load were applied in flexion–extension, left and right lateral bending, and left and right axial rotation. The total range of motion (ROM), segmental ROM, and adjacent intradiscal pressure (IDP) were calculated and analyzed in 4 different spinal models, as well as the differences between 2 disc prostheses. Compared with the intact specimens, the total ROM, segmental ROM, and IDP at the adjacent segments showed no significant difference after arthroplasty. Moreover, CDR with a mobile-core prosthesis presented a little higher values of target segment (C5/6) and total ROM than CDR with a fixed-core prosthesis (P > .05). Besides, the difference in IDP at C4/5 after CDR with 2 prostheses was without statistical significance in all the directions of motion. However, the IDP at C6/7 after CDR with a mobile-core prosthesis was lower than CDR with a fixed-core prosthesis in flexion, extension, and lateral bending, with significant difference (P < .05), but not under axial rotation. CDR with a novel prosthesis was effective to maintain the ROM at the target segment and did not affect the ROM and IDP at the adjacent segments. Moreover, CDR with a mobile-core prosthesis presented a little higher values of target segment and total ROM, but lower IDP at the inferior adjacent segment than CDR with a fixed-core prosthesis. PMID:29019902

Biomechanical Modeling of the Deadlift Exercise on the HULK Device to Improve the Efficacy of Resistive Exercise Microgravity Countermeasures

NASA Technical Reports Server (NTRS)

Jagodnik, K. M.; Thompson, W. K.; Gallo, C. A.; Crentsil, L.; Funk, J. H.; Funk, N. W.; Perusek, G. P.; Sheehan, C. C.; Lewandowski, B. E.

2016-01-01

Extended spaceflight typically results in the loss of muscular strength and bone density due to exposure to microgravity. Resistive exercise countermeasures have been developed to maintain musculoskeletal health during spaceflight. The Advanced Resistive Exercise Device (ARED) is the "gold standard" of available devices; however, its footprint and volume are too large for use in space capsules employed in exploration missions. The Hybrid Ultimate Lifting Kit (HULK) device, with its smaller footprint, is a prototype exercise device for exploration missions. This work models the deadlift exercise being performed on the HULK device using biomechanical simulation, with the long-term goal to improve and optimize astronauts' exercise prescriptions, to maximize the benefit of exercise while minimizing time and effort invested.

Expression of the CDR1 efflux pump in clinical Candida albicans isolates is controlled by a negative regulatory element

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

Gaur, Naseem Akhtar; Manoharlal, Raman; Saini, Preeti

2005-06-24

Resistance to azole antifungal drugs in clinical isolates of the human fungal pathogen Candida albicans is often caused by constitutive overexpression of the CDR1 gene, which encodes a multidrug efflux pump of the ABC transporter superfamily. To understand the relevance of a recently identified negative regulatory element (NRE) in the CDR1 promoter for the control of CDR1 expression in the clinical scenario, we investigated the effect of mutation or deletion of the NRE on CDR1 expression in two matched pairs of azole-sensitive and resistant clinical isolates of C. albicans. Expression of GFP or lacZ reporter genes from the wild typemore » CDR1 promoter was much higher in the azole-resistant C. albicans isolates than in the azole-susceptible isolates, reflecting the known differences in CDR1 expression in these strains. Deletion or mutation of the NRE resulted in enhanced reporter gene expression in azole-sensitive strains, but did not further increase the already high CDR1 promoter activity in the azole-resistant strains. In agreement with these findings, electrophoretic mobility shift assays showed a reduced binding to the NRE of nuclear extracts from the resistant C. albicans isolates as compared with extracts from the sensitive isolates. These results demonstrate that the NRE is involved in maintaining CDR1 expression at basal levels and that this repression is overcome in azole-resistant clinical C. albicans isolates, resulting in constitutive CDR1 overexpression and concomitant drug resistance.« less

Association between late-onset depression and incident dementia in Chinese older persons.

PubMed

Tam, C W C; Lam, L C W

2013-12-01

OBJECTIVE. Previous studies have shown that depression is a precursor / prodrome or susceptible state for the development of dementia. This study aimed to examine the relationship between late-onset depression and subsequent cognitive and functional decline in a cohort of non-demented older Chinese persons at their 2-year follow-up and investigate for possible predictors of cognitive decline. METHODS. A total of 81 depressed subjects and 468 non-depressed community controls were recruited. RESULTS. Subjects with late-onset depression showed significantly more incident Clinical Dementia Rating (CDR) scale decline (odds ratio = 3.87, 95% confidence interval = 2.23-6.70) and dementia (odds ratio = 3.44, 95% confidence interval = 1.75-6.77) than those without depression. A higher proportion of depressed CDR 0 subjects had CDR and functional decline than their non-depressed counterparts. Depressed CDR 0.5 subjects had significantly higher rates of functional decline and lower rates of improvement in CDR than their non-depressed counterparts. CONCLUSION. Diagnosis of depression was a robust predictor of incident very mild dementia (i.e. CDR of 0.5) and depression severity was a predictor of progression to dementia from CDR of 0.5. The association between depression and the risk of CDR decline and dementia was observed in non-demented Chinese subjects. Depression was also associated with persistent mild cognitive deficits in CDR 0.5 subjects.

Bias-correction of PERSIANN-CDR Extreme Precipitation Estimates Over the United States

NASA Astrophysics Data System (ADS)

Faridzad, M.; Yang, T.; Hsu, K. L.; Sorooshian, S.

2017-12-01

Ground-based precipitation measurements can be sparse or even nonexistent over remote regions which make it difficult for extreme event analysis. PERSIANN-CDR (CDR), with 30+ years of daily rainfall information, provides an opportunity to study precipitation for regions where ground measurements are limited. In this study, the use of CDR annual extreme precipitation for frequency analysis of extreme events over limited/ungauged basins is explored. The adjustment of CDR is implemented in two steps: (1) Calculated CDR bias correction factor at limited gauge locations based on the linear regression analysis of gauge and CDR annual maxima precipitation; and (2) Extend the bias correction factor to the locations where gauges are not available. The correction factors are estimated at gauge sites over various catchments, elevation zones, and climate regions and the results were generalized to ungauged sites based on regional and climatic similarity. Case studies were conducted on 20 basins with diverse climate and altitudes in the Eastern and Western US. Cross-validation reveals that the bias correction factors estimated on limited calibration data can be extended to regions with similar characteristics. The adjusted CDR estimates also outperform gauge interpolation on validation sites consistently. It is suggested that the CDR with bias adjustment has a potential for study frequency analysis of extreme events, especially for regions with limited gauge observations.

Construction of a scFv Library with Synthetic, Non-combinatorial CDR Diversity.

PubMed

Bai, Xuelian; Shim, Hyunbo

2017-01-01

Many large synthetic antibody libraries have been designed, constructed, and successfully generated high-quality antibodies suitable for various demanding applications. While synthetic antibody libraries have many advantages such as optimized framework sequences and a broader sequence landscape than natural antibodies, their sequence diversities typically are generated by random combinatorial synthetic processes which cause the incorporation of many undesired CDR sequences. Here, we describe the construction of a synthetic scFv library using oligonucleotide mixtures that contain predefined, non-combinatorially synthesized CDR sequences. Each CDR is first inserted to a master scFv framework sequence and the resulting single-CDR libraries are subjected to a round of proofread panning. The proofread CDR sequences are assembled to produce the final scFv library with six diversified CDRs.

Exer-Genie(Registered Trademark) Exercise Device Hardware Evaluation

NASA Technical Reports Server (NTRS)

Schaffner, Grant; Sharp,Carwyn; Stroud, Leah

2008-01-01

An engineering evaluation was performed on the ExerGenie(r) exercise device to quantify its capabilities and limitations to address questions from the Constellation Program. Three subjects performed rowing and circuit training sessions to assess the suitability of the device for aerobic exercise. Three subjects performed a resistive exercise session to assess the suitability of the device for resistive exercise. Since 1 subject performed both aerobic and resistive exercise sessions, a total of 5 subjects participated.

Multiplexed Immunoassay Panel Identifies Novel CSF Biomarkers for Alzheimer's Disease Diagnosis and Prognosis

PubMed Central

Craig-Schapiro, Rebecca; Kuhn, Max; Xiong, Chengjie; Pickering, Eve H.; Liu, Jingxia; Misko, Thomas P.; Perrin, Richard J.; Bales, Kelly R.; Soares, Holly; Fagan, Anne M.; Holtzman, David M.

2011-01-01

Background Clinicopathological studies suggest that Alzheimer's disease (AD) pathology begins ∼10–15 years before the resulting cognitive impairment draws medical attention. Biomarkers that can detect AD pathology in its early stages and predict dementia onset would, therefore, be invaluable for patient care and efficient clinical trial design. We utilized a targeted proteomics approach to discover novel cerebrospinal fluid (CSF) biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers (Aβ42, tau, p-tau181). Methods and Findings Using a multiplexed Luminex platform, 190 analytes were measured in 333 CSF samples from cognitively normal (Clinical Dementia Rating [CDR] 0), very mildly demented (CDR 0.5), and mildly demented (CDR 1) individuals. Mean levels of 37 analytes (12 after Bonferroni correction) were found to differ between CDR 0 and CDR>0 groups. Receiver-operating characteristic curve analyses revealed that small combinations of a subset of these markers (cystatin C, VEGF, TRAIL-R3, PAI-1, PP, NT-proBNP, MMP-10, MIF, GRO-α, fibrinogen, FAS, eotaxin-3) enhanced the ability of the best-performing established CSF biomarker, the tau/Aβ42 ratio, to discriminate CDR>0 from CDR 0 individuals. Multiple machine learning algorithms likewise showed that the novel biomarker panels improved the diagnostic performance of the current leading biomarkers. Importantly, most of the markers that best discriminated CDR 0 from CDR>0 individuals in the more targeted ROC analyses were also identified as top predictors in the machine learning models, reconfirming their potential as biomarkers for early-stage AD. Cox proportional hazards models demonstrated that an optimal panel of markers for predicting risk of developing cognitive impairment (CDR 0 to CDR>0 conversion) consisted of calbindin, Aβ42, and age. Conclusions/Significance Using a targeted proteomic screen, we identified novel candidate biomarkers that complement the best current CSF biomarkers for distinguishing very mildly/mildly demented from cognitively normal individuals. Additionally, we identified a novel biomarker (calbindin) with significant prognostic potential. PMID:21526197

Candida Drug Resistance Protein 1, a Major Multidrug ATP Binding Cassette Transporter of Candida albicans, Translocates Fluorescent Phospholipids in a Reconstituted System†

PubMed Central

Shukla, Sudhanshu; Rai, Versha; Saini, Preeti; Banerjee, Dibyendu; Menon, Anant K.; Prasad, Rajendra

2008-01-01

Candida albicans drug resistance protein 1 (Cdr1p), an ATP-dependent drug efflux pump, contributes to multidrug resistance in Candida-infected immunocompromised patients. Previous cell-based assays suggested that Cdr1p also acts as a phospholipid translocator. To investigate this, we reconstituted purified Cdr1p into sealed membrane vesicles. Comparison of the ATPase activities of sealed and permeabilized proteoliposomes indicated that Cdr1p was asymmetrically reconstituted such that ~70% of the molecules had their ATP binding sites accessible to the extravesicular space. Fluorescent glycerophospholipids were incorporated into the outer leaflet of the proteoliposomes, and their transport into the inner leaflet was tracked with a quenching assay using membrane-impermeant dithionite. We observed ATP-dependent transport of the fluorescent lipids into the inner leaflet of the vesicles. With ~6 molecules of Cdr1p per vesicle on average, the half-time to reach the maximal extent of transport was ~15 min. Transport was reduced in vesicles reconstituted with Cdr1p variants with impaired ATPase activity and could be competed out to different levels by a molar excess of drugs such as fluconazole and miconazole that are known to be effluxed by Cdr1p. Transport was not affected by ampicillin, a compound that is not effluxed by Cdr1p. Our results suggest a direct link between the ability of Cdr1p to translocate fluorescent phospholipids and efflux drugs. We note that only a few members of the ABC superfamily of Candida have a well-defined role as drug exporters; thus, lipid translocation mediated by Cdr1p could reflect its cellular function. PMID:17924650

Overlapping hotspots in CDRs are critical sites for V region diversification.

PubMed

Wei, Lirong; Chahwan, Richard; Wang, Shanzhi; Wang, Xiaohua; Pham, Phuong T; Goodman, Myron F; Bergman, Aviv; Scharff, Matthew D; MacCarthy, Thomas

2015-02-17

Activation-induced deaminase (AID) mediates the somatic hypermutation (SHM) of Ig variable (V) regions that is required for the affinity maturation of the antibody response. An intensive analysis of a published database of somatic hypermutations that arose in the IGHV3-23*01 human V region expressed in vivo by human memory B cells revealed that the focus of mutations in complementary determining region (CDR)1 and CDR2 coincided with a combination of overlapping AGCT hotspots, the absence of AID cold spots, and an abundance of polymerase eta hotspots. If the overlapping hotspots in the CDR1 or CDR2 did not undergo mutation, the frequency of mutations throughout the V region was reduced. To model this result, we examined the mutation of the human IGHV3-23*01 biochemically and in the endogenous heavy chain locus of Ramos B cells. Deep sequencing revealed that IGHV3-23*01 in Ramos cells accumulates AID-induced mutations primarily in the AGCT in CDR2, which was also the most frequent site of mutation in vivo. Replacing the overlapping hotspots in CDR1 and CDR2 with neutral or cold motifs resulted in a reduction in mutations within the modified motifs and, to some degree, throughout the V region. In addition, some of the overlapping hotspots in the CDRs were at sites in which replacement mutations could change the structure of the CDR loops. Our analysis suggests that the local sequence environment of the V region, and especially of the CDR1 and CDR2, is highly evolved to recruit mutations to key residues in the CDRs of the IgV region.

Assessment of Volumetric-Modulated Arc Therapy for Constant and Variable Dose Rates

PubMed Central

De Ornelas-Couto, Mariluz; Mihaylov, Ivaylo; Dogan, Nesrin

2017-01-01

Purpose: The aim of this study is to compare the effects of dose rate on volumetric-modulated arc therapy plans to determine optimal dose rates for prostate and head and neck (HN) cases. Materials and Methods: Ten prostate and ten HN cases were retrospectively studied. For each case, seven plans were generated: one variable dose rate (VDR) and six constant dose rate (CDR) (100–600 monitor units [MUs]/min) plans. Prescription doses were: 80 Gy to planning target volume (PTV) for the prostate cases, and 70, 60, and 54 Gy to PTV1, PTV2, and PTV3, respectively, for HN cases. Plans were normalized to 95% of the PTV and PTV1, respectively, with the prescription dose. Plans were assessed using Dose-Volume-Histogram metrics, homogeneity index, conformity index, MUs, and delivery time. Results: For the prostate cases, significant differences were found for rectum D35 between VDR and all CDR plans, except CDR500. Furthermore, VDR was significantly different than CDR100 and 200 for bladder D50. Delivery time for all CDR plans and MUs for CDR400–600 were significantly higher when compared to VDR. HN cases showed significant differences between VDR and CDR100, 500 and 600 for D2 to the cord and brainstem. Significant differences were found for delivery time and MUs for all CDR plans, except CDR100 for number of MUs. Conclusion: The most significant differences were observed in delivery time and number of MUs. All-in-all, the best CDR for prostate cases was found to be 300 MUs/min and 200 or 300 MUs/min for HN cases. However, VDR plans are still the choice in terms of MU efficiency and plan quality. PMID:29296033

A Sensemaking Visualization Tool with Military Doctrinal Elements

DTIC Science & Technology

2008-06-01

LeadUnderstand CDR / Staff ART / Science In short, we need to develop an integrated approach for the understanding (framing) and visualizing, describing...directing, assessing, and reframing of unified operations. Staff Running Estimates t ff i i Visualize CDR / Staff ART / Science •Planning guidance...Planning guidance •Cdr ’s Intent Describe CDR / Staff ART / Science •Plans & Orders •Preparation •Plans & Orders •Preparation •Execution WF

PERSIANN-CDR Daily Precipitation Dataset for Hydrologic Applications and Climate Studies.

NASA Astrophysics Data System (ADS)

Sorooshian, S.; Hsu, K. L.; Ashouri, H.; Braithwaite, D.; Nguyen, P.; Thorstensen, A. R.

2015-12-01

Precipitation Estimation from Remotely Sensed Information using Artificial Neural Network - Climate Data Record (PERSIANN-CDR) is a newly developed and released dataset which covers more than 3 decades (01/01/1983 - 03/31/2015 to date) of daily precipitation estimations at 0.25° resolution for 60°S-60°N latitude band. PERSIANN-CDR is processed using the archive of the Gridded Satellite IRWIN CDR (GridSat-B1) from the International Satellite Cloud Climatology Project (ISCCP), and the Global Precipitation Climatology Project (GPCP) 2.5° monthly product for bias correction. The dataset has been released and made available for public access through NOAA's National Centers for Environmental Information (NCEI) (http://www1.ncdc.noaa.gov/pub/data/sds/cdr/CDRs/PERSIANN/Overview.pdf). PERSIANN-CDR has already shown its usefulness for a wide range of applications, including climate variability and change monitoring, hydrologic applications, and water resources system planning and management. This precipitation CDR data has also been used in studying the behavior of historical extreme precipitation events. Demonstration of PERSIANN-CDR data in detecting trends and variability of precipitation over the past 30 years, the potential usefulness of the dataset for evaluating climate model performance relevant to precipitation in retrospective mode, will be presented.

The complementarity-determining region sequences in IgY antivenom hypervariable regions.

PubMed

da Rocha, David Gitirana; Fernandez, Jorge Hernandez; de Almeida, Claudia Maria Costa; da Silva, Claudia Letícia; Magnoli, Fabio Carlos; da Silva, Osmair Élder; da Silva, Wilmar Dias

2017-08-01

The data presented in this article are related to the research article entitled "Development of IgY antibodies against anti-snake toxins endowed with highly lethal neutralizing activity" (da Rocha et al., 2017) [1]. Complementarity-determining region (CDR) sequences are variable antibody (Ab) sequences that respond with specificity, duration and strength to identify and bind to antigen (Ag) epitopes. B lymphocytes isolated from hens immunized with Bitis arietans (Ba) and anti- Crotalus durissus terrificus (Cdt) venoms and expressing high specificity, affinity and toxicity neutralizing antibody titers were used as DNA sources. The VLF1, CDR1, CDR2, VLR1 and CDR3 sequences were validated by BLASTp, and values corresponding to IgY V L and V H anti-Ba or anti-Cdt venoms were identified, registered [ Gallus gallus IgY Fv Light chain (GU815099)/ Gallus gallus IgY Fv Heavy chain (GU815098)] and used for molecular modeling of IgY scFv anti-Ba. The resulting CDR1, CDR2 and CDR3 sequences were combined to construct the three - dimensional structure of the Ab paratope.

The Process of Sensemaking in Complex Human Endeavors

DTIC Science & Technology

2008-06-01

encompassing Joint, Interagency, and Multinational capabilities. The Art and Science of Battle Command LeadUnderstand CDR / Staff ART / Science In short, we...operations. Staff Running Estimates t ff i i Visualize CDR / Staff ART / Science •Planning guidance •Planning guidance •Cdr ’s Intent Describe CDR...Staff ART / Science •Plans & Orders •Preparation •Plans & Orders •Preparation •Execution WF • Intelligence •Maneuver •Fire Support • Protection

U.S. Army Training and Doctrine Command, 1973-1982: A Case Study in Successful Peacetime Military Reform

DTIC Science & Technology

2003-01-01

Member LTC Yvonne Doll, M.S...Tarpley, Cdr, US Army Infantry Center; Donn A. Starry, Cdr, US Army Armor Center; CG LeVan, Cdr, US Army Air Defense Center; William J. Maddox , Cdr, US...Ott, LeVan, Starry, Parfitt, Myer, and Maddox entitled “Field Manuals,” 10 October 1974, in DePuy Papers, MHI. 107DePuy, Letter to General Fred C

Development of the expressed Ig CDR-H3 repertoire is marked by focusing of constraints in length, amino acid use, and charge that are first established in early B cell progenitors.

PubMed

Ivanov, Ivaylo I; Schelonka, Robert L; Zhuang, Yingxin; Gartland, G Larry; Zemlin, Michael; Schroeder, Harry W

2005-06-15

To gain insight into the mechanisms that regulate the development of the H chain CDR3 (CDR-H3), we used the scheme of Hardy to sort mouse bone marrow B lineage cells into progenitor, immature, and mature B cell fractions, and then performed sequence analysis on V(H)7183-containing Cmu transcripts. The essential architecture of the CDR-H3 repertoire observed in the mature B cell fraction F was already established in the early pre-B cell fraction C. These architectural features include V(H) gene segment use preference, D(H) family usage, J(H) rank order, predicted structures of the CDR-H3 base and loop, and the amino acid composition and average hydrophobicity of the CDR-H3 loop. With development, the repertoire was focused by eliminating outliers to what appears to be a preferred repertoire in terms of length, amino acid composition, and average hydrophobicity. Unlike humans, the average length of CDR-H3 increased during development. The majority of this increase came from enhanced preservation of J(H) sequence. This was associated with an increase in the prevalence of tyrosine. With an accompanying increase in glycine, a shift in hydrophobicity was observed in the CDR-H3 loop from near neutral in fraction C (-0.08 +/- 0.03) to mild hydrophilic in fraction F (-0.17 +/- 0.02). Fundamental constraints on the sequence and structure of CDR-H3 are thus established before surface IgM expression.

Staging dementia using Clinical Dementia Rating Scale Sum of Boxes scores: a Texas Alzheimer's research consortium study.

PubMed

O'Bryant, Sid E; Waring, Stephen C; Cullum, C Munro; Hall, James; Lacritz, Laura; Massman, Paul J; Lupo, Philip J; Reisch, Joan S; Doody, Rachelle

2008-08-01

The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score is commonly used, although the utility regarding this score in staging dementia severity is not well established. To investigate the effectiveness of CDR-SOB scores in staging dementia severity compared with the global CDR score. Retrospective study. Texas Alzheimer's Research Consortium minimum data set cohort. A total of 1577 participants (110 controls, 202 patients with mild cognitive impairment, and 1265 patients with probable Alzheimer disease) were available for analysis. Receiver operating characteristic curves were generated from a derivation sample to determine optimal cutoff scores and ranges, which were then applied to the validation sample. Optimal ranges of CDR-SOB scores corresponding to the global CDR scores were 0.5 to 4.0 for a global score of 0.5, 4.5 to 9.0 for a global score of 1.0, 9.5 to 15.5 for a global score of 2.0, and 16.0 to 18.0 for a global score of 3.0. When applied to the validation sample, kappa scores ranged from 0.86 to 0.94 (P < .001 for all), with 93.0% of the participants falling within the new staging categories. The CDR-SOB score compares well with the global CDR score for dementia staging. Owing to the increased range of values, the CDR-SOB score offers several advantages over the global score, including increased utility in tracking changes within and between stages of dementia severity. Interpretive guidelines for CDR-SOB scores are provided.

CDR3 analysis of TCR Vβ repertoire of CD8⁺ T cells from chickens infected with Eimeria maxima.

PubMed

Ren, Chao; Yin, Guangwen; Qin, Mei; Suo, Jingxia; Lv, Qiyao; Xie, Li; Wang, Yunzhou; Huang, Xiaoxi; Chen, Yuchen; Liu, Xianyong; Suo, Xun

2014-08-01

CD8(+) T cells play a major role in the immune protection of host against the reinfection of Eimeria maxima, the most immunogenic species of eimerian parasites in chickens. To explore the dominant complementarity-determining regions 3 (CDR3) of CD8(+) T cell populations induced by the infection of this parasite, sequence analysis was performed in this study for CDR3 of CD8(+) T cells from E. maxima infected chickens. After 5 days post the third or forth infection, intraepithelial lymphocytes were isolated from the jejunum of bird. CD3(+)CD8(+) T cells were sorted and subjected to total RNA isolation and cDNA preparation. PCR amplification and cloning of the loci between Vβ1 and Cβ was conducted for the subsequent sequencing of CDR3 of T cell receptor (TCR). After the forth infection, 2 birds exhibited two same frequent TCR CDR3 sequences, i.e., AKQDWGTGGYSNMI and AGRVLNIQY; while the third bird showed two different frequent TCR CDR3 sequences, AKQGARGHTPLN and AKQDIEVRGPNTPLN. No frequent CDR3 sequence was detected from uninfected birds, though AGRVLNIQY was also found in two uninfected birds. Our result preliminarily demonstrates that frequent CDR3 sequences may exist in E. maxima immunized chickens, encouraging the mining of the immunodominant CD8(+) T cells against E. maxima infection. Copyright © 2014 Elsevier Inc. All rights reserved.

Overcoming the heterologous bias: An in vivo functional analysis of multidrug efflux transporter, CgCdr1p in matched pair clinical isolates of Candida glabrata

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

Puri, Nidhi; Manoharlal, Raman; Sharma, Monika

2011-01-07

Research highlights: {yields} First report to demonstrate an in vivo expression system of an ABC multidrug transporter CgCdr1p of C. glabrata. {yields} First report on the structure and functional characterization of CgCdr1p. {yields} Functional conservation of divergent but typical residues of CgCdr1p. {yields} CgCdr1p elicits promiscuity towards substrates and has a large drug binding pocket with overlapping specificities. -- Abstract: We have taken advantage of the natural milieu of matched pair of azole sensitive (AS) and azole resistant (AR) clinical isolates of Candida glabrata for expressing its major ABC multidrug transporter, CgCdr1p for structure and functional analysis. This was accomplishedmore » by tagging a green fluorescent protein (GFP) downstream of ORF of CgCDR1 and integrating the resultant fusion protein at its native chromosomal locus in AS and AR backgrounds. The characterization confirmed that in comparison to AS isolate, CgCdr1p-GFP was over-expressed in AR isolates due to its hyperactive native promoter and the GFP tag did not affect its functionality in either construct. We observed that in addition to Rhodamine 6 G (R6G) and Fluconazole (FLC), a recently identified fluorescent substrate of multidrug transporters Nile Red (NR) could also be expelled by CgCdr1p. Competition assays with these substrates revealed the presence of overlapping multiple drug binding sites in CgCdr1p. Point mutations employing site directed mutagenesis confirmed that the role played by unique amino acid residues critical to ATP catalysis and localization of ABC drug transporter proteins are well conserved in C. glabrata as in other yeasts. This study demonstrates a first in vivo novel system where over-expression of GFP tagged MDR transporter protein can be driven by its own hyperactive promoter of AR isolates. Taken together, this in vivo system can be exploited for the structure and functional analysis of CgCdr1p and similar proteins wherein the arte-factual concerns encountered in using heterologous systems are totally excluded.« less

Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species

PubMed Central

Nagayoshi, Yohsuke; Shimamura, Shintaro; Nakayama, Hironobu; Minematsu, Asuka; Yamauchi, Shunsuke; Takazono, Takahiro; Nakamura, Shigeki; Yanagihara, Katsunori; Kohno, Shigeru; Mukae, Hiroshi; Izumikawa, Koichi

2017-01-01

The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole susceptibility in C. glabrata. In the present study, we have evaluated the effects of clorgyline on susceptibility of C. glabrata to not only azoles, but also to micafungin and amphotericin B, using wild-type and several mutant strains. The addition of clorgyline to the culture media increased fluconazole susceptibility of a C. glabrata wild-type strain, whereas micafungin and amphotericin B susceptibilities were markedly decreased. These phenomena were also observed in other medically important Candida species, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida krusei. Expression levels of CDR1, CDR2 and PDR1 mRNAs and an amount of Cdr1 protein in the C. glabrata wild-type strain were highly increased in response to the treatment with clorgyline. However, loss of Cdr1, Cdr2, Pdr1, and a putative clorgyline target (Fms1), which is an ortholog of human MAO-A, or overexpression of CDR1 did not affect the decreased susceptibility to micafungin and amphotericin B in the presence of clorgyline. The presence of other azole efflux pump inhibitors including milbemycin A4 oxime and carbonyl cyanide 3-chlorophenylhydrazone also decreased micafungin susceptibility in C. glabrata wild-type, Δcdr1, Δcdr2, and Δpdr1 strains. These findings suggest that azole efflux pump inhibitors increase azole susceptibility but concurrently induce decreased susceptibility to other classes of antifungals independent of azole transporter functions. PMID:28700656

Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species.

PubMed

Nagayoshi, Yohsuke; Miyazaki, Taiga; Shimamura, Shintaro; Nakayama, Hironobu; Minematsu, Asuka; Yamauchi, Shunsuke; Takazono, Takahiro; Nakamura, Shigeki; Yanagihara, Katsunori; Kohno, Shigeru; Mukae, Hiroshi; Izumikawa, Koichi

2017-01-01

The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole susceptibility in C. glabrata. In the present study, we have evaluated the effects of clorgyline on susceptibility of C. glabrata to not only azoles, but also to micafungin and amphotericin B, using wild-type and several mutant strains. The addition of clorgyline to the culture media increased fluconazole susceptibility of a C. glabrata wild-type strain, whereas micafungin and amphotericin B susceptibilities were markedly decreased. These phenomena were also observed in other medically important Candida species, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida krusei. Expression levels of CDR1, CDR2 and PDR1 mRNAs and an amount of Cdr1 protein in the C. glabrata wild-type strain were highly increased in response to the treatment with clorgyline. However, loss of Cdr1, Cdr2, Pdr1, and a putative clorgyline target (Fms1), which is an ortholog of human MAO-A, or overexpression of CDR1 did not affect the decreased susceptibility to micafungin and amphotericin B in the presence of clorgyline. The presence of other azole efflux pump inhibitors including milbemycin A4 oxime and carbonyl cyanide 3-chlorophenylhydrazone also decreased micafungin susceptibility in C. glabrata wild-type, Δcdr1, Δcdr2, and Δpdr1 strains. These findings suggest that azole efflux pump inhibitors increase azole susceptibility but concurrently induce decreased susceptibility to other classes of antifungals independent of azole transporter functions.

The Structured Interview & Scoring Tool-Massachusetts Alzheimer's Disease Research Center (SIST-M): development, reliability, and cross-sectional validation of a brief structured clinical dementia rating interview.

PubMed

Okereke, Olivia I; Copeland, Maura; Hyman, Bradley T; Wanggaard, Taylor; Albert, Marilyn S; Blacker, Deborah

2011-03-01

The Clinical Dementia Rating (CDR) and CDR Sum-of-Boxes can be used to grade mild but clinically important cognitive symptoms of Alzheimer disease. However, sensitive clinical interview formats are lengthy. To develop a brief instrument for obtaining CDR scores and to assess its reliability and cross-sectional validity. Using legacy data from expanded interviews conducted among 347 community-dwelling older adults in a longitudinal study, we identified 60 questions (from a possible 131) about cognitive functioning in daily life using clinical judgment, inter-item correlations, and principal components analysis. Items were selected in 1 cohort (n=147), and a computer algorithm for generating CDR scores was developed in this same cohort and re-run in a replication cohort (n=200) to evaluate how well the 60 items retained information from the original 131 items. Short interviews based on the 60 items were then administered to 50 consecutively recruited older individuals, with no symptoms or mild cognitive symptoms, at an Alzheimer's Disease Research Center. Clinical Dementia Rating scores based on short interviews were compared with those from independent long interviews. In the replication cohort, agreement between short and long CDR interviews ranged from κ=0.65 to 0.79, with κ=0.76 for Memory, κ=0.77 for global CDR, and intraclass correlation coefficient for CDR Sum-of-Boxes=0.89. In the cross-sectional validation, short interview scores were slightly lower than those from long interviews, but good agreement was observed for global CDR and Memory (κ≥0.70) as well as for CDR Sum-of-Boxes (intraclass correlation coefficient=0.73). The Structured Interview & Scoring Tool-Massachusetts Alzheimer's Disease Research Center is a brief, reliable, and sensitive instrument for obtaining CDR scores in persons with symptoms along the spectrum of mild cognitive change.

Fundamental characteristics of the expressed immunoglobulin VH and VL repertoire in different canine breeds in comparison with those of humans and mice.

PubMed

Steiniger, Sebastian C J; Dunkle, William E; Bammert, Gary F; Wilson, Thomas L; Krishnan, Abhiram; Dunham, Steven A; Ippolito, Gregory C; Bainbridge, Graeme

2014-05-01

Complementarity determining regions (CDR) are responsible for binding antigen and provide substantial diversity to the antibody repertoire, with VH CDR3 of the immunoglobulin variable heavy (VH) domain playing a dominant role. In this study, we examined 1200 unique canine VH and 500 unique variable light (VL) sequences of large and small canine breeds derived from peripheral B cells. Unlike the human and murine repertoire, the canine repertoire is heavily dominated by the Canis lupus familiaris IGHV1 subgroup, evolutionarily closest to the human IGHV3 subgroup. Our studies clearly show that the productive canine repertoire of all analyzed breeds shows similarities to both human and mouse; however, there are distinct differences in terms of VH CDR3 length and amino acid paratope composition. In comparison with the human and murine antibody repertoire, canine VH CDR3 regions are shorter in length than the human counterparts, but longer than the murine VH CDR3. Similar to corresponding human and mouse VH CDR3, the amino acids at the base of the VH CDR3 loop are strictly conserved. For identical CDR positions, there were significant changes in chemical paratope composition. Similar to human and mouse repertoires, the neutral amino acids tyrosine, glycine and serine dominate the canine VH CDR3 interval (comprising 35%) although the interval is nonetheless relatively depleted of tyrosine when compared to human and mouse. Furthermore, canine VH CDR3 displays an overrepresentation of the neutral amino acid threonine and the negatively charged aspartic acid while proline content is similar to that in the human repertoire. In general, the canine repertoire shows a bias towards small, negatively charged amino acids. Overall, this analysis suggests that functional canine therapeutic antibodies can be obtained from human and mouse sequences by methods of speciation and affinity maturation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Implementation of Child Death Review in the Netherlands: results of a pilot study.

PubMed

Gijzen, Sandra; Hilhorst, Michaëla I; L'Hoir, Monique P; Boere-Boonekamp, Magda M; Need, Ariana

2016-07-08

Child mortality in the Netherlands declined gradually in the past decades. In total 1130 children and youth aged 0 to 19 years died in 2014 (i.e. 29.4 per 100,000 live births). A better understanding of the background and the circumstances surrounding the death of children as well as the manner and cause of death may lead to preventive measures. Child Death Review (CDR) is a method to systematically analyze child deaths by a multidisciplinary team to identify avoidable factors that may have contributed to the death and to give directions for prevention. CDR could be an addition to further reduce avoidable child deaths in the Netherlands. The purpose of this study is to explore the strengths, weaknesses, opportunities and threats (SWOT) of the pilot-implementation of CDR in a Dutch region. The results are translated in recommendations for future implementation of the CDR method in the Netherlands. Children who lived in the pilot region and died aged 29 days after birth until 2 years were, after parental consent, included for reviewing by a regional CDR team. Eighteen logs and seven transcribed records of CDR meetings concerning 6 deceased children were analyzed using Atlas ti. The SWOT framework was used to identify important themes. The most important strengths identified were the expertise of and cooperation within the CDR team and the available materials. An important weakness was the poor cooperation of some professional groups. The fact that parents and professionals endorse the objective of CDR was an important opportunity. The lack of statutory basis was a threat. Many obstacles need to be taken away before large-scale implementation of CDR in the Netherlands becomes possible. The most important precondition for implementation is the acceptance among professionals and the statutory basis of the CDR method.

OpenSim Model Improvements to Support High Joint Angle Resistive Exercising

NASA Technical Reports Server (NTRS)

Gallo, Christopher; Thompson, William; Lewandowski, Beth; Humphreys, Brad

2016-01-01

Long duration space travel to Mars or to an asteroid will expose astronauts to extended periods of reduced gravity. Since gravity is not present to aid loading, astronauts will use resistive and aerobic exercise regimes for the duration of the space flight to minimize the loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the area available for an exercise device in the next generation of spacecraft is limited. Therefore, compact resistance exercise device prototypes are being developed. The Advanced Resistive Exercise Device (ARED) currently on the ISS is being used as a benchmark for the functional performance of these new devices. Rigorous testing of these proposed devices in space flight is difficult so computational modeling provides an estimation of the muscle forces and joint loads during exercise to gain insight on the efficacy to protect the musculoskeletal health of astronauts. The NASA Digital Astronaut Project (DAP) is supporting the Advanced Exercise Concepts (AEC) Project, Exercise Physiology and Countermeasures (ExPC) project and the National Space Biomedical Research Institute (NSBRI) funded researchers by developing computational models of exercising with these new advanced exercise device concepts

Overview of the Exploration Exercise Device Validation Study Plans

NASA Technical Reports Server (NTRS)

DeWitt, J. K.; Swan, B. G.

2018-01-01

The NASA has determined that a multi-functional exercise device will be developed for use as an exercise device during exploration missions. The device will allow for full body resistance and metabolic exercise necessary to minimize physiological losses during space flight and to maintain fitness necessary to perform critical mission tasks. Prior to implementation as an exercise device on an Exploration vehicle, there will be verification and validation testing completed to determine device efficacy at providing the necessary training stimuli to achieve desired goals. Because the exploration device will be new device that has yet be specified, specific Verification and Validation (V&V) protocols have yet to be developed. Upon delivery of an exploration exercise device training unit, stakeholders throughout NASA will develop V&V plans that include ground-based testing and testing on the International Space Station (ISS). Stakeholders will develop test protocols that include success criterion for the device. Ground tests will occur at NASA Johnson Space Station prior to flight testing. The intents of the ground tests are to allow crew, spaceflight medicine, science, engineering, Astronaut Strength, Conditioning, and Reconditioning staff, and others to gain experience in the best utilization of the device. The goal is to obtain an evidence base for recommending use of the device on the ISS. The developed protocol will be created to achieve multiple objectives, including determining if the device provides an adequate training stimulus for 5th - 95th percentile males and females, allows for exercise modalities that protect functional capability, and is robust and can withstand extensive human use. Although protocols are yet to be determined, current expectations include use of the device by test subjects and current crew in order to obtain quantitative and qualitative feedback. Information obtained during the ground tests may be used to influence device modifications during design iterations. Assuming successful ground tests, the device will be installed on the ISS for testing during space flight. Spaceflight testing is envisioned to include an activation and checkout (ACO) phase and a V&V phase. During the ACO phase, 1-2 crewmembers will exercise with the device to ensure proper function. ACO is expected to last multiple months because of the many modes and methods of exercise that need to be assessed. However, the goal is to complete the ACO as quickly as possible. Once successful ACO occurs, the crew will be free to use the device for normal exercise pending concurrence from stakeholders. V&V tests on the ISS will ideally consist of crew using the device for all of their exercise for an entire mission. Exercise prescriptions will be supplied that replicate expected prescriptions during exploration missions. Crew that are not enrolled in the V&V studies would be also free to use the device as their schedule permits. As experience is gained by users, exercise protocols could change. The intent of all V&V testing is to ensure that all have thorough understanding of experience at optimizing device capability

Trypanosoma cruzi persistence in the native heart is associated with high-grade myocarditis, but not with Chagas' disease reactivation after heart transplantation.

PubMed

Benvenuti, Luiz A; Roggério, Alessandra; Nishiya, Anna S; Campos, Silvia V; Fiorelli, Alfredo I; Levi, José E

2014-07-01

Chagas' disease reactivation (CDR) after heart transplantation (HTx) is characterized by relapse of the infectious disease, with direct detection of Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. We investigated whether a detailed pathologic examination of the explanted heart at HTx with evaluation of myocarditis and parasitic persistence or load in the myocardium could be useful to identify patients at high risk of CDR. The native hearts of 18 chagasic patients who presented CDR after HTx (CDR+ group) were compared with the native hearts of 16 chagasic patients who never presented CDR in a follow-up of at least 18 months after HTx (CDR- group). The intensity of myocarditis was evaluated semiquantitatively. Parasite persistence/load in the myocardium was investigated through immunohistochemistry for T cruzi antigens and by qualitative and quantitative real-time PCR for T cruzi DNA. The rate of high-grade myocarditis, parasite persistence, and the median of parasitic load and parasitic load/10(6) cells in the CDR+ group were 83.3%, 77.8%, 8.43 × 10(-3), and 9.890, respectively, whereas in the CDR- group the values were 87.5%, 50%, 7.49×10(-3), and 17.800. There was no statistical difference between the groups. High-grade myocarditis was present in all 22 samples (100%) with parasite persistence and in 7 of 12 samples (58.3%) with no parasite persistence (p = 0.003). Although associated with high-grade myocarditis, T cruzi parasite persistence in the myocardium of the native heart is not associated with the occurrence of CDR after HTx. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The SIST-M: Predictive validity of a brief structured Clinical Dementia Rating interview

PubMed Central

Okereke, Olivia I.; Pantoja-Galicia, Norberto; Copeland, Maura; Hyman, Bradley T.; Wanggaard, Taylor; Albert, Marilyn S.; Betensky, Rebecca A.; Blacker, Deborah

2011-01-01

Background We previously established reliability and cross-sectional validity of the SIST-M (Structured Interview and Scoring Tool–Massachusetts Alzheimer's Disease Research Center), a shortened version of an instrument shown to predict progression to Alzheimer disease (AD), even among persons with very mild cognitive impairment (vMCI). Objective To test predictive validity of the SIST-M. Methods Participants were 342 community-dwelling, non-demented older adults in a longitudinal study. Baseline Clinical Dementia Rating (CDR) ratings were determined by either: 1) clinician interviews or 2) a previously developed computer algorithm based on 60 questions (of a possible 131) extracted from clinician interviews. We developed age+gender+education-adjusted Cox proportional hazards models using CDR-sum-of-boxes (CDR-SB) as the predictor, where CDR-SB was determined by either clinician interview or algorithm; models were run for the full sample (n=342) and among those jointly classified as vMCI using clinician- and algorithm-based CDR ratings (n=156). We directly compared predictive accuracy using time-dependent Receiver Operating Characteristic (ROC) curves. Results AD hazard ratios (HRs) were similar for clinician-based and algorithm-based CDR-SB: for a 1-point increment in CDR-SB, respective HRs (95% CI)=3.1 (2.5,3.9) and 2.8 (2.2,3.5); among those with vMCI, respective HRs (95% CI) were 2.2 (1.6,3.2) and 2.1 (1.5,3.0). Similarly high predictive accuracy was achieved: the concordance probability (weighted average of the area-under-the-ROC curves) over follow-up was 0.78 vs. 0.76 using clinician-based vs. algorithm-based CDR-SB. Conclusion CDR scores based on items from this shortened interview had high predictive ability for AD – comparable to that using a lengthy clinical interview. PMID:21986342

CD-REST: a system for extracting chemical-induced disease relation in literature.

PubMed

Xu, Jun; Wu, Yonghui; Zhang, Yaoyun; Wang, Jingqi; Lee, Hee-Jin; Xu, Hua

2016-01-01

Mining chemical-induced disease relations embedded in the vast biomedical literature could facilitate a wide range of computational biomedical applications, such as pharmacovigilance. The BioCreative V organized a Chemical Disease Relation (CDR) Track regarding chemical-induced disease relation extraction from biomedical literature in 2015. We participated in all subtasks of this challenge. In this article, we present our participation system Chemical Disease Relation Extraction SysTem (CD-REST), an end-to-end system for extracting chemical-induced disease relations in biomedical literature. CD-REST consists of two main components: (1) a chemical and disease named entity recognition and normalization module, which employs the Conditional Random Fields algorithm for entity recognition and a Vector Space Model-based approach for normalization; and (2) a relation extraction module that classifies both sentence-level and document-level candidate drug-disease pairs by support vector machines. Our system achieved the best performance on the chemical-induced disease relation extraction subtask in the BioCreative V CDR Track, demonstrating the effectiveness of our proposed machine learning-based approaches for automatic extraction of chemical-induced disease relations in biomedical literature. The CD-REST system provides web services using HTTP POST request. The web services can be accessed fromhttp://clinicalnlptool.com/cdr The online CD-REST demonstration system is available athttp://clinicalnlptool.com/cdr/cdr.html. Database URL:http://clinicalnlptool.com/cdr;http://clinicalnlptool.com/cdr/cdr.html. © The Author(s) 2016. Published by Oxford University Press.

Validity of Wearable Activity Monitors during Cycling and Resistance Exercise.

PubMed

Boudreaux, Benjamin D; Hebert, Edward P; Hollander, Daniel B; Williams, Brian M; Cormier, Corinne L; Naquin, Mildred R; Gillan, Wynn W; Gusew, Emily E; Kraemer, Robert R

2018-03-01

The use of wearable activity monitors has seen rapid growth; however, the mode and intensity of exercise could affect the validity of heart rate (HR) and caloric (energy) expenditure (EE) readings. There is a lack of data regarding the validity of wearable activity monitors during graded cycling regimen and a standard resistance exercise. The present study determined the validity of eight monitors for HR compared with an ECG and seven monitors for EE compared with a metabolic analyzer during graded cycling and resistance exercise. Fifty subjects (28 women, 22 men) completed separate trials of graded cycling and three sets of four resistance exercises at a 10-repetition-maximum load. Monitors included the following: Apple Watch Series 2, Fitbit Blaze, Fitbit Charge 2, Polar H7, Polar A360, Garmin Vivosmart HR, TomTom Touch, and Bose SoundSport Pulse (BSP) headphones. HR was recorded after each cycling intensity and after each resistance exercise set. EE was recorded after both protocols. Validity was established as having a mean absolute percent error (MAPE) value of ≤10%. The Polar H7 and BSP were valid during both exercise modes (cycling: MAPE = 6.87%, R = 0.79; resistance exercise: MAPE = 6.31%, R = 0.83). During cycling, the Apple Watch Series 2 revealed the greatest HR validity (MAPE = 4.14%, R = 0.80). The BSP revealed the greatest HR accuracy during resistance exercise (MAPE = 6.24%, R = 0.86). Across all devices, as exercise intensity increased, there was greater underestimation of HR. No device was valid for EE during cycling or resistance exercise. HR from wearable devices differed at different exercise intensities; EE estimates from wearable devices were inaccurate. Wearable devices are not medical devices, and users should be cautious when using these devices for monitoring physiological responses to exercise.

The use of high fidelity CAD models as the basis for training on complex systems

NASA Technical Reports Server (NTRS)

Miller, Kellie; Tanner, Steve

1993-01-01

During the design phases of large and complex systems such as NASA's Space Station Freedom (SSF), there are few, if any physical prototypes built. This is often due to their expense and the realization that the design is likely to change. This poses a problem for training, maintainability, and operations groups who are tasked to lay the foundation of plans for using these systems. The Virtual Reality and Visualization Laboratory at the Boeing Advanced Computing Group's Huntsville facility is supporting the use of high fidelity, detailed design models that are generated during the initial design phases, for use in training, maintainability and operations exercises. This capability was used in its non-immersive form to great effect at the SSF Critical Design Review (CDR) during February, 1993. Allowing the user to move about within a CAD design supports many efforts, including training and scenario study. We will demonstrate via a video of the Maintainability SSF CDR how this type of approach can be used and why it is so effective in conveying large amounts of information quickly and concisely. We will also demonstrate why high fidelity models are so important for this type of training system and how it's immersive aspects may be exploited as well.

Advanced resistive exercise device

NASA Technical Reports Server (NTRS)

Raboin, Jasen L. (Inventor); Niebuhr, Jason (Inventor); Cruz, Santana F. (Inventor); Lamoreaux, Christopher D. (Inventor)

2008-01-01

The present invention relates to an exercise device, which includes a vacuum cylinder and a flywheel. The flywheel provides an inertial component to the load, which is particularly well suited for use in space as it simulates exercising under normal gravity conditions. Also, the present invention relates to an exercise device, which has a vacuum cylinder and a load adjusting armbase assembly.

BCR CDR3 length distributions differ between blood and spleen and between old and young patients, and TCR distributions can be used to detect myelodysplastic syndrome

NASA Astrophysics Data System (ADS)

Pickman, Yishai; Dunn-Walters, Deborah; Mehr, Ramit

2013-10-01

Complementarity-determining region 3 (CDR3) is the most hyper-variable region in B cell receptor (BCR) and T cell receptor (TCR) genes, and the most critical structure in antigen recognition and thereby in determining the fates of developing and responding lymphocytes. There are millions of different TCR Vβ chain or BCR heavy chain CDR3 sequences in human blood. Even now, when high-throughput sequencing becomes widely used, CDR3 length distributions (also called spectratypes) are still a much quicker and cheaper method of assessing repertoire diversity. However, distribution complexity and the large amount of information per sample (e.g. 32 distributions of the TCRα chain, and 24 of TCRβ) calls for the use of machine learning tools for full exploration. We have examined the ability of supervised machine learning, which uses computational models to find hidden patterns in predefined biological groups, to analyze CDR3 length distributions from various sources, and distinguish between experimental groups. We found that (a) splenic BCR CDR3 length distributions are characterized by low standard deviations and few local maxima, compared to peripheral blood distributions; (b) healthy elderly people's BCR CDR3 length distributions can be distinguished from those of the young; and (c) a machine learning model based on TCR CDR3 distribution features can detect myelodysplastic syndrome with approximately 93% accuracy. Overall, we demonstrate that using supervised machine learning methods can contribute to our understanding of lymphocyte repertoire diversity.

Using the cost distribution report in estimating private sector payments: what adjustments should researchers make?

PubMed

Nugent, Gary; Grippen, Glen; Parris, Y C; Mitchell, Mary

2003-06-01

To reapportion Veterans Health Administration (VA) annual expenditures into benefit categories for comparison with estimated payments by private sector providers. Total expenditures for six VA medical centers for federal fiscal year 1999 were reapportioned by benefit category using the cost distribution report (CDR). Health benefit categories were based on those of health care insurers. Cost reapportionment was based on CDR data and reviews of source accounting and payroll documents. Actual expenditures for many benefits can be accurately identified and reapportioned using CDR data, but other expenditures were not identifiable in the CDR and required inspection of source documents. Inpatient expenditures amounting to $75,110,094 US dollars and outpatient expenditures amounting to $73,594,284 US dollars were reapportioned into other benefit categories, primarily professional fees. Expenditures for some VA benefits could not be identified because of differences in accounting and clinical practice between the VA and the community. Revisions to bring the CDR more in line with private sector payment categories would improve effectiveness for internal VA analyses and external expenditure comparisons. CDR revisions would require changes in recording some clinical workload (eg, rehabilitation and extended care) and classifying residential and domiciliary programs separate from inpatient care. Benefits that were not assigned expenditures for comparison with payments represent a potential liability if the VA were to purchase health care services in the marketplace. Variation among hospitals on expenditures not clearly identified in the CDR was significant and raises questions about the effectiveness of capitated budget methodologies using either the CDR or the decision support system.

An initial assessment of the consumer demand roundtable: Results and promise.

PubMed

Barker, Dianne C; Gutman, Marjorie A; Gordon, Sara R

2010-03-01

An initial assessment of the National Tobacco Cessation Collaborative's (NTCC) 2005-2007 Consumer Demand Roundtable (CDR) was conducted in 2008 to assess the results and products of CDR, and to offer recommendations to guide ongoing NTCC efforts to expand the demand, reach, and use of effective tobacco-cessation treatments. The evaluation was a small, retrospective, descriptive study, primarily using in-depth telephone interviews, supplemented by a review of CDR agendas, products, and web-based participant surveys. A sample of 30 tobacco-cessation leaders who had participated in at least one CDR meeting or conference was interviewed in May and June of 2008. Specific products implemented or influenced by CDR were identified, and organized by its six core strategies. Almost all respondents reported that the CDR was successful in its first goal to generate new ways of thinking about increasing demand for chronically underused evidence-based quit-smoking treatment, providing concrete examples of ways they had infused CDR concepts into the work of their organizations. The development of new products and communication messages suggested some progress in meeting the goal of identifying and catalyzing feasible innovations in treatment design, promotion, research, practice, and policy. Results suggest that the CDR, conceived as a "think tank" for the tobacco-cessation field, made sizable progress, especially in shifting the field to a new way of thinking. Continued leadership, funding, and proactive, sustained communication are needed to ensure these new innovations are further tested, implemented, and sustained. A longer-term follow-up evaluation to measure this impact is recommended. 2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Staging Dementia Using Clinical Dementia Rating Scale Sum of Boxes Scores

PubMed Central

O'Bryant, Sid E.; Waring, Stephen C.; Cullum, C. Munro; Hall, James; Lacritz, Laura; Massman, Paul J.; Lupo, Philip J.; Reisch, Joan S.; Doody, Rachelle

2012-01-01

Background The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score is commonly used, although the utility regarding this score in staging dementia severity is not well established. Obiective To investigate the effectiveness of CDRSOB scores in staging dementia severity compared with the global CDR score. Design Retrospective study. Setting Texas Alzheimer's Research Consortium minimum data set cohort. Participants A total of 1577 participants (110 controls, 202 patients with mild cognitive impairment, and 1265 patients with probable Alzheimer disease) were available for analysis. Main Outcome Measures Receiver operating characteristic curves were generated from a derivation sample to determine optimal cutoff scores and ranges, which were then applied to the validation sample. Results Optimal ranges of CDR-SOB scores corresponding to the global CDR scores were 0.5 to 4.0 for a global score of 0.5, 4.5 to 9.0 for a global score of 1.O, 9.5 to 15.5 for a global score of 2.0, and 16.0 to 18.0 for a global score of 3.0. When applied to the validation sample, κ scores ranged from 0.86 to 0.94 (P <.001 for all), with 93.0% of the participants falling within the new staging categories. Conclusions The CDR-SOB score compares well with the global CDR score for dementia staging. Owing to the increased range of values, the CDR-SOB score offers several advantages over the global score, including increased utility in tracking changes within and between stages of dementia severity. Interpretive guidelines for CDR-SOB scores are provided. PMID:18695059

Health technology assessment of new drugs for rare disorders in Canada: impact of disease prevalence and cost.

PubMed

Rawson, Nigel S B

2017-03-23

Authors from the Canadian Agency for Drugs and Technologies in Health (CADTH) presented an analysis of submissions to the Common Drug Review (CDR) between 2004 and February 3, 2016 for drugs for rare disorders (disorders with a prevalence of <50 per 100,000). The aim of this analysis was to examine the same CDR submissions to evaluate whether the negative reimbursement recommendation rate, clinical evidence of efficacy and statements concerning the drug's cost in the CDR reports varied with the prevalence of the disorder treated by the drug grouped into three decreasing categories: <50 to >10, ≤10 to >1, and ≤1 per 100,000. As the prevalence of the treated disorder decreased, the median daily cost of the drug, the negative recommendation rate and the proportion of submissions with statements in the CDR reports highlighting the cost of the drug increased, while the proportion of submissions with acceptable evidence of clinical efficacy decreased. Moreover, although the CADTH authors reported that only two submissions received a negative recommendation due to a "lack of cost-effectiveness/high cost," high cost was mentioned in the CDR reports of 15 drugs with negative recommendations, all for disorders with a prevalence of ≤10 per 100,000. The aggregated analysis of CDR submissions for drugs for disorders with wide ranging prevalence rates concealed information of concern to patients. The negative reimbursement recommendation rate and the significance of cost in the CDR assessments increased as the prevalence of the treated disorder decreased. Since 2012, the manner in which high cost drugs for rare disorders have been dealt with by the CDR has changed. Cost has ceased to be a factor in negative recommendations but is included in criteria accompanying positive recommendations. This trend is associated with the integration of the CDR process with the system for price negotiation between public drug plans and pharmaceutical companies.

Ibuprofen reverts antifungal resistance on Candida albicans showing overexpression of CDR genes.

PubMed

Ricardo, Elisabete; Costa-de-Oliveira, Sofia; Dias, Ana Silva; Guerra, José; Rodrigues, Acácio Gonçalves; Pina-Vaz, Cidália

2009-06-01

Several mechanisms may be associated with Candida albicans resistance to azoles. Ibuprofen was described as being able to revert resistance related to efflux activity in Candida. The aim of this study was to uncover the molecular base of antifungal resistance in C. albicans clinical strains that could be reverted by ibuprofen. Sixty-two clinical isolates and five control strains of C. albicans were studied: the azole susceptibility phenotype was determined according to the Clinical Laboratory for Standards Institute, M27-A2 protocol and minimal inhibitory concentration values were recalculated with ibuprofen (100 microg mL(-1)); synergistic studies between fluconazole and FK506, a Cdr1p inhibitor, were performed using an agar disk diffusion assay and were compared with ibuprofen results. Gene expression was quantified by real-time PCR, with and without ibuprofen, regarding CDR1, CDR2, MDR1, encoding for efflux pumps, and ERG11, encoding for azole target protein. A correlation between susceptibility phenotype and resistance gene expression profiles was determined. Ibuprofen and FK506 showed a clear synergistic effect when combined with fluconazole. Resistant isolates reverting to susceptible after incubation with ibuprofen showed CDR1 and CDR2 overexpression especially of the latter. Conversely, strains that did not revert displayed a remarkable increase in ERG11 expression along with CDR genes. Ibuprofen did not alter resistance gene expression significantly (P>0.05), probably acting as a Cdrp blocker.

Squat Biomechanical Modeling Results from Exercising on the Hybrid Ultimate Lifting Kit

NASA Technical Reports Server (NTRS)

Gallo, Christopher A.; Thompson, William K.; Lewandowski, Beth E.; Jagodnik, Kathleen M.

2016-01-01

Long duration space travel will expose astronauts to extended periods of reduced gravity. Since gravity is not present to aid loading, astronauts will use resistive and aerobic exercise regimes for the duration of the space flight to minimize loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the area available for an exercise device in the next generation of spacecraft is limited and therefore compact resistance exercise device prototypes are being developed. The Advanced Resistive Exercise Device (ARED) currently on the ISS is being used as a benchmark for the functional performance of these new devices. Biomechanical data collection and computational modeling aid the device design process by quantifying the joint torques and the musculoskeletal forces that occur during exercises performed on the prototype devices. The computational models currently under development utilize the OpenSim software, an open source code for musculoskeletal modeling, with biomechanical input data from test subjects for estimation of muscle and joint loads. The subjects are instrumented with reflective markers for motion capture data collection while exercising on the Hybrid Ultimate Lifting Kit (HULK) prototype device. Ground reaction force data is collected with force plates under the feet and device loading is recorded through load cells internal to the HULK. Test variables include applied device load, narrow or wide foot stance, slow or fast cadence and the harness or long bar interface between the test subject and the device. Data is also obtained using free weights for a comparison to the resistively loaded exercise device. This data is input into the OpenSim biomechanical model, which has been scaled to match the anthropometrics of the test subject, to calculate the body loads. The focus of this presentation is to summarize the results from the full squat exercises across the different test variables.

77 FR 73457 - Nominations for Membership on the Ocean Research Advisory Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-10

... submitted via email to CDR Stephen D. Martin, US Navy, at stephen[email protected] . Contact Information...; or CDR Stephen D. Martin, telephone 703- 696-4395. SUPPLEMENTARY INFORMATION: ORAP is a statutorily... email to CDR Stephen Martin ( stephen[email protected] ) no later than 5:00 p.m. EST, January 31, 2013...

Intelligence and Electronic Warfare (IEW) Streamlining Project. Volume 2. Directives and Related Study Documents. Revision

DTIC Science & Technology

1992-11-18

CDR INSCOM FT BELVOIR VA//IACG/IALOfa// INfO Nd DA WASH DC// DAHO -FDZ/DALO-SNIC/DANI-PI// CDR AMC ALEXANDRIA VA//AIICLG/AHCLG-SID// CDR CECON FT...Nondevelopmental Items (COTS/NDI) communications for more than 22 years. The explosion of technology has provided new capabilities and has challenged the

Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions.

PubMed

Townsend, Catherine L; Laffy, Julie M J; Wu, Yu-Chang Bryan; Silva O'Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K

2016-01-01

Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions

PubMed Central

Townsend, Catherine L.; Laffy, Julie M. J.; Wu, Yu-Chang Bryan; Silva O’Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K.

2016-01-01

Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response. PMID:27729912

Clock drawing test in elderly individuals with different education levels: correlation with clinical dementia rating.

PubMed

Cecato, Juliana Francisca; Fiorese, Bruna; Montiel, José Maria; Bartholomeu, Daniel; Martinelli, José Eduardo

2012-12-01

The aim of this study was to describe the performance in Clock Drawing Test (CDT) of the elderly individuals assessed in a geriatric clinic, with at least 1 year of schooling, comparing with other groups with higher education and with Clinical Dementia Rating (CDR) levels. The study also aims to correlate the results of CDT and other used diagnostic tests for dementia by CDR levels, providing additional validity evidence to the CDT. Cross-sectional study with 426 elderly individuals, >60 years old and at least 1 year of education. All participants searched for medical assistance at Geriatric and Gerontology Ambulatory of Jundiaí city, in Brazil. The community-dwelling outpatients previously undergone a detailed clinical examination and neuropsychological evaluation: Cambrigde Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), andCDT. To differentiate data from diagnostic groups based on CDR, it Kruskal-Wallis test was used. Pearson statistics were calculated to compare data from CDT and CDR. The statistical analyses were 2-tailed and were considered significant when P < .05. Regarding CDT, groups with more years of schooling showed similar means in CDR = 0 and CDR = 0.5 and in CDR = 1 and CDR = 2. Shulman and Sunderland scale were high score in groups with more years of education and above of cutoff points in all CDT score. On the contrary, in Mendez scale we did not observed similar means. Otherwise, in the group with less years of schooling greater means differences in the CDT were observed. The CDT did not show a strong correlation with MMSE and CAMCOG, both important instruments in Brazilian population to investigate dementia. For elderly individuals with high education levels, the CDT did not seem to be a good test to detect cognitive impairment.

[Preparation of anti-hCG single domain antibody by antibody grafting technique using an antigen-binding peptide].

PubMed

Peng, Jing; Wang, Qiong; Cheng, Xiaoling; Liu, Mengwen; Wang, Mei; Xin, Huawei

2018-04-25

We used the antibody grafting technology to prepare anti-hCG single-domain antibodies on the basis of antigen-binding peptide to simplify the single-domain antibody preparation process and improving the biochemical stability of peptide. By using a universal single-domain antibody backbone (cAbBCII10), CDR1 or CDR3 was replaced by the hCG-binding peptide, and the grafted antibody gene sequences were synthesized and cloned into the prokaryotic expression vector pET30a(+) in fusion with a C-terminal sfGFP gene, i.e. pET30a-(His6)-cAbBCII10-CDR1/hCGBP1-sfGFP and pET30a-(His6)-cAbBCII10-CDR3/hCGBP3-sfGFP. The recombinant plasmids were transformed into E. coli BL21(DE3), and the fusion proteins were induced by IPTG. Highly soluble recombinant fusion proteins were obtained and purified by Ni-NTA affinity column. SDS-PAGE confirmed the purified protein as the target protein. The antigen-antibody binding assay showed that both the CDR1 and CDR3 grafted antibodies have hCG-binding activities. While the titers of the two grafted antibodies were similar, the binding affinity of CDR3 grafted antibody was higher than that of CDR1 grafted protein (about 2-3 times). The grafted antibodies retained the relatively high biochemical stability of the single-domain antibody backbone and were relatively thermostable and alkaline tolerant. The obtained antibodies also had a relatively high antigen-binding specificity to hCG. This study provided a reliable experimental basis for further optimization of anti-hCG single domain antibody by antibody grafting technology using antigen-binding peptide.

Determinants and Heritability of Intraocular Pressure and Cup-to-Disc Ratio in a Defined Older Population

PubMed Central

Chang, Ta C.; Congdon, Nathan G.; Wojciechowski, Robert; Muñoz, Beatriz; Gilbert, Donna; Chen, Ping; Friedman, David S.; West, Sheila K.

2011-01-01

Purpose To investigate the heritability of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in an older well-defined population. Design Family-based cohort study. Participants Through the population-based Salisbury Eye Evaluation study, we recruited 726 siblings (mean age, 74.7 years) in 284 sibships. Methods Intraocular pressure and CDR were measured bilaterally for all participants. The presence or absence of glaucoma was determined by a glacuoma specialist for all probands on the basis of visual field, optic nerve appearance, and history. The heritability of IOP was calculated as twice the residual between-sibling correlation of IOP using linear regression and generalized estimating equations after adjusting for age, gender, mean arterial pressure, race, self-reported diabetes status, and history of systemic steroid use. The heritability of CDR was calculated using the same model and adjustments as above, while also adjusting for IOP. Main Outcome Measures Heritability and determinants of IOP and CDR, and impact of siblings’ glaucoma status on IOP and CDR. Results We estimated the heritability to be 0.29 (95% confidence interval [CI], 0.12–0.46) for IOP and 0.56 (95% CI, 0.35–0.76) for CDR in this population. Mean IOP in siblings of glaucomatous probands was statistically significantly higher than in siblings of normal probands (mean difference, 1.02 mmHg; P = 0.017). The mean CDR in siblings of glaucomatous probands was 0.07 (or 19%) larger than in siblings of glaucoma suspect referrals (P = 0.045) and siblings of normal probands (P = 0.004). Conclusions In this elderly population, we found CDR to be highly heritable and IOP to be moderately heritable. On average, siblings of glaucoma patients had higher IOPs and larger CDRs than siblings of nonglaucomatous probands. PMID:15939473

Iron fertilisation and century-scale effects of open ocean dissolution of olivine in a simulated CO2 removal experiment

NASA Astrophysics Data System (ADS)

Hauck, Judith; Köhler, Peter; Wolf-Gladrow, Dieter; Völker, Christoph

2016-02-01

Carbon dioxide removal (CDR) approaches are efforts to reduce the atmospheric CO2 concentration. Here we use a marine carbon cycle model to investigate the effects of one CDR technique: the open ocean dissolution of the iron-containing mineral olivine. We analyse the maximum CDR potential of an annual dissolution of 3 Pg olivine during the 21st century and focus on the role of the micro-nutrient iron for the biological carbon pump. Distributing the products of olivine dissolution (bicarbonate, silicic acid, iron) uniformly in the global surface ocean has a maximum CDR potential of 0.57 gC/g-olivine mainly due to the alkalinisation of the ocean, with a significant contribution from the fertilisation of phytoplankton with silicic acid and iron. The part of the CDR caused by ocean fertilisation is not permanent, while the CO2 sequestered by alkalinisation would be stored in the ocean as long as alkalinity is not removed from the system. For high CO2 emission scenarios the CDR potential due to the alkalinity input becomes more efficient over time with increasing ocean acidification. The alkalinity-induced CDR potential scales linearly with the amount of olivine, while the iron-induced CDR saturates at 113 PgC per century (on average ˜ 1.1 PgC yr-1) for an iron input rate of 2.3 Tg Fe yr-1 (1% of the iron contained in 3 Pg olivine). The additional iron-related CO2 uptake occurs in the Southern Ocean and in the iron-limited regions of the Pacific. Effects of this approach on surface ocean pH are small (\\lt 0.01).

Fundamental characteristics of the immunoglobulin VH repertoire of chickens in comparison with those of humans, mice, and camelids.

PubMed

Wu, Leeying; Oficjalska, Katarzyna; Lambert, Matthew; Fennell, Brian J; Darmanin-Sheehan, Alfredo; Ní Shúilleabháin, Deirdre; Autin, Bénédicte; Cummins, Emma; Tchistiakova, Lioudmila; Bloom, Laird; Paulsen, Janet; Gill, Davinder; Cunningham, Orla; Finlay, William J J

2012-01-01

Examination of 1269 unique naive chicken V(H) sequences showed that the majority of positions in the framework (FW) regions were maintained as germline, with high mutation rates observed in the CDRs. Many FW mutations could be clearly related to the modulation of CDR structure or the V(H)-V(L) interface. CDRs 1 and 2 of the V(H) exhibited frequent mutation in solvent-exposed positions, but conservation of common structural residues also found in human CDRs at the same positions. In comparison with humans and mice, the chicken CDR3 repertoire was skewed toward longer sequences, was dominated by small amino acids (G/S/A/C/T), and had higher cysteine (chicken, 9.4%; human, 1.6%; and mouse, 0.25%) but lower tyrosine content (chicken, 9.2%; human, 16.8%; and mouse 26.4%). A strong correlation (R(2) = 0.97) was observed between increasing CDR3 length and higher cysteine content. This suggests that noncanonical disulfides are strongly favored in chickens, potentially increasing CDR stability and complexity in the topology of the combining site. The probable formation of disulfide bonds between CDR3 and CDR1, FW2, or CDR2 was also observed, as described in camelids. All features of the naive repertoire were fully replicated in the target-selected, phage-displayed repertoire. The isolation of a chicken Fab with four noncanonical cysteines in the V(H) that exhibits 64 nM (K(D)) binding affinity for its target proved these constituents to be part of the humoral response, not artifacts. This study supports the hypothesis that disulfide bond-constrained CDR3s are a structural diversification strategy in the restricted germline v-gene repertoire of chickens.

Biomechanical Modeling of Split-leg Squat and Heel Raise on the Hybrid Ultimate Lifting Kit (HULK)

NASA Technical Reports Server (NTRS)

Thompson, William K.; Gallo, Christopher A.; Lewandowski, Beth E.; Jagodnik, Kathleen M.; Humphreys, Brad; Funk, Justin; Funk, Nathan; Dewitt, John K.

2016-01-01

Long duration space travel will expose astronauts to extended periods of reduced gravity. Since gravity is not present to aid loading, astronauts will use resistive and aerobic exercise regimes for the duration of the space flight to minimize the loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the area available for an exercise device in the next generation of spacecraft is limited and therefore compact resistance exercise device prototypes are being developed. The Advanced Resistive Exercise Device (ARED) currently on the ISS is being used as a benchmark for the functional performance of these new devices. Biomechanical data collection and computational modeling aid the device design process by quantifying the joint torques and musculoskeletal forces that occur during exercises performed on the prototype devices. Computational models currently use OpenSim software, an open source code for musculoskeletal modeling, with biomechanical input data from subjects for estimation of muscle and joint loads. Subjects are instrumented with reflective markers for motion capture data collection while exercising on the Hybrid Ultimate Lifting Kit (HULK) prototype device. Ground reaction force data is collected with force plates under the feet and device loading is recorded through load cells internal to the HULK. This data is input into the OpenSim biomechanical model, which has been scaled to match the anthropometrics of the test subject, to calculate the loads on the body. Multiple exercises are performed and evaluated during a test session such as a full squat, single leg squat, heel raise and dead lift. Variables for these exercises include applied device load, narrow or wide foot stance, slow or fast cadence and the harness or long bar interface between the test subject and the device. Data from free weights are compared to the resistively loaded exercise device. The focus of this presentation is to summarize the results from the single-leg squat and heel raise exercises performed during three sessions occurring in 2015. Differences in loading configuration, cadence and stance produce differences in kinematics, joint toques and force and muscle forces.

21 CFR 890.5350 - Exercise component.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Exercise component. 890.5350 Section 890.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5350 Exercise component. (a...

21 CFR 890.5350 - Exercise component.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Exercise component. 890.5350 Section 890.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5350 Exercise component. (a...

21 CFR 890.5350 - Exercise component.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Exercise component. 890.5350 Section 890.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5350 Exercise component. (a...

21 CFR 890.5350 - Exercise component.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Exercise component. 890.5350 Section 890.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5350 Exercise component. (a...

21 CFR 890.5350 - Exercise component.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Exercise component. 890.5350 Section 890.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5350 Exercise component. (a...

Biomechanical Modeling of the Deadlift Exercise to Improve the Efficacy of Resistive Exercise Microgravity Countermeasures

NASA Technical Reports Server (NTRS)

Jagodnik, K. M.; Thompson, W. K.; Gallo, C. A.; DeWitt, J. K.; Funk, J. H.; Funk, N. W.; Perusek, G. P.; Sheehan, C. C.; Lewandowski, B. E.

2016-01-01

During long-duration spaceflight missions, astronauts exposure to microgravity without adequate countermeasures can result in losses of muscular strength and endurance, as well as loss of bone mass. As a countermeasure to this challenge, astronauts engage in resistive exercise during spaceflight to maintain their musculoskeletal function. The Hybrid Ultimate Lifting Kit (HULK) has been designed as a prototype exercise device for an exploration-class vehicle; the HULK features a much smaller footprint than previous devices such as the Advanced Resistive Exercise Device (ARED) on the International Space Station (ISS), which makes the HULK suitable for extended spaceflight missions in vehicles with limited volume. As current ISS exercise countermeasure equipment represents an improvement over previous generations of such devices, the ARED is being employed as a benchmark of functional performance. This project involves the development of a biomechanical model of the deadlift exercise, and is novel in that it is the first exercise analyzed in this context to include the upper limbs in the loading path, in contrast to the squat, single-leg squat, and heel raise exercises also being modeled by our team. OpenSim software is employed to develop these biomechanical models of humans performing resistive exercises to assess and improve the new exercise device designs. Analyses include determining differences in joint and muscle forces when using different loading strategies with the device, comparing and contrasting with the ARED benchmark, and determining whether the loading is sufficient to maintain musculoskeletal health. During data collection, the number of repetitions, load, cadence, stance, and grip width are controlled in order to facilitate comparisons between loading configurations. To date, data have been collected for two human subjects performing the deadlift exercise on the HULK device using two different loading conditions. Recorded data include motion capture, electromyography (EMG), ground reaction forces, device load cell data, photos and videos, and anthropometric data. Work is ongoing to perform biomechanical analyses including inverse kinematics and inverse dynamics to compare different versions of the deadlift model in order to determine which provides an appropriate level of detail to study this exercise. This work is supported by the National Space Biomedical Research Institute through NCC 9-58.

Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme.

PubMed

Barbagallo, Davide; Condorelli, Angelo; Ragusa, Marco; Salito, Loredana; Sammito, Mariangela; Banelli, Barbara; Caltabiano, Rosario; Barbagallo, Giuseppe; Zappalà, Agata; Battaglia, Rosalia; Cirnigliaro, Matilde; Lanzafame, Salvatore; Vasquez, Enrico; Parenti, Rosalba; Cicirata, Federico; Di Pietro, Cinzia; Romani, Massimo; Purrello, Michele

2016-01-26

MiR-671-5p is encoded by a gene localized at 7q36.1, a region amplified in human glioblastoma multiforme (GBM), the most malignant brain cancer. To investigate whether expression of miR-671-5p were altered in GBM, we analyzed biopsies from a cohort of forty-five GBM patients and from five GBM cell lines. Our data show significant overexpression of miR-671-5p in both biopsies and cell lines. By exploiting specific miRNA mimics and inhibitors, we demonstrated that miR-671-5p overexpression significantly increases migration and to a less extent proliferation rates of GBM cells. Through a combined in silico and in vitro approach, we identified CDR1-AS, CDR1, VSNL1 as downstream miR-671-5p targets in GBM. Expression of these genes significantly decreased both in GBM biopsies and cell lines and negatively correlated with that of miR-671-5p. Based on our data, we propose that the axis miR-671-5p / CDR1-AS / CDR1 / VSNL1 is functionally altered in GBM cells and is involved in the modification of their biopathological profile.

Wakata exercises with Advanced Resistive Exercise Device (ARED) in Node 1 Unity

NASA Image and Video Library

2009-04-04

ISS018-E-044585 (4 April 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 18/19 flight engineer, exercises using the advanced Resistive Exercise Device (aRED) in the Unity node of the International Space Station.

Wakata exercises with Advanced Resistive Exercise Device (ARED) in Node 1 Unity

NASA Image and Video Library

2009-04-04

ISS018-E-044576 (4 April 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 18/19 flight engineer, exercises using the advanced Resistive Exercise Device (aRED) in the Unity node of the International Space Station.

Reliability of Strength Testing using the Advanced Resistive Exercise Device and Free Weights

NASA Technical Reports Server (NTRS)

English, Kirk L.; Loehr, James A.; Laughlin, Mitzi A.; Lee, Stuart M. C.; Hagan, R. Donald

2008-01-01

The Advanced Resistive Exercise Device (ARED) was developed for use on the International Space Station as a countermeasure against muscle atrophy and decreased strength. This investigation examined the reliability of one-repetition maximum (1RM) strength testing using ARED and traditional free weight (FW) exercise. Methods: Six males (180.8 +/- 4.3 cm, 83.6 +/- 6.4 kg, 36 +/- 8 y, mean +/- SD) who had not engaged in resistive exercise for at least six months volunteered to participate in this project. Subjects completed four 1RM testing sessions each for FW and ARED (eight total sessions) using a balanced, randomized, crossover design. All testing using one device was completed before progressing to the other. During each session, 1RM was measured for the squat, heel raise, and deadlift exercises. Generalizability (G) and intraclass correlation coefficients (ICC) were calculated for each exercise on each device and were used to predict the number of sessions needed to obtain a reliable 1RM measurement (G . 0.90). Interclass reliability coefficients and Pearson's correlation coefficients (R) also were calculated for the highest 1RM value (1RM9sub peak)) obtained for each exercise on each device to quantify 1RM relationships between devices.

Automated detection of kinks from blood vessels for optic cup segmentation in retinal images

NASA Astrophysics Data System (ADS)

Wong, D. W. K.; Liu, J.; Lim, J. H.; Li, H.; Wong, T. Y.

2009-02-01

The accurate localization of the optic cup in retinal images is important to assess the cup to disc ratio (CDR) for glaucoma screening and management. Glaucoma is physiologically assessed by the increased excavation of the optic cup within the optic nerve head, also known as the optic disc. The CDR is thus an important indicator of risk and severity of glaucoma. In this paper, we propose a method of determining the cup boundary using non-stereographic retinal images by the automatic detection of a morphological feature within the optic disc known as kinks. Kinks are defined as the bendings of small vessels as they traverse from the disc to the cup, providing physiological validation for the cup boundary. To detect kinks, localized patches are first generated from a preliminary cup boundary obtained via level set. Features obtained using edge detection and wavelet transform are combined using a statistical approach rule to identify likely vessel edges. The kinks are then obtained automatically by analyzing the detected vessel edges for angular changes, and these kinks are subsequently used to obtain the cup boundary. A set of retinal images from the Singapore Eye Research Institute was obtained to assess the performance of the method, with each image being clinically graded for the CDR. From experiments, when kinks were used, the error on the CDR was reduced to less than 0.1 CDR units relative to the clinical CDR, which is within the intra-observer variability of 0.2 CDR units.

Neuropsychological Test Selection for Cognitive Impairment Classification: A Machine Learning Approach

PubMed Central

Williams, Jennifer A.; Schmitter-Edgecombe, Maureen; Cook, Diane J.

2016-01-01

Introduction Reducing the amount of testing required to accurately detect cognitive impairment is clinically relevant. The aim of this research was to determine the fewest number of clinical measures required to accurately classify participants as healthy older adult, mild cognitive impairment (MCI) or dementia using a suite of classification techniques. Methods Two variable selection machine learning models (i.e., naive Bayes, decision tree), a logistic regression, and two participant datasets (i.e., clinical diagnosis, clinical dementia rating; CDR) were explored. Participants classified using clinical diagnosis criteria included 52 individuals with dementia, 97 with MCI, and 161 cognitively healthy older adults. Participants classified using CDR included 154 individuals CDR = 0, 93 individuals with CDR = 0.5, and 25 individuals with CDR = 1.0+. Twenty-seven demographic, psychological, and neuropsychological variables were available for variable selection. Results No significant difference was observed between naive Bayes, decision tree, and logistic regression models for classification of both clinical diagnosis and CDR datasets. Participant classification (70.0 – 99.1%), geometric mean (60.9 – 98.1%), sensitivity (44.2 – 100%), and specificity (52.7 – 100%) were generally satisfactory. Unsurprisingly, the MCI/CDR = 0.5 participant group was the most challenging to classify. Through variable selection only 2 – 9 variables were required for classification and varied between datasets in a clinically meaningful way. Conclusions The current study results reveal that machine learning techniques can accurately classifying cognitive impairment and reduce the number of measures required for diagnosis. PMID:26332171

Prevalence and prognosis of prodromal Alzheimer's disease as assessed by magnetic resonance imaging and 18F-fluorodeoxyglucose-positron emission tomography in a community: reanalysis from the Osaki-Tajiri Project.

PubMed

Meguro, Kenichi; Akanuma, Kyoko; Meguro, Mitsue; Yamaguchi, Satoshi; Ishii, Hiroshi; Tashiro, Manabu

2016-03-01

Dubois et al. proposed the criteria for prodromal Alzheimer's disease (AD) to detect dementia in its very early stage. Because detection requires magnetic resonance imaging and (18) F-fluorodeoxyglucose-positron emission tomography (PET), the prevalence and prognosis have not been fully investigated. Our database included 346 healthy participants (Clinical Dementia Rating (CDR) 0), 119 with questionable dementia (CDR 0.5), and 32 dementia participants (CDR 1+) and was applied to investigate the prevalence of prodromal AD. Forty-four CDR 0.5 participants (37%) were randomly selected to undergo (18) F-fluorodeoxyglucose-PET. The same percentage was applied to select 128 CDR 0 and 12 CDR 1 + participants (total: n = 184) to calculate the prevalence. A neuroradiologist classified the PET images in a blinded manner based on the criteria of Silverman et al. Participants were considered to have prodromal AD if they exhibited 'parietal/temporal +/- frontal hypometabolism' (PET) with hippocampal atrophy (magnetic resonance imaging). Eighteen CDR 0.5 participants (40.9%) met the criteria for prodromal AD, which was a prevalence rate of 9.8% among older adults aged ≥ 65 years. Thirteen prodromal AD participants (72%) converted to AD during the 5-year follow-up period. The concept and criteria for prodromal AD are useful for predicting which subjects in a community will convert to AD. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

Functional Consequences of Complementarity-determining Region Deactivation in a Multifunctional Anti-nucleic Acid Antibody*

PubMed Central

Lee, Jiyeon; Kim, Hye-Jin; Roh, Jooho; Seo, Youngsil; Kim, Minjae; Jun, Hye-Ryeong; Pham, Chuong D.; Kwon, Myung-Hee

2013-01-01

Many murine monoclonal anti-DNA antibodies (Abs) derived from mice models for systemic lupus erythematosus have additional cell-penetration and/or nucleic acid-hydrolysis properties. Here, we examined the influence of deactivating each complementarity-determining region (CDR) within a multifunctional anti-nucleic acid antibody (Ab) that possesses these activities, the catalytic 3D8 single chain variable fragment (scFv). CDR-deactivated 3D8 scFv variants were generated by replacing all of the amino acids within each CDR with Gly/Ser residues. The structure of 3D8 scFv accommodated single complete CDR deactivations. Different functional activities of 3D8 scFv were affected differently depending on which CDR was deactivated. The only exception was CDR1, located within the light chain (LCDR1); deactivation of LCDR1 abolished all of the functional activities of 3D8 scFv. A hybrid Ab, HW6/3D8L1, in which the LCDR1 from an unrelated Ab (HW6) was replaced with the LCDR1 from 3D8, acquired all activities associated with the 3D8 scFv. These results suggest that the activity of a multifunctional 3D8 scFv Ab can be modulated by single complete CDR deactivation and that the LCDR1 plays a crucial role in maintaining Ab properties. This study presents a new approach for determining the role of individual CDRs in multifunctional Abs with important implications for the future of Ab engineering. PMID:24155236

Growing C-D-R (Cedar): Working the Intersections of Interest Convergence and Whiteness as Property in the Affirmative Action Legal Debate

ERIC Educational Resources Information Center

Thompson Dorsey, Dana N.; Venzant Chambers, Terah T.

2014-01-01

In this article we extend Bell's work on interest convergence by using Harris' work on whiteness as property to articulate a cycle of interest convergence, interest divergence, and imperialistic reclamation, or convergence-divergence-reclamation (C-D-R, pronounced "cedar"). We then apply the C-D-R cycle lens to the evolution of federal…

Structural analysis, selection, and ontogeny of the shark new antigen receptor (IgNAR): identification of a new locus preferentially expressed in early development.

PubMed

Diaz, Marilyn; Stanfield, Robyn L; Greenberg, Andrew S; Flajnik, Martin F

2002-10-01

The new antigen receptor (IgNAR) family has been detected in all elasmobranch species so far studied and has several intriguing structural and functional features. IgNAR protein, found in both transmembrane and secretory forms, is a dimer of heavy chains with no associated light chains, with each chain of the dimer having a single free and flexible V region. Four rearrangement events (among 1V, 3D, and 1J germline genes) generate an expressed NAR V gene, resulting in long and diverse CDR3 regions that contain cysteine residues. IgNAR mutation frequency is very high and "selected" mutations are found only in genes encoding the secreted form, suggesting that the primary repertoire is entirely CDR3-based. Here we further analyzed the two IgNAR types, "type 1" having one cysteine in CDR3 and "type 2" with an even number (two or four) of CDR3 cysteines, and discovered that placement of the disulfide bridges in the IgNAR V domain differentially influences the selection of mutations in CDR1 and CDR2. Ontogenetic analyses showed that IgNAR sequences from young animals were infrequently mutated, consistent with the paradigm that the shark immune system must become mature before high levels of mutation accompanied with selection can occur. Nevertheless, also in agreement with the idea that the IgNAR repertoire is entirely CDR3-based, but unlike studies in most other vertebrates, N-region diversity is present in expressed IgNAR clones at birth. During the investigation of this early IgNAR repertoire we serendipitously detected a third type of IgNAR gene that is expressed in all neonatal tissues; later in life its expression is perpetuated only in the epigonal organ, a tissue recently shown to be a (the?) primary lymphoid tissue in elasmobranchs. This "type 3" IgNAR gene still undergoes three rearrangement events (two D regions are "germline-joined"), yet CDR3 sequences were exactly of the same length and very similar sequence, suggesting that "type 3" CDR3s are selected early in ontogeny, perhaps by a self-ligand.

Long-Term Historical Rainfall-Runoff Modeling Using High-Resolution Satellite-based Precipitation Products

NASA Astrophysics Data System (ADS)

Ashouri, H.; Nguyen, P.; Thorstensen, A. R.; Hsu, K. L.; Sorooshian, S.

2014-12-01

This study evaluates the performance of a newly developed long-term high-resolution satellite-based precipitation products, named Precipitation Estimation from Remotely Sensed Information using Artificial Neural Network - Climate Data Record (PERSIANN-CDR), in hydrological modeling. PERSIANN-CDR estimations are biased corrected using GPCP monthly climatology data. PERSIANN-CDR provides daily rainfall estimates at 0.25° x 0.25° grid boxes for 1983-2014 (delayed present). This newly released product makes it feasible to model the streamflow over the past 30 years. Three test basins from the Distributed Hydrologic Model Intercomparison Project - Phase 2 (DMIP 2) are chosen. Comparing with other satellite products, the Version 7 TRMM Multi-satellite Precipitation Analysis (TMPA) product is used. Stage IV radar data is used as a reference data for evaluating the PERSIANN-CDR and TMPA precipitation data. All products are scaled to 0.25° and daily spatiotemporal resolution. The study is performed in two phases. In the first phase, the 2003-2011 period where all the products are available is chosen. Precipitation evaluation results, presented on Taylor Diagrams, show that TMPA and PERSIANN-CDR have close performances. The National Weather Service (NWS) Office of Hydrologic Development (OHD) Hydrology Laboratory-Research Distributed Hydrologic Model (HL-RDHM) is then forced with the PERSIANN-CDR and the TMPA precipitation products, as well as the stage IV radar data. USGS Streamflow observations at the outlet of the basins are used as the reference streamflow data. The results show that in general, in all the three DMIP 2 basins the simulated hydrographs forced with PERSIANN-CDR and TMPA show good agreement, as the statistical measures such as root mean square error, bias, and correlation coefficient are close. In addition, with respect to the streamflow peaks, PERSIANN-CDR shows better performance than Stage IV radar data in capturing the extreme streamflow magnitudes. Based on the results from the first phase of the study and given the fact that PERSIANN-CDR covers the 1983-2014, in the second phase of the study we model the streamflow for the period of 1983-2014. The results will be presented in the meeting.

Effectiveness of carbon dioxide removal in lowering atmospheric CO2 and reversing global warming in the context of 1.5 degrees

NASA Astrophysics Data System (ADS)

Zickfeld, K.; Azevedo, D.

2017-12-01

The majority of emissions scenarios that limit warming to 2°C, and nearly all emission scenarios that do not exceed 1.5°C warming by the year 2100 require artificial removal of CO2 from the atmosphere. Carbon dioxide removal (CDR) technologies in these scenarios are required to offset emissions from sectors that are difficult or costly to decarbonize and to generate global `net negative' emissions, allowing to compensate for earlier emissions and to meet long-term climate stabilization targets after overshoot. Only a few studies have explored the Earth system response to CDR and large uncertainties exist regarding the effect of CDR on the carbon cycle and its effectiveness in reversing climate impacts after overshoot. Here we explore the effectiveness of CDR in lowering atmospheric CO2 ("carbon cycle effectiveness") and cool global climate ("cooling effectiveness"). We force the University of Victoria Earth System Climate Model, a model of intermediate complexity, with a set of negative CO2 emissions pulses of different magnitude and applied from different background atmospheric CO2 concentrations. We find the carbon cycle effectiveness of CDR - defined as the change in atmospheric CO2 per unit CO2 removed - decreases with the amount of CO2 removed from the atmosphere and increases at higher background CO2 concentrations from which CDR is applied due to nonlinear responses of carbon sinks to CO2 and climate. The cooling effectiveness - defined as the change in global mean surface air temperature per unit CO2 removed - on the other hand, is largely insensitive to the amount of CO2 removed, but decreases if CDR is applied at higher atmospheric CO2 concentrations, due to the logarithmic relationship between atmospheric CO2 and radiative forcing. Based on our results we conclude that CDR is more effective in restoring a lower atmospheric CO2 concentration and reversing impacts directly linked to CO2 at lower levels of overshoot. CDR's effectiveness in restoring a cooler climate, on the other hand, is largely insensitive to the level of overshoot.

Force and power characteristics of a resistive exercise device for use in space

NASA Astrophysics Data System (ADS)

Berg, Hans E.; Tesch, Per A.

We have developed a non-gravity dependent mechanical device, which provides resistance during coupled concentric and eccentric muscle actions, through the inertia of a spinning fly-wheel (Fly-Wheel Ergometry; FWE). Our research shows that lower-limb FWE exercise can produce forces and thus muscular stress comparable to what is typical of advanced resistance training using free weights. FWE also offers greater training stimuli during eccentric relative to concentric muscle actions, as evidenced by force and electromyographic (EMG) measurements. Muscle use of specific muscle groups, as assessed by the exercise-induced contrast shift of magnetic resonance images, is similar during lower-limb FWE and the barbell squat. Unlike free-weight exercise, FWE allows for maximal voluntary effort in each repetition of an exercise bout. Likewise, FWE exercise, not unassisted free-weight exercise, produces eccentric "overload". Collectively, the inherent features of this resistive exercise device and the results of the physiological evaluations we have performed, suggest that resistance exercise using FWE could be used as an effective exercise counter-measure in space. The flywheel principle can be employed to any exercise configuration and designed into a compact device allowing for exercises stressing those muscles and bone structures, which are thought to be most affected by long-duration spaceflight.

The diversity of H3 loops determines the antigen-binding tendencies of antibody CDR loops.

PubMed

Tsuchiya, Yuko; Mizuguchi, Kenji

2016-04-01

Of the complementarity-determining regions (CDRs) of antibodies, H3 loops, with varying amino acid sequences and loop lengths, adopt particularly diverse loop conformations. The diversity of H3 conformations produces an array of antigen recognition patterns involving all the CDRs, in which the residue positions actually in contact with the antigen vary considerably. Therefore, for a deeper understanding of antigen recognition, it is necessary to relate the sequence and structural properties of each residue position in each CDR loop to its ability to bind antigens. In this study, we proposed a new method for characterizing the structural features of the CDR loops and obtained the antigen-binding ability of each residue position in each CDR loop. This analysis led to a simple set of rules for identifying probable antigen-binding residues. We also found that the diversity of H3 loop lengths and conformations affects the antigen-binding tendencies of all the CDR loops. © 2016 The Protein Society.

Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists.

PubMed

Liu, Tao; Zhang, Yong; Liu, Yan; Wang, Ying; Jia, Haiqun; Kang, Mingchao; Luo, Xiaozhou; Caballero, Dawna; Gonzalez, Jose; Sherwood, Lance; Nunez, Vanessa; Wang, Danling; Woods, Ashley; Schultz, Peter G; Wang, Feng

2015-02-03

On the basis of the 3D structure of a bovine antibody with a well-folded, ultralong complementarity-determining region (CDR), we have developed a versatile approach for generating human or humanized antibody agonists with excellent pharmacological properties. Using human growth hormone (hGH) and human leptin (hLeptin) as model proteins, we have demonstrated that functional human antibody CDR fusions can be efficiently engineered by grafting the native hormones into different CDRs of the humanized antibody Herceptin. The resulting Herceptin CDR fusion proteins were expressed in good yields in mammalian cells and retain comparable in vitro biological activity to the native hormones. Pharmacological studies in rodents indicated a 20- to 100-fold increase in plasma circulating half-life for these antibody agonists and significantly extended in vivo activities in the GH-deficient rat model and leptin-deficient obese mouse model for the hGH and hLeptin antibody fusions, respectively. These results illustrate the utility of antibody CDR fusions as a general and versatile strategy for generating long-acting protein therapeutics.

The Dynamics of Change: Regeneration of the Indonesian Army.

DTIC Science & Technology

1984-11-15

Army Special Forces (KOPASSANDHA): COI1U11a11Idl MG Yogic Suardi Memet * it(B) CCL, W ismuy Ar i.-j MU11,1IL101 A (N4) Deputy Commander *MG Soedjasmin0...KLTG Yogic Suardi Memet Cdr KODAM, VI/Cdr Special Forces Cdr KOWILHAN II BG S. Momon HI. Ad ip)Utro) Unknown Chi Army F iulaaic L’uia’ BC IP1

Nurse Corps Training Importance Survey Report

DTIC Science & Technology

1992-06-01

Midwifery , and Psychiatry: CDR Mary Goeden NC, USN, CDR Candace Curlee NC, USN, and LCDR Phillip Harrison NC, USN. Dr. Alexander M. Gottesman and CDR...Corps subspecialty advisors to the Surgeon General for Orthopedics, Nurse Midwifery , and Psychiatry. It was mailed to a population of approximately...and analgesic drugs X 57. Identify common orthopedic injectables X ’Performed by less than 50% of staff nurses NC TIS 63 B - II. ADDITIONAL TRAINING

Increased Activity of [gamma]-Glutamylcysteine Synthetase in Tomato Cells Selected for Cadmium Tolerance.

PubMed

Chen, J.; Goldsbrough, P. B.

1994-09-01

Two cell lines of tomato (Lycopersicon esculentum Mill cv VFNT-Cherry) were systematically compared for their capacity to tolerate cadmium. Unselected CdS cells died in the presence of 0.3 mM CdCl2. CdR6-0 cells, which were selected from CdS, survived and grew in medium supplemented with 0.3 mM CdCl2. Growth of CdR6-0 cells under this condition was accompanied by synthesis of cadmium-binding phytochelatins and maintenance of cellular glutathione (GSH) levels. CdR6-0 cells also exhibited increased tolerance to buthionine sulfoximine, in both the presence and absence of 0.1 mM CdCl2. The specific activity of [gamma]-glutamylcysteine synthetase (EC 6.3.2.2) was approximately 2-fold higher in CdR6-0 cells than in CdS cells, whereas there was no difference between cell lines in specific activity of GSH synthetase (EC 6.3.2.3). Increased activity of the first enzyme of GSH biosynthesis in CdR6-0 cells, presumably a result of selection for increased cadmium tolerance, provides an enhanced capacity to synthesize GSH and to maintain the production of phytochelatins in response to cadmium. This adaptation may contribute to the enhanced cadmium tolerance of CdR6-0 cells.

Incidence of dementia and cause of death in elderly Japanese emigrants to Brazil before World War II.

PubMed

Meguro, Kenichi; Chubaci, Rosa Y S; Meguro, Mitsue; Kawamorida, Kazumi; Goto, Nobuko; Caramelli, Paulo

2011-01-01

In 1997 we examined the prevalence of dementia among the Japanese elderly immigrants living in the São Paulo metropolitan area (n=166). Herein, we followed up on these subjects for causes of death and dementia incidence. We were able to contact 108 subjects: 54 were already dead. The most common cause of death was cardiac disease. For dementia, 31.6% of the dead subjects were found to have developed dementia before they died, and 20.8 % of the living subjects were demented. As for the baseline the clinical dementia rating (CDR), 20.8 % of CDR 0 and 50.0 % of CDR 0.5 subjects developed dementia in the dead group; whereas in the living group, 23.9 % of CDR 0 and 52.6 % of CDR 0.5 developed dementia. As a whole, the incidence was 34.2 ‰ per 1000 person-years. Cardiac disease as the most common cause of death was probably due to the higher prevalence of diabetes mellitus. Compared with the previous study, the lower incidence of dementia from the CDR 0.5 group may have been due to a higher mortality rate. This is the first study on the incidence of dementia in elderly Japanese immigrants in Brazil. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Dysregulated miR-671-5p / CDR1-AS / CDR1 / VSNL1 axis is involved in glioblastoma multiforme

PubMed Central

Salito, Loredana; Sammito, Mariangela; Banelli, Barbara; Caltabiano, Rosario; Barbagallo, Giuseppe; Zappalà, Agata; Battaglia, Rosalia; Cirnigliaro, Matilde; Lanzafame, Salvatore; Vasquez, Enrico; Parenti, Rosalba; Cicirata, Federico; Di Pietro, Cinzia; Romani, Massimo; Purrello, Michele

2016-01-01

MiR-671-5p is encoded by a gene localized at 7q36.1, a region amplified in human glioblastoma multiforme (GBM), the most malignant brain cancer. To investigate whether expression of miR-671-5p were altered in GBM, we analyzed biopsies from a cohort of forty-five GBM patients and from five GBM cell lines. Our data show significant overexpression of miR-671-5p in both biopsies and cell lines. By exploiting specific miRNA mimics and inhibitors, we demonstrated that miR-671-5p overexpression significantly increases migration and to a less extent proliferation rates of GBM cells. Through a combined in silico and in vitro approach, we identified CDR1-AS, CDR1, VSNL1 as downstream miR-671-5p targets in GBM. Expression of these genes significantly decreased both in GBM biopsies and cell lines and negatively correlated with that of miR-671-5p. Based on our data, we propose that the axis miR-671-5p / CDR1-AS / CDR1 / VSNL1 is functionally altered in GBM cells and is involved in the modification of their biopathological profile. PMID:26683098

Converging evolution leads to near maximal junction diversity through parallel mechanisms in B and T cell receptors

NASA Astrophysics Data System (ADS)

Benichou, Jennifer I. C.; van Heijst, Jeroen W. J.; Glanville, Jacob; Louzoun, Yoram

2017-08-01

T and B cell receptor (TCR and BCR) complementarity determining region 3 (CDR3) genetic diversity is produced through multiple diversification and selection stages. Potential holes in the CDR3 repertoire were argued to be linked to immunodeficiencies and diseases. In contrast with BCRs, TCRs have practically no Dβ germline genetic diversity, and the question emerges as to whether they can produce a diverse CDR3 repertoire. In order to address the genetic diversity of the adaptive immune system, appropriate quantitative measures for diversity and large-scale sequencing are required. Such a diversity method should incorporate the complex diversification mechanisms of the adaptive immune response and the BCR and TCR loci structure. We combined large-scale sequencing and diversity measures to show that TCRs have a near maximal CDR3 genetic diversity. Specifically, TCR have a larger junctional and V germline diversity, which starts more 5‧ in Vβ than BCRs. Selection decreases the TCR repertoire diversity, but does not affect BCR repertoire. As a result, TCR is as diverse as BCR repertoire, with a biased CDR3 length toward short TCRs and long BCRs. These differences suggest parallel converging evolutionary tracks to reach the required diversity to avoid holes in the CDR3 repertoire.

Cumulative Delivery Rate after Providing Full Reimbursement In Vitro Fertilization Programme: A 6-Years Survey

PubMed Central

Vrtacnik, Urban; Vrtacnik Bokal, Eda

2014-01-01

Since 1983, Slovenia has been offering well-established, successful, and fully reimbursed IVF programme to infertile couples. On the grounds of data gathered at the Slovenian IVF units we aimed to determine whether the fully accessible IVF treatment system can provide notable success considering cumulative delivery rate (cDR). Longitudinal analysis of getting cDR was performed in 810 IVF cycles of 395 couples who for the first time attended the IVF programme in year 2006 and were followed until year 2012. We calculated the actual and the optimistic cDR. In women aged <38 years the actual cDR was 54% and optimistic DR was 83%, respectively. In women aged ≥38 years the actual cDR was 24 % and optimistic cDR was 27%. These results enable us to report that prospects of the treatment for the women aged <38 years, if they undergo all 6 available IVF cycles, are very positive and quite comparable to the chances of spontaneous conception. Even in older patients it is beneficial to repeat the IVF procedures. Therefore we consider the existing infertility treatment system in Slovenia as an example of good medical practice with high level of beneficence offered to the patients. PMID:24734248

An anti-hapten camelid antibody reveals a cryptic binding site with significant energetic contributions from a nonhypervariable loop

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

Fanning, Sean W.; Horn, James R.

2014-03-05

Conventional anti-hapten antibodies typically bind low-molecular weight compounds (haptens) in the crevice between the variable heavy and light chains. Conversely, heavy chain-only camelid antibodies, which lack a light chain, must rely entirely on a single variable domain to recognize haptens. While several anti-hapten VHHs have been generated, little is known regarding the underlying structural and thermodynamic basis for hapten recognition. Here, an anti-methotrexate VHH (anti-MTX VHH) was generated using grafting methods whereby the three complementarity determining regions (CDRs) were inserted onto an existing VHH framework. Thermodynamic analysis of the anti-MTX VHH CDR1-3 Graft revealed a micromolar binding affinity, while themore » crystal structure of the complex revealed a somewhat surprising noncanonical binding site which involved MTX tunneling under the CDR1 loop. Due to the close proximity of MTX to CDR4, a nonhypervariable loop, the CDR4 loop sequence was subsequently introduced into the CDR1-3 graft, which resulted in a dramatic 1000-fold increase in the binding affinity. Crystal structure analysis of both the free and complex anti-MTX CDR1-4 graft revealed CDR4 plays a significant role in both intermolecular contacts and binding site conformation that appear to contribute toward high affinity binding. Additionally, the anti-MTX VHH possessed relatively high specificity for MTX over closely related compounds aminopterin and folate, demonstrating that VHH domains are capable of binding low-molecular weight ligands with high affinity and specificity, despite their reduced interface.« less

Ten-year incidence of dementia in a rural elderly US community population: the MoVIES Project.

PubMed

Ganguli, M; Dodge, H H; Chen, P; Belle, S; DeKosky, S T

2000-03-14

To determine incidence rates by age, sex, and education of overall dementia and probable/ possible AD in a largely rural community. Ten-year prospective study of a randomly selected community sample aged 65+; biennial cognitive screening followed by standardized clinical evaluation. Incidence rates were estimated for overall dementia (Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised, criteria and Clinical Dementia Rating [CDR]) and for probable/possible AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria). The cohort consisted of 1,298 individuals free of dementia at study entry. Among these, 199 incident (new) cases of overall (all-cause) dementia with CDR stage > or = 0.5, including 110 with CDR > or = 1, were detected during follow-up. Among the incident cases, 153 (76.9%) had probable/ possible AD. Age-specific incidence rates are reported for all dementia and for probable/possible AD, by sex and CDR stage. Among all-cause dementias with CDR = 0.5, controlling for age and education, men had a higher incidence rate than women. In the same group, those with less than high school education had significantly higher incidence rates than those with more education. Rates did not vary significantly by sex or education for probable/possible AD or for dementia with CDR > or = 1. Incidence rates of all dementias and of AD increased with age; men and those with lesser education had higher rates of possible/incipient dementia (CDR = 0.5) in this community. Potential explanations for these sex and education effects are discussed.

Application of distance-dependent resolution compensation and post-reconstruction filtering for myocardial SPECT

NASA Astrophysics Data System (ADS)

Hutton, Brian F.; Lau, Yiu H.

1998-06-01

Compensation for distance-dependent resolution can be directly incorporated in maximum likelihood reconstruction. Our objective was to examine the effectiveness of this compensation using either the standard expectation maximization (EM) algorithm or an accelerated algorithm based on use of ordered subsets (OSEM). We also investigated the application of post-reconstruction filtering in combination with resolution compensation. Using the MCAT phantom, projections were simulated for data, including attenuation and distance-dependent resolution. Projection data were reconstructed using conventional EM and OSEM with subset size 2 and 4, with/without 3D compensation for detector response (CDR). Also post-reconstruction filtering (PRF) was performed using a 3D Butterworth filter of order 5 with various cutoff frequencies (0.2-). Image quality and reconstruction accuracy were improved when CDR was included. Image noise was lower with CDR for a given iteration number. PRF with cutoff frequency greater than improved noise with no reduction in recovery coefficient for myocardium but the effect was less when CDR was incorporated in the reconstruction. CDR alone provided better results than use of PRF without CDR. Results suggest that using CDR without PRF, and stopping at a small number of iterations, may provide sufficiently good results for myocardial SPECT. Similar behaviour was demonstrated for OSEM.

Compact, Controlled Resistance Exercise Device

NASA Technical Reports Server (NTRS)

Paulus, David C.; DeWitt, John K.; Reich, Alton J.; Shaw, James E.; Deaconu, Stelu S.

2011-01-01

Spaceflight leads to muscle and bone atrophy. Isoinertial (free-weight) exercises provide a sufficient stimulus to elicit increases in both muscle strength and bone mineral density in Earth-based studies. While exercise equipment is in use on the International Space Station for crewmember health maintenance, current devices are too large to place in a transport vehicle or small spacecraft. Therefore, a portable computer controlled resistance exercise device is being developed that is able to simulate the inertial loading experienced when lifting a mass on Earth. This portable device weighs less than 50 lb and can simulate the resistance of lifting and lowering up to 600 lb of free-weights. The objective is to allow crewmembers to perform resistance exercise with loads capable of maintaining muscle and bone health. The device is reconfigurable and allows for the performance of typical Earth-based free-weight exercises. Forces exerted, volume of work, range of motion, time-under-tension, and speed/ acceleration of movement are recorded and can be remotely monitored to track progress and modify individual protocols based on exercise session data. A performance evaluation will be completed and data will be presented that include ground-reaction force comparisons between the device and free-weight dead-lifts over a spectrum of resistance levels. Movement biomechanics will also be presented.

Development of an Integrated Countermeasure Device for Long Duration Space Flight and Exploration Missions

NASA Technical Reports Server (NTRS)

Lee, S. M. C.; Streeper, T.; Spiering, B. A.; Loehr, J. A.; Guilliams, M. E.; Bloomberg, J. J.; Mulavara, A. P.; Cavanagh, P. R.; Lang, T.

2010-01-01

Musculoskeletal, cardiovascular, and sensorimotor deconditioning have been observed consistently in astronauts and cosmonauts following long-duration spaceflight. Studies in bed rest, a spaceflight analog, have shown that high intensity resistive or aerobic exercise attenuates or prevents musculoskeletal and cardiovascular deconditioning, respectively, but complete protection has not been achieved during spaceflight. Exercise countermeasure hardware used during earlier International Space Station (ISS) missions included a cycle ergometer, a treadmill, and the interim resistive exercise device (iRED). Effectiveness of the countermeasures may have been diminished by limited loading characteristics of the iRED as well as speed restrictions and subject harness discomfort during treadmill exercise. The Advanced Resistive Exercise Device (ARED) and the second generation treadmill were designed to address many of the limitations of their predecessors, and anecdotal reports from ISS crews suggest that their conditioning is better preserved since the new hardware was delivered in 2009. However, several countermeasure devices to protect different physiologic systems will not be practical during exploration missions when the available volume and mass will be severely restricted. The combined countermeasure device (CCD) integrates a suite of hardware into one device intended to prevent spaceflight-induced musculoskeletal, cardiovascular, and sensorimotor deconditioning. The CCD includes pneumatic loading devices with attached cables for resistive exercise, a cycle for aerobic exercise, and a 6 degree of freedom motion platform for balance training. In a proof of concept test, ambulatory untrained subjects increased muscle strength (58%) as well as aerobic capacity (26%) after 12-weeks of exercise training with the CCD (without balance training), improvements comparable to those observed with traditional exercise training. These preliminary results suggest that this CCD can concurrently improve musculoskeletal and cardiovascular conditioning in ambulatory subjects, but further work is required to validate its use as countermeasure to spaceflight-induced deconditioning.

Identification of type IV collagen exposure as a molecular imaging target for early detection of thoracic aortic dissection

PubMed Central

Xu, Ke; Xu, Chen; Zhang, Yanzhenzi; Qi, Feiran; Yu, Bingran; Li, Ping; Jia, Lixin; Li, Yulin; Xu, Fu-jian; Du, Jie

2018-01-01

Thoracic aortic dissection (TAD) is an aggressive and life-threatening vascular disease and there is no effective means of early diagnosis of dissection. Type IV collagen (Col-IV) is a major component of the sub-endothelial basement membrane, which is initially exposed followed by endothelial injury as early-stage event of TAD. So, we want to build a noninvasive diagnostic method to detect early dissection by identifying the exposed Col-IV via MRI. Methods: Col-IV-targeted magnetic resonance/ fluorescence dual probe (Col-IV-DOTA-Gd-rhodamine B; CDR) was synthesized by amide reaction and coordination reaction. Flow cytometry analysis was used to evaluate the cell viability of SMC treated with CDR and fluorescence assays were used to assess the Col-IV targeting ability of CDR in vitro. We then examined the sensitivity and specificity of CDR at different stages of TAD via MRI and bioluminescence imaging in vivo. Results: The localization of Col-IV (under the intima) was observed by histology images. CDR bound specifically to Col-IV-expressing vascular smooth muscle cells and BAPN-induced dissected aorta. The CDR signal was co-detected by magnetic resonance imaging (MRI) and bioluminescence imaging as early as 2 weeks after BAPN administration (pre-dissection stage). The ability to detect rupture of dissected aorta was indicated by a strong normalized signal enhancement (NSE) in vivo. Moreover, NSE was negatively correlated with the time of dissection rupture after BAPN administration (r2 = 0.8482). Conclusion: As confirmed by in vivo studies, the CDR can identify the exposed Col-IV in degenerated aorta to monitor the progress of aortic dissection from the early stage to the rupture via MRI. Thus, CDR-enhanced MRI proposes a potential method for dissection screening, and for monitoring disease progression and therapeutic response. PMID:29290819

jsc2017m000677_SpeedyTime2–Advanced_ Resistive_Exercise_ Device

NASA Image and Video Library

2017-07-20

SpeedyTime #2 – Advanced Resistive Exercise Device Astronauts on the International Space Station have to exercise for two hours every day, but they can show off the hardware in a lot less time than that. In this “SpeedyTime” segment Expedition 52 flight engineer Peggy Whitson gives us a rapid-fire display of exercises that can be done with just one piece of equipment, the Advanced Resistive Exercise Device in the Tranquility module. _______________________________________ FOLLOW THE SPACE STATION! Twitter: https://twitter.com/Space_Station Facebook: https://www.facebook.com/ISS Instagram: https://instagram.com/iss/

[Effects of breathing exercises on breathing pattern and thoracoabdominal motion after gastroplasty].

PubMed

Tomich, Georgia Miranda; França, Danielle Corrêa; Diniz, Marco Túlio Costa; Britto, Raquel Rodrigues; Sampaio, Rosana Ferreira; Parreira, Verônica Franco

2010-01-01

To evaluate breathing pattern and thoracoabdominal motion during breathing exercises. Twenty-four patients with class II or III obesity (18 women; 6 men) were studied on the second postoperative day after gastroplasty. The mean age was 37 +/- 11 years, and the mean BMI was 44 +/- 3 kg/m(2). Diaphragmatic breathing, incentive spirometry with a flow-oriented device and incentive spirometry with a volume-oriented device were performed in random order. Respiratory inductive plethysmography was used in order to measure respiratory variables and thoracoabdominal motion. Comparisons among the three exercises showed significant differences: tidal volume was higher during incentive spirometry (with the flow-oriented device or with the volume-oriented device) than during diaphragmatic breathing; the respiratory rate was lower during incentive spirometry with the volume-oriented device than during incentive spirometry with the flow-oriented device; and minute ventilation was higher during incentive spirometry (with the flow-oriented device or with the volume-oriented device) than during diaphragmatic breathing. Rib cage motion did not vary during breathing exercises, although there was an increase in thoracoabdominal asynchrony, especially during incentive spirometry with the flow-oriented device. Among the breathing exercises evaluated, incentive spirometry with the volume-oriented device provided the best results, because it allowed slower, deeper inhalation.

The limits to global-warming mitigation by terrestrial carbon removal

NASA Astrophysics Data System (ADS)

Boysen, Lena R.; Lucht, Wolfgang; Gerten, Dieter; Heck, Vera; Lenton, Timothy M.; Schellnhuber, Hans Joachim

2017-05-01

Massive near-term greenhouse gas emissions reduction is a precondition for staying "well below 2°C" global warming as envisaged by the Paris Agreement. Furthermore, extensive terrestrial carbon dioxide removal (tCDR) through managed biomass growth and subsequent carbon capture and storage is required to avoid temperature "overshoot" in most pertinent scenarios. Here, we address two major issues: First, we calculate the extent of tCDR required to "repair" delayed or insufficient emissions reduction policies unable to prevent global mean temperature rise of 2.5°C or even 4.5°C above pre-industrial level. Our results show that those tCDR measures are unable to counteract "business-as-usual" emissions without eliminating virtually all natural ecosystems. Even if considerable (Representative Concentration Pathway 4.5 [RCP4.5]) emissions reductions are assumed, tCDR with 50% storage efficiency requires >1.1 Gha of the most productive agricultural areas or the elimination of >50% of natural forests. In addition, >100 MtN/yr fertilizers would be needed to remove the roughly 320 GtC foreseen in these scenarios. Such interventions would severely compromise food production and/or biosphere functioning. Second, we reanalyze the requirements for achieving the 160-190 GtC tCDR that would complement strong mitigation action (RCP2.6) in order to avoid 2°C overshoot anytime. We find that a combination of high irrigation water input and/or more efficient conversion to stored carbon is necessary. In the face of severe trade-offs with society and the biosphere, we conclude that large-scale tCDR is not a viable alternative to aggressive emissions reduction. However, we argue that tCDR might serve as a valuable "supporting actor" for strong mitigation if sustainable schemes are established immediately.

Farnesol-Induced Apoptosis in Candida albicans Is Mediated by Cdr1-p Extrusion and Depletion of Intracellular Glutathione

PubMed Central

Zhu, Jingsong; Krom, Bastiaan P.; Sanglard, Dominique; Intapa, Chaidan; Dawson, Clinton C.; Peters, Brian M.; Shirtliff, Mark E.; Jabra-Rizk, Mary Ann

2011-01-01

Farnesol is a key derivative in the sterol biosynthesis pathway in eukaryotic cells previously identified as a quorum sensing molecule in the human fungal pathogen Candida albicans. Recently, we demonstrated that above threshold concentrations, farnesol is capable of triggering apoptosis in C. albicans. However, the exact mechanism of farnesol cytotoxicity is not fully elucidated. Lipophilic compounds such as farnesol are known to conjugate with glutathione, an antioxidant crucial for cellular detoxification against damaging compounds. Glutathione conjugates act as substrates for ATP-dependent ABC transporters and are extruded from the cell. To that end, this current study was undertaken to validate the hypothesis that farnesol conjugation with intracellular glutathione coupled with Cdr1p-mediated extrusion of glutathione conjugates, results in total glutathione depletion, oxidative stress and ultimately fungal cell death. The combined findings demonstrated a significant decrease in intracellular glutathione levels concomitant with up-regulation of CDR1 and decreased cell viability. However, addition of exogenous reduced glutathione maintained intracellular glutathione levels and enhanced viability. In contrast, farnesol toxicity was decreased in a mutant lacking CDR1, whereas it was increased in a CDR1-overexpressing strain. Further, gene expression studies demonstrated significant up-regulation of the SOD genes, primary enzymes responsible for defense against oxidative stress, with no changes in expression in CDR1. This is the first study describing the involvement of Cdr1p-mediated glutathione efflux as a mechanism preceding the farnesol-induced apoptotic process in C. albicans. Understanding of the mechanisms underlying farnesol-cytotoxicity in C. albicans may lead to the development of this redox-cycling agent as an alternative antifungal agent. PMID:22205973

Overexpression of MDR-1 and CDR-2 genes in fluconazole resistance of Candida albicans isolated from patients with vulvovaginal candidiasis.

PubMed

Khosravi Rad, K; Falahati, M; Roudbary, M; Farahyar, S; Nami, S

2016-12-01

Candida albicans ( C. albicans ) is an opportunistic fungus that can colonize women's mucosal epithelial cell surfaces, causing vulvovaginitis in specific circumstances. The major genes contributing to drug resistance in C. albicans are the candida drug resistance ( CDR ) and multi drug resistance ( MDR ) genes. The purpose of this study was to evaluate the CDR-2 and MDR-1 gene expression patterns in C. albicans strains isolated from patients with recurrent vulvovaginal candidiasis. In this study, 40 isolates of fluconazole-resistant C. albicans were cultured on Sabouraud dextrose agar. These isolates were collected from women with vulvovaginitis who were referred to a clinic in Tehran, Iran, and transferred to a mycology laboratory. Then, RNA was extracted from the isolates using phenol-chloroform and glass beads, and the complementary DNA (cDNA) was synthetized. To detect the semi-quantitative expression of CDR-2 and MDR-1 genes, the reverse transcriptase-PCR (RT-PCR) technique was performed using specific primers. Our findings indicated that of the 40 C. albicans isolates, 35 (87.5%) strains were positive for mRNA of the CDR-2 gene, 32 (80%) strains expressed mRNA of the MDR-1 gene, and 30 (75%) strains were confirmed to express mRNA of both the CDR-2 and MDR-1 genes simultaneously using the RT-PCR assay. According to the obtained results, the expression rates of CDR-2 and MDR-1 genes were high in fluconazole-resistant C. albicans isolates, which can cause treatments to fail and result in chronic infections. Inhibiting these important genes using novel or natural agents can help with the treatment of chronic and recurrent vaginitis.

Procedures in child deaths in The Netherlands: a comparison with child death review.

PubMed

Gijzen, Sandra; Petter, Jessica; L'Hoir, Monique P; Boere-Boonekamp, Magda M; Need, Ariana

2017-01-01

Child Death Review (CDR) is a method in which every child death is systematically and multidisciplinary examined to (1) improve death statistics, (2) identify factors that give direction for prevention, (3) translate the results into possible interventions, and (4) support families. The aim of this study was to determine to what extent procedures of organizations involved in the (health) care for children in The Netherlands cover these four objectives of CDR. Organizations in the Eastern part of The Netherlands and Dutch umbrella organizations involved in child (health) care were asked to provide their protocols, guidelines or other working agreements that describe their activities and responsibilities in case of a child's death. Eighteen documents and nine interview reports were made available. For the analyses we used scorecards for each CDR objective. The procedures of Perined, the National Cot Death Study Group, Dutch Cot Death Foundation and Child Protection Service cover the largest part of the objectives of CDR. Organizations pay most attention to the translation of results into possible interventions. Family support gets the least attention in protocols, guidelines and other working agreements. Dutch organizations separately cover parts of CDR. When the procedures of organizations are combined, all CDR objectives are covered in the response to only specific groups of child deaths, i.e., perinatal deaths, Sudden Unexpected Deaths in Infants and fatal child abuse cases. Further research into the conditions that are needed for an optimal implementation of CDR in The Netherlands is necessary. This research should also evaluate the recently implemented NODOK procedure (Further Examination of the Causes of death in Children), directed to investigate unexplained deaths in minors 0-18 years old.

Overcoming the heterologous bias: an in vivo functional analysis of multidrug efflux transporter, CgCdr1p in matched pair clinical isolates of Candida glabrata.

PubMed

Puri, Nidhi; Manoharlal, Raman; Sharma, Monika; Sanglard, Dominique; Prasad, Rajendra

2011-01-07

We have taken advantage of the natural milieu of matched pair of azole sensitive (AS) and azole resistant (AR) clinical isolates of Candida glabrata for expressing its major ABC multidrug transporter, CgCdr1p for structure and functional analysis. This was accomplished by tagging a green fluorescent protein (GFP) downstream of ORF of CgCDR1 and integrating the resultant fusion protein at its native chromosomal locus in AS and AR backgrounds. The characterization confirmed that in comparison to AS isolate, CgCdr1p-GFP was over-expressed in AR isolates due to its hyperactive native promoter and the GFP tag did not affect its functionality in either construct. We observed that in addition to Rhodamine 6 G (R6G) and Fluconazole (FLC), a recently identified fluorescent substrate of multidrug transporters Nile Red (NR) could also be expelled by CgCdr1p. Competition assays with these substrates revealed the presence of overlapping multiple drug binding sites in CgCdr1p. Point mutations employing site directed mutagenesis confirmed that the role played by unique amino acid residues critical to ATP catalysis and localization of ABC drug transporter proteins are well conserved in C. glabrata as in other yeasts. This study demonstrates a first in vivo novel system where over-expression of GFP tagged MDR transporter protein can be driven by its own hyperactive promoter of AR isolates. Taken together, this in vivo system can be exploited for the structure and functional analysis of CgCdr1p and similar proteins wherein the artefactual concerns encountered in using heterologous systems are totally excluded. Copyright © 2010 Elsevier Inc. All rights reserved.

Rightsizing expectations for carbon dioxide removal towards ambitious climate goals

NASA Astrophysics Data System (ADS)

Mach, K. J.; Field, C. B.

2017-12-01

Proven approaches for reducing heat-trapping emissions are increasingly cost competitive and feasible at scale. Such approaches include renewable-energy technologies, energy efficiency, reduced deforestation, and abatement of industrial and agricultural emissions. Their pace of deployment, though, is far from sufficient to limit warming well below 2°C above preindustrial levels, the goal of the Paris Agreement. Against this backdrop, technologies for carbon removal are increasingly asserted as key to climate policy. Carbon dioxide removal (CDR), or negative emissions, technologies can compensate for ongoing emissions, helping keep ambitious warming limits in reach. The dramatic rise of CDR approaches in analysis and planning towards ambitious climate goals, however, has stirred up discomfort and debate. Focusing on rightsizing CDR expectations, this presentation will first briefly reflect on the status of the suite of CDR possibilities. The options include strategies grounded in improved ecosystem stewardship (e.g., reforestation and afforestation, conservation agriculture); strategies that are also biomass-based but with more engineering and more trade-offs (e.g., biochar additions to soils, bioenergy with carbon capture and storage); and engineered, nonbiological approaches (e.g., enhanced weathering, direct air capture). Second, the presentation will evaluate constraints surrounding CDR deployment at large scale and in peak-and-decline scenarios. These constraints involve, for example, unprecedented rates of land transformation in climate change mitigation pathways limiting warming to 2°C with high probability. They also entail the substantial, little studied risks of scenarios with temperatures peaking and then declining. Third, the presentation will review emerging lessons from CDR implementation to date, such as in legally enforceable forest-offset projects, along with near-term opportunities for catalyzing CDR, such as through low-cost opportunities for carbon capture and storage.

Anti-CDR3 Therapy for B-Cell Malignancies

DTIC Science & Technology

2013-10-01

1-5 in the report). The "Tomlinson" human antibody phage library will be used to pan for antibodies that bind these target CDR3s and not the parent...selection of phage to a test antigen. Successful expression will lead directly to the selection of CDR3-specific antibody-encoding phage : from which we... phage that bind to the purified candidate antibody and not to irrelevant antibodies. Phage are from single chain Fv library. Sequence phage that

Hypertension is associated with cognitive decline in elderly people at high risk for dementia.

PubMed

Wysocki, Michael; Luo, Xiaodong; Schmeidler, James; Dahlman, Karen; Lesser, Gerson T; Grossman, Hillel; Haroutunian, Vahram; Beeri, Michal Schnaider

2012-02-01

Cardiovascular risk factors including hypertension (HTN) have been shown to increase the risk of Alzheimer disease. The current study investigated whether individuals with HTN are more susceptible to increased cognitive decline and whether the influence of HTN on cognitive decline varied as a function of dementia severity. A total of 224 nursing home and assisted living residents, with a mean age of 84.9 (±7.6) years, were assessed longitudinally with Mini Mental State Exams (MMSEs) and Clinical Dementia Ratings (CDR). Baseline dementia status was defined by the CDR score. As described in , MMSE scores in persons with HTN and questionable dementia (CDR = 0.5) declined significantly faster than nonhypertensive questionably demented persons. Hypertensive participants did not decline significantly faster than nonhypertensive participants in persons with intact cognition (CDR = 0) or frank dementia (CDR ≥ 1). These results suggest an increased risk of subsequent cognitive decline in hypertensive individuals who are especially vulnerable to developing dementia and raises the possibility that avoiding or controlling HTN might reduce the rate of cognitive decline in cognitively vulnerable individuals, potentially delaying their conversion to full-fledged dementia.

Corrigendum to ;Diurnal dynamics of minor and trace elements in stream water draining Dongkemadi Glacier on the Tibetan Plateau and its environmental implications; [J. Hydrol. 541 (2016) 1104-1118

NASA Astrophysics Data System (ADS)

Li, Xiangying; He, Xiaobo; Kang, Shichang; Mika, Sillanpää; Ding, Yongjian; Han, Tianding; Wu, Qingbai; Yu, Zhongbo

2017-12-01

The authors regret: At the Dongkemadi Glacier (DG) basin, daily and annual meltwater discharge at gauging section S1 should be corrected. Namely, annual discharge should be 2.74 × 107 m3 throughout 1 June to 30 September of 2013. Thus, variation in solute exports is controlled by changes in discharge and specific solute concentration (Fig. 9), and the estimated solute export, cation denudation rates (CDR) and discharge-normalized CDR are 417 tons, 185 Σ∗meq+m-2 and 189 Σ∗meq+m-3 (with annual specific discharge of 0.98 m) respectively in 2013 (Table 4). In comparison, the CDR at the DG basin is within the scope of previously published CDR (94-4200 Σ∗meq+m-2) from glacial catchments (Hodson et al., 2010). The discharge-normalized CDR is lower than the rates from most glacial catchments, but is higher than those from Mittivakkat (Greenland), S Cascade (N American) and Lewis River (Arctic) (Yde et al., 2004, 2014; Hodson et al., 2000, 2010).

Therapeutic hand-exercising device with cycling pressure value

NASA Technical Reports Server (NTRS)

Barthlome, D. E.

1974-01-01

Device exercises hands of persons whose fingers are generally straight and need to be flexed inward toward palms of hands. Device is extremely simple in design, which reduces costs, and fits all hand sizes. Patient can instantly free hand from device by pulling flap free from wrist of straps.

Transit Reconfigurable Exerciser - Intern Exit Abstract

NASA Technical Reports Server (NTRS)

Gebara, Christine A.

2014-01-01

The Transit Resistive Exerciser (TREX) was developed during a 16 week period in which a clutch device filled with smart material was built and began the testing phase. The clutch serves as a passive method of creating resistance. When paired with a series of springs, the device creates a rowing machine also capable of resistive exercise configurations. The device has loading profiles similar to the exercise devices used on the International Space Station today. The prototype created was designed in a modular fashion to support parallel development on various aspects of the project. Hardware and software are currently in development and make use of commercially available parts. Similar technologies have been used in the automotive industry but have never been explored in the context of countermeasure systems for space flight. If the work done leads to successful testing and further development, this technology has the potential to cut the size and weight of exercise devices by an order of magnitude or more.

Digital Astronaut Project Biomechanical Models: Biomechanical Modeling of Squat, Single-Leg Squat and Heel Raise Exercises on the Hybrid Ultimate Lifting Kit (HULK)

NASA Technical Reports Server (NTRS)

Thompson, William K.; Gallo, Christopher A.; Crentsil, Lawton; Lewandowski, Beth E.; Humphreys, Brad T.; DeWitt, John K.; Fincke, Renita S.; Mulugeta, Lealem

2015-01-01

The NASA Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and to enhance countermeasure development. The DAP Musculoskeletal Modeling effort is developing computational models to inform exercise countermeasure development and to predict physical performance capabilities after a length of time in space. For example, integrated exercise device-biomechanical models can determine localized loading, which will be used as input to muscle and bone adaptation models to estimate the effectiveness of the exercise countermeasure. In addition, simulations of mission tasks can be used to estimate the astronaut's ability to perform the task after exposure to microgravity and after using various exercise countermeasures. The software package OpenSim (Stanford University, Palo Alto, CA) (Ref. 1) is being used to create the DAP biomechanical models and its built-in muscle model is the starting point for the DAP muscle model. During Exploration missions, such as those to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Therefore, the crew must have access to exercise countermeasures that can maintain their musculoskeletal and aerobic health. Exploration vehicles may have very limited volume and power available to accommodate such capabilities, even more so than the International Space Station (ISS). The exercise devices flown on Exploration missions must be designed to provide sufficient load during the performance of various resistance and aerobic/anaerobic exercises while meeting potential additional requirements of limited mass, volume and power. Given that it is not practical to manufacture and test (ground, analog and/or flight) all candidate devices, nor is it always possible to obtain data such as localized muscle and bone loading empirically, computational modeling can estimate the localized loading during various exercise modalities performed on a given device to help formulate exercise prescriptions and other operational considerations. With this in mind, NASA's Digital Astronaut Project (DAP) is supporting the Advanced Exercise Concepts (AEC) Project, Exercise Physiology and Countermeasures (ExPC) laboratory and NSBRI-funded researchers by developing and implementing well-validated computational models of exercises with advanced exercise device concepts. This report focuses specifically on lower-body resistance exercises performed with the Hybrid Ultimate Lifting Kit (HULK) device as a deliverable to the AEC Project.

Facile Affinity Maturation of Antibody Variable Domains Using Natural Diversity Mutagenesis

PubMed Central

Tiller, Kathryn E.; Chowdhury, Ratul; Li, Tong; Ludwig, Seth D.; Sen, Sabyasachi; Maranas, Costas D.; Tessier, Peter M.

2017-01-01

The identification of mutations that enhance antibody affinity while maintaining high antibody specificity and stability is a time-consuming and laborious process. Here, we report an efficient methodology for systematically and rapidly enhancing the affinity of antibody variable domains while maximizing specificity and stability using novel synthetic antibody libraries. Our approach first uses computational and experimental alanine scanning mutagenesis to identify sites in the complementarity-determining regions (CDRs) that are permissive to mutagenesis while maintaining antigen binding. Next, we mutagenize the most permissive CDR positions using degenerate codons to encode wild-type residues and a small number of the most frequently occurring residues at each CDR position based on natural antibody diversity. This mutagenesis approach results in antibody libraries with variants that have a wide range of numbers of CDR mutations, including antibody domains with single mutations and others with tens of mutations. Finally, we sort the modest size libraries (~10 million variants) displayed on the surface of yeast to identify CDR mutations with the greatest increases in affinity. Importantly, we find that single-domain (VHH) antibodies specific for the α-synuclein protein (whose aggregation is associated with Parkinson’s disease) with the greatest gains in affinity (>5-fold) have several (four to six) CDR mutations. This finding highlights the importance of sampling combinations of CDR mutations during the first step of affinity maturation to maximize the efficiency of the process. Interestingly, we find that some natural diversity mutations simultaneously enhance all three key antibody properties (affinity, specificity, and stability) while other mutations enhance some of these properties (e.g., increased specificity) and display trade-offs in others (e.g., reduced affinity and/or stability). Computational modeling reveals that improvements in affinity are generally not due to direct interactions involving CDR mutations but rather due to indirect effects that enhance existing interactions and/or promote new interactions between the antigen and wild-type CDR residues. We expect that natural diversity mutagenesis will be useful for efficient affinity maturation of a wide range of antibody fragments and full-length antibodies. PMID:28928732

Computerized visuo-spatial memory test as a supplementary screening test for dementia.

PubMed

Maki, Yohko; Yoshida, Hiroshi; Yamaguchi, Haruyasu

2010-06-01

To prepare for a super-aging society, effective dementia screening tests are required. The most salient deficit appearing from the early stages of dementia/Alzheimer's disease (AD) is a deterioration in memory. The Hasegawa Dementia Scale-revised (HDS-R) and the Mini-Mental State Examination (MMSE) are widely used in Japan to screen for dementia. Both place an emphasis on memory function, but neither examines visuo-spatial memory (VSM) function, even though VSM deficits are a sensitive marker for the detection of conversion to dementia. Furthermore, brief tests of VSM that are appropriate for screening have not been standardized. Thus, in the present study, we devised a brief, computer-aided short-term VSM test. Sixty-six aged people were evaluated. Using the Clinical Dementia Rating (CDR), it was found that 29 could be considered normal controls (NC; CDR 0), 10 had mild cognitive impairment (MCI; CDR 0.5), 15 had mild dementia (CDR 1), and 12 had moderate to severe dementia (CDR 2-3). The VSM test estimated how many locations each subject could memorize. Several numbered circles were shown on a monitor and subjects were required to memorize the location of these circles sequentially. After the numbers on the circles on the screen had disappeared, the subjects were required to indicate the circles in ascending order. A touch panel screen was used for this test to make it easier. The HDS-R was applied to subjects with MCI and dementia. The mean (+/-SD) VSM score in subjects with MCI (5.70 +/- 0.96) was significantly lower than that in NC subjects (6.69 +/- 0.82), but significantly higher than that in subjects classified as CDR 1 (4.67 +/- 0.87). There was no significant difference in VSM scores between subjects classified as CDR 1 and CDR 2-3 (3.80 +/- 0.80). There was a moderate significant correlation between VSM and HDS-R scores. In the present study, the VSM test detected differences in VSM function among NC subjects and subjects with MCI and mild dementia. The software program for the VSM test is distributed for free so that it can be widely used.

Computational Models of Exercise on the Advanced Resistance Exercise Device (ARED)

NASA Technical Reports Server (NTRS)

Newby, Nate; Caldwell, Erin; Scott-Pandorf, Melissa; Peters,Brian; Fincke, Renita; DeWitt, John; Poutz-Snyder, Lori

2011-01-01

Muscle and bone loss remain a concern for crew returning from space flight. The advanced resistance exercise device (ARED) is used for on-orbit resistance exercise to help mitigate these losses. However, characterization of how the ARED loads the body in microgravity has yet to be determined. Computational models allow us to analyze ARED exercise in both 1G and 0G environments. To this end, biomechanical models of the squat, single-leg squat, and deadlift exercise on the ARED have been developed to further investigate bone and muscle forces resulting from the exercises.

TSCA Chemical Data Reporting Fact Sheet: Toll Manufacturing

EPA Pesticide Factsheets

This fact sheet provides information on existing Chemical Data Reporting (CDR) regulations to persons who are involved in toll manufacturing of chemical substances which may be subject to the CDR rule.

Supplementing biomechanical modeling with EMG analysis

NASA Technical Reports Server (NTRS)

Lewandowski, Beth; Jagodnik, Kathleen; Crentsil, Lawton; Humphreys, Bradley; Funk, Justin; Gallo, Christopher; Thompson, William; DeWitt, John; Perusek, Gail

2016-01-01

It is well established that astronauts experience musculoskeletal deconditioning when exposed to microgravity environments for long periods of time. Spaceflight exercise is used to counteract these effects, and the Advanced Resistive Exercise Device (ARED) on the International Space Station (ISS) has been effective in minimizing musculoskeletal losses. However, the exercise devices of the new exploration vehicles will have requirements of limited mass, power and volume. Because of these limitations, there is a concern that the exercise devices will not be as effective as ARED in maintaining astronaut performance. Therefore, biomechanical modeling is being performed to provide insight on whether the small Multi-Purpose Crew Vehicle (MPCV) device, which utilizes a single-strap design, will provide sufficient physiological loading to maintain musculoskeletal performance. Electromyography (EMG) data are used to supplement the biomechanical model results and to explore differences in muscle activation patterns during exercises using different loading configurations.

Full Body Loading for Small Exercise Devices Project

NASA Technical Reports Server (NTRS)

Downs, Meghan; Hanson, Andrea; Newby, Nathaniel

2015-01-01

Protecting astronauts' spine, hip, and lower body musculoskeletal strength will be critical to safely and efficiently perform physically demanding vehicle egress, exploration, and habitat building activities necessary to expand human presence in the solar system. Functionally limiting decrements in musculoskeletal health are likely during Mars proving-ground and Earth-independent missions given extended transit times and the vehicle limitations for exercise devices (low-mass, small volume). Most small exercise device concepts are designed with single-cable loading, which inhibits the ability to perform full body exercises requiring two-point loading at the shoulders. Shoulder loading is critical to protect spine, hip, and lower body musculoskeletal strength. We propose a novel low-mass, low-maintenance, and rapid deploy pulley-based system that can attach to a single-cable small exercise device to enable two-point loading at the shoulders. This attachment could protect astronauts' health and save cost, space, and energy during all phases of the Journey to Mars.

Synergistic activity of magnolol with azoles and its possible antifungal mechanism against Candida albicans.

PubMed

Sun, L-M; Liao, K; Liang, S; Yu, P-H; Wang, D-Y

2015-04-01

The goal of this study was to investigate the synergic effects between magnolol and azoles, and the potential antifungal mechanisms. Microdilution checkerboard, time-kill and agar diffusion assay were employed to evaluate the synergic effects between magnolol and fluconazole (FLC). Magnolol significantly decreased the efflux of rhodamine 123 (Rh123), leading to greater intracellular accumulation of Rh123 in Candida albicans cells. Compared to the Candida drug resistance (cdr) 2 or multidrug resistance (mdr) 1 deletion mutant, the growth of cdr1 strain was most sensitive to magnolol exposure. In the presence of magnolol, MDR1 overexpressing cells were sensitive to FLC, whereas CDR1 and CDR2 overexpressing cells displayed tolerance to FLC. Magnolol treatment correlated with up-regulation of transporter and ergosterol biosynthesis pathway genes, analyzed by real-time reverse transcription-polymerase chain reaction. The ergosterol content of C. albicansSC5314 was significantly decreased after magnolol exposure. Magnolol synergizes with azoles for targeting of C. albicans by inducing a higher intracellular content of antifungals, by tapping into the competitive effect of ABC transporter Cdr1p substrates, and enhancing the effect by targeting of the ergosterol biosynthesis pathway. Our results provide the first evidence that magnolol may function as a Cdr1p substrate and as an inhibitor of ergosterol biosynthesis. This function can thus be exploited in combination with azoles to reverse multidrug resistance of C. albicans strains. © 2014 The Society for Applied Microbiology.

A Climate-Data Record (CDR) of the "Clear-Sky" Surface Temperature of the Greenland Ice Sheet

NASA Technical Reports Server (NTRS)

Hall, Dorothy K.; Comiso, Josefino C.; DiGirolamo, Nocolo E.; Shuman, Christopher A.

2011-01-01

We have developed a climate-data record (CDR) of "clear-sky" ice-surface temperature (IST) of the Greenland Ice Sheet using Moderate-Resolution Imaging Spectroradiometer (MODIS) data. The CDR provides daily and monthly-mean IST from March 2000 through December 2010 on a polar stereographic projection at a resolution of 6.25 km. The CDR is amenable to extension into the future using Visible/Infrared Imager Radiometer Suite (VIIRS) data. Regional "clear-sky" surface temperature increases since the early 1980s in the Arctic, measured using Advanced Very High Resolution Radiometer (AVHRR) infrared data, range from 0.57 +/- 0.02 to 0.72 +/- 0.1 c per decade. Arctic warming has important implications for ice-sheet mass balance because much of the periphery of the Greenland Ice Sheet is already near O C during the melt season, and is thus vulnerable to rapid melting if temperatures continue to increase. An increase in melting of the ice sheet would accelerate sea-level rise, an issue affecting potentially billions of people worldwide. The IST CDR will provide a convenient data set for modelers and for climatologists to track changes of the surface temperature of the ice sheet as a whole and of the individual drainage basins on the ice sheet. The daily and monthly maps will provide information on surface melt as well as "clear-sky" temperature. The CDR will be further validated by comparing results with automatic-weather station data and with satellite-derived surface-temperature products.

Linguistic Adaptation of the Clinical Dementia Rating Scale for a Spanish-Speaking Population

PubMed Central

Oquendo-Jiménez, Ilia; Mena, Rafaela; Antoun, Mikhail D.; Wojna, Valerie

2012-01-01

Background Alzheimer's disease (AD) is the most common form of dementia worldwide. In Hispanic populations there are few validated tests for the accurate identification and diagnosis of AD. The Clinical Dementia Rating (CDR) scale is an internationally recognized questionnaire used to stage dementia. This study's objective was to develop a linguistic adaptation of the CDR for the Puerto Rican population. Methods The linguistic adaptation consisted of the evaluation of each CDR question (item) and the questionnaire's instructions, for similarities in meaning (semantic equivalence), relevance of content (content equivalence), and appropriateness of the questionnaire's format and measuring technique (technical equivalence). A focus group methodology was used to assess cultural relevance, clarity, and suitability of the measuring technique in the Argentinean version of the CDR for use in a Puerto Rican population. Results A total of 27 semantic equivalence changes were recommended in four categories: higher than 6th grade level of reading, meaning, common use, and word preference. Four content equivalence changes were identified, all focused on improving the applicability of the test questions to the general population's concept of street addresses and common dietary choices. There were no recommendations for changes in the assessment of technical equivalence. Conclusions We developed a linguistically adapted CDR instrument for the Puerto Rican population, preserving the semantic, content, and technical equivalences of the original version. Further studies are needed to validate the CDR instrument with the staging of Alzheimer's disease in the Puerto Rican population. PMID:20496524

A systematic review protocol on the effectiveness of therapeutic exercises utilised by physiotherapists to improve function in patients with burns.

PubMed

Mudawarima, Tapfuma; Chiwaridzo, Matthew; Jelsma, Jennifer; Grimmer, Karen; Muchemwa, Faith Chengetayi

2017-10-23

Therapeutic exercises play a crucial role in the management of burn injuries. The broad objective of this review is to systematically evaluate the effectiveness, safety and applicability to low-income countries of therapeutic exercises utilised by physiotherapists to improve function in patients with burns. Population = adults and children/adolescents with burns of any aspect of their bodies. Interventions = any aerobic and/or strength exercises delivered as part of a rehabilitation programme by anyone (e.g. physiotherapists, occupational therapists, nurses, doctors, community workers and patients themselves). Comparators = any comparator. Outcomes = any measure of outcome (e.g. quality of life, pain, muscle strength, range of movement, fear or quality of movement). Settings = any setting in any country. A systematic review will be conducted by two blinded independent reviewers who will search articles on PubMed, CiNAHL, Cochrane library, Medline, Pedro, OTseeker, EMBASE, PsychINFO and EBSCOhost using predefined criteria. Studies of human participants of any age suffering from burns will be eligible, and there will be no restrictions on total body surface area. Only randomised controlled trials will be considered for this review, and the methodological quality of studies meeting the selection criteria will be evaluated using the Cochrane Collaboration tool for assessing risk of bias. The PRISMA reporting standards will be used to write the review. A narrative analysis of the findings will be done, but if pooling is possible, meta-analysis will be considered. Burns may have a long-lasting impact on both psychological and physical functioning and thus it is important to identify and evaluate the effects of current and past aerobic and strength exercises on patients with burns. By identifying the characteristics of effective exercise programmes, guidelines can be suggested for developing intervention programmes aimed at improving the function of patients with burns. The safety and precautions of exercise regimes and the optimal frequency, duration, time and intensity will also be examined to inform further intervention. PROSPERO CDR42016048370 .

Biomechanical Modeling Analysis of Loads Configuration for Squat Exercise

NASA Technical Reports Server (NTRS)

Gallo, Christopher A.; Thompson, William K.; Lewandowski, Beth E.; Jagodnik, Kathleen; De Witt, John K.

2017-01-01

INTRODUCTION: Long duration space travel will expose astronauts to extended periods of reduced gravity. Since gravity is not present to assist loading, astronauts will use resistive and aerobic exercise regimes for the duration of the space flight to minimize loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the area available for an exercise device in the next generation of spacecraft for travel to the Moon or to Mars is limited and therefore compact resistance exercise device prototypes are being developed. The Advanced Resistive Exercise Device (ARED) currently on the ISS is being used as a benchmark for the functional performance of these new devices. Biomechanical data collection and computational modeling aid the device design process by quantifying the joint torques and the musculoskeletal forces that occur during exercises performed on the prototype devices. METHODS The computational models currently under development utilize the OpenSim [1] software platform, consisting of open source code for musculoskeletal modeling, using biomechanical input data from test subjects for estimation of muscle and joint loads. The OpenSim Full Body Model [2] is used for all analyses. The model incorporates simplified wrap surfaces, a new knee model and updated lower body muscle parameters derived from cadaver measurements and magnetic resonance imaging of young adults. The upper body uses torque actuators at the lumbar and extremity joints. The test subjects who volunteer for this study are instrumented with reflective markers for motion capture data collection while performing squat exercising on the Hybrid Ultimate Lifting Kit (HULK) prototype device (ZIN Technologies, Middleburg Heights, OH). Ground reaction force data is collected with force plates under the feet, and device loading is recorded through load cells internal to the HULK. Test variables include the applied device load and the dual cable long bar or single cable T-bar interface between the test subject and the device. Data is also obtained using free weights with the identical loading for a comparison to the resistively loaded exercise device trials. The data drives the OpenSim biomechanical model, which has been scaled to match the anthropometrics of the test subject, to calculate the body loads. RESULTS Lower body kinematics, joint moments, joint forces and muscle forces are obtained from the OpenSim biomechanical analysis of the squat exercises under different loading conditions. Preliminary results from the model for the loading conditions will be presented as will hypotheses developed for follow on work.

Orbital Fitness: An Overview of Space Shuttle Cardiopulmonary Exercise Physiology Findings

NASA Technical Reports Server (NTRS)

Moore, Alan D.

2011-01-01

Limited observations regarding the cardiopulmonary responses to aerobic exercise had been conducted during short-duration spaceflight before the Space Shuttle program. This presentation focuses on the findings regarding changes observed in the cardiopulmonary exercise responses during and following Shuttle flights. During flight, maximum oxygen uptake (VO2max) remained unchanged as did the maximum work rate achievable during cycle exercise testing conducted during the last full flight day. Immediately following flight, the ubiquitous finding, confirmed by investigations conducted during the Spacelab Life Sciences missions 1 and 2 and by NASA Detailed Supplemental Objective studies, indicated that VO2max was reduced; however, the reduction in VO2max was transient and returned to preflight levels within 7 days following return. Studies regarding the influence of aerobic exercise countermeasures performed during flight on postflight performance were mostly limited to the examination of the heart rate (HR) response to submaximal exercise testing on landing day. These studies revealed that exercise HR was elevated in individuals who performed little to no exercise during their missions as compared to individuals who performed regular exercise. In addition, astronauts who performed little to no aerobic exercise during flight demonstrated an increased HR and lowered pulse pressure response to the standard stand test on landing day, indicating a decrease in orthostatic function in these individuals. With regard to exercise modality, four devices were examined during the Shuttle era: two treadmills, a cycle ergometer, and a rowing device. Although there were limited investigations regarding the use of these devices for exercise training aboard the Shuttle, there was no clear consensus reached regarding which proved to be a "superior" device. Each device had a unique operational or physiologic limitation associated with its use. In conclusion, exercise research conducted during the Shuttle Program demonstrated that attenuation of postflight deconditioning was possible through use of exercise countermeasures and the Shuttle served as a test bed for equipment destined for use on the International Space Station. Learning Objective: Overview of the Space Shuttle Program research results related to aerobic capacity and performance, including what was learned from research and effectiveness of exercise countermeasures.

Directed evolution of human T cell receptor CDR2 residues by phage display dramatically enhances affinity for cognate peptide-MHC without increasing apparent cross-reactivity

PubMed Central

Dunn, Steven M.; Rizkallah, Pierre J.; Baston, Emma; Mahon, Tara; Cameron, Brian; Moysey, Ruth; Gao, Feng; Sami, Malkit; Boulter, Jonathan; Li, Yi; Jakobsen, Bent K.

2006-01-01

The mammalian α/β T cell receptor (TCR) repertoire plays a pivotal role in adaptive immunity by recognizing short, processed, peptide antigens bound in the context of a highly diverse family of cell-surface major histocompatibility complexes (pMHCs). Despite the extensive TCR–MHC interaction surface, peptide-independent cross-reactivity of native TCRs is generally avoided through cell-mediated selection of molecules with low inherent affinity for MHC. Here we show that, contrary to expectations, the germ line-encoded complementarity determining regions (CDRs) of human TCRs, namely the CDR2s, which appear to contact only the MHC surface and not the bound peptide, can be engineered to yield soluble low nanomolar affinity ligands that retain a surprisingly high degree of specificity for the cognate pMHC target. Structural investigation of one such CDR2 mutant implicates shape complementarity of the mutant CDR2 contact interfaces as being a key determinant of the increased affinity. Our results suggest that manipulation of germ line CDR2 loops may provide a useful route to the production of high-affinity TCRs with therapeutic and diagnostic potential. PMID:16600963

Table of Comparison of 2012 CDR v 2006 IUR Definitions

EPA Pesticide Factsheets

In forming 40 CFR 711, EPA sought to simplify the definition section and remove unnecessary duplication of regulatory terms. This table is a comparison of 2006 IUR Definitions and 2012 CDR Definitions.

Secure remote access to a clinical data repository using a wireless personal digital assistant (PDA).

PubMed

Duncan, R G; Shabot, M M

2000-01-01

TCP/IP and World-Wide-Web (WWW) technology have become the universal standards for networking and delivery of information. Personal digital assistants (PDAs), cellular telephones, and alphanumeric pagers are rapidly converging on a single pocket device that will leverage wireless TCP/IP networks and WWW protocols and can be used to deliver clinical information and alerts anytime, anywhere. We describe a wireless interface to clinical information for physicians based on Palm Corp.'s Palm VII pocket computer, a wireless digital network, encrypted data transmission, secure web servers, and a clinical data repository (CDR).

Secure remote access to a clinical data repository using a wireless personal digital assistant (PDA).

PubMed Central

Duncan, R. G.; Shabot, M. M.

2000-01-01

TCP/IP and World-Wide-Web (WWW) technology have become the universal standards for networking and delivery of information. Personal digital assistants (PDAs), cellular telephones, and alphanumeric pagers are rapidly converging on a single pocket device that will leverage wireless TCP/IP networks and WWW protocols and can be used to deliver clinical information and alerts anytime, anywhere. We describe a wireless interface to clinical information for physicians based on Palm Corp.'s Palm VII pocket computer, a wireless digital network, encrypted data transmission, secure web servers, and a clinical data repository (CDR). PMID:11079875

21 CFR 890.5370 - Nonmeasuring exercise equipment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nonmeasuring exercise equipment. 890.5370 Section 890.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5370...

21 CFR 890.5370 - Nonmeasuring exercise equipment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nonmeasuring exercise equipment. 890.5370 Section 890.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5370...

21 CFR 890.5370 - Nonmeasuring exercise equipment.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nonmeasuring exercise equipment. 890.5370 Section 890.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5370...

21 CFR 890.5370 - Nonmeasuring exercise equipment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nonmeasuring exercise equipment. 890.5370 Section 890.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5370...

21 CFR 890.5370 - Nonmeasuring exercise equipment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nonmeasuring exercise equipment. 890.5370 Section 890.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5370...

Patients With Very Mild Dementia May Confuse Objective Cognitive Impairments With Subjective Physical Health of Quality of Life: The Tome City Project in Japan.

PubMed

Kasai, Mari; Meguro, Kenichi

2018-01-01

Many elderly people with cognitive dysfunction may observe a decrease in their health levels and quality of life (QOL). The basic concept of QOL consists of several categories including physical functions and mental health. The QOL domain that is most important for elderly people is physical health and, to a lesser extent, psychological health, social relationships, and/ or the environment. Our aim was to explore the relationships between the subjective measure of QOL, an abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) scale, and the objective measure of impairment, Clinical Dementia Rating (CDR), among elderly people in a community. Totally, 178 community dwellers aged 75 years and above agreed to participate and completed the WHOQOL-BREF; 66 (32 males, 34 females) scored a CDR of 0 (healthy), 86 (33, 53) scored a CDR of 0.5 (questionable dementia or very mild dementia), and 26 (12, 14) scored a CDR of 1 and above (dementia). According to Pearson's correlation coefficient analysis (significance level, p < 0.05), the physical domain of the WHOQOL-BREF had significant statistical negative correlations with all CDR subscales. The CDR subscale of memory impairment had a significant statistical negative correlation with the WHOQOL-BREF subscales of the physical ( r = -0.151, p = 0.044) and psychological ( r = -0.232, p < 0.002) domains. The CDR subscale of home and hobbies impairment had significant statistical negative correlations with all WHOQOL-BREF subscales including the physical ( r = -0.226, p = 0.002), psychological ( r = -0.226, p = 0.002), social ( r = -0.167, p = 0.026), and environmental ( r = -0.204, p = 0.006) domains. Patients with very mild dementia may confuse cognitive impairment and physical disabilities. In the future, we need to systematically combine memory clinics and all departments related to the elderly for the successful early detection and rehabilitation of, and long-term care for, dementia.

Digital I and C system upgrade integration technique

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

Huang, H. W.; Shih, C.; Wang, J. R.

2012-07-01

This work developed an integration technique for digital I and C system upgrade, the utility can replace the I and C systems step by step systematically by this method. Inst. of Nuclear Energy Research (INER) developed a digital Instrumentation and Control (I and C) replacement integration technique on the basis of requirement of the three existing nuclear power plants (NPPs), which are Chin-Shan (CS) NPP, Kuo-Sheng (KS) NPP, and Maanshan (MS) NPP, in Taiwan, and also developed the related Critical Digital Review (CDR) Procedure. The digital I and C replacement integration technique includes: (I) Establishment of Nuclear Power Plant Digitalmore » Replacement Integration Guideline, (2) Preliminary Investigation on I and C System Digitalization, (3) Evaluation on I and C System Digitalization, and (4) Establishment of I and C System Digitalization Architectures. These works can be a reference for performing I and C system digital replacement integration of the three existing NPPs of Taiwan Power Company (TPC). A CDR is the review for a critical system digital I and C replacement. The major reference of this procedure is EPRI TR- 1011710 (2005) 'Handbook for Evaluating Critical Digital Equipment and Systems' which was published by the Electric Power Research Inst. (EPRI). With this document, INER developed a TPC-specific CDR procedure. Currently, CDR becomes one of the policies for digital I and C replacement in TPC. The contents of this CDR procedure include: Scope, Responsibility, Operation Procedure, Operation Flow Chart, CDR review items. The CDR review items include the comparison of the design change, Software Verification and Validation (SVandV), Failure Mode and Effects Analysis (FMEA), Evaluation of Diversity and Defense-in-depth (D3), Evaluation of Watchdog Timer, Evaluation of Electromagnetic Compatibility (EMC), Evaluation of Grounding for System/Component, Seismic Evaluation, Witness and Inspection, Lessons Learnt from the Digital I and C Failure Events. A solid review can assure the quality of the digital I and C system replacement. (authors)« less

Relationship between global severity of patients with Alzheimer's disease and costs of care in Spain; results from the co-dependence study in Spain.

PubMed

Darbà, J; Kaskens, L; Lacey, L

2015-11-01

The objectives of this analysis were to examine how patients' global severity with Alzheimer's disease (AD) relates to costs of care and explore the incremental effects of global severity measured by the clinical dementia rating (CDR) scale on these costs for patients in Spain. The Codep-EA study is an 18-multicenter, cross-sectional, observational study among patients (343) with AD according to the CDR score and their caregivers in Spain. The data obtained included (in addition to clinical measures) also socio-demographic data concerning the patient and its caregiver. Cost analyses were based on resource use for medical care, social care, caregiver productivity losses, and informal caregiver time reported in the resource utilization in dementia (RUD). Lite instrument and a complementary questionnaire. Multivariate regression analysis was used to model the effects of global severity and other socio-demographic and clinical variables on cost of care. The mean (standard deviation) costs per patient over 6 months for direct medical, social care, indirect and informal care costs, were estimated at €1,028.1 (1,655.0), €843.8 (2,684.8), €464.2 (1,639.0) and €33,232.2 (30,898.9), respectively. Dementia severity, as having a CDR score 0.5, 2, or 3 with CDR score 1 being the reference group were all independently and significantly associated with informal care costs. Whereas having a CDR score of 2 was also significantly related with social care costs, a CDR score of 3 was associated with most cost components including direct medical, social care, and total costs, all compared to the reference group. The costs of care for patients with AD in Spain are substantial, with informal care accounting for the greatest part. Dementia severity, measured by CDR score, showed that with increasing severity of the disease, direct medical, social care, informal care and total costs augmented.

Assessing the performance and reliability of PERSIANN-CDR satellite-based rainfall estimates over Spain: case study of rainfall Dry Spell Lengths (DSL)

NASA Astrophysics Data System (ADS)

Garcia Galiano, S. G.; Giraldo Osorio, J. D.; Nguyen, P.; Hsu, K. L.; Braithwaite, D.; Olmos, P.; Sorooshian, S.

2015-12-01

Studying Spain's long-term variability and changing trends in rainfall, due to its unique position in the Mediterranean basin (i.e., the latitudinal gradient from North to South and its orographic variation), can provide a valuable insight into how hydroclimatology of the region has changed. A recently released high resolution satellite-based global daily precipitation climate dataset PERSIANN-CDR (Precipitation Estimation from Remotely Sensed Information using Artificial Neural Network - Climate Data Record), provided the opportunity to conduct such study. It covers the period 01/01/1983 - to date, at 0.25° resolution. In areas without a dense network of rain-gauges, the PERSIANN-CDR dataset could be useful for identifying the reliability of regional climate models (RCMs), in order to build robust RCMs ensemble for reducing the uncertainties in the climate and hydrological projections. However, before using this data set for RCM evaluation, an assessment of performance of PERSIANN-CDR dataset against in-situ observations is necessary. The high-resolution gridded daily rain-gauge dataset, named Spain02, was employed in this study. The variable Dry Spell Lengths (DSL) considering 1 mm and 10 mm as thresholds of daily rainfall, and the time period 1988-2007 was defined for the study. A procedure for improving the consistency and homogeneity between the two datasets was applied. The assessment is based on distributional similarity and the well-known statistical tests (Smirnov-Kolmogorov of two samples and Chi-Square) are used as fitting criteria. The results demonstrate good fit of PERSIANN-CDR over whole Spain, for threshold 10 mm/day. However, for threshold 1 mm/day PERSIANN-CDR compares well with Spain02 dataset for areas with high values of rainfall (North of Spain); while in semiarid areas (South East of Spain) there is strong overestimation of short DSLs. Overall, PERSIANN-CDR demonstrate its robustness in the simulation of DSLs for the highest thresholds.

Patients With Very Mild Dementia May Confuse Objective Cognitive Impairments With Subjective Physical Health of Quality of Life: The Tome City Project in Japan

PubMed Central

Kasai, Mari; Meguro, Kenichi

2018-01-01

Many elderly people with cognitive dysfunction may observe a decrease in their health levels and quality of life (QOL). The basic concept of QOL consists of several categories including physical functions and mental health. The QOL domain that is most important for elderly people is physical health and, to a lesser extent, psychological health, social relationships, and/ or the environment. Our aim was to explore the relationships between the subjective measure of QOL, an abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) scale, and the objective measure of impairment, Clinical Dementia Rating (CDR), among elderly people in a community. Totally, 178 community dwellers aged 75 years and above agreed to participate and completed the WHOQOL-BREF; 66 (32 males, 34 females) scored a CDR of 0 (healthy), 86 (33, 53) scored a CDR of 0.5 (questionable dementia or very mild dementia), and 26 (12, 14) scored a CDR of 1 and above (dementia). According to Pearson’s correlation coefficient analysis (significance level, p < 0.05), the physical domain of the WHOQOL-BREF had significant statistical negative correlations with all CDR subscales. The CDR subscale of memory impairment had a significant statistical negative correlation with the WHOQOL-BREF subscales of the physical (r = -0.151, p = 0.044) and psychological (r = -0.232, p < 0.002) domains. The CDR subscale of home and hobbies impairment had significant statistical negative correlations with all WHOQOL-BREF subscales including the physical (r = -0.226, p = 0.002), psychological (r = -0.226, p = 0.002), social (r = -0.167, p = 0.026), and environmental (r = -0.204, p = 0.006) domains. Patients with very mild dementia may confuse cognitive impairment and physical disabilities. In the future, we need to systematically combine memory clinics and all departments related to the elderly for the successful early detection and rehabilitation of, and long-term care for, dementia. PMID:29706921

Poster — Thur Eve — 36: Implementation of constant dose rate and gantry speed arc therapy(CDR-CAS-IMAT) for thoracic esophageal carcinoma on Varian 23EX

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

Zhang, Ruohui; Department of Medical Physics, Medical Faculty Mannheim, Heidelberg University; Fan, Xiaomei

2014-08-15

Objective: The purpose of this study is to propose an alternative planning approach for VMAT using constant dose rate and gantry speed arc therapy(CDR-CAS-IMAT) implementation on conventional Linac Varian 23EX and used IMRT as a benchmark to evaluate the performance. Methods and materials: Eighteen patients with thoracic esophageal carcinoma who were previously treated with IMRT on Varian 23EX were retrospectively planned for CDR-CAS-IMAT plans. Dose prescription was set to 60 Gy to PTVs in 30 fractions. The planning objectives for PTVs and OAR were corresponding with the IMRT plans. Dose to the PTVs and OAR were compared to IMRT withmore » respect to plan quality, MU, treatment time and delivery accuracy. Results: CDR-CAS-IMAT plans led to equivalent or superior plan quality as compared to IMRT, PTV's CI relative increased 16.2%, while small deviations were observed on minimum dose for PTV. Volumes in the cord receiving 40Gy were increased from 3.6% with IMRT to 7.0%. Treatment times were reduced significantly with CDR-CAS-IMAT(mean 85.7s vs. 232.1s, p < .05), however, MU increased by a factor of 1.3 and lung V10/5/3.5/aver were relative increase 6.7%,12%,17.9%,4.2%, respectively. And increased the E-P low dose area volume decreased the hight dose area. There were no significant difference in Delta4 measurements results between both planning techniques. Conclusion: CDR-CAS-IMAT plans can be implemented smoothly and quickly into a busy cancer center, which improved PTV CI and reduces treatment time but increased the MU and low dose irradiated area. An evaluation of weight loss must be performed during treatment for CDR-CAS-IMAT patients.« less

Real time simulation using position sensing

NASA Technical Reports Server (NTRS)

Isbell, William B. (Inventor); Taylor, Jason A. (Inventor); Studor, George F. (Inventor); Womack, Robert W. (Inventor); Hilferty, Michael F. (Inventor); Bacon, Bruce R. (Inventor)

2000-01-01

An interactive exercise system including exercise equipment having a resistance system, a speed sensor, a controller that varies the resistance setting of the exercise equipment, and a playback device for playing pre-recorded video and audio. The controller, operating in conjunction with speed information from the speed sensor and terrain information from media table files, dynamically varies the resistance setting of the exercise equipment in order to simulate varying degrees of difficulty while the playback device concurrently plays back the video and audio to create the simulation that the user is exercising in a natural setting such as a real-world exercise course.

Instructions for the 2012 TSCA Chemical Data Reporting

EPA Pesticide Factsheets

This document, which pertains to EPA CDR reporting during 2012, updates guidance issued for reporting in 2006 to incorporate instructions relevant to 2012 reporting. It provides detailed information and examples to in reporting under the CDR rule.

TSCA Chemical Data Reporting Fact Sheet: Byproducts Reporting for the Printed Circuit Board Industry

EPA Pesticide Factsheets

This fact sheet provides information on existing Chemical Data Reporting (CDR) rule requirements related to byproducts reporting by persons who manufacture printed circuit boards and may be subject to CDR.

Chemicals Reported for the 2012 Chemical Data Reporting (CDR) in Alphabetical Order

EPA Pesticide Factsheets

For the 2012 CDR, 7,674 unique chemicals were reported by manufacturers (including importers).Chemicals are listed in alphabetical order by CA Index Name (for non-confidential chemicals) or by generic chemical name.

ARED (Advanced-Resistive Exercise Device) Update

NASA Technical Reports Server (NTRS)

Ploutz-Snyder, Lori

2009-01-01

This viewgraph presentation describes ARED which is a new hardware exercise device for use on the International Space Station. Astronaut physiological adaptations, muscle parameters, and cardiovascular parameters are also reviewed.

21 CFR 890.5410 - Powered finger exerciser.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Powered finger exerciser. 890.5410 Section 890.5410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5410 Powered finger...

21 CFR 890.5360 - Measuring exercise equipment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Measuring exercise equipment. 890.5360 Section 890.5360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5360 Measuring...

21 CFR 890.5410 - Powered finger exerciser.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Powered finger exerciser. 890.5410 Section 890.5410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5410 Powered finger...

21 CFR 890.5380 - Powered exercise equipment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Powered exercise equipment. 890.5380 Section 890.5380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5380 Powered...

21 CFR 890.5380 - Powered exercise equipment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Powered exercise equipment. 890.5380 Section 890.5380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5380 Powered...

21 CFR 890.5380 - Powered exercise equipment.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Powered exercise equipment. 890.5380 Section 890.5380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5380 Powered...

21 CFR 890.5380 - Powered exercise equipment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Powered exercise equipment. 890.5380 Section 890.5380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5380 Powered...

21 CFR 890.5360 - Measuring exercise equipment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Measuring exercise equipment. 890.5360 Section 890.5360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5360 Measuring...

21 CFR 890.5410 - Powered finger exerciser.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Powered finger exerciser. 890.5410 Section 890.5410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5410 Powered finger...

21 CFR 890.5360 - Measuring exercise equipment.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Measuring exercise equipment. 890.5360 Section 890.5360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5360 Measuring...

21 CFR 890.5410 - Powered finger exerciser.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Powered finger exerciser. 890.5410 Section 890.5410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5410 Powered finger...

21 CFR 890.5380 - Powered exercise equipment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Powered exercise equipment. 890.5380 Section 890.5380 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5380 Powered...

21 CFR 890.5360 - Measuring exercise equipment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Measuring exercise equipment. 890.5360 Section 890.5360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5360 Measuring...

21 CFR 890.5360 - Measuring exercise equipment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Measuring exercise equipment. 890.5360 Section 890.5360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5360 Measuring...

21 CFR 890.5410 - Powered finger exerciser.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Powered finger exerciser. 890.5410 Section 890.5410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5410 Powered finger...

Verification, Validation and Credibility Assessment of a Computational Model of the Advanced Resistive Exercise Device (ARED)

NASA Technical Reports Server (NTRS)

Werner, C. R.; Humphreys, B. T.; Mulugeta, L.

2014-01-01

The Advanced Resistive Exercise Device (ARED) is the resistive exercise device used by astronauts on the International Space Station (ISS) to mitigate bone loss and muscle atrophy due to extended exposure to microgravity (micro g). The Digital Astronaut Project (DAP) has developed a multi-body dynamics model of biomechanics models for use in spaceflight exercise physiology research and operations. In an effort to advance model maturity and credibility of the ARED model, the DAP performed verification, validation and credibility (VV and C) assessment of the analyses of the model in accordance to NASA-STD-7009 'Standards for Models and Simulations'.

“Noncognitive” symptoms of early Alzheimer disease

PubMed Central

Masters, Mary Clare; Morris, John C.

2015-01-01

Objectives: To observe the natural time course of noncognitive symptoms before the onset of symptomatic Alzheimer disease dementia. Methods: Using the National Alzheimer's Coordinating Center Uniform Data Set from September 2005 to March 2013, data from cognitively normal individuals who were aged 50 years or older at first visit and had subsequent follow-up were analyzed. Survival analyses were used to examine the development of particular symptoms relative to each other on the Neuropsychiatric Inventory Questionnaire (NPI-Q), Functional Activities Questionnaire, and Geriatric Depression Scale, and to compare the development of individual symptoms for persons who did and did not receive a Clinical Dementia Rating (CDR) >0 (indicating abnormal cognition) during the follow-up period. Results: The order of symptom occurrence on the NPI-Q was similar for participants who remained at CDR 0 and for those who received a CDR >0 over the follow-up period, although the time to most NPI-Q symptoms was faster for participants who received a CDR >0 (p < 0.001). With the exception of memory, Geriatric Depression Scale symptoms reported by both CDR groups were similar. Conclusions: We found a significantly earlier presence of positive symptoms on the NPI-Q in cognitively normal patients who subsequently developed CDR >0. Among participants with no depression symptoms at baseline, results suggest that depressive symptoms may increase with aging regardless of incipient dementia. Such findings begin to delineate the noncognitive course of Alzheimer disease dementia in the preclinical stages. Future research must further elucidate the correlation between noncognitive changes and distinct dementia subtypes. PMID:25589671

The Carbon Dioxide Removal Model Intercomparison Project (CDRMIP): rationale and experimental protocol for CMIP6

NASA Astrophysics Data System (ADS)

Keller, David P.; Lenton, Andrew; Scott, Vivian; Vaughan, Naomi E.; Bauer, Nico; Ji, Duoying; Jones, Chris D.; Kravitz, Ben; Muri, Helene; Zickfeld, Kirsten

2018-03-01

The recent IPCC reports state that continued anthropogenic greenhouse gas emissions are changing the climate, threatening severe, pervasive and irreversible impacts. Slow progress in emissions reduction to mitigate climate change is resulting in increased attention to what is called geoengineering, climate engineering, or climate intervention - deliberate interventions to counter climate change that seek to either modify the Earth's radiation budget or remove greenhouse gases such as CO2 from the atmosphere. When focused on CO2, the latter of these categories is called carbon dioxide removal (CDR). Future emission scenarios that stay well below 2 °C, and all emission scenarios that do not exceed 1.5 °C warming by the year 2100, require some form of CDR. At present, there is little consensus on the climate impacts and atmospheric CO2 reduction efficacy of the different types of proposed CDR. To address this need, the Carbon Dioxide Removal Model Intercomparison Project (or CDRMIP) was initiated. This project brings together models of the Earth system in a common framework to explore the potential, impacts, and challenges of CDR. Here, we describe the first set of CDRMIP experiments, which are formally part of the 6th Coupled Model Intercomparison Project (CMIP6). These experiments are designed to address questions concerning CDR-induced climate reversibility, the response of the Earth system to direct atmospheric CO2 removal (direct air capture and storage), and the CDR potential and impacts of afforestation and reforestation, as well as ocean alkalinization.>

The Carbon Dioxide Removal Model Intercomparison Project (CDRMIP): rationale and experimental protocol for CMIP6

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

Keller, David P.; Lenton, Andrew; Scott, Vivian

The recent IPCC reports state that continued anthropogenic greenhouse gas emissions are changing the climate, threatening severe, pervasive and irreversible impacts. Slow progress in emissions reduction to mitigate climate change is resulting in increased attention to what is called geoengineering, climate engineering, or climate intervention – deliberate interventions to counter climate change that seek to either modify the Earth's radiation budget or remove greenhouse gases such as CO 2 from the atmosphere. When focused on CO 2, the latter of these categories is called carbon dioxide removal (CDR). Future emission scenarios that stay well below 2 °C, and all emissionmore » scenarios that do not exceed 1.5 °C warming by the year 2100, require some form of CDR. At present, there is little consensus on the climate impacts and atmospheric CO 2 reduction efficacy of the different types of proposed CDR. To address this need, the Carbon Dioxide Removal Model Intercomparison Project (or CDRMIP) was initiated. This project brings together models of the Earth system in a common framework to explore the potential, impacts, and challenges of CDR. Here, we describe the first set of CDRMIP experiments, which are formally part of the 6th Coupled Model Intercomparison Project (CMIP6). These experiments are designed to address questions concerning CDR-induced climate reversibility, the response of the Earth system to direct atmospheric CO 2 removal (direct air capture and storage), and the CDR potential and impacts of afforestation and reforestation, as well as ocean alkalinization.>« less

SU-E-T-421: Feasibility Study of Volumetric Modulated Arc Therapy with Constant Dose Rate for Endometrial Cancer

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

Yang, R; Wang, J

2014-06-01

Purpose: To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. Methods: The nine-Field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry Run was performed to assess the dosimetric accuracy with MatriXX from IBA. Results: Compared withmore » IMRT, the VMAT-CDR plans delivered a slightly greater V20 of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs Decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. Conclusion: VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability. This work is supported by the grant project, National Natural; Science Foundation of China (No. 81071237)« less

Is exercise training safe and beneficial in patients receiving left ventricular assist device therapy?

PubMed

Alsara, Osama; Perez-Terzic, Carmen; Squires, Ray W; Dandamudi, Sanjay; Miranda, William R; Park, Soon J; Thomas, Randal J

2014-01-01

Because a limited number of patients receive heart transplantation, alternative therapies, such as left ventricular assist device (LVAD) therapy, have emerged. Published studies have shown that LVAD implantation, by itself, improves exercise tolerance to the point where it is comparable to those with mild heart failure. The improvement in exercise capacity is maximally achieved 12 weeks after LVAD therapy and can continue even after explantation of the device. This effect varies, depending on the type of LVAD and exercise training. The available data in the literature on safety and benefits of exercise training in patients after LVAD implantation are limited, but the data that are available suggest that training trends to be safe and have an impact on exercise capacity in LVAD patients. Although no studies were identified on the role of cardiac rehabilitation programs in the management of LVAD patients, it appears that cardiac rehabilitation programs offer an ideal setting for the provision of supervised exercise training in this patient group.

Chemical Data Reporting Byproduct and Recycling Scenarios

EPA Pesticide Factsheets

This document addresses a series of 18 industry scenarios and questions related to EPA’s Chemical Data Reporting (CDR) rule. The primary goal of this document is to help the regulated community comply with the requirements of the CDR rule.

The T-cell receptor beta chain CDR3 region of BV8S1/BJ1S5 transcripts in type 1 diabetes.

PubMed

Naserke, H E; Durinovic-Bellò, I; Seidel, D; Ziegler, A G

1996-01-01

We recently described the T-cell receptor (TCR) beta chain CDR3 motif S-SDRLG-NQPQH (BV8S1-BJ1S5) in an islet-specific T-cell clone (K2.12) from a type 1 diabetic patient (AS). A similar motif (RLGNQ) was also reported in a T-cell clone of non-obese diabetic (NOD) mice by others. In order to determine the frequency of our motif in selected and unselected T-cell populations, we cloned and sequenced the CDR3 region of BV8S1-BJ1S5 transcripts. These transcripts were derived from unstimulated peripheral blood T lymphocytes from two type 1 diabetic patients (AS and FS) and their non-diabetic sibling (WS), as well as from an islet-specific T-cell line of one of the patients. In addition, we compared the structure and composition of the CDR3 region in BV8S1-BJ1S5 transcripts from peripheral blood T cells between the patients and their non-diabetic sibling (>50 sequences each). We found that 30% of the islet-specific T-cell line cDNA clones expressed the entire sequence-motif, whereas it was absent in the clones of unstimulated peripheral blood T cells from both patients and their non-diabetic sibling. The average length of the CDR3 region was shorter in the patients (mean AS 9.9, FS 9.9, versus WS 10.7, p = 0.0037) and the number of inserted nucleotides in N nucleotide addition at the DJ-junction lower (mean AS 3.5, FS 3. 2, versus WS 5.2, P = <10(-4)) as compared with their non-diabetic sibling. Moreover, the pattern of amino acid usage in the CDR3 region was dissimilar at positions 5 and 6, where polar amino acids predominated in both diabetic siblings. In contrast, basic amino acids are preferentially used at position 5 in the clones of the non-diabetic sibling. These data provide information on the general structure of the TCR(BV8S1-BJ1S5) CDR3 region in type 1 diabetes and may indicate differences in the amino and nucleic acid composition of the TCR beta chain CDR3 region between two type 1 diabetic patients and their non-diabetic sibling.

Advanced Resistive Exercise Device

NASA Technical Reports Server (NTRS)

Raboin, Jasen; Niebuhr, Jason; Cruz, Santana; Lamoreaux, chris

2007-01-01

The advanced resistive exercise device (ARED), now at the prototype stage of development, is a versatile machine that can be used to perform different customized exercises for which, heretofore, it has been necessary to use different machines. Conceived as a means of helping astronauts and others to maintain muscle and bone strength and endurance in low-gravity environments, the ARED could also prove advantageous in terrestrial settings (e.g., health clubs and military training facilities) in which many users are exercising simultaneously and there is heavy demand for use of exercise machines.

Computational Modeling Using OpenSim to Simulate a Squat Exercise Motion

NASA Technical Reports Server (NTRS)

Gallo, C. A.; Thompson, W. K.; Lewandowski, B. E.; Humphreys, B. T.; Funk, J. H.; Funk, N. H.; Weaver, A. S.; Perusek, G. P.; Sheehan, C. C.; Mulugeta, L.

2015-01-01

Long duration space travel to destinations such as Mars or an asteroid will expose astronauts to extended periods of reduced gravity. Astronauts will use an exercise regime for the duration of the space flight to minimize the loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Since the area available in the spacecraft for an exercise device is limited and gravity is not present to aid loading, compact resistance exercise device prototypes are being developed. Since it is difficult to rigorously test these proposed devices in space flight, computational modeling provides an estimation of the muscle forces, joint torques and joint loads during exercise to gain insight on the efficacy to protect the musculoskeletal health of astronauts.

Chemical Data Reporting Fact Sheet: Basic Information

EPA Pesticide Factsheets

EPA collects information on the types and quantities of chemicals produced in the U.S under the Chemical Data Reporting (CDR) requirements. This fact sheet outlines key information about CDR, including what data are collected and how the data are used.

Chemical Data Reporting Fact Sheet: Chemicals Snapshot

EPA Pesticide Factsheets

This fact sheet provides a brief overview of the chemical manufacturing, processing, and use information collected for the 2012 Chemical Data Reporting (CDR) rule. Users do not have access to the complete CDR data set and should draw conclusions with care.

Integrated Assessment of Carbon Dioxide Removal

NASA Astrophysics Data System (ADS)

Rickels, W.; Reith, F.; Keller, D.; Oschlies, A.; Quaas, M. F.

2018-03-01

To maintain the chance of keeping the average global temperature increase below 2°C and to limit long-term climate change, removing carbon dioxide from the atmosphere (carbon dioxide removal, CDR) is becoming increasingly necessary. We analyze optimal and cost-effective climate policies in the dynamic integrated assessment model (IAM) of climate and the economy (DICE2016R) and investigate (1) the utilization of (ocean) CDR under different climate objectives, (2) the sensitivity of policies with respect to carbon cycle feedbacks, and (3) how well carbon cycle feedbacks are captured in the carbon cycle models used in state-of-the-art IAMs. Overall, the carbon cycle model in DICE2016R shows clear improvements compared to its predecessor, DICE2013R, capturing much better long-term dynamics and also oceanic carbon outgassing due to excess oceanic storage of carbon from CDR. However, this comes at the cost of a (too) tight short-term remaining emission budget, limiting the model suitability to analyze low-emission scenarios accurately. With DICE2016R, the compliance with the 2°C goal is no longer feasible without negative emissions via CDR. Overall, the optimal amount of CDR has to take into account (1) the emission substitution effect and (2) compensation for carbon cycle feedbacks.

Systemic Lupus Erythematosus: Molecular Mimicry between Anti-dsDNA CDR3 Idiotype, Microbial and Self Peptides-As Antigens for Th Cells.

PubMed

Aas-Hanssen, Kristin; Thompson, Keith M; Bogen, Bjarne; Munthe, Ludvig A

2015-01-01

Systemic lupus erythematosus (SLE) is marked by a T helper (Th) cell-dependent B cell hyperresponsiveness, with frequent germinal center reactions, and gammaglobulinemia. A feature of SLE is the finding of IgG autoantibodies specific for dsDNA. The specificity of the Th cells that drive the expansion of anti-dsDNA B cells is unresolved. However, anti-microbial, anti-histone, and anti-idiotype Th cell responses have been hypothesized to play a role. It has been entirely unclear if these seemingly disparate Th cell responses and hypotheses could be related or unified. Here, we describe that H chain CDR3 idiotypes from IgG(+) B cells of lupus mice have sequence similarities with both microbial and self peptides. Matched sequences were more frequent within the mutated CDR3 repertoire and when sequences were derived from lupus mice with expanded anti-dsDNA B cells. Analyses of histone sequences showed that particular histone peptides were similar to VDJ junctions. Moreover, lupus mice had Th cell responses toward histone peptides similar to anti-dsDNA CDR3 sequences. The results suggest that Th cells in lupus may have multiple cross-reactive specificities linked to the IgVH CDR3 Id-peptide sequences as well as similar DNA-associated protein motifs.

Amyloid-β--associated clinical decline occurs only in the presence of elevated P-tau.

PubMed

Desikan, Rahul S; McEvoy, Linda K; Thompson, Wesley K; Holland, Dominic; Brewer, James B; Aisen, Paul S; Sperling, Reisa A; Dale, Anders M

2012-06-01

To elucidate the relationship between the 2 hallmark proteins of Alzheimer disease (AD), amyloid-(Aβ) and tau, and clinical decline over time among cognitively normal older individuals. A longitudinal cohort of clinically and cognitively normal older individuals assessed with baseline lumbar puncture and longitudinal clinical assessments. Research centers across the United States and Canada. We examined 107 participants with a Clinical Dementia Rating (CDR) of 0 at baseline examination. Using linear mixed effects models, we investigated the relationship between cerebrospinal fluid (CSF) phospho-tau 181 (p-tau(181p)),CSF Aβ(1-42), and clinical decline as assessed using longitudinal change in global CDR, CDR-Sum of Boxes, and the Alzheimer Disease Assessment Scale-cognitive subscale. We found a significant relationship between decreased CSF Aβ(1-42) and longitudinal change in global CDR,CDR-Sum of Boxes, and Alzheimer Disease Assessment Scale-cognitive subscale in individuals with elevated CSFp-tau(181p). In the absence of CSF p-tau(181p), the effect of CSF Aβ(1-42) on longitudinal clinical decline was not significantly different from 0. In cognitively normal older individuals,A-associated clinical decline during a mean of 3 years may occur only in the presence of ongoing downstream neurodegeneration.

Collimator optimization and collimator-detector response compensation in myocardial perfusion SPECT using the ideal observer with and without model mismatch and an anthropomorphic model observer

NASA Astrophysics Data System (ADS)

Ghaly, Michael; Links, Jonathan M.; Frey, Eric C.

2016-03-01

The collimator is the primary factor that determines the spatial resolution and noise tradeoff in myocardial perfusion SPECT images. In this paper, the goal was to find the collimator that optimizes the image quality in terms of a perfusion defect detection task. Since the optimal collimator could depend on the level of approximation of the collimator-detector response (CDR) compensation modeled in reconstruction, we performed this optimization for the cases of modeling the full CDR (including geometric, septal penetration and septal scatter responses), the geometric CDR, or no model of the CDR. We evaluated the performance on the detection task using three model observers. Two observers operated on data in the projection domain: the Ideal Observer (IO) and IO with Model-Mismatch (IO-MM). The third observer was an anthropomorphic Channelized Hotelling Observer (CHO), which operated on reconstructed images. The projection-domain observers have the advantage that they are computationally less intensive. The IO has perfect knowledge of the image formation process, i.e. it has a perfect model of the CDR. The IO-MM takes into account the mismatch between the true (complete and accurate) model and an approximate model, e.g. one that might be used in reconstruction. We evaluated the utility of these projection domain observers in optimizing instrumentation parameters. We investigated a family of 8 parallel-hole collimators, spanning a wide range of resolution and sensitivity tradeoffs, using a population of simulated projection (for the IO and IO-MM) and reconstructed (for the CHO) images that included background variability. We simulated anterolateral and inferior perfusion defects with variable extents and severities. The area under the ROC curve was estimated from the IO, IO-MM, and CHO test statistics and served as the figure-of-merit. The optimal collimator for the IO had a resolution of 9-11 mm FWHM at 10 cm, which is poorer resolution than typical collimators used for MPS. When the IO-MM and CHO used a geometric or no model of the CDR, the optimal collimator shifted toward higher resolution than that obtained using the IO and the CHO with full CDR modeling. With the optimal collimator, the IO-MM and CHO using geometric modeling gave similar performance to full CDR modeling. Collimators with poorer resolution were optimal when CDR modeling was used. The agreement of rankings between the IO-MM and CHO confirmed that the IO-MM is useful for optimization tasks when model mismatch is present due to its substantially reduced computational burden compared to the CHO.

A comparison between conductive and infrared devices for measuring mean skin temperature at rest, during exercise in the heat, and recovery.

PubMed

Bach, Aaron J E; Stewart, Ian B; Disher, Alice E; Costello, Joseph T

2015-01-01

Skin temperature assessment has historically been undertaken with conductive devices affixed to the skin. With the development of technology, infrared devices are increasingly utilised in the measurement of skin temperature. Therefore, our purpose was to evaluate the agreement between four skin temperature devices at rest, during exercise in the heat, and recovery. Mean skin temperature ([Formula: see text]) was assessed in thirty healthy males during 30 min rest (24.0 ± 1.2°C, 56 ± 8%), 30 min cycle in the heat (38.0 ± 0.5°C, 41 ± 2%), and 45 min recovery (24.0 ± 1.3°C, 56 ± 9%). [Formula: see text] was assessed at four sites using two conductive devices (thermistors, iButtons) and two infrared devices (infrared thermometer, infrared camera). Bland-Altman plots demonstrated mean bias ± limits of agreement between the thermistors and iButtons as follows (rest, exercise, recovery): -0.01 ± 0.04, 0.26 ± 0.85, -0.37 ± 0.98°C; thermistors and infrared thermometer: 0.34 ± 0.44, -0.44 ± 1.23, -1.04 ± 1.75°C; thermistors and infrared camera (rest, recovery): 0.83 ± 0.77, 1.88 ± 1.87°C. Pairwise comparisons of [Formula: see text] found significant differences (p < 0.05) between thermistors and both infrared devices during resting conditions, and significant differences between the thermistors and all other devices tested during exercise in the heat and recovery. These results indicate poor agreement between conductive and infrared devices at rest, during exercise in the heat, and subsequent recovery. Infrared devices may not be suitable for monitoring [Formula: see text] in the presence of, or following, metabolic and environmental induced heat stress.

Mouth-opening device as a treatment modality in trismus patients with head and neck cancer and oral submucous fibrosis: a prospective study.

PubMed

Li, Yu-Hsuan; Chang, Wei-Chin; Chiang, Tien-En; Lin, Chiun-Shu; Chen, Yuan-Wu

2018-04-26

This study investigated the clinical effectiveness of intervention with an open-mouth exercise device designed to facilitate maximal interincisal opening (MIO) and improve quality of life in patients with head and neck (H&N) cancer and oral submucous fibrosis (OSF). Sixty patients with H&N cancer, OSF, and trismus (MIO < 35 mm) participated in the functional rehabilitation program. An open-mouth exercise device intervention group and conventional group, each consisting of 20 patients, underwent a 12-week training and exercising program and follow-up. For the control group, an additional 20 patients were randomly selected to match the demographic characteristics of the aforementioned two groups. The patients' MIO improvements in the aforementioned three groups were 14.0, 10.5, and 1.3 mm, respectively. Results of this study confirm the significant improvement in average mouth-opening range. In addition, according to patient feedback, significant improvements in health-related quality of life and reductions in trismus symptoms occurred in the open-mouth exercise device group. This newly designed open-mouth exercise device can facilitate trismus patients with H&N cancer and OSF and improve mouth-opening range and quality of life.

Effects of integrated treatment with LED and microcurrent on muscle tone and stiffness in the calf muscle during moderate aerobic exercise.

PubMed

Han, Sang-Wan; Lee, Jeong-Woo

2018-06-01

[Purpose] This study aimed to investigate the effects of the therapeutic device combined with LED and microcurrent (MC) on muscle tone and stiffness in the calf muscle after its application during moderate aerobic exercise. [Subjects and Methods] Twenty healthy adult subjects were randomized to either the test group of the therapeutic device combined with LED and MC or the control group, and they walked on a 10%-sloped treadmill with a 5 km/hr speed for 30 minutes. Each of the subjects in the test group performed treadmill exercise with the therapeutic device attached to the edge of his or her calf muscle. After the exercise, the muscle tone and stiffness at the edge of the calf muscle were measured. [Results] With respect to the muscle tone, a statistically significant difference was found between the two groups only 5 minutes after the exercise. Concerning muscle stiffness, significant differences were shown between the two groups right after the exercise and 5 minutes after the exercise. [Conclusion] Integrated treatment with LED and MC on is considered helpful for lowering the muscle tone 5 minutes after the exercise, and for lowering the muscle stiffness right after the exercise and 5 minutes after the exercise.

Benefits, Consequences, and Uncertainties of Conventional (Exercise) Countermeasure Approaches

NASA Technical Reports Server (NTRS)

Ploutz-Snyder, Lori

2013-01-01

This presentation will review the pros, cons, and uncertainties of using exercise countermeasures in hypothetical long duration exploration missions. The use of artificial gravity and exercise will be briefly discussed. One benefit to continued use of exercise is related to our extensive experience with spaceflight exercise hardware and programming. Exercise has been a part of each space mission dating back to the 1960's when simple isometric and bungee exercises were performed in the Gemini capsule. Over the next 50 years, exercise hardware improved cumulating in today's ISS suite of exercise equipment: Cycle Ergometer with Vibration Isolation and Stabilization System (CEVIS), Treadmill (T2) and Advanced Resistive Exercise Device (ARED). Today's exercise equipment is the most robust ever to be flown in space and allows the variety and intensity of exercise that might reasonably be expected to maintain muscle mass and function, bone density and cardiovascular fitness. A second benefit is related to the large body of research literature on exercise training. There is a considerable body of supporting research literature including >40,000 peer reviewed research articles on exercise training in humans. A third benefit of exercise is its effectiveness. With the addition of T2 and ARED to our ISS exercise suite, crew member outcomes on standard medical tests have improved. Additionally exercise has other positive side effects such as stress relief, possible improvement of immune function, improved sleep, etc. Exercise is not without its consequences. The major cons to performance of in-flight exercise are the time and equipment required. Currently crew are scheduled 2.5 hrs/day for exercise and there is considerable cost to develop, fly and maintain exercise hardware. While no major injuries have been reported on ISS, there is always some risk of injury with any form of exercise There are several uncertainties going forward; these relate mostly to the development of small compact robust effective exercise devices for the next generation of space vehicles. It is becoming increasingly apparent that high intensity exercise is required for maintenance of fitness and functional capability and so future hardware will need to be developed, tested and implemented that allow for a wide variety of exercise, at high intensity while likely involving low mass, volume and power. There are many unanswered issues related to the minimum number and type of exercise devices required for exploration, optimizing exercise prescriptions for these devices, whether a treadmill is absolutely required, and even whether any single countermeasure can adequately protect muscle, bone, cardiovascular and sensorimotor function.

The Economics of Carbon Dioxide Removal: The Case against Free Disposal

NASA Astrophysics Data System (ADS)

Keller, D. P.; Rickels, W.; Quaas, M.; Oschlies, A.; Reith, F.

2016-12-01

Facing the challenge to keep the average global temperature increase below 2°C and to limit long-term climate change, removing carbon dioxide from the atmosphere (Carbon Dioxide Removal, CDR) and disposing of it in non-atmospheric carbon reservoirs is becoming increasingly necessary. The social cost of removing carbon into the terrestrial biosphere (e.g. by afforestation) or the ocean (e.g. by spreading olivine in coastal areas) arises from carbon-cycle feedbacks and saturation effects. Yet they are ignored in existing economic studies on CDR. Neglecting non-atmospheric social cost results in inconsistent estimates with regard to the share and timing of CDR measures in climate policy. Here, we use an intermediate-complexity earth system model, the University of Victoria (UVic) model, to calibrate a dynamic economic model, capturing the temperature feedback and saturation effect of terrestrial carbon uptake and the saturation effect of oceanic carbon uptake to obtain an improved understanding of the net social carbon value of terrestrial and oceanic CDR. We show that planning horizons beyond the year 2100 are required to properly reflect long-term scarcity issues of non-atmospheric carbon reservoirs in current carbon prices and that neglecting non-atmospheric social cost results in too low abatement efforts and in turn in too large and earlier application of CDR measures than if applied optimally. The figure shows the carbon prices for the different carbon reservoirs in the year 2100 in dependence of the planning horizon (for a climate policy aiming to limit global mean temperature increase to 2°C). The difference between the atmospheric and the non-atmospheric carbon prices indicates the benefits of the different CDR options.

Airport Traffic Conflict Detection and Resolution Algorithm Evaluation

NASA Technical Reports Server (NTRS)

Jones, Denise R.; Chartrand, Ryan C.; Wilson, Sara R.; Commo, Sean A.; Ballard, Kathryn M.; Otero, Sharon D.; Barker, Glover D.

2016-01-01

Two conflict detection and resolution (CD&R) algorithms for the terminal maneuvering area (TMA) were evaluated in a fast-time batch simulation study at the National Aeronautics and Space Administration (NASA) Langley Research Center. One CD&R algorithm, developed at NASA, was designed to enhance surface situation awareness and provide cockpit alerts of potential conflicts during runway, taxi, and low altitude air-to-air operations. The second algorithm, Enhanced Traffic Situation Awareness on the Airport Surface with Indications and Alerts (SURF IA), was designed to increase flight crew awareness of the runway environment and facilitate an appropriate and timely response to potential conflict situations. The purpose of the study was to evaluate the performance of the aircraft-based CD&R algorithms during various runway, taxiway, and low altitude scenarios, multiple levels of CD&R system equipage, and various levels of horizontal position accuracy. Algorithm performance was assessed through various metrics including the collision rate, nuisance and missed alert rate, and alert toggling rate. The data suggests that, in general, alert toggling, nuisance and missed alerts, and unnecessary maneuvering occurred more frequently as the position accuracy was reduced. Collision avoidance was more effective when all of the aircraft were equipped with CD&R and maneuvered to avoid a collision after an alert was issued. In order to reduce the number of unwanted (nuisance) alerts when taxiing across a runway, a buffer is needed between the hold line and the alerting zone so alerts are not generated when an aircraft is behind the hold line. All of the results support RTCA horizontal position accuracy requirements for performing a CD&R function to reduce the likelihood and severity of runway incursions and collisions.

Trade-offs for food production, nature conservation and climate limit the terrestrial carbon dioxide removal potential.

PubMed

Boysen, Lena R; Lucht, Wolfgang; Gerten, Dieter

2017-10-01

Large-scale biomass plantations (BPs) are a common factor in climate mitigation scenarios as they promise double benefits: extracting carbon from the atmosphere and providing a renewable energy source. However, their terrestrial carbon dioxide removal (tCDR) potentials depend on important factors such as land availability, efficiency of capturing biomass-derived carbon and the timing of operation. Land availability is restricted by the demands of future food production depending on yield increases and population growth, by requirements for nature conservation and, with respect to climate mitigation, avoiding unfavourable albedo changes. We integrate these factors in one spatially explicit biogeochemical simulation framework to explore the tCDR opportunity space on land available after these constraints are taken into account, starting either in 2020 or 2050, and lasting until 2100. We find that assumed future needs for nature protection and food production strongly limit tCDR potentials. BPs on abandoned crop and pasture areas (~1,300 Mha in scenarios of either 8.0 billion people and yield gap reductions of 25% until 2020 or 9.5 billion people and yield gap reductions of 50% until 2050) could, theoretically, sequester ~100 GtC in land carbon stocks and biomass harvest by 2100. However, this potential would be ~80% lower if only cropland was available or ~50% lower if albedo decreases were considered as a factor restricting land availability. Converting instead natural forest, shrubland or grassland into BPs could result in much larger tCDR potentials ̶ but at high environmental costs (e.g. biodiversity loss). The most promising avenue for effective tCDR seems to be improvement of efficient carbon utilization pathways, changes in dietary trends or the restoration of marginal lands for the implementation of tCDR. © 2017 John Wiley & Sons Ltd.

Immune repertoire: A potential biomarker and therapeutic for hepatocellular carcinoma.

PubMed

Han, Yingxin; Li, Hongmei; Guan, Yanfang; Huang, Jian

2016-09-01

The immune repertoire (IR) refers to the sum of B cells and T cells with functional diversity in the circulatory system of one individual at any given time. Immune cells, which reside within microenvironments and are responsible for protecting the human body, include T cells, B cells, macrophages, and dendritic cells. These dedicated immune cells have a characteristic structure and function. T and B cells are the main lymphocytes and are responsible for cellular immunity and humoral immunity, respectively. The T cell receptor (TCR) and B cell receptor (BCR) are composed of multiple peptide chains with antigen specificity. The amino acid composition and sequence order are more diverse in the complementarity-determining regions (including CDR1, CDR2 and CDR3) of each peptide chain, allowing a vast library of TCRs and BCRs. IR research is becoming increasingly focused on the study of CDR3 diversity. Deep profiling of CDR3s using high-throughput sequencing is a powerful approach for elucidating the composition and distribution of the CDR3s in a given sample, with in-depth information at the sequence level. Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. To identify novel biomarkers for diagnosis and drug targets for therapeutic interventions, several groups attempted to describe immune repertoire characteristics of the liver in the physiological environment or/and pathological conditions. This paper reviews the recent progress in IR research on human diseases, including hepatocellular carcinoma, attempting to depict the relationships between hepatocellular carcinogenesis and the IR, and discusses the possibility of IR as a potential biomarker and therapeutic for hepatocellular carcinoma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

SU-F-T-344: Commissioning Constant Dose Rate VMAT in the Raystation Treatment Planning System for a Varian Clinac IX

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

Pursley, J; Gueorguiev, G; Prichard, H

Purpose: To demonstrate the commissioning of constant dose rate volumetric modulated arc therapy (VMAT) in the Raystation treatment planning system for a Varian Clinac iX with Exact couch. Methods: Constant dose rate (CDR) VMAT is an option in the Raystation treatment planning system, enabling VMAT delivery on Varian linacs without a RapidArc upgrade. Raystation 4.7 was used to commission CDR-VMAT for a Varian Clinac iX. Raystation arc model parameters were selected to match machine deliverability characteristics. A Varian Exact couch model was added to Raystation 4.7 and commissioned for use in VMAT optimization. CDR-VMAT commissioning checks were performed on themore » linac, including patient-specific QA measurements for 10 test patients using both the ArcCHECK from Sun Nuclear Corporation and COMPASS from IBA Dosimetry. Multi-criteria optimization (MCO) in Raystation was used for CDR-VMAT planning. Results: Raystation 4.7 generated clinically acceptable and deliverable CDR-VMAT plans for the Varian Clinac. VMAT plans were optimized including a model of the Exact couch with both rails in the out positions. CDR-VMAT plans generated with MCO in Raystation were dosimetrically comparable to Raystation MCO-generated IMRT plans. Patient-specific QA measurements with the ArcCHECK on the couch showed good agreement with the treatment planning system prediction. Patient-specific, structure-specific, multi-statistical parameter 3D QA measurements with gantry-mounted COMPASS also showed good agreement. Conclusion: Constant dose rate VMAT was successfully modeled in Raystation 4.7 for a Varian Clinac iX, and Raystation’s multicriteria optimization generated constant dose rate VMAT plans which were deliverable and dosimetrically comparable to IMRT plans.« less

The Unusual Genetics and Biochemistry of Bovine Immunoglobulins.

PubMed

Stanfield, Robyn L; Haakenson, Jeremy; Deiss, Thaddeus C; Criscitiello, Michael F; Wilson, Ian A; Smider, Vaughn V

2018-01-01

Antibodies are the key circulating molecules that have evolved to fight infection by the adaptive immune system of vertebrates. Typical antibodies of most species contain six complementarity-determining regions (CDRs), where the third CDR of the heavy chain (CDR H3) has the greatest diversity and often makes the most significant contact with antigen. Generally, the process of V(D)J recombination produces a vast repertoire of antibodies; multiple V, D, and J gene segments recombine with additional junctional diversity at the V-D and D-J joints, and additional combinatorial possibilities occur through heavy- and light-chain pairing. Despite these processes, the overall structure of the resulting antibody is largely conserved, and binding to antigen occurs predominantly through the CDR loops of the immunoglobulin V domains. Bovines have deviated from this general paradigm by having few VH regions and thus little germline combinatorial diversity, but their antibodies contain long CDR H3 regions, with substantial diversity generated through somatic hypermutation. A subset of the repertoire comprises antibodies with ultralong CDR H3s, which can reach over 70 amino acids in length. Structurally, these unusual antibodies form a β-ribbon "stalk" and disulfide-bonded "knob" that protrude far from the antibody surface. These long CDR H3s allow cows to mount a particularly robust immune response when immunized with viral antigens, particularly to broadly neutralizing epitopes on a stabilized HIV gp140 trimer, which has been a challenge for other species. The unusual genetics and structural biology of cows provide for a unique paradigm for creation of immune diversity and could enable generation of antibodies against especially challenging targets and epitopes. © 2018 Elsevier Inc. All rights reserved.

Development of the dementia assessment sheet for community-based integrated care system.

PubMed

Awata, Shuichi; Sugiyama, Mika; Ito, Kae; Ura, Chiaki; Miyamae, Fumiko; Sakuma, Naoko; Niikawa, Hirotoshi; Okamura, Tsuyoshi; Inagaki, Hiroki; Ijuin, Mutsuo

2016-03-01

A series of our studies on the development of the Dementia Assessment Sheet for Community-based Integrated Care System 21-items (DASC-21) were reviewed. Study 1: to examine the distribution of scores and internal reliability of DASC-21, trained nurses and researchers visited the homes of 1341 participants aged 65 years and older and living in the community. The nurses interviewed the participants and, when possible, their family members, to complete the DASC-21. Then, the Mini-Mental State Examination was carried out to select the participants of study 2. Study 2: to examine the concurrent and discriminant validity, experienced psychiatrists and psychologists, who were blind to the findings of study 1, visited the homes of 131 subjects who were selected from the participants of study 1 and completed the Clinical Dementia Rating (CDR), the Mini-Mental State Examination and the Frontal Assessment Battery (FAB). Cronbach's coefficient alpha of the DASC-21 was 0.808-0.950. Scores of the DASC-21 significantly correlated with CDR total and box scores, Mini-Mental State Examination and Frontal Assessment Battery. In an analysis of variance, CDR had the main effect on the score of the DASC-21. Receiver operating characteristic analysis showed that the DASC-21 had sufficient discriminatory ability between dementia (CDR1+) and non-dementia (CDR0 or CDR0.5; area under the curve = 0.804-0.895). When using a cut-off point of 30/31, sensitivity was 83.3-94.1% and specificity was 77.3-86.4%. The DASC-21 has sufficient reliability and validity as a tool to evaluate impairments in daily functioning and in cognitive functions, to detect dementia, and to assess the severity of dementia in the community. © 2016 Japan Geriatrics Society.

Phasic-to-tonic shift in trunk muscle activity relative to walking during low-impact weight bearing exercise

NASA Astrophysics Data System (ADS)

Caplan, Nick; Gibbon, Karl; Hibbs, Angela; Evetts, Simon; Debuse, Dorothée

2014-11-01

The aim of this study was to investigate the influence of an exercise device, designed to improve the function of lumbopelvic muscles via low-impact weight-bearing exercise, on electromyographic (EMG) activity of lumbopelvic, including abdominal muscles. Surface EMG activity was collected from lumbar multifidus (LM), erector spinae (ES), internal oblique (IO), external oblique (EO) and rectus abdominis (RA) during overground walking (OW) and exercise device (EX) conditions. During walking, most muscles showed peaks in activity which were not seen during EX. Spinal extensors (LM, ES) were more active in EX. Internal oblique and RA were less active in EX. In EX, LM and ES were active for longer than during OW. Conversely, EO and RA were active for a shorter duration in EX than OW. The exercise device showed a phasic-to-tonic shift in activation of both local and global lumbopelvic muscles and promoted increased activation of spinal extensors in relation to walking. These features could make the exercise device a useful rehabilitative tool for populations with lumbopelvic muscle atrophy and dysfunction, including those recovering from deconditioning due to long-term bed rest and microgravity in astronauts.

Agreement between Electrocardiogram and Heart Rate Meter Is Low for the Measurement of Heart Rate Variability during Exercise in Young Endurance Horses.

PubMed

Lenoir, Augustin; Trachsel, Dagmar S; Younes, Mohamed; Barrey, Eric; Robert, Céline

2017-01-01

Analysis of the heart rate variability (HRV) gains more and more importance in the assessment of training practice and welfare in equine industry. It relies on mathematical analyses of reliably and accurately measured variations in successive inter-beat intervals, measured as RR intervals. Nowadays, the RR intervals can be obtained through two different techniques: a heart rate meter (HRM) or an electrocardiogram (ECG). The agreement and reliability of these devices has not been fully assessed, especially for recordings during exercise. The purpose of this study was to assess the agreement of two commercially available devices using the two mentioned techniques (HRM vs ECG) for HRV analysis during a standardized exercise test. Simultaneous recordings obtained during light exercise and during canter with both devices were available for 36 horses. Data were compared using a Bland-Altman analysis and the Lin's coefficient. The agreement between the assessed HRV measures from the data obtained from the ECG and HRM was acceptable only for the mean RR interval and the mean heart rate. For the other studied measures (SDNN, root mean square of successive differences, SD1, SD2, low frequency, high frequency), the agreement between the devices was too poor for them to be considered as interchangeable in these recording conditions. The agreement tended also to be worse when speed of the exercise increased. Therefore, it is necessary to be careful when interpreting and comparing results of HRV analysis during exercise, as the results will depend upon recording devices. Furthermore, corrections and data processing included in the software of the devices affect largely the output used in the subsequent HRV analysis; this must be considered in the choice of the device.

Similarity regularized sparse group lasso for cup to disc ratio computation.

PubMed

Cheng, Jun; Zhang, Zhuo; Tao, Dacheng; Wong, Damon Wing Kee; Liu, Jiang; Baskaran, Mani; Aung, Tin; Wong, Tien Yin

2017-08-01

Automatic cup to disc ratio (CDR) computation from color fundus images has shown to be promising for glaucoma detection. Over the past decade, many algorithms have been proposed. In this paper, we first review the recent work in the area and then present a novel similarity-regularized sparse group lasso method for automated CDR estimation. The proposed method reconstructs the testing disc image based on a set of reference disc images by integrating the similarity between testing and the reference disc images with the sparse group lasso constraints. The reconstruction coefficients are then used to estimate the CDR of the testing image. The proposed method has been validated using 650 images with manually annotated CDRs. Experimental results show an average CDR error of 0.0616 and a correlation coefficient of 0.7, outperforming other methods. The areas under curve in the diagnostic test reach 0.843 and 0.837 when manual and automatically segmented discs are used respectively, better than other methods as well.

Establishment of cell lines from adult T-cell leukemia cells dependent on negatively charged polymers.

PubMed

Kagami, Yoshitoyo; Uchiyama, Susumu; Kato, Harumi; Okada, Yasutaka; Seto, Masao; Kinoshita, Tomohiro

2017-07-05

Growing adult T-cell leukemia/lymphoma (ATLL) cells in vitro is difficult. Here, we examined the effects of static electricity in the culture medium on the proliferation of ATLL cells. Six out of 10 ATLL cells did not proliferate in vitro and thus had to be cultured in a medium containing negatively charged polymers. In the presence of poly-γ-glutamic acid (PGA) or chondroitin sulfate (CDR), cell lines (HKOX3-PGA, HKOX3-CDR) were established from the same single ATLL case using interleukin (IL)-2, IL-4, and feeder cells expressing OX40L (OX40L + HK). Dextran sulfate inhibited growth in both HKOX3 cell lines. Both PGA and OX40L + HK were indispensable for HKOX3-PGA growth, but HKOX3-CDR could proliferate in the presence of CDR or OX40L + HK alone. Thus, the specific action of each negatively charged polymer promoted the growth of specific ATLL cells in vitro.

Humanization of Antibodies Using Heavy Chain Complementarity-determining Region 3 Grafting Coupled with in Vitro Somatic Hypermutation*

PubMed Central

Bowers, Peter M.; Neben, Tamlyn Y.; Tomlinson, Geoffery L.; Dalton, Jennifer L.; Altobell, Larry; Zhang, Xue; Macomber, John L.; Wu, Betty F.; Toobian, Rachelle M.; McConnell, Audrey D.; Verdino, Petra; Chau, Betty; Horlick, Robert A.; King, David J.

2013-01-01

A method for simultaneous humanization and affinity maturation of monoclonal antibodies has been developed using heavy chain complementarity-determining region (CDR) 3 grafting combined with somatic hypermutation in vitro. To minimize the amount of murine antibody-derived antibody sequence used during humanization, only the CDR3 region from a murine antibody that recognizes the cytokine hβNGF was grafted into a nonhomologous human germ line V region. The resulting CDR3-grafted HC was paired with a CDR-grafted light chain, displayed on the surface of HEK293 cells, and matured using in vitro somatic hypermutation. A high affinity humanized antibody was derived that was considerably more potent than the parental antibody, possessed a low pm dissociation constant, and demonstrated potent inhibition of hβNGF activity in vitro. The resulting antibody contained half the heavy chain murine donor sequence compared with the same antibody humanized using traditional methods. PMID:23355464

Ecological Limits to Terrestrial Carbon Dioxide Removal Strategies

NASA Astrophysics Data System (ADS)

Smith, L. J.; Torn, M. S.; Jones, A. D.

2011-12-01

Carbon dioxide removal from the atmosphere through terrestrial carbon sequestration and bioenergy (biological CDR) is a proposed climate change mitigation strategy. Biological CDR increases the carbon storage capacity of soils and biomass through changes in land cover and use, including reforestation, afforestation, conversion of land to agriculture for biofuels, conversion of degraded land to grassland, and alternative management practices such as conservation tillage. While biological CDR may play a valuable role in future climate change mitigation, many of its proponents fail to account for the full range of biological, biophysical, hydrologic, and economic complexities associated with proposed land use changes. In this analysis, we identify and discuss a set of ecological limits and impacts associated with terrestrial CDR. The capacity of biofuels, soils, and other living biomass to sequester carbon may be constrained by nutrient and water availability, soil dynamics, and local climate effects, all of which can change spatially and temporally in unpredictable ways. Even if CDR is effective at sequestering CO2, its associated land use and land cover changes may negatively impact ecological resources by compromising water quality and availability, degrading soils, reducing biodiversity, displacing agriculture, and altering local climate through albedo and evapotranspiration changes. Measures taken to overcome ecological limitations, such as fertilizer addition and irrigation, may exacerbate these impacts even further. The ecological considerations and quantitative analyses that we present highlight uncertainties introduced by ecological complexity, disagreements between models, perverse economic incentives, and changing environmental factors. We do not reject CDR as a potentially valuable strategy for climate change mitigation; ecosystem protection, restoration, and improved management practices could enhance soil fertility and protect biodiversity while reducing increases in atmospheric CO2. Rather, we emphasize the importance of evaluating the full set of biological, physical, economic, and political realities that accompany land-use changes and manipulations to the carbon cycle. While the immediate goal of biological CDR is to reduce atmospheric CO2 concentrations, its ultimate goal in mitigating climate change is to reduce the threats to ecosystems and society. Sequestering carbon at the cost of ecosystem health would not be a sensible approach.

Generation and analysis of the improved human HAL9/10 antibody phage display libraries.

PubMed

Kügler, Jonas; Wilke, Sonja; Meier, Doris; Tomszak, Florian; Frenzel, André; Schirrmann, Thomas; Dübel, Stefan; Garritsen, Henk; Hock, Björn; Toleikis, Lars; Schütte, Mark; Hust, Michael

2015-02-19

Antibody phage display is a proven key technology that allows the generation of human antibodies for diagnostics and therapy. From naive antibody gene libraries - in theory - antibodies against any target can be selected. Here we describe the design, construction and characterization of an optimized antibody phage display library. The naive antibody gene libraries HAL9 and HAL10, with a combined theoretical diversity of 1.5×10(10) independent clones, were constructed from 98 healthy donors using improved phage display vectors. In detail, most common phagemids employed for antibody phage display are using a combined His/Myc tag for detection and purification. We show that changing the tag order to Myc/His improved the production of soluble antibodies, but did not affect antibody phage display. For several published antibody libraries, the selected number of kappa scFvs were lower compared to lambda scFvs, probably due to a lower kappa scFv or Fab expression rate. Deletion of a phenylalanine at the end of the CL linker sequence in our new phagemid design increased scFv production rate and frequency of selected kappa antibodies significantly. The HAL libraries and 834 antibodies selected against 121 targets were analyzed regarding the used germline V-genes, used V-gene combinations and CDR-H3/-L3 length and composition. The amino acid diversity and distribution in the CDR-H3 of the initial library was retrieved in the CDR-H3 of selected antibodies showing that all CDR-H3 amino acids occurring in the human antibody repertoire can be functionally used and is not biased by E. coli expression or phage selection. Further, the data underline the importance of CDR length variations. The highly diverse universal antibody gene libraries HAL9/10 were constructed using an optimized scFv phagemid vector design. Analysis of selected antibodies revealed that the complete amino acid diversity in the CDR-H3 was also found in selected scFvs showing the functionality of the naive CDR-H3 diversity.

Asteroid Bennu Temperature Maps for OSIRIS-REx Spacecraft and Instrument Thermal Analyses

NASA Technical Reports Server (NTRS)

Choi, Michael K.; Emery, Josh; Delbo, Marco

2014-01-01

A thermophysical model has been developed to generate asteroid Bennu surface temperature maps for OSIRIS-REx spacecraft and instrument thermal design and analyses at the Critical Design Review (CDR). Two-dimensional temperature maps for worst hot and worst cold cases are used in Thermal Desktop to assure adequate thermal design margins. To minimize the complexity of the Bennu geometry in Thermal Desktop, it is modeled as a sphere instead of the radar shape. The post-CDR updated thermal inertia and a modified approach show that the new surface temperature predictions are more benign. Therefore the CDR Bennu surface temperature predictions are conservative.

Emergency Fuels Technology

DTIC Science & Technology

1982-06-01

starting and running in multifuel engines. D. FEF for Ground Turbine Engines Operation of the simple-cycle, gas-turbine engine is based on the Brayton or...MR R LAYNE) CAMERON STATION WASHINGTON DC 20362 ALEXANDRIA VA 22314 CDR CDR DAVID TAYLOR NAVAL SHIP R&D CTR MARINE CORPS LOGISTICS SUPPORT CODE 2830

Is volumetric modulated arc therapy with constant dose rate a valid option in radiation therapy for head and neck cancer patients?

PubMed

Didona, Annamaria; Lancellotta, Valentina; Zucchetti, Claudio; Panizza, Bianca Moira; Frattegiani, Alessandro; Iacco, Martina; Di Pilato, Anna Concetta; Saldi, Simonetta; Aristei, Cynthia

2018-01-01

Intensity-modulated radiotherapy (IMRT) improves dose distribution in head and neck (HN) radiation therapy. Volumetric-modulated arc therapy (VMAT), a new form of IMRT, delivers radiation in single or multiple arcs, varying dose rates (VDR-VMAT) and gantry speeds, has gained considerable attention. Constant dose rate VMAT (CDR-VMAT) associated with a fixed gantry speed does not require a dedicated linear accelerator like VDR-VMAT. The present study explored the feasibility, efficiency and delivery accuracy of CDR-VMAT, by comparing it with IMRT and VDR-VMAT in treatment planning for HN cancer. Step and shoot IMRT (SS-IMRT), CDR-VMAT and VDR-VMAT plans were created for 15 HN cancer patients and were generated by Pinnacle 3 TPS (v 9.8) using 6 MV photon energy. Three PTVs were defined to receive respectively prescribed doses of 66 Gy, 60 Gy and 54 Gy, in 30 fractions. Organs at risk (OARs) included the mandible, spinal cord, brain stem, parotids, salivary glands, esophagus, larynx and thyroid. SS-IMRT plans were based on 7 co-planar beams at fixed gantry angles. CDR-VMAT and VDR-VMAT plans, generated by the SmartArc module, used a 2-arc technique: one clockwise from 182° to 178° and the other one anti-clockwise from 178° to 182°. Comparison parameters included dose distribution to PTVs ( D mean , D 2% , D 50% , D 95% , D 98% and Homogeneity Index), maximum or mean doses to OARs, specific dose-volume data, the monitor units and treatment delivery times. Compared with SS-IMRT, CDR-VMAT significantly reduced the maximum doses to PTV1 and PTV2 and significantly improved all PTV3 parameters, except D 98% and D 95% . It significantly spared parotid and submandibular glands and was associated with a lower D mean to the larynx. Compared with VDR-VMAT, CDR-VMAT was linked to a significantly better D mean , to the PTV3 but results were worse for the parotids, left submandibular gland, esophagus and mandible. Furthermore, the D mean to the larynx was also worse. Compared with SS-IMRT and VDR-VMAT, CDR-VMAT was associated with higher average monitor unit values and significantly shorter average delivery times. CDR-VMAT appeared to be a valid option in Radiation Therapy Centers that lack a dedicated linear accelerator for volumetric arc therapy with variable dose-rates and gantry velocities, and are unwilling or unable to sanction major expenditure at present but want to adopt volumetric techniques.

Mechanism Development, Testing, and Lessons Learned for the Advanced Resistive Exercise Device

NASA Technical Reports Server (NTRS)

Lamoreaux, Christopher D.; Landeck, Mark E.

2006-01-01

The Advanced Resistive Exercise Device (ARED) has been developed at NASA Johnson Space Center, for the International Space Station (ISS) program. ARED is a multi-exercise, high-load resistive exercise device, designed for long duration, human space missions. ARED will enable astronauts to effectively maintain their muscle strength and bone mass in the micro-gravity environment more effectively than any other existing devices. ARED's resistance is provided via two, 20.3 cm (8 in) diameter vacuum cylinders, which provide a nearly constant resistance source. ARED also has a means to simulate the inertia that is felt during a 1-G exercise routine via the flywheel subassembly, which is directly tied to the motion of the ARED cylinders. ARED is scheduled to fly on flight ULF 2 to the ISS and will be located in Node 1. Presently, ARED is in the middle of its qualification and acceptance test program. An extensive testing program and engineering evaluation has increased the reliability of ARED by bringing potential design issues to light before flight production. Some of those design issues, resolutions, and design details will be discussed in this paper.

Defining Exercise Performance Metrics for Flight Hardware Development

NASA Technical Reports Server (NTRS)

Beyene, Nahon M.

2004-01-01

The space industry has prevailed over numerous design challenges in the spirit of exploration. Manned space flight entails creating products for use by humans and the Johnson Space Center has pioneered this effort as NASA's center for manned space flight. NASA Astronauts use a suite of flight exercise hardware to maintain strength for extravehicular activities and to minimize losses in muscle mass and bone mineral density. With a cycle ergometer, treadmill, and the Resistive Exercise Device available on the International Space Station (ISS), the Space Medicine community aspires to reproduce physical loading schemes that match exercise performance in Earth s gravity. The resistive exercise device presents the greatest challenge with the duty of accommodating 20 different exercises and many variations on the core set of exercises. This paper presents a methodology for capturing engineering parameters that can quantify proper resistive exercise performance techniques. For each specified exercise, the method provides engineering parameters on hand spacing, foot spacing, and positions of the point of load application at the starting point, midpoint, and end point of the exercise. As humans vary in height and fitness levels, the methodology presents values as ranges. In addition, this method shows engineers the proper load application regions on the human body. The methodology applies to resistive exercise in general and is in use for the current development of a Resistive Exercise Device. Exercise hardware systems must remain available for use and conducive to proper exercise performance as a contributor to mission success. The astronauts depend on exercise hardware to support extended stays aboard the ISS. Future plans towards exploration of Mars and beyond acknowledge the necessity of exercise. Continuous improvement in technology and our understanding of human health maintenance in space will allow us to support the exploration of Mars and the future of space exploration.

Disturbed social recognition and impaired risk judgement in older residents with mild cognitive impairment after the Great East Japan Earthquake of 2011: the Tome Project.

PubMed

Akanuma, Kyoko; Nakamura, Kei; Meguro, Kenichi; Chiba, Masanori; Gutiérrez Ubeda, Sergio Ramón; Kumai, Keiichi; Kato, Yuka; Oonuma, Jiro; Kasai, Mari; Nakatsuka, Masahiro; Seki, Takashi; Tomita, Hiroaki

2016-11-01

After the Great East Japan Earthquake of 2011, we investigated the safety of residents in the affected communities. Most of the people requiring help were elderly and had previously been assessed as Clinical Dementia Rating (CDR) 0.5 (i.e. as having mild cognitive impairment (MCI)). We examined how well they understood the television news and whether they could make appropriate decisions. This community-based study of dementia and difficulties following a disaster started in Tome, northern Japan. The subjects were 188 randomly selected older residents who underwent CDR, blood tests, magnetic resonance imaging, and cognitive tests, including an original visual risk cognition task. They were shown NHK news broadcasts from the day of the earthquake to determine whether they could understand the content. Neither the CDR 0 (healthy) nor the CDR 0.5 (MCI) subjects fully understood the television news. Some subjects did not recognize the danger of aftershocks and engaged in risky behaviour. CDR 0.5 subjects who exhibited such behaviour scored lower on the visual risk cognition task. It is noteworthy that television news is difficult to understand, even for healthy older adults. We found that MCI subjects had particular difficulties due to the disaster and suggest that risk cognition could be evaluated using visually presented materials. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.

Digital radiography of crush thoracic trauma in the Sichuan earthquake

PubMed Central

Dong, Zhi-Hui; Shao, Heng; Chen, Tian-Wu; Chu, Zhi-Gang; Deng, Wen; Tang, Si-Shi; Chen, Jing; Yang, Zhi-Gang

2011-01-01

AIM: To investigate the features of crush thoracic trauma in Sichuan earthquake victims using chest digital radiography (CDR). METHODS: We retrospectively reviewed 772 CDR of 417 females and 355 males who had suffered crush thoracic trauma in the Sichuan earthquake. Patient age ranged from 0.5 to 103 years. CDR was performed between May 12, 2008 and June 7, 2008. We looked for injury to the thoracic cage, pulmonary parenchyma and the pleura. RESULTS: Antero-posterior (AP) and lateral CDR were obtained in 349 patients, the remaining 423 patients underwent only AP CDR. Thoracic cage fractures, pulmonary contusion and pleural injuries were noted in 331 (42.9%; 95% CI: 39.4%-46.4%), 67 and 135 patients, respectively. Of the 256 patients with rib fractures, the mean number of fractured ribs per patient was 3. Rib fractures were mostly distributed from the 3rd through to the 8th ribs and the vast majority involved posterior and lateral locations along the rib. Rib fractures had a significant positive association with non-rib thoracic fractures, pulmonary contusion and pleural injuries (P < 0.001). The number of rib fractures and pulmonary contusions were significant factors associated with patient death. CONCLUSION: Earthquake-related crush thoracic trauma has the potential for multiple fractures. The high number of fractured ribs and pulmonary contusions were significant factors which needed appropriate medical treatment. PMID:22132298

Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

NASA Technical Reports Server (NTRS)

Humphreys, B. T.; Thompson, W. K.; Lewandowski, B. E.; Cadwell, E. E.; Newby, N. J.; Fincke, R. S.; Sheehan, C.; Mulugeta, L.

2012-01-01

NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the development of the Adams ARED module including its capabilities, limitations, and assumptions. Preliminary results, validation activities, and a practical application of the module to inform the relative effect of the flywheels on exercise will be discussed.

Feasibility test on green energy harvesting from physical exercise devices

NASA Astrophysics Data System (ADS)

Mustafi, Nirendra N.; Mourshed, M.; Masud, M. H.; Hossain, M. S.; Kamal, M. R.

2017-06-01

The demand of power is increasing day by day due to the increase of world population as well as the industrialization and modernization. Depletion of the world's fossil fuel reserves and the adverse effects of their uses on the environment insist the researchers to find out some means of efficient and cost effective alternative energy sources from small to large scales. In a gymnasium the human metabolism power is used to drive the physical exercise devices. However there are a number of exercise device which can have the potential to generate electricity during physical exercise. By converting the available mechanical energy from these exercise devices into kinetic energy, electric power can be produced. In this work, energy was harvested from the most commonly used physical exercise devices used in the gymnasium - paddling and chin up. The paddle pulley and the chin up pulley were connected to the couple pulley which in turn coupled to an alternator by a V-belt to produce electrical energy and a rechargeable battery was used to store electrical energy. The power generation from the device depends upon the speed at which the alternator runs and the age limit. The electrical energy output was observed 83.6 watt at 1300 rpm and 62.5 watt at1150 rpm alternator speed for the paddling and chin up respectively recorded for an average adult. The device was designed for a constant 49N load on the alternator for both paddling and chin up operation. By running each of these devices for about 12 hours in a day, any gymnasium can avoid burning of almost 23.67 kg and 31.6 kg of diesel fuel per year for chin up and paddling respectively. Also it can cut off the CO2 emission to the environment which reveals itself a standalone green micro gym.

The Latin American Challenge and Army Hispanic Soldier Policy

DTIC Science & Technology

1986-02-18

FLA MG Edward Baca, TAG, New Mexico National Guard, New Mexico MG Belisario Flores, Asst AG, Air National Guard, Texas RA Diego Hernandez , Roosevelt...Marc A. Cisneros, Div Arty Cdr, Ft Hood, TX COL Samuel Malave-Garcia, Port Cdr, Rotterdam, Neth COL(ARNG Ret) Gustavo Leon, Former ARNG Senior Advisor

Model Development and Replication: Introducing and Sustaining Change

ERIC Educational Resources Information Center

Garland, Corinne W.

2005-01-01

This article describes the three-decade experience in model development and replication and in introducing and sustaining organization change of Child Development Resources (CDR), of Williamsburg, Virginia. CDR provides an integrated system of services for children with disabilities and developmental delays as well as for children who are at risk.…

[Exercise-induced oedema due to hormone-containing intrauterine device].

PubMed

Franssen, Laurens E; Bos, Willem-Jan W

2012-01-01

Oedema is a known adverse effect of the levonorgestrel-containing intrauterine device (Mirena IUD). However, exercise-induced oedema has not been described before. A 38-year-old woman presented with symptoms of diffuse, exercise-induced oedema and dyspnoea. Tests for heart failure and other causes of oedema showed no abnormalities. All symptoms resolved spontaneously after the patient initiated removal of the IUD. The pathophysiology of exercise-induced oedema is still poorly understood. When confronted with a patient with oedema (induced by exercise or other cause), the most common causes must first be excluded. If no explanation can be found, then the effects of medication must not be overlooked.

Novel Musculoskeletal Loading and Assessment System

NASA Technical Reports Server (NTRS)

Downs, Meghan E.

2017-01-01

Ground based and ISS (International Space Station) exercise research have shown that axial loading via two-point loading at the shoulders and load quality (i.e. consistent load and at least 1:1 concentric to eccentric ratio) are extremely important to optimize musculoskeletal adaptations to resistance exercise. The Advanced Resistance Exercise Device (ARED) is on ISS now and is the "state of the art" for resistance exercise capabilities in microgravity; however, the ARED is far too large and power consuming for exploration vehicles. The single cable exercise device design selected for MPCV (Multi-Purpose Crew Vehicle), does not readily allow for the two-point loading at the shoulders.

[Physical exercise versus exercise program using electrical stimulation devices for home use].

PubMed

Santos, F M; Rodrigues, R G S; Trindade-Filho, E M

2008-02-01

To evaluate the effects of electrical muscle stimulation with devices for home use on neuromuscular conditioning. The study sample comprised 20 sedentary, right-handed, voluntary women aged from 18 to 25 years in the city of Maceió, Northeastern Brazil, in 2006. Subjects were randomly divided into two groups: group A included women who underwent muscle stimulation using commercial electrical devices; group B included those women who performed physical activities with loads. The training program for both groups consisted of two weekly sessions for two months, in a total of 16 sessions. Comparisons of body weight, cirtometry, fleximetry, and muscle strength before and after exercise were determined using the paired t-test. For the comparisons between both groups, Student's t-test was used and a 5% significance level was adopted. Muscle strength subjectively assessed before and after each intervention was increased in both groups. Significant increases in muscle mass and strength were seen only in those subjects who performed voluntary physical activity. Resisted knee flexion and extension exercises effectively increased muscle mass and strength when compared to electrical stimulation at 87 Hz which did not produce a similar effect. The study results showed that electrical stimulation devices for passive physical exercising commercially available are less effective than voluntary physical exercise.

Accuracy of an infrared LED device to measure heart rate and energy expenditure during rest and exercise.

PubMed

Lee, C Matthew; Gorelick, Mark; Mendoza, Albert

2011-12-01

The purpose of this study was to examine the accuracy of the ePulse Personal Fitness Assistant, a forearm-worn device that provides measures of heart rate and estimates energy expenditure. Forty-six participants engaged in 4-minute periods of standing, 2.0 mph walking, 3.5 mph walking, 4.5 mph jogging, and 6.0 mph running. Heart rate and energy expenditure were simultaneously recorded at 60-second intervals using the ePulse, an electrocardiogram (EKG), and indirect calorimetry. The heart rates obtained from the ePulse were highly correlated (intraclass correlation coefficients [ICCs] ≥0.85) with those from the EKG during all conditions. The typical errors progressively increased with increasing exercise intensity but were <5 bpm only during rest and 2.0 mph. Energy expenditure from the ePulse was poorly correlated with indirect calorimetry (ICCs: 0.01-0.36) and the typical errors for energy expenditure ranged from 0.69-2.97 kcal · min(-1), progressively increasing with exercise intensity. These data suggest that the ePulse Personal Fitness Assistant is a valid device for monitoring heart rate at rest and low-intensity exercise, but becomes less accurate as exercise intensity increases. However, it does not appear to be a valid device to estimate energy expenditure during exercise.

Smart Rehabilitation Devices: Part I – Force Tracking Control

PubMed Central

Dong, Shufang; Lu, Ke-Qian; Sun, J. Q.; Rudolph, Katherine

2008-01-01

Resistance exercise has been widely reported to have positive rehabilitation effects for patients with neuromuscular and orthopaedic conditions. This article presents prototypes of smart variable resistance exercise devices using magneto-rheological fluid dampers. An intelligent supervisory control for regulating the resistive force or torque of the device is developed, and is validated both numerically and experimentally. The device provides both isometric and isokinetic strength training for the human joints including knee, elbow, hip, and ankle. PMID:18504509

Body Building Boons From Apollo

NASA Technical Reports Server (NTRS)

1978-01-01

The Exer-Genie program utilizes familiar types of exercise, such as isometrics (pushing or pulling against an immovable object) and isotonics (motive exercises such as calisthenics or weight lifting) but with the important added factor of controlled resistance. The device is an arrangement of hand grips and nylon cord wrapped around an aluminum shaft. Controlled friction determines the resistance and the user can set the amount of resistive force to his own physical conditioning needs. Since Apollo days, the Exer-Genie and a similar device called the Apollo Exerciser have found wide acceptance among professional, collegiate and high school athletic teams, and among the growing number of individuals interested in physical fitness. These devices are efficient and economical replacements for conventional conditioning equipment and extremely versatile, allowing more than 100 basic exercises for shaping up specific muscle groups.

Current State of Commercial Wearable Technology in Physical Activity Monitoring 2015–2017

PubMed Central

BUNN, JENNIFER A.; NAVALTA, JAMES W.; FOUNTAINE, CHARLES J.; REECE, JOEL D.

2018-01-01

Wearable physical activity trackers are a popular and useful method to collect biometric information at rest and during exercise. The purpose of this systematic review was to summarize recent findings of wearable devices for biometric information related to steps, heart rate, and caloric expenditure for several devices that hold a large portion of the market share. Searches were conducted in both PubMed and SPORTdiscus. Filters included: humans, within the last 5 years, English, full-text, and adult 19+ years. Manuscripts were retained if they included an exercise component of 5-min or greater and had 20 or more participants. A total of 10 articles were retained for this review. Overall, wearable devices tend to underestimate energy expenditure compared to criterion laboratory measures, however at higher intensities of activity energy expenditure is underestimated. All wrist and forearm devices had a tendency to underestimate heart rate, and this error was generally greater at higher exercise intensities and those that included greater arm movement. Heart rate measurement was also typically better at rest and while exercising on a cycle ergometer compared to exercise on a treadmill or elliptical machine. Step count was underestimated at slower walking speeds and in free-living conditions, but improved accuracy at faster speeds. The majority of the studies reviewed in the present manuscript employed different methods to assess validity and reliability of wearable technology, making it difficult to compare devices. Standardized protocols would provide guidance for researchers to evaluate research-grade devices as well as commercial devices used by the lay public. PMID:29541338

Current State of Commercial Wearable Technology in Physical Activity Monitoring 2015-2017.

PubMed

Bunn, Jennifer A; Navalta, James W; Fountaine, Charles J; Reece, Joel D

2018-01-01

Wearable physical activity trackers are a popular and useful method to collect biometric information at rest and during exercise. The purpose of this systematic review was to summarize recent findings of wearable devices for biometric information related to steps, heart rate, and caloric expenditure for several devices that hold a large portion of the market share. Searches were conducted in both PubMed and SPORTdiscus. Filters included: humans, within the last 5 years, English, full-text, and adult 19+ years. Manuscripts were retained if they included an exercise component of 5-min or greater and had 20 or more participants. A total of 10 articles were retained for this review. Overall, wearable devices tend to underestimate energy expenditure compared to criterion laboratory measures, however at higher intensities of activity energy expenditure is underestimated. All wrist and forearm devices had a tendency to underestimate heart rate, and this error was generally greater at higher exercise intensities and those that included greater arm movement. Heart rate measurement was also typically better at rest and while exercising on a cycle ergometer compared to exercise on a treadmill or elliptical machine. Step count was underestimated at slower walking speeds and in free-living conditions, but improved accuracy at faster speeds. The majority of the studies reviewed in the present manuscript employed different methods to assess validity and reliability of wearable technology, making it difficult to compare devices. Standardized protocols would provide guidance for researchers to evaluate research-grade devices as well as commercial devices used by the lay public.

A Comparison between Conductive and Infrared Devices for Measuring Mean Skin Temperature at Rest, during Exercise in the Heat, and Recovery

PubMed Central

Bach, Aaron J. E.; Stewart, Ian B.; Disher, Alice E.; Costello, Joseph T.

2015-01-01

Purpose Skin temperature assessment has historically been undertaken with conductive devices affixed to the skin. With the development of technology, infrared devices are increasingly utilised in the measurement of skin temperature. Therefore, our purpose was to evaluate the agreement between four skin temperature devices at rest, during exercise in the heat, and recovery. Methods Mean skin temperature (T-sk) was assessed in thirty healthy males during 30 min rest (24.0 ± 1.2°C, 56 ± 8%), 30 min cycle in the heat (38.0 ± 0.5°C, 41 ± 2%), and 45 min recovery (24.0 ± 1.3°C, 56 ± 9%). T-sk was assessed at four sites using two conductive devices (thermistors, iButtons) and two infrared devices (infrared thermometer, infrared camera). Results Bland–Altman plots demonstrated mean bias ± limits of agreement between the thermistors and iButtons as follows (rest, exercise, recovery): -0.01 ± 0.04, 0.26 ± 0.85, -0.37 ± 0.98°C; thermistors and infrared thermometer: 0.34 ± 0.44, -0.44 ± 1.23, -1.04 ± 1.75°C; thermistors and infrared camera (rest, recovery): 0.83 ± 0.77, 1.88 ± 1.87°C. Pairwise comparisons of T-sk found significant differences (p < 0.05) between thermistors and both infrared devices during resting conditions, and significant differences between the thermistors and all other devices tested during exercise in the heat and recovery. Conclusions These results indicate poor agreement between conductive and infrared devices at rest, during exercise in the heat, and subsequent recovery. Infrared devices may not be suitable for monitoring T-sk in the presence of, or following, metabolic and environmental induced heat stress. PMID:25659140

Importance of heart rate during exercise for response to cardiac resynchronization therapy.

PubMed

Maass, Alexander H; Buck, Sandra; Nieuwland, Wybe; Brügemann, Johan; van Veldhuisen, Dirk J; Van Gelder, Isabelle C

2009-07-01

Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60-70% of patients. To study exercise-related factors predicting response to CRT. We retrospectively examined consecutive patients in whom a CRT device was implanted. All underwent cardiopulmonary exercise testing prior to implantation and after 6 months. The occurrence of chronotropic incompetence and heart rates exceeding the upper rate of the device, thereby compromising biventricular stimulation, was studied. Response was defined as a decrease in LVESV of 10% or more after 6 months. We included 144 patients. After 6 months 86 (60%) patients were responders. Peak VO2 significantly increased in responders. Chronotropic incompetence was more frequently seen in nonresponders (21 [36%] vs 9 [10%], P = 0.03), mostly in patients in SR. At moderate exercise, defined as 25% of the maximal exercise tolerance, that is, comparable to daily life exercise, nonresponders more frequently went above the upper rate of the device (13 [22%] vs 2 [3%], P < 0.0001), most of whom were patients in permanent AF. Multivariate analysis revealed heart rates not exceeding the upper rate of the device during moderate exercise (OR 15.8 [3.3-76.5], P = 0.001) and nonischemic cardiomyopathy (OR 2.4 [1.0-5.7], P = 0.04) as predictive for response. Heart rate exceeding the upper rate during moderate exercise is an independent predictor for nonresponse to CRT in patients with AF, whereas chronotropic incompetence is a predictor for patients in SR.

Left ventricular assist device: exercise capacity evolution and rehabilitation added value.

PubMed

Lamotte, Michel X; Chimenti, Sara; Deboeck, Gael; Gillet, Alexis; Kacelenenbogen, Raymond; Strapart, Jonathan; Vandeneynde, Frédéric; Van Nooten, Guido; Antoine, Martine

2018-06-01

With more than 15,000 implanted patients worldwide and a survival rate of 80% at 1-year and 59% at 5-years, left ventricular assist device (LVAD) implantation has become an interesting strategy in the management of heart failure patients who are resistant to other kinds of treatment. There are limited data in the literature on the change over time of exercise capacity in LVAD patients, as well as limited knowledge about the beneficial effects that rehabilitation might have on these patients. Therefore, the aim of our study was to evaluate the evolution of exercise capacity on a cohort of patients implanted with the same device (HeartWare © ) and to analyse the potential impact of rehabilitation. Sixty-two patients implanted with a LVAD between June 2011 and June 2015 were screened. Exercise capacity was evaluated by cardiopulmonary exercise testing at 6 weeks, 6 and 12 months after implantation. We have observed significant differences in the exercise capacity and evolution between the trained and non-trained patients. Some of the trained patients nearly normalised their exercise capacity at the end of the rehabilitation programme. Exercise capacity of patient implanted with a HeartWare © LVAD increased in the early period after implantation. Rehabilitation allowed implanted patients to have a significantly better evolution compared to non-rehabilitated patients.

TSCA Chemical Data Reporting Fact Sheet: Articles

EPA Pesticide Factsheets

This fact sheet provides guidance on classifying articles under the Toxic Substances Control Act (TSCA) and determining the applicability of EPA’s articles exclusion policy for purposes of the Chemical Data Reporting (CDR) rule. The primary goal of this document is to help the regulated community comply with the requirements of the CDR rule.

A complementarity-determining region synthetic peptide acts as a miniantibody and neutralizes human immunodeficiency virus type 1 in vitro.

PubMed Central

Levi, M; Sällberg, M; Rudén, U; Herlyn, D; Maruyama, H; Wigzell, H; Marks, J; Wahren, B

1993-01-01

A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constructed with specificity to a neutralization-inducing region of human immunodeficiency virus type 1 (HIV-1). The mAb has its major reactivity to the amino acid sequence I--GPGRA in the V3 viral envelope region. All CDRs including several framework amino acids were synthesized from the sequence deduced by cloning and sequencing mAb F58 heavy- and light-chain variable domains. Peptides derived from the third heavy-chain domain (CDR-H3) alone or in combination with the other CDR sequences competed with F58 mAb for the V3 region. The CDR-H3 peptide was chemically modified by cyclization and then inhibited HIV-1 replication as well as syncytium formation by infected cells. Both the homologous IIIB viral strain to which the F58 mAb was induced and the heterologous SF2 strain were inhibited. This synthetic peptide had unexpectedly potent antiviral activity and may be a potential tool for treatment of HIV-infected persons. PMID:7685100

Optimal bioenergy power generation for climate change mitigation with or without carbon sequestration.

PubMed

Woolf, Dominic; Lehmann, Johannes; Lee, David R

2016-10-21

Restricting global warming below 2 °C to avoid catastrophic climate change will require atmospheric carbon dioxide removal (CDR). Current integrated assessment models (IAMs) and Intergovernmental Panel on Climate Change scenarios assume that CDR within the energy sector would be delivered using bioenergy with carbon capture and storage (BECCS). Although bioenergy-biochar systems (BEBCS) can also deliver CDR, they are not included in any IPCC scenario. Here we show that despite BECCS offering twice the carbon sequestration and bioenergy per unit biomass, BEBCS may allow earlier deployment of CDR at lower carbon prices when long-term improvements in soil fertility offset biochar production costs. At carbon prices above $1,000 Mg -1 C, BECCS is most frequently (P>0.45, calculated as the fraction of Monte Carlo simulations in which BECCS is the most cost effective) the most economic biomass technology for climate-change mitigation. At carbon prices below $1,000 Mg -1 C, BEBCS is the most cost-effective technology only where biochar significantly improves agricultural yields, with pure bioenergy systems being otherwise preferred.

Optimal bioenergy power generation for climate change mitigation with or without carbon sequestration

PubMed Central

Woolf, Dominic; Lehmann, Johannes; Lee, David R.

2016-01-01

Restricting global warming below 2 °C to avoid catastrophic climate change will require atmospheric carbon dioxide removal (CDR). Current integrated assessment models (IAMs) and Intergovernmental Panel on Climate Change scenarios assume that CDR within the energy sector would be delivered using bioenergy with carbon capture and storage (BECCS). Although bioenergy-biochar systems (BEBCS) can also deliver CDR, they are not included in any IPCC scenario. Here we show that despite BECCS offering twice the carbon sequestration and bioenergy per unit biomass, BEBCS may allow earlier deployment of CDR at lower carbon prices when long-term improvements in soil fertility offset biochar production costs. At carbon prices above $1,000 Mg−1 C, BECCS is most frequently (P>0.45, calculated as the fraction of Monte Carlo simulations in which BECCS is the most cost effective) the most economic biomass technology for climate-change mitigation. At carbon prices below $1,000 Mg−1 C, BEBCS is the most cost-effective technology only where biochar significantly improves agricultural yields, with pure bioenergy systems being otherwise preferred. PMID:27767177

Using satellite microwave sensors to develop climate data records

NASA Astrophysics Data System (ADS)

Ferraro, Ralph; Meng, Huan; Luo, Zhengzhao

2011-08-01

NOAA Workshop on Climate Data Records From Satellite Passive Microwave Sounders: AMSU/MHS/SSMT2; College Park, Maryland, 2-3 March 2011 ; The National Oceanic and Atmospheric Administration's (NOAA) Climate Data Record (CDR) program (http://www.ncdc.noaa.gov/cdr/index.html) is an effort to create long-term homogeneous records of satellite measurements and derived products. As part of this effort, scientists at two related projects that focus on passive microwave sensors with the goal of hydrological applications—one led by a National Environmental Satellite, Data, and Information Service/Center for Satellite Applications and Research (STAR) team and one led by the City College of New York (CCNY)—held a joint workshop with the following objectives: To allow the CDR teams to interact with satellite data and product users and other CDR developers on relevant aspects of sensor characteristics and intercalibration that will lead to mature CDRs; To provide a formal mechanism for input by subject matter experts, in particular, sensor scientists and engineers; and> To move toward a community consensus approach for NOAA microwave sounder CDRs.

T cell receptor repertoires of mice and humans are clustered in similarity networks around conserved public CDR3 sequences

PubMed Central

Madi, Asaf; Poran, Asaf; Shifrut, Eric; Reich-Zeliger, Shlomit; Greenstein, Erez; Zaretsky, Irena; Arnon, Tomer; Laethem, Francois Van; Singer, Alfred; Lu, Jinghua; Sun, Peter D; Cohen, Irun R; Friedman, Nir

2017-01-01

Diversity of T cell receptor (TCR) repertoires, generated by somatic DNA rearrangements, is central to immune system function. However, the level of sequence similarity of TCR repertoires within and between species has not been characterized. Using network analysis of high-throughput TCR sequencing data, we found that abundant CDR3-TCRβ sequences were clustered within networks generated by sequence similarity. We discovered a substantial number of public CDR3-TCRβ segments that were identical in mice and humans. These conserved public sequences were central within TCR sequence-similarity networks. Annotated TCR sequences, previously associated with self-specificities such as autoimmunity and cancer, were linked to network clusters. Mechanistically, CDR3 networks were promoted by MHC-mediated selection, and were reduced following immunization, immune checkpoint blockade or aging. Our findings provide a new view of T cell repertoire organization and physiology, and suggest that the immune system distributes its TCR sequences unevenly, attending to specific foci of reactivity. DOI: http://dx.doi.org/10.7554/eLife.22057.001 PMID:28731407

Evaluating the streamflow simulation capability of PERSIANN-CDR daily rainfall products in two river basins on the Tibetan Plateau

DOE PAGES

Liu, Xiaomang; Yang, Tiantian; Hsu, Koulin; ...

2017-01-10

On the Tibetan Plateau, the limited ground-based rainfall information owing to a harsh environment has brought great challenges to hydrological studies. Satellite-based rainfall products, which allow for a better coverage than both radar network and rain gauges on the Tibetan Plateau, can be suitable alternatives for studies on investigating the hydrological processes and climate change. In this study, a newly developed daily satellite-based precipitation product, termed Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks $-$ Climate Data Record (PERSIANN-CDR), is used as input for a hydrologic model to simulate streamflow in the upper Yellow and Yangtze River basinsmore » on the Tibetan Plateau. The results show that the simulated streamflows using PERSIANN-CDR precipitation and the Global Land Data Assimilation System (GLDAS) precipitation are closer to observation than that using limited gauge-based precipitation interpolation in the upper Yangtze River basin. The simulated streamflow using gauge-based precipitation are higher than the streamflow observation during the wet season. In the upper Yellow River basin, gauge-based precipitation, GLDAS precipitation, and PERSIANN-CDR precipitation have similar good performance in simulating streamflow. Finally, the evaluation of streamflow simulation capability in this study partly indicates that the PERSIANN-CDR rainfall product has good potential to be a reliable dataset and an alternative information source of a limited gauge network for conducting long-term hydrological and climate studies on the Tibetan Plateau.« less

Effects of education on very mild dementia among Chinese people in Hong Kong: potential mediators in the Cantonese Mini-Mental State Examination tasks.

PubMed

Tse, C S; Chang, J F; Leung, Grace T Y; Fung, Ada W T; Hau, K T; Chiu, Helen F K; Lam, Linda C W

2013-01-01

In Hong Kong, older Chinese adults generally have a low level of education. This study examined the effect of education on very mild Alzheimer's disease (AD), as quantified by Clinical Dementia Rating (CDR) scale (CDR 0.5 versus 0), in a Chinese community. The Cantonese version of the Mini-Mental State Examination (C-MMSE) was used to estimate cognitive abilities that were related to the level of education, and that in turn serve as protective factors for AD. A total of 788 community-dwelling older adults (383 CDR 0 and 405 CDR 0.5) were recruited in this cross-sectional study, which was derived from a population-based prevalence project. The participants' number of years of education and C-MMSE scores were used to predict their CDR scores using logistic regression and the mediation effects of C-MMSE scores were analyzed. Consistent with previous studies, the chance of being rated as having very mild AD increased with age, but decreased with years of education, among the older adult community of Hong Kong. The effect of education on very mild dementia was weakened substantially when C-MMSE scores were included as mediating variables. The findings indicate that the protective effects of education on dementia were mediated by an enhancement of older adults' performance on some C-MMSE items, including attention and orientation to time and place.

Digital breast tomosynthesis for breast cancer screening and diagnosis in women with dense breasts - a systematic review and meta-analysis.

PubMed

Phi, Xuan-Anh; Tagliafico, Alberto; Houssami, Nehmat; Greuter, Marcel J W; de Bock, Geertruida H

2018-04-03

This study aimed to systematically review and to meta-analyse the accuracy of digital breast tomosynthesis (DBT) versus digital mammography (DM) in women with mammographically dense breasts in screening and diagnosis. Two independent reviewers identified screening or diagnostic studies reporting at least one of four outcomes (cancer detection rate-CDR, recall rate, sensitivity and specificity) for DBT and DM in women with mammographically dense breasts. Study quality was assessed using QUADAS-2. Meta-analysis of CDR and recall rate used a random effects model. Summary ROC curve summarized sensitivity and specificity. Sixteen studies were included (five diagnostic; eleven screening). In diagnosis, DBT increased sensitivity (84%-90%) versus DM alone (69%-86%) but not specificity. DBT improved CDR versus DM alone (RR: 1.16, 95% CI 1.02-1.31). In screening, DBT + DM increased CDR versus DM alone (RR: 1.33, 95% CI 1.20-1.47 for retrospective studies; RR: 1.52, 95% CI 1.08-2.11 for prospective studies). Recall rate was significantly reduced by DBT + DM in retrospective studies (RR: 0.72, 95% CI 0.64-0.80) but not in two prospective studies (RR: 1.12, 95% CI 0.76-1.63). In women with mammographically dense breasts, DBT+/-DM increased CDR significantly (versus DM) in screening and diagnosis. In diagnosis, DBT+/-DM increased sensitivity but not specificity. The effect of DBT + DM on recall rate in screening dense breasts varied between studies.

γδ T cell receptors recognize the non-classical major histocompatibility complex (MHC) molecule T22 via conserved anchor residues in a MHC peptide-like fashion.

PubMed

Sandstrom, Andrew; Scharf, Louise; McRae, Gabrielle; Hawk, Andrew J; Meredith, Stephen C; Adams, Erin J

2012-02-17

The molecular mechanisms by which γδ T cells recognize ligand remain a mystery. The non-classical MHC molecule T22 represents the best characterized ligand for murine γδ T cells, with a motif (W … EGYEL) present in the γδ T cell receptor complementary-determining region 3δ (CDR3δ) loop mediating γδ T cell recognition of this molecule. Produced through V(D)J recombination, this loop is quite diverse, with different numbers and chemical types of amino acids between Trp and EGYEL, which have unknown functional consequences for T22 recognition. We have investigated the biophysical and structural effects of CDR3δ loop diversity, revealing a range of affinities for T22 but a common thermodynamic pattern. Mutagenesis of these CDR3δ loops defines the key anchor residues involved in T22 recognition as W … EGYEL, similar to those found for the G8 CDR3δ loop, and demonstrates that spacer residues modulate but are not required for T22 recognition. Comparison of the location of these residues in the T22 interface reveals a striking similarity to peptide anchor residues in classically presented MHC peptides, with the key Trp residue of the CDR3δ motif completing the deficient peptide-binding groove of T22. This suggests that γδ T cell recognition of T22 utilizes the conserved ligand-presenting nature of the MHC fold.

Multitemporal Snow Cover Mapping in Mountainous Terrain for Landsat Climate Data Record Development

NASA Technical Reports Server (NTRS)

Crawford, Christopher J.; Manson, Steven M.; Bauer, Marvin E.; Hall, Dorothy K.

2013-01-01

A multitemporal method to map snow cover in mountainous terrain is proposed to guide Landsat climate data record (CDR) development. The Landsat image archive including MSS, TM, and ETM+ imagery was used to construct a prototype Landsat snow cover CDR for the interior northwestern United States. Landsat snow cover CDRs are designed to capture snow-covered area (SCA) variability at discrete bi-monthly intervals that correspond to ground-based snow telemetry (SNOTEL) snow-water-equivalent (SWE) measurements. The June 1 bi-monthly interval was selected for initial CDR development, and was based on peak snowmelt timing for this mountainous region. Fifty-four Landsat images from 1975 to 2011 were preprocessed that included image registration, top-of-the-atmosphere (TOA) reflectance conversion, cloud and shadow masking, and topographic normalization. Snow covered pixels were retrieved using the normalized difference snow index (NDSI) and unsupervised classification, and pixels having greater (less) than 50% snow cover were classified presence (absence). A normalized SCA equation was derived to independently estimate SCA given missing image coverage and cloud-shadow contamination. Relative frequency maps of missing pixels were assembled to assess whether systematic biases were embedded within this Landsat CDR. Our results suggest that it is possible to confidently estimate historical bi-monthly SCA from partially cloudy Landsat images. This multitemporal method is intended to guide Landsat CDR development for freshwaterscarce regions of the western US to monitor climate-driven changes in mountain snowpack extent.

Feasibility study of volumetric modulated arc therapy with constant dose rate for endometrial cancer

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

Yang, Ruijie; Wang, Junjie, E-mail: junjiewang47@yahoo.com; Xu, Feng

2013-10-01

To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. The nine-field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry run was performed to assess the dosimetric accuracy with MatriXX from IBA. Compared with IMRT, the VMAT-CDRmore » plans delivered a slightly greater V{sub 20} of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability.« less

Evaluating the streamflow simulation capability of PERSIANN-CDR daily rainfall products in two river basins on the Tibetan Plateau

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

Liu, Xiaomang; Yang, Tiantian; Hsu, Koulin

On the Tibetan Plateau, the limited ground-based rainfall information owing to a harsh environment has brought great challenges to hydrological studies. Satellite-based rainfall products, which allow for a better coverage than both radar network and rain gauges on the Tibetan Plateau, can be suitable alternatives for studies on investigating the hydrological processes and climate change. In this study, a newly developed daily satellite-based precipitation product, termed Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks $-$ Climate Data Record (PERSIANN-CDR), is used as input for a hydrologic model to simulate streamflow in the upper Yellow and Yangtze River basinsmore » on the Tibetan Plateau. The results show that the simulated streamflows using PERSIANN-CDR precipitation and the Global Land Data Assimilation System (GLDAS) precipitation are closer to observation than that using limited gauge-based precipitation interpolation in the upper Yangtze River basin. The simulated streamflow using gauge-based precipitation are higher than the streamflow observation during the wet season. In the upper Yellow River basin, gauge-based precipitation, GLDAS precipitation, and PERSIANN-CDR precipitation have similar good performance in simulating streamflow. Finally, the evaluation of streamflow simulation capability in this study partly indicates that the PERSIANN-CDR rainfall product has good potential to be a reliable dataset and an alternative information source of a limited gauge network for conducting long-term hydrological and climate studies on the Tibetan Plateau.« less

Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative.

PubMed

Sun, Baoguo; Meng, Jun; Xiang, Ting; Zhang, Lei; Deng, Liuxiang; Chen, Yan; Luo, Haoxuan; Yang, Zhangbin; Chen, Zexiong; Zhang, Shijun

2016-03-01

The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (P<0.05), reduced weight loss (P<0.01) and stable visceral indices (P<0.05). Furthermore, the JPJD treatment appeared to improve Simpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire.

Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative

PubMed Central

SUN, BAOGUO; MENG, JUN; XIANG, TING; ZHANG, LEI; DENG, LIUXIANG; CHEN, YAN; LUO, HAOXUAN; YANG, ZHANGBIN; CHEN, ZEXIONG; ZHANG, SHIJUN

2016-01-01

The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (P<0.05), reduced weight loss (P<0.01) and stable visceral indices (P<0.05). Furthermore, the JPJD treatment appeared to improve Simpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire. PMID:26997998

ECOSYSTEM IMPACTS OF GEOENGINEERING: A Review for Developing a Science Plan

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

Russell, Lynn M; Jackson, Robert B; Norby, Richard J

2012-01-01

Geoengineering methods are intended to reduce the magnitude of climate change, which is already having demonstrable effects on ecosystem structure and functioning. Two different types of activities have been proposed: solar radiation management (SRM), or sunlight reflection methods, which involves reflecting a small percentage of solar light back into space to offset the warming due to greenhouse gases, and carbon dioxide removal (CDR), which includes a range of engineered and biological processes to remove carbon dioxide (CO2) from the atmosphere. This report evaluates some of the possible impacts of CDR and SRM on the physical climate and their subsequent influencemore » on ecosystems, which include the risks and uncertainties associated with new kinds of purposeful perturbations to the Earth. Therefore, the question considered in this review is whether CDR and SRM methods would exacerbate or alleviate the deleterious impacts on ecosystems associated with climate changes that might occur in the foreseeable future.Geoengineering methods are intended to reduce the magnitude of climate change, which is already having demonstrable effects on ecosystem structure and functioning. Two different types of activities have been proposed: solar radiation management (SRM), or sunlight reflection methods, which involves reflecting a small percentage of solar light back into space to offset the warming due to greenhouse gases, and carbon dioxide removal (CDR), which includes a range of engineered and biological processes to remove carbon dioxide (CO2) from the atmosphere. This report evaluates some of the possible impacts of CDR and SRM on the physical climate and their subsequent influence on ecosystems, which include the risks and uncertainties associated with new kinds of purposeful perturbations to the Earth. Therefore, the question considered in this review is whether CDR and SRM methods would exacerbate or alleviate the deleterious impacts on ecosystems associated with climate changes that might occur in the foreseeable future.« less

HIV-1 gp140 epitope recognition is influenced by immunoglobulin DH gene segment sequence

PubMed Central

Wang, Yuge; Kapoor, Pratibha; Parks, Robert; Silva-Sanchez, Aaron; Alam, S. Munir; Verkoczy, Laurent; Liao, Hua-Xin; Zhuang, Yingxin; Burrows, Peter; Levinson, Michael; Elgavish, Ada; Cui, Xiangqin; Haynes, Barton F.; Schroeder, Harry

2015-01-01

Complementarity determining region 3 of the immunoglobulin (Ig) H chain (CDR-H3) lies at the center of the antigen binding site where it often plays a decisive role in antigen recognition and binding. Amino acids encoded by the diversity (DH) gene segment are the main component of CDR-H3. Each DH has the potential to rearrange into one of six DH reading frames (RFs), each of which exhibits a characteristic amino acid hydrophobicity signature that has been conserved among jawed vertebrates by natural selection. A preference for use of RF1 promotes the incorporation of tyrosine into CDR-H3 while suppressing the inclusion of hydrophobic or charged amino acids. To test the hypothesis that these evolutionary constraints on DH sequence influence epitope recognition, we used mice with a single DH that has been altered to preferentially use RF2 or inverted RF1. B cells in these mice produce a CDR-H3 repertoire that is enriched for valine or arginine in place of tyrosine. We serially immunized this panel of mice with gp140 from HIV-1 JR-FL isolate and then used ELISA or peptide microarray to assess antibody binding to key or overlapping HIV-1 envelope epitopes. By ELISA, serum reactivity to key epitopes varied by DH sequence. By microarray, sera with Ig CDR-H3s enriched for arginine bound to linear peptides with a greater range of hydrophobicity, but had a lower intensity of binding than sera containing Ig CDR-H3s enriched for tyrosine or valine. We conclude that patterns of epitope recognition and binding can be heavily influenced by DH germline sequence. This may help explain why antibodies in HIV infected patients must undergo extensive somatic mutation in order to bind to specific viral epitopes and achieve neutralization. PMID:26687685

The dynamic of tuberculosis case finding in the era of the public–private mix strategy for tuberculosis control in Central Java, Indonesia

PubMed Central

Reviono, Reviono; Setianingsih, Wahyu; Damayanti, Kusmadewi Eka; Ekasari, Ratna

2017-01-01

ABSTRACT Background: The public–private mix (PPM) strategy has strengthened tuberculosis care and control in many countries. Indonesia, a country with a high tuberculosis burden, has a low tuberculosis case detection rate (CDR), despite PPM implementation in 2003. The PPM in Indonesia involves primary healthcare centers, hospitals, and specialized chest clinics. The long-term impact of the strategy is unknown. Objective: We aimed to explore the case detection achievements of the tuberculosis program since PPM implementation in Central Java in 2003. Methods: This retrospective cohort study covered the period 1 January 2000 to 31 December 2014. The data from tuberculosis patients treated in all health facilities in Central Java implementing directly observed treatment short-course, recorded via a standardized form, were analyzed after being validated by the Office of Health of Central Java Province. We evaluated the CDR, case notification rate, and total number of cases, using linear regression to analyze the temporal trends of those indicators in the phases of PPM implementation. Results: The CDR increased during the initial phase (2000–2005), decreased during the mid-phase (2006–2009), and increased slightly during the late phase (2010–2014), ranging from 13 to 61.72. These trends were observed despite a steady increase in the number of participating healthcare facilities. The regression analysis showed that the CDR of referral institutions contributed the most to the total CDR of Central Java Province. Many of the smear-negative tuberculosis cases recorded at primary healthcare centers may have been smear positive; this probable misclassification could have been partially avoided if more specific and sensitive diagnostic tools were available. Conclusions: The CDR remains below the national target (70%). Early awareness of a negative trend in certain program indicators is important to ensure program sustainability. Careful observation of the indicator pattern will secure the long-term success of the program. PMID:28766465

The dynamic of tuberculosis case finding in the era of the public-private mix strategy for tuberculosis control in Central Java, Indonesia.

PubMed

Reviono, Reviono; Setianingsih, Wahyu; Damayanti, Kusmadewi Eka; Ekasari, Ratna

2017-01-01

The public-private mix (PPM) strategy has strengthened tuberculosis care and control in many countries. Indonesia, a country with a high tuberculosis burden, has a low tuberculosis case detection rate (CDR), despite PPM implementation in 2003. The PPM in Indonesia involves primary healthcare centers, hospitals, and specialized chest clinics. The long-term impact of the strategy is unknown.  We aimed to explore the case detection achievements of the tuberculosis program since PPM implementation in Central Java in 2003. This retrospective cohort study covered the period 1 January 2000 to 31 December 2014. The data from tuberculosis patients treated in all health facilities in Central Java implementing directly observed treatment short-course, recorded via a standardized form, were analyzed after being validated by the Office of Health of Central Java Province. We evaluated the CDR, case notification rate, and total number of cases, using linear regression to analyze the temporal trends of those indicators in the phases of PPM implementation. The CDR increased during the initial phase (2000-2005), decreased during the mid-phase (2006-2009), and increased slightly during the late phase (2010-2014), ranging from 13 to 61.72. These trends were observed despite a steady increase in the number of participating healthcare facilities. The regression analysis showed that the CDR of referral institutions contributed the most to the total CDR of Central Java Province. Many of the smear-negative tuberculosis cases recorded at primary healthcare centers may have been smear positive; this probable misclassification could have been partially avoided if more specific and sensitive diagnostic tools were available. The CDR remains below the national target (70%). Early awareness of a negative trend in certain program indicators is important to ensure program sustainability. Careful observation of the indicator pattern will secure the long-term success of the program.

Mechanism of action of tetrandrine, a natural inhibitor of Candida albicans drug efflux pumps.

PubMed

Zhang, Hong; Gao, Aili; Li, Fengxia; Zhang, Gehua; Ho, Hon In; Liao, Wanqing

2009-05-01

Synergistic effects have previously been observed for a natural compound, tetrandrine (TET), with fluconazole (FLC) in vitro and in the treatment of Candida albicans-infected mice. To investigate the mechanisms of these synergistic effects, 16 strains of C. albicans from the same parent but with different FLC sensitivities were examined using flow cytometry and fluorescent spectrophotometry. Rhodamine 123 (Rh123)-positive cells and intracellular Rh123 fluorescence intensity were determined in accumulation/efflux experiments involving no or a noncytotoxic dose of TET. Total RNA extracted from each strain was used to compare the expressions of drug efflux pump genes in FLC-susceptible, -susceptible dose-dependent, and -resistant strains before and 24 h after TET administration. Accumulation experiments determined that mean percentages of Rh123-positive cells were 26.65% (TET-free) and 70.99% (TET 30 microg/ml), and mean respective intracellular Rh123 fluorescence intensities were 11.34 and 18.00. Efflux experiments showed that percentages of Rh123-positive cells were 1.79% (TET free) and 42.57% (TET 30 microg/ml), respectively, and respective mean intracellular Rh123 fluorescence intensities were 0.74 and 2.19. Differences in MDR1, FLU1, CDR1, and CDR2 expression levels in the absence of TET were statistically significant (p<0.05) between FLC-susceptible, -susceptible dose-dependent, and -resistant strains. Compared with TET-free conditions, 24 h TET-treated strains showed statistically different (p<0.05) expression of MDR1 (FLC-resistant strain), FLU1 (FLC-susceptible dose-dependent and -resistant strains), and CDR1 and CDR2 (FLC-susceptible, -susceptible dose-dependent, and -resistant strains). Thus TET can inhibit the C. albicans drug efflux system and reduce drug efflux. Its mechanism of action is related to the inhibition of expression of the drug efflux pump genes MDR1, FLU1, CDR1, and CDR2.

An analysis of redactions in Canada’s Common Drug Review Clinical Review Reports and how they relate to the patients’ voice

PubMed Central

Soprovich, Allison; El Kurdi, Sylvia; Eurich, Dean T

2017-01-01

Importance Canada’s Common Drug Review (CDR) evaluates drug data from published and unpublished research, as well as input from patient groups, to recommend provincial coverage. Currently, the CDR process gives manufacturers the opportunity to redact information in the final publicly available report. Patients often have strong feelings regarding the efficacy, harms, health-related quality of life (HRQL), and cost associated with the drugs under review and their redacted data. Highlighting Canada’s approach will hopefully build on the growing international concern regarding transparency of clinical study data. Objective The purpose was to objectively examine and classify completed, publicly available CDR-Clinical Review Reports (CRR) for redactions, and compare them to the patients’ reported interests as patient-centred outcomes. Methods Two independent reviewers searched for and examined publicly available CDR-CRR from November 2013-September 2016 through the Canadian Agency for Drugs and Technologies in Health (CADTH) on-line database. Both reviewers separately classified the redactions and patient-reported interests into the following categories: efficacy, harms, HRQL and costs. All discrepancies were rectified by consensus involving a third reviewer. Results Fifty-two completed CDR-CRR were reviewed. 48 (92%) included patient-reported interests and 40 (77%) had redactions classified in the following categories: efficacy (75%), costs (48%), harms (38%), HRQL (23%). 89% of redactions were outcomes identified as patient-reported interests (69% efficacy, 42% harms, 36% cost, 33% HRQL). When examining drug characteristics, biological agents were statistically associated with increased odds of redactions with respect to either efficacy (OR 3.4, 95% CI 1.0 to 11.6) or harms (OR 3.5, 95% CI 1.02 to 12.4) compared with non-biological agents. Conclusions Whether data from the CDR-CRR used in the decision-making should be fully disclosed to the public is controversial. Our findings suggest clinical data (efficacy, harms, HRQL) matters to patients and should be publicly available within the CDR-CRR. Canada trails Europe and the USA regarding the transparency of clinical study data. This lack of transparency relates to the patient voice, and limits movement towards patient-centred care and patient-engaged research, restricting real-world value measurement. PMID:28893743

An analysis of redactions in Canada's Common Drug Review Clinical Review Reports and how they relate to the patients' voice.

PubMed

Soprovich, Allison; El Kurdi, Sylvia; Eurich, Dean T

2017-09-11

Canada's Common Drug Review (CDR) evaluates drug data from published and unpublished research, as well as input from patient groups, to recommend provincial coverage. Currently, the CDR process gives manufacturers the opportunity to redact information in the final publicly available report. Patients often have strong feelings regarding the efficacy, harms, health-related quality of life (HRQL), and cost associated with the drugs under review and their redacted data. Highlighting Canada's approach will hopefully build on the growing international concern regarding transparency of clinical study data. The purpose was to objectively examine and classify completed, publicly available CDR-Clinical Review Reports (CRR) for redactions, and compare them to the patients' reported interests as patient-centred outcomes. Two independent reviewers searched for and examined publicly available CDR-CRR from November 2013-September 2016 through the Canadian Agency for Drugs and Technologies in Health (CADTH) on-line database. Both reviewers separately classified the redactions and patient-reported interests into the following categories: efficacy, harms, HRQL and costs. All discrepancies were rectified by consensus involving a third reviewer. Fifty-two completed CDR-CRR were reviewed. 48 (92%) included patient-reported interests and 40 (77%) had redactions classified in the following categories: efficacy (75%), costs (48%), harms (38%), HRQL (23%). 89% of redactions were outcomes identified as patient-reported interests (69% efficacy, 42% harms, 36% cost, 33% HRQL). When examining drug characteristics, biological agents were statistically associated with increased odds of redactions with respect to either efficacy (OR 3.4, 95% CI 1.0 to 11.6) or harms (OR 3.5, 95% CI 1.02 to 12.4) compared with non-biological agents. Whether data from the CDR-CRR used in the decision-making should be fully disclosed to the public is controversial. Our findings suggest clinical data (efficacy, harms, HRQL) matters to patients and should be publicly available within the CDR-CRR. Canada trails Europe and the USA regarding the transparency of clinical study data. This lack of transparency relates to the patient voice, and limits movement towards patient-centred care and patient-engaged research, restricting real-world value measurement. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Candidate Exercise Technologies and Prescriptions

NASA Technical Reports Server (NTRS)

Loerch, Linda H.

2010-01-01

This slide presentation reviews potential exercise technologies to counter the effects of space flight. It includes a overview of the exercise countermeasures project, a review of some of the candidate exercise technologies being considered and a few of the analog exercise hardware devices, and a review of new studies that are designed to optimize the current and future exercise protocols.

A haptic-robotic platform for upper-limb reaching stroke therapy: Preliminary design and evaluation results

PubMed Central

Lam, Paul; Hebert, Debbie; Boger, Jennifer; Lacheray, Hervé; Gardner, Don; Apkarian, Jacob; Mihailidis, Alex

2008-01-01

Background It has been shown that intense training can significantly improve post-stroke upper-limb functionality. However, opportunities for stroke survivors to practice rehabilitation exercises can be limited because of the finite availability of therapists and equipment. This paper presents a haptic-enabled exercise platform intended to assist therapists and moderate-level stroke survivors perform upper-limb reaching motion therapy. This work extends on existing knowledge by presenting: 1) an anthropometrically-inspired design that maximizes elbow and shoulder range of motions during exercise; 2) an unobtrusive upper body postural sensing system; and 3) a vibratory elbow stimulation device to encourage muscle movement. Methods A multi-disciplinary team of professionals were involved in identifying the rehabilitation needs of stroke survivors incorporating these into a prototype device. The prototype system consisted of an exercise device, postural sensors, and a elbow stimulation to encourage the reaching movement. Eight experienced physical and occupational therapists participated in a pilot study exploring the usability of the prototype. Each therapist attended two sessions of one hour each to test and evaluate the proposed system. Feedback about the device was obtained through an administered questionnaire and combined with quantitative data. Results Seven of the nine questions regarding the haptic exercise device scored higher than 3.0 (somewhat good) out of 4.0 (good). The postural sensors detected 93 of 96 (97%) therapist-simulated abnormal postures and correctly ignored 90 of 96 (94%) of normal postures. The elbow stimulation device had a score lower than 2.5 (neutral) for all aspects that were surveyed, however the therapists felt the rehabilitation system was sufficient for use without the elbow stimulation device. Conclusion All eight therapists felt the exercise platform could be a good tool to use in upper-limb rehabilitation as the prototype was considered to be generally well designed and capable of delivering reaching task therapy. The next stage of this project is to proceed to clinical trials with stroke patients. PMID:18498641

Padalka exercises with ARED

NASA Image and Video Library

2009-04-27

ISS019-E-011053 (27 April 2009) --- Cosmonaut Gennady Padalka, Expedition 19/20 commander, exercises using the advanced Resistive Exercise Device (aRED) in the Unity node of the International Space Station.

Deep Sea Memory of High Atmospheric CO2 Concentration

NASA Astrophysics Data System (ADS)

Mathesius, Sabine; Hofmann, Matthias; Caldeira, Ken; Schellnhuber, Hans Joachim

2015-04-01

Carbon dioxide removal (CDR) from the atmosphere has been proposed as a powerful measure to mitigate global warming and ocean acidification. Planetary-scale interventions of that kind are often portrayed as "last-resort strategies", which need to weigh in if humankind keeps on enhancing the climate-system stock of CO2. Yet even if CDR could restore atmospheric CO2 to substantially lower concentrations, would it really qualify to undo the critical impacts of past emissions? In the study presented here, we employed an Earth System Model of Intermediate Complexity (EMIC) to investigate how CDR might erase the emissions legacy in the marine environment, focusing on pH, temperature and dissolved oxygen. Against a background of a world following the RCP8.5 emissions path ("business-as-usual") for centuries, we simulated the effects of two massive CDR interventions with CO2 extraction rates of 5 GtC yr-1 and 25 GtC yr-1, respectively, starting in 2250. We found that the 5 GtC yr-1 scheme would have only minor ameliorative influence on the oceans, even after several centuries of application. By way of contrast, the extreme 25 GtC yr-1 scheme eventually leads to tangible improvements. However, even with such an aggressive measure, past CO2 emissions leave a substantial legacy in the marine environment within the simulated period (i.e., until 2700). In summary, our study demonstrates that anthropogenic alterations of the oceans, caused by continued business-as-usual emissions, may not be reversed on a multi-centennial time scale by the most aspirational geoengineering measures. We also found that a transition from the RCP8.5 state to the state of a strong mitigation scenario (RCP2.6) is not possible, even under the assumption of extreme extraction rates (25 GtC yr-1). This is explicitly demonstrated by simulating additional scenarios, starting CDR already in 2150 and operating until the atmospheric CO2 concentration reaches 280 ppm and 180 ppm, respectively. The simulated massive CDR interventions eventually bring down the global mean pH value to the RCP2.6 level, yet cannot restore a similarly homogenous distribution - while the pH of the upper ocean returns to the preindustrial value or even exceed it (in the 180 ppm scenario), the deep ocean remains acidified. The deep ocean is out of contact with the atmosphere and therefore unreachable by atmospheric CDR. Our results suggest that the proposition that the marine consequences of early emissions reductions are comparable to those of delayed reductions plus CDR is delusive and that a policy that allows for emitting CO2 today in the hopes of removing it tomorrow is bound to generate substantial regrets.

Variable dose rate single-arc IMAT delivered with a constant dose rate and variable angular spacing

NASA Astrophysics Data System (ADS)

Tang, Grace; Earl, Matthew A.; Yu, Cedric X.

2009-11-01

Single-arc intensity-modulated arc therapy (IMAT) has gained worldwide interest in both research and clinical implementation due to its superior plan quality and delivery efficiency. Single-arc IMAT techniques such as the Varian RapidArc™ deliver conformal dose distributions to the target in one single gantry rotation, resulting in a delivery time in the order of 2 min. The segments in these techniques are evenly distributed within an arc and are allowed to have different monitor unit (MU) weightings. Therefore, a variable dose-rate (VDR) is required for delivery. Because the VDR requirement complicates the control hardware and software of the linear accelerators (linacs) and prevents most existing linacs from delivering IMAT, we propose an alternative planning approach for IMAT using constant dose-rate (CDR) delivery with variable angular spacing. We prove the equivalence by converting VDR-optimized RapidArc plans to CDR plans, where the evenly spaced beams in the VDR plan are redistributed to uneven spacing such that the segments with larger MU weighting occupy a greater angular interval. To minimize perturbation in the optimized dose distribution, the angular deviation of the segments was restricted to <=± 5°. This restriction requires the treatment arc to be broken into multiple sectors such that the local MU fluctuation within each sector is reduced, thereby lowering the angular deviation of the segments during redistribution. The converted CDR plans were delivered with a single gantry sweep as in the VDR plans but each sector was delivered with a different value of CDR. For four patient cases, including two head-and-neck, one brain and one prostate, all CDR plans developed with the variable spacing scheme produced similar dose distributions to the original VDR plans. For plans with complex angular MU distributions, the number of sectors increased up to four in the CDR plans in order to maintain the original plan quality. Since each sector was delivered with a different dose rate, extra mode-up time (xMOT) was needed between the transitions of the successive sectors during delivery. On average, the delivery times of the CDR plans were approximately less than 1 min longer than the treatment times of the VDR plans, with an average of about 0.33 min of xMOT per sector transition. The results have shown that VDR may not be necessary for single-arc IMAT. Using variable angular spacing, VDR RapidArc plans can be implemented into the clinics that are not equipped with the new VDR-enabled machines without compromising the plan quality or treatment efficiency. With a prospective optimization approach using variable angular spacing, CDR delivery times can be further minimized while maintaining the high delivery efficiency of single-arc IMAT treatment.

The impact of legally restricted embryo transfer and reimbursement policy on cumulative delivery rate after treatment with assisted reproduction technology.

PubMed

Peeraer, K; Debrock, S; Laenen, A; De Loecker, P; Spiessens, C; De Neubourg, D; D'Hooghe, T M

2014-02-01

What is the impact of the Belgian legislation (1 July 2003), coupling reimbursement of six assisted reproduction technology (ART) cycles per patient to restricted embryo transfer policy, on cumulative delivery rate (CDR) per patient? The introduction of Belgian legislation in ART had no negative impact on the CDR per patient based on realistic estimates within six cycles or 36 months. The introduction of Belgian legislation limiting the number of embryos for transfer resulted in a reduction of the multiple pregnancy rate (MPR) per cycle by 50%. A retrospective cohort study with a study group after implementation of the new ART legislation (July 2003 to June 2006) and the control group, before legislation (July 1999 to June 2002). CDR was compared in an academic tertiary setting between a study group after legislation (n = 795 patients, 1927 fresh and 383 frozen-thawed embryo transfer (FET) cycles) and a control group before legislation (n = 463 patients, 876 fresh and 185 FET cycles) within six cycles or 36 months, delivery or discontinuation of treatment. The CDR was estimated using life table analysis considering pessimistic, optimistic and realistic scenarios and compared after adjustment for confounding variables. In the realistic scenario we included information on embryo quality to define the prognosis of each patient discontinuing treatment. In the realistic scenario, CDR within 36 months was comparable (all ages, P = 0.221) in study group (60.8%) and control group (65.6%), as well as in different age groups (<36 years, P = 0.242; 36-39 years, P = 0.851; 40-42 years, P = 0.840). In the realistic scenario applied to six cycles, we found lower CDRs in the study group than in the control group within the two first cycles (all ages, P = 0.009; <36 years, P = 0.007) but no difference in CDRs between the two groups within the four subsequent cycles (all ages P = 0.232; <36 years, P = 0.198). The CDR within six cycles was 60 and 65.3% for study group and control group, respectively, for all ages, and 65.8 and 70.4%, respectively, in the subgroup younger than 36 years. In women ≥36 years, CDR within six cycles was comparable in both groups (36-39 years, 43% in study versus 44.4% in control group, P = 0.730; 40-42 years, 21% in study versus 23% in control group, P = 0.786). A retrospective cohort study design was the only way to study the impact of legislation on CDR. Owing to the retrospective nature of this analysis over a long period of time, our data are potentially influenced by improvements in techniques and therefore improved success rates in ART over time. This 'Belgian model' can now be considered for application worldwide in countries with the aim to reduce the main ART side effect (high MPR) and its associated costs without a negative effect on the main intended effect (high CDR). The authors have no conflict of interest to declare. No funding was obtained for this study.

Using Mobile Devices for Motor-Learning Laboratory Exercises

ERIC Educational Resources Information Center

Hill, Kory

2014-01-01

When teaching motor-learning concepts, laboratory experiments can be valuable tools for promoting learning. In certain circumstances, traditional laboratory exercises are often impractical due to facilities, time, or cost. Inexpensive or free applications (apps) that run on mobile devices can serve as useful alternatives. This article details…

Analog Exercise Hardware to Implement a High Intensity Exercise Program During Bed Rest

NASA Technical Reports Server (NTRS)

Loerch, Linda; Newby, Nate; Ploutz-Snyder, Lori

2012-01-01

Background: In order to evaluate novel countermeasure protocols in a space flight analog prior to validation on the International Space Station (ISS), NASA's Human Research Program (HRP) is sponsoring a multi-investigator bedrest campaign that utilizes a combination of commercial and custom-made exercise training hardware to conduct daily resistive and aerobic exercise protocols. This paper will describe these pieces of hardware and how they are used to support current bedrest studies at NASA's Flight Analog Research Unit in Galveston, TX. Discussion: To implement candidate exercise countermeasure studies during extended bed rest studies the following analog hardware are being utilized: Stand alone Zero-Gravity Locomotion Simulator (sZLS) -- a custom built device by NASA, the sZLS allows bedrest subjects to remain supine as they run on a vertically-oriented treadmill (0-15 miles/hour). The treadmill includes a pneumatic subject loading device to provide variable body loading (0-100%) and a harness to keep the subject in contact with the motorized treadmill to provide a ground reaction force at their feet that is quantified by a Kistler Force Plate. Supine Cycle Ergometer -- a commercially available supine cycle ergometer (Lode, Groningen, Netherlands) is used for all cycle ergometer sessions. The ergometer has adjustable shoulder supports and handgrips to help stabilize the subject during exercise. Horizontal Squat Device (HSD) -- a custom built device by Quantum Fitness Corp (Stafford, TX), the HSD allows for squat exercises to be performed while lying in a supine position. The HSD can provide 0 to 600 pounds of force in selectable 5 lb increments, and allows hip translation in both the vertical and horizontal planes. Prone Leg Curl -- a commercially available prone leg curl machine (Cybex International Inc., Medway, MA) is used to complete leg curl exercises. Horizontal Leg Press -- a commercially available horizontal leg press (Quantum Fitness Corporation) is used for leg press and heel raise exercises. Minor modifications were made to the device including adding 200 lbs to the weight stack, raising the frame by 12 inches, making the footplate adjustable, and providing removable handles. Conclusion: A combination of novel and commercial exercise hardware are used to mimic the exercise hardware capabilities aboard the ISS, allowing scientific investigation of new countermeasure protocols in a space flight analog prior to flight validation

Physical therapy applications of MR fluids and intelligent control

NASA Astrophysics Data System (ADS)

Dong, Shufang; Lu, Ke-Qian; Sun, J. Q.; Rudolph, Katherine

2005-05-01

Resistance exercise has been widely reported to have positive rehabilitation effects for patients with neuromuscular and orthopaedic conditions. This paper presents an optimal design of magneto-rheological fluid dampers for variable resistance exercise devices. Adaptive controls for regulating the resistive force or torque of the device as well as the joint motion are presented. The device provides both isometric and isokinetic strength training for various human joints.

Estimated Muscle Loads During Squat Exercise in Microgravity Conditions

NASA Technical Reports Server (NTRS)

Fregly, Christopher D.; Kim, Brandon T.; Li, Zhao; DeWitt, John K.; Fregly, Benjamin J.

2012-01-01

Loss of muscle mass in microgravity is one of the primary factors limiting long-term space flight. NASA researchers have developed a number of exercise devices to address this problem. The most recent is the Advanced Resistive Exercise Device (ARED), which is currently used by astronauts on the International Space Station (ISS) to emulate typical free-weight exercises in microgravity. ARED exercise on the ISS is intended to reproduce Earth-level muscle loads, but the actual muscle loads produced remain unknown as they cannot currently be measured directly. In this study we estimated muscle loads experienced during squat exercise on ARED in microgravity conditions representative of Mars, the moon, and the ISS. The estimates were generated using a subject-specific musculoskeletal computer model and ARED exercise data collected on Earth. The results provide insight into the capabilities and limitations of the ARED machine.

Results of the International Space Station Interim Resistance Exercise Device Man-in-the-Loop Test

NASA Technical Reports Server (NTRS)

Moore, A. D., Jr.; Amonette, W. E.; Bentley, J. R.; Rapley, M. G.; Blazine, K. L.; Loehr, J. A.; Collier, K. R.; Boettcher, C. R.; Skrocki, J. S.; Hohrnann, R. J.

2004-01-01

The Interim Resistance Exercise Device (iRED), developed for the International Space Station (ISS), was evaluated using human subjects for a Man-In-The-Loop Test (MILT). Thirty-two human subjects exercised using the iRED in a test that was conducted over a 63-working-day period. The subjects performed the same exercises will be used on board ISS, and the iRED operating constraints that are to be used on ISS were followed. In addition, eight of the subjects were astronauts who volunteered to be in the evaluation in order to become familiar with the iRED and provide a critique of the device. The MILT was scheduled to last for 57,000 exercise repetitions on the iRED. This number of repetitions was agreed to as a number typical of that expected during a 3-person, 17-week ISS Increment. One of the canisters of the iRED failed at the 49,683- repetition mark (87.1% of targeted goal). The remaining canister was operated using the plan for operations if one canister fails during flight (contingency operations). This canister remained functional past the 57,000-repetition mark. This report details the results of the iRED MILT, and lists specific recommendations regarding both operation of the iRED and future resistance exercise device development.

eCDRweb User Guide–Primary Support

EPA Pesticide Factsheets

This document presents the user guide for the Office of Pollution Prevention and Toxics’ (OPPT) e-CDR web tool. E-CDRweb is the electronic, web-based tool provided by the Environmental Protection Agency (EPA) for the submission of Chemical Data Reporting (CDR) information. This document is the user guide for the Primary Support user of the e-CDRweb tool.

eCDRweb User Guide–Primary Authorized Official

EPA Pesticide Factsheets

This document presents the user guide for the Office of Pollution Prevention and Toxics’ (OPPT) e-CDRweb tool. E-CDRweb is the electronic, web-based tool provided by the Environmental Protection Agency (EPA) for the submission of Chemical Data Reporting (CDR) information. This document is the user guide for the Primary Authorized Official (AO) user of the e-CDR webtool

eCDRweb User Guide–Secondary Support

EPA Pesticide Factsheets

This document presents the user guide for the Office of Pollution Prevention and Toxics’ (OPPT) e-CDR web tool. E-CDRweb is the electronic, web-based tool provided by the Environmental Protection Agency (EPA) for the submission of Chemical Data Reporting (CDR) information. This document is the user guide for the Secondary Support user of the e-CDRweb tool.

Development of Magnetorheological Resistive Exercise Device for Rowing Machine

PubMed Central

Žiliukas, Pranas

2016-01-01

Training equipment used by professional sportsmen has a great impact on their sport performance. Most universal exercisers may help only to improve the general physical condition due to the specific kinematics and peculiar resistance generated by their loading units. Training of effective techniques and learning of psychomotor skills are possible only when exercisers conform to the movements and resistance typical for particular sports kinematically and dynamically. Methodology of developing a magnetorheological resistive exercise device for generating the desired law of passive resistance force and its application in a lever-type rowing machine are described in the paper. The structural parameters of a controllable hydraulic cylinder type device were found by means of the computational fluid dynamics simulation performed by ANSYS CFX software. Parameters describing the magnetorheological fluid as non-Newtonian were determined by combining numerical and experimental research of the resistance force generated by the original magnetorheological damper. A structural scheme of the device control system was developed and the variation of the strength of magnetic field that affects the magnetorheological fluid circulating in the device was determined, ensuring a variation of the resistance force on the oar handle adequate for the resistance that occurs during a real boat rowing stroke. PMID:27293479

Development of Magnetorheological Resistive Exercise Device for Rowing Machine.

PubMed

Grigas, Vytautas; Šulginas, Anatolijus; Žiliukas, Pranas

2015-01-01

Training equipment used by professional sportsmen has a great impact on their sport performance. Most universal exercisers may help only to improve the general physical condition due to the specific kinematics and peculiar resistance generated by their loading units. Training of effective techniques and learning of psychomotor skills are possible only when exercisers conform to the movements and resistance typical for particular sports kinematically and dynamically. Methodology of developing a magnetorheological resistive exercise device for generating the desired law of passive resistance force and its application in a lever-type rowing machine are described in the paper. The structural parameters of a controllable hydraulic cylinder type device were found by means of the computational fluid dynamics simulation performed by ANSYS CFX software. Parameters describing the magnetorheological fluid as non-Newtonian were determined by combining numerical and experimental research of the resistance force generated by the original magnetorheological damper. A structural scheme of the device control system was developed and the variation of the strength of magnetic field that affects the magnetorheological fluid circulating in the device was determined, ensuring a variation of the resistance force on the oar handle adequate for the resistance that occurs during a real boat rowing stroke.

Shkaplerov exercises on the aRED

NASA Image and Video Library

2012-01-05

ISS030-E-235507 (5 Jan. 2012) --- Russian cosmonaut Anton Shkaplerov, Expedition 30 flight engineer, exercises using the advanced Resistive Exercise Device (aRED) in the Tranquility node of the International Space Station.

Kuipers exercises on the ARED

NASA Image and Video Library

2012-06-05

ISS031-E-157839 (5 June 2012) --- European Space Agency astronaut Andre Kuipers, Expedition 31 flight engineer, exercises using the advanced Resistive Exercise Device (aRED) in the Tranquility node of the International Space Station.

Wakata exercises on the aRED

NASA Image and Video Library

2013-11-15

View of Koichi Wakata, Expedition 38 Flight Engineer (FE), exercising on the Advanced Resistive Exercise Device (aRED), in the Node 3. Photo was taken during Expedition 38. Image was released by astronaut on Twitter.

Rehabilitation device with variable resistance and intelligent control

PubMed Central

Dong, Shufang; Lu, Ke-Qian; Sun, J.Q.; Rudolph, Katherine

2008-01-01

Resistance exercise has been widely reported to have positive rehabilitation effects for patients with neuromuscular and orthopaedic conditions. This paper presents an optimal design of magneto-rheological fluid dampers for variable resistance exercise device in the form of a knee brace. An intelligent supervisory control for regulating the resistive force or torque of the knee brace has also been studied. The device provides both isometric and isokinetic strength training for the knee. PMID:15694609

Cognitive decline and brain volume loss are signatures of cerebral Aβ deposition identified with PIB

PubMed Central

Storandt, Martha; Mintun, Mark A.; Head, Denise; Morris, John C.

2009-01-01

Objective To examine the relation of amyloid-beta (Aβ) levels in cerebral cortex with structural brain integrity and cognitive performance in older people with a Clinical Dementia Rating (CDR) of 0 (cognitively normal). Methods The relations between mean cortical [11C] PIB binding potential values, proportional to the density of fibrillar Aβ binding sites in the brain, concurrent regional brain volumes as assessed by magnetic resonance imaging, and both concurrent and longitudinal (up to 19 years) cognitive performance in multiple domains were examined in 135 CDR 0 individuals aged 65 to 88 years. Results Elevated cerebral Aβ levels, in some cases comparable to that seen in individuals with Alzheimer's disease, were observed in 29 CDR 0 individuals. Significantly smaller regional volumes in the hippocampus, temporal neocortex, anterior cingulate, and posterior cingulate were observed in these CDR 0 individuals with elevated Aβ levels. Concurrent cognitive performance was unrelated to Aβ levels but was related to regional brain volumes with the exception of caudate. Longitudinal cognitive decline was associated with elevated Aβ levels and decreased hippocampal volume. Decline was not limited to episodic memory but included working memory and visuospatial abilities as well. Interpretation [11C] PIB, an in vivo measure of cerebral amyloidosis, is associated with regionally specific brain atrophy cross-sectionally and a pattern of longitudinal cognitive decline in multiple cognitive domains that occurs prior to the clinical diagnosis of Alzheimer' disease. These findings contribute to the understanding of the cognitive and structural consequences of Aβ levels in CDR 0 older adults. PMID:20008651

T cells to a dominant epitope of GAD65 express a public CDR3 motif.

PubMed

Quinn, Anthony; McInerney, Marcia; Huffman, Donald; McInerney, Brigid; Mayo, Stella; Haskins, Kathryn; Sercarz, Eli

2006-06-01

Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes, and serve as a model for type 1 diabetes (T1D) and natural autoimmunity. T cell responses to the pancreatic islet antigen glutamic acid decarboxylase 65 (GAD65) can be detected in the spleens of young prediabetic NOD mice, which display a unique MHC class II molecule. Here, we report that a distinct TcR beta chain and CDR3 motif are utilized by all NOD mice in response to a dominant determinant on GAD65, establishing a public repertoire in the spontaneous autoimmunity to an important islet cell antigen. GAD65 530-543 (p530)-reactive T cells preferentially utilize the Vbeta4, Dbeta2.1 and Jbeta2.7 gene segments, with a CDR3 that is characterized by a triad of amino acids, DWG, preceded by a polar residue. In addition, we used CDR3 length spectratyping, CDR3-specific reverse transcriptase-PCR and direct TcR sequencing to show that the TcR beta chain structural patterns associated with p530-specific T cells consistently appeared in the islets of young NOD mice with insulitis, but not in the inflamed islets of streptozotocin-treated C57BL/6 mice, or in inflamed NOD salivary glands. To our knowledge, this is the first report to demonstrate that a public T cell repertoire is used in spontaneous autoimmunity to a dominant self-determinant. These findings suggest that defined clonotypes and repertoires may be preferentially selected in haplotypes predisposed to spontaneous autoimmunity.

Analysis of brief language tests in the detection of cognitive decline and dementia

PubMed Central

Radanovic, Marcia; Carthery-Goulart, Maria Teresa; Charchat-Fichman, Helenice; Herrera Jr., Emílio; Lima, Edson Erasmo Pereira; Smid, Jerusa; Porto, Cláudia Sellitto; Nitrini, Ricardo

2007-01-01

Lexical access difficulties are frequent in normal aging and initial stages of dementia.Verbal fluency tests are valuable to detect cognitive decline, evidencing lexico-semantic and executive dysfunction. Objectives To establish which language tests can contribute in detecting dementia and to verify schooling influence on subject performance. Method 74 subjects: 33 controls, 17 Clinical Dementia Rating (CDR) 0.5 and 24 (Brief Cognitive Battery - BCB e Boston Naming Test - BNT) 1 were compared in tests of semantic verbal fluency (animal and fruit), picture naming (BCB and BNT) and the language items of Mini Mental State Examination (MMSE). Results There were significant differences between the control group and both CDR 0.5 and CDR 1 in all tests. Cut-off scores were: 11 and 10 for animal fluency, 8 for fruit fluency (in both), 8 and 9 for BCB naming. The CDR 0.5 group performed better than the CDR 1 group only in animal fluency. Stepwise multiple regression revealed fruit fluency, animal fluency and BCB naming as the best discriminators between patients and controls (specificity: 93.8%; sensitivity: 91.3%). In controls, comparison between illiterates and literates evidenced schooling influence in all tests, except for fruit fluency and BCB naming. In patients with dementia, only fruit fluency was uninfluenced by schooling. Conclusion The combination of verbal fluency tests in two semantic categories along with a simple picture naming test is highly sensitive in detecting cognitive decline. Comparison between literate and illiterate subjects shows a lesser degree of influence of schooling on the selected tests, thus improving discrimination between low performance and incipient cognitive decline. PMID:29213366

Updated systematic review and meta-analysis of the performance of risk prediction rules in children and young people with febrile neutropenia.

PubMed

Phillips, Robert S; Lehrnbecher, Thomas; Alexander, Sarah; Sung, Lillian

2012-01-01

Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia.

Wealth and under-nourishment among married women in two impoverished nations: evidence from Burkina Faso and Congo Democratic Republic.

PubMed

Adebowale, Ayo Stephen; Palamuleni, Martin Enoch; Odimegwu, Clifford Obby

2015-02-08

Burkina Faso (BF) and Congo Democratic Republic (CDR) are among the top-ten poverty and hunger stricken countries globally. The influence of poverty and hunger on health is enormous. The objectives of the study are to; examine the association between poverty and nutritional status, it also identified socio-demographic and health related mediating factors that contribute to the relationship between poverty and poor nutritional status. The study focused on married or cohabiting women aged 15-49 years and utilized 2010 and 2007 DHS dataset from BF and CDR respectively. Mean age of the women in BF and CDR were 34.4 ± 9.3 and 34.7 ± 9.0 years respectively. About 19.4% and 18.4% of the poor were malnourished as against 7.7% and 9.7% of the rich women in BF and CDR respectively. Obesity and overweight were more prominent among the rich than the poor. Higher prevalence of under-nourish women was found among the older than the younger women in BF. In the countries, the prevalence of malnutrition was significantly higher among women; in the rural areas, with no formal education, anaemic and those who are not working. Multivariate analysis revealed that in the countries, the risk of under-nourishment was significantly higher among poor and middle class than the rich women despite controlling for confounding variables. Undernourished women were more common among the poor and those with no formal education. Programs that target nutrition of women of reproductive age should be strengthened in BF and CDR.

Updated Systematic Review and Meta-Analysis of the Performance of Risk Prediction Rules in Children and Young People with Febrile Neutropenia

PubMed Central

Phillips, Robert S.; Lehrnbecher, Thomas; Alexander, Sarah; Sung, Lillian

2012-01-01

Introduction Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. Methods The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. Results We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. Conclusion The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia. PMID:22693615

Novel mouth-exercising device for oral submucous fibrosis.

PubMed

Patil, Pravinkumar G; Patil, Smita P

2012-10-01

Oral submucous fibrosis (OSMF) is a chronic inflammatory disease resulting in progressive juxtaepithelial fibrosis of the oral soft tissues and can cause increasing difficulty in mastication, swallowing, speaking, and mouth opening. The treatment of severe trismus requires a combination of surgical release and physiotherapy. Often physiotherapy alone can modify tissue remodeling in OSMF to increase oral opening. This article describes the fabrication and use of a new mouth-exercising device that helps the patient to squeeze/stretch the cheek mucosa to increase elasticity. The device can be used as a sole treatment modality or can be used in association with pharmacological and surgical treatment modalities for OSMF. Improvement in mouth opening was observed in four OSMF patients treated with a mouth-exercising device for 6 months as a sole treatment modality. © 2012 by the American College of Prosthodontists.

Joint Training In Combined Entry Operations

DTIC Science & Technology

2014-02-13

AIR WAR COLLEGE AIR UNIVERSITY JOINT TRAINING IN COMBINED ENTRY OPERATIONS by Ethan Mitchell, CDR, USN A Research Report Submitted...government. DISTRIBUTION A . Approved for public release: distribution unlimited. 2 Biography CDR Ethan Mitchell is assigned to the Air War College...Areas of Responsibility. Ashore, her served in the requirements directorate on the Commander, Second Fleet staff and earned a Master’s of Science

Examples and Case Studies for the 2012 Chemical Data Reporting

EPA Pesticide Factsheets

This document presents examples and case studies to help you in reporting for 2012 Chemical Data Reporting (CDR), formerly known as Inventory Update Reporting (IUR).EPA designed these examples to illustrate the new reporting requirements, which were published as part of the CDR Rule (published August 16, 2011), and to address general reporting issues from the 2006 IUR.

U.S. Naval Strategy in the 1990s: Selected Documents

DTIC Science & Technology

2006-09-01

Crawshaw , USN; Capt. Eric Briggs, USN; Capt. Charles Schaefer, USN; Cdr. Joseph Connelly, USN; Cdr. Al Seifert, USN; Capt. Frank Dobrydney, USN. † Vice...countermeasures 33 counter-terrorism 206, 208 courage 107 CPAM See CNO Program Analysis Memorandum Crawshaw , Robert 88 U . S . N A V A L S T R A T E G Y I N T

e-CDRweb User Guide – Secondary Authorized Official

EPA Pesticide Factsheets

This document presents the user guide for the Office of Pollution Prevention and Toxics’ (OPPT) e-CDRweb tool. E-CDRweb is the electronic, web-based tool provided by the Environmental Protection Agency (EPA) for the submission of Chemical Data Reporting (CDR) information. This document is the user guide for the Secondary Authorized Official (AO) user of the e-CDR web tool.

Dynamic inter-limb resistance exercise device for long-duration space flight

NASA Technical Reports Server (NTRS)

Schwandt, Douglas F.; Watenpaugh, Donald E.; Parazynski, Scott E.; Hargens, Alan R.

1991-01-01

Essential for fitness on Earth, resistive exercise is even more important for astronauts, who must maintain muscle and bone strength in the absence of gravity. To meet this need, designers and scientists at NASA Ames Research Center, Life Science Division, have worked to develop more effective exercise devices for long-duration exposure to microgravity. One of these concepts is the Inter-Limb Resistance Device which allows the subject to exercise one limb directly against another, strengthening muscle groups in the arms, legs, and back. It features a modular harness with an inelastic cable and instrumented pulley. Forces similar to other high resistance exercise equipment are generated. Sensors in the pulley measure force and velocity for performance feedback display and data acquisition. This free-floating apparatus avoids vibration of sensitive experiments on board spacecraft. Compact with low mass, this hardware is also well suited for a 'safe haven' from radiation on board Space Station Freedom, and may prove useful in confined environments on Earth, such as Antarctic stations, submarines, and other underwater habitats. Potential spin-offs of this technology include products for personal strengthening and cardiovascular conditioning, rehabilitation of hospital patients, fitness exercise for the disabled, and retraining after sports injuries.

Portable Load Measurement Device for Use During ARED Exercise on ISS

NASA Technical Reports Server (NTRS)

Hanson, A.; Peters, B.; Caldwell, E.; Sinka, J.; Kreutzburg, G.; Ploutz-Snyder, L.

2014-01-01

The Advanced Resistive Exercise Device (ARED) (Fig.1) is unique countermeasure hardware available to crewmembers aboard the International Space Station (ISS) used for resistance exercise training to protect against bone and muscle loss during long duration space missions. ARED instrumentation system was designed to measure and record exercise load data, but: - Reliably accurate data has not been available due to a defective force platform. - No ARED data has been recorded since mid-2011 due to failures in the instrumentation power system. ARED load data supports on-going HRP funded research, and is available to extramural researchers through LSDA-Repository. Astronaut Strength, Conditioning, and Rehabilitation specialists (ASCRs) use ARED data to track training progress and advance exercise prescriptions. ARED load data is necessary to fulfill medical requirements. HRP directed task intends to reduce to program risk (HRP IRMA Risk 1735), and evaluate the XSENS ForceShoeTM as a means of obtaining ARED load data during exercise sessions. The XSENS ForceShoes"TM" will fly as a hardware demonstration to ISS in May 2014 (39S). Additional portable load monitoring devices (PLMDs) are under evaluation in the ExPC Lab. PLMDs are favored over platform redesign as they support future exploration needs.

Effects of transcatheter closure of Fontan fenestration on exercise tolerance. kidecho@yahoo.com.

PubMed

Momenah, Tarek S; Eltayb, Haifa; Oakley, Reida El; Qethamy, Howeida Al; Faraidi, Yahya Al

2008-05-01

Baffle fenestration is associated with a significantly better outcome in standard and high-risk patients undergoing completion of Fontan. We report the effects of subsequent transcatheter closure of fenestration on exercise capacity and oxygen saturation. Sixteen patients with a mean age of 10.3 years underwent Amplatzer septal occluder (ASO) device transcatheter closure of Fontan fenestration. All had a fenestrated Fontan operation 6 month to 8 years prior to the procedure. A stress test was performed before and after device closure of fenestration in 14 patients (2 patients did not tolerate stress test before the procedure). The fenestrations in all patients were successfully occluded with the use of the Amplatzer device occluder. No complications occurred during or after the procedure. O2 saturation increased from a mean 85.1 +/- 7.89% to 94.5 +/- 3.63% (p < 0.01) at rest and from 66.2 +/- 12.86% to 87.2 +/- 8.64% (p < 0.01) following exercise. Exercise duration has also increased from 8.22 +/- 2.74 min to 10.29 +/- 1.91 min (p < 0.05). Transcatheter closure of Fontan fenestration increases the duration of exercise capacity and increases O2 saturation at rest and after exercise.

Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function.

PubMed

Piwecka, Monika; Glažar, Petar; Hernandez-Miranda, Luis R; Memczak, Sebastian; Wolf, Susanne A; Rybak-Wolf, Agnieszka; Filipchyk, Andrei; Klironomos, Filippos; Cerda Jara, Cledi Alicia; Fenske, Pascal; Trimbuch, Thorsten; Zywitza, Vera; Plass, Mireya; Schreyer, Luisa; Ayoub, Salah; Kocks, Christine; Kühn, Ralf; Rosenmund, Christian; Birchmeier, Carmen; Rajewsky, Nikolaus

2017-09-22

Hundreds of circular RNAs (circRNAs) are highly abundant in the mammalian brain, often with conserved expression. Here we show that the circRNA Cdr1as is massively bound by the microRNAs (miRNAs) miR-7 and miR-671 in human and mouse brains. When the Cdr1as locus was removed from the mouse genome, knockout animals displayed impaired sensorimotor gating-a deficit in the ability to filter out unnecessary information-which is associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression of miR-7 and miR-671 was specifically and posttranscriptionally misregulated in all brain regions analyzed. Expression of immediate early genes such as Fos , a direct miR-7 target, was enhanced in Cdr1as -deficient brains, providing a possible molecular link to the behavioral phenotype. Our data indicate an in vivo loss-of-function circRNA phenotype and suggest that interactions between Cdr1as and miRNAs are important for normal brain function. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Efficient Planning of Wind-Optimal Routes in North Atlantic Oceanic Airspace

NASA Technical Reports Server (NTRS)

Rodionova, Olga; Sridhar, Banavar

2017-01-01

The North Atlantic oceanic airspace (NAT) is crossed daily by more than a thousand flights, which are greatly affected by strong jet stream air currents. Several studies devoted to generating wind-optimal (WO) aircraft trajectories in the NAT demonstrated great efficiency of such an approach for individual flights. However, because of the large separation norms imposed in the NAT, previously proposed WO trajectories induce a large number of potential conflicts. Much work has been done on strategic conflict detection and resolution (CDR) in the NAT. The work presented here extends previous methods and attempts to take advantage of the NAT traffic structure to simplify the problem and improve the results of CDR. Four approaches are studied in this work: 1) subdividing the existing CDR problem into sub-problems of smaller sizes, which are easier to handle; 2) more efficient data reorganization within the considered time period; 3) problem localization, i.e. concentrating the resolution effort in the most conflicted regions; 4) applying CDR to the pre-tactical decision horizon (a couple of hours in advance). Obtained results show that these methods efficiently resolve potential conflicts at the strategic and pre-tactical levels by keeping the resulting trajectories close to the initial WO ones.

The three-dimensional structure of a T-cell antigen receptor V alpha V beta heterodimer reveals a novel arrangement of the V beta domain.

PubMed Central

Housset, D; Mazza, G; Grégoire, C; Piras, C; Malissen, B; Fontecilla-Camps, J C

1997-01-01

The crystal structure of a mouse T-cell antigen receptor (TCR) Fv fragment complexed to the Fab fragment of a specific anti-clonotypic antibody has been determined to 2.6 A resolution. The polypeptide backbone of the TCR V alpha domain is very similar to those of other crystallographically determined V alphas, whereas the V beta structure is so far unique among TCR V beta domains in that it displays a switch of the c" strand from the inner to the outer beta-sheet. The beta chain variable region of this TCR antigen-binding site is characterized by a rather elongated third complementarity-determining region (CDR3beta) that packs tightly against the CDR3 loop of the alpha chain, without leaving any intervening hydrophobic pocket. Thus, the conformation of the CDR loops with the highest potential diversity distinguishes the structure of this TCR antigen-binding site from those for which crystallographic data are available. On the basis of all these results, we infer that a significant conformational change of the CDR3beta loop found in our TCR is required for binding to its cognate peptide-MHC ligand. PMID:9250664

Carbon dioxide removal and the futures market

NASA Astrophysics Data System (ADS)

Coffman, D.'Maris; Lockley, Andrew

2017-01-01

Futures contracts are exchange-traded financial instruments that enable parties to fix a price in advance, for later performance on a contract. Forward contracts also entail future settlement, but they are traded directly between two parties. Futures and forwards are used in commodities trading, as producers seek financial security when planning production. We discuss the potential use of futures contracts in Carbon Dioxide Removal (CDR) markets; concluding that they have one principal advantage (near-term price security to current polluters), and one principal disadvantage (a combination of high price volatility and high trade volume means contracts issued by the private sector may cause systemic economic risk). Accordingly, we note the potential for the development of futures markets in CDR, but urge caution about the prospects for market failure. In particular, we consider the use of regulated markets: to ensure contracts are more reliable, and that moral hazard is minimised. While regulation offers increased assurances, we identify major insufficiencies with this approach—finding it generally inadequate. In conclusion, we suggest that only governments can realistically support long-term CDR futures markets. We note existing long-term CDR plans by governments, and suggest the use of state-backed futures for supporting these assurances.

Classification of maltreatment-related mortality by Child Death Review teams: How reliable are they?

PubMed

Parrish, Jared W; Schnitzer, Patricia G; Lanier, Paul; Shanahan, Meghan E; Daniels, Julie L; Marshall, Stephen W

2017-05-01

Accurate estimation of the incidence of maltreatment-related child mortality depends on reliable child fatality review. We examined the inter-rater reliability of maltreatment designation for two Alaskan Child Death Review (CDR) panels. Two different multidisciplinary CDR panels each reviewed a series of 101 infant and child deaths (ages 0-4 years) in Alaska. Both panels independently reviewed identical medical, autopsy, law enforcement, child welfare, and administrative records for each death utilizing the same maltreatment criteria. Percent agreement for maltreatment was 64.7% with a weighted Kappa of 0.61 (95% CI 0.51, 0.70). Across maltreatment subtypes, agreement was highest for abuse (69.3%) and lowest for negligence (60.4%). Discordance was higher if the mother was unmarried or a smoker, if residence was rural, or if there was a family history of child protective services report(s). Incidence estimates did not depend on which panel's data were used. There is substantial room for improvement in the reliability of CDR panel assessment of maltreatment related mortality. Standardized decision guidance for CDR panels may improve the reliability of their data. Copyright © 2017 Elsevier Ltd. All rights reserved.

In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer

PubMed Central

Kwon, Hye Youn; Kim, Im-kyung; Kang, Jeonghyun; Sohn, Seung-Kook; Lee, Kang Young

2016-01-01

Purpose We evaluated the usefulness of the in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) for prediction of clinical response to fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer. Materials and Methods Tumor specimens of 86 patients with pathologically confirmed stage II colorectal adenocarcinoma were tested for chemosensitivity to fluorouracil. Chemosensitivity was determined by cell death rate (CDR) of drug-exposed cells, calculated by comparing the intracellular ATP level with that of untreated controls. Results Among the 86 enrolled patients who underwent radical surgery followed by fluorouracil-based adjuvant chemotherapy, recurrence was found in 11 patients (12.7%). The CDR ≥ 20% group was associated with better disease-free survival than the CDR < 20% group (89.4% vs. 70.1%, p=0.027). Multivariate analysis showed that CDR < 20% and T4 stage were poor prognostic factors for disease-free survival after fluorouracil-based adjuvant chemotherapy. Conclusion In stage II colorectal cancer, the in vitro ATP-CRA may be useful in identifying patients likely to benefit from fluorouracil-based adjuvant chemotherapy. PMID:26511802

Rational Design of Peptide-Functionalized Surface Plasmon Resonance Sensor for Specific Detection of TNT Explosive.

PubMed

Wang, Jin; Muto, Masaki; Yatabe, Rui; Onodera, Takeshi; Tanaka, Masayoshi; Okochi, Mina; Toko, Kiyoshi

2017-09-30

In this study, a rationally-designed 2,4,6-trinitrotoluene (TNT) binding peptide derived from an amino acid sequence of the complementarity-determining region (CDR) of an anti-TNT monoclonal antibody was used for TNT detection based on a maleimide-functionalized surface plasmon resonance (SPR) sensor. By antigen-docking simulation and screening, the TNT binding candidate peptides were obtained as TNTHCDR1 derived from the heavy chain of CDR1, TNTHCDR2 derived from CDR2, and TNTHCDR3 from CDR3 of an anti-TNT antibody. The binding events between candidate peptides and TNT were evaluated using the SPR sensor by direct determination based on the 3-aminopropyltriethoxysilane (APTES) surface. The TNT binding peptide was directly immobilized on the maleimide-functionalized sensor chip surface from N-γ-maleimidobutyryl-oxysuccinimide ester (GMBS). The results demonstrated that peptide TNTHCDR3 was identified and selected as a TNT binding peptide among the other two candidate peptides. Five kinds of TNT analogues were also investigated to testify the selectivity of TNT binding peptide TNTHCDR3. Furthermore, the results indicated that the APTES-GMBS-based SPR sensor chip procedure featured a great potential application for the direct detection of TNT.

Rational Design of Peptide-Functionalized Surface Plasmon Resonance Sensor for Specific Detection of TNT Explosive

PubMed Central

Wang, Jin; Muto, Masaki; Yatabe, Rui; Onodera, Takeshi; Okochi, Mina; Toko, Kiyoshi

2017-01-01

In this study, a rationally-designed 2,4,6-trinitrotoluene (TNT) binding peptide derived from an amino acid sequence of the complementarity-determining region (CDR) of an anti-TNT monoclonal antibody was used for TNT detection based on a maleimide-functionalized surface plasmon resonance (SPR) sensor. By antigen-docking simulation and screening, the TNT binding candidate peptides were obtained as TNTHCDR1 derived from the heavy chain of CDR1, TNTHCDR2 derived from CDR2, and TNTHCDR3 from CDR3 of an anti-TNT antibody. The binding events between candidate peptides and TNT were evaluated using the SPR sensor by direct determination based on the 3-aminopropyltriethoxysilane (APTES) surface. The TNT binding peptide was directly immobilized on the maleimide-functionalized sensor chip surface from N-γ-maleimidobutyryl-oxysuccinimide ester (GMBS). The results demonstrated that peptide TNTHCDR3 was identified and selected as a TNT binding peptide among the other two candidate peptides. Five kinds of TNT analogues were also investigated to testify the selectivity of TNT binding peptide TNTHCDR3. Furthermore, the results indicated that the APTES-GMBS-based SPR sensor chip procedure featured a great potential application for the direct detection of TNT. PMID:28973962

Lysophospholipid presentation by CD1d and recognition by a human Natural Killer T-cell receptor

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

López-Sagaseta, Jacinto; Sibener, Leah V.; Kung, Jennifer E.

2014-10-02

Invariant Natural Killer T (iNKT) cells use highly restricted {alpha}{beta} T cell receptors (TCRs) to probe the repertoire of lipids presented by CD1d molecules. Here, we describe our studies of lysophosphatidylcholine (LPC) presentation by human CD1d and its recognition by a native, LPC-specific iNKT TCR. Human CD1d presenting LPC adopts an altered conformation from that of CD1d presenting glycolipid antigens, with a shifted {alpha}1 helix resulting in an open A pocket. Binding of the iNKT TCR requires a 7-{angstrom} displacement of the LPC headgroup but stabilizes the CD1d-LPC complex in a closed conformation. The iNKT TCR CDR loop footprint onmore » CD1d-LPC is anchored by the conserved positioning of the CDR3{alpha} loop, whereas the remaining CDR loops are shifted, due in part to amino-acid differences in the CDR3{beta} and J{beta} segment used by this iNKT TCR. These findings provide insight into how lysophospholipids are presented by human CD1d molecules and how this complex is recognized by some, but not all, human iNKT cells.« less

2 kWe Solar Dynamic Ground Test Demonstration Project. Volume 2; Design Report

NASA Technical Reports Server (NTRS)

Alexander, Dennis

1997-01-01

Critical Design Reviews (CDR's) were held on the Solar Dynamic Ground Test Demonstrator (SDGTD). This CDR summary report will provide the following information for each of the system components and the system integration: (1) A bibliography of design/design review documentation; (2) A summary of the major discussion issues from issues from each design review; (3) A definition of the component and system detail designs along with the bottom line from the supporting analysis; (4) Status and key results from pertinent development activities on-going in the CDR time period; (5) A brief description of planned testing; and (6) A discussion of issues stiff open at the completion of CDR. Appendix 1 to this report contains a listing and status (as of 28 June 1993) of all the action items generated during all SDGTD CDRs. The reader should remember that the SDGTD program is being conducted in an open communication forum, and program participants are encouraged to ask questions or request information. Team members are allowed and encouraged to participate in the reviews on an equal basis. No request for information, as long as it is within the work scope, is refused, so many action items are generated.

Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function.

PubMed

Balzar, Silvana

2017-01-01

Idiopathic chronic inflammatory conditions (ICIC) such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR) of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system's thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way) resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system's compartmentalization in the pathogenesis of ICIC. The CDR concept's relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function.

EFFECTIVENESS OF AN UPPER EXTREMITY EXERCISE DEVICE AND TEXT MESSAGE REMINDERS TO EXERCISE IN ADULTS WITH SPINA BIFIDA: A PILOT STUDY

PubMed Central

Crytzer, Theresa M.; Dicianno, Brad E.; Fairman, Andrea D.

2013-01-01

Background Obesity, deconditioning, cognitive impairment, and poor exercise tolerance are health issues concerning adults with spina bifida (SB). Our aim is to describe exercise participation and identify motivating tactics and exercise devices that increase participation. Design In a quasi-experimental randomized crossover design, the GameCycle was compared to a Saratoga Silver I arm ergometer. Personalized free or low cost text/voice message reminders to exercise were sent. Methods Nineteen young adults with SB were assigned to either the GameCycle or Saratoga exercise group. Within each group, participants were randomized to receive reminders to exercise, or no reminders, then crossed over to the opposite message group after eight weeks. Before and after a 16 week exercise program we collected anthropometric, metabolic, exercise testing and questionnaire data, and recorded participation. Results Miles traveled by the GameCycle group were significantly higher than the Saratoga exercise groups. No significant differences were found in participation between the message reminder groups. Low participation rates were seen overall. Conclusions Those using the GameCycle traveled more miles. Barriers to exercise participation may have superseded ability to motivate adults with SB to exercise even with electronic reminders. Support from therapists to combat deconditioning and develop coping skills may be needed. PMID:24620701

A clinical data repository enhances hospital infection control.

PubMed Central

Samore, M.; Lichtenberg, D.; Saubermann, L.; Kawachi, C.; Carmeli, Y.

1997-01-01

We describe the benefits of a relational database of hospital clinical data (Clinical Data Repository; CDR) for an infection control program. The CDR consists of > 40 Sybase tables, and is directly accessible for ad hoc queries by members of the infection control unit who have been granted privileges for access by the Information Systems Department. The data elements and functional requirements most useful for surveillance of nosocomial infections, antibiotic use, and resistant organisms are characterized. Specific applications of the CDR are presented, including the use of automated definitions of nosocomial infection, graphical monitoring of resistant organisms with quality control limits, and prospective detection of inappropriate antibiotic use. Hospital surveillance and quality improvement activities are significantly benefited by the availability of a querable set of tables containing diverse clinical data. PMID:9357588

Development of the Internet-Enabled System for Exercise Telerehabilitation and Cardiovascular Training.

PubMed

Dedov, Vadim N; Dedova, Irina V

2015-07-01

Sustained exercise training could significantly improve patient rehabilitation and management of noncommunicable diseases in the community. This study aimed to develop a universal telecare system for delivery of exercise rehabilitation and cardiovascular training services at home. An innovative bilateral leg training device was equipped with an electronic system for the ongoing measurement of training activities with the device. A single-item parameter reflecting the intensity of training was monitored using several modern telecommunication technologies. According to the application protocol, eight volunteers first tried the device for 30-60 min to determine their personal training capacity. Then, they were provided with equipment to use at home for 4 weeks. Adherence to daily training was assessed by the number of training days per week, training intensity, and duration of training sessions. The system provided reliable recording of training activities with the device using (1) long-term data logging without an ongoing connection to the computer, (2) wireless monitoring and recording of training activities on a stand-alone computer, and (3) a secure cloud-based monitoring over the Internet connection using electronic devices, including smartphones. Overall analysis of recordings and phone feedbacks to participants took only approximately 5 h for the duration of study. This study, although of a pilot nature, described the comprehensive exercise telerehabilitation system integrating mobile training equipment with personalized training protocols and remote monitoring. A single-item electronic parameter of the system usage facilitated time-effective data management. Wireless connection allowed various locations of device application and several monitoring arrangements ranging from real-time monitoring to long-term recording of exercise activities. A cloud-based software platform enabled management of multiple users at distance. Implementation of this model may facilitate both accessibility and availability of personalized exercise telerehabilitation services. Further studies would validate it in the clinical and healthcare environment.

Articulating Support for Horizontal Resistive Exercise

NASA Technical Reports Server (NTRS)

Gundo, Daniel; Schaffner, Grant; Bentley, Jason; Loehr, James A.

2005-01-01

A versatile mechanical device provides support for a user engaged in any of a variety of resistive exercises in a substantially horizontal orientation. The unique features and versatility of the device promise to be useful in bedrest studies, rehabilitation, and specialized strength training. The device affords a capability for selectively loading and unloading of portions of the user s body through its support mechanisms, so that specific parts of the body can be trained with little or no effect on other parts that may be disabled or in the process of recovery from injury. Thus, the device is ideal for rehabilitation exercise programs prescribed by physicians and physical therapists. The capability for selective loading and support also offers potential benefits to strength and conditioning trainers and athletes who wish to selectively strengthen selected parts. The principal innovative aspect of the device is that it supports the subject s weight while enabling the subject, lying substantially horizontally, to perform an exercise that closely approximates a full standing squat. The device includes mechanisms that support the subject in such a way that the hips are free to translate both horizontally and vertically and are free to rotate about the line connecting the hips. At the same time, the shoulders are free to translate horizontally while the upper back is free to rotate about the line connecting the shoulders. Among the mechanisms for hip motion and support is a counterbalance that offsets the weight of the subject as the subject s pelvis translates horizontally and vertically and rotates the pelvis about the line connecting the hips. The counterbalance is connected to a pelvic support system that allows these pelvic movements. The subject is also supported at the shoulder by a mechanism that can tilt to provide continuous support of the upper back while allowing the rotation required for arching the back as the pelvis is displaced. The shoulder support also affords a capability for horizontal motion, and acts as the point of attachment of a load that is provided for squat and heel-raise exercises. The device is compatible with any resistive-exercise machine that provides bilateral loading via a moving cable or other mechanical linkage. The hip-translation and shoulder-translation and -rotation degrees of freedom of the supports can be locked individually or in combination in order to support the subject as necessary for exercises other than the standing squat. If necessary, for such exercises, the load can be applied directly to the subject by use of various attachments. In addition to the aforementioned heel raise, such exercises include the upright row, leg press, curls, extension of the triceps, front raise, lateral raise, and rear raise.

Lindgren exercises in Node 3 module

NASA Image and Video Library

2015-07-28

ISS044E024392 (07/28/2015) --- Newly arrived NASA astronaut Kjell Lindgren exercises on the International Space Station using the Advanced Resistive Exercise Device to help mitigate the potentially adverse effects of long duration stays in microgravity.

Effect of a Metal Deactivator Fuel Additive on Fuel Deposition in Fuel Atomizers at High Temperature

DTIC Science & Technology

1992-08-01

ARMY NATICK RD&E CENTER DEVELOPMENT AND ENGINEERING CTR ATTN: SATNC-U ATUN : SATBE-F I NATICK MA 01760-5020 SATBE-FL 10 SATBE-BT 2 DIRECTOR SATBE-TQ 1...SFT (MR MAKRIS) I WASHINGTON DC 20330 SAALC/LDPE (MR ELLIOT) 1 KELLY AIR FORCE BASE TX 78241 CDR US AIR FORCE WRIGHT AERO LAB CDR ATUN : POSF (MR

The Climate Potentials and Side-Effects of Large-Scale terrestrial CO2 Removal - Insights from Quantitative Model Assessments

NASA Astrophysics Data System (ADS)

Boysen, L.; Heck, V.; Lucht, W.; Gerten, D.

2015-12-01

Terrestrial carbon dioxide removal (tCDR) through dedicated biomass plantations is considered as one climate engineering (CE) option if implemented at large-scale. While the risks and costs are supposed to be small, the effectiveness depends strongly on spatial and temporal scales of implementation. Based on simulations with a dynamic global vegetation model (LPJmL) we comprehensively assess the effectiveness, biogeochemical side-effects and tradeoffs from an earth system-analytic perspective. We analyzed systematic land-use scenarios in which all, 25%, or 10% of natural and/or agricultural areas are converted to tCDR plantations including the assumption that biomass plantations are established once the 2°C target is crossed in a business-as-usual climate change trajectory. The resulting tCDR potentials in year 2100 include the net accumulated annual biomass harvests and changes in all land carbon pools. We find that only the most spatially excessive, and thus undesirable, scenario would be capable to restore the 2° target by 2100 under continuing high emissions (with a cooling of 3.02°C). Large-scale biomass plantations covering areas between 1.1 - 4.2 Gha would produce a climate reduction potential of 0.8 - 1.4°C. tCDR plantations at smaller scales do not build up enough biomass over this considered period and the potentials to achieve global warming reductions are substantially lowered to no more than 0.5-0.6°C. Finally, we demonstrate that the (non-economic) costs for the Earth system include negative impacts on the water cycle and on ecosystems, which are already under pressure due to both land use change and climate change. Overall, tCDR may lead to a further transgression of land- and water-related planetary boundaries while not being able to set back the crossing of the planetary boundary for climate change. tCDR could still be considered in the near-future mitigation portfolio if implemented on small scales on wisely chosen areas.

Sulfamethoxazole Induces a Switch Mechanism in T Cell Receptors Containing TCRVβ20-1, Altering pHLA Recognition

PubMed Central

Watkins, Stephan; Pichler, Werner J.

2013-01-01

T cell receptors (TCR) containing Vβ20-1 have been implicated in a wide range of T cell mediated disease and allergic reactions, making it a target for understanding these. Mechanics of T cell receptors are largely unexplained by static structures available from x-ray crystallographic studies. A small number of molecular dynamic simulations have been conducted on TCR, however are currently lacking either portions of the receptor or explanations for differences between binding and non-binding TCR recognition of respective peptide-HLA. We performed molecular dynamic simulations of a TCR containing variable domain Vβ20-1, sequenced from drug responsive T cells. These were initially from a patient showing maculopapular eruptions in response to the sulfanilamide-antibiotic sulfamethoxazole (SMX). The CDR2β domain of this TCR was found to dock SMX with high affinity. Using this compound as a perturbation, overall mechanisms involved in responses mediated by this receptor were explored, showing a chemical action on the TCR free from HLA or peptide interaction. Our simulations show two completely separate modes of binding cognate peptide-HLA complexes, with an increased affinity induced by SMX bound to the Vβ20-1. Overall binding of the TCR is mediated through a primary recognition by either the variable β or α domain, and a switch in recognition within these across TCR loops contacting the peptide and HLA occurs when SMX is present in the CDR2β loop. Large binding affinity differences are induced by summed small amino acid changes primarily by SMX modifying only three critical CDR2β loop amino acid positions. These residues, TYRβ57, ASPβ64, and LYSβ65 initially hold hydrogen bonds from the CDR2β to adjacent CDR loops. Effects from SMX binding are amplified and traverse longer distances through internal TCR hydrogen bonding networks, controlling the overall TCR conformation. Thus, the CDR2β of Vβ20-1 acts as a ligand controlled switch affecting overall TCR binding affinity. PMID:24116097

A Multireader Exploratory Evaluation of Individual Pulse Sequence Cancer Detection on Prostate Multiparametric Magnetic Resonance Imaging (MRI).

PubMed

Gaur, Sonia; Harmon, Stephanie; Gupta, Rajan T; Margolis, Daniel J; Lay, Nathan; Mehralivand, Sherif; Merino, Maria J; Wood, Bradford J; Pinto, Peter A; Shih, Joanna H; Choyke, Peter L; Turkbey, Baris

2018-04-25

To determine independent contribution of each prostate multiparametric magnetic resonance imaging (mpMRI) sequence to cancer detection when read in isolation. Prostate mpMRI at 3-Tesla with endorectal coil from 45 patients (n = 30 prostatectomy cases, n = 15 controls with negative magnetic resonance imaging [MRI] or biopsy) were retrospectively interpreted. Sequences (T2-weighted [T2W] MRI, diffusion-weighted imaging [DWI], and dynamic contrast-enhanced [DCE] MRI; N = 135) were separately distributed to three radiologists at different institutions. Readers evaluated each sequence blinded to other mpMRI sequences. Findings were correlated to whole-mount pathology. Cancer detection sensitivity, positive predictive value for whole prostate (WP), transition zone, and peripheral zone were evaluated per sequence by reader, with reader concordance measured by index of specific agreement. Cancer detection rates (CDRs) were calculated for combinations of independently read sequences. 44 patients were evaluable (cases median prostate-specific antigen 6.83 [ range 1.95-51.13] ng/mL, age 62 [45-71] years; controls prostate-specific antigen 6.85 [2.4-10.87] ng/mL, age 65.5 [47-71] years). Readers had highest sensitivity on DWI (59%) vs T2W MRI (48%) and DCE (23%) in WP. DWI-only positivity (DWI+/T2W-/DCE-) achieved highest CDR in WP (38%), compared to T2W-only (CDR 24%) and DCE-only (CDR 8%). DWI+/T2W+/DCE- achieved CDR 80%, an added benefit of 56.4% from T2W-only and of 42% from DWI-only (P < .0001). All three sequences interpreted independently positive gave highest CDR of 90%. Reader agreement was moderate (index of specific agreement: T2W = 54%, DWI = 58%, DCE = 33%). When prostate mpMRI sequences are interpreted independently by multiple observers, DWI achieves highest sensitivity and CDR in transition zone and peripheral zone. T2W and DCE MRI both add value to detection; mpMRI achieves highest detection sensitivity when all three mpMRI sequences are positive. Published by Elsevier Inc.

Human factors evaluations of Free Flight Issues solved and issues remaining.

PubMed

Ruigrok, Rob C J; Hoekstra, Jacco M

2007-07-01

The Dutch National Aerospace Laboratory (NLR) has conducted extensive human-in-the-loop simulation experiments in NLR's Research Flight Simulator (RFS), focussed on human factors evaluation of Free Flight. Eight years of research, in co-operation with partners in the United States and Europe, has shown that Free Flight has the potential to increase airspace capacity by at least a factor of 3. Expected traffic loads and conflict rates for the year 2020 appear to be no major problem for professional airline crews participating in flight simulation experiments. Flight efficiency is significantly improved by user-preferred routings, including cruise climbs, while pilot workload is only slightly increased compared to today's reference. Detailed results from three projects and six human-in-the-loop experiments in NLR's Research Flight Simulator are reported. The main focus of these results is on human factors issues and particularly workload, measured both subjectively and objectively. An extensive discussion is included on many human factors issues resolved during the experiments, but also open issues are identified. An intent-based Conflict Detection and Resolution (CD&R) system provides "benefits" in terms of reduced pilot workload, but also "costs" in terms of complexity, need for priority rules, potential compatibility problems between different brands of Flight Management Systems and large bandwidth. Moreover, the intent-based system is not effective at solving multi-aircraft conflicts. A state-based CD&R system also provides "benefits" and "costs". Benefits compared to the full intent-based system are simplicity, low bandwidth requirements, easy to retrofit (no requirements to change avionics infrastructure) and the ability to solve multi-aircraft conflicts in parallel. The "costs" involve a somewhat higher pilot workload in similar circumstances, the smaller look-ahead time which results in less efficient resolution manoeuvres and the sometimes false/nuisance alerts due to missing intent information. The optimal CD&R system (in terms of costs versus benefits) has been suggested to be state-based CD&R with the addition of intended or target flight level. This combination of state-based CD&R with a limited amount of intent provides "the best of both worlds". Studying this CD&R system is still an open issue.

Parabolic Flight Investigation for Advanced Exercise Concept Hardware Hybrid Ultimate Lifting Kit (HULK)

NASA Technical Reports Server (NTRS)

Weaver, A. S.; Funk, J. H.; Funk, N. W.; Sheehan, C. C.; Humphreys, B. T.; Perusek, G. P.

2015-01-01

Long-duration space flight poses many hazards to the health of the crew. Among those hazards is the physiological deconditioning of the musculoskeletal and cardiovascular systems due to prolonged exposure to microgravity. To combat this erosion of physical condition space flight may take on the crew, the Human Research Program (HRP) is charged with developing Advanced Exercise Concepts to maintain astronaut health and fitness during long-term missions, while keeping device mass, power, and volume to a minimum. The goal of this effort is to preserve the physical capability of the crew to perform mission critical tasks in transit and during planetary surface operations. The HULK is a pneumatic-based exercise system, which provides both resistive and aerobic modes to protect against human deconditioning in microgravity. Its design targeted the International Space Station (ISS) Advanced Resistive Exercise Device (ARED) high level performance characteristics and provides up to 600 foot pounds resitive loading with the capability to allow for eccentric to concentric (E:C) ratios of higher than 1:1 through a DC motor assist component. The device's rowing mode allows for high cadence aerobic activity. The HULK parabolic flight campaign, conducted through the NASA Flight Opportunities Program at Ellington Field, resulted in the creation of device specific data sets including low fidelity motion capture, accelerometry and both inline and ground reaction forces. These data provide a critical link in understanding how to vibration isolate the device in both ISS and space transit applications. Secondarily, the study of human exercise and associated body kinematics in microgravity allows for more complete understanding of human to machine interface designs to allow for maximum functionality of the device in microgravity.

The Clock Is Ticking

NASA Technical Reports Server (NTRS)

Gundo, Dan

2003-01-01

Recently, I worked on creating a one-of-a-kind device for a Space Station group studying exercise physiology at another NASA Center. They approached my department at Ames Research Center to design and build an exercise bed that allowed users to perform the motions that they needed for ground-based research. The real challenge was that they needed the device designed, built, and delivered in just one month. The bed was intended to simulate doing squats while in a horizontal position as if on a moving sled. They wanted to incorporate a resistant device called an Interim Resistive Exercise Device (IRED), an adjustable cable tied into a reel to provide a measured amount of resistance. This device was used on the Station for exercising in space; we were taking the same resistant reel and incorporating it in this bed. In the early stages of a design project, I communicate with a customer as much as I can and as often as they will tolerate. There s a lot of learning that needs to go on, and I prefer to spend a little bit of extra time here because that can save a lot of time later. In the beginning, you need to volley the information back-and-forth, so that you understand the customer s requirements and they know what you re capable of doing.

Mobile selected ion flow tube mass spectrometry (SIFT-MS) devices and their use for pollution exposure monitoring in breath and ambient air-pilot study.

PubMed

Storer, Malina; Salmond, Jennifer; Dirks, Kim N; Kingham, Simon; Epton, Michael

2014-09-01

Studies of health effects of air pollution exposure are limited by inability to accurately determine dose and exposure of air pollution in field trials. We explored the feasibility of using a mobile selected ion flow tube mass spectrometry (SIFT-MS) device, housed in a van, to determine ambient air and breath levels of benzene, xylene and toluene following exercise in areas of high motor vehicle traffic. The breath toluene, xylene and benzene concentration of healthy subjects were measured before and after exercising close to a busy road. The concentration of the volatile organic compounds (VOCs), in ambient air were also analysed in real time. Exercise close to traffic pollution is associated with a two-fold increase in breath VOCs (benzene, xylene and toluene) with levels returning to baseline within 20 min. This effect is not seen when exercising away from traffic pollution sources. Situating the testing device 50 m from the road reduced any confounding due to VOCs in the inspired air prior to the breath testing manoeuvre itself. Real-time field testing for air pollution exposure is possible using a mobile SIFT-MS device. This device is suitable for exploring exposure and dose relationships in a number of large scale field test scenarios.

Self-generating oscillating pressure exercise device

NASA Technical Reports Server (NTRS)

Watenpaugh, Donald E. (Inventor)

1994-01-01

An exercise device, especially suitable for zero gravity workouts, has a collapsible chamber which generates negative pressure on the lower portion of a body situated therein. The negative pressure is generated by virtue of leg, hand and shoulder interaction which contracts and expands the chamber about the person and by virtue of air flow regulation by valve action.

Technical aspects of oxygen saving devices.

PubMed

Brambilla, I; Arlati, S; Chiusa, I; Micallef, E

1990-01-01

Oxygen economizing devices have been extensively studied, both at rest and during muscular exercise, in an attempt to increase the autonomy of a portable oxygen apparatus. The aim of this study is threefold: first, to suggest a simple method to verify in a simple way the technical accuracy of a demand flow oxygen delivery device; second, to suggest how we can monitor in a simple way the clinical efficacy of an economizer; and third, to remember that we can utilize an oxygen saving device to give a better protection than nasal prongs against the worsening of HbO2 desaturation induced by exercise.

Federal research, development, and demonstration priorities for carbon dioxide removal in the United States

NASA Astrophysics Data System (ADS)

Sanchez, Daniel L.; Amador, Giana; Funk, Jason; Mach, Katharine J.

2018-01-01

Atmospheric carbon dioxide removal (CDR) technologies may be critical to achieving deep decarbonization. Yet a lack of technical and commercial maturity of CDR technologies hinders potential deployment. Needs for commercialization span research, development, and demonstration (RD&D) activities, including development of new materials, reactors, and processes, and rigorous monitoring of a portfolio of demonstration projects. As a world leader in supporting science and engineering, the United States (US) can play an important role in reducing costs and clarifying the sustainable scale of CDR. To date, federal agencies have focused on voluntary or piecemeal CDR programs. Here, we present a synthesis of research and developement needs, relevant agency authority, barriers to coordination, and interventions to enhance RD&D across the federal government of the US. On the basis of agency authority and expertise, the Department of Energy, Department of Agriculture, Department of the Interior, National Oceanic and Atmospheric Administration, and National Science Foundation are most central to conducting research, funding projects, monitoring effects, and promulgating regulations. Key enablers for successful programs include embracing technological diversity and administrative efficiency, fostering agency buy-in, and achieving commercial deployment. Based on these criteria, the executive branch could effectively coordinate RD&D strategy through two complementary pathways: (1) renewing intra-agency commitment to CDR in five primary agencies, including both research and demonstration, and (2) coordinating research prioritization and outcomes across agencies, led by the Office of Science and Technology Policy and loosely based on the National Nanotechnology Initiative. Both pathways can be stimulated by executive order or Congressional mandate. Executive branch implementation can begin at any time; future Farm and Energy Bills provide legislative vehicles for enhancing programs.

Cerebrospinal Fluid proNGF: A Putative Biomarker for Early Alzheimer’s Disease

PubMed Central

Counts, Scott E.; He, Bin; Prout, John G.; Michalski, Bernadeta; Farotti, Lucia; Fahnestock, Margaret; Mufson, Elliott J.

2018-01-01

The discovery of biomarkers for the onset of Alzheimer’s disease (AD) is essential for disease modification strategies. To date, AD biomarker studies have focused on brain imaging and cerebrospinal fluid (CSF) changes in amyloid-β (Aβ) peptide and tau proteins. While reliable to an extent, this panel could be improved by the inclusion of novel biomarkers that optimize sensitivity and specificity. In this study, we determined whether CSF levels of the nerve growth factor (NGF) precursor protein, proNGF, increased during the progression of AD, mirroring its up regulation in postmortem brain samples of people who died with a clinical diagnosis of mild cognitive impairment (MCI) or AD. Immunoblot analysis was performed on ventricular CSF harvested from participants in the Rush Religious Orders Study with an antemortem clinical diagnosis of no cognitive impairment (NCI), amnestic MCI (aMCI, a putative prodromal AD stage), or mild/moderate AD. ProNGF levels were increased 55% in aMCI and 70% in AD compared to NCI. Increasing CSF proNGF levels correlated with impairment on cognitive test scores. In a complementary study, we found that proNGF was significantly increased by 30% in lumbar CSF samples derived from patients with a clinical dementia rating (CDR) of 0.5 or 1 compared to those with a CDR = 0. Notably, proNGF/Aβ1-42 levels were 50% higher in CDR 0.5 and CDR 1 compared to CDR 0 controls. By contrast, ELISA measurements of CSF brain-derived neurotrophic factor (BDNF) did not distinguish aMCI from NCI. Taken together, these results suggest that proNGF protein levels may augment the diagnostic accuracy of currently used CSF biomarker panels. PMID:26825093

Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification

PubMed Central

Jeliazkov, Jeliazko R.; Sljoka, Adnan; Kuroda, Daisuke; Tsuchimura, Nobuyuki; Katoh, Naoki; Tsumoto, Kouhei; Gray, Jeffrey J.

2018-01-01

Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibody’s antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the complementarity determining region (CDR) loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop for thousands of recent homology models of the human peripheral blood cell antibody repertoire using rigidity theory. We found no clear delineation in the flexibility of naïve and antigen-experienced antibodies. To account for possible sources of error, we additionally analyzed hundreds of human and mouse antibodies in the Protein Data Bank through both rigidity theory and B-factor analysis. By both metrics, we observed only a slight decrease in the CDR-H3 loop flexibility when comparing affinity matured antibodies to naïve antibodies, and the decrease was not as drastic as previously reported. Further analysis, incorporating molecular dynamics simulations, revealed a spectrum of changes in flexibility. Our results suggest that rigidification may be just one of many biophysical mechanisms for increasing affinity. PMID:29545810

Elderly Japanese emigrants to Brazil before World War II: II. Prevalence of senile dementia.

PubMed

Meguro, K; Meguro, M; Caramelli, P; Ishizaki, J; Ambo, H; Chubaci, R Y; Hamada, G S; Nitrini, R; Yamadori, A

2001-08-01

We previously showed the prevalence of dementia in the town of Tajiri (Miyagi Prefecture, Japan), and found it to be 8.0%. The first population-based study on dementia in Brazil (Catanduva) disclosed the prevalence as being 7.1%. To evaluate the effects of environment on development of dementia, elderly Japanese immigrants living in Brazil were examined. Brazil is the country with the largest number of Japanese immigrants. All immigrants aged 65 years and over from Miyagi Prefecture, living in the four cities of the São Paulo Metropolitan area were targeted (n = 192). We were able to examine 166 subjects (86.5%). The diagnosis of dementia was based on the DSM-IV with the severity assessed by the CDR (clinical dementia rating) scales. The cognitive ability screening instrument (CASI) was used for neuropsychological assessment. Thirteen subjects were diagnosed with dementia, CDR 1-3, the prevalence being 7.8%. Older subjects suffered more from dementia, and, paradoxically, the more highly educated subjects also suffered more. All the CASI items, except for long-term memory and visual construction, significantly deteriorated in the CDR 0.5 group compared with the CDR 0 group. The prevalence of dementia was not thought to be affected by environmental factors. A paradoxically higher rate of dementia in the more educated subjects was probably due to the historical problems of the immigrants. Intact CASI item long-term memory in the CDR 0.5 group indicated that suspected dementia patients could maintain this function. This is the first epidemiological study on dementia in elderly Japanese immigrants in Brazil. Copyright 2001 John Wiley & Sons, Ltd.

The Manchester Acute Coronary Syndromes (MACS) decision rule for suspected cardiac chest pain: derivation and external validation

PubMed Central

Body, Richard; Carley, Simon; McDowell, Garry; Pemberton, Philip; Burrows, Gillian; Cook, Gary; Lewis, Philip S; Smith, Alexander; Mackway-Jones, Kevin

2014-01-01

Objective We aimed to derive and validate a clinical decision rule (CDR) for suspected cardiac chest pain in the emergency department (ED). Incorporating information available at the time of first presentation, this CDR would effectively risk-stratify patients and immediately identify: (A) patients for whom hospitalisation may be safely avoided; and (B) high-risk patients, facilitating judicious use of resources. Methods In two sequential prospective observational cohort studies at heterogeneous centres, we included ED patients with suspected cardiac chest pain. We recorded clinical features and drew blood on arrival. The primary outcome was major adverse cardiac events (MACE) (death, prevalent or incident acute myocardial infarction, coronary revascularisation or new coronary stenosis >50%) within 30 days. The CDR was derived by logistic regression, considering reliable (κ>0.6) univariate predictors (p<0.05) for inclusion. Results In the derivation study (n=698) we derived a CDR including eight variables (high sensitivity troponin T; heart-type fatty acid binding protein; ECG ischaemia; diaphoresis observed; vomiting; pain radiation to right arm/shoulder; worsening angina; hypotension), which had a C-statistic of 0.95 (95% CI 0.93 to 0.97) implying near perfect diagnostic performance. On external validation (n=463) the CDR identified 27.0% of patients as ‘very low risk’ and potentially suitable for discharge from the ED. 0.0% of these patients had prevalent acute myocardial infarction and 1.6% developed MACE (n=2; both coronary stenoses without revascularisation). 9.9% of patients were classified as ‘high-risk’, 95.7% of whom developed MACE. Conclusions The Manchester Acute Coronary Syndromes (MACS) rule has the potential to safely reduce unnecessary hospital admissions and facilitate judicious use of high dependency resources. PMID:24780911

Brain bank of the Brazilian aging brain study group - a milestone reached and more than 1,600 collected brains.

PubMed

Grinberg, Lea Tenenholz; Ferretti, Renata Eloah de Lucena; Farfel, José Marcelo; Leite, Renata; Pasqualucci, Carlos Augusto; Rosemberg, Sérgio; Nitrini, Ricardo; Saldiva, Paulo Hilário Nascimento; Filho, Wilson Jacob

2007-01-01

Brain banking remains a necessity for the study of aging brain processes and related neurodegenerative diseases. In the present paper, we report the methods applied at and the first results of the Brain Bank of the Brazilian Aging Brain Study Group (BBBABSG) which has two main aims: (1) To collect a large number of brains of elderly comprising non-demented subjects and a large spectrum of pathologies related to aging brain processes, (2) To provide quality material to a multidisciplinar research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases. The subjects are selected from the Sao Paulo Autopsy Service. Brain parts are frozen and fixated. CSF, carotids, kidney, heart and blood are also collected and DNA is extracted. The neuropathological examinations are carried out based on accepted criteria, using immunohistochemistry. Functional status are assessed through a collateral source based on a clinical protocol. Protocols are approved by the local ethics committee and a written informed consent form is obtained. During the first 21 months, 1,602 samples were collected and were classified by Clinical Dementia Rating as CDR0: 65.7%; CDR0.5:12.6%, CDR1:8.2%, CDR2:5.4%, and CDR3:8.1%. On average, the cost for the processing each case stood at 400 US dollars. To date, 14 laboratories have been benefited by the BBBABSG. The high percentage of non- demented subjects and the ethnic diversity of this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since BBBABSG outcomes may provide investigators the answers to some additional questions.

Mediator Tail Module Is Required for Tac1-Activated CDR1 Expression and Azole Resistance in Candida albicans.

PubMed

Liu, Zhongle; Myers, Lawrence C

2017-11-01

The human fungal pathogen Candida albicans develops drug resistance after long-term exposure to azole drugs in the treatment of chronic candidiasis. Gain-of-function (GOF) mutations in the transcription factor Tac1 and the consequent expression of its targets, drug efflux pumps Cdr1 and Cdr2, are a common mechanism by which C. albicans acquires fluconazole resistance. The mechanism by which GOF mutations hyperactivate Tac1 is currently unknown. Here, we define a transcriptional activation domain (TAD) at the C terminus of Tac1. GOF mutations within the Tac1 TAD, outside the context of full-length Tac1, generally do not enhance its absolute potential as a transcriptional activator. Negative regulation of the Tac1 TAD by the Tac1 middle region is necessary for the activating effect of GOF mutations or fluphenazine to be realized. We have found that full-length Tac1, when hyperactivated by xenobiotics or GOF mutations, facilitates the recruitment of the Mediator coactivator complex to the CDR1 promoter. Azole resistance and the activation of Tac1 target genes, such as CDR1 , are dependent on the Tac1 TAD and subunits of the Mediator tail module. The dependence of different Tac1 target promoters on the Mediator tail module, however, varies widely. Lastly, we show that hyperactivation of Tac1 is correlated with its Mediator-dependent phosphorylation, a potentially useful biomarker for Tac1 hyperactivation. The role of Mediator in events downstream of Tac1 hyperactivation in fluconazole-resistant clinical isolates is complex and provides opportunities and challenges for therapeutic intervention. Copyright © 2017 American Society for Microbiology.

A better understanding of POLDER's cloud droplet size retrieval: impact of cloud horizontal inhomogeneity and directional sampling

NASA Astrophysics Data System (ADS)

Shang, H.; Chen, L.; Bréon, F.-M.; Letu, H.; Li, S.; Wang, Z.; Su, L.

2015-07-01

The principles of the Polarization and Directionality of the Earth's Reflectance (POLDER) cloud droplet size retrieval requires that clouds are horizontally homogeneous. Nevertheless, the retrieval is applied by combining all measurements from an area of 150 km × 150 km to compensate for POLDER's insufficient directional sampling. Using the POLDER-like data simulated with the RT3 model, we investigate the impact of cloud horizontal inhomogeneity and directional sampling on the retrieval, and then analyze which spatial resolution is potentially accessible from the measurements. Case studies show that the sub-scale variability in droplet effective radius (CDR) can mislead both the CDR and effective variance (EV) retrievals. Nevertheless, the sub-scale variations in EV and cloud optical thickness (COT) only influence the EV retrievals and not the CDR estimate. In the directional sampling cases studied, the retrieval is accurate using limited observations and is largely independent of random noise. Several improvements have been made to the original POLDER droplet size retrieval. For example, the measurements in the primary rainbow region (137-145°) are used to ensure accurate large droplet (> 15 μm) retrievals and reduce the uncertainties caused by cloud heterogeneity. We apply the improved method using the POLDER global L1B data for June 2008, the new CDR results are compared with the operational CDRs. The comparison show that the operational CDRs tend to be underestimated for large droplets. The reason is that the cloudbow oscillations in the scattering angle region of 145-165° are weak for cloud fields with CDR > 15 μm. Lastly, a sub-scale retrieval case is analyzed, illustrating that a higher resolution, e.g., 42 km × 42 km, can be used when inverting cloud droplet size parameters from POLDER measurements.

A Bayesian hierarchical model for mortality data from cluster-sampling household surveys in humanitarian crises.

PubMed

Heudtlass, Peter; Guha-Sapir, Debarati; Speybroeck, Niko

2018-05-31

The crude death rate (CDR) is one of the defining indicators of humanitarian emergencies. When data from vital registration systems are not available, it is common practice to estimate the CDR from household surveys with cluster-sampling design. However, sample sizes are often too small to compare mortality estimates to emergency thresholds, at least in a frequentist framework. Several authors have proposed Bayesian methods for health surveys in humanitarian crises. Here, we develop an approach specifically for mortality data and cluster-sampling surveys. We describe a Bayesian hierarchical Poisson-Gamma mixture model with generic (weakly informative) priors that could be used as default in absence of any specific prior knowledge, and compare Bayesian and frequentist CDR estimates using five different mortality datasets. We provide an interpretation of the Bayesian estimates in the context of an emergency threshold and demonstrate how to interpret parameters at the cluster level and ways in which informative priors can be introduced. With the same set of weakly informative priors, Bayesian CDR estimates are equivalent to frequentist estimates, for all practical purposes. The probability that the CDR surpasses the emergency threshold can be derived directly from the posterior of the mean of the mixing distribution. All observation in the datasets contribute to the estimation of cluster-level estimates, through the hierarchical structure of the model. In a context of sparse data, Bayesian mortality assessments have advantages over frequentist ones already when using only weakly informative priors. More informative priors offer a formal and transparent way of combining new data with existing data and expert knowledge and can help to improve decision-making in humanitarian crises by complementing frequentist estimates.

Collateral transgression of planetary boundaries due to climate engineering by terrestrial carbon dioxide removal

NASA Astrophysics Data System (ADS)

Heck, Vera; Donges, Jonathan F.; Lucht, Wolfgang

2016-10-01

The planetary boundaries framework provides guidelines for defining thresholds in environmental variables. Their transgression is likely to result in a shift in Earth system functioning away from the relatively stable Holocene state. As the climate system is approaching critical thresholds of atmospheric carbon, several climate engineering methods are discussed, aiming at a reduction of atmospheric carbon concentrations to control the Earth's energy balance. Terrestrial carbon dioxide removal (tCDR) via afforestation or bioenergy production with carbon capture and storage are part of most climate change mitigation scenarios that limit global warming to less than 2 °C. We analyse the co-evolutionary interaction of societal interventions via tCDR and the natural dynamics of the Earth's carbon cycle. Applying a conceptual modelling framework, we analyse how the degree of anticipation of the climate problem and the intensity of tCDR efforts with the aim of staying within a "safe" level of global warming might influence the state of the Earth system with respect to other carbon-related planetary boundaries. Within the scope of our approach, we show that societal management of atmospheric carbon via tCDR can lead to a collateral transgression of the planetary boundary of land system change. Our analysis indicates that the opportunities to remain in a desirable region within carbon-related planetary boundaries only exist for a small range of anticipation levels and depend critically on the underlying emission pathway. While tCDR has the potential to ensure the Earth system's persistence within a carbon-safe operating space under low-emission pathways, it is unlikely to succeed in a business-as-usual scenario.

Manufacturing and NDE of Large Composite Structures for Space Transportation at MSFC

NASA Technical Reports Server (NTRS)

McGill, Preston; Russell, Sam

2000-01-01

This paper presents the Marshall Space Flight Center's (MSFC's) vision to manufacture, increase safety and reduce the cost of launch vehicles. Nondestructive evaluations of large composite structures are tested for space transportation at MSFC. The topics include: 1) 6 1/2 Generations of Airplanes in a Century; 2) Shuttle Safety Upgrades; 3) Generations of Reusable Launch Vehicles; 4) RLV Technology Demonstration Path; 5) Second Generation; 6) Key NASA Requirements; 7) X-33 Elements; 8) Future-X Pathfinder Projects and Experiments; 9) Focus Area Technical Goals; 10) X-34 Expanded View; 11) X-38 Spacecraft with De-Orbit Propulsion Stage (DPS); 12) Deorbit Module (DM) Critical Design Review (CDR) Design; 13) Forward Structural Adapter (FSA) CDR Design; 14) X-38 DPS CDR Design; 15) RLV Focused Propulsion Technologies; and 16) Challenges in Technology. This paper is presented in viewgraph form.

Efficacy of a heat exchanger mask in cold exercise-induced asthma.

PubMed

Beuther, David A; Martin, Richard J

2006-05-01

To determine the efficacy of a novel mask device in limiting cold air exercise-induced decline in lung function in subjects with a history of exercise-induced asthma (EIA). In spite of appropriate medical therapy, many asthma patients are limited in cold weather activities. In study 1, 13 asthmatic subjects performed two randomized, single-blind treadmill exercise tests while breathing cold air (- 25 to - 15 degrees C) through a placebo or active heat exchanger mask. In study 2, five subjects with EIA performed three treadmill exercise tests while breathing cold air: one test using the heat exchanger mask, one test without the mask but with albuterol pretreatment, and one test with neither the mask nor albuterol pretreatment (unprotected exercise). For all studies, spirometry was performed before and at 5, 15, and 30 min after exercise challenge. For both studies, a total of 15 subjects with a history of asthma symptoms during cold air exercise were recruited. In study 1, the mean decrease (+/- SE) in FEV1 was 19 +/- 4.9% with placebo, and 4.3 +/- 1.6% with the active device (p = 0.0002). The mean decrease in maximum mid-expiratory flow (FEF(25-75)) was 31 +/- 5.7% with placebo and 4.7 +/- 1.7% with the active device (p = 0.0002). In study 2, the mean decrease in FEV1 was 6.3 +/- 3.9%, 11 +/- 3.7%, and 28 +/- 10% for the heat exchanger mask, albuterol pretreatment, and unprotected exercises, respectively (p = 0.4375 for mask vs albuterol, p = 0.0625 for mask vs unprotected exercise). The mean decrease in FEF(25-75) was 10 +/- 4.8%, 23 +/- 6.0%, and 36 +/- 11%, respectively (p = 0.0625 for mask vs albuterol, p = 0.0625 for mask vs unprotected exercise). This heat exchanger mask blocks cold exercise-induced decline in lung function at least as effectively as albuterol pretreatment.

Performance comparison of the MOXY and PortaMon near-infrared spectroscopy muscle oximeters at rest and during exercise

NASA Astrophysics Data System (ADS)

McManus, Chris J.; Collison, Jay; Cooper, Chris E.

2018-01-01

The purpose of the study was to compare muscle oxygenation as measured by two portable, wireless near-infrared spectroscopy (NIRS) devices under resting and dynamic conditions. A recently developed low-cost NIRS device (MOXY) was compared against an established PortaMon system that makes use of the spatially resolved spectroscopy algorithm. The influence of increasing external pressure on tissue oxygen saturation index (TSI) indicated that both devices are stable between 2 and 20 mmHg. However, above this pressure, MOXY reports declining TSI values. Analysis of adipose tissue thickness (ATT) and TSI shows a significant, nonlinear difference between devices at rest. The devices report similar TSI (%) values at a low ATT (<7 mm) (PortaMon minus MOXY difference is +1.1±2.8%) with the major subsequent change between the devices occurring between 7 and 10 mm at ATT values >10 mm the difference remains constant (-14.7±2.8%). The most likely explanation for this difference is the small source-detector separation (2.5 cm) in the MOXY resulting in lower tissue penetration into muscle in subjects with higher ATT. Interday test-retest reliability of resting TSI was evaluated on five separate occasions, with the PortaMon reporting a lower coefficient of variation (1.8% to 2.5% versus 5.7% to 6.2%). In studies on male subjects with low ATT, decreases in the TSI were strongly correlated during isometric exercise, arterial occlusion, and incremental arm crank exercise. However, the MOXY reports a greater dynamic range, particularly during ischemia induced by isometric contraction or occlusion (Δ74.3% versus Δ43.7% hyperemia MAX-occlusion MIN). This study shows that in this subject group both MOXY and PortaMon produce physiologically credible TSI measures during rest and exercise. However, the absolute values obtained during exercise are generally not comparable between devices unless corrected by physiological calibration following an arterial occlusion.

Combat Service Support (CSS) Enabler Functional Assessment (CEFA)

DTIC Science & Technology

1998-07-01

CDR), Combined Arms Support Command (CASCOM) with a tool to aid decision making related to mitigating E/I peacetime (programmatic) and wartime risks...not be fielded by Fiscal Year (FY) 10. Based on their estimates, any decisions , especially reductions in manpower, which rely on the existence of the E...Support (CSS) enablers/initiatives (E/I), thereby providing the Commander (CDR), Combined Arms Support Command (CASCOM) with a tool to aid decision

Verification of a New NOAA/NSIDC Passive Microwave Sea-Ice Concentration Climate Record

NASA Technical Reports Server (NTRS)

Meier, Walter N.; Peng, Ge; Scott, Donna J.; Savoie, Matt H.

2014-01-01

A new satellite-based passive microwave sea-ice concentration product developed for the National Oceanic and Atmospheric Administration (NOAA)Climate Data Record (CDR) programme is evaluated via comparison with other passive microwave-derived estimates. The new product leverages two well-established concentration algorithms, known as the NASA Team and Bootstrap, both developed at and produced by the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center (GSFC). The sea ice estimates compare well with similar GSFC products while also fulfilling all NOAA CDR initial operation capability (IOC) requirements, including (1) self describing file format, (2) ISO 19115-2 compliant collection-level metadata,(3) Climate and Forecast (CF) compliant file-level metadata, (4) grid-cell level metadata (data quality fields), (5) fully automated and reproducible processing and (6) open online access to full documentation with version control, including source code and an algorithm theoretical basic document. The primary limitations of the GSFC products are lack of metadata and use of untracked manual corrections to the output fields. Smaller differences occur from minor variations in processing methods by the National Snow and Ice Data Center (for the CDR fields) and NASA (for the GSFC fields). The CDR concentrations do have some differences from the constituent GSFC concentrations, but trends and variability are not substantially different.

Genetic alterations and tumor immune attack in Yo paraneoplastic cerebellar degeneration.

PubMed

Small, Mathilde; Treilleux, Isabelle; Couillault, Coline; Pissaloux, Daniel; Picard, Géraldine; Paindavoine, Sandrine; Attignon, Valery; Wang, Qing; Rogemond, Véronique; Lay, Stéphanie; Ray-Coquard, Isabelle; Pfisterer, Jacobus; Joly, Florence; Du Bois, Andreas; Psimaras, Dimitri; Bendriss-Vermare, Nathalie; Caux, Christophe; Dubois, Bertrand; Honnorat, Jérôme; Desestret, Virginie

2018-04-01

Paraneoplastic cerebellar degenerations with anti-Yo antibodies (Yo-PCD) are rare syndromes caused by an auto-immune response against neuronal antigens (Ags) expressed by tumor cells. However, the mechanisms responsible for such immune tolerance breakdown are unknown. We characterized 26 ovarian carcinomas associated with Yo-PCD for their tumor immune contexture and genetic status of the 2 onconeural Yo-Ags, CDR2 and CDR2L. Yo-PCD tumors differed from the 116 control tumors by more abundant T and B cells infiltration occasionally organized in tertiary lymphoid structures harboring CDR2L protein deposits. Immune cells are mainly in the vicinity of apoptotic tumor cells, revealing tumor immune attack. Moreover, contrary to un-selected ovarian carcinomas, 65% of our Yo-PCD tumors presented at least one somatic mutation in Yo-Ags, with a predominance of missense mutations. Recurrent gains of the CDR2L gene with tumor protein overexpression were also present in 59% of Yo-PCD patients. Overall, each Yo-PCD ovarian carcinomas carried at least one genetic alteration of Yo-Ags. These data demonstrate an association between massive infiltration of Yo-PCD tumors by activated immune effector cells and recurrent gains and/or mutations in autoantigen-encoding genes, suggesting that genetic alterations in tumor cells trigger immune tolerance breakdown and initiation of the auto-immune disease.

ARGALI: an automatic cup-to-disc ratio measurement system for glaucoma detection and AnaLysIs framework

NASA Astrophysics Data System (ADS)

Liu, J.; Wong, D. W. K.; Lim, J. H.; Li, H.; Tan, N. M.; Wong, T. Y.

2009-02-01

Glaucoma is an irreversible ocular disease leading to permanent blindness. However, early detection can be effective in slowing or halting the progression of the disease. Physiologically, glaucoma progression is quantified by increased excavation of the optic cup. This progression can be quantified in retinal fundus images via the optic cup to disc ratio (CDR), since in increased glaucomatous neuropathy, the relative size of the optic cup to the optic disc is increased. The ARGALI framework constitutes of various segmentation approaches employing level set, color intensity thresholds and ellipse fitting for the extraction of the optic cup and disc from retinal images as preliminary steps. Following this, different combinations of the obtained results are then utilized to calculate the corresponding CDR values. The individual results are subsequently fused using a neural network. The learning function of the neural network is trained with a set of 100 retinal images For testing, a separate set 40 images is then used to compare the obtained CDR against a clinically graded CDR, and it is shown that the neural network-based result performs better than the individual components, with 96% of the results within intra-observer variability. The results indicate good promise for the further development of ARGALI as a tool for the early detection of glaucoma.

Executive function impairment in community elderly subjects with questionable dementia.

PubMed

Lam, Linda C W; Lui, Victor W C; Chiu, Helen F K; Chan, Sandra S M; Tam, Cindy W C

2005-01-01

The neurocognitive profile of community-dwelling Chinese subjects with 'questionable' dementia was studied. One hundred and fifty-four ambulatory Chinese subjects were recruited from local social centers for the elderly. Each subject was examined using the Clinical Dementia Rating (CDR), the Cantonese version of the Mini-Mental State Examination (CMMSE), the Chinese version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Category Verbal Fluency Test (CVFT), digit and visual span tests, and the Cambridge Neurological Inventory. The neurocognitive profile of nondemented subjects (CDR 0) was compared with that of subjects with 'questionable' dementia (CDR 0.5). Subjects with 'questionable' dementia were older, and had lower educational levels and global cognitive assessment scores than the controls (CMMSE and ADAS-Cog; t tests, p < 0.001). In addition, they also had significantly lower scores in delayed recall, reverse span, verbal fluency tests and worse performance in complex motor tasks related to executive function (Mann-Whitney tests, p < 0.001). Logistic regression analysis revealed that ADAS-Cog, CVFT, and reverse visual span were significant predictors for the CDR of 'questionable' dementia. Aside from memory impairment, executive function deficits were also present in subjects with 'questionable' dementia. To identify groups cognitively at risk for dementia, concomitant assessments of memory and executive function are suggested.

Carbon Dioxide Removal and the futures market

NASA Astrophysics Data System (ADS)

Lockley, A.; Coffman, D.

2016-12-01

Futures contracts are exchange-traded financial instruments that enable parties to fix a price in advance, for performance on a contract at some later date. Forward contracts also entail future settlement, but they are traded over-the-counter between two independent parties. Both futures and forward contracts are commonly used in commodities trading, as producers seek financial security when planning production. We discuss the use of potential use of exchange-traded futures contracts in Carbon Dioxide Removal (CDR) markets. We conclude that they have one principal advantage (in that they give near-term price security to current polluters), and one principal disadvantage (in that a combination of high price volatility and high trade volume means contracts issued by the private sector may cause systemic economic risk). Accordingly, we note the potential for the development of futures markets in CDR, but urge great caution in the use of this approach. In particular, we consider the use of regulated markets: to ensure contracts are more reliable, and that moral hazard is minimised. Whilst regulation offers generally increased assurances, we identify major insufficiencies with this approach - finding it generally inadequate. In conclusion, we suggest that only governments can realistically support long-term CDR futures markets. We note existing long-term CDR plans by governments, and suggest the use of state-backed futures for supporting these assurances.

Improved prediction of antibody VL–VH orientation

PubMed Central

Marze, Nicholas A.; Lyskov, Sergey; Gray, Jeffrey J.

2016-01-01

Antibodies are important immune molecules with high commercial value and therapeutic interest because of their ability to bind diverse antigens. Computational prediction of antibody structure can quickly reveal valuable information about the nature of these antigen-binding interactions, but only if the models are of sufficient quality. To achieve high model quality during complementarity-determining region (CDR) structural prediction, one must account for the VL–VH orientation. We developed a novel four-metric VL–VH orientation coordinate frame. Additionally, we extended the CDR grafting protocol in RosettaAntibody with a new method that diversifies VL–VH orientation by using 10 VL–VH orientation templates rather than a single one. We tested the multiple-template grafting protocol on two datasets of known antibody crystal structures. During the template-grafting phase, the new protocol improved the fraction of accurate VL–VH orientation predictions from only 26% (12/46) to 72% (33/46) of targets. After the full RosettaAntibody protocol, including CDR H3 remodeling and VL–VH re-orientation, the new protocol produced more candidate structures with accurate VL–VH orientation than the standard protocol in 43/46 targets (93%). The improved ability to predict VL–VH orientation will bolster predictions of other parts of the paratope, including the conformation of CDR H3, a grand challenge of antibody homology modeling. PMID:27276984

A Long-Term and Reproducible Passive Microwave Sea Ice Concentration Data Record for Climate Studies and Monitoring

NASA Technical Reports Server (NTRS)

Peng, G.; Meier, W. N.; Scott, D. J.; Savoie, M. H.

2013-01-01

A long-term, consistent, and reproducible satellite-based passive microwave sea ice concentration climate data record (CDR) is available for climate studies, monitoring, and model validation with an initial operation capability (IOC). The daily and monthly sea ice concentration data are on the National Snow and Ice Data Center (NSIDC) polar stereographic grid with nominal 25 km × 25 km grid cells in both the Southern and Northern Hemisphere polar regions from 9 July 1987 to 31 December 2007. The data files are available in the NetCDF data format at http://nsidc.org/data/g02202.html and archived by the National Climatic Data Center (NCDC) of the National Oceanic and Atmospheric Administration (NOAA) under the satellite climate data record program (http://www.ncdc.noaa.gov/cdr/operationalcdrs.html). The description and basic characteristics of the NOAA/NSIDC passive microwave sea ice concentration CDR are presented here. The CDR provides similar spatial and temporal variability as the heritage products to the user communities with the additional documentation, traceability, and reproducibility that meet current standards and guidelines for climate data records. The data set, along with detailed data processing steps and error source information, can be found at http://dx.doi.org/10.7265/N5B56GN3.

National Ignition Facility: Experimental plan

NASA Astrophysics Data System (ADS)

1994-05-01

As part of the Conceptual Design Report (CDR) for the National Ignition Facility (NIF), scientists from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Sandia National Laboratory (SNL), the University of Rochester's Laboratory for Laser Energetics (UR/LLE), and EG&G formed an NIF Target Diagnostics Working Group. The purpose of the Target Diagnostics Working Group is to prepare conceptual designs of target diagnostics for inclusion in the facility CDR and to determine how these specifications impact the CDR. To accomplish this, a subgroup has directed its efforts at constructing an approximate experimental plan for the ignition campaign of the NIF CDR. The results of this effort are contained in this document, the Experimental Plan for achieving fusion ignition in the NIF. This group initially concentrated on the flow-down requirements of the experimental campaign leading to ignition, which will dominate the initial efforts of the NIF. It is envisaged, however, that before ignition, there will be parallel campaigns supporting weapons physics, weapons effects, and other research. This plan was developed by analyzing the sequence of activities required to finally fire the laser at the level of power and precision necessary to achieve the conditions of an ignition hohlraum target, and to then use our experience in activating and running Nova experiments to estimate the rate of completing these activities.

Exercise physiology, testing, and training in patients supported by a left ventricular assist device.

PubMed

Loyaga-Rendon, Renzo Y; Plaisance, Eric P; Arena, Ross; Shah, Keyur

2015-08-01

The left ventricular assist device (LVAD) is an accepted treatment alternative for the management of end-stage heart failure. As we move toward implantation of LVADs in less severe cases of HF, scrutiny of functional capacity and quality of life becomes more important. Patients demonstrate improvements in exercise capacity after LVAD implantation, but the effect is less than predicted. Exercise training produces multiple beneficial effects in heart failure patients, which would be expected to improve quality of life. In this review, we describe factors that are thought to participate in the persistent exercise impairment in LVAD-supported patients, summarize current knowledge about the effect of exercise training in LVAD-supported patients, and suggest areas for future research. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Wakata uses Advanced Resistive Exercise Device (ARED) in Node 1 Unity

NASA Image and Video Library

2009-03-22

ISS018-E-042651 (22 March 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 18 flight engineer, uses the short bar for the advanced Resistive Exercise Device (aRED) equipment to perform upper body strengthening pull-ups in the Unity node of the International Space Station while Space Shuttle Discovery (STS-119) remains docked with the station.

Design of a resistive exercise device for use on the Space Shuttle

NASA Technical Reports Server (NTRS)

Carlson, Dennis L.; Durrani, Mohammed; Redilla, Christi L.

1992-01-01

The National Aeronautics and Space Administration in conjunction with the Universities Space Research Association sponsored the design of a Resistive Exercise Device (RED) for use on the Space Shuttle. The device must enable the astronauts to perform a number of exercises to prevent skeletal muscle atrophy and neuromuscular deconditioning in microgravity environments. The RED must fit the requirements for limited volume and weight and must provide a means of restraint during exercise. The design team divided the functions of the device into three major groups: methods of supplying force, methods of adjusting force, and methods of transmitting the force to the user. After analyzing the three main functions of the RED and developing alternatives for each, the design team used a comparative decision process to choose the most feasible components for the overall design. The design team selected the constant force spring alternative for further embodiment. The device consists of an array of different sized constant force springs which can be pinned in different combinations to produce the required output forces. The force is transmitted by means of a shaft and gear system. The final report is divided into four sections. An introduction section discusses the sponsor background, problem background and requirements of the device. The second section covers the alternative designs for each of the main functions. The design solution and pertinent calculations comprises the third section. The final section contains design conclusions and recommendations including topics of future work.

77 FR 31333 - Taking and Importing Marine Mammals: Taking Marine Mammals Incidental to Navy Training Exercises...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

... VACAPES Range Complex, the Navy conducted 14 5-lb charge, 28 10-lb charge, and 3 20-lb charge mine... missile) exercises and 1 AGM-65 (Maverick missile) exercise (MISSIEX); and 13 5' explosive Naval gunfire... (PAM) devices. The monitoring efforts for 2011 were conducted within the mine neutralization exercise...

Scapulothoracic Muscle Activity during Use of a Wall Slide Device (WSD), a Comparison with the General Wall Push up Plus

PubMed Central

Park, Se-yeon; Ahn, Tae-kyung; Eom, Ji-hwan; Youn, Hyun-ji; Kim, In-kwang; Yoo, Won-gyu

2014-01-01

[Purpose] The purpose of this study was to evaluate the effect of the wall slide device on activation of the scapulothoracic musculature. [Subjects] We recruited 15 healthy male subjects. [Methods] The subjects performed the general wall push-up plus (WPUP) and the wall slide with device (WSD) exercises. During the exercises, the muscle activities of the upper and lower trapezius (UT, LT), middle and lower serratus anterior (MSA, LSA), and pectoralis major (PM) were measured. [Results] The normalized muscle activity data of the WSD were significantly higher in UT, MSA and LSA than the WPUP. [Conclusion] Our results suggest that exercise using the WSD can more effectively activate the scapulothoracic musculature than the general WPUP. PMID:25013271

Monitoring ventricular function at rest and during exercise with a nonimaging nuclear detector.

PubMed

Wagner, H N; Rigo, P; Baxter, R H; Alderson, P O; Douglass, K H; Housholder, D F

1979-05-01

A portable nonimaging device, the nuclear stethoscope, for measuring beat to beat ventricular time-activity curves in normal people and patients with heart disease, both at rest and during exercise, is being developed and evaluated. The latest device has several operating modes that facilitate left ventricular and background localization, measurement of transit times and automatic calculation and display of left ventricular ejection fraction. The correlation coefficient of left ventricular ejection fraction obtained with the device and with a camera-computer system was 0.92 in 35 subjects. During bicycle exercise the ejection fraction in 15 normal persons increased from 44 to 64 percent (P less than 0.001), whereas among 12 patients with heart disease it was unchanged in 5 and decreased in 7.

Validation of Heart Rate Monitor Polar RS800 for Heart Rate Variability Analysis During Exercise.

PubMed

Hernando, David; Garatachea, Nuria; Almeida, Rute; Casajús, Jose A; Bailón, Raquel

2018-03-01

Hernando, D, Garatachea, N, Almeida, R, Casajús, JA, and Bailón, R. Validation of heart rate monitor Polar RS800 for heart rate variability analysis during exercise. J Strength Cond Res 32(3): 716-725, 2018-Heart rate variability (HRV) analysis during exercise is an interesting noninvasive tool to measure the cardiovascular response to the stress of exercise. Wearable heart rate monitors are a comfortable option to measure interbeat (RR) intervals while doing physical activities. It is necessary to evaluate the agreement between HRV parameters derived from the RR series recorded by wearable devices and those derived from an electrocardiogram (ECG) during dynamic exercise of low to high intensity. Twenty-three male volunteers performed an exercise stress test on a cycle ergometer. Subjects wore a Polar RS800 device, whereas ECG was also recorded simultaneously to extract the reference RR intervals. A time-frequency spectral analysis was performed to extract the instantaneous mean heart rate (HRM), and the power of low-frequency (PLF) and high-frequency (PHF) components, the latter centered on the respiratory frequency. Analysis was done in intervals of different exercise intensity based on oxygen consumption. Linear correlation, reliability, and agreement were computed in each interval. The agreement between the RR series obtained from the Polar device and from the ECG is high throughout the whole test although the shorter the RR is, the more differences there are. Both methods are interchangeable when analyzing HRV at rest. At high exercise intensity, HRM and PLF still presented a high correlation (ρ > 0.8) and excellent reliability and agreement indices (above 0.9). However, the PHF measurements from the Polar showed reliability and agreement coefficients around 0.5 or lower when the level of the exercise increases (for levels of O2 above 60%).

Exercise therapy for an older patient with left ventricular assist device.

PubMed

Park, Won Hah; Seo, Yong Gon; Sung, Ji Dong

2014-06-01

A left ventricular assist device (LVAD) is a mechanical circulation support implanted for patients with end-stage heart failure. It may be used either as a bridge to cardiac transplantation or as a destination therapy. The health of a 75-year-old man with a medical history of systolic heart failure worsened. Therefore, he was recommended to have implanted a LVAD (Thoratec Corp.) as a destination therapy. After the surgery, he was enrolled in patient cardiac rehabilitation for the improvement of dyspnea and exercise capacity. In results, there is an improvement on his exercise capacity and quality of life. For the first time in Korea, we reported a benefit of exercise therapy after being implanted with a LVAD.

Field Organizations: Unit Status Reporting

DTIC Science & Technology

2001-11-15

3 15 PSYOP DEV DET Detachment CDR 12/8 15 TAC PSYOP DET Detachment CDR 13/8 15 TAC PSYOP team Team leader 5/3 15 UAV TBD TBD 16 MAV/ IAV TBD TBD 16 Fox...AR 600–110 Identification, Surveillance, and Administration of Personnel Infected with Human Immuno-deficiency Virus (HIV) AR 601–210 Regular Army...HIV human immunodeficiency virus HMMWV high mobility multipurpose wheeled vehicle HO hospitalized/convalescent leave category of personnel non

XML Schema Guide for Primary CDR Submissions

EPA Pesticide Factsheets

This document presents the extensible markup language (XML) schema guide for the Office of Pollution Prevention and Toxics’ (OPPT) e-CDRweb tool. E-CDRweb is the electronic, web-based tool provided by Environmental Protection Agency (EPA) for the submission of Chemical Data Reporting (CDR) information. This document provides the user with tips and guidance on correctly using the version 1.7 XML schema. Please note that the order of the elements must match the schema.

A Comparison of Reliability Measures for Continuous and Discontinuous Recording Methods: Inflated Agreement Scores with Partial Interval Recording and Momentary Time Sampling for Duration Events

ERIC Educational Resources Information Center

Rapp, John T.; Carroll, Regina A.; Stangeland, Lindsay; Swanson, Greg; Higgins, William J.

2011-01-01

The authors evaluated the extent to which interobserver agreement (IOA) scores, using the block-by-block method for events scored with continuous duration recording (CDR), were higher when the data from the same sessions were converted to discontinuous methods. Sessions with IOA scores of 89% or less with CDR were rescored using 10-s partial…

Maximising biohydrogen yields via continuous electrochemical hydrogen removal and carbon dioxide scrubbing.

PubMed

Massanet-Nicolau, Jaime; Jones, Rhys Jon; Guwy, Alan; Dinsdale, Richard; Premier, Giuliano; Mulder, Martijn J J

2016-10-01

The use of electrochemical hydrogen removal (EHR) together with carbon dioxide removal (CDR) was demonstrated for the first time using a continuous hydrogen producing fermenter. CDR alone was found to increase hydrogen yields from 0.07molH2molhexose to 0.72molH2molhexose. When CDR was combined with EHR, hydrogen yields increased further to 1.79molH2molhexose. The pattern of carbohydrate utilisation and volatile fatty acid (VFA) production are consistent with the hypothesis that increased yields are the result of relieving end product inhibition and inhibition of microbial hydrogen consumption. In situ removal of hydrogen and carbon dioxide as demonstrated here not only increase hydrogen yield but also produces a relatively pure product gas and unlike other approaches can be used to enhance conventional, mesophilic, CSTR type fermentation of low grade/high solids biomass. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Chemical-induced disease relation extraction via convolutional neural network.

PubMed

Gu, Jinghang; Sun, Fuqing; Qian, Longhua; Zhou, Guodong

2017-01-01

This article describes our work on the BioCreative-V chemical-disease relation (CDR) extraction task, which employed a maximum entropy (ME) model and a convolutional neural network model for relation extraction at inter- and intra-sentence level, respectively. In our work, relation extraction between entity concepts in documents was simplified to relation extraction between entity mentions. We first constructed pairs of chemical and disease mentions as relation instances for training and testing stages, then we trained and applied the ME model and the convolutional neural network model for inter- and intra-sentence level, respectively. Finally, we merged the classification results from mention level to document level to acquire the final relations between chemical and disease concepts. The evaluation on the BioCreative-V CDR corpus shows the effectiveness of our proposed approach. http://www.biocreative.org/resources/corpora/biocreative-v-cdr-corpus/. © The Author(s) 2017. Published by Oxford University Press.

The J beta segment of the T cell receptor contributes to the V beta-specific T cell expansion caused by staphylococcal enterotoxin B and Urtica dioica superantigens.

PubMed

Musette, P; Galelli, A; Truffa-Bachi, P; Peumans, W; Kourilsky, P; Gachelin, G

1996-03-01

We have used a new polymerase chain reaction-based technique to analyze at the clonal level the CDR3 diversity and the J beta usage associated with the V beta-dependent T cell receptor (TCR) recognition of two superantigens: the staphylococcal enterotoxin B and the Urtica dioica agglutinin. Our results show that subset of J beta elements is preferentially expanded in a given V beta family, independently of the nature of the superantigen. By contrast, the CDR3 loop does not contribute significantly to the T cell expansion induced by the superantigens. We conclude that the J beta segment of the TCR beta chain, but not the CDR3 region, participates in superantigen binding, presumably by influencing the quaternary structure of the TCR beta chain.

Comprehensive analysis of the T-cell receptor beta chain gene in rhesus monkey by high throughput sequencing

PubMed Central

Li, Zhoufang; Liu, Guangjie; Tong, Yin; Zhang, Meng; Xu, Ying; Qin, Li; Wang, Zhanhui; Chen, Xiaoping; He, Jiankui

2015-01-01

Profiling immune repertoires by high throughput sequencing enhances our understanding of immune system complexity and immune-related diseases in humans. Previously, cloning and Sanger sequencing identified limited numbers of T cell receptor (TCR) nucleotide sequences in rhesus monkeys, thus their full immune repertoire is unknown. We applied multiplex PCR and Illumina high throughput sequencing to study the TCRβ of rhesus monkeys. We identified 1.26 million TCRβ sequences corresponding to 643,570 unique TCRβ sequences and 270,557 unique complementarity-determining region 3 (CDR3) gene sequences. Precise measurements of CDR3 length distribution, CDR3 amino acid distribution, length distribution of N nucleotide of junctional region, and TCRV and TCRJ gene usage preferences were performed. A comprehensive profile of rhesus monkey immune repertoire might aid human infectious disease studies using rhesus monkeys. PMID:25961410

RosettaAntibodyDesign (RAbD): A general framework for computational antibody design

PubMed Central

Adolf-Bryfogle, Jared; Kalyuzhniy, Oleks; Kubitz, Michael; Hu, Xiaozhen; Adachi, Yumiko; Schief, William R.

2018-01-01

A structural-bioinformatics-based computational methodology and framework have been developed for the design of antibodies to targets of interest. RosettaAntibodyDesign (RAbD) samples the diverse sequence, structure, and binding space of an antibody to an antigen in highly customizable protocols for the design of antibodies in a broad range of applications. The program samples antibody sequences and structures by grafting structures from a widely accepted set of the canonical clusters of CDRs (North et al., J. Mol. Biol., 406:228–256, 2011). It then performs sequence design according to amino acid sequence profiles of each cluster, and samples CDR backbones using a flexible-backbone design protocol incorporating cluster-based CDR constraints. Starting from an existing experimental or computationally modeled antigen-antibody structure, RAbD can be used to redesign a single CDR or multiple CDRs with loops of different length, conformation, and sequence. We rigorously benchmarked RAbD on a set of 60 diverse antibody–antigen complexes, using two design strategies—optimizing total Rosetta energy and optimizing interface energy alone. We utilized two novel metrics for measuring success in computational protein design. The design risk ratio (DRR) is equal to the frequency of recovery of native CDR lengths and clusters divided by the frequency of sampling of those features during the Monte Carlo design procedure. Ratios greater than 1.0 indicate that the design process is picking out the native more frequently than expected from their sampled rate. We achieved DRRs for the non-H3 CDRs of between 2.4 and 4.0. The antigen risk ratio (ARR) is the ratio of frequencies of the native amino acid types, CDR lengths, and clusters in the output decoys for simulations performed in the presence and absence of the antigen. For CDRs, we achieved cluster ARRs as high as 2.5 for L1 and 1.5 for H2. For sequence design simulations without CDR grafting, the overall recovery for the native amino acid types for residues that contact the antigen in the native structures was 72% in simulations performed in the presence of the antigen and 48% in simulations performed without the antigen, for an ARR of 1.5. For the non-contacting residues, the ARR was 1.08. This shows that the sequence profiles are able to maintain the amino acid types of these conserved, buried sites, while recovery of the exposed, contacting residues requires the presence of the antigen-antibody interface. We tested RAbD experimentally on both a lambda and kappa antibody–antigen complex, successfully improving their affinities 10 to 50 fold by replacing individual CDRs of the native antibody with new CDR lengths and clusters. PMID:29702641

RosettaAntibodyDesign (RAbD): A general framework for computational antibody design.

PubMed

Adolf-Bryfogle, Jared; Kalyuzhniy, Oleks; Kubitz, Michael; Weitzner, Brian D; Hu, Xiaozhen; Adachi, Yumiko; Schief, William R; Dunbrack, Roland L

2018-04-01

A structural-bioinformatics-based computational methodology and framework have been developed for the design of antibodies to targets of interest. RosettaAntibodyDesign (RAbD) samples the diverse sequence, structure, and binding space of an antibody to an antigen in highly customizable protocols for the design of antibodies in a broad range of applications. The program samples antibody sequences and structures by grafting structures from a widely accepted set of the canonical clusters of CDRs (North et al., J. Mol. Biol., 406:228-256, 2011). It then performs sequence design according to amino acid sequence profiles of each cluster, and samples CDR backbones using a flexible-backbone design protocol incorporating cluster-based CDR constraints. Starting from an existing experimental or computationally modeled antigen-antibody structure, RAbD can be used to redesign a single CDR or multiple CDRs with loops of different length, conformation, and sequence. We rigorously benchmarked RAbD on a set of 60 diverse antibody-antigen complexes, using two design strategies-optimizing total Rosetta energy and optimizing interface energy alone. We utilized two novel metrics for measuring success in computational protein design. The design risk ratio (DRR) is equal to the frequency of recovery of native CDR lengths and clusters divided by the frequency of sampling of those features during the Monte Carlo design procedure. Ratios greater than 1.0 indicate that the design process is picking out the native more frequently than expected from their sampled rate. We achieved DRRs for the non-H3 CDRs of between 2.4 and 4.0. The antigen risk ratio (ARR) is the ratio of frequencies of the native amino acid types, CDR lengths, and clusters in the output decoys for simulations performed in the presence and absence of the antigen. For CDRs, we achieved cluster ARRs as high as 2.5 for L1 and 1.5 for H2. For sequence design simulations without CDR grafting, the overall recovery for the native amino acid types for residues that contact the antigen in the native structures was 72% in simulations performed in the presence of the antigen and 48% in simulations performed without the antigen, for an ARR of 1.5. For the non-contacting residues, the ARR was 1.08. This shows that the sequence profiles are able to maintain the amino acid types of these conserved, buried sites, while recovery of the exposed, contacting residues requires the presence of the antigen-antibody interface. We tested RAbD experimentally on both a lambda and kappa antibody-antigen complex, successfully improving their affinities 10 to 50 fold by replacing individual CDRs of the native antibody with new CDR lengths and clusters.

Phillips exercises with RED in Node 1/Unity module

NASA Image and Video Library

2005-05-18

ISS011-E-06404 (18 May 2005) --- Astronaut John L. Phillips, Expedition 11 NASA space station science officer and flight engineer, wearing squat harness pads, exercises using the Interim Resistive Exercise Device (IRED) equipment in the Unity node of the International Space Station.

High-Intensity Interval Training for Severe Left Ventricular Dysfunction Treated with Left Ventricular Assist Device.

PubMed

Ugata, Yusuke; Wada, Hiroshi; Sakakura, Kenichi; Ibe, Tatsuro; Ito, Miyuki; Ikeda, Nahoko; Fujita, Hideo; Momomura, Shin-Ichi

2018-01-27

Aerobic training based on anaerobic threshold (AT) is well-known to improve cardiac function, exercise capacity, and long-term outcomes of patients with heart failure. Recent reports suggested that high-intensity interval training (HIIT) for patients with cardiovascular disease may improve cardiopulmonary exercise capacity. We present a 61-year-old male patient of severe left ventricular dysfunction with left ventricular assisted device (LVAD). Following HIIT for 8 weeks, exercise capacity and muscle strength have improved without worsening left ventricular function. Our case showed the possibility that HIIT was feasible and effective even in patients with LVAD.

Development of the Vibration Isolation System for the Advanced Resistive Exercise Device

NASA Technical Reports Server (NTRS)

Niebuhr, Jason H.; Hagen, Richard A.

2011-01-01

This paper describes the development of the Vibration Isolation System for the Advanced Resistive Exercise Device from conceptual design to lessons learned. Maintaining a micro-g environment on the International Space Station requires that experiment racks and major vibration sources be isolated. The challenge in characterizing exercise loads and testing the system in the presence of gravity led to a decision to qualify the system by analysis. Available data suggests that the system is successful in attenuating loads, yet there has been a major component failure and several procedural issues during its 3 years of operational use.

Validation of a dual-cycle ergometer for exercise during 100 percent oxygen prebreathing

NASA Technical Reports Server (NTRS)

Wiegman, Janet F.; Ohlhausen, John H.; Webb, James T.; Pilmanis, Andrew A.

1992-01-01

A study has been designed to determine if exercise, while prebreathing 100 percent oxygen prior to decompression, can reduce the current resting-prebreathe time requirements for extravehicular activity and high altitude reconnaissance flight. For that study, a suitable exercise mode was required. Design considerations included space limitations, cost, pressure suit compatibility, ease and maintenance of calibration, accuracy of work output, and assurance that no significant mechanical advantage or disadvantage would be introduced into the system. In addition, the exercise device must enhance denitrogenation by incorporation of both upper and lower body musculature at high levels of oxygen consumption. The purpose of this paper is to describe the specially constructed, dual-cycle ergometer developed for simultaneous arm and leg exercise during prebreathing, and to compare maximal oxygen uptake obtained on the device to that obtained during leg-only cycle ergometry and treadmill testing. Results demonstrate the suitability of the dual-cycle ergometer as an appropriate tool for exercise research during 100 percent oxygen prebreathing.

An affordable, computerised, table-based exercise system for stroke survivors.

PubMed

King, Marcus; Hale, Leigh; Pekkari, Anna; Persson, Martin; Gregorsson, Malin; Nilsson, Mikaela

2010-07-01

Loss of hand function as a result of upper limb paresis after a stroke leads to reduced independence. Robotic-assisted therapy with virtual reality leads to improvements in motor function, but there is a need to improve the cost-benefit ratio of these therapies. This case series study investigated augmented reality computer games which provided a rewarded, goal-directed task to upper limb rehabilitation via a gravity supported reaching task. A computer game was developed to motivate chronic stroke survivors to undertake gravity supported reaching tasks performed on a table, and a focus group study investigated the application of this device for rehabilitation. From the focus group, a simple device was developed to improve the quality of the exercise and a further focus group study investigated a variety of computer games to determine motivations for undertaking rehabilitation exercises. Of the four participants in the case study, two showed improvement in ability to play the game and in arm function. Participants enjoyed playing a range of computer games and felt that the system provided a worthwhile exercise. Motivation for undertaking exercise with the system included: intellectual stimulation during game play, feedback such as game score, gaining physical benefits from the exercise, the system tolerating varying levels of disability, ability to relate to the game and ability to use the system in social groups. A low-cost device has been developed which increases the exercise of gravity supported reaching movements, provides goal-directed tasks with rewards and motivates the user to undertake extended rehabilitation.

Interstitial Glucose and Physical Exercise in Type 1 Diabetes: Integrative Physiology, Technology, and the Gap In-Between

PubMed Central

Moser, Othmar; Yardley, Jane E.; Bracken, Richard M.

2018-01-01

Continuous and flash glucose monitoring systems measure interstitial fluid glucose concentrations within a body compartment that is dramatically altered by posture and is responsive to the physiological and metabolic changes that enable exercise performance in individuals with type 1 diabetes. Body fluid redistribution within the interstitial compartment, alterations in interstitial fluid volume, changes in rate and direction of fluid flow between the vasculature, interstitium and lymphatics, as well as alterations in the rate of glucose production and uptake by exercising tissues, make for caution when interpreting device read-outs in a rapidly changing internal environment during acute exercise. We present an understanding of the physiological and metabolic changes taking place with acute exercise and detail the blood and interstitial glucose responses with different forms of exercise, namely sustained endurance, high-intensity, and strength exercises in individuals with type 1 diabetes. Further, we detail novel technical information on currently available patient devices. As more health services and insurance companies advocate their use, understanding continuous and flash glucose monitoring for its strengths and limitations may offer more confidence for patients aiming to manage glycemia around exercise. PMID:29342932

A new device to study isoload eccentric exercise.

PubMed

Guilhem, Gaël; Cornu, Christophe; Nordez, Antoine; Guével, Arnaud

2010-12-01

This study was designed to develop a new device allowing mechanical analysis of eccentric exercise against a constant load, with a view in mind to compare isoload (IL) and isokinetic (IK) eccentric exercises. A plate-loaded resistance training device was integrated to an IK dynamometer, to perform the acquisition of mechanical parameters (i.e., external torque, angular velocity). To determine the muscular torque produced by the subject, load torque was experimentally measured (TLexp) at 11 different loads from 30° to 90° angle (0° = lever arm in horizontal position). TLexp was modeled to take friction effect and torque variations into account. Validity of modeled load torque (TLmod) was tested by determining the root mean square (RMS) error, bias, and 2SD between the descending part of TLexp (from 30° to 90°) and TLmod. Validity of TLexp was tested by a linear regression and a Passing-Bablok regression. A pilot analysis on 10 subjects was performed to determine the contribution of the torque because of the moment of inertia to the amount of external work (W). Results showed the validity of TLmod (bias = 0%; RMS error = 0.51%) and TLexp SEM = 4.1 N·m; Intraclass correlation coefficient (ICC) = 1.00; slope = 0.99; y-intercept = -0.13). External work calculation showed a satisfactory reproducibility (SEM = 38.3 J; ICC = 0.98) and moment of inertia contribution to W showed a low value (3.2 ± 2.0%). Results allow us to validate the new device developed in this study. Such a device could be used in future work to study IL eccentric exercise and to compare the effect of IL and IK eccentric exercises in standardized conditions.

CD4 molecules with a diversity of mutations encompassing the CDR3 region efficiently support human immunodeficiency virus type 1 envelope glycoprotein-mediated cell fusion.

PubMed Central

Broder, C C; Berger, E A

1993-01-01

The third complementarity-determining region (CDR3) within domain 1 of the human CD4 molecule has been suggested to play a critical role in membrane fusion mediated by the interaction of CD4 with the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein. To analyze in detail the role of CDR3 and adjacent regions in the fusion process, we used cassette mutagenesis to construct a panel of 30 site-directed mutations between residues 79 and 96 of the full-length CD4 molecule. The mutant proteins were transiently expressed by using recombinant vaccinia virus vectors and were analyzed for cell surface expression, recombinant gp120-binding activity, and overall structural integrity as assessed by reactivity with a battery of anti-CD4 monoclonal antibodies. Cells expressing the CD4 mutants were assayed for their ability to form syncytia when mixed with cells expressing the HIV-1 envelope glycoprotein. Surprisingly in view of published data from others, most of the mutations had little effect on syncytium-forming activity. Normal fusion was observed in 21 mutants, including substitution of human residues 85 to 95 with the corresponding sequences from either chimpanzee, rhesus, or mouse CD4; a panel of Ser-Arg double insertions after each residue from 86 to 91; and a number of other charge, hydrophobic, and proline substitutions and insertions within this region. The nine mutants that showed impaired fusion all displayed defective gp120 binding and disruption of overall structural integrity. In further contrast with results of other workers, we observed that transformant human cell lines expressing native chimpanzee or rhesus CD4 efficiently formed syncytia when mixed with cells expressing the HIV-1 envelope glycoprotein. These data refute the conclusion that certain mutations in the CDR3 region of CD4 abolish cell fusion activity, and they suggest that a wide variety of sequences can be functionally tolerated in this region, including those from highly divergent mammalian species. Syncytium formation mediated by several of the CDR3 mutants was partially or completely resistant to inhibition by the CDR3-directed monoclonal antibody L71, suggesting that the corresponding epitope is not directly involved in the fusion process.(ABSTRACT TRUNCATED AT 400 WORDS) Images PMID:8419649

CD4 molecules with a diversity of mutations encompassing the CDR3 region efficiently support human immunodeficiency virus type 1 envelope glycoprotein-mediated cell fusion.

PubMed

Broder, C C; Berger, E A

1993-02-01

The third complementarity-determining region (CDR3) within domain 1 of the human CD4 molecule has been suggested to play a critical role in membrane fusion mediated by the interaction of CD4 with the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein. To analyze in detail the role of CDR3 and adjacent regions in the fusion process, we used cassette mutagenesis to construct a panel of 30 site-directed mutations between residues 79 and 96 of the full-length CD4 molecule. The mutant proteins were transiently expressed by using recombinant vaccinia virus vectors and were analyzed for cell surface expression, recombinant gp120-binding activity, and overall structural integrity as assessed by reactivity with a battery of anti-CD4 monoclonal antibodies. Cells expressing the CD4 mutants were assayed for their ability to form syncytia when mixed with cells expressing the HIV-1 envelope glycoprotein. Surprisingly in view of published data from others, most of the mutations had little effect on syncytium-forming activity. Normal fusion was observed in 21 mutants, including substitution of human residues 85 to 95 with the corresponding sequences from either chimpanzee, rhesus, or mouse CD4; a panel of Ser-Arg double insertions after each residue from 86 to 91; and a number of other charge, hydrophobic, and proline substitutions and insertions within this region. The nine mutants that showed impaired fusion all displayed defective gp120 binding and disruption of overall structural integrity. In further contrast with results of other workers, we observed that transformant human cell lines expressing native chimpanzee or rhesus CD4 efficiently formed syncytia when mixed with cells expressing the HIV-1 envelope glycoprotein. These data refute the conclusion that certain mutations in the CDR3 region of CD4 abolish cell fusion activity, and they suggest that a wide variety of sequences can be functionally tolerated in this region, including those from highly divergent mammalian species. Syncytium formation mediated by several of the CDR3 mutants was partially or completely resistant to inhibition by the CDR3-directed monoclonal antibody L71, suggesting that the corresponding epitope is not directly involved in the fusion process.(ABSTRACT TRUNCATED AT 400 WORDS)

Validation of a Climate-Data Record of the "Clear-Kky" Surface Temperature of the Greenland Ice Sheet

NASA Technical Reports Server (NTRS)

Hall, Dorothy K.; Box, Jason E.; Koenig, Lora S.; DiGirolamo, Nicolo E.; Comiso, Josefino C.; Shuman, Christopher A.

2011-01-01

Surface temperatures on the Greenland Ice Sheet have been studied on the ground, using automatic weather station (AWS) data from the Greenland-Climate Network (GC-Net), and from analysis of satellite sensor data. Using Advanced Very High Frequency Radiometer (AVHRR) weekly surface temperature maps, warming of the surface of the Greenland Ice Sheet has been documented since 1981. We extended and refined this record using higher-resolution Moderate-Resolution Imaging Spectroradiometer (MODIS) data from March 2000 to the present. We developed a daily and monthly climate-data record (CDR) of the "clear-sky" surface temperature of the Greenland Ice Sheet using an ice-surface temperature (1ST) algorithm developed for use with MODIS data. Validation of this CDR is ongoing. MODIS Terra swath data are projected onto a polar stereographic grid at 6.25-km resolution to develop binary, gridded daily and mean-monthly 1ST maps. Each monthly map also has a color-coded image map that is available to download. Also included with the monthly maps is an accompanying map showing number of days in the month that were used to calculate the mean-monthly 1ST. This is important because no 1ST decision is made by the algorithm for cells that are considered cloudy by the internal cloud mask, so a sufficient number of days must be available to produce a mean 1ST for each grid cell. Validation of the CDR consists of several facets: 1) comparisons between ISTs and in-situ measurements; 2) comparisons between ISTs and AWS data; and 3) comparisons of ISTs with surface temperatures derived from other satellite instruments such as the Thermal Emission and Reflection Radiometer (ASTER) and Enhanced Thematic Mapper Plus (ETM+). Previous work shows that Terra MODIS ISTs are about 3 C lower than in-situ temperatures measured at Summit Camp, during the winter of 2008-09 under clear skies. In this work we begin to compare surface temperatures derived from AWS data with ISTs from the MODIS CDR. The Greenland Ice Sheet 1ST CDR will be useful for monitoring surface-temperature trends and can be used as input or for validation of climate models. The CDR can be extended into the future using MODIS Terra, Aqua and NPOESS Preparatory Project Visible Infrared Imager Radiometer Suite (VII RS) data.

Extracorporeal Membrane Oxygenation for End-Stage Interstitial Lung Disease With Secondary Pulmonary Hypertension at Rest and Exercise: Insights From Simulation Modeling.

PubMed

Chicotka, Scott; Burkhoff, Daniel; Dickstein, Marc L; Bacchetta, Matthew

Interstitial lung disease (ILD) represents a collection of lung disorders with a lethal trajectory with few therapeutic options with the exception of lung transplantation. Various extracorporeal membrane oxygenation (ECMO) configurations have been used for bridge to transplant (BTT), yet no optimal configuration has been clearly demonstrated. Using a cardiopulmonary simulation, we assessed different ECMO configurations for patients with end-stage ILD to assess the physiologic deficits and help guide the development of new long-term pulmonary support devices. A cardiopulmonary ECMO simulation was created, and changes in hemodynamics and blood gases were compared for different inflow and outflow anatomic locations and for different sweep gas and blood pump flow rates. The system simulated the physiologic response of patients with severe ILD at rest and during exercise with central ECMO, peripheral ECMO, and with no ECMO. The output parameters were total cardiac output (CO), mixed venous oxygen (O2) saturation, arterial pH, and O2 delivery (DO2)/O2 utilization (VO2) at different levels of exercise. The model described the physiologic state of progressive ILD and showed the relative effects of using various ECMO configurations to support them. It elucidated the optimal device configurations and required physiologic pump performance and provided insight into the physiologic demands of exercise in ILD patients. The simulation program was able to model the pathophysiologic state of progressive ILD with PH and demonstrate how mechanical support devices can be implemented to improve cardiopulmonary function at rest and during exercise. The information generated from simulation can be used to optimize ECMO configuration selection for BTT patients and provide design guidance for new devices to better meet the physiologic demands of exercise associated with normal activities of daily living.

Comparison of active cooling devices to passive cooling for rehabilitation of firefighters performing exercise in thermal protective clothing: A report from the Fireground Rehab Evaluation (FIRE) trial

PubMed Central

Hostler, David; Reis, Steven E; Bednez, James C; Kerin, Sarah; Suyama, Joe

2010-01-01

Background Thermal protective clothing (TPC) worn by firefighters provides considerable protection from the external environment during structural fire suppression. However, TPC is associated with physiological derangements that may have adverse cardiovascular consequences. These derangements should be treated during on-scene rehabilitation periods. Objective The present study examined heart rate and core temperature responses during the application of four active cooling devices, currently being marketed to the fire service for on-scene rehab, and compared them to passive cooling in a moderate temperature (approximately 24°C) and to an infusion of cold (4°C) saline. Methods Subjects exercised in TPC in a heated room. Following an initial exercise period (BOUT 1) the subjects exited the room, removed TPC, and for 20 minutes cooled passively at room temperature, received an infusion of cold normal saline, or were cooled by one of four devices (fan, forearm immersion in water, hand cooling, water perfused cooling vest). After cooling, subjects donned TPC and entered the heated room for another 50-minute exercise period (BOUT 2). Results Subjects were not able to fully recover core temperature during a 20-minute rehab period when provided rehydration and the opportunity to completely remove TPC. Exercise duration was shorter during BOUT 2 when compared to BOUT 1 but did not differ by cooling intervention. The overall magnitude and rate of cooling and heart rate recovery did not differ by intervention. Conclusions No clear advantage was identified when active cooling devices and cold intravenous saline were compared to passive cooling in a moderate temperature after treadmill exercise in TPC. PMID:20397868

Cardiovascular responses to rowing on a novel ergometer designed for both resistance and aerobic training in space.

PubMed

Tesch, Per A; Pozzo, Marco; Ainegren, Mats; Swarén, Mikael; Linnehan, Richard M

2013-05-01

Astronauts are required to perform both resistance and aerobic exercise while in orbit. This study assessed the aerobic energy yield and related physiological measurements using a nongravity dependent flywheel device designed for both resistance and aerobic exercise (RAD) in space. Eight physically active men and women performed all-out rowing on the RAD. For comparison, exercise was also carried out employing a commercially available rowing ergometer (C2). Peak oxygen uptake during exercise using RAD and C2 averaged 3.11 +/- 0.49 and 3.18 +/- 0.50 L x min(-1), respectively. Similarly, peak plasma lactate concentration (9.6 vs. 11.2 mmol x L(-1)), heart rate (183 vs. 184 bpm), and rate of perceived exertion (15.8 vs. 16.0) were comparable across exercise using the two devices. Collectively, the results suggest that this novel exercise modality offers cardiovascular and metabolic responses, and thus aerobic exercise stimulus that is equally effective as that evoked by established technology for indoor rowing. Given the need for physiologically sound and highly effective exercise countermeasures that features small mass and envelope, and allows for resistance and aerobic exercise in a single apparatus, we believe this novel hardware should be considered for use in space.

XML Schema Guide for Secondary CDR Submissions

EPA Pesticide Factsheets

This document presents the extensible markup language (XML) schema guide for the Office of Pollution Prevention and Toxics’ (OPPT) e-CDRweb tool. E-CDRweb is the electronic, web-based tool provided by Environmental Protection Agency (EPA) for the submission of Chemical Data Reporting (CDR) information. This document provides the user with tips and guidance on correctly using the version 1.1 XML schema for the Joint Submission Form. Please note that the order of the elements must match the schema.

Evaluating Navy’s Funded Graduate Education Program. A Return-on-Investment Framework

DTIC Science & Technology

2010-01-01

decisionmaking, and increased retention. Some of this value can be monetized , and costs and benefits to the Navy can be estimated using enhanced...support of LCDR Claude McRoberts, CAPT Karen Emmel, CDR Darin Evenson, CAPT John Coronado, CDR Rob Tortora, CAPT Richard Moyer, LCDR Joseph Scott...step is to monetize the data on education effects by assigning values to the education outcomes predicted in step two and calculating an annual

Central Nervous System Oxygen Toxicity in Closed-Circuit Scuba Divers

DTIC Science & Technology

1986-03-01

CENTRAL NERVOUS SYSTEM OXYGEN TOXICITY IN CLOSED -CIRCUIT SCUBA DIVERS III By F. K. Butler, Jr., LCDR, MC, USN NAVY EXPERIMENTAL DIVING UNIT DTIC...PANAMA CITY. FLORIDA 321407 IN. aLV OMW Vol NAVY EXPERIMENTAL DIVING UNIT REPORT NO. 5-86 CENTRAL NERVOUS SYSTEM OXYGEN TOXICITY IN CLOSED -CIRCUIT SCUBA...BUTLER, Jr. J . .d.M. HAMILTON LCDR, MC, USK CDR, MC, USK CDR, USKN Medical Research Officer Senior Medical Officer Comanding Officer UNCLASSIFIED 4

HFI Bolometer Detectors Programmatic CDR

NASA Technical Reports Server (NTRS)

Lange, Andrew E.

2002-01-01

Programmatic Critical Design Review (CDR) of the High Frequency Instrument (HFI) Bolometer Detector on the Planck Surveyor is presented. The topics include: 1) Scientific Requirements and Goals; 2) Silicon Nitride Micromesh 'Spider-Web' Bolometers; 3) Sub-Orbital Heritage: BOOMERANG; 4) Noise stability demonstrated in BOOMERANG; 5) Instrument Partners; 6) Bolometer Environment on Planck/HFI; 7) Bolometer Modules; and 8) Mechanical Interface. Also included are the status of the receivables and delivery plans with Europe. This paper is presented in viewgraph form.

Airport Traffic Conflict Detection and Resolution Algorithm Evaluation

NASA Technical Reports Server (NTRS)

Jones, Denise R.; Chartrand, Ryan C.; Wilson, Sara R.; Commo, Sean A.; Otero, Sharon D.; Barker, Glover D.

2012-01-01

A conflict detection and resolution (CD&R) concept for the terminal maneuvering area (TMA) was evaluated in a fast-time batch simulation study at the National Aeronautics and Space Administration (NASA) Langley Research Center. The CD&R concept is being designed to enhance surface situation awareness and provide cockpit alerts of potential conflicts during runway, taxi, and low altitude air-to-air operations. The purpose of the study was to evaluate the performance of aircraft-based CD&R algorithms in the TMA, as a function of surveillance accuracy. This paper gives an overview of the CD&R concept, simulation study, and results. The Next Generation Air Transportation System (NextGen) concept for the year 2025 and beyond envisions the movement of large numbers of people and goods in a safe, efficient, and reliable manner [1]. NextGen will remove many of the constraints in the current air transportation system, support a wider range of operations, and provide an overall system capacity up to three times that of current operating levels. Emerging NextGen operational concepts [2], such as four-dimensional trajectory based airborne and surface operations, equivalent visual operations, and super density arrival and departure operations, require a different approach to air traffic management and as a result, a dramatic shift in the tasks, roles, and responsibilities for the flight deck and air traffic control (ATC) to ensure a safe, sustainable air transportation system.

Satellite-based Monitoring of global Precipitation using the PERSIANN system: from Weather- to Climate-scales with some application examples

NASA Astrophysics Data System (ADS)

Switzer, A.; Yap, W.; Lauro, F.; Gouramanis, C.; Dominey-Howes, D.; Labbate, M.

2016-12-01

This presentation provides an overview of the PERSIANN precipitation products from the near real time high-resolution (4km, 30 min) PERSIANN-CCS to the most recent 34+-year PERSIANN-CDR (25km, daily). It is widely believed that the hydrologic cycle has been intensifying due to global warming and the frequency and the intensity of hydrologic extremes has also been increasing. Using the long-term historical global high resolution (daily, 0.25 degree) PERSIANN-CDR dataset covering over three decades from 1983 to the present day, we assess changes in global precipitation across different spatial scales. Our results show differences in trends, depending on which spatial scale is used, highlighting the importance of spatial scale in trend analysis. In addition, while there is an easily observable increasing global temperature trend, the global precipitation trend results created by the PERSIANN-CDR dataset used in this study are inconclusive. In addition, we use PERSIANN-CDR to assess the performance of the 32 CMIP5 models in terms of extreme precipitation indices in various continent-climate zones. The assessment can provide a guide for both model developers to target regions and processes that are not yet fully captured in certain climate types, and for climate model output users to be able to select the models and/or the study areas that may best fit their applications of interest.

Satellite-based Monitoring of global Precipitation using the PERSIANN system: from Weather- to Climate-scales with some application examples

NASA Astrophysics Data System (ADS)

Sorooshian, S.; Nguyen, P.; Hsu, K. L.

2017-12-01

This presentation provides an overview of the PERSIANN precipitation products from the near real time high-resolution (4km, 30 min) PERSIANN-CCS to the most recent 34+-year PERSIANN-CDR (25km, daily). It is widely believed that the hydrologic cycle has been intensifying due to global warming and the frequency and the intensity of hydrologic extremes has also been increasing. Using the long-term historical global high resolution (daily, 0.25 degree) PERSIANN-CDR dataset covering over three decades from 1983 to the present day, we assess changes in global precipitation across different spatial scales. Our results show differences in trends, depending on which spatial scale is used, highlighting the importance of spatial scale in trend analysis. In addition, while there is an easily observable increasing global temperature trend, the global precipitation trend results created by the PERSIANN-CDR dataset used in this study are inconclusive. In addition, we use PERSIANN-CDR to assess the performance of the 32 CMIP5 models in terms of extreme precipitation indices in various continent-climate zones. The assessment can provide a guide for both model developers to target regions and processes that are not yet fully captured in certain climate types, and for climate model output users to be able to select the models and/or the study areas that may best fit their applications of interest.

Initial Concept for Terminal Area Conflict Detection, Alerting, and Resolution Capability On or Near the Airport Surface, Version 2.0

NASA Technical Reports Server (NTRS)

Otero, Sharon D.; Barker, Glover D.; Jones, Denise R.

2013-01-01

The Next Generation Air Transportation System (NextGen) concept for 2025 envisions the movement of large numbers of people and goods in a safe, efficient, and reliable manner. The NextGen will remove many of the constraints in the current air transportation system, support a wider range of operations, and deliver an overall system capacity up to 3 times that of current operating levels. In order to achieve the NextGen vision, research is necessary in the areas of surface traffic optimization, maximum runway capacity, reduced runway occupancy time, simultaneous single runway operations, and terminal area conflict prevention, among others. The National Aeronautics and Space Administration (NASA) is conducting Collision Avoidance for Airport Traffic (CAAT) research to develop technologies, data, and guidelines to enable Conflict Detection and Resolution (CD&R) in the Airport Terminal Maneuvering Area (ATMA) under current and emerging NextGen operating concepts. The term ATMA was created to reflect the fact that the CD&R concept area of operation is focused near the airport within the terminal maneuvering area. In the following, an initial concept for an aircraft-based method for CD&R in the ATMA is presented. This method is based upon previous NASA work in CD&R for runway incursion prevention, the Runway Incursion Prevention System (RIPS).

A complete, multi-level conformational clustering of antibody complementarity-determining regions

PubMed Central

Nikoloudis, Dimitris; Pitts, Jim E.

2014-01-01

Classification of antibody complementarity-determining region (CDR) conformations is an important step that drives antibody modelling and engineering, prediction from sequence, directed mutagenesis and induced-fit studies, and allows inferences on sequence-to-structure relations. Most of the previous work performed conformational clustering on a reduced set of structures or after application of various structure pre-filtering criteria. In this study, it was judged that a clustering of every available CDR conformation would produce a complete and redundant repertoire, increase the number of sequence examples and allow better decisions on structure validity in the future. In order to cope with the potential increase in data noise, a first-level statistical clustering was performed using structure superposition Root-Mean-Square Deviation (RMSD) as a distance-criterion, coupled with second- and third-level clustering that employed Ramachandran regions for a deeper qualitative classification. The classification of a total of 12,712 CDR conformations is thus presented, along with rich annotation and cluster descriptions, and the results are compared to previous major studies. The present repertoire has procured an improved image of our current CDR Knowledge-Base, with a novel nesting of conformational sensitivity and specificity that can serve as a systematic framework for improved prediction from sequence as well as a number of future studies that would aid in knowledge-based antibody engineering such as humanisation. PMID:25071986

Thal Amyloid Stages Do Not Significantly Impact the Correlation Between Neuropathological Change and Cognition in the Alzheimer Disease Continuum.

PubMed

Serrano-Pozo, Alberto; Qian, Jing; Muzikansky, Alona; Monsell, Sarah E; Montine, Thomas J; Frosch, Matthew P; Betensky, Rebecca A; Hyman, Bradley T

2016-06-01

The 2012 neuropathological criteria for the diagnosis of Alzheimer disease (AD) summarize the extent of AD neuropathological change with an ABC score, which is a composite of the Thal stage of amyloid deposition (A), the Braak stage of neurofibrillary tangles (NFTs) (B), and the CERAD neuritic plaque score (C). NFTs and neuritic plaques are well-established contributors to cognitive impairment, but whether the Thal amyloid stage independently predicts antemortem cognition remains unknown. We used the National Alzheimer's Coordinating Center autopsy data set to build adjacent-categories logit regression models with CDR-SOB and Mini-Mental State Examination (MMSE) scores as cognitive outcome variables. Increasing CERAD scores were independently associated with higher CDR-SOB scores, whereas increasing Braak NFT stages predicted both higher CDR-SOB and lower MMSE scores. Increasing Thal amyloid stages were not significantly independently associated with either outcome measure. Increasing ABC scores predicted higher CDR-SOB and lower MMSE scores. These results raise the possibility that Thal amyloid stages do not substantially contribute to predicting antemortem cognition compared to CERAD neuritic plaque scores and Braak NFT stages, and suggest that the diffuse amyloid deposits participating in the assignment of Thal amyloid stages are neutral with respect to clinically detectable cognitive and functional changes. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

A comprehensive whole-genome integrated cytogenetic map for the alpaca (Lama pacos).

PubMed

Avila, Felipe; Baily, Malorie P; Perelman, Polina; Das, Pranab J; Pontius, Joan; Chowdhary, Renuka; Owens, Elaine; Johnson, Warren E; Merriwether, David A; Raudsepp, Terje

2014-01-01

Genome analysis of the alpaca (Lama pacos, LPA) has progressed slowly compared to other domestic species. Here, we report the development of the first comprehensive whole-genome integrated cytogenetic map for the alpaca using fluorescence in situ hybridization (FISH) and CHORI-246 BAC library clones. The map is comprised of 230 linearly ordered markers distributed among all 36 alpaca autosomes and the sex chromosomes. For the first time, markers were assigned to LPA14, 21, 22, 28, and 36. Additionally, 86 genes from 15 alpaca chromosomes were mapped in the dromedary camel (Camelus dromedarius, CDR), demonstrating exceptional synteny and linkage conservation between the 2 camelid genomes. Cytogenetic mapping of 191 protein-coding genes improved and refined the known Zoo-FISH homologies between camelids and humans: we discovered new homologous synteny blocks (HSBs) corresponding to HSA1-LPA/CDR11, HSA4-LPA/CDR31 and HSA7-LPA/CDR36, and revised the location of breakpoints for others. Overall, gene mapping was in good agreement with the Zoo-FISH and revealed remarkable evolutionary conservation of gene order within many human-camelid HSBs. Most importantly, 91 FISH-mapped markers effectively integrated the alpaca whole-genome sequence and the radiation hybrid maps with physical chromosomes, thus facilitating the improvement of the sequence assembly and the discovery of genes of biological importance. © 2015 S. Karger AG, Basel.

Optic disc boundary segmentation from diffeomorphic demons registration of monocular fundus image sequences versus 3D visualization of stereo fundus image pairs for automated early stage glaucoma assessment

NASA Astrophysics Data System (ADS)

Gatti, Vijay; Hill, Jason; Mitra, Sunanda; Nutter, Brian

2014-03-01

Despite the current availability in resource-rich regions of advanced technologies in scanning and 3-D imaging in current ophthalmology practice, world-wide screening tests for early detection and progression of glaucoma still consist of a variety of simple tools, including fundus image-based parameters such as CDR (cup to disc diameter ratio) and CAR (cup to disc area ratio), especially in resource -poor regions. Reliable automated computation of the relevant parameters from fundus image sequences requires robust non-rigid registration and segmentation techniques. Recent research work demonstrated that proper non-rigid registration of multi-view monocular fundus image sequences could result in acceptable segmentation of cup boundaries for automated computation of CAR and CDR. This research work introduces a composite diffeomorphic demons registration algorithm for segmentation of cup boundaries from a sequence of monocular images and compares the resulting CAR and CDR values with those computed manually by experts and from 3-D visualization of stereo pairs. Our preliminary results show that the automated computation of CDR and CAR from composite diffeomorphic segmentation of monocular image sequences yield values comparable with those from the other two techniques and thus may provide global healthcare with a cost-effective yet accurate tool for management of glaucoma in its early stage.

The Elbow-EpiTrainer: a method of delivering graded resistance to the extensor carpi radialis brevis. Effectiveness of a prototype device in a healthy population.

PubMed

Navsaria, Rishi; Ryder, Dionne M; Lewis, Jeremy S; Alexander, Caroline M

2015-03-01

Tennis elbow or lateral epicondylopathy (LE) is experienced as the lateral elbow has a reported prevalence of 1.3%, with symptoms lasting up to 18 months. LE is most commonly attributed to tendinopathy involving the extensor carpi radialis brevis (ECRB) tendon. The aim of tendinopathy management is to alleviate symptoms and restore function that initially involves relative rest followed by progressive therapeutic exercise. To assess the effectiveness of two prototype exercises using commonly available clinical equipment to progressively increase resistance and activity of the ECRB. Eighteen healthy participants undertook two exercise progressions. Surface electromyography was used to record ECRB activity during the two progressions, involving eccentric exercises of the wrist extensors and elbow pronation exercises using a prototype device. The two progressions were assessed for their linearity of progression using repeated ANOVA and linear regression analysis. Five participants repeated the study to assess reliability. The exercise progressions led to an increase in ECRB electromyographic (EMG) activity (p<0.001). A select progression of exercises combining the two protocols increased EMG activity in a linear fashion (p<0.001). The ICC values indicated good reliability (ICC>0.7) between the first and second tests for five participants. Manipulation of resistance and leverage with the prototype exercises was effective in creating significant increases of ECRB normalised EMG activity in a linear manner that may, with future research, become useful to clinicians treating LE. In addition, between trial reliability for the device to generate a consistent load was acceptable. 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.

Closed Loop Control Compact Exercise Device for Use on MPCV

NASA Technical Reports Server (NTRS)

Sheehan, Chris; Funk, Justin; Funk, Nathan; Kutnick, Gilead; Humphreys, Brad; Bruinsma, Douwe; Perusek, Gail

2016-01-01

Long duration space travel to Mars or to an asteroid will expose astronauts to extended periods of reduced gravity. To combat spaceflight physiological deconditioning, astronauts will use resistive and aerobic exercise regimens for the duration of the space flight to minimize the loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the mass and volume available for an exercise device in the next generation of spacecraft is limited. Therefore, compact exercise device prototypes are being developed for human in the loop evaluations. The NASA Human Research Program (HRP) is managing Advanced Exercise Concepts (AEC) requirements development and candidate technology maturation for all exploration mission profiles from Multi-Purpose Crew Vehicle (MPCV) exploration missions (e.g., EM-2, up to 21 day) to Mars Transit (up to 1000 day) missions. Numerous technologies have been considered and evaluated against HRP-approved functional requirements and include flywheel, pneumatic and closed-loop microprocessor-controlled motor driven power plants. Motor driven technologies offer excellent torque density and load accuracy characteristics as well as the ability to create custom mechanical impedance (the dynamic relationship between force and velocity) and custom load versus position exercise algorithms. Further, closed-loop motor-driven technologies offer the ability to monitor exercise dose parameters and adapt to the needs of the crewmember for real time optimization of exercise prescriptions. A simple proportional-integral-derivative (PID) controller is demonstrated in a prototype motor driven exercise device with comparison to resistive static and dynamic load set points and aerobic work rate targets. The resistive load term in the algorithm includes a constant force component (Fcmg) as well as inertial component (Fima) and a discussion of system tuning is presented in terms of addressing key functional requirements and human interfaces. The device aerobic modality is modelled as a rowing exercise using ground data sets obtained from Concept 2 rowers as well as competitive rowing1. A discussion of software and electronic implementations are presented which demonstrate unique approaches to meeting the constrained mass, volume and power requirements of the MPCV. . In addition to utilizing traditional PID control, controllers utilizing state feedback with gains solved using a Linear Quadratic Regulator will be developed. Controllability and observability will be utilized to investigate the need for state measurement in the design. As the control system directly interacts with human test subjects, robust methods such as H-infinity are also being investigated.1. Kleshnev V. Biomechanics. In: Rowing, Handbook of Sports Medicine and Science. ed. by Secher N., Voliantis S. IOC Medical Commission, Blackwell Pub. pp. 22-34, 2007

Adaptive force regulation of muscle strengthening rehabilitation device with magnetorheological fluids.

PubMed

Dong, Shufang; Lu, Ke-Qian; Sun, Jian Qiao; Rudolph, Katherine

2006-03-01

In rehabilitation from neuromuscular trauma or injury, strengthening exercises are often prescribed by physical therapists to recover as much function as possible. Strengthening equipment used in clinical settings range from low-cost devices, such as sandbag weights or elastic bands to large and expensive isotonic and isokinetic devices. The low-cost devices are incapable of measuring strength gains and apply resistance based on the lowest level of torque that is produced by a muscle group. Resistance that varies with joint angle can be achieved with isokinetic devices in which angular velocity is held constant and variable torque is generated when the patient attempts to move faster than the device but are ineffective if a patient cannot generate torque rapidly. In this paper, we report the development of a versatile rehabilitation device that can be used to strengthen different muscle groups based on the torque generating capability of the muscle that changes with joint angle. The device is low cost, is smaller than other commercially available machines, and can be programmed to apply resistance that is unique to a particular patient and that will optimize strengthening. The core of the device, a damper with smart magnetorheological fluids, provides passive exercise force. A digital adaptive control is capable of regulating exercise force precisely following the muscle strengthening profile prescribed by a physical therapist. The device could be programmed with artificial intelligence to dynamically adjust the target force profile to optimize rehabilitation effects. The device provides both isometric and isokinetic strength training and can be developed into a small, low-cost device that may be capable of providing optimal strengthening in the home.

The Manchester Acute Coronary Syndromes (MACS) decision rule for suspected cardiac chest pain: derivation and external validation.

PubMed

Body, Richard; Carley, Simon; McDowell, Garry; Pemberton, Philip; Burrows, Gillian; Cook, Gary; Lewis, Philip S; Smith, Alexander; Mackway-Jones, Kevin

2014-09-15

We aimed to derive and validate a clinical decision rule (CDR) for suspected cardiac chest pain in the emergency department (ED). Incorporating information available at the time of first presentation, this CDR would effectively risk-stratify patients and immediately identify: (A) patients for whom hospitalisation may be safely avoided; and (B) high-risk patients, facilitating judicious use of resources. In two sequential prospective observational cohort studies at heterogeneous centres, we included ED patients with suspected cardiac chest pain. We recorded clinical features and drew blood on arrival. The primary outcome was major adverse cardiac events (MACE) (death, prevalent or incident acute myocardial infarction, coronary revascularisation or new coronary stenosis >50%) within 30 days. The CDR was derived by logistic regression, considering reliable (κ>0.6) univariate predictors (p<0.05) for inclusion. In the derivation study (n=698) we derived a CDR including eight variables (high sensitivity troponin T; heart-type fatty acid binding protein; ECG ischaemia; diaphoresis observed; vomiting; pain radiation to right arm/shoulder; worsening angina; hypotension), which had a C-statistic of 0.95 (95% CI 0.93 to 0.97) implying near perfect diagnostic performance. On external validation (n=463) the CDR identified 27.0% of patients as 'very low risk' and potentially suitable for discharge from the ED. 0.0% of these patients had prevalent acute myocardial infarction and 1.6% developed MACE (n=2; both coronary stenoses without revascularisation). 9.9% of patients were classified as 'high-risk', 95.7% of whom developed MACE. The Manchester Acute Coronary Syndromes (MACS) rule has the potential to safely reduce unnecessary hospital admissions and facilitate judicious use of high dependency resources. 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.

Comparison of the incidence of patient-reported post-operative dysphagia between ACDF with a traditional anterior plate and artificial cervical disc replacement.

PubMed

Yang, Yi; Ma, Litai; Liu, Hao; Liu, Yilian; Hong, Ying; Wang, Beiyu; Ding, Chen; Deng, Yuxiao; Song, Yueming; Liu, Limin

2016-09-01

Compared with anterior cervical discectomy and fusion (ACDF), cervical disc replacement (CDR) has provided satisfactory clinical results. The incidence of post-operative dysphagia between ACDF with a traditional anterior plate and CDR remains controversial. Considering the limited studies and knowledge in this area, a retrospective study focusing on post-operative dysphagia was conducted. The Bazaz grading system was used to assess the severity of dysphagia at post-operative intervals including 1 week, 1 month, 3 months, 6 months, 12 months and 24 months respectively. The Chi-square test, Student t-test, Mann-Whitney U tests and Ordinal Logistic regression were used for data analysis when appropriate. Statistical significance was accepted at a probability value of <0.05. Two hundred and thirty-one patients in the CDR group and one hundred and fifty-eight patients in Plate group were included in this study. The total incidences of dysphagia in the CDR and plate group were 36.58% and 60.43% at one week, 29.27% and 38.85% at one month, 21.95% and 31.65% at three months, 6.83% and 17.99% at six months, 5.85% and 14.39% at 12 months, and 4.39% and 10.07% at the final follow-up respectively (All P<0.05, Mann-Whitney U test). Ordinal Logistic regression analysis showed that female patients, two-level surgery, C4/5 surgery, and anterior cervical plating were significant risk factors for post-operative dysphagia (all P<0.05). Comparing ACDF with a plate, CDR with a Prestige LP can significantly reduce both transient and persistent post-operative dysphagia. Female patients, two-level surgery, C4/5 surgery and anterior cervical plating were associated with a higher incidence of dysphagia. Future prospective, randomized, controlled studies are needed to further validate these findings. Copyright © 2016 Elsevier B.V. All rights reserved.

Carbon Dioxide Removal and Conversion to Ocean Alkalinity: Why and How

NASA Astrophysics Data System (ADS)

Rau, G. H.

2014-12-01

Drastic reduction in anthropogenic CO2 emissions is the most obvious way to stabilize atmospheric CO2. However, there is growing risk that effective emissions reduction policies and technologies will not engage soon enough to avoid significant CO2-induced climate and ocean acidification impacts. This realization has lead to increased interest (e.g., IPCC AR5, 2014; NRC/NAS, 2014) in the possibility of pro-actively increasing CO2 removal (CDR) from the atmosphere above the 55% of our emissions that are already removed from air by natural land and ocean processes. While a variety of biotic, abiotic, and hybrid CDR methods have been proposed, those involving geochemistry have much to recommend them. These methods employ the same geochemical reactions that naturally and effectively remove excess planetary CO2 and neutralize ocean acidity on geologic time scales. These reactions proceed when the hydrosphere, acidified by excess air CO2, contacts and reacts with carbonate and silicate minerals (>90% of the Earth's crust), producing dissolved bicarbonates and carbonates, i.e., ocean alkalinity. This alkalinity is eventually removed and the excess carbon stored via carbonate precipitation. So while the importance and global effectiveness of such reactions are not in question, it remains to be seen if this very slow, natural CDR could be safely and cost-effectively accelerated to help manage air CO2 levels on human rather than geologic time scales. Various terrestrial and marine, geochemistry-based CDR methods will be reviewed including: 1) the addition of minerals to soils and the ocean, 2) removal of CO2 from waste streams, esp. from biomass energy, via wet mineral contacting, and 3) the production and use of mineral derivatives, e.g. oxides or hydroxides, as CDR agents. The additional potential environmental benefits (e.g., reversal of ocean carbonate saturation loss) and impacts (e.g., increased mineral extraction), as well as potential economics will also be discussed.

Predictors of functional disability in mild cognitive impairment and dementia.

PubMed

van Rossum, M E; Koek, H L

2016-08-01

Knowledge about factors predicting functional disability in mild cognitive impairment (MCI) and dementia would help health care providers to identify those patients who are at high risk of functional disability. Previous research is scarce and focused on only a small number of possible predictors. The aim of this study was to identify predictors of functional disability in patients with MCI and dementia. Cross-sectional cohort study. Data from patients who visited a memory clinic between 2011 and 2015 were evaluated. The Disability Assessment for Dementia (DAD) was used to assess functional disability. Patients diagnosed with MCI or dementia and with a DAD score available were included. This led to the inclusion of 474 patients. Univariate analyses with a broad range of variables were performed to detect factors that had a significant relationship to the DAD score. Age, gender and variables with a p-value of 0.1 or lower in the univariate analyses were taken into a multivariable analysis. This multiple linear regression analysis was performed to determine which variables were independently associated with the DAD score. Our multivariable model explained 42% of the variance in the DAD score. Independent predictors of the DAD score were age (B=0.03, 95%CI=0.002-0.05), gender (B=-0.43, 95%CI=-0.78 to -0.07), score on the Clinical Dementia Rating scale (CDR) (B=1.53, 95%CI=1.07-1.99 for CDR 1, B=2.93, 95%CI=2.28-3.58 for CDR 2, B=3.96, 95%CI=2.65-5.27 for CDR 3) and level of physical activity (B=0.56, 95%CI=0.05-1.07). Older age, male gender, higher CDR score and lower levels of physical activity are independent predictors of functional disability in MCI and dementia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Partial versus Productive Immunoglobulin Heavy Locus Rearrangements in Chronic Lymphocytic Leukemia: Implications for B-Cell Receptor Stereotypy

PubMed Central

Tsakou, Eugenia; Agathagelidis, Andreas; Boudjoghra, Myriam; Raff, Thorsten; Dagklis, Antonis; Chatzouli, Maria; Smilevska, Tatjana; Bourikas, George; Merle-Beral, Helene; Manioudaki-Kavallieratou, Eleni; Anagnostopoulos, Achilles; Brüggemann, Monika; Davi, Frederic; Stamatopoulos, Kostas; Belessi, Chrysoula

2012-01-01

The frequent occurrence of stereotyped heavy complementarity-determining region 3 (VH CDR3) sequences among unrelated cases with chronic lymphocytic leukemia (CLL) is widely taken as evidence for antigen selection. Stereotyped VH CDR3 sequences are often defined by the selective association of certain immunoglobulin heavy diversity (IGHD) genes in specific reading frames with certain immunoglobulin heavy joining (IGHJ ) genes. To gain insight into the mechanisms underlying VH CDR3 restrictions and also determine the developmental stage when restrictions in VH CDR3 are imposed, we analyzed partial IGHD-IGHJ rearrangements (D-J) in 829 CLL cases and compared the productively rearranged D-J joints (that is, in-frame junctions without junctional stop codons) to (a) the productive immunoglobulin heavy variable (IGHV )-IGHD-IGHJ rearrangements (V-D-J) from the same cases and (b) 174 D-J rearrangements from 160 precursor B-cell acute lymphoblastic leukemia cases (pre-B acute lymphoblastic leukemia [ALL]). Partial D-J rearrangements were detected in 272/829 CLL cases (32.8%). Sequence analysis was feasible in 238 of 272 D-J rearrangements; 198 of 238 (83.2%) were productively rearranged. The D-J joints in CLL did not differ significantly from those in pre-B ALL, except for higher frequency of the IGHD7-27 and IGHJ6 genes in the latter. Among CLL carrying productively rearranged D-J, comparison of the IGHD gene repertoire in productive V-D-J versus D-J revealed the following: (a) overuse of IGHD reading frames encoding hydrophilic peptides among V-D-J and (b) selection of the IGHD3-3 and IGHD6-19 genes in V-D-J junctions. These results document that the IGHD and IGHJ gene biases in the CLL expressed VH CDR3 repertoire are not stochastic but are directed by selection operating at the immunoglobulin protein level. PMID:21968789

B cell Variable genes have evolved their codon usage to focus the targeted patterns of somatic mutation on the complementarity determining regions

PubMed Central

Saini, Jasmine; Hershberg, Uri

2015-01-01

The exceptional ability of B cells to diversify through somatic mutation and improve affinity of the repertoire towards the antigens is the cornerstone of adaptive immunity. Somatic mutation is not evenly distributed and exhibits certain micro-sequence specificities. We show here that the combination of somatic mutation targeting and the codon usage in human B cell receptor (BCR) Variable (V) genes create expected patterns of mutation and post mutation changes that are focused on their complementarity determining regions (CDR). T cell V genes are also skewed in targeting mutations but to a lesser extent and are lacking the codon usage bias observed in BCRs. This suggests that the observed skew in T cell receptors is due to their amino acid usage, which is similar to that of BCRs. The mutation targeting and the codon bias allow B cell CDRs to diversify by specifically accumulating nonconservative changes. We counted the distribution of mutations to CDR in 4 different human datasets. In all four cases we found that the number of actual mutations in the CDR correlated significantly with the V gene mutation biases to the CDR predicted by our models. Finally, it appears that the mutation bias in V genes indeed relates to their long-term survival in actual human repertoires. We observed that resting repertoires of B cells overexpressed V genes that were especially biased towards focused mutation and change in the CDR. This bias in V gene usage was somewhat relaxed at the height of the immune response to a vaccine, presumably because of the need for a wider diversity in a primary response. However, older patients did not retain this flexibility and were biased towards using only highly skewed V genes at all stages of their response. PMID:25660968

B cell variable genes have evolved their codon usage to focus the targeted patterns of somatic mutation on the complementarity determining regions.

PubMed

Saini, Jasmine; Hershberg, Uri

2015-05-01

The exceptional ability of B cells to diversify through somatic mutation and improve affinity of the repertoire toward the antigens is the cornerstone of adaptive immunity. Somatic mutation is not evenly distributed and exhibits certain micro-sequence specificities. We show here that the combination of somatic mutation targeting and the codon usage in human B cell receptor (BCR) Variable (V) genes create expected patterns of mutation and post mutation changes that are focused on their complementarity determining regions (CDR). T cell V genes are also skewed in targeting mutations but to a lesser extent and are lacking the codon usage bias observed in BCRs. This suggests that the observed skew in T cell receptors is due to their amino acid usage, which is similar to that of BCRs. The mutation targeting and the codon bias allow B cell CDRs to diversify by specifically accumulating nonconservative changes. We counted the distribution of mutations to CDR in 4 different human datasets. In all four cases we found that the number of actual mutations in the CDR correlated significantly with the V gene mutation biases to the CDR predicted by our models. Finally, it appears that the mutation bias in V genes indeed relates to their long-term survival in actual human repertoires. We observed that resting repertoires of B cells overexpressed V genes that were especially biased toward focused mutation and change in the CDR. This bias in V gene usage was somewhat relaxed at the height of the immune response to a vaccine, presumably because of the need for a wider diversity in a primary response. However, older patients did not retain this flexibility and were biased toward using only highly skewed V genes at all stages of their response. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of cloud horizontal inhomogeneity and directional sampling on the retrieval of cloud droplet size by the POLDER instrument

NASA Astrophysics Data System (ADS)

Shang, H.; Chen, L.; Bréon, F. M.; Letu, H.; Li, S.; Wang, Z.; Su, L.

2015-11-01

The principles of cloud droplet size retrieval via Polarization and Directionality of the Earth's Reflectance (POLDER) requires that clouds be horizontally homogeneous. The retrieval is performed by combining all measurements from an area of 150 km × 150 km to compensate for POLDER's insufficient directional sampling. Using POLDER-like data simulated with the RT3 model, we investigate the impact of cloud horizontal inhomogeneity and directional sampling on the retrieval and analyze which spatial resolution is potentially accessible from the measurements. Case studies show that the sub-grid-scale variability in droplet effective radius (CDR) can significantly reduce valid retrievals and introduce small biases to the CDR (~ 1.5 μm) and effective variance (EV) estimates. Nevertheless, the sub-grid-scale variations in EV and cloud optical thickness (COT) only influence the EV retrievals and not the CDR estimate. In the directional sampling cases studied, the retrieval using limited observations is accurate and is largely free of random noise. Several improvements have been made to the original POLDER droplet size retrieval. For example, measurements in the primary rainbow region (137-145°) are used to ensure retrievals of large droplet (> 15 μm) and to reduce the uncertainties caused by cloud heterogeneity. We apply the improved method using the POLDER global L1B data from June 2008, and the new CDR results are compared with the operational CDRs. The comparison shows that the operational CDRs tend to be underestimated for large droplets because the cloudbow oscillations in the scattering angle region of 145-165° are weak for cloud fields with CDR > 15 μm. Finally, a sub-grid-scale retrieval case demonstrates that a higher resolution, e.g., 42 km × 42 km, can be used when inverting cloud droplet size distribution parameters from POLDER measurements.

Regulation of the CgPdr1 Transcription Factor from the Pathogen Candida glabrata ▿

PubMed Central

Paul, Sanjoy; Schmidt, Jennifer A.; Moye-Rowley, W. Scott

2011-01-01

Candida glabrata is an opportunistic human pathogen that is increasingly associated with candidemia, owing in part to the intrinsic and acquired high tolerance the organism exhibits for the important clinical antifungal drug fluconazole. This elevated fluconazole resistance often develops through gain-of-function mutations in the zinc cluster-containing transcriptional regulator C. glabrata Pdr1 (CgPdr1). CgPdr1 induces the expression of an ATP-binding cassette (ABC) transporter-encoding gene, CgCDR1. Saccharomyces cerevisiae has two CgPdr1 homologues called ScPdr1 and ScPdr3. These factors control the expression of an ABC transporter-encoding gene called ScPDR5, which encodes a homologue of CgCDR1. Loss of the mitochondrial genome (ρ0 cell) or overexpression of the mitochondrial enzyme ScPsd1 induces ScPDR5 expression in a strictly ScPdr3-dependent fashion. ScPdr3 requires the presence of a transcriptional Mediator subunit called Gal11 (Med15) to fully induce ScPDR5 transcription in response to ρ0 signaling. ScPdr1 does not respond to either ρ0 signals or ScPsd1 overproduction. In this study, we employed transcriptional fusions between CgPdr1 target promoters, like CgCDR1, to demonstrate that CgPdr1 stimulates gene expression via binding to elements called pleiotropic drug response elements (PDREs). Deletion mapping and electrophoretic mobility shift assays demonstrated that a single PDRE in the CgCDR1 promoter was capable of supporting ρ0-induced gene expression. Removal of one of the two ScGal11 homologues from C. glabrata caused a major defect in drug-induced expression of CgCDR1 but had a quantitatively minor effect on ρ0-stimulated transcription. These data demonstrate that CgPdr1 appears to combine features of ScPdr1 and ScPdr3 to produce a transcription factor with chimeric regulatory properties. PMID:21131438

Cognitive changes after parathyroidectomy in patients with secondary hyperparathyroidism.

PubMed

Chou, Fong-Fu; Chen, Jin-Bor; Hsieh, Kun-Chou; Liou, Chia-Wei

2008-04-01

Cognitive impairment was frequently reported in uremic patients with dialysis, but improvements of cognition after parathyroidectomy for symptomatic secondary hyperparathyroidism have never been reported before. Thirty-nine patients, who were successfully operated on with total parathyroidectomy plus autotransplantation were enrolled. Twenty-three dialysis patients, age >50 years, who had a serum level of intact parathyroid hormone (iPTH) greater than 650 pg/ml, and who did not undergo parathyroidectomy were selected as the control group. The mini-mental state examination (MMSE) and the clinical dementia rating (CDR) test were administered to all patients. Before the operation, educational level, symptoms of bone pain, skin itching, general weakness and insomnia were recorded and serum levels of calcium, phosphorus, alkaline phosphatase (Alk-ptase), iPTH, aluminum, and hemoglobin were measured in the study and control groups. At 12-week postoperatively, serum levels of calcium, phosphorus, Alk-ptase, iPTH, and aluminum were measured again and at 16-week postoperatively, the MMSE and the CDR test were administered again. In the control group, both MMSE and CDR test were administered again after the period or 16-week. Serum calcium level was only significant difference (p = 0.002), whereas clinical symptoms, gender, etiologies of secondary hyperparathyroidism, duration of dialysis, educational level, age, and serum levels of phosphorus, Alk-ptase, iPTH, aluminum, and hemoglobin were not significantly different between the two groups. The educational level was the only factor affecting MMSE scores (p = 0.003). In the study group, at 12-week postoperatively, symptoms improved significantly, serum levels of calcium, phosphorus, Alk-ptase, iPTH, and aluminum decreased significantly, and at 16-week postoperatively, MMSE scores increased from 25 +/- 5 (mean +/- SD) to 26 +/- 5 (p < 0.001) and CDR scales decreased significantly (p < 0.001). Neither MMSE scores nor CDR scales of the control group changed significantly after the 16-week period. Parathyroidectomy for symptomatic secondary hyperparathyroidism can improve cognition.

Diaphragmatic mobility in healthy subjects during incentive spirometry with a flow-oriented device and with a volume-oriented device.

PubMed

Yamaguti, Wellington Pereira dos Santos; Sakamoto, Eliana Takahama; Panazzolo, Danilo; Peixoto, Corina da Cunha; Cerri, Giovanni Guido; Albuquerque, André Luis Pereira

2010-01-01

To compare the diaphragmatic mobility of healthy subjects during incentive spirometry with a volume-oriented device, during incentive spirometry with a flow-oriented device, and during diaphragmatic breathing. To compare men and women in terms of diaphragmatic mobility during these three types of breathing exercises. We evaluated the pulmonary function and diaphragmatic mobility of 17 adult healthy volunteers (9 women and 8 men). Diaphragmatic mobility was measured via ultrasound during diaphragmatic breathing and during the use of the two types of incentive spirometers. Diaphragmatic mobility was significantly greater during the use of the volume-oriented incentive spirometer than during the use of the flow-oriented incentive spirometer (70.16 ± 12.83 mm vs. 63.66 ± 10.82 mm; p = 0.02). Diaphragmatic breathing led to a greater diaphragmatic mobility than did the use of the flow-oriented incentive spirometer (69.62 ± 11.83 mm vs. 63.66 ± 10.82 mm; p = 0.02). During all three types of breathing exercises, the women showed a higher mobility/FVC ratio than did the men. Incentive spirometry with a volume-oriented device and diaphragmatic breathing promoted greater diaphragmatic mobility than did incentive spirometry with a flow-oriented device. Women performed better on the three types of breathing exercises than did men.

The Art of Space Flight Exercise Hardware: Design and Implementation

NASA Technical Reports Server (NTRS)

Beyene, Nahom M.

2004-01-01

The design of space flight exercise hardware depends on experience with crew health maintenance in a microgravity environment, history in development of flight-quality exercise hardware, and a foundation for certifying proper project management and design methodology. Developed over the past 40 years, the expertise in designing exercise countermeasures hardware at the Johnson Space Center stems from these three aspects of design. The medical community has steadily pursued an understanding of physiological changes in humans in a weightless environment and methods of counteracting negative effects on the cardiovascular and musculoskeletal system. The effects of weightlessness extend to the pulmonary and neurovestibular system as well with conditions ranging from motion sickness to loss of bone density. Results have shown losses in water weight and muscle mass in antigravity muscle groups. With the support of university-based research groups and partner space agencies, NASA has identified exercise to be the primary countermeasure for long-duration space flight. The history of exercise hardware began during the Apollo Era and leads directly to the present hardware on the International Space Station. Under the classifications of aerobic and resistive exercise, there is a clear line of development from the early devices to the countermeasures hardware used today. In support of all engineering projects, the engineering directorate has created a structured framework for project management. Engineers have identified standards and "best practices" to promote efficient and elegant design of space exercise hardware. The quality of space exercise hardware depends on how well hardware requirements are justified by exercise performance guidelines and crew health indicators. When considering the microgravity environment of the device, designers must consider performance of hardware separately from the combined human-in-hardware system. Astronauts are the caretakers of the hardware while it is deployed and conduct all sanitization, calibration, and maintenance for the devices. Thus, hardware designs must account for these issues with a goal of minimizing crew time on orbit required to complete these tasks. In the future, humans will venture to Mars and exercise countermeasures will play a critical role in allowing us to continue in our spirit of exploration. NASA will benefit from further experimentation on Earth, through the International Space Station, and with advanced biomechanical models to quantify how each device counteracts specific symptoms of weightlessness. With the continued support of international space agencies and the academic research community, we will usher the next frontier in human space exploration.

A CMOS merged CDR and continuous-time adaptive equalizer

NASA Astrophysics Data System (ADS)

Sánchez-Azqueta, C.; Aguirre, J.; Gimeno, C.; Aldea, C.; Celma, S.

2015-06-01

We present a low-voltage merged CDR and cntinuous-time adaptive equalizer capable to compensate the attenu- ation of a SI-POF channel while at the same time synchronizing and regenerating the incoming signal in a single stage. The system operates at 1.25 Gbps for NRZ modulation through a 50-m SI-POF channel and it is designed in standard 0.18-μm CMOS fed at 1 V with a power consumption of 43.4 mW.

Journal of Special Operations Medicine Volume 1, Edition 2

DTIC Science & Technology

2001-01-01

news.... New Group Surgeons at ONE: LCDR Kevin Walters and CDR Scott Flin; at TWO: LT Jose Henao�, at DEVGRU: CDR Fenton , and at BUD/s: LT Ware. Look...be eligible for this surgery. A common belief is that refractive surgery is a � cosmetic � surgical procedure only designed to free one from wearing...corrective glasses, and that the mili- tary should not be in the � cosmetic � business. How- ever, this is a technique for enhancement of soldier readi

Thickener/Fluid Interaction in Lubricating Greases

DTIC Science & Technology

1984-05-01

I) p V * .’ .. 21 ___ to & - -9 01 o0 lw0 ca 4 C., trn u ’ ri" cU, 23z "iFQ Ig. C14i~~ z NAii W -W_; 24 C49 c - C-, cn4 II 1- .0, co 4 fa1 41 t 1-4...STRNA-YE (DR KAPLAN ) 1 AITN: STECR-TA STRNA-U I APO SEATTLE 98733 NATICK MA 01760 CDR CDR US ARMY RSCH & STDZN GROUP US ARMY RESEARCH OFFICE (EUROPE

Validity and Reliability of Devices That Assess Body Temperature During Indoor Exercise in the Heat

PubMed Central

Ganio, Matthew S; Brown, Christopher M; Casa, Douglas J; Becker, Shannon M; Yeargin, Susan W; McDermott, Brendon P; Boots, Lindsay M; Boyd, Paul W; Armstrong, Lawrence E; Maresh, Carl M

2009-01-01

Context: When assessing exercise hyperthermia outdoors, the validity of certain commonly used body temperature measuring devices has been questioned. A controlled laboratory environment is generally less influenced by environmental factors (eg, ambient temperature, solar radiation, wind) than an outdoor setting. The validity of these temperature measuring devices in a controlled environment may be more acceptable. Objective: To assess the validity and reliability of commonly used temperature devices compared with rectal temperature in individuals exercising in a controlled, high environmental temperature indoor setting and then resting in a cool environment. Design: Time series study. Setting: Laboratory environmental chamber (temperature  =  36.4 ± 1.2°C [97.5 ± 2.16°F], relative humidity  =  52%) and cool laboratory (temperature  =  approximately 23.3°C [74.0°F], relative humidity  =  40%). Patients or Other Participants: Fifteen males and 10 females. Intervention(s): Rectal, gastrointestinal, forehead, oral, aural, temporal, and axillary temperatures were measured with commonly used temperature devices. Temperature was measured before and 20 minutes after entering the environmental chamber, every 30 minutes during a 90-minute treadmill walk in the heat, and every 20 minutes during a 60-minute rest in mild conditions. Device validity and reliability were assessed with various statistical measures to compare the measurements using each device with rectal temperature. A device was considered invalid if the mean bias (average difference between rectal and device temperatures) was more than ±0.27°C (±0.50°F). Main Outcome Measure(s): Measured temperature from each device (mean and across time). Results: The following devices provided invalid estimates of rectal temperature: forehead sticker (0.29°C [0.52°F]), oral temperature using an inexpensive device (−1.13°C [−2.03°F]), temporal temperature measured according to the instruction manual (−0.87°C [−1.56°F]), temporal temperature using a modified technique (−0.63°C [−1.13°F]), oral temperature using an expensive device (−0.86°C, [−1.55°F]), aural temperature (−0.67°C, [−1.20°F]), axillary temperature using an inexpensive device (−1.25°C, [−2.24°F]), and axillary temperature using an expensive device (−0.94°F [−1.70°F]). Measurement of intestinal temperature (mean bias of −0.02°C [−0.03°F]) was the only device considered valid. Devices measured in succession (intestinal, forehead, temporal, and aural) showed acceptable reliability (all had a mean bias  =  0.09°C [0.16°F] and r ≥ 0.94]). Conclusions: Even during laboratory exercise in a controlled environment, devices used to measure forehead, temporal, oral, aural, and axillary body sites did not provide valid estimates of rectal temperature. Only intestinal temperature measurement met the criterion. Therefore, we recommend that rectal or intestinal temperature be used to assess hyperthermia in individuals exercising indoors in the heat. PMID:19295956

Thirsk on ARED

NASA Image and Video Library

2009-06-05

ISS020-E-007089 (5 June 2009) --- European Space Agency astronaut Frank De Winne, Expedition 20 flight engineer, exercises using the advanced Resistive Exercise Device (aRED) in the Unity node of the International Space Station.

Validity and Reliability of the PUSH Wearable Device to Measure Movement Velocity During the Back Squat Exercise.

PubMed

Balsalobre-Fernández, Carlos; Kuzdub, Matt; Poveda-Ortiz, Pedro; Campo-Vecino, Juan Del

2016-07-01

Balsalobre-Fernández, C, Kuzdub, M, Poveda-Ortiz, P, and Campo-Vecino, Jd. Validity and reliability of the PUSH wearable device to measure movement velocity during the back squat exercise. J Strength Cond Res 30(7): 1968-1974, 2016-The purpose of this study was to analyze the validity and reliability of a wearable device to measure movement velocity during the back squat exercise. To do this, 10 recreationally active healthy men (age = 23.4 ± 5.2 years; back squat 1 repetition maximum [1RM] = 83 ± 8.2 kg) performed 3 repetitions of the back squat exercise with 5 different loads ranging from 25 to 85% 1RM on a Smith Machine. Movement velocity for each of the total 150 repetitions was simultaneously recorded using the T-Force linear transducer (LT) and the PUSH wearable band. Results showed a high correlation between the LT and the wearable device mean (r = 0.85; standard error of estimate [SEE] = 0.08 m·s) and peak velocity (r = 0.91, SEE = 0.1 m·s). Moreover, there was a very high agreement between these 2 devices for the measurement of mean (intraclass correlation coefficient [ICC] = 0.907) and peak velocity (ICC = 0.944), although a systematic bias between devices was observed (PUSH peak velocity being -0.07 ± 0.1 m·s lower, p ≤ 0.05). When measuring the 3 repetitions with each load, both devices displayed almost equal reliability (Test-retest reliability: LT [r = 0.98], PUSH [r = 0.956]; ICC: LT [ICC = 0.989], PUSH [ICC = 0.981]; coefficient of variation [CV]: LT [CV = 4.2%], PUSH [CV = 5.0%]). Finally, individual load-velocity relationships measured with both the LT (R = 0.96) and the PUSH wearable device (R = 0.94) showed similar, very high coefficients of determination. In conclusion, these results support the use of an affordable wearable device to track velocity during back squat training. Wearable devices, such as the one in this study, could have valuable practical applications for strength and conditioning coaches.

Countermeasures (iRED, ARED CEVIS, MEC, TVIS, T2, Periodic Fitness Evaluation, BP-ECG, HRM). Critical Readiness Review Increment 23 and 24

NASA Technical Reports Server (NTRS)

Toder, Carly; Gipson, Iona; Conly, Danielle; Nieschwitz, Linda; Perk, Austin

2010-01-01

This slide presentation reviews attempts to counteract the effects of being in space. It includes information on the Resistive Exercise Device (RED), the Advanced Resistive Exercise Device (ARED), Cycle Ergometer with Vibration Isolation and Stabilization (CEVIS), Treadmill with Vibration Isolation and Stabilization (TVIS) and periodic fitness evaluation with specific information on BP/ECG, heart rate monitor 2 and data distribution.

Using Non-Traditional Interfaces to Support Physical Therapy for Knee Strengthening.

PubMed

Torres, Andrea; López, Gustavo; Guerrero, Luis A

2016-09-01

Physical therapy consists mainly in the execution of rehabilitation processes that aim to help overcome injuries, as well as develop, maintain, or restore maximum body movement. Knee rehabilitation is one kind of physical therapy that requires daily exercises which could be considered monotonous and boring by the patients, discouraging their improvement. This is coupled with the fact that most physical therapists assess exercise performance through verbal and visual means with mostly manual measurements, making it difficult to constantly verify and validate if patients perform the exercises correctly. This article describes a physical therapy monitoring system that uses wearable technology to assess exercise performance and patient progress. This wearable device is able to measure and transfer the movement's data from the patient's limb to a mobile device. Moreover, the user interface is a game, which provides an entertaining approach to therapy exercising. In this article, it is shown that the developed system significantly increases daily user engagement in rehabilitation exercises, through a gameplay that matches physical therapy requirements for knee rehabilitation, as well as offering useful quantitative information to therapists.

Intercomparison of PERSIANN-CDR and TRMM-3B42V7 precipitation estimates at monthly and daily time scales

NASA Astrophysics Data System (ADS)

Katiraie-Boroujerdy, Pari-Sima; Akbari Asanjan, Ata; Hsu, Kuo-lin; Sorooshian, Soroosh

2017-09-01

In the first part of this paper, monthly precipitation data from Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks-Climate Data Record (PERSIANN-CDR) and Tropical Rainfall Measuring Mission 3B42 algorithm Version 7 (TRMM-3B42V7) are evaluated over Iran using the Generalized Three-Cornered Hat (GTCH) method which is self-sufficient of reference data as input. Climate Data Unit (CRU) is added to the GTCH evaluations as an independent gauge-based dataset thus, the minimum requirement of three datasets for the model is satisfied. To ensure consistency of all datasets, the two satellite products were aggregated to 0.5° spatial resolution, which is the minimum resolution of CRU. The results show that the PERSIANN-CDR has higher Signal to Noise Ratio (SNR) than TRMM-3B42V7 for the monthly rainfall estimation, especially in the northern half of the country. All datasets showed low SNR in the mountainous area of southwestern Iran, as well as the arid parts in the southeast region of the country. Additionally, in order to evaluate the efficacy of PERSIANN-CDR and TRMM-3B42V7 in capturing extreme daily-precipitation amounts, an in-situ rain-gauge dataset collected by the Islamic Republic of the Iran Meteorological Organization (IRIMO) was employed. Given the sparsity of the rain gauges, only 0.25° pixels containing three or more gauges were used for this evaluation. There were 228 such pixels where daily and extreme rainfall from PERSIANN-CDR and TRMM-3B42V7 could be compared. However, TRMM-3B42V7 overestimates most of the intensity indices (correlation coefficients; R between 0.7648-0.8311, Root Mean Square Error; RMSE between 3.29mm/day-21.2mm/5day); PERSIANN-CDR underestimates these extremes (R between 0.6349-0.7791 and RMSE between 3.59mm/day-30.56mm/5day). Both satellite products show higher correlation coefficients and lower RMSEs for the annual mean of consecutive dry spells than wet spells. The results show that TRMM-3B42V7 can capture the annual mean of the absolute indices (the number of wet days in which daily precipitation > 10 mm, 20 mm) better than PERSIANN-CDR. The results of daily evaluations show that the similarity of Empirical Cumulative Density Function (ECDF) of satellite products and IRIMO gauges daily precipitation, as well as dry spells with different thresholds in some selected pixels (include at least five gauges), are significant. The results also indicate that ECDFs become more significant when threshold increases. In terms of regional analyses, the higher SNR of the products on monthly (based on the GTCH method) and daily evaluations (significant ECDFs) is mostly consistent.

Vibration Isolation and Stabilization System for Spacecraft Exercise Treadmill Devices

NASA Technical Reports Server (NTRS)

Fialho, Ian; Tyer, Craig; Murphy, Bryan; Cotter, Paul; Thampi, Sreekumar

2011-01-01

A novel, passive system has been developed for isolating an exercise treadmill device from a spacecraft in a zero-G environment. The Treadmill 2 Vibration Isolation and Stabilization System (T2-VIS) mechanically isolates the exercise treadmill from the spacecraft/space station, thereby eliminating the detrimental effect that high impact loads generated during walking/running would have on the spacecraft structure and sensitive microgravity science experiments. This design uses a second stage spring, in series with the first stage, to achieve an order of magnitude higher exercise- frequency isolation than conventional systems have done, while maintaining desirable low-frequency stability performance. This novel isolator design, in conjunction with appropriately configured treadmill platform inertia properties, has been shown (by on-orbit zero-G testing onboard the International Space Station) to deliver exceedingly high levels of isolation/ stability performance.

Ground Reaction Force and Mechanical Differences Between the Interim Resistive Exercise Device (iRED) and Smith Machine While Performing a Squat

NASA Technical Reports Server (NTRS)

Amonette, William E.; Bentley, Jason R.; Lee, Stuart M. C.; Loehr, James A.; Schneider, Suzanne

2004-01-01

Musculoskeletal unloading in microgravity has been shown to induce losses in bone mineral density, muscle cross-sectional area, and muscle strength. Currently, an Interim Resistive Exercise Device (iRED) is being flown on board the ISS to help counteract these losses. Free weight training has shown successful positive musculoskeletal adaptations. In biomechanical research, ground reaction forces (GRF) trajectories are used to define differences between exercise devices. The purpose of this evaluation is to quantify the differences in GRF between the iRED and free weight exercise performed on a Smith machine during a squat. Due to the differences in resistance properties, inertial loading and load application to the body between the two devices, we hypothesize that subjects using iRED will produce GRF that are significantly different from the Smith machine. There will be differences in bar/harness range of motion and the time when peak GRF occurred in the ROMbar. Three male subjects performed three sets of ten squats on the iRED and on the Smith Machine on two separate days at a 2-second cadence. Statistically significant differences were found between the two devices in all measured GRF variables. Average Fz and Fx during the Smith machine squat were significantly higher than iRED. Average Fy (16.82 plus or minus.23; p less than .043) was significantly lower during the Smith machine squat. The mean descent/ascent ratio of the magnitude of the resultant force vector of all three axes for the Smith machine and iRED was 0.95 and 0.72, respectively. Also, the point at which maximum Fz occurred in the range of motion (Dzpeak) was at different locations with the two devices.

Alternative pathways to the 1.5 °C target reduce the need for negative emission technologies

NASA Astrophysics Data System (ADS)

van Vuuren, Detlef P.; Stehfest, Elke; Gernaat, David E. H. J.; van den Berg, Maarten; Bijl, David L.; de Boer, Harmen Sytze; Daioglou, Vassilis; Doelman, Jonathan C.; Edelenbosch, Oreane Y.; Harmsen, Mathijs; Hof, Andries F.; van Sluisveld, Mariësse A. E.

2018-05-01

Mitigation scenarios that achieve the ambitious targets included in the Paris Agreement typically rely on greenhouse gas emission reductions combined with net carbon dioxide removal (CDR) from the atmosphere, mostly accomplished through large-scale application of bioenergy with carbon capture and storage, and afforestation. However, CDR strategies face several difficulties such as reliance on underground CO2 storage and competition for land with food production and biodiversity protection. The question arises whether alternative deep mitigation pathways exist. Here, using an integrated assessment model, we explore the impact of alternative pathways that include lifestyle change, additional reduction of non-CO2 greenhouse gases and more rapid electrification of energy demand based on renewable energy. Although these alternatives also face specific difficulties, they are found to significantly reduce the need for CDR, but not fully eliminate it. The alternatives offer a means to diversify transition pathways to meet the Paris Agreement targets, while simultaneously benefiting other sustainability goals.

Homogeneity of a Global Multisatellite Soil Moisture Climate Data Record

NASA Technical Reports Server (NTRS)

Su, Chun-Hsu; Ryu, Dongryeol; Dorigo, Wouter; Zwieback, Simon; Gruber, Alexander; Albergel, Clement; Reichle, Rolf H.; Wagner, Wolfgang

2016-01-01

Climate Data Records (CDR) that blend multiple satellite products are invaluable for climate studies, trend analysis and risk assessments. Knowledge of any inhomogeneities in the CDR is therefore critical for making correct inferences. This work proposes a methodology to identify the spatiotemporal extent of the inhomogeneities in a 36-year, global multisatellite soil moisture CDR as the result of changing observing systems. Inhomogeneities are detected at up to 24 percent of the tested pixels with spatial extent varying with satellite changeover times. Nevertheless, the contiguous periods without inhomogeneities at changeover times are generally longer than 10 years. Although the inhomogeneities have measurable impact on the derived trends, these trends are similar to those observed in ground data and land surface reanalysis, with an average error less than 0.003 cubic meters per cubic meter per year. These results strengthen the basis of using the product for long-term studies and demonstrate the necessity of homogeneity testing of multisatellite CDRs in general.

ECOSYSTEM IMPACTS OF GEOENGINEERING: A Review for Developing a Science Plan

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

Russell, Lynn M.; Rasch, Philip J.; Mace, Georgina

2012-06-01

Geoengineering methods are intended to reduce the magnitude of climate change. Climate change in some regions is already having demonstrable effects on ecosystem structure and functioning. Two different types of geoengineering activities have been proposed: carbon dioxide removal (CDR), which includes a range of engineered and biological processes to remove carbon dioxide (CO2) from the atmosphere, and solar radiation management (SRM, or sunlight reflection methods), whereby a small percentage of sunlight is reflected back into space to offset warming from greenhouse gases. In this review, we evaluate some of the possible impacts of CDR and SRM on the physical climatemore » and their subsequent influence on ecosystems, including the risks and uncertainties associated with new kinds of purposeful perturbations to Earth. Specifically, we find evidence that, if implemented successfully, some CDR methods and continue use of some SRM methods) could alleviate some of the deleterious ecosystem impacts associated with climate changes that might occur in the foreseeable future.« less

Department of the Navy Fiscal Year (FY) 2000/2001 Biennial Budget Estimates, Justification of Estimates, February 1999 Research, Development, Test & Evaluation, Navy Budget Activity 5.

DTIC Science & Technology

1999-02-01

jjAi id ß g§s(ö rH^^-H ■J a) wm 4J ft & ü o o P .y rHrH id CDrH (D 0, > id 01 _Ö <D pQw > a oi rr) OCD lj 01a id *^r5 CD ft...Old cu-O § d id u cu •H u d co P P CD 3 M Ol O rH -H (D &CÜH43P CD 5H d CtJ d CDrH CU O PrH P ■O CO d-H CD d U-H s ^ Id CD QH...H P CN CD P P I -H <D drH EH M43 CDrH H O P-H 10 CD S-0 >iP PS drH g IdrH > CD CD Id Ol Ä4JJJ3S P 01 CU C0-H >ld"H Ol

Summary and recommendations for initial exercise prescription

NASA Technical Reports Server (NTRS)

Stewart, Donald F.; Harris, Bernard A., Jr.

1989-01-01

The recommendations summarized herein constitute a basis on which an initial exercise prescription can be formulated. It is noteworthy that any exercise program designed currently would be an approximation. Examination of the existing space-flight data reveals a scarcity of in-flight data on which to rigorously design an exercise program. The relevant experience within the U.S. space program (with regard to long-duration space flight) is limited to the Skylab Program. Lessons learned from Skylab are relevant to the design of a Space Station exercise program, especially with regard to the total length of exercise time required, cardiovascular (CV) deconditioning/reconditioning, and bone loss. Certain observations of the U.S.S.R. exercise activities can also contribute to the formulation of an exercise prescription of Space Station. Reportedly, the U.S.S.R. uses both a bicycle ergometer and a treadmill device on long-duration missions with some degree of success. Using the third crew of Salyut 6, which was a 175-day stay, as a representative mission, the typical time dedicated to exercise varies from 2 to 3 hours per day. In addition, the cosmonauts wear an elasticized suit, called a penquin suit, for time periods ranging from 12 to 16 hours per day. This device provides a load across the axial skeleton against which the wearer must exert himself. Despite these extensive countermeasures, the effects of adaptation are not totally prevented.

Epitope mapping of anti-interleukin-13 neutralizing antibody CNTO607.

PubMed

Teplyakov, Alexey; Obmolova, Galina; Wu, Sheng-Jiun; Luo, Jinquan; Kang, James; O'Neil, Karyn; Gilliland, Gary L

2009-05-29

CNTO607 is a neutralizing anti-interleukin-13 (IL-13) human monoclonal antibody obtained from a phage display library. To determine how this antibody inhibits the biological effect of IL-13, we determined the binding epitope by X-ray crystallography. The crystal structure of the complex between CNTO607 Fab and IL-13 reveals the antibody epitope at the surface formed by helices A and D of IL-13. This epitope overlaps with the IL-4Ralpha/IL-13Ralpha1 receptor-binding site, which explains the neutralizing effect of CNTO607. The extensive antibody interface covers an area of 1000 A(2), which is consistent with the high binding affinity. The key features of the interface are the charge and shape complementarity of the molecules that include two hydrophobic pockets on IL-13 that accommodate Phe32 [complementarity-determining region (CDR) L2] and Trp100a (CDR H3) and a number of salt bridges between basic residues of IL-13 and acidic residues of the antibody. Comparison with the structure of the free Fab shows that the CDR residues do not change their conformation upon complex formation, with the exception of two residues in CDR H3, Trp100a and Asp100b, which change rotamer conformations. To evaluate the relative contribution of the epitope residues to CNTO607 binding, we performed alanine-scanning mutagenesis of the A-D region of IL-13. This study confirmed the primary role of electrostatic interactions for antigen recognition.

Crystal Structure of the Neutralizing Llama VHH D7 and Its Mode of HIV-1 gp120 Interaction

PubMed Central

Hinz, Andreas; Lutje Hulsik, David; Forsman, Anna; Koh, Willie Wee-Lee; Belrhali, Hassan; Gorlani, Andrea; de Haard, Hans; Weiss, Robin A.; Verrips, Theo; Weissenhorn, Winfried

2010-01-01

HIV-1 entry into host cells is mediated by the sequential binding of the envelope glycoprotein gp120 to CD4 and a chemokine receptor. Antibodies binding to epitopes overlapping the CD4-binding site on gp120 are potent inhibitors of HIV entry, such as the llama heavy chain antibody fragment VHH D7, which has cross-clade neutralizing properties and competes with CD4 and mAb b12 for high affinity binding to gp120. We report the crystal structure of the D7 VHH at 1.5 Å resolution, which reveals the molecular details of the complementarity determining regions (CDR) and substantial flexibility of CDR3 that could facilitate an induced fit interaction with gp120. Structural comparison of CDRs from other CD4 binding site antibodies suggests diverse modes of interaction. Mutational analysis identified CDR3 as a key component of gp120 interaction as determined by surface plasmon resonance. A decrease in affinity is directly coupled to the neutralization efficiency since mutations that decrease gp120 interaction increase the IC50 required for HIV-1 IIIB neutralization. Thus the structural study identifies the long CDR3 of D7 as the key determinant of interaction and HIV-1 neutralization. Furthermore, our data confirm that the structural plasticity of gp120 can accommodate multiple modes of antibody binding within the CD4 binding site. PMID:20463957

Translation, cross-cultural adaptation and applicability of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS)

PubMed Central

Lima-Silva, Thais Bento; Bahia, Valéria Santoro; Carvalho, Viviane Amaral; Guimarães, Henrique Cerqueira; Caramelli, Paulo; Balthazar, Márcio; Damasceno, Benito; Bottino, Cássio Machado de Campos; Brucki, Sônia Maria Dozzi; Mioshi, Eneida; Nitrini, Ricardo; Yassuda, Mônica Sanches

2013-01-01

BACKGROUND Staging scales for dementia have been devised for grading Alzheimer's disease (AD) but do not include the specific symptoms of frontotemporal lobar degeneration (FTLD). OBJECTIVE To translate and adapt the Frontotemporal Dementia Rating Scale (FTD-FRS) to Brazilian Portuguese. METHODS The cross-cultural adaptation process consisted of the following steps: translation, back-translation (prepared by independent translators), discussion with specialists, and development of a final version after minor adjustments. A pilot application was carried out with 12 patients diagnosed with bvFTD and 11 with AD, matched for disease severity (CDR=1.0). The evaluation protocol included: Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), Executive Interview (EXIT-25), Neuropsychiatric Inventory (NPI), Frontotemporal Dementia Rating Scale (FTD-FRS) and Clinical Dementia Rating scale (CDR). RESULTS The Brazilian version of the FTD-FRS seemed appropriate for use in this country. Preliminary results revealed greater levels of disability in bvFTD than in AD patients (bvFTD: 25% mild, 50% moderate and 25% severe; AD: 36.36% mild, 63.64% moderate). It appears that the CDR underrates disease severity in bvFTD since a relevant proportion of patients rated as having mild dementia (CDR=1.0) in fact had moderate or severe levels of disability according to the FTD-FRS. CONCLUSION The Brazilian version of the FTD-FRS seems suitable to aid staging and determining disease progression. PMID:29213863

Impacts devalue the potential of large-scale terrestrial CO2 removal through biomass plantations

NASA Astrophysics Data System (ADS)

Boysen, L. R.; Lucht, W.; Gerten, D.; Heck, V.

2016-09-01

Large-scale biomass plantations (BPs) are often considered a feasible and safe climate engineering proposal for extracting carbon from the atmosphere and, thereby, reducing global mean temperatures. However, the capacity of such terrestrial carbon dioxide removal (tCDR) strategies and their larger Earth system impacts remain to be comprehensively studied—even more so under higher carbon emissions and progressing climate change. Here, we use a spatially explicit process-based biosphere model to systematically quantify the potentials and trade-offs of a range of BP scenarios dedicated to tCDR, representing different assumptions about which areas are convertible. Based on a moderate CO2 concentration pathway resulting in a global mean warming of 2.5 °C above preindustrial level by the end of this century—similar to the Representative Concentration Pathway (RCP) 4.5—we assume tCDR to be implemented when a warming of 1.5 °C is reached in year 2038. Our results show that BPs can slow down the progression of increasing cumulative carbon in the atmosphere only sufficiently if emissions are reduced simultaneously like in the underlying RCP4.5 trajectory. The potential of tCDR to balance additional, unabated emissions leading towards a business-as-usual pathway alike RCP8.5 is therefore very limited. Furthermore, in the required large-scale applications, these plantations would induce significant trade-offs with food production and biodiversity and exert impacts on forest extent, biogeochemical cycles and biogeophysical properties.

Correlation between overactive bladder symptom score and neuropsychological parameters in Alzheimer's disease patients with lower urinary tract symptom.

PubMed

Jung, Ha Bum; Choi, Don Kyoung; Lee, Seong Ho; Cho, Sung Tae; Na, Hae Ri; Park, Moon Ho

2017-01-01

To examine an association between the overactive bladder symptom score (OABSS) and neuropsychological parameters. Moreover, we investigate the factors that affect each item in the questionnaire. A total of 376 patients (males: 184; females: 192) with probable Alzheimer's disease (AD) were recruited. Cognitive testing was conducted using the Mini Mental Status Examination (MMSE), Clinical Dementia Rating (CDR) scale, Global Deterioration Scale (GDS), and Barthel Activities of Daily Living (ADL). Lower urinary tract symptom (LUTS) was assessed using OABSS and voiding diary. The prevalence of overactive bladder (OAB) (defined as OABSS ≥3 with na urgency score of ≥2) in patients with AD was 72.6%. Among the OAB subjects, the most common severity of symptom was moderate (72.6%), followed by mild (21.2%), and severe (5.8%). It was found that OABSS had a very high correlation with aging (r=0.75; p<0.001). When compared with neuropsychological parameters, it was found that OABSS was highly correlated with the CDR scores (r=0.446; p<0.001). However, no significant correlation was found between the changes in OABSS scores and those in other neuropsychological parameters. Based on the individual symptom scores, urgency incontinence was highly correlated with the CDR scores (r=0.43; p<0.001). OABSS is a useful tool in assessing AD patients with LUTS. There was a consistent positive association between OABSS severity, including urgency incontinence, and CDR scores. Copyright® by the International Brazilian Journal of Urology.

Anti-tumor activities of peptides corresponding to conserved complementary determining regions from different immunoglobulins.

PubMed

Figueiredo, Carlos R; Matsuo, Alisson L; Massaoka, Mariana H; Polonelli, Luciano; Travassos, Luiz R

2014-09-01

Short synthetic peptides corresponding to sequences of complementarity-determining regions (CDRs) from different immunoglobulin families have been shown to induce antimicrobial, antiviral and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). Presently, we studied the in vitro and in vivo antitumor activity of synthetic peptides derived from conserved CDR sequences of different immunoglobulins against human tumor cell lines and murine B16F10-Nex2 melanoma aiming at the discovery of candidate molecules for cancer therapy. Four light- and heavy-chain CDR peptide sequences from different antibodies (C36-L1, HA9-H2, 1-H2 and Mg16-H2) showed cytotoxic activity against murine melanoma and a panel of human tumor cell lineages in vitro. Importantly, they also exerted anti-metastatic activity using a syngeneic melanoma model in mice. Other peptides (D07-H3, MN20v1, MS2-H3) were also protective against metastatic melanoma, without showing significant cytotoxicity against tumor cells in vitro. In this case, we suggest that these peptides may act as immune adjuvants in vivo. As observed, peptides induced nitric oxide production in bone-marrow macrophages showing that innate immune cells can also be modulated by these CDR peptides. The present screening supports the search in immunoglobulins of rather frequent CDR sequences that are endowed with specific antitumor properties and may be candidates to be developed as anti-cancer drugs. Copyright © 2014 Elsevier Inc. All rights reserved.

Results of the first interim analysis of the RAPPER II trial in patients with spinal cord injury: ambulation and functional exercise programs in the REX powered walking aid.

PubMed

Birch, Nick; Graham, Jon; Priestley, Tom; Heywood, Chris; Sakel, Mohamed; Gall, Angela; Nunn, Andrew; Signal, Nada

2017-06-19

The RAPPER II study investigates the feasibility, safety and acceptability of using the REX self-stabilising robotic exoskeleton in people with spinal cord injury (SCI) who are obligatory wheelchair users. Feasibility is assessed by the completion of transfer into the REX device, competency in achieving autonomous control and completion of upper body exercise in an upright position in the REX device. Safety is measured by the occurrence of serious adverse events. Device acceptability is assessed with a user questionnaire. RAPPER II is a prospective, multi-centre, open label, non-randomised, non-comparative cohort study in people with SCI recruited from neurological rehabilitation centres in the United Kingdom, Australia and New Zealand. This is the planned interim report of the first 20 participants. Each completed a transfer into the REX, were trained to achieve machine control and completed Timed Up and Go (TUG) tests as well as upper body exercises in standing in a single first time session. The time to achieve each task as well as the amount of assistance required was recorded. After finishing the trial tasks a User Experience questionnaire, exploring device acceptability, was completed. All participants could transfer into the REX. The mean transfer time was 439 s. Nineteen completed the exercise regime. Eighteen could achieve autonomous control of the REX, 17 of whom needed either no assistance or the help of just one therapist. Eighteen participants completed at least one TUG test in a mean time of 313 s, 15 with the assistance of just one therapist. The questionnaire demonstrated high levels of acceptability amongst users. There were no Serious Adverse Events. This first interim analysis of RAPPER II shows that it is feasible and safe for people with SCI to use the REX powered assisted walking device to ambulate and exercise in. Participants with tetraplegia and paraplegia could walk and perform a functional exercise program when standing needing only modest levels of assistance in most cases. User acceptability was high. ClinicalTrials.gov , NCT02417532 . Registered 11 April 2015.

Limb Lengthening Surgery: Internal Lengthening Device (For Parents)

MedlinePlus

... and bathing. Your child will need help doing stretching and strengthening exercises. These are a very important ... therapy in a pool). Help your child with stretching and strengthening exercises. Give your child medicine for ...

Cardiovascular fitness strengthening using portable device.

PubMed

Alqudah, Hamzah; Kai Cao; Tao Zhang; Haddad, Azzam; Su, Steven; Celler, Branko; Nguyen, Hung T

2016-08-01

The paper describes a reliable and valid Portable Exercise Monitoring system developed using TI eZ430-Chronos watch, which can control the exercise intensity through audio stimulation in order to increase the Cardiovascular fitness strengthening.

Pelvic Support Problems

MedlinePlus

... pelvic exam, or special tests. Treatments include special pelvic muscle exercises called Kegel exercises. A mechanical support device called a pessary helps some women. Surgery and medicines are other treatments. NIH: National Institute of Child Health and Human Development

Rehabilitation interventions for pain and disability in osteoarthritis: a review of interventions including exercise, manual techniques, and assistive devices.

PubMed

Iversen, Maura Daly

2012-01-01

Osteoarthritis (OA) results in progressive destruction of articular cartilage and bone at the joint margins, leading to impairments extending far beyond the synovial joint. Rehabilitation interventions that target specific impairments and activity restrictions can help restore independence and promote healthy living. Such interventions include exercise, physical modalities (ice, heat, ultrasonography), manual techniques (mobilization and manipulation), and assistive devices. The predominance of evidence on the effects of rehabilitation interventions for knee and hip OA suggest that they afford modest pain relief, reduced disability, and improved function. Research is needed to identify the modes of exercise and the effective doses for relief of symptoms and functional limitations.

Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark.

PubMed

Rumfelt, Lynn L; Lohr, Rebecca L; Dooley, Helen; Flajnik, Martin F

2004-05-06

Adult cartilaginous fish express three immunoglobulin (Ig) isotypes, IgM, IgNAR and IgW. Newborn nurse sharks, Ginglymostoma cirratum, produce 19S (multimeric) IgM and monomeric/dimeric IgM1gj, a germline-joined, IgM-related VH, and very low amounts of 7S (monomeric) IgM and IgNAR proteins. Newborn IgNAR VH mRNAs are diverse in the complementarity-determining region 3 (CDR3) with non-templated nucleotide (N-region) addition, which suggests that, unlike in many other vertebrates, terminal deoxynucleotidyl transferase (TdT) expressed at birth is functional. IgW is present in the lungfish, a bony fish sharing a common ancestor with sharks 460 million years ago, implying that the IgW VH family is as old as the IgM VH family. This nurse shark study examined the IgM and IgW VH repertoire from birth through adult life, and analyzed the phylogenetic relationships of these gene families. IgM and IgW VH cDNA clones isolated from newborn nurse shark primary and secondary lymphoid tissues had highly diverse and unique CDR3 with N-region addition and VDJ gene rearrangement, implicating functional TdT and RAG gene activity. Despite the clear presence of N-region additions, newborn CDR3 were significantly shorter than those of adults. The IgM clones are all included in a conventional VH family that can be classified into five discrete groups, none of which is orthologous to IgM VH genes in other elasmobranchs. In addition, a novel divergent VH family was orthologous to a published monotypic VH horn shark family. IgW VH genes have diverged sufficiently to form three families. IgM and IgW VH serine codons using the potential somatic hypermutation hotspot sequence occur mainly in VH framework 1 (FR1) and CDR1. Phylogenetic analysis of cartilaginous fish and lungfish IgM and IgW demonstrated they form two major ancient gene groups; furthermore, these VH genes generally diversify (duplicate and diverge) within a species. As in ratfish, sandbar and horn sharks, most nurse shark IgM VH genes are from one family with multiple, heterogeneous loci. Their IgW VH genes have diversified, forming at least three families. The neonatal shark Ig VH CDR3 repertoire, diversified via N-region addition, is shorter than the adult VDJ junction, suggesting one means of postnatal repertoire diversification is expression of longer CDR3 junctions.

Uncertainty information in climate data records from Earth observation

NASA Astrophysics Data System (ADS)

Merchant, Christopher J.; Paul, Frank; Popp, Thomas; Ablain, Michael; Bontemps, Sophie; Defourny, Pierre; Hollmann, Rainer; Lavergne, Thomas; Laeng, Alexandra; de Leeuw, Gerrit; Mittaz, Jonathan; Poulsen, Caroline; Povey, Adam C.; Reuter, Max; Sathyendranath, Shubha; Sandven, Stein; Sofieva, Viktoria F.; Wagner, Wolfgang

2017-07-01

The question of how to derive and present uncertainty information in climate data records (CDRs) has received sustained attention within the European Space Agency Climate Change Initiative (CCI), a programme to generate CDRs addressing a range of essential climate variables (ECVs) from satellite data. Here, we review the nature, mathematics, practicalities, and communication of uncertainty information in CDRs from Earth observations. This review paper argues that CDRs derived from satellite-based Earth observation (EO) should include rigorous uncertainty information to support the application of the data in contexts such as policy, climate modelling, and numerical weather prediction reanalysis. Uncertainty, error, and quality are distinct concepts, and the case is made that CDR products should follow international metrological norms for presenting quantified uncertainty. As a baseline for good practice, total standard uncertainty should be quantified per datum in a CDR, meaning that uncertainty estimates should clearly discriminate more and less certain data. In this case, flags for data quality should not duplicate uncertainty information, but instead describe complementary information (such as the confidence in the uncertainty estimate provided or indicators of conditions violating the retrieval assumptions). The paper discusses the many sources of error in CDRs, noting that different errors may be correlated across a wide range of timescales and space scales. Error effects that contribute negligibly to the total uncertainty in a single-satellite measurement can be the dominant sources of uncertainty in a CDR on the large space scales and long timescales that are highly relevant for some climate applications. For this reason, identifying and characterizing the relevant sources of uncertainty for CDRs is particularly challenging. The characterization of uncertainty caused by a given error effect involves assessing the magnitude of the effect, the shape of the error distribution, and the propagation of the uncertainty to the geophysical variable in the CDR accounting for its error correlation properties. Uncertainty estimates can and should be validated as part of CDR validation when possible. These principles are quite general, but the approach to providing uncertainty information appropriate to different ECVs is varied, as confirmed by a brief review across different ECVs in the CCI. User requirements for uncertainty information can conflict with each other, and a variety of solutions and compromises are possible. The concept of an ensemble CDR as a simple means of communicating rigorous uncertainty information to users is discussed. Our review concludes by providing eight concrete recommendations for good practice in providing and communicating uncertainty in EO-based climate data records.

Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark

PubMed Central

Rumfelt, Lynn L; Lohr, Rebecca L; Dooley, Helen; Flajnik, Martin F

2004-01-01

Background Adult cartilaginous fish express three immunoglobulin (Ig) isotypes, IgM, IgNAR and IgW. Newborn nurse sharks, Ginglymostoma cirratum, produce 19S (multimeric) IgM and monomeric/dimeric IgM1gj, a germline-joined, IgM-related VH, and very low amounts of 7S (monomeric) IgM and IgNAR proteins. Newborn IgNAR VH mRNAs are diverse in the complementarity-determining region 3 (CDR3) with non-templated nucleotide (N-region) addition, which suggests that, unlike in many other vertebrates, terminal deoxynucleotidyl transferase (TdT) expressed at birth is functional. IgW is present in the lungfish, a bony fish sharing a common ancestor with sharks 460 million years ago, implying that the IgW VH family is as old as the IgM VH family. This nurse shark study examined the IgM and IgW VH repertoire from birth through adult life, and analyzed the phylogenetic relationships of these gene families. Results IgM and IgW VH cDNA clones isolated from newborn nurse shark primary and secondary lymphoid tissues had highly diverse and unique CDR3 with N-region addition and VDJ gene rearrangement, implicating functional TdT and RAG gene activity. Despite the clear presence of N-region additions, newborn CDR3 were significantly shorter than those of adults. The IgM clones are all included in a conventional VH family that can be classified into five discrete groups, none of which is orthologous to IgM VH genes in other elasmobranchs. In addition, a novel divergent VH family was orthologous to a published monotypic VH horn shark family. IgW VH genes have diverged sufficiently to form three families. IgM and IgW VH serine codons using the potential somatic hypermutation hotspot sequence occur mainly in VH framework 1 (FR1) and CDR1. Phylogenetic analysis of cartilaginous fish and lungfish IgM and IgW demonstrated they form two major ancient gene groups; furthermore, these VH genes generally diversify (duplicate and diverge) within a species. Conclusion As in ratfish, sandbar and horn sharks, most nurse shark IgM VH genes are from one family with multiple, heterogeneous loci. Their IgW VH genes have diversified, forming at least three families. The neonatal shark Ig VH CDR3 repertoire, diversified via N-region addition, is shorter than the adult VDJ junction, suggesting one means of postnatal repertoire diversification is expression of longer CDR3 junctions. PMID:15132758

Individual Characteristics and Unit Performance: A Review of Research and Methods

DTIC Science & Technology

1985-02-01

behavioral segments, improves performance. Simu- lation exercises , especially those employing new high-technology devices, provide surrogate...high-technology training simulation exercise MOB Military Occupational Specialty ORTT Operational Readiness Training Test-a field test REALTRAIN A...REAListic TRAINing simulation exercise SAM Surface-to-Air Missile SAT Scholastic Aptitude Test SQT Skill Qualification Test-an Army performance meas

Estimating Accuracy at Exercise Intensities: A Comparative Study of Self-Monitoring Heart Rate and Physical Activity Wearable Devices

PubMed Central

Dooley, Erin E; Golaszewski, Natalie M

2017-01-01

Background Physical activity tracking wearable devices have emerged as an increasingly popular method for consumers to assess their daily activity and calories expended. However, whether these wearable devices are valid at different levels of exercise intensity is unknown. Objective The objective of this study was to examine heart rate (HR) and energy expenditure (EE) validity of 3 popular wrist-worn activity monitors at different exercise intensities. Methods A total of 62 participants (females: 58%, 36/62; nonwhite: 47% [13/62 Hispanic, 8/62 Asian, 7/62 black/ African American, 1/62 other]) wore the Apple Watch, Fitbit Charge HR, and Garmin Forerunner 225. Validity was assessed using 2 criterion devices: HR chest strap and a metabolic cart. Participants completed a 10-minute seated baseline assessment; separate 4-minute stages of light-, moderate-, and vigorous-intensity treadmill exercises; and a 10-minute seated recovery period. Data from devices were compared with each criterion via two-way repeated-measures analysis of variance and Bland-Altman analysis. Differences are expressed in mean absolute percentage error (MAPE). Results For the Apple Watch, HR MAPE was between 1.14% and 6.70%. HR was not significantly different at the start (P=.78), during baseline (P=.76), or vigorous intensity (P=.84); lower HR readings were measured during light intensity (P=.03), moderate intensity (P=.001), and recovery (P=.004). EE MAPE was between 14.07% and 210.84%. The device measured higher EE at all stages (P<.01). For the Fitbit device, the HR MAPE was between 2.38% and 16.99%. HR was not significantly different at the start (P=.67) or during moderate intensity (P=.34); lower HR readings were measured during baseline, vigorous intensity, and recovery (P<.001) and higher HR during light intensity (P<.001). EE MAPE was between 16.85% and 84.98%. The device measured higher EE at baseline (P=.003), light intensity (P<.001), and moderate intensity (P=.001). EE was not significantly different at vigorous (P=.70) or recovery (P=.10). For Garmin Forerunner 225, HR MAPE was between 7.87% and 24.38%. HR was not significantly different at vigorous intensity (P=.35). The device measured higher HR readings at start, baseline, light intensity, moderate intensity (P<.001), and recovery (P=.04). EE MAPE was between 30.77% and 155.05%. The device measured higher EE at all stages (P<.001). Conclusions This study provides one of the first validation assessments for the Fitbit Charge HR, Apple Watch, and Garmin Forerunner 225. An advantage and novel approach of the study is the examination of HR and EE at specific physical activity intensities. Establishing validity of wearable devices is of particular interest as these devices are being used in weight loss interventions and could impact findings. Future research should investigate why differences between exercise intensities and the devices exist. PMID:28302596

Computer Managed Instruction by Satellite: Phase I, A Feasibility Study.

DTIC Science & Technology

1976-12-01

Harry O’Neil, ARPA; Dr. A. F. Smode, TAEG; Dr. N. J. Applegate, CNET; Mr. Andrew W . Bright, OP-124; Mr. John Campbell, DSS- W ; CDR J. Davis, CNTT...Ms. Bonnie W . Dunning, OASD (M&RA); CAPT R. E. Enright, OP-941E; Dr. Marshall Farr, ONR; LCDR T. L. Ferrier, COMTRAPAC 31; Dr. John D. Ford, NPRDC...CAPT R. B. King, BUPERS; CDR W . H. Leuker, OP-983; Mr. Wasyl Lew, NASA; Mr, M. K. Malehorn, OP-099; Mr. C. S. Mathews, MARAD; CAPT D. F. X. McPadden

Space Station Freedom - Approaching the critical design phase

NASA Technical Reports Server (NTRS)

Kohrs, Richard H.; Huckins, Earle, III

1992-01-01

The status and future developments of the Space Station Freedom are discussed. To date detailed design drawings are being produced to manufacture SSF hardware. A critical design review (CDR) for the man-tended capability configuration is planned to be performed in 1993 under the SSF program. The main objective of the CDR is to enable the program to make a full commitment to proceed to manufacture parts and assemblies. NASA recently signed a contract with the Russian space company, NPO Energia, to evaluate potential applications of various Russian space hardware for on-going NASA programs.

Vulnerability Science: A Response to a Criticism of the Ballistic Research Laboratory’s Vulnerability Modeling Strategy

DTIC Science & Technology

1990-06-01

SMCAR-CCB-TL AMXSY-MP, H. Cohen Watervliet, NY 12189-4050 1 Cdr, USATECOM ATTN: AMSTE- TD Commander 3 Cdr, CRDEC, AMCCOM US Army Armament, Munitions ATIN...Laboratory Command Armament RD&E Center ATTN: SLCTO (Marcos Sola) US Army AMCCOM 2800 Powder Mill Road ATTN: SMCAR- TDS (Vic Lindner) Adelphi, MD 20783-1145...ASQNC-ELC-1-T, Myer Center US Army AMCCOM Fort Monmouth, NJ 07703-5000 ATTN: SMCAR- TD (Jim Killen) Picatinny Arsenal, NJ 07806-5000 14 DISTRIBUTION

Using internet enabled mobile devices and social networking technologies to promote exercise as an intervention for young first episode psychosis patients.

PubMed

Killackey, Eoin; Anda, Anna Lee; Gibbs, Martin; Alvarez-Jimenez, Mario; Thompson, Andrew; Sun, Pamela; Baksheev, Gennady N

2011-05-12

Young people with first episode psychosis are at an increased risk for a range of poor health outcomes. In contrast to the growing body of evidence that suggests that exercise therapy may benefit the physical and mental health of people diagnosed with schizophrenia, there are no studies to date that have sought to extend the use of exercise therapy among patients with first episode psychosis. The aim of the study is to test the feasibility and acceptability of an exercise program that will be delivered via internet enabled mobile devices and social networking technologies among young people with first episode psychosis. This study is a qualitative pilot study being conducted at Orygen Youth Health Research Centre in Melbourne, Australia. Participants are young people aged 15-24 who are receiving clinical care at a specialist first episode psychosis treatment centre. Participants will also comprise young people from the general population. The exercise intervention is a 9-week running program, designed to gradually build a person's level of fitness to be able to run 5 kilometres (3 miles) towards the end of the program. The program will be delivered via an internet enabled mobile device. Participants will be asked to post messages about their running experiences on the social networking website, and will also be asked to attend three face-to-face interviews. This paper describes the development of a qualitative study to pilot a running program coupled with the use of internet enabled mobile devices among young people with first episode psychosis. If the program is found to be feasible and acceptable to patients, it is hoped that further rigorous evaluations will ultimately lead to the introduction of exercise therapy as part of an evidence-based, multidisciplinary approach in routine clinical care.

Exercise guidelines for inpatients following ventricular assist device placement: a systematic review of the literature.

PubMed

Scheiderer, Rachel; Belden, Courtney; Schwab, Darla; Haney, Casey; Paz, Jaime

2013-06-01

For patients with end-stage heart failure awaiting transplantation, lack of donor organs has created an increased need for alternatives such as left ventricular assist device (LVAD) implantation. The purpose of this study is to determine safe and effective exercise parameters for physical therapy in the acute care setting. A systematic literature review was conducted according to PRISMA guidelines using Sackett's Levels of Evidence to rate the evidence. Multiple databases were searched with inclusion criteria of: available in English, inpatient care up to 6 months postoperatively, description of intervention type and exercise parameters. no defined exercise parameters, outpatient treatment, infection post VAD, or palliative or hospice care post VAD. Six studies out of 1,291 articles met inclusion criteria. Common exercise parameters used were the Borg Rating of Perceived Exertion scale 11-13 (6-20 scale) or > 4 (0-10 scale), Dyspnea scale > 2 (0-4 scale) and > 5 (0-10 scale), mean arterial pressure (MAP) 70-95 mmHg, and LVAD flow > 3L/min. Levels of evidence ranged from case controlled to expert opinion. Current evidence on inpatient exercise parameters for patient's status post LVAD implantation is not sufficient to suggest definitive guidelines; however, these exercise parameters provide a reference for patient care.

Crew Exercise Fact Sheet

NASA Technical Reports Server (NTRS)

Rafalik, Kerrie

2017-01-01

Johnson Space Center (JSC) provides research, engineering, development, integration, and testing of hardware and software technologies for exercise systems applications in support of human spaceflight. This includes sustaining the current suite of on-orbit exercise devices by reducing maintenance, addressing obsolescence, and increasing reliability through creative engineering solutions. Advanced exercise systems technology development efforts focus on the sustainment of crew's physical condition beyond Low Earth Orbit for extended mission durations with significantly reduced mass, volume, and power consumption when compared to the ISS.

Crew Exercise

NASA Technical Reports Server (NTRS)

Rafalik, Kerrie K.

2017-01-01

Johnson Space Center (JSC) provides research, engineering, development, integration, and testing of hardware and software technologies for exercise systems applications in support of human spaceflight. This includes sustaining the current suite of on-orbit exercise devices by reducing maintenance, addressing obsolescence, and increasing reliability through creative engineering solutions. Advanced exercise systems technology development efforts focus on the sustainment of crew's physical condition beyond Low Earth Orbit for extended mission durations with significantly reduced mass, volume, and power consumption when compared to the ISS.

The fly wheel exercise device (FWED): A countermeasure against bone loss and muscle atrophy

NASA Astrophysics Data System (ADS)

Hueser, Detlev; Wolff, Christian; Berg, Hans E.; Tesch, Per A.; Cork, Michael

2008-01-01

The flywheel exercise device (FWED) is planned for use as an in-flight exercise system, to demonstrate its efficacy as a countermeasure device to prevent muscle atrophy, bone loss and impairment of muscle function in human beings in response to long duration spaceflight. It is intended to be used on the International Space Station (ISS) and will be launched by the European cargo carrier, the automated transfer vehicle (ATV) in late 2005. The FWED is a non-gravity-dependent mechanical device based on the Yo-Yo principle, which provides resistance during coupled concentric and eccentric muscle actions, through the inertia of a spinning flywheel. Currently, the development of a FWED Flight and Ground Model is in progress and is due to be completed in May 2004. An earlier developed prototype is available that has been used for various ground studies. Our FWED design provides a maximum of built-in safety and support to the operation by one astronaut. This is achieved in particular by innovative mechanical design features and an easy, safe to use man-machine interface. The modular design is optimized for efficient set-up and maintenance operations to be performed in orbit by the crew. The mechanical subsystem of the FWED includes a μg disturbance suspension, which minimizes the mechanical disturbances of the exercising subject at the mechanical interface to the ISS. During the FWED operation the astronaut is guided through the exercises by the data management subsystem, which acquires sensor data from the FWED, calculates and displays real-time feedback to the subject, and stores all data on hard disk and personalized storage media for later scientific analysis.

Heat extraction through the palm of one hand improves aerobic exercise endurance in a hot environment.

PubMed

Grahn, Dennis A; Cao, Vinh H; Heller, H Craig

2005-09-01

In situations where the accumulation of internal heat limits physical performance, enhanced heat extraction from the body should improve performance capacity. The combined application of local subatmospheric pressure (35-45 mmHg) to an entire hand (to increase blood volume) and a heat sink (18-22 degrees C) to the palmar surface were used to draw heat out of the circulating blood. Subjects walked uphill (5.63 km/h) on a treadmill in a 40 degree C environment. Slopes of the treadmill were held constant during paired experimental trials (with and without the device). Heat extraction attenuated the rate of esophageal temperature rise during exercise (2.1 +/- 0.4 degrees and 2.9 +/- 0.5 degrees C/h, mean +/- SE, with and without the device, respectively; n = 8) and increased exercise duration (46.1 +/- 3.4 and 32.3 +/- 1.7 min with and without the device, respectively; n = 18). Hand cooling alone had little effect on exercise duration (34.1 +/- 3.0, 38.0 +/- 3.5, and 57.0 +/- 6.4 min, for control, cooling only, and cooling, and subatmospheric pressure, respectively; n = 6). In a longer term study, nine subjects participated in two or four trials per week for 8 wk. The individual workloads (treadmill slope) were varied weekly. Use of the device had a beneficial effect on exercise endurance at all workloads, but the benefit proportionally decreased at higher workloads. It is concluded that heat can be efficiently removed from the body by using the described technology and that such treatment can provide a substantial performance benefit in thermally stressful conditions.

Development of a Ground-Based Analog to the Advanced Resistive Exercise Device Aboard the International Space Station

NASA Technical Reports Server (NTRS)

Newby, Nathaniel J.; Scott-Pandorf, M. M.; Caldwell, E.; DeWitt, J.K.; Fincke, R.; Peters, B.T.

2010-01-01

NASA and Wyle engineers constructed a Horizontal Exercise Fixture (HEF) that was patented in 2006. Recently modifications were made to HEF with the goal of creating a device that mimics squat exercise on the Advanced Resistive Exercise Device (ARED) and can be used by bed rest subjects who must remain supine during exercise. This project posed several engineering challenges, such as how best to reproduce the hip motions (we used a sled that allowed hip motion in the sagittal plane), how to counterweight the pelvis against gravity (we used a pulley and free-weight mechanism), and how to apply large loads (body weight plus squat load) to the shoulders while simultaneously supporting the back against gravity (we tested a standard and a safety bar that allowed movement in the subject s z-axis, both of which used a retractable plate for back support). METHODS An evaluation of the HEF was conducted with human subjects (3F, 3M), who performed sets of squat exercises of increasing load from 10-repetition maximum (RM) up to 1-RM. Three pelvic counterweight loads were tested along with each of the two back-support squat bars. Data collection included 3-dimensional ground reaction forces (GRF), muscle activation (EMG), body motion (video-based motion capture), and subjective comments. These data were compared with previous ground-based ARED study data. RESULTS All subjects in the evaluation were able to perform low- to high-loading squats on the HEF. Four of the 6 subjects preferred a pelvic counterweight equivalent to 60 percent of their body weight. Four subjects preferred the standard squat bar, whereas 2 female subjects preferred the safety bar. EMG data showed muscle activation in the legs and low back typical of squat motion. GRF trajectories and eccentric-concentric loading ratios were similar to ARED. CONCLUSION: Squat exercise performed on HEF approximated squat exercise on ARED.

Exercise countermeasures for spaceflight.

PubMed

Convertino, V A; Sandler, H

1995-01-01

The authors present a physiological basis for the use of exercise as a weightlessness countermeasure, outline special considerations for the development of exercise countermeasures, review and evaluate exercise used during space flight, and provide new approaches and concepts for the implementation of novel exercise countermeasures for future space flight. The discussion of the physiological basis for countermeasures examines maximal oxygen uptake, blood volume, metabolic responses to work, muscle function, bone loss, and orthostatic instability. The discussion of considerations for exercise prescriptions during space flight includes operational considerations, type of exercise, fitness considerations, age and gender, and psychological considerations. The discussion of exercise currently used in space flight examines cycle ergometry, the treadmill, strength training devices, electrical stimulation, and the Penguin suit worn by Russian crews. New approaches to exercise countermeasures include twin bicycles, dynamic resistance exercisers, maximal exercise effects, grasim (gravity simulators), and the relationship between exercise and LBNP.

ISS Squat and Deadlift Kinematics on the Advanced Resistive Exercise Device

NASA Technical Reports Server (NTRS)

Newby, N.; Caldwell, E.; Sibonga, J.; Ploutz-Snyder, L.

2014-01-01

Visual assessment of exercise form on the Advanced Resistive Exercise Device (ARED) on orbit is difficult due to the motion of the entire device on its Vibration Isolation System (VIS). The VIS allows for two degrees of device translational motion, and one degree of rotational motion. In order to minimize the forces that the VIS must damp in these planes of motion, the floor of the ARED moves as well during exercise to reduce changes in the center of mass of the system. To help trainers and other exercise personnel better assess squat and deadlift form a tool was developed that removes the VIS motion and creates a stick figure video of the exerciser. Another goal of the study was to determine whether any useful kinematic information could be obtained from just a single camera. Finally, the use of these data may aid in the interpretation of QCT hip structure data in response to ARED exercises performed in-flight. After obtaining informed consent, four International Space Station (ISS) crewmembers participated in this investigation. Exercise was videotaped using a single camera positioned to view the side of the crewmember during exercise on the ARED. One crewmember wore reflective tape on the toe, heel, ankle, knee, hip, and shoulder joints. This technique was not available for the other three crewmembers, so joint locations were assessed and digitized frame-by-frame by lab personnel. A custom Matlab program was used to assign two-dimensional coordinates to the joint locations throughout exercise. A second custom Matlab program was used to scale the data, calculate joint angles, estimate the foot center of pressure (COP), approximate normal and shear loads, and to create the VIS motion-corrected stick figure videos. Kinematics for the squat and deadlift vary considerably for the four crewmembers in this investigation. Some have very shallow knee and hip angles, and others have quite large ranges of motion at these joints. Joint angle analysis showed that crewmembers do not return to a normal upright stance during squat, but remain somewhat bent at the hips. COP excursions were quite large during these exercises covering the entire length of the base of support in most cases. Anterior-posterior shear was very pronounced at the bottom of the squat and deadlift correlating with a COP shift to the toes at this part of the exercise. The stick figure videos showing a feet fixed reference frame have made it visually much easier for exercise personnel and trainers to assess exercise kinematics. Not returning to fully upright, hips extended position during squat exercises could have implications for the amount of load that is transmitted axially along the skeleton. The estimated shear loads observed in these crewmembers, along with a concomitant reduction in normal force, may also affect bone loading. The increased shear is likely due to the surprisingly large deviations in COP. Since the footplate on ARED moves along an arced path, much of the squat and deadlift movement is occurring on a tilted foot surface. This leads to COP movements away from the heel. The combination of observed kinematics and estimated kinetics make squat and deadlift exercises on the ARED distinctly different from their ground-based counterparts. CONCLUSION This investigation showed that some useful exercise information can be obtained at low cost, using a single video camera that is readily available on ISS. Squat and deadlift kinematics on the ISS ARED differ from ground-based ARED exercise. The amount of COP shift during these exercises sometimes approaches the limit of stability leading to modifications in the kinematics. The COP movement and altered kinematics likely reduce the bone loading experienced during these exercises. Further, the stick figure videos may prove to be a useful tool in assisting trainers to identify exercise form and make suggestions for improvements

Use of the International Space Station as an Exercise Physiology Lab

NASA Technical Reports Server (NTRS)

Ploutz-Snyder, Lori

2013-01-01

The International Space Station (ISS) is now in its prime utilization phase with great opportunity to use the ISS as a lab. With respect to exercise physiology there is considerable research opportunity. Crew members exercise for up to 2 hours per day using a cycle ergometer, treadmill, and advanced resistive exercise device (ARED). There are several ongoing exercise research studies by NASA, ESA and CSA. These include studies related to evaluation of new exercise prescriptions (SPRINT), evaluation of aerobic capacity (VO2max), biomechanics (Treadmill Kinematics), energy expenditure during spaceflight (Energy), evaluation of cartilage (Cartilage), and evaluation of cardiovascular health (Vascular). Examples of how ISS is used for exercise physiology research will be presented.

Lower sulfurtransferase detoxification rates of cyanide in konzo-A tropical spastic paralysis linked to cassava cyanogenic poisoning.

PubMed

Kambale, K J; Ali, E R; Sadiki, N H; Kayembe, K P; Mvumbi, L G; Yandju, D L; Boivin, M J; Boss, G R; Stadler, D D; Lambert, W E; Lasarev, M R; Okitundu, L A; Mumba Ngoyi, D; Banea, J P; Tshala-Katumbay, D D

2017-03-01

Using a matched case-control design, we sought to determine whether the odds of konzo, a distinct spastic paraparesis associated with food (cassava) cyanogenic exposure in the tropics, were associated with lower cyanide detoxification rates (CDR) and malnutrition. Children with konzo (N=122, 5-17 years of age) were age- and sex-matched with presumably healthy controls (N=87) and assessed for motor and cognition performances, cyanogenic exposure, nutritional status, and cyanide detoxification rates (CDR). Cyanogenic exposure was ascertained by thiocyanate (SCN) concentrations in plasma (P-SCN) and urine (U-SCN). Children with a height-for-age z-score (HAZNCHS)<-2 were classified as nutritionally stunted. CDR was measured as time required to convert cyanide to SCN, and expressed as ms/μmol SCN/mg protein or as mmolSCN/ml plasma/min. Mean (SD) U-SCN in children with konzo was 521.9 (353.6) μmol/l and was, significantly higher than 384.6 (223.7) μmol/l in those without konzo. Conditional regression analysis of data for age- and sex- matched case-control pairs showed that konzo was associated with stunting (OR: 5.8; 95% CI: 2.7-12.8; p<0.01; N=83 paired groups) and higher U-SCN (OR: 1.1; 95% CI: 1.02-1.20 per 50-μmol increase in U-SCN; p=0.02; N=47 paired groups). After adjusting for stunting and U-SCN, the odds of developing konzo was reduced by 63% (95% CI: 11-85%, p=0.03; N=41 paired groups) for each 5mmol SCN/(ml plasma/min)-increase in CDR. Linear regression analysis indicated a significant association between BOT-2 or KABC-II scores and both the HAZNCHS z-score and the U-SCN concentration, but not the CDR. Our findings provide evidence in support of interventions to remove cyanogenic compounds from cassava prior to human consumption or, peharps, enhance the detoxification of cyanide in those relying on the cassava as the main source of food. Copyright © 2016 Elsevier B.V. All rights reserved.

Lower sulfurtransferase detoxification rates of cyanide in konzo—A tropical spastic paralysis linked to cassava cyanogenic poisoning

PubMed Central

Kambale, K.J.; Ali, E.R.; Sadiki, N.H.; Kayembe, K.P.; Mvumbi, L.G.; Yandju, D.L.; Boivin, M.J.; Boss, G.R.; Stadler, D.D.; Lambert, W.E.; Lasarev, M.R.; Okitundu, L.A.; Ngoyi, D. Mumba; Banea, J.P.; Tshala-Katumbay, D.D.

2016-01-01

Using a matched case-control design, we sought to determine whether the odds of konzo, a distinct spastic paraparesis associated with food (cassava) cyanogenic exposure in the tropics, were associated with lower cyanide detoxification rates (CDR) and malnutrition. Children with konzo (N= 122, 5–17 years of age) were age- and sex-matched with presumably healthy controls (N = 87) and assessed for motor and cognition performances, cyanogenic exposure, nutritional status, and cyanide detoxification rates (CDR). Cyanogenic exposure was ascertained by thiocyanate (SCN) concentrations in plasma (P-SCN) and urine (U-SCN). Children with a height-for-age z-score (HAZNCHS) < −2 were classified as nutritionally stunted. CDR was measured as time required to convert cyanide to SCN, and expressed as ms/μmol SCN/mg protein or as mmolSCN/ml plasma/min. Mean (SD) U-SCN in children with konzo was 521.9 (353.6) μmol/l and was, significantly higher than 384.6 (223.7) μmol/l in those without konzo. Conditional regression analysis of data for age- and sex- matched case-control pairs showed that konzo was associated with stunting (OR: 5.8; 95% CI: 2.7–12.8; p <0.01; N = 83 paired groups) and higher U-SCN (OR: 1.1; 95% CI: 1.02–1.20 per 50-μmol increase in U-SCN; p = 0.02; N = 47 paired groups). After adjusting for stunting and U-SCN, the odds of developing konzo was reduced by 63% (95% CI: 11–85%, p = 0.03; N = 41 paired groups) for each 5 mmol SCN/(ml plasma/min)-increase in CDR. Linear regression analysis indicated a significant association between BOT-2 or KABC-II scores and both the HAZNCHS z-score and the U-SCN concentration, but not the CDR. Our findings provide evidence in support of interventions to remove cyanogenic compounds from cassava prior to human consumption or, peharps, enhance the detoxification of cyanide in those relying on the cassava as the main source of food. PMID:27246648

A new clustering of antibody CDR loop conformations

PubMed Central

North, Benjamin; Lehmann, Andreas; Dunbrack, Roland L.

2010-01-01

Previous analyses of the complementarity determining regions (CDRs) of antibodies have focused on a small number of “canonical” conformations for each loop. This is primarily the result of the work of Chothia and colleagues, most recently in 1997. Because of the widespread utility of antibodies, we have revisited the clustering of conformations of the six CDR loops with the much larger amount of structural information currently available. In this work, we were careful to use a high-quality data set by eliminating low-resolution structures and CDRs with high B-factors or high conformational energies. We used a distance function based on directional statistics and an effective clustering algorithm using affinity propagation. With this data set of over 300 non-redundant antibody structures, we were able to cover 28 CDR-length combinations (e.g., L1 length 11, or “L1-11” in our nomenclature) for L1, L2, L3, H1 and H2. The Chothia analysis covered only 20 CDR-lengths. Only four of these had more than one conformational cluster, of which two could easily be distinguished by gene source (mouse/human; κ/λ) and one purely by the presence and positions of Pro residues (L3-9). Thus using the Chothia analysis does not require the complicated set of “structure-determining residues” that is often assumed. Of our 28 CDR-lengths, 15 of them have multiple conformational clusters including ten for which Chothia had only one canonical class. We have a total of 72 clusters for the non-H3 CDRs; approximately 85% of the non-H3 sequences can be assigned to a conformational cluster based on gene source and/or sequence. We found that earlier predictions of “bulged” vs. “non-bulged” conformations based on the presence or absence of anchor residues Arg/Lys94 and Asp101 of H3 have not held up, since all four combinations lead to a majority of conformations that are bulged. Thus the earlier analyses have been significantly enhanced by the increased data. We believe the new classification will lead to improved methods for antibody structure prediction and design. PMID:21035459

The Effect of Preoperative Cognitive Behavior and Exercise Therapy for a Patient With an Implanted Left Ventricular Assist Device in Korea.

PubMed

Seo, Yong Gon; Park, Won Hah; Jeon, Eun Seok; Sung, Ji Dong; Jang, Mi Ja

2017-10-01

Left ventricular assist devices (LVADs) are used in patients with progressive heart failure symptoms to provide circulatory support. Patients with LVADs are referred to inpatient cardiac rehabilitation to prevent postoperative complications and improve aerobic capacity and quality of life. Preoperative exercise therapy for cardiac patients is an emerging treatment modality, and several studies have reported that it improves postoperative outcomes, such as length of hospital stay and postoperative complications. This case report describes the benefits of preoperative cognitive behavioral and exercise therapy in a Korean patient undergoing LVAD implantation. V. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Novel Musculoskeletal Loading System for Small Exercise Devices

NASA Technical Reports Server (NTRS)

Downs, Meghan; Newby, Nate; Trinh, Tinh; Hanson, Andrea

2016-01-01

Long duration spaceflight places astronauts at increased risk for muscle strain and bone fracture upon return to a 1-g or partial gravity environment. Functionally limiting decrements in musculoskeletal health are likely during Mars proving-ground and Earth-independent missions given extended transit times and the vehicle limitations for exercise devices (low-mass, small volume, little to no power). This is particularly alarming for exploration missions because astronauts will be required to perform novel and physically demanding tasks (i.e. vehicle egress, exploration, and habitat building activities) on unfamiliar terrain. Accordingly, NASA's exploration roadmap identifies the need for development of small exercise equipment that can prevent musculoskeletal atrophy and has the ability to assess musculoskeletal health at multiple time points during long-duration missions.

Promoting physical activity in people with intellectual and multiple disabilities through a basic technology-aided program.

PubMed

Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Alberti, Gloria; Perilli, Viviana; Zimbaro, Carmen; Boccasini, Adele; Mazzola, Carlo; Russo, Roberto

2018-06-01

This study assessed a technology-aided program (monitoring responding, and ensuring preferred stimulation and encouragements) for promoting physical activity with 11 participants with severe/profound intellectual and multiple disabilities. Each participant was provided with an exercise device (e.g. a static bicycle and a stepper) and exposed to the program according to an ABAB design, in which A and B represented baseline and intervention phases, respectively. Data recording concerned (a) the participants' responses with the exercise device (e.g. pedaling) during baseline and intervention phases and (b) their heart rates during the last intervention phase. The results showed that all participants had significant increases in responding with the exercise devices during the intervention phases. Heart-rate values during the intervention sessions indicated that the participants' responding during those sessions mostly amounted to moderate-intensity physical activity, with potential benefits for their overall physical condition. Implications of the findings and questions for future research in the area were discussed.

Detection of Glaucoma and Its Association With Diabetic Retinopathy in a Diabetic Retinopathy Screening Program.

PubMed

Gangwani, Rita A; McGhee, Sarah M; Lai, Jimmy S M; Chan, Christina K W; Wong, David

2016-01-01

To determine the type of glaucoma in subjects with diabetes mellitus detected during a diabetic retinopathy screening program and to determine any association between diabetic retinopathy (DR) and glaucoma. This is a population-based prospective cross-sectional study, in which subjects with diabetes mellitus underwent screening for DR in a primary care outpatient clinic. Digital fundus photographs were taken and graded for presence/absence and severity of DR. During this grading, those fundus photographs showing increased cup-to-disc ratio (CDR) (≥0.6) were identified and these patients were referred to the specialist ophthalmology clinic for detailed examination. The presence of glaucoma was established based on CDR and abnormal visual field (VF) defects according to Hodapp-Parrish-Anderson's criteria. An elevation of intraocular pressure was not required for the diagnosis of glaucoma. The patients said to have definite glaucoma were those with vertical CDR>/=0.6, glaucomatous defects on VF examination, or retinal nerve fiber thinning if VF was unreliable. Of the 2182 subjects who underwent screening, 81 subjects (3.7%) had increased CDR and 40 subjects (1.8%) had confirmed glaucoma. Normal-tension variant of primary open-angle glaucoma was the most prevalent type (1.2%) We did not find any evidence that DR is a risk factor for glaucoma [odds ratio for DR vs. no DR=1.22 (95% confidence interval, 0.59-2.51)]. The overall prevalence of glaucoma in this diabetic population, based on finding increased cupping of optic disc in a teleretinal screening program was 1.8% (95% confidence interval, 1.0-3.0).

Highly conserved CDR3 region in circulating CD4+Vβ5+ T cells may be associated with cytotoxic activity in Chagas disease

PubMed Central

Menezes, C A S; Sullivan, A K; Falta, M T; Mack, D G; Freed, B M; Rocha, M O C; Gollob, K J; Fontenot, A P; Dutra, W O

2012-01-01

Human infection with Trypanosoma cruzi leads to Chagas disease, which presents as several different clinical conditions ranging from an asymptomatic form to a severe dilated cardiomyopathy. Several studies have demonstrated that T cells play a critical role in the development of cardiac pathology, as well as in immunoregulation during chronic disease. However, the mechanisms that drive protective or pathogenic T cell response are not known. We have shown that CD4+ T cells from chagasic patients preferentially express T cell receptor (TCR) β-chain variable region (Vβ) 5. The aim of this work was to determine whether T cells expressing this particular Vβ region displayed variable or restricted CDR3 sequences, as an indicator of the nature of the stimulus leading to the activation of these T cells in vivo. Additionally, we aimed to evaluate phenotypic characteristics of these cells that might be associated with pathology. CDR3 junctional region sequencing of Vβ5·1 expressing CD4+ T cells revealed the occurrence of a highly homologous CDR3 region with conserved TCR Jβ region usage among patients with cardiac, but not indeterminate, Chagas disease. Moreover, correlation analysis indicated that the frequency of CD4+Vβ5·1+ cells is associated with granzyme A expression, suggesting that these cells might display cytotoxic function. Together these results provide new insight into T cell recognition of antigens involved in Chagas disease and suggest that these cells may be implicated in the pathogenesis of chagasic cardiomyopathy. PMID:22774985

Trajectories of depressive symptoms and their relationship to the progression of dementia.

PubMed

Barca, Maria Lage; Persson, Karin; Eldholm, Rannveig; Benth, Jūratė Šaltytė; Kersten, Hege; Knapskog, Anne-Brita; Saltvedt, Ingvild; Selbaek, Geir; Engedal, Knut

2017-11-01

The relationship between progression of Alzheimer's disease and depression and its underlying mechanisms has scarcely been studied. A sample of 282 outpatients with Alzheimer's disease (AD; 105 with amnestic AD and 177 with Alzheimer's dementia) from Norway were followed up for an average of two years. Assessment included Cornell Scale for Depression in Dementia and Clinical Dementia Rating Scale (CDR) at baseline and follow-up to examine the relationship between AD and depression. Additionally, MRI of the brain, CSF dementia biomarkers and APOE status were assessed at baseline. Progression of dementia was defined as the difference between CDR sum of boxes at follow-up and baseline (CDR-SB change). Trajectories of depressive symptoms on the Cornell Scale were identified using growth mixture modeling. Differences between the trajectories in regard to patients' characteristics were investigated. Three distinct trajectories of depressive symptoms were identified: 231 (82.8%) of the patients had stable low-average scores on the Cornell Scale (Class 1); 11 (3.9%) had high and decreasing scores (Class 2); and 37 (13.3%) had moderate and increasing scores (Class 3). All classes had average probabilities over 80%, and confidence intervals were non-overlapping. The only significant characteristic associated with membership in class 3 was CDR-SB change. Not all patients screened for participation were included in the study, but the included and non-included patients did not differ significantly. Some patients with amnestic MCI might have been misdiagnosed. A more rapid progression of dementia was found in a group of patients with increasing depressive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a Climate-Data Record (CDR) of the Surface Temperature of the Greenland Ice Sheet

NASA Technical Reports Server (NTRS)

Hall, Dorthy K.; Comiso, Josefino C.; Shuman, Christopher A.; DiGirolamo, Nicolo E.; Stock, Larry V.

2010-01-01

Regional "clear sky" surface temperature increases since the early 1980s in the Arctic, measured using Advanced Very High Resolution Radiometer (AVHRR) infrared data, range from 0.57+/-0.02 deg C to 72+/-0.10 deg C per decade. Arctic warming has important implications for ice-sheet mass balance because much of the periphery of the Greenland Ice Sheet is already near 0 deg C during the melt season, and is thus vulnerable to rapid melting if temperatures continue to increase. An increase in melting of the ice sheet would accelerate sea-level rise, an issue affecting potentially billions of people worldwide. To quantify the ice-surface temperature (IST) of the Greenland Ice Sheet, and to provide an IST dataset of Greenland for modelers that provides uncertainties, we are developing a climate-data record (CDR) of daily "clear-sky" IST of the Greenland Ice Sheet, from 1982 to the present using AVHRR (1982 - present) and Moderate-Resolution Imaging Spectroradiometer (MODIS) data (2000 - present) at a resolution of approximately 5 km. Known issues being addressed in the production of the CDR are: time-series bias caused by cloud cover (surface temperatures can be different under clouds vs. clear areas) and cross-calibration in the overlap period between AVHRR instruments, and between AVHRR and MODIS instruments. Because of uncertainties, mainly due to clouds, time-series of satellite IST do not necessarily correspond with actual surface temperatures. The CDR will be validated by comparing results with automatic-weather station data and with satellite-derived surface-temperature products and biases will be calculated.

The efficacy of using computer-aided detection (CAD) for detection of breast cancer in mammography screening: a systematic review.

PubMed

Henriksen, Emilie L; Carlsen, Jonathan F; Vejborg, Ilse Mm; Nielsen, Michael B; Lauridsen, Carsten A

2018-01-01

Background Early detection of breast cancer (BC) is crucial in lowering the mortality. Purpose To present an overview of studies concerning computer-aided detection (CAD) in screening mammography for early detection of BC and compare diagnostic accuracy and recall rates (RR) of single reading (SR) with SR + CAD and double reading (DR) with SR + CAD. Material and Methods PRISMA guidelines were used as a review protocol. Articles on clinical trials concerning CAD for detection of BC in a screening population were included. The literature search resulted in 1522 records. A total of 1491 records were excluded by abstract and 18 were excluded by full text reading. A total of 13 articles were included. Results All but two studies from the SR vs. SR + CAD group showed an increased sensitivity and/or cancer detection rate (CDR) when adding CAD. The DR vs. SR + CAD group showed no significant differences in sensitivity and CDR. Adding CAD to SR increased the RR and decreased the specificity in all but one study. For the DR vs. SR + CAD group only one study reported a significant difference in RR. Conclusion All but two studies showed an increase in RR, sensitivity and CDR when adding CAD to SR. Compared to DR no statistically significant differences in sensitivity or CDR were reported. Additional studies based on organized population-based screening programs, with longer follow-up time, high-volume readers, and digital mammography are needed to evaluate the efficacy of CAD.

Driving Simulator Performance in Patients with Possible and Probable Alzheimer’s Disease

PubMed Central

Stein, Anthony C.; Dubinsky, Richard M.

2011-01-01

Drivers with more advanced stages of Alzheimer’s disease (AD) have been previously associated with an increased rate of motor vehicle accidents. Drivers suffering from early AD are also involved in, and may even cause motor vehicle accidents with greater frequency than “normal” drivers. Consequently there is considerable public concern regarding traffic safety issues for those with AD and subsequently for society, but there has been little research in understanding whether deterioration in driving ability is progressive, or has a sudden onset once the disease has reached a certain severity. The purpose of this study was to identify possible degradation in simulated driving performance that may occur at the earliest stages of AD, and compare these decrements to a control group of normal drivers. Using a single blind design, seventeen AD subjects, eight at a Clinical Dementia Rating (CDR) of 0.5 (possible AD) and nine at a CDR of 1 (probable AD), were compared to 63 cognitively normal, elderly controls. All subjects were trained to drive a computerized interactive driving simulator and then tested on a 19.3 km (12 mile) test course. The AD subjects demonstrated impaired driving performance when compared to the controls. The simulated driving performance of the CDR 1 AD subjects was so degraded that it would be regarded as unsafe by standard assessment criteria. The CDR 0.5 subjects made similar errors, suggesting that driving impairment may occur at the earliest stages of the disease. Further work will be necessary to determine the significance of these findings. PMID:22105407

Use of Product Listing Agreements by Canadian Provincial Drug Benefit Plans

PubMed Central

Friesen, Melissa K.; Thomson, Paige A.; Daw, Jamie R.

2013-01-01

Background: Product listing agreements (PLAs) between drug manufacturers and drug plans are increasingly common worldwide. Use of PLAs by Canadian provinces has not previously been documented. Methods: We collected data from all provinces on funding and PLA use for 25 drugs that were reviewed by the Common Drug Review (CDR) in 2010 or 2011 and funded by at least one province as of May 2012. We measured correlations between coverage and PLA use, and CDR recommendations and PLA use. Results: The number of drugs from our sample funded by provinces ranged from three in Prince Edward Island to 21 in Ontario. PLA use ranged from zero in Quebec, Prince Edward Island, and Newfoundland and Labrador to 20 in Ontario. The correlation between drugs funded and PLAs used by each province was statistically significant (r=0.57, p=0.04); excluding Ontario, however, the correlation was not significant (r=0.10, p=0.40). There was a stronger correlation between the number of provinces funding a drug and the number using PLAs among the subset of drugs with negative CDR recommendations (r=0.87, p<0.01) versus those with positive recommendations (r=0.52, p=0.03). Of the 12 drugs sampled with a negative CDR recommendation, 10 were funded with a PLA in at least one province. Interpretation: There is wide interprovincial variation in PLA use and evidence that PLAs may be used to fund drugs that are not otherwise cost-effective. If global pricing strategies are making PLAs necessary, Canadian governments should collaborate to improve the equity, transparency and effectiveness of PLAs across provinces. PMID:23968637

Correlation between overactive bladder symptom score and neuropsychological parameters in Alzheimer’s disease patients with lower urinary tract symptom

PubMed Central

Jung, Ha Bum; Choi, Don Kyoung; Lee, Seong Ho; Cho, Sung Tae; Na, Hae Ri; Park, Moon Ho

2017-01-01

ABSTRACT Purpose To examine an association between the overactive bladder symptom score (OABSS) and neuropsychological parameters. Moreover, we investigate the factors that affect each item in the questionnaire. Materials and Methods A total of 376 patients (males: 184; females: 192) with probable Alzheimer’s disease (AD) were recruited. Cognitive testing was conducted using the Mini Mental Status Examination (MMSE), Clinical Dementia Rating (CDR) scale, Global Deterioration Scale (GDS), and Barthel Activities of Daily Living (ADL). Lower urinary tract symptom (LUTS) was assessed using OABSS and voiding diary. Results The prevalence of overactive bladder (OAB) (defined as OABSS ≥3 with an urgency score of ≥2) in patients with AD was 72.6%. Among the OAB subjects, the most common severity of symptom was moderate (72.6%), followed by mild (21.2%), and severe (5.8%). It was found that OABSS had a very high correlation with aging (r=0.75; p<0.001). When compared with neuropsychological parameters, it was found that OABSS was highly correlated with the CDR scores (r=0.446; p<0.001). However, no significant correlation was found between the changes in OABSS scores and those in other neuropsychological parameters. Based on the individual symptom scores, urgency incontinence was highly correlated with the CDR scores (r=0.43; p<0.001). Conclusions OABSS is a useful tool in assessing AD patients with LUTS. There was a consistent positive association between OABSS severity, including urgency incontinence, and CDR scores. PMID:27802001

THE EFFECT OF DOUBLE VERSUS SINGLE OSCILLATING EXERCISE DEVICES ON TRUNK AND LIMB MUSCLE ACTIVATION

PubMed Central

Arora, Shruti; Button, Duane C.; Basset, Fabien A.

2013-01-01

Purpose/Background: Proper strengthening of the core and upper extremities is important for muscular health, performance, and rehabilitation. Exercise devices have been developed that attempt to disrupt the center of gravity in order to activate the trunk stabilizing muscles. The objective of this study was to analyze the trunk and shoulder girdle muscle activation with double and single oscillating exercise devices (DOD and SOD respectively) in various planes. Methods: Twelve male subjects performed three interventions using both devices under randomized conditions: single-handed vertical orientation of DOD and SOD to produce 1) medio-lateral oscillation in the frontal plane 2) dorso-ventral oscillation in the sagittal plane and 3) single-handed horizontal orientation for superior and inferior oscillation in the transverse plane. Electromyographic (EMG) activity during the interventions of the anterior deltoid, triceps brachii, biceps brachii, forearm flexors as well as lower abdominal and back stabilizer muscles was collected, and were normalized to maximal voluntary contractions. A two way repeated measures ANOVA (2x3) was conducted to assess the influence of the devices and movement planes on muscle activation. Results: The DOD provided 35.9%, 40.8%, and 52.3% greater anterior deltoid, transverse abdominus (TA)/internal oblique (IO) and lumbo-sacral erector spinae (LSES) activation than did the SOD respectively. Effect size calculations revealed that these differences were of moderate to large magnitude (0.86, 0.48, and 0.61 respectively). There were no significant differences in muscular activation achieved between devices for the triceps brachii, biceps brachii and forearm flexor muscles. Exercise in the transverse plane resulted in 30.5%, 29.5%, and 19.5% greater activation than the sagittal and 21.8%, 17.2%, and 26.3% greater activation than the frontal plane for the anterior deltoid, TA/IO and LSES respectively. Conclusions: A DOD demonstrated greater muscular activity for trunk and shoulder muscle activation but does not provide an advantage for limb activation. Overall, oscillating the devices in the transverse plane provided greater muscular activation of the anterior deltoid, TA/IO and LSES than use of the devices during frontal or sagittal plane movements. Level of evidence: 2c: Outcomes research. PMID:24175124

Web-based emergency response exercise management systems and methods thereof

DOEpatents

Goforth, John W.; Mercer, Michael B.; Heath, Zach; Yang, Lynn I.

2014-09-09

According to one embodiment, a method for simulating portions of an emergency response exercise includes generating situational awareness outputs associated with a simulated emergency and sending the situational awareness outputs to a plurality of output devices. Also, the method includes outputting to a user device a plurality of decisions associated with the situational awareness outputs at a decision point, receiving a selection of one of the decisions from the user device, generating new situational awareness outputs based on the selected decision, and repeating the sending, outputting and receiving steps based on the new situational awareness outputs. Other methods, systems, and computer program products are included according to other embodiments of the invention.

Foot pedal operated fluid type exercising device

NASA Technical Reports Server (NTRS)

Crum, G. W.; Sauter, R. J. (Inventor)

1973-01-01

A foot pedal operated exercising device is reported that contains a dynamometer formed of a pair of cylinders each containing a piston. The pistons are linked to each other. The upper portions of the two cylinders are joined together by a common opening to provide a common fluid reservoir and each piston is provided with a one way check valve to maintain an adequate supply of working fluid. Fluid from the driven cylinder is transmitted to the other cylinder through separate constant force spring biased valves each valve takes the predominant portion of the pressure drop thereby providing a constant force hydraulic dynamometer. A device is provided to determine the amount of movement of piston travel.

Foot-Ground Reaction Force During Resistance Exercise in Parabolic Flight

NASA Technical Reports Server (NTRS)

Lee, Stuart M. C.; Cobb, Kendall; Loehr, James A.; Nguyen, Daniel; Schneider, Suzanne M.

2003-01-01

An interim Resistance Exercise Device (iRED) was designed to provide resistive exercise as a countermeasure to space flight-induced loss of muscle strength and endurance as well as decreased bone mineral density. The purpose of this project was to compare foot-ground reaction force during iRED exercise in normal gravity (l-g) versus micro gravity (O-g) achieved during parabolic flight. METHODS: Four subjects performed three exercises using the iRED (squat, heel raise, and deadlift) during I-g and O-g at a moderate intensity (60% of maximum strength during deadlift exercise). Foot-ground reaction force was measured in three axes (x,y,z) using a force plate, and the magnitude of the resultant force vector was calculated (r = X 2 + y2 + Z2 ). Range of motion (ROM) was measured using a linear encoder. Peak force (PkF) and total work (TW) were calculated using a customized computer program. Paired t-tests were used to test if significant differences (p.::::0.05) were observed between I-g and O-g exercise. RESULTS: PkF and TW measured in the resultant axis were significantly less in O-g for each of the exercises tested. During O-g, PkF was 42-46% and TW was 33- 37% of that measured during I-g. ROM and average time to complete each repetition were not different from I-g to O-g. CONCLUSIONS: When performing exercises in which body mass is a portion of the resistance during I-g, PkF and TW measured during resistive exercise were reduced approximately 60-70% during O-g. Thus, a resistive exercise device during O-g will be required to provided higher resistances to induce a similar training stimulus to that on Earth.

Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies

PubMed Central

Doria-Rose, Nicole A.; Schramm, Chaim A.; Gorman, Jason; Moore, Penny L.; Bhiman, Jinal N.; DeKosky, Brandon J.; Ernandes, Michael J.; Georgiev, Ivelin S.; Kim, Helen J.; Pancera, Marie; Staupe, Ryan P.; Altae-Tran, Han R.; Bailer, Robert T.; Crooks, Ema T.; Cupo, Albert; Druz, Aliaksandr; Garrett, Nigel J.; Hoi, Kam H.; Kong, Rui; Louder, Mark K.; Longo, Nancy S.; McKee, Krisha; Nonyane, Molati; O’Dell, Sijy; Roark, Ryan S.; Rudicell, Rebecca S.; Schmidt, Stephen D.; Sheward, Daniel J.; Soto, Cinque; Wibmer, Constantinos Kurt; Yang, Yongping; Zhang, Zhenhai; Mullikin, James C.; Binley, James M.; Sanders, Rogier W.; Wilson, Ian A.; Moore, John P.; Ward, Andrew B.; Georgiou, George; Williamson, Carolyn; Abdool Karim, Salim S.; Morris, Lynn; Kwong, Peter D.; Shapiro, Lawrence; Mascola, John R.

2015-01-01

Summary Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from CAPRISA-donor CAP256; each antibody contained the protruding tyrosine-sulfated, anionic antigen-binding loop (CDR H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30–38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation, an important vaccine insight. PMID:24590074

Triclosan Antagonizes Fluconazole Activity against Candida albicans

PubMed Central

Higgins, J.; Pinjon, E.; Oltean, H.N.; White, T.C.; Kelly, S.L.; Martel, C.M.; Sullivan, D.J.; Coleman, D.C.; Moran, G.P.

2012-01-01

Triclosan is a broad-spectrum antimicrobial compound commonly used in oral hygiene products. Investigation of its activity against Candida albicans showed that triclosan was fungicidal at concentrations of 16 mg/L. However, at subinhibitory concentrations (0.5-2 mg/L), triclosan antagonized the activity of fluconazole. Although triclosan induced CDR1 expression in C. albicans, antagonism was still observed in cdr1Δ and cdr2Δ strains. Triclosan did not affect fluconazole uptake or alter total membrane sterol content, but did induce the expression of FAS1 and FAS2, indicating that its mode of action may involve inhibition of fatty acid synthesis, as it does in prokaryotes. However, FAS2 mutants did not exhibit increased susceptibility to triclosan, and overexpression of both FAS1 and FAS2 alleles did not alter triclosan susceptibility. Unexpectedly, the antagonistic effect was specific for C. albicans under hypha-inducing conditions and was absent in the non-filamentous efg1Δ strain. This antagonism may be due to the membranotropic activity of triclosan and the unique composition of hyphal membranes. PMID:21972257

In vitro radiographic determination of distances from working length files to root ends comparing Kodak RVG 6000, Schick CDR, and Kodak insight film.

PubMed

Radel, Robert T; Goodell, Gary G; McClanahan, Scott B; Cohen, Mark E

2006-06-01

Previous studies suggest that digital and film-based radiography are similar for endodontic measurements. This study compared the accuracy and acceptability of measured distances from the tips of size #10 and #15 files to molar root apices in cadaver jaw sections using the newly developed Kodak RVG 6000, and the Schick CDR digital systems to digitized Kodak film. Standardized images were taken of files placed 0.5 to 1.5 mm short of true radiographic lengths. Images were imported into Adobe PhotoShop 7.0, thereby blinding observers who measured distances from files to root apices and assessed images for clarity (acceptability). Repeated measures ANOVA and Tukey-Kramer post hoc tests demonstrated that Kodak RVG 6000 images with enhanced contrast produced significantly less measurement error than unenhanced contrast Schick CDR images (p < 0.05) and significantly higher acceptability ratings than all other systems (all p < 0.002). Among these conditions, the newly developed Kodak RVG 6000 system provided the best overall images.

Validity of field expedient devices to assess core temperature during exercise in the cold.

PubMed

Bagley, James R; Judelson, Daniel A; Spiering, Barry A; Beam, William C; Bartolini, J Albert; Washburn, Brian V; Carney, Keven R; Muñoz, Colleen X; Yeargin, Susan W; Casa, Douglas J

2011-12-01

Exposure to cold environments affects human performance and physiological function. Major medical organizations recommend rectal temperature (TREC) to evaluate core body temperature (TcORE) during exercise in the cold; however, other field expedient devices claim to measure TCORE. The purpose of this study was to determine if field expedient devices provide valid measures of TcRE during rest and exercise in the cold. Participants included 13 men and 12 women (age = 24 +/- 3 yr, height = 170.7 +/- 10.6 cm, mass = 73.4 +/- 16.7 kg, body fat = 18 +/- 7%) who reported being healthy and at least recreationally active. During 150 min of cold exposure, subjects sequentially rested for 30 min, cycled for 90 min (heart rate = 120-140 bpm), and rested for an additional 30 min. Investigators compared aural (T(AUR)), expensive axillary (T(AXLe)), inexpensive axillary (T(AXLi)), forehead (T(FOR)), gastrointestinal (T(GI)), expensive oral (T(ORLe)), inexpensive oral (T(ORLi)), and temporal (T(TEM)) temperatures to T(REc) every 15 min. Researchers used mean difference between each device and T(REC) (i.e., mean bias) as the primary criterion for validity. T(AUR), T(AXLe), T(AXLi), T(FOR), TORLe, T(ORLi), and TTEM provided significantly lower measures compared to T(REC) and fell below our validity criterion. T(GI) significantly exceeded T(REC) at three of eleven time points, but no significant difference existed between mean T(REC) and T(GI) across time. Only T(GI) achieved our validity criterion and compared favorably to T(REC). T(GI) offers a valid measurement with which to assess T(CORE) during rest and exercise in the cold; athletic trainers, mountain rescuers, and military medical personnel should avoid other field expedient devices in similar conditions.

Cardiac rhythm management devices

PubMed

Stevenson, Irene; Voskoboinik, Alex

2018-05-01

The last decade has seen ongoing evolution and use of cardiac rhythm management devices, including pacemakers, cardiac resynchronisation therapy, implantable cardioverter defibrillators and loop recorders. General practitioners are increasingly involved in follow-up and management of patients with these devices. The aim of this article is to provide an overview of different cardiac rhythm management devices, including their role, implant procedure, post-procedural care, potential complications and follow‑up. We also include practical advice for patients regarding driving, exercise, sexual intimacy and precautions with regards to electromagnetic interference. Cardiac rhythm management devices perform many functions, including bradycardia pacing, monitoring for arrhythmias, cardiac resynchronisation for heart failure, defibrillation and anti-tachycardia pacing for tachyarrhythmias. Concerns regarding potential device-related complications should be discussed with the implanting physician. In the post-implant period, patients with cardiac rhythm management devices can expect to lead normal, active lives. However, caution must occasionally be exercised in certain situations, such as near appliances with electromagnetic interference. Future innovations will move away from transvenous leads to leadless designs with combinations of different components on a 'modular' basis according to the function required.

Astronaut Hammond gets microgravity exercise on rowing machine

NASA Image and Video Library

1994-09-10

STS064-09-026 (9-20 Sept. 1994) --- Astronaut L. Blaine Hammond, STS-64 pilot, gets microgravity exercise on the rowing machine. This area of the space shuttle Discovery's middeck was also used for the treadmill exercising device. Blaine and five other NASA astronauts spent almost 11 days in Earth orbit in support of the mission. Photo credit: NASA or National Aeronautics and Space Administration

Mobile, Virtual Enhancements for Rehabilitation (MOVER)

DTIC Science & Technology

2015-08-28

bottom of the figure. The patient uses COTS input devices, such as the Microsoft Kinect and the Wii Balance Board , to perform therapeutic exercises...specific, commonly used balance exercises into the system and enabling the therapists to select and customize pre-identified parameters for these exercises... balance disorder patients. We made these games highly customizable to enable therapists to tune each game to the capabilities of individual

Exercise physiology with a left ventricular assist device: Analysis of heart-pump interaction with a computational simulator.

PubMed

Fresiello, Libera; Rademakers, Frank; Claus, Piet; Ferrari, Gianfranco; Di Molfetta, Arianna; Meyns, Bart

2017-01-01

Patients with a Ventricular Assist Device (VAD) are hemodynamically stable but show an impaired exercise capacity. Aim of this work is to identify and to describe the limiting factors of exercise physiology with a VAD. We searched for data concerning exercise in heart failure condition and after VAD implantation from the literature. Data were analyzed by using a cardiorespiratory simulator that worked as a collector of inputs coming from different papers. As a preliminary step the simulator was used to reproduce the evolution of hemodynamics from rest to peak exercise (ergometer cycling) in heart failure condition. Results evidence an increase of cardiac output of +2.8 l/min and a heart rate increase to 67% of the expected value. Then, we simulated the effect of a continuous-flow VAD at both rest and exercise. Total cardiac output increases of +3.0 l/min (+0.9 l/min due to the VAD and +2.1 l/min to the native ventricle). Since the left ventricle works in a non-linear portion of the diastolic stiffness line, we observed a consistent increase of pulmonary capillary wedge pressure (from 14 to 20 mmHg) for a relatively small increase of end-diastolic volume (from 182 to 189 cm3). We finally increased VAD speed during exercise to the maximum possible value and we observed a reduction of wedge pressure (-4.5 mmHg), a slight improvement of cardiac output (8.0 l/min) and a complete unloading of the native ventricle. The VAD can assure a proper hemodynamics at rest, but provides an insufficient unloading of the left ventricle and does not prevent wedge pressure from rising during exercise. Neither the VAD provides major benefits during exercise in terms of total cardiac output, which increases to a similar extend to an unassisted heart failure condition. VAD speed modulation can contribute to better unload the ventricle but the maximal flow reachable with the current devices is below the cardiac output observed in a healthy heart.

Estimating Accuracy at Exercise Intensities: A Comparative Study of Self-Monitoring Heart Rate and Physical Activity Wearable Devices.

PubMed

Dooley, Erin E; Golaszewski, Natalie M; Bartholomew, John B

2017-03-16

Physical activity tracking wearable devices have emerged as an increasingly popular method for consumers to assess their daily activity and calories expended. However, whether these wearable devices are valid at different levels of exercise intensity is unknown. The objective of this study was to examine heart rate (HR) and energy expenditure (EE) validity of 3 popular wrist-worn activity monitors at different exercise intensities. A total of 62 participants (females: 58%, 36/62; nonwhite: 47% [13/62 Hispanic, 8/62 Asian, 7/62 black/ African American, 1/62 other]) wore the Apple Watch, Fitbit Charge HR, and Garmin Forerunner 225. Validity was assessed using 2 criterion devices: HR chest strap and a metabolic cart. Participants completed a 10-minute seated baseline assessment; separate 4-minute stages of light-, moderate-, and vigorous-intensity treadmill exercises; and a 10-minute seated recovery period. Data from devices were compared with each criterion via two-way repeated-measures analysis of variance and Bland-Altman analysis. Differences are expressed in mean absolute percentage error (MAPE). For the Apple Watch, HR MAPE was between 1.14% and 6.70%. HR was not significantly different at the start (P=.78), during baseline (P=.76), or vigorous intensity (P=.84); lower HR readings were measured during light intensity (P=.03), moderate intensity (P=.001), and recovery (P=.004). EE MAPE was between 14.07% and 210.84%. The device measured higher EE at all stages (P<.01). For the Fitbit device, the HR MAPE was between 2.38% and 16.99%. HR was not significantly different at the start (P=.67) or during moderate intensity (P=.34); lower HR readings were measured during baseline, vigorous intensity, and recovery (P<.001) and higher HR during light intensity (P<.001). EE MAPE was between 16.85% and 84.98%. The device measured higher EE at baseline (P=.003), light intensity (P<.001), and moderate intensity (P=.001). EE was not significantly different at vigorous (P=.70) or recovery (P=.10). For Garmin Forerunner 225, HR MAPE was between 7.87% and 24.38%. HR was not significantly different at vigorous intensity (P=.35). The device measured higher HR readings at start, baseline, light intensity, moderate intensity (P<.001), and recovery (P=.04). EE MAPE was between 30.77% and 155.05%. The device measured higher EE at all stages (P<.001). This study provides one of the first validation assessments for the Fitbit Charge HR, Apple Watch, and Garmin Forerunner 225. An advantage and novel approach of the study is the examination of HR and EE at specific physical activity intensities. Establishing validity of wearable devices is of particular interest as these devices are being used in weight loss interventions and could impact findings. Future research should investigate why differences between exercise intensities and the devices exist. ©Erin E Dooley, Natalie M Golaszewski, John B Bartholomew. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 16.03.2017.

Can Wearable Devices Accurately Measure Heart Rate Variability? A Systematic Review.

PubMed

Georgiou, Konstantinos; Larentzakis, Andreas V; Khamis, Nehal N; Alsuhaibani, Ghadah I; Alaska, Yasser A; Giallafos, Elias J

2018-03-01

A growing number of wearable devices claim to provide accurate, cheap and easily applicable heart rate variability (HRV) indices. This is mainly accomplished by using wearable photoplethysmography (PPG) and/or electrocardiography (ECG), through simple and non-invasive techniques, as a substitute of the gold standard RR interval estimation through electrocardiogram. Although the agreement between pulse rate variability (PRV) and HRV has been evaluated in the literature, the reported results are still inconclusive especially when using wearable devices. The purpose of this systematic review is to investigate if wearable devices provide a reliable and precise measurement of classic HRV parameters in rest as well as during exercise. A search strategy was implemented to retrieve relevant articles from MEDLINE and SCOPUS databases, as well as, through internet search. The 308 articles retrieved were reviewed for further evaluation according to the predetermined inclusion/exclusion criteria. Eighteen studies were included. Sixteen of them integrated ECG - HRV technology and two of them PPG - PRV technology. All of them examined wearable devices accuracy in RV detection during rest, while only eight of them during exercise. The correlation between classic ECG derived HRV and the wearable RV ranged from very good to excellent during rest, yet it declined progressively as exercise level increased. Wearable devices may provide a promising alternative solution for measuring RV. However, more robust studies in non-stationary conditions are needed using appropriate methodology in terms of number of subjects involved, acquisition and analysis techniques implied.

Bias in discriminating very mild dementia for older adults with different levels of education in Hong Kong.

PubMed

Chang, Jianfang; Tse, Chi-Shing; Leung, Grace Tak Yu; Fung, Ada Wai Tung; Hau, Kit-Tai; Chiu, Helen Fung Kum; Lam, Linda Chiu Wa

2014-06-01

Education has a profound effect on older adults' cognitive performance. In Hong Kong, some dementia screening tasks were originally designed for developed population with, on average, higher education. We compared the screening power of these tasks for Chinese older adults with different levels of education. Community-dwelling older adults who were healthy (N = 383) and with very mild dementia (N = 405) performed the following tasks: Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive subscales, Verbal Fluency, Abstract Thinking, and Visual/Digit Span. Logistic regression was used to examine the power of these tasks to predict Clinical Dementia Rating (CDR 0.5 vs. 0). Logistic regression analysis showed that while the screening power of the total scores in all tasks was similar for high and low education groups, there were education biases in some items of these tasks. The differential screening power in high and low education groups was not identical across items in some tasks. Thus, in cognitive assessments, we should exercise great caution when using these potentially biased items for older adults with limited education.

Evaluation of Liquid Dynamic Loads in Slack LNG Cargo Tanks

DTIC Science & Technology

1980-05-01

Syjateno Cmwr.~ d U. S. Geohogioal Survey MW. W. N. HANNAN W. C. J. ITFSTCOhE Vio. Pr. dent Chief Engineer American Bu au of Shipping Mlitary SeaZift C...CDR J. C. CARD MR. T. V. CHAPMN CDRJ. A. SAZAL JR. MR. A. B. STAVOVY (Chaiman) CDR W. N. SItEPSOk. JR. MR. D . STEIN NAVAL SEA SYSTEMS COMMAND U. S...0. NAWR DR. D . I, DR. W. M4CLIAN MR. I. L. STIN MW. F. SEBOLD Mr. N. TOULA N40NAL ACADEfY OF SCIENCES INTURNATIONAL SHIr STRUCTURES CONGRESS SHIP

Single-Molecule Fluorescence In Situ Hybridization (FISH) of Circular RNA CDR1as.

PubMed

Kocks, Christine; Boltengagen, Anastasiya; Piwecka, Monika; Rybak-Wolf, Agnieszka; Rajewsky, Nikolaus

2018-01-01

Individual mRNA molecules can be imaged in fixed cells by hybridization with multiple, singly labeled oligonucleotide probes, followed by computational identification of fluorescent signals. This approach, called single-molecule RNA fluorescence in situ hybridization (smRNA FISH), allows subcellular localization and absolute quantification of RNA molecules in individual cells. Here, we describe a simple smRNA FISH protocol for two-color imaging of a circular RNA, CDR1as, simultaneously with an unrelated messenger RNA. The protocol can be adapted to circRNAs that coexist with overlapping, noncircular mRNA isoforms produced from the same genetic locus.

Exercise in space: the European Space Agency approach to in-flight exercise countermeasures for long-duration missions on ISS.

PubMed

Petersen, Nora; Jaekel, Patrick; Rosenberger, Andre; Weber, Tobias; Scott, Jonathan; Castrucci, Filippo; Lambrecht, Gunda; Ploutz-Snyder, Lori; Damann, Volker; Kozlovskaya, Inessa; Mester, Joachim

2016-01-01

To counteract microgravity (µG)-induced adaptation, European Space Agency (ESA) astronauts on long-duration missions (LDMs) to the International Space Station (ISS) perform a daily physical exercise countermeasure program. Since the first ESA crewmember completed an LDM in 2006, the ESA countermeasure program has strived to provide efficient protection against decreases in body mass, muscle strength, bone mass, and aerobic capacity within the operational constraints of the ISS environment and the changing availability of on-board exercise devices. The purpose of this paper is to provide a description of ESA's individualised approach to in-flight exercise countermeasures and an up-to-date picture of how exercise is used to counteract physiological changes resulting from µG-induced adaptation. Changes in the absolute workload for resistive exercise, treadmill running and cycle ergometry throughout ESA's eight LDMs are also presented, and aspects of pre-flight physical preparation and post-flight reconditioning outlined. With the introduction of the advanced resistive exercise device (ARED) in 2009, the relative contribution of resistance exercise to total in-flight exercise increased (33-46 %), whilst treadmill running (42-33 %) and cycle ergometry (26-20 %) decreased. All eight ESA crewmembers increased their in-flight absolute workload during their LDMs for resistance exercise and treadmill running (running speed and vertical loading through the harness), while cycle ergometer workload was unchanged across missions. Increased or unchanged absolute exercise workloads in-flight would appear contradictory to typical post-flight reductions in muscle mass and strength, and cardiovascular capacity following LDMs. However, increased absolute in-flight workloads are not directly linked to changes in exercise capacity as they likely also reflect the planned, conservative loading early in the mission to allow adaption to µG exercise, including personal comfort issues with novel exercise hardware (e.g. the treadmill harness). Inconsistency in hardware and individualised support concepts across time limit the comparability of results from different crewmembers, and questions regarding the difference between cycling and running in µG versus identical exercise here on Earth, and other factors that might influence in-flight exercise performance, still require further investigation.

Pneumatic strength assessment device: design and isometric measurement.

PubMed

Paulus, David C; Reiser, Raoul F; Troxell, Wade O

2004-01-01

In order to load a muscle optimally during resistance exercise, it should be heavily taxed throughout the entire range of motion for that exercise. However, traditional constant resistance squats only tax the lower-extremity muscles to their limits at the "sticking region" or a critical joint configuration of the exercise cycle. Therefore, a linear motion (Smith) exercise machine was modified with pneumatics and appropriate computer control so that it could be capable of adjusting force to control velocity within a repetition of the squat exercise or other exercise performed with the device. Prior to application of this device in a dynamic squat setting, the maximum voluntary isometric force (MVIF) produced over a spectrum of knee angles is needed. This would reveal the sticking region and overall variation in strength capacity. Five incremental knee angles (90, 110, 130, 150, and 170 degrees, where 180 degrees defined full extension) were examined. After obtaining university-approved informed consent, 12 men and 12 women participated in the study. The knee angle was set, and the pneumatic cylinder was pressurized such that the subject could move the barbell slightly but no more than two-centimeters. The peak pressure exerted over a five-second maximum effort interval was recorded at each knee angle in random order and then repeated. The average of both efforts was then utilized for further analysis. The sticking region occurred consistently at a 90 degrees knee angle, however, the maximum force produced varied between 110 degrees and 170 degrees with the greatest frequency at 150 degrees for both men and women. The percent difference between the maximum and minimum MVIF was 46% for men and 57% for women.

Effectiveness of an upper extremity exercise device integrated with computer gaming for aerobic training in adolescents with spinal cord dysfunction.

PubMed

Widman, Lana M; McDonald, Craig M; Abresch, R Ted

2006-01-01

To determine whether a new upper extremity exercise device integrated with a video game (GameCycle) requires sufficient metabolic demand and effort to induce an aerobic training effect and to explore the feasibility of using this system as an exercise modality in an exercise intervention. Pre-post intervention. University-based research facility. SUBJECT POPULATION: A referred sample of 8 adolescent subjects with spina bifida (4 girls, 15.5 +/- 0.6 years; 4 boys, 17.5 +/- 0.9 years) was recruited to participate in the project. All subjects had some level of mobility impairment that did not allow them to participate in mainstream sports available to their nondisabled peers. Five subjects used a wheelchair full time, one used a wheelchair occasionally, but walked with forearm crutches, and 2 were fully ambulatory, but had impaired gait. Peak oxygen uptake, maximum work output, aerobic endurance, peak heart rate, rating of perceived exertion, and user satisfaction. Six of the 8 subjects were able to reach a Vo2 of at least 50% of their Vo2 reserve while using the GameCycle. Seven of the 8 subjects reached a heart rate of at least 50% of their heart rate reserve. One subject did not reach either 50% of Vo2 reserve or 50% of heart rate reserve. Seven of the 8 subjects increased their maximum work capability after training with the GameCycle at least 3 times per week for 16 weeks. The data suggest that the GameCycle seems to be adequate as an exercise device to improve oxygen uptake and maximum work capability in adolescents with lower extremity disability caused by spinal cord dysfunction. The subjects in this study reported that the video game component was enjoyable and provided a motivation to exercise.

Next Gen One Portal Usability Evaluation

NASA Technical Reports Server (NTRS)

Cross, E. V., III; Perera, J. S.; Hanson, A. M.; English, K.; Vu, L.; Amonette, W.

2018-01-01

Each exercise device on the International Space Station (ISS) has a unique, customized software system interface with unique layouts / hierarchy, and operational principles that require significant crew training. Furthermore, the software programs are not adaptable and provide no real-time feedback or motivation to enhance the exercise experience and/or prevent injuries. Additionally, the graphical user interfaces (GUI) of these systems present information through multiple layers resulting in difficulty navigating to the desired screens and functions. These limitations of current exercise device GUI's lead to increased crew time spent on initiating, loading, performing exercises, logging data and exiting the system. To address these limitations a Next Generation One Portal (NextGen One Portal) Crew Countermeasure System (CMS) was developed, which utilizes the latest industry guidelines in GUI designs to provide an intuitive ease of use approach (i.e., 80% of the functionality gained within 5-10 minutes of initial use without/limited formal training required). This is accomplished by providing a consistent interface using common software to reduce crew training, increase efficiency & user satisfaction while also reducing development & maintenance costs. Results from the usability evaluations showed the NextGen One Portal UI having greater efficiency, learnability, memorability, usability and overall user experience than the current Advanced Resistive Exercise Device (ARED) UI used by astronauts on ISS. Specifically, the design of the One-Portal UI as an app interface similar to those found on the Apple and Google's App Store, assisted many of the participants in grasping the concepts of the interface with minimum training. Although the NextGen One-Portal UI was shown to be an overall better interface, observations by the test facilitators noted specific exercise tasks appeared to have a significant impact on the NextGen One-Portal UI efficiency. Future updates to the NextGen One Portal UI will address these inefficiencies.

Mobile, Virtual Enhancements for Rehabilitation (MOVER)

DTIC Science & Technology

2015-05-31

patient uses COTS input devices, such as the Microsoft Kinect and the Wii Balance Board , to perform therapeutic exercises that are mapped to controls...in place of having an exercise creation tool for the therapists, we have simplified the process by hardcoding specific, commonly used balance

FE Furukawa exercising with the ARED

NASA Image and Video Library

2011-07-30

ISS028-E-019507 (30 July 2011) --- Japan Aerospace Exploration Agency astronaut Satoshi Furukawa, Expedition 28 flight engineer, uses the short bar for the advanced Resistive Exercise Device (aRED) equipment to perform upper body strengthening pull-ups in the Tranquility node of the International Space Station.

Comparison of energy expenditure on a treadmill vs. an elliptical device at a self-selected exercise intensity.

PubMed

Brown, Gregory A; Cook, Chad M; Krueger, Ryan D; Heelan, Kate A

2010-06-01

Treadmills (TM) and elliptical devices (EL) are popular forms of exercise equipment. The differences in the training stimulus presented by TM or EL are unknown. The purpose of this investigation was to evaluate oxygen consumption, energy expenditure, and heart rate on a TM or EL when persons exercise at the same perceived level of exertion. After measuring peak oxygen uptake (VO2peak) in 9 male and 9 female untrained college-aged participants, the subjects performed 2 separate 15-minute submaximal exercise tests on the TM and EL at a rating of perceived exertion (RPE) of 12-13. VO2peak was higher (p<0.05) in the males (48.6+/-1.5 vs. 45.2+/-1.6 ml/kg/min) than the females (41.7+/-1.8 vs. 38.8+/-2.2 ml/kg/min) for both TM and EL (means+/-standard error of the mean; for TM vs. EL respectively), but there were no differences in the measured VO2peak between TM or EL. During submaximal exercise there were no differences in RPE between TM and EL. Total oxygen consumption was higher (p<0.05) in males (30.8+/-2.2 vs. 34.9+/-2.2 L) than females (24.1+/-1.8 vs. 26.9+/-1.7 L) but did not differ between TM and EL. Energy expenditure was not different between TM (569+/-110 J) or EL (636+/-120 kJ). Heart rate was higher (p<0.05) on the EL (164+/-16 beats/min) compared to the TM (145+/-15 beats/min). When subjects exercise at the same RPE on TM or EL, oxygen consumption and energy expenditure are similar in spite of a higher heart rate on the EL. These data indicate that during cross training or noncompetition-specific exercise, an elliptical device is an acceptable alternative to a treadmill.

A novel architecture of recovered data comparison for high speed clock and data recovery

NASA Astrophysics Data System (ADS)

Gao, Susan; Li, Fei; Wang, Zhigong; Cui, Hongliang

2005-05-01

A clock and data recovery (CDR) circuit is one of the crucial blocks in high-speed serial link communication systems. The data received in these systems are asynchronous and noisy, requiring that a clock be extracted to allow synchronous operations. Furthermore, the data must be "retimed" so that the jitter accumulated during transmission is removed. This paper presents a novel architecture of CDR, which is very tolerant to long sequences of serial ones or zeros and also robust to occasional long absence of transitions. The design is based on the fact that a basic clock recovery having a clock recovery circuit (CRC) and a data decision circuit separately would generate a high jitter clock when the received non-return-to-zero (NRZ) data with long sequences of ones or zeros. To eliminate this drawback, the proposed architecture incorporates a data circuit decision circuit within the phase-locked loop (PLL) CRC. Other than this, a new phase detector (PD) is also proposed, which was easy to accomplish and robust at high speed. This PD is functional with a random input and automatically turns to disable during both the locked state and long absence of transitions. The voltage-controlled oscillator (VCO) is also designed delicately to suppress the jitter. Due to the high stability, the jitter is highly reduced when the loop is locked. The simulation results of such CDR working at 1.25Gb/s particularly for 1000BASE-X Gigabit Ethernet by using TSMC 0.25μm technology are presented to prove the feasibility of this architecture. One more CDR based on edge detection architecture is also built in the circuit for performance comparisons.

Pathways limiting warming to 1.5°C: a tale of turning around in no time?

NASA Astrophysics Data System (ADS)

Kriegler, Elmar; Luderer, Gunnar; Bauer, Nico; Baumstark, Lavinia; Fujimori, Shinichiro; Popp, Alexander; Rogelj, Joeri; Strefler, Jessica; van Vuuren, Detlef P.

2018-05-01

We explore the feasibility of limiting global warming to 1.5°C without overshoot and without the deployment of carbon dioxide removal (CDR) technologies. For this purpose, we perform a sensitivity analysis of four generic emissions reduction measures to identify a lower bound on future CO2 emissions from fossil fuel combustion and industrial processes. Final energy demand reductions and electrification of energy end uses as well as decarbonization of electricity and non-electric energy supply are all considered. We find the lower bound of cumulative fossil fuel and industry CO2 emissions to be 570 GtCO2 for the period 2016-2100, around 250 GtCO2 lower than the lower end of available 1.5°C mitigation pathways generated with integrated assessment models. Estimates of 1.5°C-consistent CO2 budgets are highly uncertain and range between 100 and 900 GtCO2 from 2016 onwards. Based on our sensitivity analysis, limiting warming to 1.5°C will require CDR or terrestrial net carbon uptake if 1.5°C-consistent budgets are smaller than 650 GtCO2. The earlier CDR is deployed, the more it neutralizes post-2020 emissions rather than producing net negative emissions. Nevertheless, if the 1.5°C budget is smaller than 550 GtCO2, temporary overshoot of the 1.5°C limit becomes unavoidable if CDR cannot be ramped up faster than to 4 GtCO2 in 2040 and 10 GtCO2 in 2050. This article is part of the theme issue `The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.

Impact of reconstruction parameters on quantitative I-131 SPECT

NASA Astrophysics Data System (ADS)

van Gils, C. A. J.; Beijst, C.; van Rooij, R.; de Jong, H. W. A. M.

2016-07-01

Radioiodine therapy using I-131 is widely used for treatment of thyroid disease or neuroendocrine tumors. Monitoring treatment by accurate dosimetry requires quantitative imaging. The high energy photons however render quantitative SPECT reconstruction challenging, potentially requiring accurate correction for scatter and collimator effects. The goal of this work is to assess the effectiveness of various correction methods on these effects using phantom studies. A SPECT/CT acquisition of the NEMA IEC body phantom was performed. Images were reconstructed using the following parameters: (1) without scatter correction, (2) with triple energy window (TEW) scatter correction and (3) with Monte Carlo-based scatter correction. For modelling the collimator-detector response (CDR), both (a) geometric Gaussian CDRs as well as (b) Monte Carlo simulated CDRs were compared. Quantitative accuracy, contrast to noise ratios and recovery coefficients were calculated, as well as the background variability and the residual count error in the lung insert. The Monte Carlo scatter corrected reconstruction method was shown to be intrinsically quantitative, requiring no experimentally acquired calibration factor. It resulted in a more accurate quantification of the background compartment activity density compared with TEW or no scatter correction. The quantification error relative to a dose calibrator derived measurement was found to be  <1%,-26% and 33%, respectively. The adverse effects of partial volume were significantly smaller with the Monte Carlo simulated CDR correction compared with geometric Gaussian or no CDR modelling. Scatter correction showed a small effect on quantification of small volumes. When using a weighting factor, TEW correction was comparable to Monte Carlo reconstruction in all measured parameters, although this approach is clinically impractical since this factor may be patient dependent. Monte Carlo based scatter correction including accurately simulated CDR modelling is the most robust and reliable method to reconstruct accurate quantitative iodine-131 SPECT images.

Pathways limiting warming to 1.5°C: a tale of turning around in no time?

PubMed

Kriegler, Elmar; Luderer, Gunnar; Bauer, Nico; Baumstark, Lavinia; Fujimori, Shinichiro; Popp, Alexander; Rogelj, Joeri; Strefler, Jessica; van Vuuren, Detlef P

2018-05-13

We explore the feasibility of limiting global warming to 1.5°C without overshoot and without the deployment of carbon dioxide removal (CDR) technologies. For this purpose, we perform a sensitivity analysis of four generic emissions reduction measures to identify a lower bound on future CO 2 emissions from fossil fuel combustion and industrial processes. Final energy demand reductions and electrification of energy end uses as well as decarbonization of electricity and non-electric energy supply are all considered. We find the lower bound of cumulative fossil fuel and industry CO 2 emissions to be 570 GtCO 2 for the period 2016-2100, around 250 GtCO 2 lower than the lower end of available 1.5°C mitigation pathways generated with integrated assessment models. Estimates of 1.5°C-consistent CO 2 budgets are highly uncertain and range between 100 and 900 GtCO 2 from 2016 onwards. Based on our sensitivity analysis, limiting warming to 1.5°C will require CDR or terrestrial net carbon uptake if 1.5°C-consistent budgets are smaller than 650 GtCO 2 The earlier CDR is deployed, the more it neutralizes post-2020 emissions rather than producing net negative emissions. Nevertheless, if the 1.5°C budget is smaller than 550 GtCO 2 , temporary overshoot of the 1.5°C limit becomes unavoidable if CDR cannot be ramped up faster than to 4 GtCO 2 in 2040 and 10 GtCO 2 in 2050.This article is part of the theme issue 'The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'. © 2018 The Author(s).

The frequent mutation Gly/Asp in CDR1H may determine a cross-reactive idiotope in anti-I cold agglutinins

PubMed Central

ABATANGELO, C; PLOTKIN, L; MATHOV, I; SQUIQUERA, L; LEONI, J

1996-01-01

Variable domains (VH) of all known anti i/I cold agglutinin (CA) heavy chains are codified by the VH4–21 gene. While anti-i CAs are the expression of gene rearrangement without mutations represented by amino acid changes, anti-I CAs present, among others, a frequent somatic mutation of Gly by Asp at position 31. The hydropathy profile calculated for the CDR1H (position 30 to position 35), as well as some adjacent positions of the heavy chain belonging to anti-i and anti-I antibodies, showed the conformational changes accompanying the replacement of Gly by Asp. A MoAb (LP91), which had been obtained in BALB/c mice immunized with a Fabμ fragment from a monoclonal IgMκIIIb anti-I CA (protein KAU), proved capable of inhibiting human adult erythrocyte cryoagglutination by anti-I CAs but not that of fetal erythrocytes by anti-i CAs. Western blot analysis disclosed that such MoAbs recognized a sequential epitope located in the Fd fragment of all anti-I CAs employed in this study. With the purpose of checking whether Asp31 was involved in the epitope recognized by the MoAb, two peptides, D and G, were synthesized which mimicked the CDR1H structure of anti-I and anti-i, respectively; the MoAb only reacted with peptide D by ELISA. Subsequent experimental results indicate that the Gly/Asp mutation could be associated with the diverse specificity presented by these autoantibodies, a change determining a characteristic epitope/idiotope, recognized by LP91 in the CDR1H. PMID:8603526

Statistical inference of the generation probability of T-cell receptors from sequence repertoires.

PubMed

Murugan, Anand; Mora, Thierry; Walczak, Aleksandra M; Callan, Curtis G

2012-10-02

Stochastic rearrangement of germline V-, D-, and J-genes to create variable coding sequence for certain cell surface receptors is at the origin of immune system diversity. This process, known as "VDJ recombination", is implemented via a series of stochastic molecular events involving gene choices and random nucleotide insertions between, and deletions from, genes. We use large sequence repertoires of the variable CDR3 region of human CD4+ T-cell receptor beta chains to infer the statistical properties of these basic biochemical events. Because any given CDR3 sequence can be produced in multiple ways, the probability distribution of hidden recombination events cannot be inferred directly from the observed sequences; we therefore develop a maximum likelihood inference method to achieve this end. To separate the properties of the molecular rearrangement mechanism from the effects of selection, we focus on nonproductive CDR3 sequences in T-cell DNA. We infer the joint distribution of the various generative events that occur when a new T-cell receptor gene is created. We find a rich picture of correlation (and absence thereof), providing insight into the molecular mechanisms involved. The generative event statistics are consistent between individuals, suggesting a universal biochemical process. Our probabilistic model predicts the generation probability of any specific CDR3 sequence by the primitive recombination process, allowing us to quantify the potential diversity of the T-cell repertoire and to understand why some sequences are shared between individuals. We argue that the use of formal statistical inference methods, of the kind presented in this paper, will be essential for quantitative understanding of the generation and evolution of diversity in the adaptive immune system.

Increased Susceptibility to Oxidative Death of Lymphocytes from Alzheimer Patients Correlates with Dementia Severity

PubMed Central

Ponce, Daniela P.; Salech, Felipe; SanMartin, Carol D.; Silva, Monica; Xiong, Chengjie; Roe, Catherine M.; Henriquez, Mauricio; Quest, Andrew F.; Behrens, Maria I.

2015-01-01

We previously reported on enhanced susceptibility to death of lymphocytes from Alzheimer’s disease (AD) patients when exposed to hydrogen peroxide (H2O2)-induced oxidative stress and an increased resistance to death in those of patients with a history of skin cancer. This is consistent with our hypothesis proposing that the cellular machinery controlling cell death is deregulated in opposite directions in Alzheimer’s disease (AD) and cancer, to explain the inverse association observed in epidemiological studies. Here we investigated whether the observed increased susceptibility correlates with the degree of dementia severity. Peripheral lymphocytes from 23 AD patients, classified using the Clinical Dementia Rating (CDR) into severe dementia (CDR 3, n=10) and mild-to-moderate dementia (CDR 1–2, n=13), and 15 healthy controls (HC) (CDR 0), were exposed to H2O2 for 20 hours. Lymphocyte death was determined by flow cytometry and propidium iodide staining. The greatest susceptibility to H2O2-induced death was observed for lymphocytes from severe dementia patients, whereas those with mild-to-moderate dementia exhibited intermediate values, compared to healthy controls. A significant increase in the apoptosis/necrosis ratio was found in AD patients. Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibition significantly protected from H2O2-induced death of lymphocytes, whereby a lower degree of protection was observed in severe AD patients. Moreover, inhibition of PARP-1 abolished the differences in apoptosis/necrosis ratios observed between the three groups of patients. These results support the notion that AD is a systemic disorder, whereby enhanced susceptibility to H2O2-induced death in peripheral lymphocytes correlates with dementia severity and enhanced death in AD patients is attributable to a PARP-dependent increase in the apoptosis/necrosis ratio. PMID:25274115

Estimation and Uncertainty of Recent Carbon Accumulation and Vertical Accretion in Drained and Undrained Forested Peatlands of the Southeastern USA

NASA Astrophysics Data System (ADS)

Drexler, Judith Z.; Fuller, Christopher C.; Orlando, James; Salas, Antonia; Wurster, Frederic C.; Duberstein, Jamie A.

2017-10-01

The purpose of this study was to determine how drainage impacts carbon densities and recent rates (past 50 years) of vertical accretion and carbon accumulation in southeastern forested peatlands. We compared these parameters in drained maple-gum (MAPL), Atlantic white cedar (CDR), and pocosin (POC) communities in the Great Dismal Swamp National Wildlife Refuge (GDS) of Virginia/North Carolina and in an intact (undrained) CDR swamp in the Alligator River National Wildlife Refuge (AR) of North Carolina. Peat cores were analyzed for bulk density, percent organic carbon, and 137Cs and 210Pb. An uncertainty analysis of both 137Cs and 210Pb approaches was used to constrain error at least partially related to mobility of both radioisotopes. GDS peats had lower porosities (89.6% (SD = 1.71) versus 95.3% (0.18)) and higher carbon densities (0.082 (0.021) versus 0.037 (0.009) g C cm-3) than AR. Vertical accretion rates (0.10-0.56 cm yr-1) were used to estimate a time period of 84-362 years for reestablishment of peat lost during the 2011 Lateral West fire at the GDS. Carbon accumulation rates ranged from 51 to 389 g C m-2 yr-1 for all sites. In the drained (GDS) versus intact (AR) CDR sites, carbon accumulation rates were similar with 137Cs (87GDS versus 92AR g C m-2 yr-1) and somewhat less at the GDS than AR as determined with 210Pb (111GDS versus 159AR g C m-2 yr-1). Heightened productivity and high polyphenol content of peat may be responsible for similar rates of carbon accumulation in both drained and intact CDR peatlands.

BioCreative V CDR task corpus: a resource for chemical disease relation extraction.

PubMed

Li, Jiao; Sun, Yueping; Johnson, Robin J; Sciaky, Daniela; Wei, Chih-Hsuan; Leaman, Robert; Davis, Allan Peter; Mattingly, Carolyn J; Wiegers, Thomas C; Lu, Zhiyong

2016-01-01

Community-run, formal evaluations and manually annotated text corpora are critically important for advancing biomedical text-mining research. Recently in BioCreative V, a new challenge was organized for the tasks of disease named entity recognition (DNER) and chemical-induced disease (CID) relation extraction. Given the nature of both tasks, a test collection is required to contain both disease/chemical annotations and relation annotations in the same set of articles. Despite previous efforts in biomedical corpus construction, none was found to be sufficient for the task. Thus, we developed our own corpus called BC5CDR during the challenge by inviting a team of Medical Subject Headings (MeSH) indexers for disease/chemical entity annotation and Comparative Toxicogenomics Database (CTD) curators for CID relation annotation. To ensure high annotation quality and productivity, detailed annotation guidelines and automatic annotation tools were provided. The resulting BC5CDR corpus consists of 1500 PubMed articles with 4409 annotated chemicals, 5818 diseases and 3116 chemical-disease interactions. Each entity annotation includes both the mention text spans and normalized concept identifiers, using MeSH as the controlled vocabulary. To ensure accuracy, the entities were first captured independently by two annotators followed by a consensus annotation: The average inter-annotator agreement (IAA) scores were 87.49% and 96.05% for the disease and chemicals, respectively, in the test set according to the Jaccard similarity coefficient. Our corpus was successfully used for the BioCreative V challenge tasks and should serve as a valuable resource for the text-mining research community.Database URL: http://www.biocreative.org/tasks/biocreative-v/track-3-cdr/. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.

Unprecedented rates of land-use transformation in modeled climate change mitigation pathways

NASA Astrophysics Data System (ADS)

Turner, P. A.; Field, C. B.; Lobell, D. B.; Sanchez, D.; Mach, K. J.

2017-12-01

Integrated assessment models (IAMs) generate climate change mitigation scenarios consistent with global temperature targets. To limit warming to 2°, stylized cost-effective mitigation pathways rely on extensive deployments of carbon dioxide (CO2) removal (CDR) technologies, including multi-gigatonne yearly carbon removal from the atmosphere through bioenergy with carbon capture and storage (BECCS) and afforestation/reforestation. These assumed CDR deployments keep ambitious temperature limits in reach, but associated rates of land-use transformation have not been evaluated. For IAM scenarios from the IPCC Fifth Assessment Report, we compare rates of modeled land-use conversion to recent observed commodity crop expansions. In scenarios with a likely chance of limiting warming to 2° in 2100, the rate of energy cropland expansion supporting BECCS exceeds past commodity crop rates by several fold. In some cases, mitigation scenarios include abrupt reversal of deforestation, paired with massive afforestation/reforestation. Specifically, energy cropland in <2° scenarios expands, on average, by 8.2 Mha yr-1 and 11.7% p.a. across scenarios. This rate exceeds, by more than 3-fold, the observed expansion of soybean, the most rapidly expanding commodity crop. If energy cropland instead increases at rates equal to recent soybean and oil palm expansions, the scale of CO2 removal possible with BECCS is 2.6 to 10-times lower, respectively, than the deployments <2° IAM scenarios rely upon in 2100. IAM mitigation pathways may favor multi-gigatonne biomass-based CDR given undervalued sociopolitical and techno-economic deployment barriers. Heroic modeled rates for land-use transformation imply that large-scale biomass-based CDR is not an easy solution to the climate challenge.

A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions

PubMed Central

Shimizu, Kiminori; Paul, Sanjoy; Ohba, Ayumi; Gonoi, Tohru; Watanabe, Akira; Gomi, Katsuya

2017-01-01

Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans. This fungal-specific Zn2-Cys6 type transcription factor AtrR was found to regulate expression of the genes related to ergosterol biosynthesis, including cyp51A that encodes a target protein of azoles. The atrR deletion mutant showed impaired growth under hypoxic conditions and attenuation of virulence in murine infection model for aspergillosis. These results were similar to the phenotypes for a mutant strain lacking SrbA that is also a direct regulator for the cyp51A gene. Notably, AtrR was responsible for the expression of cdr1B that encodes an ABC transporter related to azole resistance, whereas SrbA was not involved in the regulation. Chromatin immunoprecipitation assays indicated that AtrR directly bound both the cyp51A and cdr1B promoters. In the clinically isolated itraconazole resistant strain that harbors a mutant Cyp51A (G54E), deletion of the atrR gene resulted in a hypersensitivity to the azole drugs. Together, our results revealed that AtrR plays a pivotal role in a novel azole resistance mechanism by co-regulating the drug target (Cyp51A) and putative drug efflux pump (Cdr1B). PMID:28052140

Surrogate outcomes: experiences at the Common Drug Review

PubMed Central

2013-01-01

Background Surrogate outcomes are a significant challenge in drug evaluation for health technology assessment (HTA) agencies. The research objectives were to: identify factors associated with surrogate use and acceptability in Canada’s Common Drug Review (CDR) recommendations, and compare the CDR with other HTA or regulatory agencies regarding surrogate concerns. Methods Final recommendations were identified from CDR inception (September 2003) to December 31, 2010. Recommendations were classified by type of outcome (surrogate, final, other) and acceptability of surrogates (determined by the presence/absence of statements of concern regarding surrogates). Descriptive and statistical analyses examined factors related to surrogate use and acceptability. For thirteen surrogate-based submissions, recommendations from international HTA and regulatory agencies were reviewed for statements about surrogate acceptability. Results Of 156 final recommendations, 68 (44%) involved surrogates. The overall ‘do not list’ (DNL) rate was 48%; the DNL rate for surrogates was 41% (p = 0.175). The DNL rate was 64% for non-accepted surrogates (n = 28) versus 25% for accepted surrogates (odds ratio 5.4, p = 0.002). Clinical uncertainty, use of economic evidence over price alone, and a premium price were significantly associated with non-accepted surrogates. Surrogates were used most commonly for HIV, diabetes, rare diseases, cardiovascular disease and cancer. For the subset of drugs studied, other HTA agencies did not express concerns for most recommendations, while regulatory agencies frequently stated surrogate acceptance. Conclusions The majority of surrogates were accepted at the CDR. Non-accepted surrogates were significantly associated with clinical uncertainty and a DNL recommendation. There was inconsistency of surrogate acceptability across several international agencies. Stakeholders should consider collaboratively establishing guidelines on the use, validation, and acceptability of surrogates. PMID:24341379

Evaluation of a new satellite-based precipitation dataset for climate studies in the Xiang River basin, Southern China

NASA Astrophysics Data System (ADS)

Zhu, Q.; Xu, Y. P.; Hsu, K. L.

2017-12-01

A new satellite-based precipitation dataset, Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks-Climate Data Record (PERSIANN-CDR) with long-term time series dating back to 1983 can be one valuable dataset for climate studies. This study investigates the feasibility of using PERSIANN-CDR as a reference dataset for climate studies. Sixteen CMIP5 models are evaluated over the Xiang River basin, southern China, by comparing their performance on precipitation projection and streamflow simulation, particularly on extreme precipitation and streamflow events. The results show PERSIANN-CDR is a valuable dataset for climate studies, even on extreme precipitation events. The precipitation estimates and their extreme events from CMIP5 models are improved significantly compared with rain gauge observations after bias-correction by the PERSIANN-CDR precipitation estimates. Given streamflows simulated with raw and bias-corrected precipitation estimates from 16 CMIP5 models, 10 out of 16 are improved after bias-correction. The impact of bias-correction on extreme events for streamflow simulations are unstable, with eight out of 16 models can be clearly claimed they are improved after the bias-correction. Concerning the performance of raw CMIP5 models on precipitation, IPSL-CM5A-MR excels the other CMIP5 models, while MRI-CGCM3 outperforms on extreme events with its better performance on six extreme precipitation metrics. Case studies also show that raw CCSM4, CESM1-CAM5, and MRI-CGCM3 outperform other models on streamflow simulation, while MIROC5-ESM-CHEM, MIROC5-ESM and IPSL-CM5A-MR behaves better than the other models after bias-correction.

Evaluation of DVD-R for Archival Applications

NASA Technical Reports Server (NTRS)

Martin, Michael D.; Hyon, Jason J.

2000-01-01

For more than a decade, CD-ROM and CD-R have provided an unprecedented level of reliability, low cost and cross-platform compatibility to support federal data archiving and distribution efforts. However, it should be remembered that years of effort were required to achieve the standardization that has supported the growth of the CD industry. Incompatibilities in the interpretation of the ISO-9660 standard on different operating systems had to be dealt with, and the imprecise specifications in the Orange Book Part n and Part Hi led to incompatibilities between CD-R media and CD-R recorders. Some of these issues were presented by the authors at Optical Data Storage '95. The major current problem with the use of CD technology is the growing volume of digital data that needs to be stored. CD-ROM collections of hundreds of volumes and CD-R collections of several thousand volumes are becoming almost too cumbersome to be useful. The emergence of Digital Video Disks Recorder (DVD-R) technology promises to reduce the number of discs required for archive applications by a factor of seven while providing improved reliability. It is important to identify problem areas for DVD-R media and provide guidelines to manufacturers, file system developers and users in order to provide reliable data storage and interchange. The Data Distribution Laboratory (DDL) at NASA's Jet Propulsion Laboratory began its evaluation of DVD-R technology in early 1998. The initial plan was to obtain a DVD-Recorder for preliminary testing, deploy reader hardware to user sites for compatibility testing, evaluate the quality and longevity of DVD-R media and develop proof-of-concept archive collections to test the reliability and usability of DVD-R media and jukebox hardware.

Effect of pupillary dilatation on glaucoma assessments using optical coherence tomography

PubMed Central

Smith, Michael; Frost, Andrew; Graham, Christopher Mark; Shaw, Steven

2007-01-01

Aims To examine the effect of pupillary dilatation on the reliability of retinal nerve fibre layer (RNFL) and optic nerve head (ONH) assessments using Stratus OCT in a glaucoma clinic. Methods Observational study of 38 patients attending a glaucoma clinic. The “fast optic disc” and “fast RNFL thickness” programs on Stratus OCT were used to measure the RNFL thickness and ONH cup to disc ratio (CDR). Two scans were done before dilatation and two after dilatation with tropicamide 1% drops. The mean values and reproducibility before and after dilatation were compared, along with the quality of scans as indicated by the “signal strength” score. Results In nine patients (23.7%) no images were obtained undilated but after dilatation examination was possible in all patients. Inability to obtain an undilated scan was associated with smaller pupil size and increasing cataract. The scan quality, as judged by the signal strength score, was higher dilated than undilated for both RNFL thickness (p = 0.011) and ONH CDR (p = 0.007). Reproducibility was higher with dilated scans for RNFL thickness but not for ONH CDR. There were significant differences between the dilated and undilated examinations for three of the five RNFL thickness variables and two of the three ONH CDR categories. Conclusions Acquisition of high quality OCT images was not possible without pupillary dilatation in about 25% of the patients. The dilated scans were more reproducible and of higher quality than the undilated scans. The two methods of examination do not appear to be interchangeable, suggesting that in follow up examinations the pupil should be in the same condition as at baseline. Pupillary dilatation is recommended before glaucoma assessments using Stratus OCT. PMID:17556429

Validation of PI-RADS version 2 for the detection of prostate cancer.

PubMed

Hofbauer, Sebastian L; Kittner, Beatrice; Maxeiner, Andreas; Heckmann, Robin; Reimann, Maximillian; Wiemer, Laura; Asbach, Patrick; Haas, Matthias; Penzkofer, Tobias; Stephan, Carsten; Friedersdorff, Frank; Fuller, Florian; Miller, Kurt; Cash, Hannes

2018-05-04

The second version of the Prostate Imaging Reporting and Data System (PI-RADSv2) was introduced in 2015 to standardize the interpretation and reporting of multiparametric prostate magnetic resonance imaging (mpMRI). Recently, low cancer detection rates (CDR) for PI-RADSv2 category 4 lesions were reported. Therefore the aim of the study was to evaluate the CDR of PI-RADSv2 in a large prospective cohort. The study included 704 consecutive men with primary or prior negative biopsies who underwent MRI/ultrasound fusion-guided targeted biopsy (TB) and 10-core systematic prostate biopsy (SB) between September 2015 and May 2017. All lesions were rated according to PI-RADSv2 and lesions with PI-RADSv2 category ≥ 3 were biopsied. An ISUP (International Society of Urological Pathology) score of 2 or greater (i.e. Gleason 3+4 or greater) was defined as clinically significant prostate cancer (csPCa). The overall CDR for PI-RADSv2 categories 3, 4, and 5 was 39%, 72%, and 91% for all PCa, and 23%, 49%, and 77% for all csPCa, respectively. Fifty-nine (16%) clinically significant tumors would have been missed if only TB was performed. The PI-RADSv2 score was significantly associated with the presence of PCa (p<0.001), the presence of csPCa (p<0.001), and the ISUP grading (p<0.001). PI-RADSv2 is significantly associated with the presence of csPCa. The CDR for PI-RADSv2 category 4 lesions was considerably higher than previously reported. When performing TB, the combination with a SB still warrants the highest detection of csPCa. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies

PubMed Central

Hwang, Joyce K.; Wang, Chong; Du, Zhou; Meyers, Robin M.; Kepler, Thomas B.; Neuberg, Donna; Kwong, Peter D.; Mascola, John R.; Joyce, M. Gordon; Bonsignori, Mattia; Haynes, Barton F.; Yeap, Leng-Siew; Alt, Frederick W.

2017-01-01

Variable regions of Ig chains provide the antigen recognition portion of B-cell receptors and derivative antibodies. Ig heavy-chain variable region exons are assembled developmentally from V, D, J gene segments. Each variable region contains three antigen-contacting complementarity-determining regions (CDRs), with CDR1 and CDR2 encoded by the V segment and CDR3 encoded by the V(D)J junction region. Antigen-stimulated germinal center (GC) B cells undergo somatic hypermutation (SHM) of V(D)J exons followed by selection for SHMs that increase antigen-binding affinity. Some HIV-1–infected human subjects develop broadly neutralizing antibodies (bnAbs), such as the potent VRC01-class bnAbs, that neutralize diverse HIV-1 strains. Mature VRC01-class bnAbs, including VRC-PG04, accumulate very high SHM levels, a property that hinders development of vaccine strategies to elicit them. Because many VRC01-class bnAb SHMs are not required for broad neutralization, high overall SHM may be required to achieve certain functional SHMs. To elucidate such requirements, we used a V(D)J passenger allele system to assay, in mouse GC B cells, sequence-intrinsic SHM-targeting rates of nucleotides across substrates representing maturation stages of human VRC-PG04. We identify rate-limiting SHM positions for VRC-PG04 maturation, as well as SHM hotspots and intrinsically frequent deletions associated with SHM. We find that mature VRC-PG04 has low SHM capability due to hotspot saturation but also demonstrate that generation of new SHM hotspots and saturation of existing hotspot regions (e.g., CDR3) does not majorly influence intrinsic SHM in unmutated portions of VRC-PG04 progenitor sequences. We discuss implications of our findings for bnAb affinity maturation mechanisms. PMID:28747530

A Climate-Data Record (CDR) of the "Clear Sky" Surface Temperature of the Greenland Ice Sheet

NASA Technical Reports Server (NTRS)

Hall, Dorothy K.; Comiso, J. C.; DiGirolamo, N. E.; Shuman, C. A.

2011-01-01

To quantify the ice-surface temperature (IST) we are developing a climate-data record (CDR) of monthly IST of the Greenland ice sheet, from 1982 to the present using Advanced Very High Resolution Radiometer (AVHRR) and Moderate-Resolution Imaging Spectroradiometer (MODIS) data at 5-km resolution. "Clear-sky" surface temperature increases have been measured from the early 1980s to the early 2000s in the Arctic using AVHRR data, showing increases ranging from 0.57-0.02 (Wang and Key, 2005) to 0.72 0.10 deg C per decade (Comiso, 2006). Arctic warming has implications for ice-sheet mass balance because much of the periphery of the ice sheet is near 0 deg C in the melt season and is thus vulnerable to more extensive melting (Hanna et al., 2008). The algorithm used for this work has a long history of measuring IST in the Arctic with AVHRR (Key and Haefliger, 1992). The data are currently available from 1981 to 2004 in the AVHRR Polar Pathfinder (APP) dataset (Fowler et al., 2000). J. Key1NOAA modified the AVHRR algorithm for use with MODIS (Hall et al., 2004). The MODIS algorithm is now being processed over Greenland. Issues being addressed in the production of the CDR are: time-series bias caused by cloud cover, and cross-calibration between AVHRR and MODIS instruments. Because of uncertainties, time series of satellite ISTs do not necessarily correspond with actual surface temperatures. The CDR will be validated by comparing results with in-situ (see Koenig and Hall, in press) and automatic-weather station data (e.g., Shuman et al., 2001).

Combining select neuropsychological assessment with blood-based biomarkers to detect mild Alzheimer's disease: a molecular neuropsychology approach.

PubMed

Edwards, Melissa; Balldin, Valerie Hobson; Hall, James; O'Bryant, Sid

2014-01-01

Current work has sought to establish a rapid and cost effective means of screening for Alzheimer's disease (AD) with the most recent findings showing utility of integrating blood-based biomarkers with cognitive measures. The current project sought to create a combined biomarker-cognitive profile to detect mild AD. Data was analyzed from 266 participants (129 AD cases [Early AD n = 93; Very Early AD n = 36]; 137 controls) enrolled in the Texas Alzheimer's Research and Care Consortium (TARCC). Non-fasting serum samples were collected from each participant and assayed via a multi-plex biomarker assay platform using electrochemiluminescence. Logistic Regression was utilized to detect early AD using two serum biomarkers (TNFα and IL7), demographic information (age), and one neuropsychological measure (Clock 4-point) as predictor variable. Disease severity was determined via Clinical Dementia Rating (CDR) scale global scores. In the total sample (all levels of CDR scores), the combination of biomarkers, cognitive test score, and demographics yielded the obtained sensitivity (SN) of 0.94, specificity (SP) of 0.90, and an overall accuracy of 0.92. When examining early AD cases (i.e.m CDR = 0.5-1), the biomarker-cognitive profile yielded SN of 0.94, SP of 0.85, and an overall accuracy of 0.91. When restricted to very early AD cases (i.e., CDR = 0.5), the biomarker-cognitive profile yielded SN of 0.97 and SP of 0.72, with an overall accuracy of 0.91. The combination of demographics, two biomarkers, and one cognitive test created a biomarker-cognitive profile that was highly accurate in detecting the presence of AD, even in the very early stages.

Directly observed treatment short-course (DOTS) for treatment of new tuberculosis cases in Somali Regional State, Eastern Ethiopia: ten years retrospective study.

PubMed

Woldeyohannes, Desalegn; Sisay, Solomon; Mengistu, Belete; Kassa, Hiwot

2015-08-19

A third of the world population is infected with tuberculosis (TB) bacilli. TB accounts for 25% of all avoidable deaths in developing countries. The objective of the study was to assess impact of directly observed treatment short-course (DOTS) strategy on new tuberculosis case finding and treatment outcomes in Somali Regional State, Ethiopia from 2003 up to 2012 and from 2004 up to 2013, respectively. A health facility based retrospective study was employed. Quarterly reports were collected using World Health Organization (WHO) reporting format for TB case finding and treatment outcome from all zones in the region to the Federal Ministry of Health. A total of 31, 198 all types of new TB cases were registered and reported during the period from 2003 up to 2012, in the region. Out of these, smear positive pulmonary TB cases were 12,466 (40%), and 10,537 (33.8%) and 8195 (26.2%) for smear negative pulmonary TB and extra-pulmonary TB cases, respectively. An average case detection rate (CDR) of 19.1% (SD 3.6) and treatment success rate (TSR) of 85.5% (SD 5.0) for smear positive pulmonary TB were reported for the specified years period. For the overall study period, trend chi-squire analysis for CDR was X(2) = 2.1; P > 0.05 and X(2) = 5.64; P < 0.05 for TSR. The recommended TSR set by WHO was achieved (85.5%) and the CDR reported was far below (19.1%) from the recommended target. Extensive efforts should be established to maintain the achieved TSR and to increase the low CDR for the smear positive pulmonary TB cases through implementing alternative case finding strategies.

Analysis of the binding loops configuration and surface adaptation of different crystallized single-domain antibodies in response to various antigens.

PubMed

Al Qaraghuli, Mohammed M; Ferro, Valerie A

2017-04-01

Monoclonal antibodies have revolutionized the biomedical field through their ubiquitous utilization in different diagnostics and therapeutic applications. Despite this widespread use, their large size and structural complexity have limited their versatility in specific applications. The antibody variable region that is responsible for binding antigen is embodied within domains that can be rescued individually as single-domain antibody (sdAb) fragments. Because of the unique characteristics of sdAbs, such as low molecular weight, high physicochemical stability, and the ability to bind antigens inaccessible to conventional antibodies, they represent a viable alternative to full-length antibodies. Consequently, 149 crystal structures of sdAbs, originating from human (VH), camelids (VHH), or sharks (VNAR), were retrieved from the Protein Data Bank, and their structures were compared. The 3 types of sdAbs displayed complementarity determining regions (CDRs) with different lengths and configurations. CDR3 of the VHH and VNAR domains were dominated by pleated and extended orientations, respectively. Although VNAR showed the smallest average molecular weight and molecular surface area compared with VHH and VH antibodies. However, the solvent accessible surface area measurements of the 3 tested sdAbs types were very similar. All the antihapten VHH antibodies showed pleated CDR3, which were sufficient to create a binding pocket to accommodate haptens (methotrexate and azo dyes) in terms of shape and electrostatic potential. The sdAbs that recognized lysozyme showed more diversity in their CDR3 orientation to enable them to recognize various topographies of lysozyme. Subsequently, the three sdAb classes were different in size and surface area and have shown distinguishable ability to optimize their CDR length and orientation to recognize different antigen classes. Copyright © 2016 John Wiley & Sons, Ltd.

Contrasting in vitro effects for the combination of fludarabine, cytosine arabinoside (Ara-C) and granulocyte colony-stimulating factor (FLAG) compared with daunorubicin and Ara-C in P-glycoprotein-positive and P-glycoprotein-negative acute myeloblastic leukaemia.

PubMed

Higashi, Y; Turzanski, J; Pallis, M; Russell, N H

2000-11-01

It has been suggested that the FLAG remission induction regimen comprising fludarabine (F-ara), cytosine arabinoside (Ara-C) and granulocyte colony-stimulating factor (G-CSF) may be capable of overcoming P-glycoprotein (P-gp)-related multidrug resistance (MDR) in patients with acute myeloblastic leukaemia (AML). We have investigated the in vitro response of P-gp-positive and -negative AML clones to FLAG and compared this with their response to treatment with Ara-C and daunorubicin (DNR). Twenty-four cryopreserved samples from patients with AML were studied using a flow cytometric technique for the enumeration of viable (7-amino actinomycin D negative) cells. Samples consisted of 12 P-gp-positive and 12 P-gp-negative cases, as measured by the MRK16 antibody. The results were analysed by calculating the comparative drug resistance (CDR), i.e. the percentage cell death caused by Ara-C + DNR subtracted from the percentage cell death, caused by FLAG after 48 h incubation in suspension culture. P-gp-positive clones were shown to have a significantly higher CDR than P-gp-negative clones (P = 0. 001). Furthermore, a significant positive correlation (r2 = 0.40, P < 0.01) was found between P-gp protein expression and CDR. However, P-gp function, measured using cyclosporin modulation of rhodamine 123 (R123) uptake, was not associated with the CDR, demonstrating that there are other properties of P-gp, besides its role in drug efflux, that modulate the responsiveness of AML blasts to chemotherapy. These results are consistent with a potential benefit for FLAG in P-gp-positive AML, but not P-gp-negative AML, compared with standard anthracycline and Ara-C therapy.