Left inferior frontal cortex and syntax: function, structure and behaviour in patients with left hemisphere damage

PubMed Central

Marslen-Wilson, William D.; Randall, Billi; Wright, Paul; Devereux, Barry J.; Zhuang, Jie; Papoutsi, Marina; Stamatakis, Emmanuel A.

2011-01-01

For the past 150 years, neurobiological models of language have debated the role of key brain regions in language function. One consistently debated set of issues concern the role of the left inferior frontal gyrus in syntactic processing. Here we combine measures of functional activity, grey matter integrity and performance in patients with left hemisphere damage and healthy participants to ask whether the left inferior frontal gyrus is essential for syntactic processing. In a functional neuroimaging study, participants listened to spoken sentences that either contained a syntactically ambiguous or matched unambiguous phrase. Behavioural data on three tests of syntactic processing were subsequently collected. In controls, syntactic processing co-activated left hemisphere Brodmann areas 45/47 and posterior middle temporal gyrus. Activity in a left parietal cluster was sensitive to working memory demands in both patients and controls. Exploiting the variability in lesion location and performance in the patients, voxel-based correlational analyses showed that tissue integrity and neural activity—primarily in left Brodmann area 45 and posterior middle temporal gyrus—were correlated with preserved syntactic performance, but unlike the controls, patients were insensitive to syntactic preferences, reflecting their syntactic deficit. These results argue for the essential contribution of the left inferior frontal gyrus in syntactic analysis and highlight the functional relationship between left Brodmann area 45 and the left posterior middle temporal gyrus, suggesting that when this relationship breaks down, through damage to either region or to the connections between them, syntactic processing is impaired. On this view, the left inferior frontal gyrus may not itself be specialized for syntactic processing, but plays an essential role in the neural network that carries out syntactic computations. PMID:21278407

Insights into the structure and function of membrane-integrated processive glycosyltransferases

DOE PAGES

Bi, Yunchen; Hubbard, Caitlin; Purushotham, Pallinti; ...

2015-09-02

Complex carbohydrates perform essential functions in life, including energy storage, cell signaling, protein targeting, quality control, as well as supporting cell structure and stability. Extracellular polysaccharides (EPS) represent mainly structural polymers and are found in essentially all kingdoms of life. For example, EPS are important biofilm and capsule components in bacteria, represent major constituents in cell walls of fungi, algae, arthropods and plants, and modulate the extracellular matrix in vertebrates. Different mechanisms evolved by which EPS are synthesized. In this paper, we review the structures and functions of membrane-integrated processive glycosyltransferases (GTs) implicated in the synthesis and secretion of chitin,more » alginate, hyaluronan and poly-N-acetylglucosamine (PNAG).« less

Insights into the structure and function of membrane-integrated processive glycosyltransferases

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

Bi, Yunchen; Hubbard, Caitlin; Purushotham, Pallinti

Complex carbohydrates perform essential functions in life, including energy storage, cell signaling, protein targeting, quality control, as well as supporting cell structure and stability. Extracellular polysaccharides (EPS) represent mainly structural polymers and are found in essentially all kingdoms of life. For example, EPS are important biofilm and capsule components in bacteria, represent major constituents in cell walls of fungi, algae, arthropods and plants, and modulate the extracellular matrix in vertebrates. Different mechanisms evolved by which EPS are synthesized. In this paper, we review the structures and functions of membrane-integrated processive glycosyltransferases (GTs) implicated in the synthesis and secretion of chitin,more » alginate, hyaluronan and poly-N-acetylglucosamine (PNAG).« less

29 CFR 1630.9 - Not making reasonable accommodation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... assistance authorized by section 506 of the ADA, including any failure in the development or dissemination of... functions of the position held or desired, and cannot, as a result of that rejection, perform the essential functions of the position, the individual will not be considered a qualified individual with a disability. ...

Elements of a Sound Education.

ERIC Educational Resources Information Center

Brooks, Christopher

2003-01-01

Discusses what do to about the poor acoustics in school multipurpose rooms, asserting that because the auditorium is the most critical function of a typical multipurpose room, the stage house is superficial and noise control is essential. Features to enhance auditorium function include a performance platform and reverberation control. The article…

49 CFR 109.11 - Assistance of properly qualified personnel.

Code of Federal Regulations, 2013 CFR

2013-10-01

... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS AND OIL TRANSPORTATION... properly qualified to perform a function that is essential to the agent's exercise of authority under this...

Relationships between Handwriting Performance and Organizational Abilities among Children with and without Dysgraphia: A Preliminary Study

ERIC Educational Resources Information Center

Rosenblum, Sara; Aloni, Tsipi; Josman, Naomi

2010-01-01

Organizational ability constitutes one executive function (EF) component essential for common everyday performance. The study aim was to explore the relationship between handwriting performance and organizational ability in school-aged children. Participants were 58 males, aged 7-8 years, 30 with dysgraphia and 28 with proficient handwriting.…

The role of rabbit meat as functional food.

PubMed

Dalle Zotte, Antonella; Szendro, Zsolt

2011-07-01

Increasing consumer knowledge of the link between diet and health has raised the awareness and demand for functional food ingredients. Meat and its derivatives may be considered functional foods to the extent that they contain numerous compounds thought to be functional. This review will attempt to outline the excellent nutritional and dietetic properties of rabbit meat and offer an overview of the studies performed on the strategies adopted to improve the functional value of rabbit meat. Dietary manipulation has been seen to be very effective in increasing the levels of essential FA, EPA, DHA, CLA, branched chain FA, vitamin E, and selenium in rabbit meat. Dietary fortification with vitamin E or natural products such as oregano essential oil, chia seed oil, and Spirulina platensis microalga seem promising in improving the oxidative stability of rabbit meat while also adding functional ingredients. Copyright © 2011 Elsevier Ltd. All rights reserved.

Association between urine aldosterone and diastolic function in patients with primary aldosteronism and essential hypertension.

PubMed

Chang, Yi-Yao; Lee, Hsiu-Hao; Hung, Chi-Sheng; Wu, Xue-Ming; Lee, Jen-Kuang; Wang, Shuo-Meng; Liao, Min-Tsun; Chen, Ying-Hsien; Wu, Vin-Cent; Wu, Kwan-Dun; Lin, Yen-Hung

2014-09-01

To investigate the association between aldosterone and cardiac diastolic dysfunction. We prospectively enrolled 20 patients with primary aldosteronism (PA) and 22 patients with essential hypertension (EH). Plasma aldosterone concentration, plasma renin activity, and 24-h urine aldosterone level were measured. Echocardiography, including tissue Doppler image recordings, was performed. PA patients had a significantly higher left ventricular (LV) mass index and worse LV diastolic function than those in EH patients. Among various measures of aldosterone, log-transformed 24-h urine aldosterone level had the most consistent correlation with diastolic function. Aldosterone is strongly associated with LV diastolic dysfunction. Twenty-four hour urine aldosterone is a good indicator to evaluate the impact of aldosterone on LV diastolic function. Copyright © 2014. Published by Elsevier Inc.

Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways.

PubMed

Chen, Lei; Zhang, Yu-Hang; Wang, ShaoPeng; Zhang, YunHua; Huang, Tao; Cai, Yu-Dong

2017-01-01

Identifying essential genes in a given organism is important for research on their fundamental roles in organism survival. Furthermore, if possible, uncovering the links between core functions or pathways with these essential genes will further help us obtain deep insight into the key roles of these genes. In this study, we investigated the essential and non-essential genes reported in a previous study and extracted gene ontology (GO) terms and biological pathways that are important for the determination of essential genes. Through the enrichment theory of GO and KEGG pathways, we encoded each essential/non-essential gene into a vector in which each component represented the relationship between the gene and one GO term or KEGG pathway. To analyze these relationships, the maximum relevance minimum redundancy (mRMR) was adopted. Then, the incremental feature selection (IFS) and support vector machine (SVM) were employed to extract important GO terms and KEGG pathways. A prediction model was built simultaneously using the extracted GO terms and KEGG pathways, which yielded nearly perfect performance, with a Matthews correlation coefficient of 0.951, for distinguishing essential and non-essential genes. To fully investigate the key factors influencing the fundamental roles of essential genes, the 21 most important GO terms and three KEGG pathways were analyzed in detail. In addition, several genes was provided in this study, which were predicted to be essential genes by our prediction model. We suggest that this study provides more functional and pathway information on the essential genes and provides a new way to investigate related problems.

49 CFR 109.11 - Assistance of properly qualified personnel.

Code of Federal Regulations, 2014 CFR

2014-10-01

... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS AND OIL TRANSPORTATION... conducted under this part if the agent is not properly qualified to perform a function that is essential to...

49 CFR 109.11 - Assistance of properly qualified personnel.

Code of Federal Regulations, 2011 CFR

2011-10-01

... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS AND OIL TRANSPORTATION... this part if the agent is not properly qualified to perform a function that is essential to the agent's...

49 CFR 109.11 - Assistance of properly qualified personnel.

Code of Federal Regulations, 2012 CFR

2012-10-01

... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS AND OIL TRANSPORTATION... this part if the agent is not properly qualified to perform a function that is essential to the agent's...

Potential Interrelationships Between Library and Other Mass Media Systems.

ERIC Educational Resources Information Center

Parker, Edwin B.

The function of libraries is to make it easy for the people in their community to obtain information from other people or environments that may be distant is space, time or imagination. To perform this function libraries require communication media. Storage media are essential, but duplication and transmission media can improve the service of…

78 FR 72124 - Information Collection Request; Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-02

... INFORMATION: Method: Applicants gain access to the form via a secure online portal. Applicants have to... perform the essential functions of a Peace Corps Volunteer and complete a tour of service without undue... functions of the Peace Corps, including whether the information will have practical use; the accuracy of the...

Tetrahydrolipstatin Inhibition, Functional Analyses, and Three-dimensional Structure of a Lipase Essential for Mycobacterial Viability

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

Crellin, Paul K.; Vivian, Julian P.; Scoble, Judith

2010-09-17

The highly complex and unique mycobacterial cell wall is critical to the survival of Mycobacteria in host cells. However, the biosynthetic pathways responsible for its synthesis are, in general, incompletely characterized. Rv3802c from Mycobacterium tuberculosis is a partially characterized phospholipase/thioesterase encoded within a genetic cluster dedicated to the synthesis of core structures of the mycobacterial cell wall, including mycolic acids and arabinogalactan. Enzymatic assays performed with purified recombinant proteins Rv3802c and its close homologs from Mycobacterium smegmatis (MSMEG{_}6394) and Corynebacterium glutamicum (NCgl2775) show that they all have significant lipase activities that are inhibited by tetrahydrolipstatin, an anti-obesity drug that coincidentlymore » inhibits mycobacterial cell wall biosynthesis. The crystal structure of MSMEG{_}6394, solved to 2.9 {angstrom} resolution, revealed an {alpha}/{beta} hydrolase fold and a catalytic triad typically present in esterases and lipases. Furthermore, we demonstrate direct evidence of gene essentiality in M. smegmatis and show the structural consequences of loss of MSMEG{_}6394 function on the cellular integrity of the organism. These findings, combined with the predicted essentiality of Rv3802c in M. tuberculosis, indicate that the Rv3802c family performs a fundamental and indispensable lipase-associated function in mycobacteria.« less

Tetrahydrolipstatin inhibition, functional analyses, and three-dimensional structure of a lipase essential for mycobacterial viability.

PubMed

Crellin, Paul K; Vivian, Julian P; Scoble, Judith; Chow, Frances M; West, Nicholas P; Brammananth, Rajini; Proellocks, Nicholas I; Shahine, Adam; Le Nours, Jerome; Wilce, Matthew C J; Britton, Warwick J; Coppel, Ross L; Rossjohn, Jamie; Beddoe, Travis

2010-09-24

The highly complex and unique mycobacterial cell wall is critical to the survival of Mycobacteria in host cells. However, the biosynthetic pathways responsible for its synthesis are, in general, incompletely characterized. Rv3802c from Mycobacterium tuberculosis is a partially characterized phospholipase/thioesterase encoded within a genetic cluster dedicated to the synthesis of core structures of the mycobacterial cell wall, including mycolic acids and arabinogalactan. Enzymatic assays performed with purified recombinant proteins Rv3802c and its close homologs from Mycobacterium smegmatis (MSMEG_6394) and Corynebacterium glutamicum (NCgl2775) show that they all have significant lipase activities that are inhibited by tetrahydrolipstatin, an anti-obesity drug that coincidently inhibits mycobacterial cell wall biosynthesis. The crystal structure of MSMEG_6394, solved to 2.9 Å resolution, revealed an α/β hydrolase fold and a catalytic triad typically present in esterases and lipases. Furthermore, we demonstrate direct evidence of gene essentiality in M. smegmatis and show the structural consequences of loss of MSMEG_6394 function on the cellular integrity of the organism. These findings, combined with the predicted essentiality of Rv3802c in M. tuberculosis, indicate that the Rv3802c family performs a fundamental and indispensable lipase-associated function in mycobacteria.

Preplacement evaluation: thriving within the ADA guidelines.

PubMed

Pruitt, R H

1995-03-01

1. The intent of the Americans With Disabilities Act (ADA) is to remove barriers against those with known disabilities and to require reasonable accommodation to enable qualified employees to perform a job. The ADA is not meant to facilitate those with covert preexisting conditions in setting up workers' compensation and disability claims. 2. Essential job functions are physical and mental requirements for a job that are developed by the supervisor and the occupational health department. These functions should be included with the posting of any position. 3. Preplacement evaluation requirements: essential job functions that are used to determine what is included in the assessment; employee capability statement (with reasonable accommodation); and conditional offer of employment pending a satisfactory post-offer evaluation prior to beginning the job.

Chemical characterization (GC/MS and NMR Fingerprinting) and bioactivities of South-African Pelargonium capitatum (L.) L' Her. (Geraniaceae) essential oil.

PubMed

Guerrini, Alessandra; Rossi, Damiano; Paganetto, Guglielmo; Tognolini, Massimiliano; Muzzoli, Mariavittoria; Romagnoli, Carlo; Antognoni, Fabiana; Vertuani, Silvia; Medici, Alessandro; Bruni, Alessandro; Useli, Chiara; Tamburini, Elena; Bruni, Renato; Sacchetti, Gianni

2011-04-01

Chemical fingerprinting of commercial Pelargonium capitatum (Geraniaceae) essential oil samples of south African origin was performed by GC, GC/MS, and (13) C- and (1) H-NMR. Thirty-seven compounds were identified, among which citronellol (32.71%) and geraniol (19.58%) were the most abundant. NMR Spectra of characteristic chemicals were provided. Broad-spectrum bioactivity properties of the oil were evaluated and compared with those of commercial Thymus vulgaris essential oil with the aim to obtain a functional profile in terms of efficacy and safety. P. capitatum essential oil provides a good performance as antimicrobial, with particular efficacy against Candida albicans strains. Antifungal activity performed against dermatophyte and phytopathogen strains revealed the latter as more sensitive, while antibacterial activity was not remarkable against both Gram-positive and Gram-negative bacteria. P. capitatum oil provided a lower antioxidant activity (IC(50) ) than that expressed by thyme essential oil, both in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and β-carotene bleaching tests. Results in photochemiluminescence (PCL) assay were negligible. To test the safety aspects of P. capitatum essential oil, mutagenic and toxicity properties were assayed by Ames test, with and without metabolic activation. Possible efficacy of P. capitatum essential oil as mutagenic protective agent against NaN(3) , 2-nitrofluorene, and 2-aminoanthracene was also assayed, providing interesting and significant antigenotoxic properties. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.

26 CFR 301.7701(i)-4 - Special rules for certain entities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the debt obligations in the performance of a governmental purpose; and (iii) The entity holds the... packaging of debt obligations for re-sale on the secondary market even if any profits from the sale are used in the performance of an essential governmental function. (3) Determinations by the Commissioner. If...

47 CFR 27.4 - Terms and definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Radiated Power (ERP) (in a given direction). The product of the power supplied to the antenna and its gain... product of the power supplied to the antenna and the antenna gain in a given direction relative to an... performance of the essential functions that could be performed at the transmitter. Satellite Digital Audio...

Intraoperative Functional Ultrasound Imaging of Human Brain Activity.

PubMed

Imbault, Marion; Chauvet, Dorian; Gennisson, Jean-Luc; Capelle, Laurent; Tanter, Mickael

2017-08-04

The functional mapping of brain activity is essential to perform optimal glioma surgery and to minimize the risk of postoperative deficits. We introduce a new, portable neuroimaging modality of the human brain based on functional ultrasound (fUS) for deep functional cortical mapping. Using plane-wave transmissions at an ultrafast frame rate (1 kHz), fUS is performed during surgery to measure transient changes in cerebral blood volume with a high spatiotemporal resolution (250 µm, 1 ms). fUS identifies, maps and differentiates regions of brain activation during task-evoked cortical responses within the depth of a sulcus in both awake and anaesthetized patients.

Jamaican families.

PubMed

Miner, Dianne Cooney

2003-01-01

The study of the family in the Caribbean originated with European scholars who assumed the universality of the patriarchal nuclear family and the primacy of this structure to the healthy functioning of society. Matrifocal Caribbean families thus were seen as chaotic and disorganized and inadequate to perform the essential tasks of the social system. This article provides a more current discussion of the Jamaican family. It argues that its structure is the result of the agency and adaptation of its members and not the root cause of the increasing marginalization of peoples in the developing world. The article focuses on families living in poverty and how the family structure supports essential family functions, adaptations, and survival.

Restoring a smooth function from its noisy integrals

NASA Astrophysics Data System (ADS)

Goulko, Olga; Prokof'ev, Nikolay; Svistunov, Boris

2018-05-01

Numerical (and experimental) data analysis often requires the restoration of a smooth function from a set of sampled integrals over finite bins. We present the bin hierarchy method that efficiently computes the maximally smooth function from the sampled integrals using essentially all the information contained in the data. We perform extensive tests with different classes of functions and levels of data quality, including Monte Carlo data suffering from a severe sign problem and physical data for the Green's function of the Fröhlich polaron.

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD.

PubMed

Roshanravan, Baback; Gamboa, Jorge; Wilund, Kenneth

2017-06-01

Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high risk for mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment that includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle, and physical performance in chronic kidney disease. Kidney health providers need to identify patient and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can use in clinical practice to prevent functional decline and disability. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The Integrated Clinical Anatomy Program at Alfaisal University: An Innovative Model of Teaching Clinically Applied Functional Anatomy in a Hybrid Curriculum

ERIC Educational Resources Information Center

Yaqinuddin, Ahmed; Ikram, Muhammad Faisal; Zafar, Muhammad; Eldin, Nivin Sharaf; Mazhar, Muhammad Atif; Qazi, Sadia; Shaikh, Aftab Ahmed; Obeidat, Akef; Al-Kattan, Khaled; Ganguly, Paul

2016-01-01

Anatomy has historically been a cornerstone in medical education regardless of specialty. It is essential for physicians to be able to perform a variety of tasks, including performing invasive procedures, examining radiological images, performing a physical examination of a patient, etc. Medical students have to be prepared for such tasks, and we…

Motor network disruption in essential tremor: a functional and effective connectivity study.

PubMed

Buijink, Arthur W G; van der Stouwe, A M Madelein; Broersma, Marja; Sharifi, Sarvi; Groot, Paul F C; Speelman, Johannes D; Maurits, Natasha M; van Rootselaar, Anne-Fleur

2015-10-01

Although involvement of the cerebello-thalamo-cortical network has often been suggested in essential tremor, the source of oscillatory activity remains largely unknown. To elucidate mechanisms of tremor generation, it is of crucial importance to study the dynamics within the cerebello-thalamo-cortical network. Using a combination of electromyography and functional magnetic resonance imaging, it is possible to record the peripheral manifestation of tremor simultaneously with brain activity related to tremor generation. Our first aim was to study the intrinsic activity of regions within the cerebello-thalamo-cortical network using dynamic causal modelling to estimate effective connectivity driven by the concurrently recorded tremor signal. Our second aim was to objectify how the functional integrity of the cerebello-thalamo-cortical network is affected in essential tremor. We investigated the functional connectivity between cerebellar and cortical motor regions showing activations during a motor task. Twenty-two essential tremor patients and 22 healthy controls were analysed. For the effective connectivity analysis, a network of tremor-signal related regions was constructed, consisting of the left primary motor cortex, premotor cortex, supplementary motor area, left thalamus, and right cerebellar motor regions lobule V and lobule VIII. A measure of variation in tremor severity over time, derived from the electromyogram, was included as modulatory input on intrinsic connections and on the extrinsic cerebello-thalamic connections, giving a total of 128 models. Bayesian model selection and random effects Bayesian model averaging were used. Separate seed-based functional connectivity analyses for the left primary motor cortex, left supplementary motor area and right cerebellar lobules IV, V, VI and VIII were performed. We report two novel findings that support an important role for the cerebellar system in the pathophysiology of essential tremor. First, in the effective connectivity analysis, tremor variation during the motor task has an excitatory effect on both the extrinsic connection from cerebellar lobule V to the thalamus, and the intrinsic activity of cerebellar lobule V and thalamus. Second, the functional integrity of the motor network is affected in essential tremor, with a decrease in functional connectivity between cortical and cerebellar motor regions. This decrease in functional connectivity, related to the motor task, correlates with an increase in clinical tremor severity. Interestingly, increased functional connectivity between right cerebellar lobules I-IV and the left thalamus correlates with an increase in clinical tremor severity. In conclusion, our findings suggest that cerebello-dentato-thalamic activity and cerebello-cortical connectivity is disturbed in essential tremor, supporting previous evidence of functional cerebellar changes in essential tremor. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

New genes often acquire male-specific functions but rarely become essential in Drosophila.

PubMed

Kondo, Shu; Vedanayagam, Jeffrey; Mohammed, Jaaved; Eizadshenass, Sogol; Kan, Lijuan; Pang, Nan; Aradhya, Rajaguru; Siepel, Adam; Steinhauer, Josefa; Lai, Eric C

2017-09-15

Relatively little is known about the in vivo functions of newly emerging genes, especially in metazoans. Although prior RNAi studies reported prevalent lethality among young gene knockdowns, our phylogenomic analyses reveal that young Drosophila genes are frequently restricted to the nonessential male reproductive system. We performed large-scale CRISPR/Cas9 mutagenesis of "conserved, essential" and "young, RNAi-lethal" genes and broadly confirmed the lethality of the former but the viability of the latter. Nevertheless, certain young gene mutants exhibit defective spermatogenesis and/or male sterility. Moreover, we detected widespread signatures of positive selection on young male-biased genes. Thus, young genes have a preferential impact on male reproductive system function. © 2017 Kondo et al.; Published by Cold Spring Harbor Laboratory Press.

Defining the ABC of gene essentiality in streptococci.

PubMed

Charbonneau, Amelia R L; Forman, Oliver P; Cain, Amy K; Newland, Graham; Robinson, Carl; Boursnell, Mike; Parkhill, Julian; Leigh, James A; Maskell, Duncan J; Waller, Andrew S

2017-05-31

Utilising next generation sequencing to interrogate saturated bacterial mutant libraries provides unprecedented information for the assignment of genome-wide gene essentiality. Exposure of saturated mutant libraries to specific conditions and subsequent sequencing can be exploited to uncover gene essentiality relevant to the condition. Here we present a barcoded transposon directed insertion-site sequencing (TraDIS) system to define an essential gene list for Streptococcus equi subsp. equi, the causative agent of strangles in horses, for the first time. The gene essentiality data for this group C Streptococcus was compared to that of group A and B streptococci. Six barcoded variants of pGh9:ISS1 were designed and used to generate mutant libraries containing between 33,000-66,000 unique mutants. TraDIS was performed on DNA extracted from each library and data were analysed separately and as a combined master pool. Gene essentiality determined that 19.5% of the S. equi genome was essential. Gene essentialities were compared to those of group A and group B streptococci, identifying concordances of 90.2% and 89.4%, respectively and an overall concordance of 83.7% between the three species. The use of barcoded pGh9:ISS1 to generate mutant libraries provides a highly useful tool for the assignment of gene function in S. equi and other streptococci. The shared essential gene set of group A, B and C streptococci provides further evidence of the close genetic relationships between these important pathogenic bacteria. Therefore, the ABC of gene essentiality reported here provides a solid foundation towards reporting the functional genome of streptococci.

Critical Thinking and EFL Learners' Performance on Different Writing Modes

ERIC Educational Resources Information Center

Golpour, Farhad

2014-01-01

The essential function of critical thinking in education is obvious by many studies done in this field. The main purpose of this article is to find the relationship between critical thinking levels of Iranian EFL learners and their performance on different modes of writing. The sample of the study selected among those who studying English at the…

The back squat: A proposed assessment of functional deficits and technical factors that limit performance

PubMed Central

Myer, Gregory D.; Kushner, Adam M.; Brent, Jensen L.; Schoenfeld, Brad J.; Hugentobler, Jason; Lloyd, Rhodri S.; Vermeil, Al; Chu, Donald A.; Harbin, Jason; McGill, Stuart M.

2014-01-01

Fundamental movement competency is essential for participation in physical activity and for mitigating the risk of injury, which are both key elements of health throughout life. The squat movement pattern is arguably one of the most primal and critical fundamental movements necessary to improve sport performance, to reduce injury risk and to support lifelong physical activity. Based on current evidence, this first (1 of 2) report deconstructs the technical performance of the back squat as a foundation training exercise and presents a novel dynamic screening tool that incorporates identification techniques for functional deficits that limit squat performance and injury resilience. The follow-up report will outline targeted corrective methodology for each of the functional deficits presented in the assessment tool. PMID:25506270

48 CFR 48.101 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ENGINEERING Policies and Procedures 48.101 General. (a) Value engineering is the formal technique by which... performing more economically. Value engineering attempts to eliminate, without impairing essential functions... two value engineering approaches: (1) The first is an incentive approach in which contractor...

Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens. | Office of Cancer Genomics

Cancer.gov

Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity.

Inhaled peppermint, rosemary and eucalyptus essential oils do not change spirometry in healthy individuals.

PubMed

Köteles, Ferenc; Babulka, Péter; Szemerszky, Renáta; Dömötör, Zsuzsanna; Boros, Szilvia

2018-06-18

Essential oils of herbal origin are widely used in the treatment of diseases of the upper and lower respiratory tract primarily due to their antibacterial and antiviral effects. Menthol, the major component of the essential oil of mint (Mentha) species, exhibits antispasmodic activity, which might result in improved lung function. In a randomized experiment, 106 healthy participants received nebulized peppermint, eucalyptus, or rosemary essential oil for 15 min or no treatment (control). None of the essential oils had an impact on the measured spirometric variables (forced vital capacity, peak expiratory flow, the ratio of the volume of air forcibly blown out in the first second to forced vital capacity). Participants' expectations regarding the effects of essential oils did not affect their objective performance, however, they predicted perceived (subjective) changes. Perceived and measured changes were not connected with each other. In conclusion, inhaled rosemary, peppermint, and eucalyptus essential oils' subjective (perceived) effect on spirometry is mediated at least partly by expectations. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of Functional Oils on Coccidiosis and Apparent Metabolizable Energy in Broiler Chickens

PubMed Central

Murakami, A. E.; Eyng, C.; Torrent, J.

2014-01-01

The objective of the present study was to investigate the effects of a mixture of functional oils (Essential, Oligo Basics Agroind. Ltda) on performance response of chickens challenged with coccidiosis and the determination of apparent metabolizable energy (AME), nitrogen-corrected apparent metabolizable energy (AMEn), the coefficients of protein and ether extract digestibility and intestinal morphology of broilers fed with diets containing Essential. In Exp. 1, a completely randomized design (CRD) was used, with one control diet without Essential inclusion with coccidiosis (Eimeria acervulina, Eimeria maxima, and Eimeria tenella) challenged birds and two different inclusion rates of Essential (1.5 kg/ton and 2 kg/ton) with coccidiosis-challenged and non-challenged birds for each inclusion rate, using 10 replicates and 50 birds per experimental unit. After 7 d of coccidiosis challenge, the livability was approximately 10% lower (p<0.05) for the control group. Intestinal lesion scores were lower (p<0.05) in the anterior intestine and the cecum for the chickens supplemented. Feed efficiency and growth rate were improved in birds supplemented with Essential (p<0.05) before the coccidiosis challenge and during the first 7 d post infection. In Exp. 2, a CRD was used, with one control diet without Essential inclusion and one diet with inclusion of Essential (1.5 kg/ton), using nine replications and 33 chicks per pen. The diets with Essential yielded approximately 4% higher AME (p = 0.003) and AMEn (p = 0.001). Essential supplementation increased villus height in the jejunum on d 14 (p<0.05). Villus height:crypt depth ratio for the supplemented birds was larger (p<0.05) in the jejunum on d 7, larger (p<0.05) in the jejunum and ileum on d 14. In conclusion, these functional oils improved the energy utilization and the livability and decreased lesions caused by coccidiosis in supplemented birds. PMID:25050040

[A clinical study on the relationship of autonomic nervous function and arteriosclerosis in patients with essential hypertension].

PubMed

Zhao, G; Li, S H; Tan, X

2016-03-01

To investigate the relationship between autonomic nervous function and arteriosclerosis in patients with essential hypertension. From January 2011 to December 2013, a total of 269 patients with essential hypertension hospitalized in Chang'an Branch of First People's Hospital of Liangshan were divided into normal PWV group (PWV<9 m/s, n=178) and high PWV group (PWV≥9 m/s, n=91) via the results of carotid-femoral pulse wave velocity (PWV). Synchronic 24 hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed for all participants to simultaneously monitor the heart rate variability (HRV) and blood pressure variability (BPV) in these patients. Pearson single factor analysis and multivariate logistic regression analysis were performed to define the relationship between PWV and HRV, BPV respectively. The level of nHR/dHR (index of heart rate variability), 24 hour'sSSD, dSSD, nSSD (indexes of blood pressure variability) increased significantly (all P<0.05), while the level of SDANN (index of heart rate variability) decreased significantly (P<0.05) in high PWV group compared with normal PWV group. Multiple linear regression analysis showed that PWV was positively correlated with 24 hour'sSSD, 24 hour'sPP, LF, LF/HF and night/day heart rate ratio (all P<0.05). HRV (LF, LF/HF, nHR/dHR) and BPV (24 hours'SSD, dSSD, nSSD) are positively correlated to arteriosclerosis in patients with essential hypertension. Our results show that sympathetic activation and vascular injury are closely related in patients with essential hypertension.

48 CFR 252.237-7023 - Continuation of Essential Contractor Services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... prescribed in 237.7603, use the following clause: Continuation of Mission Essential Functions (Date) (a) The... contractor services in support of mission-essential functions. The contractor-provided services that have been determined to be essential contractor services in support of mission-essential functions are...

Brain regions essential for improved lexical access in an aged aphasic patient: a case report.

PubMed

Meinzer, Marcus; Flaisch, Tobias; Obleser, Jonas; Assadollahi, Ramin; Djundja, Daniela; Barthel, Gabriela; Rockstroh, Brigitte

2006-08-17

The relationship between functional recovery after brain injury and concomitant neuroplastic changes is emphasized in recent research. In the present study we aimed to delineate brain regions essential for language performance in aphasia using functional magnetic resonance imaging and acquisition in a temporal sparse sampling procedure, which allows monitoring of overt verbal responses during scanning. An 80-year old patient with chronic aphasia (2 years post-onset) was investigated before and after intensive language training using an overt picture naming task. Differential brain activation in the right inferior frontal gyrus for correct word retrieval and errors was found. Improved language performance following therapy was mirrored by increased fronto-thalamic activation while stability in more general measures of attention/concentration and working memory was assured. Three healthy age-matched control subjects did not show behavioral changes or increased activation when tested repeatedly within the same 2-week time interval. The results bear significance in that the changes in brain activation reported can unequivocally be attributed to the short-term training program and a language domain-specific plasticity process. Moreover, it further challenges the claim of a limited recovery potential in chronic aphasia, even at very old age. Delineation of brain regions essential for performance on a single case basis might have major implications for treatment using transcranial magnetic stimulation.

Calcium, essential for health

PubMed

Martínez de Victoria, Emilio

2016-07-12

Calcium (Ca) is the most abundant mineral element in our body. It accounts for about 2% of body weight. The functions of calcium are: a) functions skeletal and b) regulatory functions. Bone consists of a protein matrix that mineralizes mainly with calcium (the most abundant), phosphate and magnesium, for it is essential an adequate dietary intake of Ca, phosphorus and vitamin D. The ionic Ca (Ca2+) is essential to maintain and / or perform different specialized functions of, virtually, all body cells cellular. Because of its important functions Ca2+ must be closely regulated, keeping plasma concentrations within narrow ranges. For this reason there is an accurate response against hypocalcemia or hypercalcemia in which the parathormone, calcitriol, calcitonin and vitamin K are involved. Ca intakes in the Spanish population are low in a significant percentage of the older adult’s population, especially in women. The main source of Ca in the diet is milk and milk derivatives. Green leafy vegetables, fruits and legumes can be important sources of Ca in a Mediterranean dietary pattern. The bioavailability of dietary Ca depends on physiological and dietary factors. Physiological include age, physiological status (gestation and lactation) Ca and vitamin D status and disease. Several studies relate Ca intake in the diet and various diseases, such as osteoporosis, cancer, cardiovascular disease and obesity.

45 CFR 2553.12 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... to help determine the impact of an RSVP project on the community, including the volunteers... reasonable accommodation, can perform the essential functions of a volunteer position that such individual... application, in which RSVP volunteers are recruited, enrolled, and placed on assignments. (p) Sponsor. A...

45 CFR 2553.12 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... to help determine the impact of an RSVP project on the community, including the volunteers... reasonable accommodation, can perform the essential functions of a volunteer position that such individual... application, in which RSVP volunteers are recruited, enrolled, and placed on assignments. (p) Sponsor. A...

45 CFR 2553.12 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... to help determine the impact of an RSVP project on the community, including the volunteers... reasonable accommodation, can perform the essential functions of a volunteer position that such individual... application, in which RSVP volunteers are recruited, enrolled, and placed on assignments. (p) Sponsor. A...

45 CFR 2553.12 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... to help determine the impact of an RSVP project on the community, including the volunteers... reasonable accommodation, can perform the essential functions of a volunteer position that such individual... application, in which RSVP volunteers are recruited, enrolled, and placed on assignments. (p) Sponsor. A...

48 CFR 48.101 - General.

Code of Federal Regulations, 2013 CFR

2013-10-01

... engineering effort is applied to areas of the contract that offer opportunities for considerable savings... ENGINEERING Policies and Procedures 48.101 General. (a) Value engineering is the formal technique by which... performing more economically. Value engineering attempts to eliminate, without impairing essential functions...

48 CFR 48.101 - General.

Code of Federal Regulations, 2014 CFR

2014-10-01

... engineering effort is applied to areas of the contract that offer opportunities for considerable savings... ENGINEERING Policies and Procedures 48.101 General. (a) Value engineering is the formal technique by which... performing more economically. Value engineering attempts to eliminate, without impairing essential functions...

48 CFR 48.101 - General.

Code of Federal Regulations, 2012 CFR

2012-10-01

... engineering effort is applied to areas of the contract that offer opportunities for considerable savings... ENGINEERING Policies and Procedures 48.101 General. (a) Value engineering is the formal technique by which... performing more economically. Value engineering attempts to eliminate, without impairing essential functions...

30 CFR 822.11 - Essential hydrologic functions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Essential hydrologic functions. 822.11 Section... IN ALLUVIAL VALLEY FLOORS § 822.11 Essential hydrologic functions. (a) The operator of a surface coal... throughout the mining and reclamation process the essential hydrologic functions of an alluvial valley floor...

Note: The performance of new density functionals for a recent blind test of non-covalent interactions

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

Mardirossian, Narbe; Head-Gordon, Martin

Benchmark datasets of non-covalent interactions are essential for assessing the performance of density functionals and other quantum chemistry approaches. In a recent blind test, Taylor et al. benchmarked 14 methods on a new dataset consisting of 10 dimer potential energy curves calculated using coupled cluster with singles, doubles, and perturbative triples (CCSD(T)) at the complete basis set (CBS) limit (80 data points in total). Finally, the dataset is particularly interesting because compressed, near-equilibrium, and stretched regions of the potential energy surface are extensively sampled.

Principles of Protein Recognition and Properties of Protein-protein Interfaces

NASA Astrophysics Data System (ADS)

Keskin, Ozlem; Gursoy, Attila; Nussinov, Ruth

In this chapter we address two aspects - the static physical interactions which allow the information transfer for the function to be performed; and the dynamic, i.e. how the information is transmitted between the binding sites in the single protein molecule and in the network. We describe the single protein molecules and their complexes; and the analogy between protein folding and protein binding. Eventually, to fully understand the interactome and how it performs the essential cellular functions, we have to put all together - and hierarchically progress through the system.

Note: The performance of new density functionals for a recent blind test of non-covalent interactions

DOE PAGES

Mardirossian, Narbe; Head-Gordon, Martin

2016-11-09

Benchmark datasets of non-covalent interactions are essential for assessing the performance of density functionals and other quantum chemistry approaches. In a recent blind test, Taylor et al. benchmarked 14 methods on a new dataset consisting of 10 dimer potential energy curves calculated using coupled cluster with singles, doubles, and perturbative triples (CCSD(T)) at the complete basis set (CBS) limit (80 data points in total). Finally, the dataset is particularly interesting because compressed, near-equilibrium, and stretched regions of the potential energy surface are extensively sampled.

The influence of essential oils on human attention. I: alertness.

PubMed

Ilmberger, J; Heuberger, E; Mahrhofer, C; Dessovic, H; Kowarik, D; Buchbauer, G

2001-03-01

Scientific research on the effects of essential oils on human behavior lags behind the promises made by popular aromatherapy. Nearly all aspects of human behavior are closely linked to processes of attention, the basic level being that of alertness, which ranges from sleep to wakefulness. In our study we measured the influence of essential oils and components of essential oils [peppermint, jasmine, ylang-ylang, 1,8-cineole (in two different dosages) and menthol] on this core attentional function, which can be experimentally defined as speed of information processing. Substances were administered by inhalation; levels of alertness were assessed by measuring motor and reaction times in a reaction time paradigm. The performances of the six experimental groups receiving substances (n = 20 in four groups, n = 30 in two groups) were compared with those of corresponding control groups receiving water. Between-group analysis, i.e. comparisons between experimental groups and their respective control groups, mainly did not reach statistical significance. However, within-group analysis showed complex correlations between subjective evaluations of substances and objective performance, indicating that effects of essentials oils or their components on basic forms of attentional behavior are mainly psychological.

Neuroimaging essentials in essential tremor: A systematic review

PubMed Central

Sharifi, Sarvi; Nederveen, Aart J.; Booij, Jan; van Rootselaar, Anne-Fleur

2014-01-01

Background Essential tremor is regarded to be a disease of the central nervous system. Neuroimaging is a rapidly growing field with potential benefits to both diagnostics and research. The exact role of imaging techniques with respect to essential tremor in research and clinical practice is not clear. A systematic review of the different imaging techniques in essential tremor is lacking in the literature. Methods We performed a systematic literature search combining the terms essential tremor and familial tremor with the following keywords: imaging, MRI, VBM, DWI, fMRI, PET and SPECT, both in abbreviated form as well as in full form. We summarize and discuss the quality and the external validity of each study and place the results in the context of existing knowledge regarding the pathophysiology of essential tremor. Results A total of 48 neuroimaging studies met our search criteria, roughly divided into 19 structural and 29 functional and metabolic studies. The quality of the studies varied, especially concerning inclusion criteria. Functional imaging studies indicated cerebellar hyperactivity during rest and during tremor. The studies also pointed to the involvement of the thalamus, the inferior olive and the red nucleus. Structural studies showed less consistent results. Discussion and conclusion Neuroimaging techniques in essential tremor give insight into the pathophysiology of essential tremor indicating the involvement of the cerebellum as the most consistent finding. GABAergic dysfunction might be a major premise in the pathophysiological hypotheses. Inconsistencies between studies can be partly explained by the inclusion of heterogeneous patient groups. Improvement of scientific research requires more stringent inclusion criteria and application of advanced analysis techniques. Also, the use of multimodal neuroimaging techniques is a promising development in movement disorders research. Currently, the role of imaging techniques in essential tremor in daily clinical practice is limited. PMID:25068111

Identification of essential genes in Streptococcus pneumoniae by allelic replacement mutagenesis.

PubMed

Song, Jae-Hoon; Ko, Kwan Soo; Lee, Ji-Young; Baek, Jin Yang; Oh, Won Sup; Yoon, Ha Sik; Jeong, Jin-Yong; Chun, Jongsik

2005-06-30

To find potential targets of novel antimicrobial agents, we identified essential genes of Streptococcus pneumoniae using comparative genomics and allelic replacement mutagenesis. We compared the genome of S. pneumoniae R6 with those of Bacillus subtilis, Enterococcus faecalis, Escherichia coli, and Staphylococcus aureus, and selected 693 candidate target genes with > 40% amino acid sequence identity to the corresponding genes in at least two of the other species. The 693 genes were disrupted and 133 were found to be essential for growth. Of these, 32 encoded proteins of unknown function, and we were able to identify orthologues of 22 of these genes by genomic comparisons. The experimental method used in this study is easy to perform, rapid and efficient for identifying essential genes of bacterial pathogens.

21 CFR 225.30 - Equipment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS Construction and Maintenance of Facilities and Equipment § 225.30 Equipment. (a) Equipment which is designed to perform its intended function and is properly installed and used is essential to the manufacture of medicated feeds. Such equipment permits...

13 CFR 113.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of religious observance and practice, as well as belief. (d) The term qualified handicapped person means (1) with respect to employment, a handicapped person who, with reasonable accommodation, can perform the essential functions of the job in question and (2) with respect to services, a handicapped...

44 CFR 206.373 - Eligibility criteria.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Eligibility criteria. 206.373 Section 206.373 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... order to perform essential governmental functions, the maintenance of an annual operating budget, and...

The Metabolic Core and Catalytic Switches Are Fundamental Elements in the Self-Regulation of the Systemic Metabolic Structure of Cells

PubMed Central

De la Fuente, Ildefonso M.; Cortes, Jesus M.; Perez-Pinilla, Martin B.; Ruiz-Rodriguez, Vicente; Veguillas, Juan

2011-01-01

Background Experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a metabolic core formed by a set of enzymatic reactions which are always active under all environmental conditions, while the rest of catalytic processes are only intermittently active. The reactions of the metabolic core are essential for biomass formation and to assure optimal metabolic performance. The on-off catalytic reactions and the metabolic core are essential elements of a Systemic Metabolic Structure which seems to be a key feature common to all cellular organisms. Methodology/Principal Findings In order to investigate the functional importance of the metabolic core we have studied different catalytic patterns of a dissipative metabolic network under different external conditions. The emerging biochemical data have been analysed using information-based dynamic tools, such as Pearson's correlation and Transfer Entropy (which measures effective functionality). Our results show that a functional structure of effective connectivity emerges which is dynamical and characterized by significant variations of bio-molecular information flows. Conclusions/Significance We have quantified essential aspects of the metabolic core functionality. The always active enzymatic reactions form a hub –with a high degree of effective connectivity- exhibiting a wide range of functional information values being able to act either as a source or as a sink of bio-molecular causal interactions. Likewise, we have found that the metabolic core is an essential part of an emergent functional structure characterized by catalytic modules and metabolic switches which allow critical transitions in enzymatic activity. Both, the metabolic core and the catalytic switches in which also intermittently-active enzymes are involved seem to be fundamental elements in the self-regulation of the Systemic Metabolic Structure. PMID:22125607

[Diagnosis of capacity to perform essential public health functions in the Central American countries, the Dominican Republic, and the Mexican states of Chiapas and Quintana Roo].

PubMed

González Block, Miguel Ángel; González Robledo, Luz María; Cuadra Hernández, Silvia Magali

2013-04-01

Characterize the capacity of public and private institutions in the Central American countries, the Dominican Republic, and the Mexican states of Chiapas and Quintana Roo to perform essential public health functions (EPHFs). An online survey of 83 organizations in Belize, Costa Rica, the Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama, and the Mexican states of Chiapas and Quintana Roo was conducted to learn about their capacity to perform each of the 11 EPHFs. The results were validated in a workshop with representatives of the ministries of health from the seven countries and the two participating Mexican states. High levels of performance capacity were found most often for EPHF 1 (monitoring, evaluation, and analysis of health status of the population), EPHF 2.1.1 (surveillance, research, and control of risks and threats to public health from infectious diseases), and EPHF 5 (policy development and health planning). The greatest weakness was found in EPHF 2.1.2 (surveillance, research, and monitoring of noninfectious diseases). Asymmetries in EPHF performance within each country mainly revealed weaknesses in the laboratory and public health research functions. In the countries and territories analyzed, there is a need to improve strategic performance in most of the EPHFs, as well as to strengthen infrastructure, upgrade equipment, and further develop human resources at both the strategic and the tactical levels. A regional approach should be used to take advantage of the different levels of capacity, with a view to greater strengthening and enhanced technical support and cooperation.

Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells.

PubMed

Meyers, Robin M; Bryan, Jordan G; McFarland, James M; Weir, Barbara A; Sizemore, Ann E; Xu, Han; Dharia, Neekesh V; Montgomery, Phillip G; Cowley, Glenn S; Pantel, Sasha; Goodale, Amy; Lee, Yenarae; Ali, Levi D; Jiang, Guozhi; Lubonja, Rakela; Harrington, William F; Strickland, Matthew; Wu, Ting; Hawes, Derek C; Zhivich, Victor A; Wyatt, Meghan R; Kalani, Zohra; Chang, Jaime J; Okamoto, Michael; Stegmaier, Kimberly; Golub, Todd R; Boehm, Jesse S; Vazquez, Francisca; Root, David E; Hahn, William C; Tsherniak, Aviad

2017-12-01

The CRISPR-Cas9 system has revolutionized gene editing both at single genes and in multiplexed loss-of-function screens, thus enabling precise genome-scale identification of genes essential for proliferation and survival of cancer cells. However, previous studies have reported that a gene-independent antiproliferative effect of Cas9-mediated DNA cleavage confounds such measurement of genetic dependency, thereby leading to false-positive results in copy number-amplified regions. We developed CERES, a computational method to estimate gene-dependency levels from CRISPR-Cas9 essentiality screens while accounting for the copy number-specific effect. In our efforts to define a cancer dependency map, we performed genome-scale CRISPR-Cas9 essentiality screens across 342 cancer cell lines and applied CERES to this data set. We found that CERES decreased false-positive results and estimated sgRNA activity for both this data set and previously published screens performed with different sgRNA libraries. We further demonstrate the utility of this collection of screens, after CERES correction, for identifying cancer-type-specific vulnerabilities.

Computational correction of copy-number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells

PubMed Central

Meyers, Robin M.; Bryan, Jordan G.; McFarland, James M.; Weir, Barbara A.; Sizemore, Ann E.; Xu, Han; Dharia, Neekesh V.; Montgomery, Phillip G.; Cowley, Glenn S.; Pantel, Sasha; Goodale, Amy; Lee, Yenarae; Ali, Levi D.; Jiang, Guozhi; Lubonja, Rakela; Harrington, William F.; Strickland, Matthew; Wu, Ting; Hawes, Derek C.; Zhivich, Victor A.; Wyatt, Meghan R.; Kalani, Zohra; Chang, Jaime J.; Okamoto, Michael; Stegmaier, Kimberly; Golub, Todd R.; Boehm, Jesse S.; Vazquez, Francisca; Root, David E.; Hahn, William C.; Tsherniak, Aviad

2017-01-01

The CRISPR-Cas9 system has revolutionized gene editing both on single genes and in multiplexed loss-of-function screens, enabling precise genome-scale identification of genes essential to proliferation and survival of cancer cells1,2. However, previous studies reported that a gene-independent anti-proliferative effect of Cas9-mediated DNA cleavage confounds such measurement of genetic dependency, leading to false positive results in copy number amplified regions3,4. We developed CERES, a computational method to estimate gene dependency levels from CRISPR-Cas9 essentiality screens while accounting for the copy-number-specific effect. As part of our efforts to define a cancer dependency map, we performed genome-scale CRISPR-Cas9 essentiality screens across 342 cancer cell lines and applied CERES to this dataset. We found that CERES reduced false positive results and estimated sgRNA activity for both this dataset and previously published screens performed with different sgRNA libraries. Here, we demonstrate the utility of this collection of screens, upon CERES correction, in revealing cancer-type-specific vulnerabilities. PMID:29083409

Complex-valued multistate associative memory with nonlinear multilevel functions for gray-level image reconstruction.

PubMed

Tanaka, Gouhei; Aihara, Kazuyuki

2009-09-01

A widely used complex-valued activation function for complex-valued multistate Hopfield networks is revealed to be essentially based on a multilevel step function. By replacing the multilevel step function with other multilevel characteristics, we present two alternative complex-valued activation functions. One is based on a multilevel sigmoid function, while the other on a characteristic of a multistate bifurcating neuron. Numerical experiments show that both modifications to the complex-valued activation function bring about improvements in network performance for a multistate associative memory. The advantage of the proposed networks over the complex-valued Hopfield networks with the multilevel step function is more outstanding when a complex-valued neuron represents a larger number of multivalued states. Further, the performance of the proposed networks in reconstructing noisy 256 gray-level images is demonstrated in comparison with other recent associative memories to clarify their advantages and disadvantages.

Evaluation of an affinity-amplified immunoassay of graphene oxide using surface plasmon resonance biosensors

NASA Astrophysics Data System (ADS)

Chiu, Nan-Fu; Huang, Teng-Yi; Kuo, Chun-Chuan

2015-05-01

We describe a fundamental study on the plasmonic properties and advanced biosensing mechanisms of functionalized graphene. We discuss a specific design using modified carboxyl groups, which can modulate surface plasmon (SP) coupling and provide an advantage for their binding to the sensing layer with high-performance affinity in an immunological reaction. The functionalized graphene-based surface plasmon resonance (SPR) biosensors have three advantages: high performance, high sensitivity, and excellent molecular kinetic response. In the future, functionalized graphene sheets will make a unique contribution to photonic and SPR diagnosis devices. We wish to highlight the essential characteristics of functionalized graphene-based SPR biosensors to assist researchers in developing and advancing suitable biosensors for unique applications.

Multifunctional G-Rich and RRM-Containing Domains of TbRGG2 Perform Separate yet Essential Functions in Trypanosome RNA Editing

PubMed Central

Foda, Bardees M.; Downey, Kurtis M.; Fisk, John C.

2012-01-01

Efficient editing of Trypanosoma brucei mitochondrial RNAs involves the actions of multiple accessory factors. T. brucei RGG2 (TbRGG2) is an essential protein crucial for initiation and 3′-to-5′ progression of editing. TbRGG2 comprises an N-terminal G-rich region containing GWG and RG repeats and a C-terminal RNA recognition motif (RRM)-containing domain. Here, we perform in vitro and in vivo separation-of-function studies to interrogate the mechanism of TbRGG2 action in RNA editing. TbRGG2 preferentially binds preedited mRNA in vitro with high affinity attributable to its G-rich region. RNA-annealing and -melting activities are separable, carried out primarily by the G-rich and RRM domains, respectively. In vivo, the G-rich domain partially complements TbRGG2 knockdown, but the RRM domain is also required. Notably, TbRGG2's RNA-melting activity is dispensable for RNA editing in vivo. Interactions between TbRGG2 and MRB1 complex proteins are mediated by both G-rich and RRM-containing domains, depending on the binding partner. Overall, our results are consistent with a model in which the high-affinity RNA binding and RNA-annealing activities of the G-rich domain are essential for RNA editing in vivo. The RRM domain may have key functions involving interactions with the MRB1 complex and/or regulation of the activities of the G-rich domain. PMID:22798390

LABORATORY CAPACITY NEEDS ASSESSMENT OF DRINKING WATER UTILITIES: A GLOBAL PERSPECTIVE

EPA Science Inventory

Fully-functioning analytical laboratories capable of producing quality data are essential components of well-run drinking water utilities. In Europe and the US, drinking water laboratory performance is closely monitored and regulated; this is not always the case in the less indu...

Types, production and assessment of biobased food packaging materials

USDA-ARS?s Scientific Manuscript database

Food packaging performs an essential function, but packaging materials can have a negative impact on the environment. This book describes the latest advances in bio-based food packaging materials. Book provides a comprehensive review on bio-based, biodegradable and recycled materials and discusses t...

Proteomic analysis of lung tissue by DIGE

USDA-ARS?s Scientific Manuscript database

Lungs perform an essential physiological function, mediated by a complex series of events that involve the coordination of multiple cell types to support not only gaseous exchange, but homeostasis and protection from infection. Guinea pigs are an important animal disease model for a number of infect...

Resistance Training Reduces Force Tremor and Improves Manual Dexterity in Older Individuals With Essential Tremor.

PubMed

Kavanagh, Justin J; Wedderburn-Bisshop, Jacob; Keogh, Justin W L

2016-01-01

Although symptoms of Essential Tremor (ET) are typically controlled with medication, it is of interest to explore additional therapies to assist with functionality. The purpose of this study was to determine if a generalized upper limb resistance training (RT) program improves manual dexterity and reduces force tremor in older individuals with ET. Ten Essential Tremor and 9 controls were recruited into a dual group, pretest-posttest intervention study. Participants performed 6 weeks of upper-limb RT, and battery of manual dexterity and isometric force tremor assessments were performed before and after the RT to determine the benefits of the program. The six-week, high-load, RT program produced strength increases in each limb for the ET and healthy older group. These changes in strength aligned with improvements in manual dexterity and tremor-most notably for the ET group. The least affected limb and the most affected limb exhibited similar improvements in functional assessments of manual dexterity, whereas reductions in force tremor amplitude following the RT program were restricted to the most affected limb of the ET group. These findings suggest that generalized upper limb RT program has the potential to improve aspects of manual dexterity and reduce force tremor in older ET patients.

Constant versus variable response signal delays in speed--accuracy trade-offs: effects of advance preparation for processing time.

PubMed

Miller, Jeff; Sproesser, Gudrun; Ulrich, Rolf

2008-07-01

In two experiments, we used response signals (RSs) to control processing time and trace out speed--accuracy trade-off(SAT) functions in a difficult perceptual discrimination task. Each experiment compared performance in blocks of trials with constant and, hence, temporally predictable RS lags against performance in blocks with variable, unpredictable RS lags. In both experiments, essentially equivalent SAT functions were observed with constant and variable RS lags. We conclude that there is little effect of advance preparation for a given processing time, suggesting that the discrimination mechanisms underlying SAT functions are driven solely by bottom-up information processing in perceptual discrimination tasks.

A functional analysis of TOEFAZ1 uncovers protein domains essential for cytokinesis in Trypanosoma brucei.

PubMed

Sinclair-Davis, Amy N; McAllaster, Michael R; de Graffenried, Christopher L

2017-11-15

The parasite Trypanosoma brucei is highly polarized, including a flagellum that is attached along the cell surface by the flagellum attachment zone (FAZ). During cell division, the new FAZ positions the cleavage furrow, which ingresses from the anterior tip of the cell towards the posterior. We recently identified TOEFAZ1 (for 'Tip of the Extending FAZ protein 1') as an essential protein in trypanosome cytokinesis. Here, we analyzed the localization and function of TOEFAZ1 domains by performing overexpression and RNAi complementation experiments. TOEFAZ1 comprises three domains with separable functions: an N-terminal α-helical domain that may be involved in FAZ recruitment, a central intrinsically disordered domain that keeps the morphogenic kinase TbPLK at the new FAZ tip, and a C-terminal zinc finger domain necessary for TOEFAZ1 oligomerization. Both the N-terminal and C-terminal domains are essential for TOEFAZ1 function, but TbPLK retention at the FAZ is not necessary for cytokinesis. The feasibility of alternative cytokinetic pathways that do not employ TOEFAZ1 are also assessed. Our results show that TOEFAZ1 is a multimeric scaffold for recruiting proteins that control the timing and location of cleavage furrow ingression. © 2017. Published by The Company of Biologists Ltd.

Are civil-law notaries rent-seeking monopolists or essential market intermediaries? Endogenous development of a property rights institution in Mexico.

PubMed

Monkkonen, Paavo

2016-01-01

As the fourth contribution in the 'Land' section, this paper forms a research 'diptych' with the next paper by Levy. Whereas she focuses on the notarial institution in mid-nineteenth century Mexico, this contribution examines it in a contemporary context. The notary is one of the chief components of property rights protection in civil-law systems, performing various public functions such as writing deeds for real estate property. Yet notaries are considered an 'inefficient' institution by many, due to the perception of rent-seeking behavior enabled by their near-monopoly over validating property rights claims. This study examines notaries in Mexico to unpack the apparent contradiction in the role of notaries in economic development. I use a combination of interviews with notaries and clients, and data on notarial practice and bureaucratic outcomes across the country, to examine notaries' social function. The theoretical lens of endogenous development and institutional functionalism reveals an alternate explanation for their seemingly high-cost services, as well as their role in economic development. Mexican notaries have a dual social function: public representative and private service provider. They perform diverse and essential activities, which in other countries are performed by multiple actors such as real estate agents, escrow offices and title insurance companies. Thus, what is perceived as inefficiency by some can be interpreted as an efficient response to the context in which they operate, and their semi-privatized nature can overcome problems found in other bureaucratic arrangements.

Design and construction of a first-generation high-throughput integrated robotic molecular biology platform for bioenergy applications.

PubMed

Hughes, Stephen R; Butt, Tauseef R; Bartolett, Scott; Riedmuller, Steven B; Farrelly, Philip

2011-08-01

The molecular biological techniques for plasmid-based assembly and cloning of gene open reading frames are essential for elucidating the function of the proteins encoded by the genes. High-throughput integrated robotic molecular biology platforms that have the capacity to rapidly clone and express heterologous gene open reading frames in bacteria and yeast and to screen large numbers of expressed proteins for optimized function are an important technology for improving microbial strains for biofuel production. The process involves the production of full-length complementary DNA libraries as a source of plasmid-based clones to express the desired proteins in active form for determination of their functions. Proteins that were identified by high-throughput screening as having desired characteristics are overexpressed in microbes to enable them to perform functions that will allow more cost-effective and sustainable production of biofuels. Because the plasmid libraries are composed of several thousand unique genes, automation of the process is essential. This review describes the design and implementation of an automated integrated programmable robotic workcell capable of producing complementary DNA libraries, colony picking, isolating plasmid DNA, transforming yeast and bacteria, expressing protein, and performing appropriate functional assays. These operations will allow tailoring microbial strains to use renewable feedstocks for production of biofuels, bioderived chemicals, fertilizers, and other coproducts for profitable and sustainable biorefineries. Published by Elsevier Inc.

Energy scale of compositional disorder in Ga(AsBi)

NASA Astrophysics Data System (ADS)

Shakfa, M. K.; Jandieri, K.; Wiemer, M.; Ludewig, P.; Volz, K.; Stolz, W.; Baranovskii, S. D.; Koch, M.

2015-10-01

We report on a study of compositional disorder in Ga(AsBi) structures. Temperature-dependent photoluminescence measurements on Ga(AsBi)/GaAs heterostructures with different Bi contents are performed. Experimental observations show an essentially non-monotonous dependence of the energy scale of disorder on the Bi content. Our theoretical analysis concludes that this peculiar behavior is a consequence of an essential bowing of the valence band edge as a function of Bi content and of a specific compositional dependence of the hole effective mass in Ga(AsBi) compounds.

Chaperone Function in Androgen-Independent Prostate Cancer

DTIC Science & Technology

2010-05-01

funding). To address this need, I have located a collaborator (Dr. Scott Lucia) at the University of Colorado who should be able to perform the IHC on his...Periyasamy, S., Chen, H., Yucel, S., Li, W., Lin, L. Y., Wolf , I. M., Cohn, M. J., Baskin, L. S., et al. (2007a). Essential role for Co-chaperone...Yucel, S., Li, W., Lin, L. Y., Wolf , I. M., Cohn, M. J., Baskin, L. S., et al. (2007b). Essential role for Co-chaperone Fkbp52 but not Fkbp51 in

Biogenesis of cytosolic ribosomes requires the essential iron–sulphur protein Rli1p and mitochondria

PubMed Central

Kispal, Gyula; Sipos, Katalin; Lange, Heike; Fekete, Zsuzsanna; Bedekovics, Tibor; Janáky, Tamás; Bassler, Jochen; Aguilar Netz, Daili J; Balk, Janneke; Rotte, Carmen; Lill, Roland

2005-01-01

Mitochondria perform a central function in the biogenesis of cellular iron–sulphur (Fe/S) proteins. It is unknown to date why this biosynthetic pathway is indispensable for life, the more so as no essential mitochondrial Fe/S proteins are known. Here, we show that the soluble ATP-binding cassette (ABC) protein Rli1p carries N-terminal Fe/S clusters that require the mitochondrial and cytosolic Fe/S protein biogenesis machineries for assembly. Mutations in critical cysteine residues of Rli1p abolish association with Fe/S clusters and lead to loss of cell viability. Hence, the essential character of Fe/S clusters in Rli1p explains the indispensable character of mitochondria in eukaryotes. We further report that Rli1p is associated with ribosomes and with Hcr1p, a protein involved in rRNA processing and translation initiation. Depletion of Rli1p causes a nuclear export defect of the small and large ribosomal subunits and subsequently a translational arrest. Thus, ribosome biogenesis and function are intimately linked to the crucial role of mitochondria in the maturation of the essential Fe/S protein Rli1p. PMID:15660134

Copper Trafficking in Plants and Its Implication on Cell Wall Dynamics

PubMed Central

Printz, Bruno; Lutts, Stanley; Hausman, Jean-Francois; Sergeant, Kjell

2016-01-01

In plants, copper (Cu) acts as essential cofactor of numerous proteins. While the definitive number of these so-called cuproproteins is unknown, they perform central functions in plant cells. As micronutrient, a minimal amount of Cu is needed to ensure cellular functions. However, Cu excess may exert in contrast detrimental effects on plant primary production and even survival. Therefore it is essential for a plant to have a strictly controlled Cu homeostasis, an equilibrium that is both tissue and developmentally influenced. In the current review an overview is presented on the different stages of Cu transport from the soil into the plant and throughout the different plant tissues. Special emphasis is on the Cu-dependent responses mediated by the SPL7 transcription factor, and the crosstalk between this transcriptional regulation and microRNA-mediated suppression of translation of seemingly non-essential cuproproteins. Since Cu is an essential player in electron transport, we also review the recent insights into the molecular mechanisms controlling chloroplastic and mitochondrial Cu transport and homeostasis. We finally highlight the involvement of numerous Cu-proteins and Cu-dependent activities in the properties of one of the major Cu-accumulation sites in plants: the cell wall. PMID:27200069

Knowledge-Acquisition Tool For Expert System

NASA Technical Reports Server (NTRS)

Disbrow, James D.; Duke, Eugene L.; Regenie, Victoria A.

1988-01-01

Digital flight-control systems monitored by computer program that evaluates and recommends. Flight-systems engineers for advanced, high-performance aircraft use knowlege-acquisition tool for expert-system flight-status monitor suppling interpretative data. Interpretative function especially important in time-critical, high-stress situations because it facilitates problem identification and corrective strategy. Conditions evaluated and recommendations made by ground-based engineers having essential knowledge for analysis and monitoring of performances of advanced aircraft systems.

Relationship between global structural parameters and Enzyme Commission hierarchy: implications for function prediction.

PubMed

Boareto, Marcelo; Yamagishi, Michel E B; Caticha, Nestor; Leite, Vitor B P

2012-10-01

In protein databases there is a substantial number of proteins structurally determined but without function annotation. Understanding the relationship between function and structure can be useful to predict function on a large scale. We have analyzed the similarities in global physicochemical parameters for a set of enzymes which were classified according to the four Enzyme Commission (EC) hierarchical levels. Using relevance theory we introduced a distance between proteins in the space of physicochemical characteristics. This was done by minimizing a cost function of the metric tensor built to reflect the EC classification system. Using an unsupervised clustering method on a set of 1025 enzymes, we obtained no relevant clustering formation compatible with EC classification. The distance distributions between enzymes from the same EC group and from different EC groups were compared by histograms. Such analysis was also performed using sequence alignment similarity as a distance. Our results suggest that global structure parameters are not sufficient to segregate enzymes according to EC hierarchy. This indicates that features essential for function are rather local than global. Consequently, methods for predicting function based on global attributes should not obtain high accuracy in main EC classes prediction without relying on similarities between enzymes from training and validation datasets. Furthermore, these results are consistent with a substantial number of studies suggesting that function evolves fundamentally by recruitment, i.e., a same protein motif or fold can be used to perform different enzymatic functions and a few specific amino acids (AAs) are actually responsible for enzyme activity. These essential amino acids should belong to active sites and an effective method for predicting function should be able to recognize them. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mapping Interactions between Myosin Relay and Converter Domains That Power Muscle Function*

PubMed Central

Kronert, William A.; Melkani, Girish C.; Melkani, Anju; Bernstein, Sanford I.

2014-01-01

Intramolecular communication within myosin is essential for its function as motor, but the specific amino acid residue interactions required are unexplored within muscle cells. Using Drosophila melanogaster skeletal muscle myosin, we performed a novel in vivo molecular suppression analysis to define the importance of three relay loop amino acid residues (Ile508, Asn509, and Asp511) in communicating with converter domain residue Arg759. We found that the N509K relay mutation suppressed defects in myosin ATPase, in vitro motility, myofibril stability, and muscle function associated with the R759E converter mutation. Through molecular modeling, we define a mechanism for this interaction and suggest why the I508K and D511K relay mutations fail to suppress R759E. Interestingly, I508K disabled motor function and myofibril assembly, suggesting that productive relay-converter interaction is essential for both processes. We conclude that the putative relay-converter interaction mediated by myosin residues 509 and 759 is critical for the biochemical and biophysical function of skeletal muscle myosin and the normal ultrastructural and mechanical properties of muscle. PMID:24627474

Seismic evaluation of I-24 bridges and embankments in Western Kentucky : summary report.

DOT National Transportation Integrated Search

2006-09-01

I-24 is considered as one of the high priority and emergency routes in the region. Hence, it is essential that I-24 remains functional and operational after an earthquake event. The objective of this study is to perform seismic evaluation and risk as...

Move Your Continuing Education Unit from Function to Performance-Based.

ERIC Educational Resources Information Center

Kodgis, Damian

This document explores the policies and practices essential for maintaining a profitable, efficient, and productive continuing education program. A continuing education organizational structure must produce results (sales) and services (delivery), and organizational roles must be clearly defined so that income is linked to expenses. Sales and…

Brain Network Interactions in Auditory, Visual and Linguistic Processing

ERIC Educational Resources Information Center

Horwitz, Barry; Braun, Allen R.

2004-01-01

In the paper, we discuss the importance of network interactions between brain regions in mediating performance of sensorimotor and cognitive tasks, including those associated with language processing. Functional neuroimaging, especially PET and fMRI, provide data that are obtained essentially simultaneously from much of the brain, and thus are…

Correlation of Understanding of Physics and Psychological Symptoms among High-School Students in Greece

ERIC Educational Resources Information Center

Aggeliki, Anagnostopoulou; Miltiades, Kyprianou; Antigoni-Elisavet, Rota; Evangelia, Pavlatou; Loizos, Zaphiris

2017-01-01

Depression may essentially influence cognitive function contributing to poor school performance. The present study undertakes to determine the existence and strength of correlation between depressive symptomatology and other mental conditions with the acquired level of understanding of Newtonian physics taught in schools. The current study…

Cognitive and Functional Correlates of NPI-Q Scores and Symptom Clusters in Mildly Demented Alzheimer Patients.

PubMed

Travis Seidl, Jennifer N; Massman, Paul J

2016-01-01

Previous research has demonstrated an association between the emotional and behavioral symptoms of dementia, known as neuropsychiatric symptoms, and cognitive and functional decline among patients with Alzheimer disease (AD). The present study aimed to identify associations between neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and cognitive and functional performance. Participants were 256 AD patients enrolled in the Alzheimer's Disease and Memory Disorders Center at Baylor College of Medicine. An exploratory factor analysis of the NPI-Q indicated a 2-factor structure consisting of Negative/Oppositional and Anxiety/Restlessness factors. Regression analyses revealed significant associations between greater total severity of neuropsychiatric symptoms and poorer performance on basic and Instrumental Activities of Daily Living. Greater severity of Anxiety/Restlessness symptoms was associated with poor performance on measures of visuospatial functioning and basic and instrumental activities of daily living. The Negative/Oppositional factor was not related to cognition or functioning. In summary, neuropsychiatric symptoms (particularly Anxiety/Restlessness symptoms) were related to cognition and everyday functioning. Proper assessment and treatment of these symptoms is essential for improving cognition and functioning in AD patients.

Essential Thrombocythaemia and Peripheral Gangrene

PubMed Central

Preston, F. E.; Emmanuel, I. G.; Winfield, D. A.; Malia, R. G.

1974-01-01

Six patients are described in whom gangrene of one or more toes occurred as the presenting feature of essential thrombocythaemia. Spontaneous platelet aggregation was observed in platelet-rich plasma from four patients and platelet aggregation after the addition of adenosine diphosphate and collagen was highly abnormal in samples from all six. All of the patients described dramatic relief of pain within six hours of ingestion of aspirin and this coincided with disappearance of the spontaneous platelet aggregation and collagen-induced platelet aggregation. Treatment with phosphorus-32 corrected the platelet count and there were no further recurrences of peripheral vascular disease. Platelet function tests performed at the time all gave normal results. It is concluded that essential thrombocythaemia is an important and treatable cause of peripheral vascular disease. PMID:4472103

Form and function in the Lower Palaeolithic: history, progress, and continued relevance.

PubMed

Key, Alastair; Stephen, Lycett

2017-12-30

Percussively flaked stone artefacts constitute a major source of evidence relating to hominin behavioural strategies and are, essentially, a product or byproduct of a past individual's decision to create a tool with respect to some broader goal. Moreover, it has long been noted that both differences and recurrent regularities exist within and between Palaeolithic stone artefact forms. Accordingly, archaeologists have frequently drawn links between form and functionality, with functional objectives and performance often being regarded consequential to a stone tool's morphological properties. Despite these factors, extensive reviews of the related concepts of form and function with respect to the Lower Palaeolithic remain surprisingly sparse. We attempt to redress this issue. First we stress the historical place of form-function concepts, and their role in establishing basic ideas that echo to this day. We then highlight methodological and conceptual progress in determining artefactual function in more recent years. Thereafter, we evaluate four specific issues that are of direct consequence for evaluating the ongoing relevance of form-function concepts, especially with respect to their relevance for understanding human evolution more generally. Our discussion highlights specifically how recent developments have been able to build on a long historical legacy, and demonstrate that direct, indirect, experimental, and evolutionary perspectives intersect in crucial ways, with each providing specific but essential insights for ongoing questions. We conclude by emphasising that our understanding of these issues and their interaction, has been, and will be, essential to accurately interpret the Lower Palaeolithic archaeological record, tool-form related behaviours of Lower Palaeolithic hominins, and their consequences for (and relationship to) wider questions of human evolution.

Bioinspired surface functionalization of metallic biomaterials.

PubMed

Su, Yingchao; Luo, Cheng; Zhang, Zhihui; Hermawan, Hendra; Zhu, Donghui; Huang, Jubin; Liang, Yunhong; Li, Guangyu; Ren, Luquan

2018-01-01

Metallic biomaterials are widely used for clinical applications because of their excellent mechanical properties and good durability. In order to provide essential biofunctionalities, surface functionalization is of particular interest and requirement in the development of high-performance metallic implants. Inspired by the functional surface of natural biological systems, many new designs and conceptions have recently emerged to create multifunctional surfaces with great potential for biomedical applications. This review firstly introduces the metallic biomaterials, important surface properties, and then elaborates some strategies on achieving the bioinspired surface functionalization for metallic biomaterials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improvement of force health protection through preventive medicine oversight of contractor support.

PubMed

Mower, Scott A

2009-01-01

Unprecedented numbers of contractors are used throughout the Iraq theater of operations to alleviate military manpower shortages. At virtually every major forward operating base, US-based contractors perform the preponderance of essential life support services. At more remote sites, local national contractors are increasingly relied upon to maintain chemical latrines, remove trash, deliver bulk water, and execute other janitorial functions. Vigorous oversight of contractor performance is essential to ensure services are delivered according to specified standards. Poor oversight can increase the risk of criminal activities, permit substandard performance, elevate disease and nonbattle injury rates, degrade morale, and diminish Soldier readiness. As the principal force health protection proponents in the Department of Defense, preventive medicine units must be tightly integrated into the oversight processes. This article defines the force health protection implications associated with service contracts and provide recommendations for strengthening preventive medicine's oversight role.

The Proposal of Key Performance Indicators in Facility Management and Determination the Weights of Significance

NASA Astrophysics Data System (ADS)

Rimbalová, Jarmila; Vilčeková, Silvia

2013-11-01

The practice of facilities management is rapidly evolving with the increasing interest in the discourse of sustainable development. The industry and its market are forecasted to develop to include non-core functions, activities traditionally not associated with this profession, but which are increasingly being addressed by facilities managers. The scale of growth in the built environment and the consequential growth of the facility management sector is anticipated to be enormous. Key Performance Indicators (KPI) are measure that provides essential information about performance of facility services delivery. In selecting KPI, it is critical to limit them to those factors that are essential to the organization reaching its goals. It is also important to keep the number of KPI small just to keep everyone's attention focused on achieving the same KPIs. This paper deals with the determination of weights of KPI of FM in terms of the design and use of sustainable buildings.

Protein domains of unknown function are essential in bacteria.

PubMed

Goodacre, Norman F; Gerloff, Dietlind L; Uetz, Peter

2013-12-31

More than 20% of all protein domains are currently annotated as "domains of unknown function" (DUFs). About 2,700 DUFs are found in bacteria compared with just over 1,500 in eukaryotes. Over 800 DUFs are shared between bacteria and eukaryotes, and about 300 of these are also present in archaea. A total of 2,786 bacterial Pfam domains even occur in animals, including 320 DUFs. Evolutionary conservation suggests that many of these DUFs are important. Here we show that 355 essential proteins in 16 model bacterial species contain 238 DUFs, most of which represent single-domain proteins, clearly establishing the biological essentiality of DUFs. We suggest that experimental research should focus on conserved and essential DUFs (eDUFs) for functional analysis given their important function and wide taxonomic distribution, including bacterial pathogens. The functional units of proteins are domains. Typically, each domain has a distinct structure and function. Genomes encode thousands of domains, and many of the domains have no known function (domains of unknown function [DUFs]). They are often ignored as of little relevance, given that many of them are found in only a few genomes. Here we show that many DUFs are essential DUFs (eDUFs) based on their presence in essential proteins. We also show that eDUFs are often essential even if they are found in relatively few genomes. However, in general, more common DUFs are more often essential than rare DUFs.

Effects of Physical-Cognitive Dual Task Training on Executive Function and Gait Performance in Older Adults: A Randomized Controlled Trial

PubMed Central

Falbo, S.; Condello, G.; Capranica, L.; Forte, R.

2016-01-01

Physical and cognitive training seem to counteract age-related decline in physical and mental function. Recently, the possibility of integrating cognitive demands into physical training has attracted attention. The purpose of this study was to evaluate the effects of twelve weeks of designed physical-cognitive training on executive cognitive function and gait performance in older adults. Thirty-six healthy, active individuals aged 72.30 ± 5.84 years were assigned to two types of physical training with major focus on physical single task (ST) training (n = 16) and physical-cognitive dual task (DT) training (n = 20), respectively. They were tested before and after the intervention for executive function (inhibition, working memory) through Random Number Generation and for gait (walking with/without negotiating hurdles) under both single and dual task (ST, DT) conditions. Gait performance improved in both groups, while inhibitory performance decreased after exercise training with ST focus but tended to increase after training with physical-cognitive DT focus. Changes in inhibition performance were correlated with changes in DT walking performance with group differences as a function of motor task complexity (with/without hurdling). The study supports the effectiveness of group exercise classes for older individuals to improve gait performance, with physical-cognitive DT training selectively counteracting the age-related decline in a core executive function essential for daily living. PMID:28053985

Effects of Physical-Cognitive Dual Task Training on Executive Function and Gait Performance in Older Adults: A Randomized Controlled Trial.

PubMed

Falbo, S; Condello, G; Capranica, L; Forte, R; Pesce, C

2016-01-01

Physical and cognitive training seem to counteract age-related decline in physical and mental function. Recently, the possibility of integrating cognitive demands into physical training has attracted attention. The purpose of this study was to evaluate the effects of twelve weeks of designed physical-cognitive training on executive cognitive function and gait performance in older adults. Thirty-six healthy, active individuals aged 72.30 ± 5.84 years were assigned to two types of physical training with major focus on physical single task (ST) training ( n = 16) and physical-cognitive dual task (DT) training ( n = 20), respectively. They were tested before and after the intervention for executive function (inhibition, working memory) through Random Number Generation and for gait (walking with/without negotiating hurdles) under both single and dual task (ST, DT) conditions. Gait performance improved in both groups, while inhibitory performance decreased after exercise training with ST focus but tended to increase after training with physical-cognitive DT focus. Changes in inhibition performance were correlated with changes in DT walking performance with group differences as a function of motor task complexity (with/without hurdling). The study supports the effectiveness of group exercise classes for older individuals to improve gait performance, with physical-cognitive DT training selectively counteracting the age-related decline in a core executive function essential for daily living.

Are civil-law notaries rent-seeking monopolists or essential market intermediaries? Endogenous development of a property rights institution in Mexico

PubMed Central

Monkkonen, Paavo

2017-01-01

As the fourth contribution in the ‘Land’ section, this paper forms a research ‘diptych’ with the next paper by Levy. Whereas she focuses on the notarial institution in mid-nineteenth century Mexico, this contribution examines it in a contemporary context. The notary is one of the chief components of property rights protection in civil-law systems, performing various public functions such as writing deeds for real estate property. Yet notaries are considered an ‘inefficient’ institution by many, due to the perception of rent-seeking behavior enabled by their near-monopoly over validating property rights claims. This study examines notaries in Mexico to unpack the apparent contradiction in the role of notaries in economic development. I use a combination of interviews with notaries and clients, and data on notarial practice and bureaucratic outcomes across the country, to examine notaries’ social function. The theoretical lens of endogenous development and institutional functionalism reveals an alternate explanation for their seemingly high-cost services, as well as their role in economic development. Mexican notaries have a dual social function: public representative and private service provider. They perform diverse and essential activities, which in other countries are performed by multiple actors such as real estate agents, escrow offices and title insurance companies. Thus, what is perceived as inefficiency by some can be interpreted as an efficient response to the context in which they operate, and their semi-privatized nature can overcome problems found in other bureaucratic arrangements. PMID:28615798

An evolutionary analysis identifies a conserved pentapeptide stretch containing the two essential lysine residues for rice L-myo-inositol 1-phosphate synthase catalytic activity

PubMed Central

Basak, Papri; Maitra-Majee, Susmita; Das, Jayanta Kumar; Mukherjee, Abhishek; Ghosh Dastidar, Shubhra; Pal Choudhury, Pabitra

2017-01-01

A molecular evolutionary analysis of a well conserved protein helps to determine the essential amino acids in the core catalytic region. Based on the chemical properties of amino acid residues, phylogenetic analysis of a total of 172 homologous sequences of a highly conserved enzyme, L-myo-inositol 1-phosphate synthase or MIPS from evolutionarily diverse organisms was performed. This study revealed the presence of six phylogenetically conserved blocks, out of which four embrace the catalytic core of the functional protein. Further, specific amino acid modifications targeting the lysine residues, known to be important for MIPS catalysis, were performed at the catalytic site of a MIPS from monocotyledonous model plant, Oryza sativa (OsMIPS1). Following this study, OsMIPS mutants with deletion or replacement of lysine residues in the conserved blocks were made. Based on the enzyme kinetics performed on the deletion/replacement mutants, phylogenetic and structural comparison with the already established crystal structures from non-plant sources, an evolutionarily conserved peptide stretch was identified at the active pocket which contains the two most important lysine residues essential for catalytic activity. PMID:28950028

Cortical localization of cognitive function by regression of performance on event-related potentials

NASA Technical Reports Server (NTRS)

Montgomery, R. W.; Montgomery, L. D.; Guisado, R.

1992-01-01

This paper demonstrates a new method of mapping cortical localization of cognitive function, using electroencephalographic data. Cross-subject regression analyses are used to identify cortical sites and post-stimulus latencies where there is a high correlation between subjects' performance and their cognitive event-related potential amplitude. The procedure was tested using a mental arithmetic task and was found to identify essentially the same cortical regions that have been associated with such tasks on the basis of research with patients suffering localized cortical lesions. Thus, it appears to offer an inexpensive, noninvasive tool for exploring the dynamics of localization in neurologically normal subjects.

The Role of Snx41-Based Pexophagy in Magnaporthe Development

PubMed Central

Deng, Yizhen; Qu, Ziwei; Naqvi, Naweed I.

2013-01-01

Pexophagy, the degradation of peroxisomes via selective autophagy, depends on Atg20/Snx42 function in Saccharomyces cerevisiae. Besides its role in selective autophagy, Atg20/Snx42 is also involved in an autophagy-independent endosomal retrieval trafficking, in cooperation with two other sorting nexins, Snx41 and Snx4. Recently, we reported that the sorting nexin MoSnx41, which showed high sequence similarity to yeast Snx41 and Snx42/Atg20 proteins, regulates the gamma-glutamyl cycle and GSH production and is essential for conidiation and pathogenicity in Magnaporthe oryzae. Pexophagy was also found to be defective in Mosnx41Δ mutant. These findings indicate that MoSnx41 likely serves combined functions of Snx42/Atg20 and Snx41 in M. oryzae.. In this study, we performed complementation analyses and demonstrate that MoSnx41 alone serves the dual function of protein sorting (ScSnx41) and pexophagy (ScSnx42/Atg20). To study the potential biological function of pexophagy in fungal pathogenic life cycle, we created deletion mutants of potential pexophagy-specific genes, and characterized them in terms of pexophagy, conidiation and pathogenesis. We identified Pex14 as an essential protein for pexophagy in M. oryzae. Overall, our results show that pexophagy per se is not essential for asexual development or virulence in M. oryzae. PMID:24302988

Implementation research to improve quality of maternal and newborn health care, Malawi.

PubMed

Brenner, Stephan; Wilhelm, Danielle; Lohmann, Julia; Kambala, Christabel; Chinkhumba, Jobiba; Muula, Adamson S; De Allegri, Manuela

2017-07-01

To evaluate the impact of a performance-based financing scheme on maternal and neonatal health service quality in Malawi. We conducted a non-randomized controlled before and after study to evaluate the effects of district- and facility-level performance incentives for health workers and management teams. We assessed changes in the facilities' essential drug stocks, equipment maintenance and clinical obstetric care processes. Difference-in-difference regression models were used to analyse effects of the scheme on adherence to obstetric care treatment protocols and provision of essential drugs, supplies and equipment. We observed 33 health facilities, 23 intervention facilities and 10 control facilities and 401 pregnant women across four districts. The scheme improved the availability of both functional equipment and essential drug stocks in the intervention facilities. We observed positive effects in respect to drug procurement and clinical care activities at non-intervention facilities, likely in response to improved district management performance. Birth assistants' adherence to clinical protocols improved across all studied facilities as district health managers supervised and coached clinical staff more actively. Despite nation-wide stock-outs and extreme health worker shortages, facilities in the study districts managed to improve maternal and neonatal health service quality by overcoming bottlenecks related to supply procurement, equipment maintenance and clinical performance. To strengthen and reform health management structures, performance-based financing may be a promising approach to sustainable improvements in quality of health care.

APPLICATION OF SUSTAINABILITY CRITERIA TO STELLA, MISSOURI-ECONOMIC PLANNING-PRELIMINARY SITE INFORMATION AND ELEMENTS OF THE MASTER PLAN-16NOV2006 (1130)

EPA Science Inventory

Economic systems constraints and performance requirements that are essential to providing goods and services, jobs, and a functioning economic system form a list of criteria for planning a sustainable economy. This presentation places these economic criteria in the context of Ste...

Nebraska State Plan Career Education Project. Final Performance Report for Period Ending June 30, 1977.

ERIC Educational Resources Information Center

Nebraska State Dept. of Education, Lincoln.

The Nebraska state career education plan was developed to assist individuals in developing essential educational and career skills for responsible functioning. The plan, linking the school and work world, extends chronologically: elementary level--career awareness, middle/junior high school level--career exploration, and senior high school…

Evaluating the Use of Learning Objects for Improving Calculus Readiness

ERIC Educational Resources Information Center

Kay, Robin; Kletskin, Ilona

2010-01-01

Pre-calculus concepts such as working with functions and solving equations are essential for students to explore limits, rates of change, and integrals. Yet many students have a weak understanding of these key concepts which impedes performance in their first year university Calculus course. A series of online learning objects was developed to…

Action Plan for Florida's Public Libraries. Addendum.

ERIC Educational Resources Information Center

Florida Library Study Commission, Tallahassee.

The introduction to this addendum (the Action Plan is LI 004 521) discusses the present use by libraries of information-handling technology and identifies some of the trends taking place in performing essential library services. While some limited inroads have been made in automating certain public library functions, the bulk of services is still…

Identification and verification of hybridoma-derived monoclonal antibody variable region sequences using recombinant DNA technology and mass spectrometry

USDA-ARS?s Scientific Manuscript database

Antibody engineering requires the identification of antigen binding domains or variable regions (VR) unique to each antibody. It is the VR that define the unique antigen binding properties and proper sequence identification is essential for functional evaluation and performance of recombinant antibo...

The use of observational diaries in in-training evaluation: student perceptions.

PubMed

Govaerts, Marjan J B; van der Vleuten, Cees P M; Schuwirth, Lambert W T; Muijtjens, Arno M M

2005-08-01

In health science education clinical clerkships serve the twofold purpose of guiding student learning and assessment of performance. Evidently, both formative and summative assessment procedures are needed in clerkship assessment. In-training evaluation (ITE) has the potential to serve both assessment functions. Implementation of effective ITE, however, has been shown to be problematic, partly because integration of assessment functions may have negative consequences for teaching and learning. This study investigates student perceptions of the impact of an integrated assessment approach, seeking to refine criteria for effective ITE. In the curriculum of Maastricht Midwifery School (MMS), clerkship assessment is based on ITE serving both assessment functions. The ITE model is based on principles of extensive work sampling, and frequent documentation of performance. A focus group technique was used to explore student perceptions on the impact of the ITE approach on student learning and supervisor teaching behaviour, and on the usefulness of information for decision making. Results indicate that the assessment approach is effective in guidance of student learning. Furthermore, students consider the frequent performance documentation essential in clerkship grading. Acceptance and effectivity of ITE requires a learning environment which is safe and respectful. Transparency of assessment processes is the key to success. Suggestions for improvement focus on variation in evaluation formats, improvement of feedback (narrative, complete) and student involvement in assessment. ITE can fulfill both its formative and summative purposes when some crucial conditions are taken into account. Careful training of both supervisors and students in the use of ITE for student learning and performance measurement is essential.

State Public Health Enabling Authorities: Results of a Fundamental Activities Assessment Examining Core and Essential Services

PubMed Central

Hoss, Aila; Menon, Akshara; Corso, Liza

2016-01-01

Context Public health enabling authorities establish the legal foundation for financing, organizing, and delivering public health services. State laws vary in terms of the content, depth, and breadth of these fundamental public health activities. Given this variance, the Institute of Medicine has identified state public health laws as an area that requires further examination. To respond to this call for further examination, the Centers for Disease Control and Prevention’s Public Health Law Program conducted a fundamental activities legal assessment on state public health laws. Objective The goal of the legal assessment was to examine state laws referencing frameworks representing public health department fundamental activities (ie, core and essential services) in an effort to identify, catalog, and describe enabling authorities of state governmental public health systems. Design In 2013, Public Health Law Program staff compiled a list of state statutes and regulations referencing different commonly-recognized public health frameworks of fundamental activities. The legal assessment included state fundamental activities laws available on WestlawNext as of July 2013. The results related to the 10 essential public health services and the 3 core public health functions were confirmed and updated in June 2016. Results Eighteen states reference commonly-recognized frameworks of fundamental activities in their laws. Thirteen states have listed the 10 essential public health services in their laws. Eight of these states have also referenced the 3 core public health functions in their laws. Five states reference only the core public health functions. Conclusions Several states reference fundamental activities in their state laws, particularly through use of the essential services framework. Further work is needed to capture the public health laws and practices of states that may be performing fundamental activities but without reference to a common framework. PMID:27682724

State Public Health Enabling Authorities: Results of a Fundamental Activities Assessment Examining Core and Essential Services.

PubMed

Hoss, Aila; Menon, Akshara; Corso, Liza

2016-01-01

Public health enabling authorities establish the legal foundation for financing, organizing, and delivering public health services. State laws vary in terms of the content, depth, and breadth of these fundamental public health activities. Given this variance, the Institute of Medicine has identified state public health laws as an area that requires further examination. To respond to this call for further examination, the Centers for Disease Control and Prevention's Public Health Law Program conducted a fundamental activities legal assessment on state public health laws. The goal of the legal assessment was to examine state laws referencing frameworks representing public health department fundamental activities (ie, core and essential services) in an effort to identify, catalog, and describe enabling authorities of state governmental public health systems. In 2013, Public Health Law Program staff compiled a list of state statutes and regulations referencing different commonly-recognized public health frameworks of fundamental activities. The legal assessment included state fundamental activities laws available on WestlawNext as of July 2013. The results related to the 10 essential public health services and the 3 core public health functions were confirmed and updated in June 2016. Eighteen states reference commonly-recognized frameworks of fundamental activities in their laws. Thirteen states have listed the 10 essential public health services in their laws. Eight of these states have also referenced the 3 core public health functions in their laws. Five states reference only the core public health functions. Several states reference fundamental activities in their state laws, particularly through use of the essential services framework. Further work is needed to capture the public health laws and practices of states that may be performing fundamental activities but without reference to a common framework.

Mycobacterium tuberculosis thymidylate synthase gene thyX is essential and potentially bifunctional, while thyA deletion confers resistance to p-aminosalicylic acid

PubMed Central

Houghton, Joanna; Davis, Elaine O.

2012-01-01

Thymidylate synthase (TS) enzymes catalyse the biosynthesis of deoxythymidine monophosphate (dTMP or thymidylate), and so are important for DNA replication and repair. Two different types of TS proteins have been described (ThyA and ThyX), which have different enzymic mechanisms and unrelated structures. Mycobacteria are unusual as they encode both thyA and thyX, and the biological significance of this is not yet understood. Mycobacterium tuberculosis ThyX is thought to be essential and a potential drug target. We therefore analysed M. tuberculosis thyA and thyX expression levels, their essentiality and roles in pathogenesis. We show that both thyA and thyX are expressed in vitro, and that this expression significantly increased within murine macrophages. Under all conditions tested, thyA expression exceeded that of thyX. Mutational studies show that M. tuberculosis thyX is essential, confirming that the enzyme is a plausible drug target. The requirement for M. tuberculosis thyX in the presence of thyA implies that the essential function of ThyX is something other than dTMP synthase. We successfully deleted thyA from the M. tuberculosis genome, and this deletion conferred an in vitro growth defect that was not observed in vivo. Presumably ThyX performs TS activity within M. tuberculosis ΔthyA at a sufficient rate in vivo for normal growth, but the rate in vitro is less than optimal. We also demonstrate that thyA deletion confers M. tuberculosis p-aminosalicylic acid resistance, and show by complementation studies that ThyA T202A and V261G appear to be functional and non-functional, respectively. PMID:22034487

Mycobacterium tuberculosis thymidylate synthase gene thyX is essential and potentially bifunctional, while thyA deletion confers resistance to p-aminosalicylic acid.

PubMed

Fivian-Hughes, Amanda S; Houghton, Joanna; Davis, Elaine O

2012-02-01

Thymidylate synthase (TS) enzymes catalyse the biosynthesis of deoxythymidine monophosphate (dTMP or thymidylate), and so are important for DNA replication and repair. Two different types of TS proteins have been described (ThyA and ThyX), which have different enzymic mechanisms and unrelated structures. Mycobacteria are unusual as they encode both thyA and thyX, and the biological significance of this is not yet understood. Mycobacterium tuberculosis ThyX is thought to be essential and a potential drug target. We therefore analysed M. tuberculosis thyA and thyX expression levels, their essentiality and roles in pathogenesis. We show that both thyA and thyX are expressed in vitro, and that this expression significantly increased within murine macrophages. Under all conditions tested, thyA expression exceeded that of thyX. Mutational studies show that M. tuberculosis thyX is essential, confirming that the enzyme is a plausible drug target. The requirement for M. tuberculosis thyX in the presence of thyA implies that the essential function of ThyX is something other than dTM synthesis [corrected].We successfully deleted thyA from the M. tuberculosis genome, and this deletion conferred an in vitro growth defect that was not observed in vivo. Presumably ThyX performs TS activity within M. tuberculosis ΔthyA at a sufficient rate in vivo for normal growth, but the rate in vitro is less than optimal. We also demonstrate that thyA deletion confers M. tuberculosis p-aminosalicylic acid resistance, and show by complementation studies that ThyA T202A and V261G appear to be functional and non-functional, respectively.

Comparison of performance-based assessment and real world skill in people with serious mental illness: Ecological validity of the Test of Grocery Shopping Skills.

PubMed

Faith, Laura A; Rempfer, Melisa V

2018-05-07

Valid functional measures are essential for clinical and research efforts that address recovery and community functioning in people with serious mental illness. Although there is a great deal of interest in functional assessment, there is limited research supporting how well current evaluation methods provide a true assessment of real world functioning or naturalistic behavior. To address this gap in the literature, the present study examined the performance of individuals with serious mental illness (i.e., diagnosis of schizophrenia-spectrum, bipolar disorder, or other depression/anxiety diagnoses and accompanying functional disability) on the Test of Grocery Shopping Skills (TOGSS), a performance-based naturalistic task. We compared TOGSS performance to two dimensions of real world functioning: directly observed real world grocery shopping and ratings of community functioning. Results indicated that the TOGSS was significantly associated with real life grocery shopping, in terms of both shopping accuracy (r = 0.424) and time (r = 0.491). Further, self-report and observer-rated methods of assessing real world shopping behaviors were significantly correlated (r = 0.455). To our knowledge, this is one of the first studies to directly compare a performance-based naturalistic skill assessment with carefully observed real world performance of that skill in people with serious mental illness. These findings support the feasibility and ecological validity of performance-based naturalistic assessment with the TOGSS. Copyright © 2018 Elsevier B.V. All rights reserved.

Is decentralization good for logistics systems? Evidence on essential medicine logistics in Ghana and Guatemala.

PubMed

Bossert, Thomas J; Bowser, Diana M; Amenyah, Johnnie K

2007-03-01

Efficient logistics systems move essential medicines down the supply chain to the service delivery point, and then to the end user. Experts on logistics systems tend to see the supply chain as requiring centralized control to be most effective. However, many health reforms have involved decentralization, which experts fear has disrupted the supply chain and made systems less effective. There is no consensus on an appropriate methodology for assessing the effectiveness of decentralization in general, and only a few studies have attempted to address decentralization of logistics systems. This paper sets out a framework and methodology of a pioneering exploratory study that examines the experiences of decentralization in two countries, Guatemala and Ghana, and presents suggestive results of how decentralization affected the performance of their logistics systems. The analytical approach assessed decentralization using the principal author's 'decision space' approach, which defines decentralization as the degree of choice that local officials have over different health system functions. In this case the approach focused on 15 different logistics functions and measured the relationship between the degree of choice and indicators of performance for each of the functions. The results of both studies indicate that less choice (i.e. more centralized) was associated with better performance for two key functions (inventory control and information systems), while more choice (i.e. more decentralized) over planning and budgeting was associated with better performance. With different systems of procurement in Ghana and Guatemala, we found that a system with some elements of procurement that are centralized (selection of firms and prices fixed by national tender) was positively related in Guatemala but negatively related in Ghana, where a system of 'cash and carry' cost recovery allowed more local choice. The authors conclude that logistics systems can be effectively decentralized for some functions while others should remain centralized. These preliminary findings, however, should be subject to alternative methodologies to confirm the findings.

Two hands, one brain, and aging.

PubMed

Maes, Celine; Gooijers, Jolien; Orban de Xivry, Jean-Jacques; Swinnen, Stephan P; Boisgontier, Matthieu P

2017-04-01

Many activities of daily living require moving both hands in an organized manner in space and time. Therefore, understanding the impact of aging on bimanual coordination is essential for prolonging functional independence and well-being in older adults. Here we investigated the behavioral and neural determinants of bimanual coordination in aging. The studies surveyed in this review reveal that aging is associated with cortical hyper-activity (but also subcortical hypo-activity) during performance of bimanual tasks. In addition to changes in activation in local areas, the interaction between distributed brain areas also exhibits age-related effects, i.e., functional connectivity is increased in the resting brain as well as during task performance. The mechanisms and triggers underlying these functional activation and connectivity changes remain to be investigated. This requires further research investment into the detailed study of interactions between brain structure, function and connectivity. This will also provide the foundation for interventional research programs towards preservation of brain health and behavioral performance by maximizing neuroplasticity potential in older adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor.

PubMed

Qu, Hong-En; Niu, Chuanxin M; Li, Si; Hao, Man-Zhao; Hu, Zi-Xiang; Xie, Qing; Lan, Ning

2017-12-01

Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

Functional Assessment of the Vanderbilt Multigrasp Myoelectric Hand: A Continuing Case Study

PubMed Central

Dalley, Skyler A.; Bennett, Daniel A.; Goldfarb, Michael

2015-01-01

This paper presents a case study involving the functional assessment of the Vanderbilt Multigrasp (VMG) hand prosthesis on a single transradial amputee subject. In particular, a transradial amputee subject performed the Southampton Hand Assessment Procedure (SHAP) using the hand prosthesis and multigrasp myoelectric controller in a series of experimental sessions occurring over a multi-week time span. The subject’s index of function (IoF) improved with each session, although essentially plateaued after the fourth session, resulting in a IoF score of 87, which compares favorably to SHAP scores published in previous studies. PMID:25571412

Facts about Volunteers. NCJW Center for the Child Fact Sheet Number 5.

ERIC Educational Resources Information Center

National Council of Jewish Women, New York, NY. Center for the Child.

Volunteering is a vital and widespread activity in the United States; in fact, volunteers perform many essential community functions. Those who believe that most volunteers are women with time on their hands, that volunteers just do "charity work," and that volunteers are a source of cheap labor who can replace paid professionals and…

Pretrial Functional Connectivity Differentiates Behavioral Outcomes during Trace Eyeblink Conditioning in the Rabbit

ERIC Educational Resources Information Center

Schroeder, Matthew P.; Weiss, Craig; Procissi, Daniel; Wang, Lei; Disterhoft, John F.

2016-01-01

Fluctuations in neural activity can produce states that facilitate and accelerate task-related performance. Acquisition of trace eyeblink conditioning (tEBC) in the rabbit is enhanced when trials are contingent on optimal pretrial activity in the hippocampus. Other regions which are essential for whisker-signaled tEBC, such as the cerebellar…

Effectiveness of Forestry Agency Personnel as Fire Prevention Contactors

Treesearch

M.L. Doolittle

1980-01-01

A major responsibility of county forest rangers in North Carolina is fire prevention. Personal contact with the public is essential to the successful performance of this function. A survey of 50 North Carolina rangers revealed that the degree of success for each ranger was directly related to the specific effort put forth as a contactor.

Viral precursor protein P3 and its processed products perform discrete and essential functions in the poliovirus RNA replication complex

USDA-ARS?s Scientific Manuscript database

The differential use of protein precursors and their products is a key strategy used during poliovirus replication. To characterize the role of protein precursors during replication, we examined the complementation profiles of mutants that inhibited 3D polymerase or 3C-RNA binding activity. We showe...

Ties that bind: Pacific Northwest truffles, trees, and animals in symbiosis

Treesearch

Marie Oliver; Randy Molina; Jane E.  Smith

2009-01-01

Soil organisms play essential roles in forest health, and truffle fungi are one of the more fascinating groups of these important organisms. After 40 years of specimen collection and study, scientists with Pacific Northwest Research Station have published a report documenting how truffle fungi affect tree survival and growth, perform valuable functions in nutrient...

Florida's Revised Prescribed Fire Law: Protection For Responsible Burners

Treesearch

Jim Brenner; Dale Wade

2003-01-01

In Florida, natural communities require periodic fires for maintenance of their ecological integrity. Because of public concerns, wildfires can no longer be allowed to perform this mandatory function so prescribed burning is essential to manage these plant and animal communities. We discuss the importance of prescribed fire in Florida, outline a history of the state...

Wetlands systems in southern Thailand: The essential resources for sustainable regional development

Treesearch

Rotchanatch Darnsawasdi; Prassert Chitpong

2000-01-01

Parts of Southern Thailand are inundated by water for months annually resulting in various wetlands including, among others, Tapi River Basin, Pak Panang River Basin, Songkhla Lake Basin, Pangnga Bay, Pattani River Basin, and Narathiwas Peat Swamp. Most wetlands perform functions such as flood retention, water filtration, bird and wildlife habitat,and tree growth....

A Study of Shared-Memory Mutual Exclusion Protocols Using CADP

NASA Astrophysics Data System (ADS)

Mateescu, Radu; Serwe, Wendelin

Mutual exclusion protocols are an essential building block of concurrent systems: indeed, such a protocol is required whenever a shared resource has to be protected against concurrent non-atomic accesses. Hence, many variants of mutual exclusion protocols exist in the shared-memory setting, such as Peterson's or Dekker's well-known protocols. Although the functional correctness of these protocols has been studied extensively, relatively little attention has been paid to their non-functional aspects, such as their performance in the long run. In this paper, we report on experiments with the performance evaluation of mutual exclusion protocols using Interactive Markov Chains. Steady-state analysis provides an additional criterion for comparing protocols, which complements the verification of their functional properties. We also carefully re-examined the functional properties, whose accurate formulation as temporal logic formulas in the action-based setting turns out to be quite involved.

A genetic replacement system for selection-based engineering of essential proteins

PubMed Central

2012-01-01

Background Essential genes represent the core of biological functions required for viability. Molecular understanding of essentiality as well as design of synthetic cellular systems includes the engineering of essential proteins. An impediment to this effort is the lack of growth-based selection systems suitable for directed evolution approaches. Results We established a simple strategy for genetic replacement of an essential gene by a (library of) variant(s) during a transformation. The system was validated using three different essential genes and plasmid combinations and it reproducibly shows transformation efficiencies on the order of 107 transformants per microgram of DNA without any identifiable false positives. This allowed for reliable recovery of functional variants out of at least a 105-fold excess of non-functional variants. This outperformed selection in conventional bleach-out strains by at least two orders of magnitude, where recombination between functional and non-functional variants interfered with reliable recovery even in recA negative strains. Conclusions We propose that this selection system is extremely suitable for evaluating large libraries of engineered essential proteins resulting in the reliable isolation of functional variants in a clean strain background which can readily be used for in vivo applications as well as expression and purification for use in in vitro studies. PMID:22898007

[Lung function tests: the pneumologist and ambulatory care].

PubMed

Reis Ferreira, J M

2004-01-01

Lung function testing (LFT) has been standardized and greatly improved in the last three decades, but its relative complexity has driven to recent sistematization and standardization of its applicability in the office and in primary care. In memorian of Prof António Couto, and of his outstanding role in the promotion of LFT in Potyugal, this conference deals with the definition of office spirometry, its application range, and the essential steps for the performance, in acceptable quality and reproducibility conditioms. The role of the specialist in promoting this method, and his support to possible spirometry performers, is aimed as an important request in the success of the practical and used technique in family practice and primary health care.

Effects of topical essential oil on exercise volume after a 12-week exercise program for women with fibromyalgia: a pilot study.

PubMed

Rutledge, Dana N; Jones, C Jessie

2007-12-01

We determined--in women with fibromyalgia (FM)--effects of essential oils used with a 12-week exercise program on exercise volume, pain, physical performance, and physical function. This was a randomized clinical trial comparing 024 essential oil with sham oil combined with exercise. SETTINGS included community sites in southern California. The study included 20 women randomized to 024 oil, 23 to sham oil. Women were trained in oil application before exercise, at bedtime on exercise days; the 12-week program included weekly group sessions with trained leaders guided by a prerecorded regimen (allowing choice of program level) plus 2 days of home exercise with the recorded regimen. Primary: Exercise volume (number of days exercised multiplied by exercise level--intensity and duration). Secondary: Pain (Brief Pain Inventory), measures of physical performance (30-second chair stands, 6-minute walk, multidimensional balance), and self-reported physical function (Composite Physical Function scale). The average participant was 54 years old, had some college education, was married, Caucasian, and minimally/mildly depressed. There was no significant difference in exercise volume between women using 024 as compared with those using sham oil after 12 weeks (depression as covariate). There were no significant group nor pre- to postexercise changes in pain intensity or interference. There were greater positive changes in 30-second chair stands, 6-minute walk distance, and multidimensional balance scores in the 024 group than in the sham group, but these were not significant. The counterirritant 024 oil was not different from the sham oil in its effect on exercise volume (frequency, exercise level--intensity and duration) for women with FM. It is unknown whether 024 actually decreases local pain when used with exercise. Increases in physical function found, while not significant, may be attributable to the exercise regimen or to the interaction of the oils and exercise regimen.

Implementation research to improve quality of maternal and newborn health care, Malawi

PubMed Central

Wilhelm, Danielle; Lohmann, Julia; Kambala, Christabel; Chinkhumba, Jobiba; Muula, Adamson S; De Allegri, Manuela

2017-01-01

Abstract Objective To evaluate the impact of a performance-based financing scheme on maternal and neonatal health service quality in Malawi. Methods We conducted a non-randomized controlled before and after study to evaluate the effects of district- and facility-level performance incentives for health workers and management teams. We assessed changes in the facilities’ essential drug stocks, equipment maintenance and clinical obstetric care processes. Difference-in-difference regression models were used to analyse effects of the scheme on adherence to obstetric care treatment protocols and provision of essential drugs, supplies and equipment. Findings We observed 33 health facilities, 23 intervention facilities and 10 control facilities and 401 pregnant women across four districts. The scheme improved the availability of both functional equipment and essential drug stocks in the intervention facilities. We observed positive effects in respect to drug procurement and clinical care activities at non-intervention facilities, likely in response to improved district management performance. Birth assistants’ adherence to clinical protocols improved across all studied facilities as district health managers supervised and coached clinical staff more actively. Conclusion Despite nation-wide stock-outs and extreme health worker shortages, facilities in the study districts managed to improve maternal and neonatal health service quality by overcoming bottlenecks related to supply procurement, equipment maintenance and clinical performance. To strengthen and reform health management structures, performance-based financing may be a promising approach to sustainable improvements in quality of health care. PMID:28670014

The anaplerotic node is essential for the intracellular survival of Mycobacterium tuberculosis

PubMed Central

Basu, Piyali; Sandhu, Noor; Bhatt, Apoorva; Singh, Albel; Balhana, Ricardo; Gobe, Irene; Crowhurst, Nicola A.; Mendum, Tom A.; Gao, Liang; Ward, Jane L.; Beale, Michael H.; McFadden, Johnjoe; Beste, Dany J. V.

2018-01-01

Enzymes at the phosphoenolpyruvate (PEP)–pyruvate–oxaloacetate or anaplerotic (ANA) node control the metabolic flux to glycolysis, gluconeogenesis, and anaplerosis. Here we used genetic, biochemical, and 13C isotopomer analysis to characterize the role of the enzymes at the ANA node in intracellular survival of the world's most successful bacterial pathogen, Mycobacterium tuberculosis (Mtb). We show that each of the four ANA enzymes, pyruvate carboxylase (PCA), PEP carboxykinase (PCK), malic enzyme (MEZ), and pyruvate phosphate dikinase (PPDK), performs a unique and essential metabolic function during the intracellular survival of Mtb. We show that in addition to PCK, intracellular Mtb requires PPDK as an alternative gateway into gluconeogenesis. Propionate and cholesterol detoxification was also identified as an essential function of PPDK revealing an unexpected role for the ANA node in the metabolism of these physiologically important intracellular substrates and highlighting this enzyme as a tuberculosis (TB)-specific drug target. We show that anaplerotic fixation of CO2 through the ANA node is essential for intracellular survival of Mtb and that Mtb possesses three enzymes (PCA, PCK, and MEZ) capable of fulfilling this function. In addition to providing a back-up role in anaplerosis we show that MEZ also has a role in lipid biosynthesis. MEZ knockout strains have an altered cell wall and were deficient in the initial entry into macrophages. This work reveals that the ANA node is a focal point for controlling the intracellular replication of Mtb, which goes beyond canonical gluconeogenesis and represents a promising target for designing novel anti-TB drugs. PMID:29475946

CTCF knockout reveals an essential role for this protein during the zebrafish development.

PubMed

Carmona-Aldana, Francisco; Zampedri, Cecilia; Suaste-Olmos, Fernando; Murillo-de-Ozores, Adrián; Guerrero, Georgina; Arzate-Mejía, Rodrigo; Maldonado, Ernesto; Navarro, Rosa; Chimal-Monroy, Jesús; Recillas-Targa, Félix

2018-05-01

Chromatin regulation and organization are essential processes that regulate gene activity. The CCCTC-binding factor (CTCF) is a protein with different and important molecular functions related with chromatin dynamics. It is conserved since invertebrates to vertebrates, posing it as a factor with an important role in the physiology. In this work, we aimed to understand the distribution and functional relevance of CTCF during the embryonic development of the zebrafish (Danio rerio). We generated a zebrafish specific anti-Ctcf antibody, and found this protein to be ubiquitous, through different stages and tissues. We used the CRISPR-Cas9 system to induce molecular alterations in the locus. This resulted in early lethality. We delayed the lethality performing knockdown morpholino experiments, and found an aberrant embryo morphology involving malformations in structures through all the length of the embryo. These phenotypes were rescued with human CTCF mRNA injections, showing the specificity of the morpholinos and a partial functional conservation between the fish and the human proteins. Lastly, we found that the pro-apoptotic genes p53 and bbc3/PUMA are deregulated in the ctcf morpholino-injected embryos. In conclusion, CTCF is a ubiquitous factor during the zebrafish development, which regulates the correct formation of different structures of the embryo, and its deregulation impacts on essential cell survival genes. Overall, this work provides a basis to look for the particular functions of CTCF in the different developing tissues and organs of the zebrafish. Copyright © 2018. Published by Elsevier B.V.

Cerebello-cortical network fingerprints differ between essential, Parkinson's and mimicked tremors.

PubMed

Muthuraman, Muthuraman; Raethjen, Jan; Koirala, Nabin; Anwar, Abdul Rauf; Mideksa, Kidist G; Elble, Rodger; Groppa, Sergiu; Deuschl, Günter

2018-06-01

Cerebello-thalamo-cortical loops play a major role in the emergence of pathological tremors and voluntary rhythmic movements. It is unclear whether these loops differ anatomically or functionally in different types of tremor. We compared age- and sex-matched groups of patients with Parkinson's disease or essential tremor and healthy controls (n = 34 per group). High-density 256-channel EEG and multi-channel EMG from extensor and flexor muscles of both wrists were recorded simultaneously while extending the hands against gravity with the forearms supported. Tremor was thereby recorded from patients, and voluntarily mimicked tremor was recorded from healthy controls. Tomographic maps of EEG-EMG coherence were constructed using a beamformer algorithm coherent source analysis. The direction and strength of information flow between different coherent sources were estimated using time-resolved partial-directed coherence analyses. Tremor severity and motor performance measures were correlated with connection strengths between coherent sources. The topography of oscillatory coherent sources in the cerebellum differed significantly among the three groups, but the cortical sources in the primary sensorimotor region and premotor cortex were not significantly different. The cerebellar and cortical source combinations matched well with known cerebello-thalamo-cortical connections derived from functional MRI resting state analyses according to the Buckner-atlas. The cerebellar sources for Parkinson's tremor and essential tremor mapped primarily to primary sensorimotor cortex, but the cerebellar source for mimicked tremor mapped primarily to premotor cortex. Time-resolved partial-directed coherence analyses revealed activity flow mainly from cerebellum to sensorimotor cortex in Parkinson's tremor and essential tremor and mainly from cerebral cortex to cerebellum in mimicked tremor. EMG oscillation flowed mainly to the cerebellum in mimicked tremor, but oscillation flowed mainly from the cerebellum to EMG in Parkinson's and essential tremor. The topography of cerebellar involvement differed among Parkinson's, essential and mimicked tremors, suggesting different cerebellar mechanisms in tremorogenesis. Indistinguishable areas of sensorimotor cortex and premotor cerebral cortex were involved in all three tremors. Information flow analyses suggest that sensory feedback and cortical efferent copy input to cerebellum are needed to produce mimicked tremor, but tremor in Parkinson's disease and essential tremor do not depend on these mechanisms. Despite the subtle differences in cerebellar source topography, we found no evidence that the cerebellum is the source of oscillation in essential tremor or that the cortico-bulbo-cerebello-thalamocortical loop plays different tremorogenic roles in Parkinson's and essential tremor. Additional studies are needed to decipher the seemingly subtle differences in cerebellocortical function in Parkinson's and essential tremors.

Identifying essential proteins based on sub-network partition and prioritization by integrating subcellular localization information.

PubMed

Li, Min; Li, Wenkai; Wu, Fang-Xiang; Pan, Yi; Wang, Jianxin

2018-06-14

Essential proteins are important participants in various life activities and play a vital role in the survival and reproduction of living organisms. Identification of essential proteins from protein-protein interaction (PPI) networks has great significance to facilitate the study of human complex diseases, the design of drugs and the development of bioinformatics and computational science. Studies have shown that highly connected proteins in a PPI network tend to be essential. A series of computational methods have been proposed to identify essential proteins by analyzing topological structures of PPI networks. However, the high noise in the PPI data can degrade the accuracy of essential protein prediction. Moreover, proteins must be located in the appropriate subcellular localization to perform their functions, and only when the proteins are located in the same subcellular localization, it is possible that they can interact with each other. In this paper, we propose a new network-based essential protein discovery method based on sub-network partition and prioritization by integrating subcellular localization information, named SPP. The proposed method SPP was tested on two different yeast PPI networks obtained from DIP database and BioGRID database. The experimental results show that SPP can effectively reduce the effect of false positives in PPI networks and predict essential proteins more accurately compared with other existing computational methods DC, BC, CC, SC, EC, IC, NC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Virtual Environments for Soldier Training via Editable Demonstrations (VESTED)

DTIC Science & Technology

2011-04-01

demonstrations as visual depictions of task performance, though sound and especially verbal communications involved with the task can also be essential...or any component cue alone (e.g., Janelle, Champenoy, Coombes , & Mousseau, 2003). Neurophysiology. Recent neurophysiological research has...provides insight about how VESTED functions, what features to modify should it yield less than optimal results, and how to encode, communicate and

Real-Time Enzyme Kinetics by Quantitative NMR Spectroscopy and Determination of the Michaelis-Menten Constant Using the Lambert-W Function

ERIC Educational Resources Information Center

Her, Cheenou; Alonzo, Aaron P.; Vang, Justin Y.; Torres, Ernesto; Krishnan, V. V.

2015-01-01

Enzyme kinetics is an essential part of a chemistry curriculum, especially for students interested in biomedical research or in health care fields. Though the concept is routinely performed in undergraduate chemistry/biochemistry classrooms using other spectroscopic methods, we provide an optimized approach that uses a real-time monitoring of the…

Teaching and Using Audiation in Classroom Instruction and Applied Lessons with Advanced Students

ERIC Educational Resources Information Center

Hiatt, James S.; Cross, Sam

2006-01-01

A musical ear is widely accepted as an essential ingredient in the education of successful music students. Most music educators believe that without a well-developed ear, it's impossible for a musician to function on a professional level as a teacher, conductor, performer, or composer. The purpose of this article is to introduce the concept of…

What Happened to the "Superior Abilities" in Adults with Dyslexia and High IQs? A Behavioral and Neurological Illustration

ERIC Educational Resources Information Center

Gilger, Jeffrey W.; Olulade, Olumide A.

2013-01-01

Observable behavior, such as test scores, is the gold standard by which we make judgments about levels of function, grade placements, and the presence/absence of pathology. Individual differences in test performance have long intrigued researchers and clinicians, and some have noted how people can come up with essentially the same answers using…

Using Mathematics Curriculum Based Measurement as an Indicator of Student Performance on State Standards

ERIC Educational Resources Information Center

Hall, Linda De Zell

2009-01-01

Math skills are essential to daily life, impacting a person's ability to function at home, work, and in the community. Although reading has been the focus in recent years, many students struggle in math. The inability to master math calculation and problem solving has contributed to the rising incidence of student failure, referrals for special…

41 CFR Appendix A to Part 60 - 300-Guidelines on a Contractor's Duty To Provide Reasonable Accommodation

Code of Federal Regulations, 2010 CFR

2010-07-01

... performing his or her job. 1. A contractor is required to make reasonable accommodations to the known... qualified with respect to that process. One is “otherwise qualified” if he or she is qualified for a job... the job's essential functions. 2. Although the contractor would not be expected to accommodate...

Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis.

PubMed

Carlson, Kaitlin S; Whitney, Meredith S; Gadziola, Marie A; Deneris, Evan S; Wesson, Daniel W

2016-01-01

The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether the olfactory system requires 5-HT for even its most basic behavioral functions. To address this question, we established a conditional genetic approach to specifically target adult brain tryptophan hydroxylase 2 ( Tph2 ), encoding the rate-limiting enzyme in brain 5-HT synthesis, and nearly eliminate 5-HT from the mouse forebrain. Using this novel model, we investigated the behavior of 5-HT-depleted mice during performance in an olfactory go/no-go task. Surprisingly, the near elimination of 5-HT from the forebrain, including the olfactory bulbs, had no detectable effect on the ability of mice to perform the odor-based task. Tph2 -targeted mice not only were able to learn the task, but also had levels of odor acuity similar to those of control mice when performing coarse odor discrimination. Both groups of mice spent similar amounts of time sampling odors during decision-making. Furthermore, odor reversal learning was identical between 5-HT-depleted and control mice. These results suggest that 5-HT neurotransmission is not necessary for the most essential aspects of olfaction, including odor learning, discrimination, and certain forms of cognitive flexibility.

Balanced Scorecards As a Tool for Developing Patient-Centered Pharmacy Services

PubMed Central

Enwere, Emmanuel N.; Keating, Ellen A.; Weber, Robert J.

2014-01-01

Having accurate data is essential for the pharmacy director to manage the department and develop patient-centered pharmacy services. A balanced scorecard (BSC) of essential department data, which is a broad view of a department’s function beyond its financial performance, is an important part of any department’s strategic plan. This column describes how the pharmacy director builds and promotes a department’s BSC. Specifically, this article reviews how the BSC supports the department’s mission and vision, describes the metrics of the BSC and how they are collected, and recommends how the pharmacy director can effectively use the scorecard results in promoting the pharmacy. If designed properly and updated consistently, a BSC can present a broad view of the pharmacy’s performance, serve as a guide for strategic decision making, and improve on the quality of its services. PMID:24958976

The Mineral–Collagen Interface in Bone

PubMed Central

2015-01-01

The interface between collagen and the mineral reinforcement phase, carbonated hydroxyapatite (cAp), is essential for bone’s remarkable functionality as a biological composite material. The very small dimensions of the cAp phase and the disparate natures of the reinforcement and matrix are essential to the material’s performance but also complicate study of this interface. This article summarizes what is known about the cAp-collagen interface in bone and begins with descriptions of the matrix and reinforcement roles in composites, of the phases bounding the interface, of growth of cAp growing within the collagen matrix, and of the effect of intra- and extrafibrilar mineral on determinations of interfacial properties. Different observed interfacial interactions with cAp (collagen, water, non-collagenous proteins) are reviewed; experimental results on interface interactions during loading are reported as are their influence on macroscopic mechanical properties; conclusions of numerical modeling of interfacial interactions are also presented. The data suggest interfacial interlocking (bending of collagen molecules around cAp nanoplatelets) and water-mediated bonding between collagen and cAp are essential to load transfer. The review concludes with descriptions of areas where new research is needed to improve understanding of how the interface functions. PMID:25824581

Origin of the performances degradation of two-dimensional-based metal-oxide-semiconductor field effect transistors in the sub-10 nm regime: A first-principles study

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

Lu, Anh Khoa Augustin; IMEC, 75 Kapeldreef, B-3001 Leuven; Pourtois, Geoffrey

2016-01-25

The impact of the scaling of the channel length on the performances of metal-oxide-semiconductor field effect transistors, based on two-dimensional (2D) channel materials, is theoretically investigated, using density functional theory combined with the non-equilibrium Green's function method. It is found that the scaling of the channel length below 10 nm leads to strong device performance degradations. Our simulations reveal that this degradation is essentially due to the tunneling current flowing between the source and the drain in these aggressively scaled devices. It is shown that this electron tunneling process is modulated by the effective mass of the 2D channel material, andmore » sets the limit of the scaling in future transistor designs.« less

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

PubMed Central

Klann, Eric

2011-01-01

Abstract The brain is a metabolically active organ exhibiting high oxygen consumption and robust production of reactive oxygen species (ROS). The large amounts of ROS are kept in check by an elaborate network of antioxidants, which sometimes fail and lead to neuronal oxidative stress. Thus, ROS are typically categorized as neurotoxic molecules and typically exert their detrimental effects via oxidation of essential macromolecules such as enzymes and cytoskeletal proteins. Most importantly, excessive ROS are associated with decreased performance in cognitive function. However, at physiological concentrations, ROS are involved in functional changes necessary for synaptic plasticity and hence, for normal cognitive function. The fine line of role reversal of ROS from good molecules to bad molecules is far from being fully understood. This review focuses on identifying the multiple sources of ROS in the mammalian nervous system and on presenting evidence for the critical and essential role of ROS in synaptic plasticity and memory. The review also shows that the inability to restrain either age- or pathology-related increases in ROS levels leads to opposite, detrimental effects that are involved in impairments in synaptic plasticity and memory function. Antioxid. Redox Signal. 14, 2013–2054. PMID:20649473

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

Brown, Nicholas R.; Carlsen, Brett W.; Dixon, Brent W.

Dynamic fuel cycle simulation tools are intended to model holistic transient nuclear fuel cycle scenarios. As with all simulation tools, fuel cycle simulators require verification through unit tests, benchmark cases, and integral tests. Model validation is a vital aspect as well. Although compara-tive studies have been performed, there is no comprehensive unit test and benchmark library for fuel cycle simulator tools. The objective of this paper is to identify the must test functionalities of a fuel cycle simulator tool within the context of specific problems of interest to the Fuel Cycle Options Campaign within the U.S. Department of Energy smore » Office of Nuclear Energy. The approach in this paper identifies the features needed to cover the range of promising fuel cycle options identified in the DOE-NE Fuel Cycle Evaluation and Screening (E&S) and categorizes these features to facilitate prioritization. Features were categorized as essential functions, integrating features, and exemplary capabilities. One objective of this paper is to propose a library of unit tests applicable to each of the essential functions. Another underlying motivation for this paper is to encourage an international dialog on the functionalities and standard test methods for fuel cycle simulator tools.« less

Determining Criteria to Predict Repeatability of Performance in Older Adults: Using Coefficients of Variation for Strength and Functional Measures.

PubMed

Raj, Isaac Selva; Bird, Stephen R; Westfold, Ben A; Shield, Anthony J

2017-01-01

Reliable measures of muscle strength and functional capacity in older adults are essential. The aim of this study was to determine whether coefficients of variation (CVs) of individuals obtained at the first session can infer repeatability of performance in a subsequent session. Forty-eight healthy older adults (mean age 68.6 ± 6.1 years; age range 60-80 years) completed two assessment sessions, and on each occasion undertook: dynamometry for isometric and isokinetic quadriceps strength, 6 meter fast walk (6MFWT), timed up and go (TUG), stair climb and descent, and vertical jump. Significant linear relationships were observed between CVs in session 1 and the percentage difference between sessions 1 and 2 for torque at 60, 120, 240 and 360°/s, 6MFWT, TUG, stair climb, and stair descent. The results of this study could be used to establish criteria for determining an acceptably reliable performance in strength and functional tests.

Laser homeostatics on delayed onset muscle soreness

NASA Astrophysics Data System (ADS)

Liu, T. C. Y.; Fu, D. R.; Liu, X. G.; Tian, Z. X.

2011-01-01

Delayed onset muscle soreness (DOMS) and its photobiomodulation were reviewed from the viewpoint of function-specific homeostasis (FSH) in this paper. FSH is a negative-feedback response of a biosystem to maintain the function-specific fluctuations inside the biosystem so that the function is perfectly performed. A stressor may destroy a FSH. A stress is a response of a biosystem to a stressor and may also be in stress-specific homeostasis (StSH). A low level light (LLL) is so defined that it has no effects on a function in its FSH or a stress in its StSH, but it modulate a function far from its FSH or a stress far from its StSH. For DOMS recovery, protein metabolism in the Z-line streaming muscular cell is the essential process, but the inflammation, pain and soreness are non-essential processes. For many DOMS phenomena, protein metabolism in the Z-line streaming muscular cell is in protein metabolism-specific homeostasis (PmSH) so that there are no effects of LLL although the inflammation can be inhibited and the pain can be relieved. An athlete or animal in the dysfunctional conditions such as blood flow restriction and exercise exhaustion is far from PmSH and the protein metabolism can be improved with LLL.

Identification of fuel cycle simulator functionalities for analysis of transition to a new fuel cycle

DOE PAGES

Brown, Nicholas R.; Carlsen, Brett W.; Dixon, Brent W.; ...

2016-06-09

Dynamic fuel cycle simulation tools are intended to model holistic transient nuclear fuel cycle scenarios. As with all simulation tools, fuel cycle simulators require verification through unit tests, benchmark cases, and integral tests. Model validation is a vital aspect as well. Although compara-tive studies have been performed, there is no comprehensive unit test and benchmark library for fuel cycle simulator tools. The objective of this paper is to identify the must test functionalities of a fuel cycle simulator tool within the context of specific problems of interest to the Fuel Cycle Options Campaign within the U.S. Department of Energy smore » Office of Nuclear Energy. The approach in this paper identifies the features needed to cover the range of promising fuel cycle options identified in the DOE-NE Fuel Cycle Evaluation and Screening (E&S) and categorizes these features to facilitate prioritization. Features were categorized as essential functions, integrating features, and exemplary capabilities. One objective of this paper is to propose a library of unit tests applicable to each of the essential functions. Another underlying motivation for this paper is to encourage an international dialog on the functionalities and standard test methods for fuel cycle simulator tools.« less

Properties of genes essential for mouse development

PubMed Central

Kabir, Mitra; Barradas, Ana; Tzotzos, George T.; Hentges, Kathryn E.

2017-01-01

Essential genes are those that are critical for life. In the specific case of the mouse, they are the set of genes whose deletion means that a mouse is unable to survive after birth. As such, they are the key minimal set of genes needed for all the steps of development to produce an organism capable of life ex utero. We explored a wide range of sequence and functional features to characterise essential (lethal) and non-essential (viable) genes in mice. Experimental data curated manually identified 1301 essential genes and 3451 viable genes. Very many sequence features show highly significant differences between essential and viable mouse genes. Essential genes generally encode complex proteins, with multiple domains and many introns. These genes tend to be: long, highly expressed, old and evolutionarily conserved. These genes tend to encode ligases, transferases, phosphorylated proteins, intracellular proteins, nuclear proteins, and hubs in protein-protein interaction networks. They are involved with regulating protein-protein interactions, gene expression and metabolic processes, cell morphogenesis, cell division, cell proliferation, DNA replication, cell differentiation, DNA repair and transcription, cell differentiation and embryonic development. Viable genes tend to encode: membrane proteins or secreted proteins, and are associated with functions such as cellular communication, apoptosis, behaviour and immune response, as well as housekeeping and tissue specific functions. Viable genes are linked to transport, ion channels, signal transduction, calcium binding and lipid binding, consistent with their location in membranes and involvement with cell-cell communication. From the analysis of the composite features of essential and viable genes, we conclude that essential genes tend to be required for intracellular functions, and viable genes tend to be involved with extracellular functions and cell-cell communication. Knowledge of the features that are over-represented in essential genes allows for a deeper understanding of the functions and processes implemented during mammalian development. PMID:28562614

Efficient O(N) integration for all-electron electronic structure calculation using numeric basis functions

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

Havu, V.; Fritz Haber Institute of the Max Planck Society, Berlin; Blum, V.

2009-12-01

We consider the problem of developing O(N) scaling grid-based operations needed in many central operations when performing electronic structure calculations with numeric atom-centered orbitals as basis functions. We outline the overall formulation of localized algorithms, and specifically the creation of localized grid batches. The choice of the grid partitioning scheme plays an important role in the performance and memory consumption of the grid-based operations. Three different top-down partitioning methods are investigated, and compared with formally more rigorous yet much more expensive bottom-up algorithms. We show that a conceptually simple top-down grid partitioning scheme achieves essentially the same efficiency as themore » more rigorous bottom-up approaches.« less

Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.

PubMed

Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

2018-02-07

Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks have not yet been detected. Structural and functional network metrics of regions related to reward, memory, and sensory performance were strongly correlated with the cognitive outcome. The use of animal models is essential for the early identification of these alterations and can contribute to the development of early biomarkers of the disease based on MRI connectomics.

The Essential Gene EMB1611 Maintains Shoot Apical Meristem Function During Arabidopsis Development

USDA-ARS?s Scientific Manuscript database

The Arabidopsis thaliana genome contains hundreds of genes essential for seed development. Because null mutations in these genes cause embryo lethality, their specific molecular and developmental functions are largely unknown. Here, we identify a role for EMB1611/MEE22, an essential gene in Arabidop...

Functional characterization of the essential tail anchor of the herpes simplex virus type 1 nuclear egress protein pUL34.

PubMed

Ott, Melanie; Tascher, Georg; Hassdenteufel, Sarah; Zimmermann, Richard; Haas, Jürgen; Bailer, Susanne M

2011-12-01

Release of herpes simplex virus type 1 (HSV-1) nucleocapsids from the host nucleus relies on the nuclear egress complex consisting of the two essential proteins pUL34 and pUL31. The cytoplasmically exposed N-terminal region of pUL34 interacts with pUL31, while a hydrophobic region followed by a short luminal part mediates membrane association. Based on its domain organization, pUL34 was postulated to be a tail-anchor (TA) protein. We performed a coupled in vitro transcription/translation assay to show that membrane insertion of pUL34 occurs post-translationally. Transient transfection and localization experiments in mammalian cells were combined with HSV-1 bacterial artificial chromosome mutagenesis to reveal the functional properties of the essential pUL34 TA. Our data show that a minimal tail length of 15 residues is sufficient for nuclear envelope targeting and pUL34 function. Permutations of the pUL34 TA with orthologous regions of human cytomegalovirus pUL50 or Epstein-Barr virus pBFRF1 as well as the heterologous HSV-1 TA proteins pUL56 or pUS9 or the cellular TA proteins Bcl-2 and Vamp2 revealed that nuclear egress tolerates TAs varying in sequence and hydrophobicity, while a non-α-helical membrane anchor failed to complement the pUL34 function. In conclusion, this study provides the first mechanistic insights into the particular role of the TA of pUL34 in membrane curving and capsid egress from the host nucleus.

Adolescent Anorexia Nervosa: cognitive performance after weight recovery.

PubMed

Lozano-Serra, Estefanía; Andrés-Perpiña, Susana; Lázaro-García, Luisa; Castro-Fornieles, Josefina

2014-01-01

Although there is no definitive consensus on the impairment of neuropsychological functions, most studies of adults with Anorexia Nervosa (AN) find impaired functioning in cognitive domains such as visual-spatial abilities. The objective of this study is to assess the cognitive functions in adolescents with AN before and after weight recovery and to explore the relationship between cognitive performance and menstruation. Twenty-five female adolescents with AN were assessed by a neuropsychological battery while underweight and then following six months of treatment and weight recovery. Twenty-six healthy female subjects of a similar age were also evaluated at both time points. Underweight patients with AN showed worse cognitive performance than control subjects in immediate recall, organization and time taken to copy the Rey's Complex Figure Test (RCFT). After weight recovery, AN patients presented significant improvements in all tests, and differences between patients and controls disappeared. Patients with AN and persistence of amenorrhea at follow-up (n=8) performed worse on Block Design, delayed recall of Visual Reproduction and Stroop Test than patients with resumed menstruation (n=14) and the control group, though the two AN groups were similar in body mass index, age and psychopathological scale scores. Weight recovery improves cognitive functioning in adolescents with AN. The normalization of neuropsychological performance is better in patients who have recovered at least one menstrual cycle. The normalization of hormonal function seems to be essential for the normalization of cognitive performance, even in adolescents with a very short recovery time. © 2013.

Calf Strength Loss During Mechanical Unloading: Does It Matter?

NASA Technical Reports Server (NTRS)

English, K. L.; Mulavara, A.; Bloomberg, J.; Ploutz-Snyder, LL

2016-01-01

During the mechanical unloading of spaceflight and its ground-based analogs, muscle mass and muscle strength of the calf are difficult to preserve despite exercise countermeasures that effectively protect these parameters in the thigh. It is unclear what effects these local losses have on balance and whole body function which will be essential for successful performance of demanding tasks during future exploration missions.

Space Environmental Effects (SEE) Testing Capability: NASA/Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

DeWittBurns, H.; Crave, Paul; Finckenor, Miria; Finchum, Charles; Nehls, Mary; Schneider, Todd; Vaughn, Jason

2012-01-01

Understanding the effects of the space environment on materials and systems is fundamental and essential for mission success. If not properly understood and designed for, the space environment can lead to materials degradation, reduction of functional lifetime, and system failure. Ground based testing is critical in predicting performance NASA/MSFC's expertise and capabilities make up the most complete SEE testing capability available.

Modeling the User for Education, Training, and Performance Aiding

DTIC Science & Technology

2004-04-01

It is a fact both obvious and frequently neglected that human competence, which is a product of human cognition, is essential to every military...approach has been called an instructional imperative and an economic impossibility. It would be maximally effective but remains unaffordable because...based on reflection) all producing different perceptual, memory, and motor functions. ( Sloman , 2001; 2003) (http://www.cs.b ham.ac.uk/~axs

Job retention and breast cancer: employee perspectives and implications for rehabilitation planning.

PubMed

Rumrill, P D; Nutter, D L; Hennessey, M; Ware, M E

1998-01-01

The article presents four case studies of employed women who have had breast cancer. Specifically, the authors examine respondents' career maintenance concerns in the areas of (a) worksite accessibility, (b) performance of essential job functions, (c) job mastery, and (d) job satisfaction. Post-employment strategies are presented to assist rehabilitation professionals in meeting the on-the-job needs of women with breast cancer.

Skilled Birth Attendants: who is who? A descriptive study of definitions and roles from nine Sub Saharan African countries.

PubMed

Adegoke, Adetoro; Utz, Bettina; Msuya, Sia E; van den Broek, Nynke

2012-01-01

Availability of a Skilled Birth Attendant (SBA) during childbirth is a key indicator for MDG5 and a strategy for reducing maternal and neonatal mortality in Africa. There is limited information on how SBAs and their functions are defined. The aim of this study was to map the cadres of health providers considered SBAs in Sub Saharan Africa (SSA); to describe which signal functions of Essential Obstetric Care (EmOC) they perform and assess whether they are legislated to perform these functions. Key personnel in the Ministries of Health, teaching institutions, referral, regional and district hospitals completed structured questionnaires in nine SSA countries in 2009-2011. A total of 21 different cadres of health care providers (HCP) were reported to be SBA. Type and number of EmOC signal functions reported to be provided, varied substantially between cadres and countries. Parenteral antibiotics, uterotonic drugs and anticonvulsants were provided by most SBAs. Removal of retained products of conception and assisted vaginal delivery were the least provided signal functions. Except for the cadres of obstetricians, medical doctors and registered nurse-midwives, there was lack of clarity regarding signal functions reported to be performed and whether they were legislated to perform these. This was particularly for manual removal of placenta, removal of retained products and assisted vaginal delivery. In some countries, cadres not considered SBA performed deliveries and provided EmOC signal functions. In other settings, cadres reported to be SBA were able to but not legislated to perform key EmOC signal functions. Comparison of cadres of HCPs reported to be SBA across countries is difficult because of lack of standardization in names, training, and functions performed. There is a need for countries to develop clear guidelines defining who is a SBA and which EmOC signal functions each cadre of HCP is expected to provide.

The effect of music performance on the transcriptome of professional musicians.

PubMed

Kanduri, Chakravarthi; Kuusi, Tuire; Ahvenainen, Minna; Philips, Anju K; Lähdesmäki, Harri; Järvelä, Irma

2015-03-25

Music performance by professional musicians involves a wide-spectrum of cognitive and multi-sensory motor skills, whose biological basis is unknown. Several neuroscientific studies have demonstrated that the brains of professional musicians and non-musicians differ structurally and functionally and that musical training enhances cognition. However, the molecules and molecular mechanisms involved in music performance remain largely unexplored. Here, we investigated the effect of music performance on the genome-wide peripheral blood transcriptome of professional musicians by analyzing the transcriptional responses after a 2-hr concert performance and after a 'music-free' control session. The up-regulated genes were found to affect dopaminergic neurotransmission, motor behavior, neuronal plasticity, and neurocognitive functions including learning and memory. Particularly, candidate genes such as SNCA, FOS and DUSP1 that are involved in song perception and production in songbirds, were identified, suggesting an evolutionary conservation in biological processes related to sound perception/production. Additionally, modulation of genes related to calcium ion homeostasis, iron ion homeostasis, glutathione metabolism, and several neuropsychiatric and neurodegenerative diseases implied that music performance may affect the biological pathways that are otherwise essential for the proper maintenance of neuronal function and survival. For the first time, this study provides evidence for the candidate genes and molecular mechanisms underlying music performance.

Spectraplakins promote microtubule-mediated axonal growth by functioning as structural MAPs and EB1-dependent +TIPs

PubMed Central

Alves-Silva, J.; Sánchez-Soriano, N.; Beaven, R.; Klein, M.; Parkin, J.; Millard, T.H.; Bellen, H. J; Venken, K. J.T.; Ballestrem, C.; Kammerer, R.A.; Prokop, A.

2013-01-01

The correct outgrowth of axons is essential for the development and regeneration of nervous systems. Axon growth is primarily driven by microtubules. Key regulators of microtubules in this context are the spectraplakins, a family of evolutionarily conserved actin-microtubule linkers. Loss of function of the mouse spectraplakin ACF7 or of its close Drosophila homologue Short stop/Shot similarly cause severe axon shortening and microtubule disorganisation. How spectraplakins perform these functions is not known. Here we show that axonal growth promoting roles of Shot require interaction with EB1 (End binding protein) at polymerising plus ends of microtubules. We show that binding of Shot to EB1 requires SxIP motifs in Shot’s carboxyterminal tail (Ctail), mutations of these motifs abolish Shot functions in axonal growth, loss of EB1 function phenocopies Shot loss, and genetic interaction studies reveal strong functional links between Shot and EB1 in axonal growth and microtubule organisation. In addition, we report that Shot localises along microtubule shafts and stabilises them against pharmacologically induced depolymerisation. This function is EB1-independent but requires net positive charges within Ctail which essentially contribute to the microtubule shaft association of Shot. Therefore, spectraplakins are true members of two important classes of neuronal microtubule regulating proteins: +TIPs (plus end regulators) and structural MAPs (microtubule associated proteins). From our data we deduce a model that relates the different features of the spectraplakin carboxy-terminus to the two functions of Shot during axonal growth. PMID:22764224

Use of tissue adhesive as a field expedient barrier dressing for hand wounds in disaster responders.

PubMed

Levy, Matthew J; Tang, Nelson

2014-02-01

Injuries sustained by disaster responders can impede the affected individuals' ability to perform critical functions and often require the redirection of already scarce resources. Soft-tissue injuries to the hand are commonly experienced by disaster workers and even seemingly mild lacerations can pose the potential for significant complications in such hazard-filled environments. In this report, the authors describe their experience utilizing tissue adhesive to create a functional and effective barrier dressing for a hand injury sustained by a responder at the West, Texas USA fertilizer plant explosion. This technique of wound management allowed the patient to continue performing essential onsite functions for a sustained period following the explosion and the subsequent investigative processes. At the 30-day follow-up, the wound was well healed and without complications. This technique proved to be a valuable method of field expedient wound management and is worthy of consideration in similar future circumstances.

Defining and Assessing Public Health Functions: A Global Analysis.

PubMed

Martin-Moreno, Jose M; Harris, Meggan; Jakubowski, Elke; Kluge, Hans

2016-01-01

Given the broad scope and intersectoral nature of public health structures and practices, there are inherent difficulties in defining which services fall under the public health remit and in assessing their capacity and performance. The aim of this study is to analyze how public health functions and practice have been defined and operationalized in different countries and regions around the world, with a specific focus on assessment tools that have been developed to evaluate the performance of essential public health functions, services, and operations. Our review has identified nearly 100 countries that have carried out assessments, using diverse analytical and methodological approaches. The assessment processes have evolved quite differently according to administrative arrangements and resource availability, but some key contextual factors emerge that seem to favor policy-oriented follow-up. These include local ownership of the assessment process, policymakers' commitment to reform, and expert technical advice for implementation.

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities.

PubMed

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-09-30

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal-occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention.

Integrated in silico analyses of regulatory and metabolic networks of Synechococcus sp. PCC 7002 reveal relationships between gene centrality and essentiality

DOE PAGES

Song, Hyun-Seob; McClure, Ryan S.; Bernstein, Hans C.; ...

2015-03-27

Cyanobacteria dynamically relay environmental inputs to intracellular adaptations through a coordinated adjustment of photosynthetic efficiency and carbon processing rates. The output of such adaptations is reflected through changes in transcriptional patterns and metabolic flux distributions that ultimately define growth strategy. To address interrelationships between metabolism and regulation, we performed integrative analyses of metabolic and gene co-expression networks in a model cyanobacterium, Synechococcus sp. PCC 7002. Centrality analyses using the gene co-expression network identified a set of key genes, which were defined here as ‘topologically important.’ Parallel in silico gene knock-out simulations, using the genome-scale metabolic network, classified what we termedmore » as ‘functionally important’ genes, deletion of which affected growth or metabolism. A strong positive correlation was observed between topologically and functionally important genes. Functionally important genes exhibited variable levels of topological centrality; however, the majority of topologically central genes were found to be functionally essential for growth. Subsequent functional enrichment analysis revealed that both functionally and topologically important genes in Synechococcus sp. PCC 7002 are predominantly associated with translation and energy metabolism, two cellular processes critical for growth. This research demonstrates how synergistic network-level analyses can be used for reconciliation of metabolic and gene expression data to uncover fundamental biological principles.« less

Integrated in silico analyses of regulatory and metabolic networks of Synechococcus sp. PCC 7002 reveal relationships between gene centrality and essentiality

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

Song, Hyun-Seob; McClure, Ryan S.; Bernstein, Hans C.

Cyanobacteria dynamically relay environmental inputs to intracellular adaptations through a coordinated adjustment of photosynthetic efficiency and carbon processing rates. The output of such adaptations is reflected through changes in transcriptional patterns and metabolic flux distributions that ultimately define growth strategy. To address interrelationships between metabolism and regulation, we performed integrative analyses of metabolic and gene co-expression networks in a model cyanobacterium, Synechococcus sp. PCC 7002. Centrality analyses using the gene co-expression network identified a set of key genes, which were defined here as ‘topologically important.’ Parallel in silico gene knock-out simulations, using the genome-scale metabolic network, classified what we termedmore » as ‘functionally important’ genes, deletion of which affected growth or metabolism. A strong positive correlation was observed between topologically and functionally important genes. Functionally important genes exhibited variable levels of topological centrality; however, the majority of topologically central genes were found to be functionally essential for growth. Subsequent functional enrichment analysis revealed that both functionally and topologically important genes in Synechococcus sp. PCC 7002 are predominantly associated with translation and energy metabolism, two cellular processes critical for growth. This research demonstrates how synergistic network-level analyses can be used for reconciliation of metabolic and gene expression data to uncover fundamental biological principles.« less

Frontal-posterior coherence and cognitive function in older adults.

PubMed

Fleck, Jessica I; Kuti, Julia; Brown, Jessica; Mahon, Jessica R; Gayda-Chelder, Christine

2016-12-01

The reliable measurement of brain health and cognitive function is essential in mitigating the negative effects associated with cognitive decline through early and accurate diagnosis of change. The present research explored the relationship between EEG coherence for electrodes within frontal and posterior regions, as well as coherence between frontal and posterior electrodes and performance on standard neuropsychological measures of memory and executive function. EEG coherence for eyes-closed resting-state EEG activity was calculated for delta, theta, alpha, beta, and gamma frequency bands. Participants (N=66; mean age=67.15years) had their resting-state EEGs recorded and completed a neuropsychological battery that assessed memory and executive function, two cognitive domains that are significantly affected during aging. A positive relationship was observed between coherence within the frontal region and performance on measures of memory and executive function for delta and beta frequency bands. In addition, an inverse relationship was observed for coherence between frontal and posterior electrode pairs, particularly within the theta frequency band, and performance on Digit Span Sequencing, a measure of working memory. The present research supports a more substantial link between EEG coherence, rather than spectral power, and cognitive function. Continued study in this area may enable EEG to be applied broadly as a diagnostic measure of cognitive ability. Copyright © 2016 Elsevier B.V. All rights reserved.

Spontaneous improvement in oculomotor function of children with cerebral palsy.

PubMed

Ego, Caroline; Orban de Xivry, Jean-Jacques; Nassogne, Marie-Cécile; Yüksel, Demet; Lefèvre, Philippe

2014-11-20

Eye movements are essential to get a clear vision of moving objects. In the present study, we assessed quantitatively the oculomotor deficits of children with cerebral palsy (CP). We recorded eye movements of 51 children with cerebral palsy (aged 5-16 years) with relatively mild motor impairment and compared their performance with age-matched control and premature children. Overall eye movements of children with CP are unexpectedly close to those of controls even though some oculomotor parameters are biased by the side of hemiplegia. Importantly, the difference in performance between children with CP and controls decreases with age, demonstrating that the oculomotor function of children with CP develops as fast as or even faster than controls for some visual tracking parameters. That is, oculomotor function spontaneously improves over the course of childhood. This evolution highlights the ability of lesioned brain of children with CP to compensate for impaired motor function beyond what would be achieved by normal development on its own. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of pole zero location on system dynamics of boost converter for micro grid

NASA Astrophysics Data System (ADS)

Lavanya, A.; Vijayakumar, K.; Navamani, J. D.; Jayaseelan, N.

2018-04-01

Green clean energy like photo voltaic, wind energy, fuel cell can be brought together by microgrid.For low voltage sources like photovoltaic cell boost converter is very much essential. This paper explores the dynamic analysis of boost converter in a continuous conduction mode (CCM). The transient performance and stability analysis is carried out in this paper using time domain analysis and frequency domain analysis techniques. Boost converter is simulated using both PSIM and MATLAB software. Furthermore, state space model obtained and the transfer function is derived. The converter behaviour when a step input is applied is analyzed and stability of the converter is analyzed from bode plot frequency for open loop. Effect of the locations of poles and zeros in the transfer function of boost converter and how the performance parameters are affected is discussed in this paper. Closed loop performance with PI controller is also analyzed for boost converter.

From service provision to function based performance - perspectives on public health systems from the USA and Israel

PubMed Central

2012-01-01

If public health agencies are to fulfill their overall mission, they need to have defined measurable targets and should structure services to reach these targets, rather than offer a combination of ill-targeted programs. In order to do this, it is essential that there be a clear definition of what public health should do- a definition that does not ebb and flow based upon the prevailing political winds, but rather is based upon professional standards and measurements. The establishment of the Essential Public Health Services framework in the U.S.A. was a major move in that direction, and the model, or revisions of the model, have been adopted beyond the borders of the U.S. This article reviews the U.S. public health system, the needs and processes which brought about the development of the 10 Essential Public Health Services (EPHS), and historical and contemporary applications of the model. It highlights the value of establishing a common delineation of public health activities such as those contained in the EPHS, and explores the validity of using the same process in other countries through a discussion of the development in Israel of a similar model, the 10 Public Health Essential Functions (PHEF), that describes the activities of Israel’s public health system. The use of the same process and framework to develop similar yet distinct frameworks suggests that the process has wide applicability, and may be beneficial to any public health system. Once a model is developed, it can be used to measure public health performance and improve the quality of services delivered through the development of standards and measures based upon the model, which could, ultimately, improve the health of the communities that depend upon public health agencies to protect their well-being. PMID:23181452

Chemical Composition of Essential Oils from Thymus vulgaris, Cymbopogon citratus, and Rosmarinus officinalis, and Their Effects on the HIV-1 Tat Protein Function.

PubMed

Feriotto, Giordana; Marchetti, Nicola; Costa, Valentina; Beninati, Simone; Tagliati, Federico; Mischiati, Carlo

2018-02-01

New drugs would be beneficial to fight resistant HIV strains, in particular those capable of interfering with essential viral functions other than those targeted by highly active antiretroviral therapy drugs. Despite the central role played by Tat protein in HIV transcription, a search for vegetable extracts able to hamper this important viral function was never carried out. In this work, we evaluated the chemical composition and possible interference of essential oil from Thymus vulgaris, Cananga odorata, Cymbopogon citratus, and Rosmarinus officinalis with the Tat/TAR-RNA interaction and with Tat-induced HIV-1 LTR transcription. GC/MS Analysis demonstrated the biodiversity of herbal species translated into essential oils composed of different blends of terpenes. In all of them, 4 - 6 constituents represent from 81.63% to 95.19% of the total terpenes. Essential oils of Thymus vulgaris, Cymbopogon citratus, and Rosmarinus officinalis were active in interfering with Tat functions, encouraging further studies to identify single terpenes responsible for the antiviral activity. In view of the quite different composition of these essential oils, we concluded that their interference on Tat function depends on specific terpene or a characteristic blend. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain-8 expression and cranial neural crest cell migration

PubMed Central

Cousin, Hélène; Abbruzzese, Genevieve; Kerdavid, Erin; Gaultier, Alban; Alfandari, Dominique

2011-01-01

Summary ADAMs are transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. The cytoplasmic domain of ADAMs can regulate the proteolytic activity by controlling the subcellular localization and/or the activation of the protease domain. Here we show that the cytoplasmic domain of ADAM13 is cleaved and translocates into the nucleus. Preventing this translocation renders the protein incapable of promoting cranial neural crest (CNC) cell migration in vivo, without affecting its proteolytic activity. In addition, the cytoplasmic domain of ADAM13 regulates the expression of multiple genes in CNC, including the protease Calpain8-a. Restoring the expression of Calpain8-a is sufficient to rescue CNC migration in the absence of the ADAM13 cytoplasmic domain. This study shows that the cytoplasmic domain of ADAM metalloproteases can perform essential functions in the nucleus of cells and may contribute substantially to the overall function of the protein. PMID:21316592

Trastuzumab Alters the Expression of Genes Essential for Cardiac Function and Induces Ultrastructural Changes of Cardiomyocytes in Mice

PubMed Central

ElZarrad, M. Khair; Mukhopadhyay, Partha; Mohan, Nishant; Hao, Enkui; Dokmanovic, Milos; Hirsch, Dianne S.; Shen, Yi; Pacher, Pal; Wu, Wen Jin

2013-01-01

Treatment with trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), very successfully improves outcomes for women with HER2-positive breast cancer. However, trastuzumab treatment was recently linked to potentially irreversible serious cardiotoxicity, the mechanisms of which are largely elusive. This study reports that trastuzumab significantly alters the expression of myocardial genes essential for DNA repair, cardiac and mitochondrial functions, which is associated with impaired left ventricular performance in mice coupled with significant ultrastructural alterations in cardiomyocytes revealed by electron microscopy. Furthermore, trastuzumab treatment also promotes oxidative stress and apoptosis in myocardium of mice, and elevates serum levels of cardiac troponin-I (cTnI) and cardiac myosin light chain-1 (cMLC1). The elevated serum levels of cMLC1 in mice treated with trastuzumab highlights the potential that cMLC1 could be a useful biomarker for trastuzumab-induced cardiotoxicity. PMID:24255707

Systematic bacterialization of yeast genes identifies a near-universally swappable pathway

PubMed Central

Kachroo, Aashiq H; Laurent, Jon M; Akhmetov, Azat; Szilagyi-Jones, Madelyn; McWhite, Claire D; Zhao, Alice; Marcotte, Edward M

2017-01-01

Eukaryotes and prokaryotes last shared a common ancestor ~2 billion years ago, and while many present-day genes in these lineages predate this divergence, the extent to which these genes still perform their ancestral functions is largely unknown. To test principles governing retention of ancient function, we asked if prokaryotic genes could replace their essential eukaryotic orthologs. We systematically replaced essential genes in yeast by their 1:1 orthologs from Escherichia coli. After accounting for mitochondrial localization and alternative start codons, 31 out of 51 bacterial genes tested (61%) could complement a lethal growth defect and replace their yeast orthologs with minimal effects on growth rate. Replaceability was determined on a pathway-by-pathway basis; codon usage, abundance, and sequence similarity contributed predictive power. The heme biosynthesis pathway was particularly amenable to inter-kingdom exchange, with each yeast enzyme replaceable by its bacterial, human, or plant ortholog, suggesting it as a near-universally swappable pathway. DOI: http://dx.doi.org/10.7554/eLife.25093.001 PMID:28661399

Yeast ERV2p is the first microsomal FAD-linked sulfhydryl oxidase of the Erv1p/Alrp protein family.

PubMed

Gerber, J; Mühlenhoff, U; Hofhaus, G; Lill, R; Lisowsky, T

2001-06-29

Saccharomyces cerevisiae Erv2p was identified previously as a distant homologue of Erv1p, an essential mitochondrial protein exhibiting sulfhydryl oxidase activity. Expression of the ERV2 (essential for respiration and vegetative growth 2) gene from a high-copy plasmid cannot substitute for the lack of ERV1, suggesting that the two proteins perform nonredundant functions. Here, we show that the deletion of the ERV2 gene or the depletion of Erv2p by regulated gene expression is not associated with any detectable growth defects. Erv2p is located in the microsomal fraction, distinguishing it from the mitochondrial Erv1p. Despite their distinct subcellular localization, the two proteins exhibit functional similarities. Both form dimers in vivo and in vitro, contain a conserved YPCXXC motif in their carboxyl-terminal part, bind flavin adenine dinucleotide (FAD) as a cofactor, and catalyze the formation of disulfide bonds in protein substrates. The catalytic activity, the ability to form dimers, and the binding of FAD are associated with the carboxyl-terminal domain of the protein. Our findings identify Erv2p as the first microsomal member of the Erv1p/Alrp protein family of FAD-linked sulfhydryl oxidases. We propose that Erv2p functions in the generation of microsomal disulfide bonds acting in parallel with Ero1p, the essential, FAD-dependent oxidase of protein disulfide isomerase.

Optical processing for future computer networks

NASA Technical Reports Server (NTRS)

Husain, A.; Haugen, P. R.; Hutcheson, L. D.; Warrior, J.; Murray, N.; Beatty, M.

1986-01-01

In the development of future data management systems, such as the NASA Space Station, a major problem represents the design and implementation of a high performance communication network which is self-correcting and repairing, flexible, and evolvable. To obtain the goal of designing such a network, it will be essential to incorporate distributed adaptive network control techniques. The present paper provides an outline of the functional and communication network requirements for the Space Station data management system. Attention is given to the mathematical representation of the operations being carried out to provide the required functionality at each layer of communication protocol on the model. The possible implementation of specific communication functions in optics is also considered.

Aeroelastic modeling for the FIT (Functional Integration Technology) team F/A-18 simulation

NASA Technical Reports Server (NTRS)

Zeiler, Thomas A.; Wieseman, Carol D.

1989-01-01

As part of Langley Research Center's commitment to developing multidisciplinary integration methods to improve aerospace systems, the Functional Integration Technology (FIT) team was established to perform dynamics integration research using an existing aircraft configuration, the F/A-18. An essential part of this effort has been the development of a comprehensive simulation modeling capability that includes structural, control, and propulsion dynamics as well as steady and unsteady aerodynamics. The structural and unsteady aerodynamics contributions come from an aeroelastic mode. Some details of the aeroelastic modeling done for the Functional Integration Technology (FIT) team research are presented. Particular attention is given to work done in the area of correction factors to unsteady aerodynamics data.

Impact of oral supplementation of Glutamate and GABA on memory performance and neurochemical profile in hippocampus of rats.

PubMed

Tabassum, Saiqa; Ahmad, Saara; Madiha, Syeda; Khaliq, Saima; Shahzad, Sidrah; Batool, Zehra; Haider, Saida

2017-05-01

Glutamate (GLU) and gamma-amino butyric acid (GABA) are essential amino acids (AA) for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water (control group) or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests (Novel object recognition test, Morris water maze, Passive avoidance test) measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine (ACh) were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance.

Membrane-Based Functions in the Origin of Cellular Life

NASA Technical Reports Server (NTRS)

Chipot, Christophe; New, Michael H.; Schweighofer, Karl; Pohorille, Andrew; Wilson, Michael A.

1999-01-01

Our objective is to help explain how the earliest ancestors of contemporary cells (protocells) performed their essential functions employing only the molecules available in the protobiological milieu. Our hypothesis is that vesicles, built of amphiphilic, membrane-forming materials, emerged early in protobiological evolution and served as precursors to protocells. We further assume that the cellular functions associated with contemporary membranes, such as capturing and, transducing of energy, signaling, or sequestering organic molecules and ions, evolved in these membrane environments. An alternative hypothesis is that these functions evolved in different environments and were incorporated into membrane-bound structures at some later stage of evolution. We focus on the application of the fundamental principles of physics and chemistry to determine how they apply to the formation of a primitive, functional cell. Rather than attempting to develop specific models for cellular functions and to identify the origin of the molecules which perform these functions, our goal is to define the structural and energetic conditions that any successful model must fulfill, therefore providing physico-chemical boundaries for these models. We do this by carrying out large-scale, molecular level computer simulations on systems of interest.

Automation of reliability evaluation procedures through CARE - The computer-aided reliability estimation program.

NASA Technical Reports Server (NTRS)

Mathur, F. P.

1972-01-01

Description of an on-line interactive computer program called CARE (Computer-Aided Reliability Estimation) which can model self-repair and fault-tolerant organizations and perform certain other functions. Essentially CARE consists of a repository of mathematical equations defining the various basic redundancy schemes. These equations, under program control, are then interrelated to generate the desired mathematical model to fit the architecture of the system under evaluation. The mathematical model is then supplied with ground instances of its variables and is then evaluated to generate values for the reliability-theoretic functions applied to the model.

Energy acceptance and on momentum aperture optimization for the Sirius project

NASA Astrophysics Data System (ADS)

Dester, P. S.; Sá, F. H.; Liu, L.

2017-07-01

A fast objective function to calculate Touschek lifetime and on momentum aperture is essential to explore the vast search space of strength of quadrupole and sextupole families in Sirius. Touschek lifetime is estimated by using the energy aperture (dynamic and physical), RF system parameters and driving terms. Non-linear induced betatron oscillations are considered to determine the energy aperture. On momentum aperture is estimated by using a chaos indicator and resonance crossing considerations. Touschek lifetime and on momentum aperture constitute the objective function, which was used in a multi-objective genetic algorithm to perform an optimization for Sirius.

Complementary Information Derived from CRISPR Cas9 Mediated Gene Deletion and Suppression. | Office of Cancer Genomics

Cancer.gov

CRISPR-Cas9 provides the means to perform genome editing and facilitates loss-of-function screens. However, we and others demonstrated that expression of the Cas9 endonuclease induces a gene-independent response that correlates with the number of target sequences in the genome. An alternative approach to suppressing gene expression is to block transcription using a catalytically inactive Cas9 (dCas9). Here we directly compare genome editing by CRISPR-Cas9 (cutting, CRISPRc) and gene suppression using KRAB-dCas9 (CRISPRi) in loss-of-function screens to identify cell essential genes.

Higher Order Heavy Quark Corrections to Deep-Inelastic Scattering

NASA Astrophysics Data System (ADS)

Blümlein, Johannes; DeFreitas, Abilio; Schneider, Carsten

2015-04-01

The 3-loop heavy flavor corrections to deep-inelastic scattering are essential for consistent next-to-next-to-leading order QCD analyses. We report on the present status of the calculation of these corrections at large virtualities Q2. We also describe a series of mathematical, computer-algebraic and combinatorial methods and special function spaces, needed to perform these calculations. Finally, we briefly discuss the status of measuring αs (MZ), the charm quark mass mc, and the parton distribution functions at next-to-next-to-leading order from the world precision data on deep-inelastic scattering.

VeriClick: an efficient tool for table format verification

NASA Astrophysics Data System (ADS)

Nagy, George; Tamhankar, Mangesh

2012-01-01

The essential layout attributes of a visual table can be defined by the location of four critical grid cells. Although these critical cells can often be located by automated analysis, some means of human interaction is necessary for correcting residual errors. VeriClick is a macro-enabled spreadsheet interface that provides ground-truthing, confirmation, correction, and verification functions for CSV tables. All user actions are logged. Experimental results of seven subjects on one hundred tables suggest that VeriClick can provide a ten- to twenty-fold speedup over performing the same functions with standard spreadsheet editing commands.

Teaming up to crack innovation and enterprise integration.

PubMed

Cash, James I; Earl, Michael J; Morison, Robert

2008-11-01

In the continuing quest for business growth, many CEOs are turning to their CIOs and IT organizations because technology is essential to two compelling sources of growth: innovation and integration. Innovation, of course, is doing new things that customers ultimately appreciate and value--not only developing new generations of products, services, channels, and customer experience but also conceiving new business processes and models. Integration is making the multiple units, functions, and sites of large organizations work together to increase capacity, improve performance, lower cost structure, and discover opportunities for improvement that don't appear until you look across functions.

Systems Design Factors: The Essential Ingredients of System Design, Version 0.4

DTIC Science & Technology

1994-03-18

Reliability Function). 4. Barry . W. Johnson, Design and Analysis of Fault Tolerant Digital Systems, p. 4, Addison- Wesley Publishing Company, 1985. METRICS...the system was performing correctly at time t. The unreliability is often referred to as the probability of failure. SOURCE: 1. Barry W. Johnson...Systems Enuineerinf. 3. Barry W. Johnson, Design and Analysis of Fault Tolerant Digital Systems, Addison-Wesley Publishing Company, 1985, p. 5

Loss of function of Saccharomyces cerevisiae kinesin-related CIN8 and KIP1 is suppressed by KAR3 motor domain mutations.

PubMed

Hoyt, M A; He, L; Totis, L; Saunders, W S

1993-09-01

The kinesin-related products of the CIN8 and KIP1 genes of Saccharomyces cerevisiae redundantly perform an essential function in mitosis. The action of either gene-product is required for an outwardly directed force that acts upon the spindle poles. We have selected mutations that suppress the temperature-sensitivity of a cin8-temperature-sensitive kip1-delta strain. The extragenic suppressors analyzed were all found to be alleles of the KAR3 gene. KAR3 encodes a distinct kinesin-related protein whose action antagonizes Cin8p/Kip1p function. All seven alleles analyzed were altered within the region of KAR3 that encodes the putative force-generating (or "motor") domain. These mutations also suppressed the inviability associated with the cin8-delta kip1-delta genotype, a property not shared by a deletion of KAR3. Other properties of the suppressing alleles revealed that they were not null for function. Six of the seven were unaffected for the essential karyogamy and meiosis properties of KAR3 and the seventh was dominant for the suppressing trait. Our findings suggest that despite an antagonistic relationship between Cin8p/Kip1p and Kar3p, aspects of their mitotic roles may be similar.

Characterization of the functional interactions of plastidial starch phosphorylase and starch branching enzymes from rice endosperm during reserve starch biosynthesis.

PubMed

Nakamura, Yasunori; Ono, Masami; Sawada, Takayuki; Crofts, Naoko; Fujita, Naoko; Steup, Martin

2017-11-01

Functional interactions of plastidial phosphorylase (Pho1) and starch branching enzymes (BEs) from the developing rice endosperm are the focus of this study. In the presence of both Pho1 and BE, the same branched primer molecule is elongated and further branched almost simultaneously even at very low glucan concentrations present in the purified enzyme preparations. By contrast, in the absence of any BE, glucans are not, to any significant extent, elongated by Pho1. Based on our in vitro data, in the developing rice endosperm, Pho1 appears to be weakly associated with any of the BE isozymes. By using fluorophore-labeled malto-oligosaccharides, we identified maltose as the smallest possible primer for elongation by Pho1. Linear dextrins act as carbohydrate substrates for BEs. By functionally interacting with a BE, Pho1 performs two essential functions during the initiation of starch biosynthesis in the rice endosperm: First, it elongates maltodextrins up to a degree of polymerization of at least 60. Second, by closely interacting with BEs, Pho1 is able to elongate branched glucans efficiently and thereby synthesizes branched carbohydrates essential for the initiation of amylopectin biosynthesis. Copyright © 2017 Elsevier B.V. All rights reserved.

The RtcB RNA ligase is an essential component of the metazoan unfolded protein response.

PubMed

Kosmaczewski, Sara Guckian; Edwards, Tyson James; Han, Sung Min; Eckwahl, Matthew J; Meyer, Benjamin Isaiah; Peach, Sally; Hesselberth, Jay R; Wolin, Sandra L; Hammarlund, Marc

2014-12-01

RNA ligation can regulate RNA function by altering RNA sequence, structure and coding potential. For example, the function of XBP1 in mediating the unfolded protein response requires RNA ligation, as does the maturation of some tRNAs. Here, we describe a novel in vivo model in Caenorhabditis elegans for the conserved RNA ligase RtcB and show that RtcB ligates the xbp-1 mRNA during the IRE-1 branch of the unfolded protein response. Without RtcB, protein stress results in the accumulation of unligated xbp-1 mRNA fragments, defects in the unfolded protein response, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves, and RtcB mutants have defects in growth and lifespan that can be bypassed by expression of pre-spliced tRNAs. In addition, animals that lack RtcB have defects that are independent of tRNA maturation and the unfolded protein response. Thus, RNA ligation by RtcB is required for the function of multiple endogenous target RNAs including both xbp-1 and tRNAs. RtcB is uniquely capable of performing these ligation functions, and RNA ligation by RtcB mediates multiple essential processes in vivo. © 2014 The Authors.

The RtcB RNA ligase is an essential component of the metazoan unfolded protein response

PubMed Central

Kosmaczewski, Sara Guckian; Edwards, Tyson James; Han, Sung Min; Eckwahl, Matthew J; Meyer, Benjamin Isaiah; Peach, Sally; Hesselberth, Jay R; Wolin, Sandra L; Hammarlund, Marc

2014-01-01

RNA ligation can regulate RNA function by altering RNA sequence, structure and coding potential. For example, the function of XBP1 in mediating the unfolded protein response requires RNA ligation, as does the maturation of some tRNAs. Here, we describe a novel in vivo model in Caenorhabditis elegans for the conserved RNA ligase RtcB and show that RtcB ligates the xbp-1 mRNA during the IRE-1 branch of the unfolded protein response. Without RtcB, protein stress results in the accumulation of unligated xbp-1 mRNA fragments, defects in the unfolded protein response, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves, and RtcB mutants have defects in growth and lifespan that can be bypassed by expression of pre-spliced tRNAs. In addition, animals that lack RtcB have defects that are independent of tRNA maturation and the unfolded protein response. Thus, RNA ligation by RtcB is required for the function of multiple endogenous target RNAs including both xbp-1 and tRNAs. RtcB is uniquely capable of performing these ligation functions, and RNA ligation by RtcB mediates multiple essential processes in vivo. Subject Categories Protein Biosynthesis & Quality Control; RNA Biology PMID:25366321

Fission yeast Lem2 and Man1 perform fundamental functions of the animal cell nuclear lamina.

PubMed

Gonzalez, Yanira; Saito, Akira; Sazer, Shelley

2012-01-01

In animal cells the nuclear lamina, which consists of lamins and lamin-associated proteins, serves several functions: it provides a structural scaffold for the nuclear envelope and tethers proteins and heterochromatin to the nuclear periphery. In yeast, proteins and large heterochromatic domains including telomeres are also peripherally localized, but there is no evidence that yeast have lamins or a fibrous nuclear envelope scaffold. Nonetheless, we found that the Lem2 and Man1 proteins of the fission yeast Schizosaccharomyces pombe, evolutionarily distant relatives of the Lap2/Emerin/Man1 (LEM) sub-family of animal cell lamin-associated proteins, perform fundamental functions of the animal cell lamina. These integral inner nuclear membrane localized proteins, with nuclear localized DNA binding Helix-Extension-Helix (HEH) domains, impact nuclear envelope structure and integrity, are essential for the enrichment of telomeres at the nuclear periphery and by means of their HEH domains anchor chromatin, most likely transcriptionally repressed heterochromatin, to the nuclear periphery. These data indicate that the core functions of the nuclear lamina are conserved between fungi and animal cells and can be performed in fission yeast, without lamins or other intermediate filament proteins.

Improving health research governance and management in the Western Pacific: a WHO expert consultation.

PubMed

Rani, Manju; Bekedam, Hendrik; Buckley, Brian S

2011-11-01

Repeated calls have been made in recent decades to increase investments in health research, especially in low- and middle-income countries (LMIC). However, the perceived low relevance and quality of health research, poor visibility of outputs, and difficulties in tracking current levels of and returns on investments have undermined efforts to advocate for additional investments in these countries. Some of these issues emanate from inadequate governance and management systems for health research at the national level, which are ineffective in tracking and steering the research portfolio and investments, ensuring quality, and facilitating access to research outputs. In spite of this, the value, necessity, and cost of performing health research management and governance functions are not well appreciated, especially in LMIC. To address this, the World Health Organization (WHO) Regional Office for the Western Pacific organized an expert consultation in August 2011, involving experts from 14 of its developed and developing member states and from leading research organizations such as the Wellcome Trust. The consultation identified essential health research governance and management functions that must be performed by appropriate organizational entities to maximize returns on health research investments. In addition, three specific areas for intervention were considered: (1) prospective research registration in publicly accessible national health research registries; (2) systematic health research data archiving and wider access; and (3) national research ethics systems. A consensus was reached on the need to invest more in essential health research and management functions, including establishing publicly accessible web-based national health research registries for prospective registration of health research, setting up systems to archive and share health research data, and improving the governance of research ethics committees. The consultation also concluded that the costs of performing these functions are legitimate and necessary research costs that must be shouldered by research funding organizations. © 2011 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Effects of Economy Type and Nicotine on the Essential Value of Food in Rats

ERIC Educational Resources Information Center

Cassidy, Rachel N.; Dallery, Jesse

2012-01-01

The exponential demand equation proposed by Hursh and Silberberg (2008) provides an estimate of the essential value of a good as a function of price. The model predicts that essential value should remain constant across changes in the magnitude of a reinforcer, but may change as a function of motivational operations. In Experiment 1, rats' demand…

Evaluation of Language Function under Awake Craniotomy

PubMed Central

KANNO, Aya; MIKUNI, Nobuhiro

2015-01-01

Awake craniotomy is the only established way to assess patients’ language functions intraoperatively and to contribute to their preservation, if necessary. Recent guidelines have enabled the approach to be used widely, effectively, and safely. Non-invasive brain functional imaging techniques, including functional magnetic resonance imaging and diffusion tensor imaging, have been used preoperatively to identify brain functional regions corresponding to language, and their accuracy has increased year by year. In addition, the use of neuronavigation that incorporates this preoperative information has made it possible to identify the positional relationships between the lesion and functional regions involved in language, conduct functional brain mapping in the awake state with electrical stimulation, and intraoperatively assess nerve function in real time when resecting the lesion. This article outlines the history of awake craniotomy, the current state of pre- and intraoperative evaluation of language function, and the clinical usefulness of such functional evaluation. When evaluating patients’ language functions during awake craniotomy, given the various intraoperative stresses involved, it is necessary to carefully select the tasks to be undertaken, quickly perform all examinations, and promptly evaluate the results. As language functions involve both input and output, they are strongly affected by patients’ preoperative cognitive function, degree of intraoperative wakefulness and fatigue, the ability to produce verbal articulations and utterances, as well as perform synergic movement. Therefore, it is essential to appropriately assess the reproducibility of language function evaluation using awake craniotomy techniques. PMID:25925758

Evaluation of Language Function under Awake Craniotomy.

PubMed

Kanno, Aya; Mikuni, Nobuhiro

2015-01-01

Awake craniotomy is the only established way to assess patients' language functions intraoperatively and to contribute to their preservation, if necessary. Recent guidelines have enabled the approach to be used widely, effectively, and safely. Non-invasive brain functional imaging techniques, including functional magnetic resonance imaging and diffusion tensor imaging, have been used preoperatively to identify brain functional regions corresponding to language, and their accuracy has increased year by year. In addition, the use of neuronavigation that incorporates this preoperative information has made it possible to identify the positional relationships between the lesion and functional regions involved in language, conduct functional brain mapping in the awake state with electrical stimulation, and intraoperatively assess nerve function in real time when resecting the lesion. This article outlines the history of awake craniotomy, the current state of pre- and intraoperative evaluation of language function, and the clinical usefulness of such functional evaluation. When evaluating patients' language functions during awake craniotomy, given the various intraoperative stresses involved, it is necessary to carefully select the tasks to be undertaken, quickly perform all examinations, and promptly evaluate the results. As language functions involve both input and output, they are strongly affected by patients' preoperative cognitive function, degree of intraoperative wakefulness and fatigue, the ability to produce verbal articulations and utterances, as well as perform synergic movement. Therefore, it is essential to appropriately assess the reproducibility of language function evaluation using awake craniotomy techniques.

Assessment of Emergency Medical Services in the Ashanti Region of Ghana.

PubMed

Mould-Millman, N K; Oteng, R; Zakariah, A; Osei-Ampofo, M; Oduro, G; Barsan, W; Donkor, P; Kowalenko, T

2015-09-01

We aimed to assess the structure, function and performance of Ashanti Region's emergency medical services system in the context of the regional need for prehospital emergency care. A mixed-methods approach was employed, using retrospective collection of quantitative data and prospectively gathered qualitative data. Setting - pertinent data were collected from Ghanaian and international sources; interviews and technical assessments were performed primarily in the Ashanti Region of Ghana. All stakeholders relevant to emergency medical services in the Ashanti Region of Ghana were assessed; there was a special focus on National Ambulance Service (NAS) and Ashanti Region healthcare personnel. This was an observational study using qualitative and quantitative assessment techniques. The structure, function and performance of the Ashanti emergency medical services system, guided by a relevant technical assessment framework. NAS is the premier and only true prehospital agency in the Ashanti Region. NAS has developed almost every essential aspect of an EMS system necessary to achieve its mission within a low-resource setting. NAS continues to increase its number of response units to address the overwhelming Ashanti region demand, especially primary calls. Deficient areas in need of development are governance, reliable revenue, public access, community integration, clinical care guidelines, research and quality assurance processes. The Ashanti Region has a growing and thriving emergency medical services system. Although many essential areas for development were identified, NAS is well poised to meet the regional demand for prehospital emergency care and transport.

FAPRS Manual: Manual for the Functional Analytic Psychotherapy Rating Scale

ERIC Educational Resources Information Center

Callaghan, Glenn M.; Follette, William C.

2008-01-01

The Functional Analytic Psychotherapy Rating Scale (FAPRS) is behavioral coding system designed to capture those essential client and therapist behaviors that occur during Functional Analytic Psychotherapy (FAP). The FAPRS manual presents the purpose and rules for documenting essential aspects of FAP. The FAPRS codes are exclusive and exhaustive…

HPC in a HEP lab: lessons learned from setting up cost-effective HPC clusters

NASA Astrophysics Data System (ADS)

Husejko, Michal; Agtzidis, Ioannis; Baehler, Pierre; Dul, Tadeusz; Evans, John; Himyr, Nils; Meinhard, Helge

2015-12-01

In this paper we present our findings gathered during the evaluation and testing of Windows Server High-Performance Computing (Windows HPC) in view of potentially using it as a production HPC system for engineering applications. The Windows HPC package, an extension of Microsofts Windows Server product, provides all essential interfaces, utilities and management functionality for creating, operating and monitoring a Windows-based HPC cluster infrastructure. The evaluation and test phase was focused on verifying the functionalities of Windows HPC, its performance, support of commercial tools and the integration with the users work environment. We describe constraints imposed by the way the CERN Data Centre is operated, licensing for engineering tools and scalability and behaviour of the HPC engineering applications used at CERN. We will present an initial set of requirements, which were created based on the above constraints and requests from the CERN engineering user community. We will explain how we have configured Windows HPC clusters to provide job scheduling functionalities required to support the CERN engineering user community, quality of service, user- and project-based priorities, and fair access to limited resources. Finally, we will present several performance tests we carried out to verify Windows HPC performance and scalability.

Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior.

PubMed

Ryglewski, Stefanie; Kadas, Dimitrios; Hutchinson, Katie; Schuetzler, Natalie; Vonhoff, Fernando; Duch, Carsten

2014-12-16

Dendrites are highly complex 3D structures that define neuronal morphology and connectivity and are the predominant sites for synaptic input. Defects in dendritic structure are highly consistent correlates of brain diseases. However, the precise consequences of dendritic structure defects for neuronal function and behavioral performance remain unknown. Here we probe dendritic function by using genetic tools to selectively abolish dendrites in identified Drosophila wing motoneurons without affecting other neuronal properties. We find that these motoneuron dendrites are unexpectedly dispensable for synaptic targeting, qualitatively normal neuronal activity patterns during behavior, and basic behavioral performance. However, significant performance deficits in sophisticated motor behaviors, such as flight altitude control and switching between discrete courtship song elements, scale with the degree of dendritic defect. To our knowledge, our observations provide the first direct evidence that complex dendrite architecture is critically required for fine-tuning and adaptability within robust, evolutionarily constrained behavioral programs that are vital for mating success and survival. We speculate that the observed scaling of performance deficits with the degree of structural defect is consistent with gradual increases in intellectual disability during continuously advancing structural deficiencies in progressive neurological disorders.

Exploring the Relationship Between Surgical Capacity and Output in Ghana: Current Capacity Assessments May Not Tell the Whole Story.

PubMed

Stewart, Barclay T; Gyedu, Adam; Gaskill, Cameron; Boakye, Godfred; Quansah, Robert; Donkor, Peter; Volmink, Jimmy; Mock, Charles

2018-03-13

Capacity assessments serve as surrogates for surgical output in low- and middle-income countries where detailed registers do not exist. The relationship between surgical capacity and output was evaluated in Ghana to determine whether a more critical interpretation of capacity assessment data is needed on which to base health systems strengthening initiatives. A standardized surgical capacity assessment was performed at 37 hospitals nationwide using WHO guidelines; availability of 25 essential resources and capabilities was used to create a composite capacity score that ranged from 0 (no availability of essential resources) to 75 (constant availability) for each hospital. Data regarding the number of essential operations performed over 1 year, surgical specialties available, hospital beds, and functional operating rooms were also collected. The relationship between capacity and output was explored. The median surgical capacity score was 37 [interquartile range (IQR) 29-48; range 20-56]. The median number of essential operations per year was 1480 (IQR 736-1932) at first-level hospitals; 1545 operations (IQR 984-2452) at referral hospitals; and 11,757 operations (IQR 3769-21,256) at tertiary hospitals. Surgical capacity and output were not correlated (p > 0.05). Contrary to current understanding, surgical capacity assessments may not accurately reflect surgical output. To improve the validity of surgical capacity assessments and facilitate maximal use of available resources, other factors that influence output should also be considered, including demand-side factors; supply-side factors and process elements; and health administration and management factors.

Functions and Mechanisms of Sleep

PubMed Central

Zielinski, Mark R.; McKenna, James T.; McCarley, Robert W.

2017-01-01

Sleep is a complex physiological process that is regulated globally, regionally, and locally by both cellular and molecular mechanisms. It occurs to some extent in all animals, although sleep expression in lower animals may be co-extensive with rest. Sleep regulation plays an intrinsic part in many behavioral and physiological functions. Currently, all researchers agree there is no single physiological role sleep serves. Nevertheless, it is quite evident that sleep is essential for many vital functions including development, energy conservation, brain waste clearance, modulation of immune responses, cognition, performance, vigilance, disease, and psychological state. This review details the physiological processes involved in sleep regulation and the possible functions that sleep may serve. This description of the brain circuitry, cell types, and molecules involved in sleep regulation is intended to further the reader’s understanding of the functions of sleep. PMID:28413828

Functional performance following selective posterior rhizotomy: long-term results determined using a validated evaluative measure.

PubMed

Mittal, Sandeep; Farmer, Jean-Pierre; Al-Atassi, Borhan; Montpetit, Kathleen; Gervais, Nathalie; Poulin, Chantal; Benaroch, Thierry E; Cantin, Marie-André

2002-09-01

Selective posterior rhizotomy (SPR) may result in considerable benefit for children with spastic cerebral palsy. To date, however, there have been few studies in which validated functional outcome measures have been used to report surgical results beyond 3 years. The authors analyzed data obtained from the McGill Rhizotomy Database to determine long-term functional performance outcomes in patients who underwent lumbosacral dorsal rhizotomy performed using intraoperative electrophysiological monitoring. The study population was composed of children with debilitating spasticity who underwent SPR and were evaluated by a multidisciplinary team preoperatively and at 6 months and 1 year postoperatively. Quantitative standardized assessments of activities of daily living (ADL) were obtained using the Pediatric Evaluation of Disability Inventory (PEDI). Of 57 patients who met the entry criteria for the study, 41 completed the 3-year assessments and 30 completed the 5-year assessments. Statistical analysis demonstrated significant improvement in the mobility and self-care domains of the functional skills dimension at 1 year after SPR. The preoperative and 1-, 3-, and 5-year postoperative scaled scores for the mobility domain were 56, 64, 77.2, and 77.8, respectively. The scaled score for the self-care domain increased from 59 presurgery to 67.9, 81.6, and 82.4 at the 1-, 3-, and 5-year postoperative assessments, respectively. The results of this study support the presence of significant improvements in functional performance, based on PEDI scores obtained 1 year after SPR. The improvements persisted at the 3- and 5-year follow-up examinations. The authors conclude that SPR performed using intraoperative stimulation is valuable in the augmentation of motor function and self-care skills essential to the performance of ADL.

Spectraplakins promote microtubule-mediated axonal growth by functioning as structural microtubule-associated proteins and EB1-dependent +TIPs (tip interacting proteins).

PubMed

Alves-Silva, Juliana; Sánchez-Soriano, Natalia; Beaven, Robin; Klein, Melanie; Parkin, Jill; Millard, Thomas H; Bellen, Hugo J; Venken, Koen J T; Ballestrem, Christoph; Kammerer, Richard A; Prokop, Andreas

2012-07-04

The correct outgrowth of axons is essential for the development and regeneration of nervous systems. Axon growth is primarily driven by microtubules. Key regulators of microtubules in this context are the spectraplakins, a family of evolutionarily conserved actin-microtubule linkers. Loss of function of the mouse spectraplakin ACF7 or of its close Drosophila homolog Short stop/Shot similarly cause severe axon shortening and microtubule disorganization. How spectraplakins perform these functions is not known. Here we show that axonal growth-promoting roles of Shot require interaction with EB1 (End binding protein) at polymerizing plus ends of microtubules. We show that binding of Shot to EB1 requires SxIP motifs in Shot's C-terminal tail (Ctail), mutations of these motifs abolish Shot functions in axonal growth, loss of EB1 function phenocopies Shot loss, and genetic interaction studies reveal strong functional links between Shot and EB1 in axonal growth and microtubule organization. In addition, we report that Shot localizes along microtubule shafts and stabilizes them against pharmacologically induced depolymerization. This function is EB1-independent but requires net positive charges within Ctail which essentially contribute to the microtubule shaft association of Shot. Therefore, spectraplakins are true members of two important classes of neuronal microtubule regulating proteins: +TIPs (tip interacting proteins; plus end regulators) and structural MAPs (microtubule-associated proteins). From our data we deduce a model that relates the different features of the spectraplakin C terminus to the two functions of Shot during axonal growth.

Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis.

PubMed

Du, Yushen; Wu, Nicholas C; Jiang, Lin; Zhang, Tianhao; Gong, Danyang; Shu, Sara; Wu, Ting-Ting; Sun, Ren

2016-11-01

Identification and annotation of functional residues are fundamental questions in protein sequence analysis. Sequence and structure conservation provides valuable information to tackle these questions. It is, however, limited by the incomplete sampling of sequence space in natural evolution. Moreover, proteins often have multiple functions, with overlapping sequences that present challenges to accurate annotation of the exact functions of individual residues by conservation-based methods. Using the influenza A virus PB1 protein as an example, we developed a method to systematically identify and annotate functional residues. We used saturation mutagenesis and high-throughput sequencing to measure the replication capacity of single nucleotide mutations across the entire PB1 protein. After predicting protein stability upon mutations, we identified functional PB1 residues that are essential for viral replication. To further annotate the functional residues important to the canonical or noncanonical functions of viral RNA-dependent RNA polymerase (vRdRp), we performed a homologous-structure analysis with 16 different vRdRp structures. We achieved high sensitivity in annotating the known canonical polymerase functional residues. Moreover, we identified a cluster of noncanonical functional residues located in the loop region of the PB1 β-ribbon. We further demonstrated that these residues were important for PB1 protein nuclear import through the interaction with Ran-binding protein 5. In summary, we developed a systematic and sensitive method to identify and annotate functional residues that are not restrained by sequence conservation. Importantly, this method is generally applicable to other proteins about which homologous-structure information is available. To fully comprehend the diverse functions of a protein, it is essential to understand the functionality of individual residues. Current methods are highly dependent on evolutionary sequence conservation, which is usually limited by sampling size. Sequence conservation-based methods are further confounded by structural constraints and multifunctionality of proteins. Here we present a method that can systematically identify and annotate functional residues of a given protein. We used a high-throughput functional profiling platform to identify essential residues. Coupling it with homologous-structure comparison, we were able to annotate multiple functions of proteins. We demonstrated the method with the PB1 protein of influenza A virus and identified novel functional residues in addition to its canonical function as an RNA-dependent RNA polymerase. Not limited to virology, this method is generally applicable to other proteins that can be functionally selected and about which homologous-structure information is available. Copyright © 2016 Du et al.

Relationship Between Soil and Essential Oil Profiles in Salvia desoleana Populations: Preliminary Results.

PubMed

Rapposelli, Emma; Melito, Sara; Barmina, Giovanni Gabriele; Foddai, Marzia; Azara, Emanuela; Scarpa, Grazia Maria

2015-09-01

Salvia desoleana is a herbaceous perennial shrub endemic of Sardinia (Italy). The leaves are a source of essential oil, used in pharmaceutical and cosmetic industries. The therapeutic function of this species has been associated to the presence of essential oils rich in α/β-pinene, p-cimene, linalool, linalyl acetate and 1,8-cineole. Today.the industrial request of Salvia essential oils is increasing and most of the biomass is exploited from the natural populations which are under severe risk of genetic erosion. In order to improve the essential oil production, the study of the environmental parameters that influence composition, quality and quantity of the essential oils, turns out to be necessary. Soil physical and chemical structure represents one of the determinant factors in secondary metabolites production, and could also be involved in volatiles fraction composition in the same species. The main aim of this research was to explore the relationship between essential oil profiles and soil characteristics in S. desoleana populations. GC/MS analysis performed on the essential oil extracts identified 22 principal compounds, which were extremely variable among the five S. desoleana populations studied. The analysis of the essential oils revealed different compositions in the terpenes fractions: 68.2% of monoterpenes, 27.3% of sesquiterpenes and 4.5% of diterpenes. Analysis of chemical and physical soil parameters at the collection sites revealed that silt and sand contents were correlated with α-pinene and sclareol fractions and the total K20 was significantly correlated to several compounds belonging to the three terpene fractions identified. These results will provide guidelines for the in site conservation and for the improvement of the commercial value of the species.

Important aspects of participation and participation restrictions in people with a mild intellectual disability.

PubMed

Arvidsson, Patrik; Granlund, Mats; Thyberg, Ingrid; Thyberg, Mikael

2014-01-01

This study explored a possibility to assess the concepts of participation and participation restrictions in the International Classification of Functioning, Disability and Health (ICF) by combining self-ratings of the perceived importance with the actual performance of different everyday activities in people with a mild intellectual disability. Structured interviews regarding 68 items from the ICF activity/participation domain were conducted (n = 69). The items were ranked by perceived importance, performance and by combined measures. Furthermore, the measures were related to a single question about subjective general well-being. Rankings of performance highlighted about the same items as "important participation", while rankings of low performance addressed quite different items compared with "important participation restriction". Significant correlations were found between subjective general well-being and high performance (r = 0.56), high performance/high importance (important participation) (r = 0.56), low performance (r = -0.56) and low performance/high importance (important participation restriction; r = -0.55). The results support the clinical relevance of the ICF and the studied selection of 68 items. Although performance only may sometimes be a relevant aspect, knowledge about the relationship between the perceived importance and the actual performance is essential for clinical interventions and for research aiming to understand specific needs regarding participation. The concepts of participation and participation restriction are highly relevant in people with a mild intellectual disability. Self-rated performance might be sufficient to assess participation at a group level. In clinical practices, the relationship between the perceived importance and the actual performance of an activity is essential to assess.

Analysis of the human operator subsystems

NASA Technical Reports Server (NTRS)

Jones, Lynette A.; Hunter, Ian W.

1991-01-01

Except in low-bandwidth systems, knowledge of the human operator transfer function is essential for high-performance telerobotic systems. This information has usually been derived from detailed analyses of tracking performance, in which the human operator is considered as a complete system rather than as a summation of a number of subsystems, each of which influences the operator's output. Studies of one of these subsystems, the limb mechanics system, demonstrate that large parameter variations can occur that can have a profound effect on the stability of force-reflecting telerobot systems. An objective of this research was to decompose the performance of the human operator system in order to establish how the dynamics of each of the elements influence the operator's responses.

Assessing Language Dominance with Functional MRI: The Role of Control Tasks and Statistical Analysis

ERIC Educational Resources Information Center

Dodoo-Schittko, Frank; Rosengarth, Katharina; Doenitz, Christian; Greenlee, Mark W.

2012-01-01

There is a discrepancy between the brain regions revealed by functional neuroimaging techniques and those brain regions where a loss of function, either by lesion or by electrocortical stimulation, induces language disorders. To differentiate between essential and non-essential language-related processes, we investigated the effects of linguistic…

On the interconnection of stable protein complexes: inter-complex hubs and their conservation in Saccharomyces cerevisiae and Homo sapiens networks.

PubMed

Guerra, Concettina

2015-01-01

Protein complexes are key molecular entities that perform a variety of essential cellular functions. The connectivity of proteins within a complex has been widely investigated with both experimental and computational techniques. We developed a computational approach to identify and characterise proteins that play a role in interconnecting complexes. We computed a measure of inter-complex centrality, the crossroad index, based on disjoint paths connecting proteins in distinct complexes and identified inter-complex hubs as proteins with a high value of the crossroad index. We applied the approach to a set of stable complexes in Saccharomyces cerevisiae and in Homo sapiens. Just as done for hubs, we evaluated the topological and biological properties of inter-complex hubs addressing the following questions. Do inter-complex hubs tend to be evolutionary conserved? What is the relation between crossroad index and essentiality? We found a good correlation between inter-complex hubs and both evolutionary conservation and essentiality.

Chaperones in maturation of molybdoenzymes: Why specific is better than general?

PubMed

Lemaire, Olivier N; Bouillet, Sophie; Méjean, Vincent; Iobbi-Nivol, Chantal; Genest, Olivier

2017-03-04

Molybdoenzymes play essential functions in living organisms and, as a result, in various geochemical cycles. It is thus crucial to understand how these complex proteins become highly efficient enzymes able to perform a wide range of catalytic activities. It has been established that specific chaperones are involved during their maturation process. Here, we raise the question of the involvement of general chaperones acting in concert with dedicated chaperones or not.

Software Manages Documentation in a Large Test Facility

NASA Technical Reports Server (NTRS)

Gurneck, Joseph M.

2001-01-01

The 3MCS computer program assists and instrumentation engineer in performing the 3 essential functions of design, documentation, and configuration management of measurement and control systems in a large test facility. Services provided by 3MCS are acceptance of input from multiple engineers and technicians working at multiple locations;standardization of drawings;automated cross-referencing; identification of errors;listing of components and resources; downloading of test settings; and provision of information to customers.

Solving the Schroedinger equation for helium atom and its isoelectronic ions with the free iterative complement interaction (ICI) method

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

Nakashima, Hiroyuki; Nakatsuji, Hiroshi

2007-12-14

The Schroedinger equation was solved very accurately for helium atom and its isoelectronic ions (Z=1-10) with the free iterative complement interaction (ICI) method followed by the variational principle. We obtained highly accurate wave functions and energies of helium atom and its isoelectronic ions. For helium, the calculated energy was -2.903 724 377 034 119 598 311 159 245 194 404 446 696 905 37 a.u., correct over 40 digit accuracy, and for H{sup -}, it was -0.527 751 016 544 377 196 590 814 566 747 511 383 045 02 a.u. These results prove numerically that with the free ICImore » method, we can calculate the solutions of the Schroedinger equation as accurately as one desires. We examined several types of scaling function g and initial function {psi}{sub 0} of the free ICI method. The performance was good when logarithm functions were used in the initial function because the logarithm function is physically essential for three-particle collision area. The best performance was obtained when we introduce a new logarithm function containing not only r{sub 1} and r{sub 2} but also r{sub 12} in the same logarithm function.« less

Insights into the evolution of enzyme substrate promiscuity after the discovery of (βα)₈ isomerase evolutionary intermediates from a diverse metagenome.

PubMed

Noda-García, Lianet; Juárez-Vázquez, Ana L; Ávila-Arcos, María C; Verduzco-Castro, Ernesto A; Montero-Morán, Gabriela; Gaytán, Paul; Carrillo-Tripp, Mauricio; Barona-Gómez, Francisco

2015-06-10

Current sequence-based approaches to identify enzyme functional shifts, such as enzyme promiscuity, have proven to be highly dependent on a priori functional knowledge, hampering our ability to reconstruct evolutionary history behind these mechanisms. Hidden Markov Model (HMM) profiles, broadly used to classify enzyme families, can be useful to distinguish between closely related enzyme families with different specificities. The (βα)8-isomerase HisA/PriA enzyme family, involved in L-histidine (HisA, mono-substrate) biosynthesis in most bacteria and plants, but also in L-tryptophan (HisA/TrpF or PriA, dual-substrate) biosynthesis in most Actinobacteria, has been used as model system to explore evolutionary hypotheses and therefore has a considerable amount of evolutionary, functional and structural knowledge available. We searched for functional evolutionary intermediates between the HisA and PriA enzyme families in order to understand the functional divergence between these families. We constructed a HMM profile that correctly classifies sequences of unknown function into the HisA and PriA enzyme sub-families. Using this HMM profile, we mined a large metagenome to identify plausible evolutionary intermediate sequences between HisA and PriA. These sequences were used to perform phylogenetic reconstructions and to identify functionally conserved amino acids. Biochemical characterization of one selected enzyme (CAM1) with a mutation within the functionally essential N-terminus phosphate-binding site, namely, an alanine instead of a glycine in HisA or a serine in PriA, showed that this evolutionary intermediate has dual-substrate specificity. Moreover, site-directed mutagenesis of this alanine residue, either backwards into a glycine or forward into a serine, revealed the robustness of this enzyme. None of these mutations, presumably upon functionally essential amino acids, significantly abolished its enzyme activities. A truncated version of this enzyme (CAM2) predicted to adopt a (βα)6-fold, and thus entirely lacking a C-terminus phosphate-binding site, was identified and shown to have HisA activity. As expected, reconstruction of the evolution of PriA from HisA with HMM profiles suggest that functional shifts involve mutations in evolutionarily intermediate enzymes of otherwise functionally essential residues or motifs. These results are in agreement with a link between promiscuous enzymes and intragenic epistasis. HMM provides a convenient approach for gaining insights into these evolutionary processes.

Magnetic Resonance-Guided Focused Ultrasound Neurosurgery for Essential Tremor: A Health Technology Assessment

PubMed Central

Schaink, Alexis; Li, Chunmei; Gajic-Veljanoski, Olga; Wells, David; Higgins, Caroline

2018-01-01

Background The standard treatment option for medication-refractory essential tremor is invasive neurosurgery. A new, noninvasive alternative is magnetic resonance-guided focused ultrasound (MRgFUS) neurosurgery. We aimed to determine the effectiveness, safety, and cost-effectiveness of MRgFUS neurosurgery for the treatment of moderate to severe, medication-refractory essential tremor in Ontario. We also spoke with people with essential tremor to gain an understanding of their experiences and thoughts regarding treatment options, including MRgFUS neurosurgery. Methods We performed a systematic review of the clinical literature published up to April 11, 2017, that examined MRgFUS neurosurgery alone or compared with other interventions for the treatment of moderate to severe, medication-refractory essential tremor. We assessed the risk of bias of each study and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic review of the economic literature and created Markov cohort models to assess the cost-effectiveness of MRgFUS neurosurgery compared with other treatment options, including no surgery. We also estimated the budget impact of publicly funding MRgFUS neurosurgery in Ontario for the next 5 years. To contextualize the potential value of MRgFUS neurosurgery as a treatment option for essential tremor, we spoke with people with essential tremor and their families. Results Nine studies met our inclusion criteria for the clinical evidence review. In noncomparative studies, MRgFUS neurosurgery was found to significantly improve tremor severity and quality of life and to significantly reduce functional disability (GRADE: very low). It was also found to be significantly more effective than a sham procedure (GRADE: high). We found no significant difference in improvements in tremor severity, functional disability, or quality of life between MRgFUS neurosurgery and deep brain stimulation (GRADE: very low). We found no significant difference in improvement in tremor severity compared with radiofrequency thalamotomy (GRADE: low). MRgFUS neurosurgery has a favourable safety profile. We estimated that MRgFUS neurosurgery has a mean cost of $23,507 and a mean quality-adjusted survival of 3.69 quality-adjusted life-years (QALYs). We also estimated that the mean costs and QALYs of radiofrequency thalamotomy and deep brain stimulation are $14,978 and 3.61 QALYs, and $57,535 and 3.94 QALYs, respectively. For people ineligible for invasive neurosurgery, we estimated the incremental cost-effectiveness ratio (ICER) of MRgFUS neurosurgery compared with no surgery as $43,075 per QALY gained. In people eligible for invasive neurosurgery, the ICER of MRgFUS neurosurgery compared with radiofrequency thalamotomy is $109,795 per QALY gained; when deep brain stimulation is compared with MRgFUS neurosurgery, the ICER is $134,259 per QALY gained. Of note however, radiofrequency thalamotomy is performed very infrequently in Ontario. We also estimated that the budget impact of publicly funding MRgFUS neurosurgery in Ontario at the current case load (i.e., 48 cases/year) would be about $1 million per year for the next 5 years. People with essential tremor who had undergone MRgFUS neurosurgery reported positive experiences with the procedure. The tremor reduction they experienced improved their ability to perform activities of daily living and improved their quality of life. Conclusions MRgFUS neurosurgery is an effective and generally safe treatment option for moderate to severe, medication-refractory essential tremor. It provides a treatment option for people ineligible for invasive neurosurgery and offers a noninvasive option for all people considering neurosurgery. For people ineligible for invasive neurosurgery, MRgFUS neurosurgery is cost-effective compared with no surgery. In people eligible for invasive neurosurgery, MRgFUS neurosurgery may be one of several reasonable options. Publicly funding MRgFUS neurosurgery for the treatment of moderate to severe, medication-refractory essential tremor in Ontario at the current case load would have a net budget impact of about $1 million per year for the next 5 years. People with essential tremor who had undergone MRgFUS neurosurgery reported positive experiences. They liked that it was a noninvasive procedure and reported a substantial reduction in tremor that resulted in an improvement in their quality of life. PMID:29805721

Photorespiratory glycolate oxidase is essential for the survival of the red alga Cyanidioschyzon merolae under ambient CO2 conditions

PubMed Central

Rademacher, Nadine; Kern, Ramona; Fujiwara, Takayuki; Mettler-Altmann, Tabea; Miyagishima, Shin-ya; Hagemann, Martin; Eisenhut, Marion; Weber, Andreas P.M.

2016-01-01

Photorespiration is essential for all organisms performing oxygenic photosynthesis. The evolution of photorespiratory metabolism began among cyanobacteria and led to a highly compartmented pathway in plants. A molecular understanding of photorespiration in eukaryotic algae, such as glaucophytes, rhodophytes, and chlorophytes, is essential to unravel the evolution of this pathway. However, mechanistic detail of the photorespiratory pathway in red algae is scarce. The unicellular red alga Cyanidioschyzon merolae represents a model for the red lineage. Its genome is fully sequenced, and tools for targeted gene engineering are available. To study the function and importance of photorespiration in red algae, we chose glycolate oxidase (GOX) as the target. GOX catalyses the conversion of glycolate into glyoxylate, while hydrogen peroxide is generated as a side-product. The function of the candidate GOX from C. merolae was verified by the fact that recombinant GOX preferred glycolate over L-lactate as a substrate. Yellow fluorescent protein-GOX fusion proteins showed that GOX is targeted to peroxisomes in C. merolae. The GOX knockout mutant lines showed a high-carbon-requiring phenotype with decreased growth and reduced photosynthetic activity compared to the wild type under ambient air conditions. Metabolite analyses revealed glycolate and glycine accumulation in the mutant cells after a shift from high CO2 conditions to ambient air. In summary, or results demonstrate that photorespiratory metabolism is essential for red algae. The use of a peroxisomal GOX points to a high photorespiratory flux as an ancestral feature of all photosynthetic eukaryotes. PMID:26994474

A novel essential domain perspective for exploring gene essentiality.

PubMed

Lu, Yao; Lu, Yulan; Deng, Jingyuan; Peng, Hai; Lu, Hui; Lu, Long Jason

2015-09-15

Genes with indispensable functions are identified as essential; however, the traditional gene-level studies of essentiality have several limitations. In this study, we characterized gene essentiality from a new perspective of protein domains, the independent structural or functional units of a polypeptide chain. To identify such essential domains, we have developed an Expectation-Maximization (EM) algorithm-based Essential Domain Prediction (EDP) Model. With simulated datasets, the model provided convergent results given different initial values and offered accurate predictions even with noise. We then applied the EDP model to six microbial species and predicted 1879 domains to be essential in at least one species, ranging 10-23% in each species. The predicted essential domains were more conserved than either non-essential domains or essential genes. Comparing essential domains in prokaryotes and eukaryotes revealed an evolutionary distance consistent with that inferred from ribosomal RNA. When utilizing these essential domains to reproduce the annotation of essential genes, we received accurate results that suggest protein domains are more basic units for the essentiality of genes. Furthermore, we presented several examples to illustrate how the combination of essential and non-essential domains can lead to genes with divergent essentiality. In summary, we have described the first systematic analysis on gene essentiality on the level of domains. huilu.bioinfo@gmail.com or Long.Lu@cchmc.org Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Habitat and Biodiversity: One out of five essential soil functions for agricultural soils

NASA Astrophysics Data System (ADS)

Trinsoutrot Gattin, Isabelle; Creamer, Rachel; van Leeuwen, Jeroen; Vrebos, Dirk; Gatti, Fabio; Bampa, Francesca; Schulte, Rogier; Rutgers, Michiel

2017-04-01

Current agricultural challenges require developing new agricultural systems that can optimize the ecological functioning of soils in order to limit the use of chemical inputs (i.e. disease suppression) and maintain a high organic matter content. This implies our ability to evaluate the effects of management practices on immediate performance objectives (i.e. fertility linked to nutrient cycling) but also in longer-term objective (i.e. C cycling and storage) in a variety of agro-climatic conditions. These issues demand the development of systemic approaches for understanding the determinants of soil functioning. In ecology, it is generally accepted that there are many positive relationships between soil biodiversity indicators and the functioning of ecosystems. Indeed, soil organisms and their interactions are essential drivers of ecosystem processes and impact the response, resilience and adaptability of ecosystems to environmental pressures. Thus, maintaining soil biodiversity is a condition for the sustainability of cropping systems. In this new context, the European project Landmark considers soil functions as a key to the improvement of agricultural land management towards sustainable development goals, amongst the five functions is soil biodiversity and habitat provisioning. We propose to present how we manage within this project to deal with this challenging objective at three spatial scales : field, landscape (regional) and European (policy). We aim to define a link between the physical, chemical and biological soil properties and "habitat & biodiversity" soil function in order to identify key indicators which modulate biodiversity. This will allow us to quantify and assess this soil function, in order to provide insight in win wins and tradeoffs in soil functions to enhance management practices which optimise the biodiversity in European agricultural systems.

Old Maids: Aging and Its Impact on Microglia Function

PubMed Central

Koellhoffer, Edward C.; McCullough, Louise D.; Ritzel, Rodney M.

2017-01-01

Microglia are highly active and vigilant housekeepers of the central nervous system that function to promote neuronal growth and activity. With advanced age, however, dysregulated inflammatory signaling and defects in phagocytosis impede their ability to perform the most essential of homeostatic functions, including immune surveillance and debris clearance. Microglial activation is one of the hallmarks of the aging brain and coincides with age-related neurodegeneration and cognitive decline. Age-associated microglial dysfunction leads to cellular senescence and can profoundly alter the response to sterile injuries and immune diseases, often resulting in maladaptive responses, chronic inflammation, and worsened outcomes after injury. Our knowledge of microglia aging and the factors that regulate age-related microglial dysfunction remain limited, as the majority of pre-clinical studies are performed in young animals, and human brain samples are difficult to obtain quickly post-mortem or in large numbers. This review outlines the impact of normal aging on microglial function, highlights the potential mechanisms underlying age-related changes in microglia, and discusses how aging can shape the recovery process following injury. PMID:28379162

Automatic measurement of voice onset time using discriminative structured prediction.

PubMed

Sonderegger, Morgan; Keshet, Joseph

2012-12-01

A discriminative large-margin algorithm for automatic measurement of voice onset time (VOT) is described, considered as a case of predicting structured output from speech. Manually labeled data are used to train a function that takes as input a speech segment of an arbitrary length containing a voiceless stop, and outputs its VOT. The function is explicitly trained to minimize the difference between predicted and manually measured VOT; it operates on a set of acoustic feature functions designed based on spectral and temporal cues used by human VOT annotators. The algorithm is applied to initial voiceless stops from four corpora, representing different types of speech. Using several evaluation methods, the algorithm's performance is near human intertranscriber reliability, and compares favorably with previous work. Furthermore, the algorithm's performance is minimally affected by training and testing on different corpora, and remains essentially constant as the amount of training data is reduced to 50-250 manually labeled examples, demonstrating the method's practical applicability to new datasets.

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities

PubMed Central

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-01-01

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal–occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention. PMID:26419418

Effects of fluency, oral language, and executive function on reading comprehension performance

PubMed Central

Materek, April; Cole, Carolyn A. S.; Levine, Terry M.; Mahone, E. Mark

2009-01-01

Reading disability (RD) typically consists of deficits in word reading accuracy and/or reading comprehension. While it is well known that word reading accuracy deficits lead to comprehension deficits (general reading disability, GRD), less is understood about neuropsychological profiles of children who exhibit adequate word reading accuracy but nevertheless develop specific reading comprehension deficits (S-RCD). Establishing the underlying neuropsychological processes associated with different RD types is essential for ultimately understanding core neurobiological bases of reading comprehension. To this end, the present study investigated isolated and contextual word fluency, oral language, and executive function on reading comprehension performance in 56 9- to 14-year-old children [21 typically developing (TD), 18 GRD, and 17 S-RCD]. Results indicated that TD and S-RCD participants read isolated words at a faster rate than participants with GRD; however, both RD groups had contextual word fluency and oral language weaknesses. Additionally, S-RCD participants showed prominent weaknesses in executive function. Implications for understanding the neuropsychological bases for reading comprehension are discussed. PMID:19396550

Functional cooperation between exonucleases and endonucleases—basis for the evolution of restriction enzymes

PubMed Central

Raghavendra, Nidhanapathi K.; Rao, Desirazu N.

2003-01-01

Many types of restriction enzymes cleave DNA away from their recognition site. Using the type III restriction enzyme, EcoP15I, which cleaves DNA 25–27 bp away from its recognition site, we provide evidence to show that an intact recognition site on the cleaved DNA sequesters the restriction enzyme and decreases the effective concentration of the enzyme. EcoP15I restriction enzyme is shown here to perform only a single round of DNA cleavage. Significantly, we show that an exonuclease activity is essential for EcoP15I restriction enzyme to perform multiple rounds of DNA cleavage. This observation may hold true for all restriction enzymes cleaving DNA sufficiently far away from their recognition site. Our results highlight the importance of functional cooperation in the modulation of enzyme activity. Based on results presented here and other data on well-characterised restriction enzymes, a functional evolutionary hierarchy of restriction enzymes is discussed. PMID:12655005

Sparse regressions for predicting and interpreting subcellular localization of multi-label proteins.

PubMed

Wan, Shibiao; Mak, Man-Wai; Kung, Sun-Yuan

2016-02-24

Predicting protein subcellular localization is indispensable for inferring protein functions. Recent studies have been focusing on predicting not only single-location proteins, but also multi-location proteins. Almost all of the high performing predictors proposed recently use gene ontology (GO) terms to construct feature vectors for classification. Despite their high performance, their prediction decisions are difficult to interpret because of the large number of GO terms involved. This paper proposes using sparse regressions to exploit GO information for both predicting and interpreting subcellular localization of single- and multi-location proteins. Specifically, we compared two multi-label sparse regression algorithms, namely multi-label LASSO (mLASSO) and multi-label elastic net (mEN), for large-scale predictions of protein subcellular localization. Both algorithms can yield sparse and interpretable solutions. By using the one-vs-rest strategy, mLASSO and mEN identified 87 and 429 out of more than 8,000 GO terms, respectively, which play essential roles in determining subcellular localization. More interestingly, many of the GO terms selected by mEN are from the biological process and molecular function categories, suggesting that the GO terms of these categories also play vital roles in the prediction. With these essential GO terms, not only where a protein locates can be decided, but also why it resides there can be revealed. Experimental results show that the output of both mEN and mLASSO are interpretable and they perform significantly better than existing state-of-the-art predictors. Moreover, mEN selects more features and performs better than mLASSO on a stringent human benchmark dataset. For readers' convenience, an online server called SpaPredictor for both mLASSO and mEN is available at http://bioinfo.eie.polyu.edu.hk/SpaPredictorServer/.

An Active Learning Exercise to Facilitate Understanding of Nephron Function: Anatomy and Physiology of Renal Transporters

ERIC Educational Resources Information Center

Dirks-Naylor, Amie J.

2016-01-01

Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…

Essential and non-essential paediatric surgery: implications for the future delivery of state health care in the UK.

PubMed

Farrelly, Paul J; Losty, Paul D

2015-09-01

Delivery of health care in the UK faces enormous challenges with the Department of Health driving significant financial cost savings to ensure viability of public health services. We have analysed and modelled the concept of 'essential' and 'non-essential' paediatric surgery linked to the delivery of children's surgery in the NHS in England. Operation codes for surgical operations in newborns, children and adolescents were identified and Healthcare Resource Group tariffs-£Stg matched. Operations were designated as 'essential' or 'non-essential' based on the criteria-(1) life saving-neonatal surgery, emergency general surgery of childhood, cancer surgery; (2) debility if uncorrected; (3) aesthetics and (4) culture/attitude. Hospital Episode Statistics (HES) data were accessed and sampled for the total number of paediatric surgical operations-(age range 0-14 years) performed in NHS hospitals from 2009 to 2010. Annual costs (£) of both 'essential' and 'non-essential' operations were then calculated. The commonest 'essential' operations performed in children and adolescents in the year 2009-2010 was appendicectomy at a cost of over £51 million pounds. Costs of performing a selection of 'non-essential' paediatric surgery operations were >£14 million pounds/year. The NHs funds for example almost 11,000 paediatric circumcisions annually at a cost of >£8 million pounds-50% are performed for non-therapeutic reasons. Surgeons must engage and work actively with health care systems to ensure diminishing financial resources prioritise 'essential' operations for children. Commissioners must embrace evidence-based surgery. 'Essential' and 'non-essential' surgery has wide implications for the sustainability of the NHS and concepts herein developed can be applied to nations worldwide.

Reorganization of functional brain networks mediates the improvement of cognitive performance following real-time neurofeedback training of working memory.

PubMed

Zhang, Gaoyan; Yao, Li; Shen, Jiahui; Yang, Yihong; Zhao, Xiaojie

2015-05-01

Working memory (WM) is essential for individuals' cognitive functions. Neuroimaging studies indicated that WM fundamentally relied on a frontoparietal working memory network (WMN) and a cinguloparietal default mode network (DMN). Behavioral training studies demonstrated that the two networks can be modulated by WM training. Different from the behavioral training, our recent study used a real-time functional MRI (rtfMRI)-based neurofeedback method to conduct WM training, demonstrating that WM performance can be significantly improved after successfully upregulating the activity of the target region of interest (ROI) in the left dorsolateral prefrontal cortex (Zhang et al., [2013]: PloS One 8:e73735); however, the neural substrate of rtfMRI-based WM training remains unclear. In this work, we assessed the intranetwork and internetwork connectivity changes of WMN and DMN during the training, and their correlations with the change of brain activity in the target ROI as well as with the improvement of post-training behavior. Our analysis revealed an "ROI-network-behavior" correlation relationship underlying the rtfMRI training. Further mediation analysis indicated that the reorganization of functional brain networks mediated the effect of self-regulation of the target brain activity on the improvement of cognitive performance following the neurofeedback training. The results of this study enhance our understanding of the neural basis of real-time neurofeedback and suggest a new direction to improve WM performance by regulating the functional connectivity in the WM related networks. © 2014 Wiley Periodicals, Inc.

The micro and macro of nutrients across biological scales.

PubMed

Warne, Robin W

2014-11-01

During the past decade, we have gained new insights into the profound effects that essential micronutrients and macronutrients have on biological processes ranging from cellular function, to whole-organism performance, to dynamics in ecological communities, as well as to the structure and function of ecosystems. For example, disparities between intake and organismal requirements for specific nutrients are known to strongly affect animal physiological performance and impose trade-offs in the allocations of resources. However, recent findings have demonstrated that life-history allocation trade-offs and even microevolutionary dynamics may often be a result of molecular-level constraints on nutrient and metabolic processing, in which limiting reactants are routed among competing biochemical pathways. In addition, recent work has shown that complex ecological interactions between organismal physiological states such as exposure to environmental stressors and infectious pathogens can alter organismal requirements for, and, processing of, nutrients, and even alter subsequent nutrient cycling in ecosystems. Furthermore, new research is showing that such interactions, coupled with evolutionary and biogeographical constraints on the biosynthesis and availability of essential nutrients and micronutrients play an important, but still under-studied role in the structuring and functioning of ecosystems. The purpose of this introduction to the symposium "The Micro and Macro of Nutrient Effects in Animal Physiology and Ecology" is to briefly review and highlight recent research that has dramatically advanced our understanding of how nutrients in their varied forms profoundly affect and shape ecological and evolutionary processes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Transport Advances in Disposable Bioreactors for Liver Tissue Engineering

NASA Astrophysics Data System (ADS)

Catapano, Gerardo; Patzer, John F.; Gerlach, Jörg Christian

Acute liver failure (ALF) is a devastating diagnosis with an overall survival of approximately 60%. Liver transplantation is the therapy of choice for ALF patients but is limited by the scarce availability of donor organs. The prognosis of ALF patients may improve if essential liver functions are restored during liver failure by means of auxiliary methods because liver tissue has the capability to regenerate and heal. Bioartificial liver (BAL) approaches use liver tissue or cells to provide ALF patients with liver-specific metabolism and synthesis products necessary to relieve some of the symptoms and to promote liver tissue regeneration. The most promising BAL treatments are based on the culture of tissue engineered (TE) liver constructs, with mature liver cells or cells that may differentiate into hepatocytes to perform liver-specific functions, in disposable continuous-flow bioreactors. In fact, adult hepatocytes perform all essential liver functions. Clinical evaluations of the proposed BALs show that they are safe but have not clearly proven the efficacy of treatment as compared to standard supportive treatments. Ambiguous clinical results, the time loss of cellular activity during treatment, and the presence of a necrotic core in the cell compartment of many bioreactors suggest that improvement of transport of nutrients, and metabolic wastes and products to or from the cells in the bioreactor is critical for the development of therapeutically effective BALs. In this chapter, advanced strategies that have been proposed over to improve mass transport in the bioreactors at the core of a BAL for the treatment of ALF patients are reviewed.

Pre-Participation Screening: The Use of Fundamental Movements as an Assessment of Function – Part 1

PubMed Central

Burton, Lee; Hoogenboom, Barb

2006-01-01

To prepare an athlete for the wide variety of activities needed to participate in their sport, the analysis of fundamental movements should be incorporated into pre-participation screening in order to determine who possesses, or lacks, the ability to perform certain essential movements. In a series of two articles, the background and rationale for the analysis of fundamental movement will be provided. In addition, one such evaluation tool that attempts to assess the fundamental movement patterns performed by an individual, the Functional Movement Screen (FMS™), will be described. Three of the seven fundamental movement patterns that comprise the FMS™ are described in detail in Part I: deep squat, hurdle step, and in-line lunge. Part II of this series, which will be published in the August issue of NAJSPT, will provide a brief review of the analysis of fundamental movements, as well a detailed description of the four additional patterns that complement those presented in Part I (to complete the total of seven fundamental movement patterns which comprise the FMS™): shoulder mobility, active straight leg raise, trunk stability push-up, and rotary stability. The intent of this two part series is to introduce the concept of the evaluation of fundamental movements, whether it is the FMS™ system or a different system devised by another clinician. Such a functional assessment should be incorporated into pre-participation screening in order to determine whether the athlete has the essential movements needed to participate in sports activities with a decreased risk of injury. PMID:21522216

Effect of Functional Status on the Quality of Bowel Preparation in Elderly Patients Undergoing Screening and Surveillance Colonoscopy

PubMed Central

Kumar, Akash; Lin, Lisa; Bernheim, Oren; Bagiella, Emilia; Jandorf, Lina; Itzkowitz, Steven H.; Shah, Brijen J.

2016-01-01

Background/Aims Optimal bowel preparation is essential for successful screening or for surveillance colonoscopy (SC). Inadequate bowel preparation is associated with older age, the male gender, and the presence of certain comorbidities. However, the association between patients’ functional status and bowel preparation quality has not been studied. We prospectively examined the relationship between functional status, namely, the ability to perform activities of daily living (ADLs) and ambulate, and the quality of bowel preparation in elderly patients undergoing SC. Methods Before undergoing SC, 88 elderly patients were surveyed regarding their functional status, specifically regarding their ability to perform ADLs and ambulate a quarter of a mile. Gastroenterologists then determined the quality of the bowel preparation, which was classified as either adequate or inadequate. Then, the frequency of inadequate bowel preparation in patients who did or did not experience difficulty performing ADLs and ambulating was calculated. Results Difficulty ambulating (unadjusted odds ratio [OR], 4.83; p<0.001), difficulty performing ADLs (OR, 2.93; p=0.001), and history of diabetes (OR, 2.88; p=0.007) were significant univariate predictors of inadequate bowel preparation. After adjusting for the above variables, only difficulty ambulating (adjusted OR, 5.78; p=0.004) was an independent predictor of inadequate bowel preparation. Conclusions Difficulty with ambulation is a strong predictor of inadequate bowel preparation in elderly patients undergoing SC. PMID:27021501

Including the people with disabilities at work: a case study of the job of bricklayer in civil construction in Brazil.

PubMed

Martins, L B; Barkokébas Junior, B; Guimarães, B M

2012-01-01

The aim of this paper is to present the results of the evaluation of the job of bricklayer in the construction industry to determine the profile of workers with disabilities who could perform this function and what adjustments are needed. The methods and techniques used in the field study were: direct observation of the activities and the environment, interviews with bricklayers on building sites, a video and photographic record of tasks being carried out to analyze the job of bricklayer, software resources were used. This study set out the disabilities most commonly caused by work accidents in the civil construction industry and simulated the conditions of the individuals to determine whether they could perform the activities of this function and what adaptations are needed. It was observed that workers with hearing impairments could perform activities without any change in the workplace and individuals who had had a leg or foot amputated need to use appropriate prostheses to perform the activities of the function. Thus, it was shown that the activity of professionals with experience in Ergonomics is essential since, by the activity of gathering data and analysing the physical, cognitive and organizational requirements of jobs and by collecting data on and analysing the functional capabilities of the worker with a disability, adaptations to jobs can be adequately defined.

Effects of cilnidipine, a novel dihydropyridine calcium antagonist, on autonomic function, ambulatory blood pressure and heart rate in patients with essential hypertension.

PubMed

Minami, J; Kawano, Y; Makino, Y; Matsuoka, H; Takishita, S

2000-12-01

The aim of the present study was to evaluate the effects of cilnidipine, a novel dihydropyridine calcium antagonist, on autonomic function, ambulatory blood pressure and heart rate in patients with essential hypertension. Ten inpatients with mild to moderate essential hypertension (four men and six women; age: 44-64 years) underwent a drug-free period for 7 days and a treatment period with cilnidipine 10 mg orally for another 7 days, in a randomized crossover study. On the sixth day of each period, they underwent autonomic function tests including a mental arithmetic test, a cold pressor test and a Valsalva manoeuvre. After these tests, 24 h ambulatory blood pressure, heart rate, and the electrocardiogram R-R intervals were monitored every 30 min. A power spectral analysis of R-R intervals was performed to obtain the low-and high-frequency components. Cilnidipine significantly decreased the 24 h blood pressure by 6.5 +/- 1.7 mm Hg systolic (mean +/- s.e.mean; P < 0.01) and 5.0 +/- 1.1 mmHg diastolic (P < 0.01), whereas cilnidipine did not change heart rate or any indices of power spectral components. During the cold pressor test, the maximum change in systolic blood pressure and percentage changes in both systolic and diastolic blood pressures were significantly lower during the treatment period with cilnidipine than during the drug-free period. The baroreflex sensitivity measured from the overshoot phase of the Valsalva manoeuvre did not differ significantly between the two periods. Cilnidipine is effective as a once-daily antihypertensive agent and causes little influence on heart rate and the autonomic nervous system in patients with mild to moderate essential hypertension. Moreover, it is suggested that cilnidipine has an additional clinical benefit in the inhibition of the pressor response induced by acute cold stress.

MUSCULOSKELETAL SCREENING AND FUNCTIONAL TESTING: CONSIDERATIONS FOR BASKETBALL ATHLETES

PubMed Central

Markwick, William J.

2016-01-01

Background and Purpose Youth participation in basketball is on the rise, with basketball one of the top five participation sports in Australia. With increased participation there is a need for greater awareness of the importance of the pre-participation examination, including musculoskeletal screening and functional performance testing as part of a multidisciplinary approach to reducing the risk for future injuries. As majority of all basketball injuries affect the lower extremities, pre-participation musculoskeletal screening and functional performance testing should assess fundamental movement qualities throughout the kinetic chain with an emphasis on lower extremity force characteristics, specifically eccentric loading tasks. Thus, the purpose of this clinical commentary is to review the existing literature elucidating pre-participation musculoskeletal screening and functional performance tests that can be used as a framework for rehabilitation professionals in assessing basketball athletes’ readiness to safely perform the movement demands of their sport. Methods Relevant articles published between 2000 and 2016 using the search terms ‘musculoskeletal screening’, ‘functional testing’, ‘youth athletes’, and ‘basketball’ were identified using MEDLINE. From a basketball-specific perspective, several relevant musculoskeletal assessments were identified, including: the Functional Hop Test Combination, the Landing Error Scoring System, the Tuck Jump Assessment, the Weight-Bearing Lunge Test, and the Star Excursion Balance Test. Each of these assessments creates movement demands that allow for easy identification of inefficient and/or compensatory movement tendencies. A basic understanding of musculoskeletal deficits including bilateral strength and flexibility imbalances, lower crossed syndrome, and dominance-related factors are key components in determination of injury risk. Discussion Assessment of sport-specific movement demands through musculoskeletal screening and functional performance testing is essential for rehabilitation professionals to determine movement competency during performance of fundamental movements related to basketball performance. Youth athletes represent a unique population due to their developing musculoskeletal and neuromuscular systems and should undergo pre-participation musculoskeletal screening for identification of movement limitations. Such an approach to musculoskeletal screening and functional performance may assist in identifying injury risk and also be useful at the end of rehabilitation in determining readiness to return to sport models. Level of Evidence Level 5 PMID:27757291

MUSCULOSKELETAL SCREENING AND FUNCTIONAL TESTING: CONSIDERATIONS FOR BASKETBALL ATHLETES.

PubMed

Bird, Stephen P; Markwick, William J

2016-10-01

Youth participation in basketball is on the rise, with basketball one of the top five participation sports in Australia. With increased participation there is a need for greater awareness of the importance of the pre-participation examination, including musculoskeletal screening and functional performance testing as part of a multidisciplinary approach to reducing the risk for future injuries. As majority of all basketball injuries affect the lower extremities, pre-participation musculoskeletal screening and functional performance testing should assess fundamental movement qualities throughout the kinetic chain with an emphasis on lower extremity force characteristics, specifically eccentric loading tasks. Thus, the purpose of this clinical commentary is to review the existing literature elucidating pre-participation musculoskeletal screening and functional performance tests that can be used as a framework for rehabilitation professionals in assessing basketball athletes' readiness to safely perform the movement demands of their sport. Relevant articles published between 2000 and 2016 using the search terms 'musculoskeletal screening', 'functional testing', 'youth athletes', and 'basketball' were identified using MEDLINE. From a basketball-specific perspective, several relevant musculoskeletal assessments were identified, including: the Functional Hop Test Combination, the Landing Error Scoring System, the Tuck Jump Assessment, the Weight-Bearing Lunge Test, and the Star Excursion Balance Test. Each of these assessments creates movement demands that allow for easy identification of inefficient and/or compensatory movement tendencies. A basic understanding of musculoskeletal deficits including bilateral strength and flexibility imbalances, lower crossed syndrome, and dominance-related factors are key components in determination of injury risk. Assessment of sport-specific movement demands through musculoskeletal screening and functional performance testing is essential for rehabilitation professionals to determine movement competency during performance of fundamental movements related to basketball performance. Youth athletes represent a unique population due to their developing musculoskeletal and neuromuscular systems and should undergo pre-participation musculoskeletal screening for identification of movement limitations. Such an approach to musculoskeletal screening and functional performance may assist in identifying injury risk and also be useful at the end of rehabilitation in determining readiness to return to sport models. Level 5.

The Origin and Early Evolution of Membrane Proteins

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Schweighofer, Karl; Wilson, Michael A.

2005-01-01

Membrane proteins mediate functions that are essential to all cells. These functions include transport of ions, nutrients and waste products across cell walls, capture of energy and its transduction into the form usable in chemical reactions, transmission of environmental signals to the interior of the cell, cellular growth and cell volume regulation. In the absence of membrane proteins, ancestors of cell (protocells), would have had only very limited capabilities to communicate with their environment. Thus, it is not surprising that membrane proteins are quite common even in simplest prokaryotic cells. Considering that contemporary membrane channels are large and complex, both structurally and functionally, a question arises how their presumably much simpler ancestors could have emerged, perform functions and diversify in early protobiological evolution. Remarkably, despite their overall complexity, structural motifs in membrane proteins are quite simple, with a-helices being most common. This suggests that these proteins might have evolved from simple building blocks. To explain how these blocks could have organized into functional structures, we performed large-scale, accurate computer simulations of folding peptides at a water-membrane interface, their insertion into the membrane, self-assembly into higher-order structures and function. The results of these simulations, combined with analysis of structural and functional experimental data led to the first integrated view of the origin and early evolution of membrane proteins.

Key properties of expert movement systems in sport : an ecological dynamics perspective.

PubMed

Seifert, Ludovic; Button, Chris; Davids, Keith

2013-03-01

This paper identifies key properties of expertise in sport predicated on the performer-environment relationship. Weaknesses of traditional approaches to expert performance, which uniquely focus on the performer and the environment separately, are highlighted by an ecological dynamics perspective. Key properties of expert movement systems include 'multi- and meta-stability', 'adaptive variability', 'redundancy', 'degeneracy' and the 'attunement to affordances'. Empirical research on these expert system properties indicates that skill acquisition does not emerge from the internal representation of declarative and procedural knowledge, or the imitation of expert behaviours to linearly reduce a perceived 'gap' separating movements of beginners and a putative expert model. Rather, expert performance corresponds with the ongoing co-adaptation of an individual's behaviours to dynamically changing, interacting constraints, individually perceived and encountered. The functional role of adaptive movement variability is essential to expert performance in many different sports (involving individuals and teams; ball games and outdoor activities; land and aquatic environments). These key properties signify that, in sport performance, although basic movement patterns need to be acquired by developing athletes, there exists no ideal movement template towards which all learners should aspire, since relatively unique functional movement solutions emerge from the interaction of key constraints.

Sleep As A Strategy For Optimizing Performance.

PubMed

Yarnell, Angela M; Deuster, Patricia

2016-01-01

Recovery is an essential component of maintaining, sustaining, and optimizing cognitive and physical performance during and after demanding training and strenuous missions. Getting sufficient amounts of rest and sleep is key to recovery. This article focuses on sleep and discusses (1) why getting sufficient sleep is important, (2) how to optimize sleep, and (3) tools available to help maximize sleep-related performance. Insufficient sleep negatively impacts safety and readiness through reduced cognitive function, more accidents, and increased military friendly-fire incidents. Sufficient sleep is linked to better cognitive performance outcomes, increased vigor, and better physical and athletic performance as well as improved emotional and social functioning. Because Special Operations missions do not always allow for optimal rest or sleep, the impact of reduced rest and sleep on readiness and mission success should be minimized through appropriate preparation and planning. Preparation includes periods of "banking" or extending sleep opportunities before periods of loss, monitoring sleep by using tools like actigraphy to measure sleep and activity, assessing mental effectiveness, exploiting strategic sleep opportunities, and consuming caffeine at recommended doses to reduce fatigue during periods of loss. Together, these efforts may decrease the impact of sleep loss on mission and performance. 2016.

Quasi-finite-time control for high-order nonlinear systems with mismatched disturbances via mapping filtered forwarding technique

NASA Astrophysics Data System (ADS)

Zhang, X.; Huang, X. L.; Lu, H. Q.

2017-02-01

In this study, a quasi-finite-time control method for designing stabilising control laws is developed for high-order strict-feedback nonlinear systems with mismatched disturbances. By using mapping filtered forwarding technique, a virtual control is designed to force the off-the-manifold coordinate to converge to zero in quasi-finite time at each step of the design; at the same time, the manifold is rendered insensitive to time-varying, bounded and unknown disturbances. In terms of standard forwarding methodology, the algorithm proposed here not only does not require the Lyapunov function for controller design, but also avoids to calculate the derivative of sign function. As far as the dynamic performance of closed-loop systems is concerned, we essentially obtain the finite-time performances, which is typically reflected in the following aspects: fast and accurate responses, high tracking precision, and robust disturbance rejection. Spring, mass, and damper system and flexible joints robot are tested to demonstrate the proposed controller performance.

Combining Shigella Tn-seq data with gold-standard E. coli gene deletion data suggests rare transitions between essential and non-essential gene functionality.

PubMed

Freed, Nikki E; Bumann, Dirk; Silander, Olin K

2016-09-06

Gene essentiality - whether or not a gene is necessary for cell growth - is a fundamental component of gene function. It is not well established how quickly gene essentiality can change, as few studies have compared empirical measures of essentiality between closely related organisms. Here we present the results of a Tn-seq experiment designed to detect essential protein coding genes in the bacterial pathogen Shigella flexneri 2a 2457T on a genome-wide scale. Superficial analysis of this data suggested that 481 protein-coding genes in this Shigella strain are critical for robust cellular growth on rich media. Comparison of this set of genes with a gold-standard data set of essential genes in the closely related Escherichia coli K12 BW25113 revealed that an excessive number of genes appeared essential in Shigella but non-essential in E. coli. Importantly, and in converse to this comparison, we found no genes that were essential in E. coli and non-essential in Shigella, implying that many genes were artefactually inferred as essential in Shigella. Controlling for such artefacts resulted in a much smaller set of discrepant genes. Among these, we identified three sets of functionally related genes, two of which have previously been implicated as critical for Shigella growth, but which are dispensable for E. coli growth. The data presented here highlight the small number of protein coding genes for which we have strong evidence that their essentiality status differs between the closely related bacterial taxa E. coli and Shigella. A set of genes involved in acetate utilization provides a canonical example. These results leave open the possibility of developing strain-specific antibiotic treatments targeting such differentially essential genes, but suggest that such opportunities may be rare in closely related bacteria.

The role of assessment in enhancing the vocational success of people with multiple sclerosis.

PubMed

Roessler, R T

1996-01-01

The person/environment or ecological perspective on vocational evaluation provides a comprehensive assessment strategy for people with multiple sclerosis. The ecological model requires assessment of both personal variables such as rehabilitation outlook and MS symptoms and environmental variables such as barriers to workplace accessibility and performance of essential job functions. Measures of person and environment constructs are presented as are applications of the resulting information in vocational counseling and disability management services.

USSR Report World Economy and International Relations No. 11, November 1983.

DTIC Science & Technology

1984-02-07

calculation is obvious: destroy the evolved structure of the Soviet nuclear potential, but keep its own hands free in the nuclear arms buildup...exploited and oppressed throughout the world an example of successful struggle for the right of each people to free and independent development and the...here are essentially of a cosmetic nature and more often than not amount to a simple increase in the number of simple operations or functions performed

Active-passive bistatic surveillance for long range air defense

NASA Astrophysics Data System (ADS)

Wardrop, B.; Molyneux-Berry, M. R. B.

1992-06-01

A hypothetical mobile support receiver capable of working within existing and future air defense networks as a means to maintain essential surveillance functions is considered. It is shown how multibeam receiver architecture supported by digital signal processing can substantially improve surveillance performance against chaff and jamming threats. A dual-mode support receiver concept is proposed which is based on the state-of-the-art phased-array technology, modular processing in industry standard hardware and existing networks.

Three-Dimensional Mapping of Atmospheric Boundary Layer Structure and Winds with a High Performance Lidar

DTIC Science & Technology

1991-04-01

convective plumes which originate from the surface through solar heating. Unlike tower, sodar, and airplane measurements, lidar can provide essentially...average spacing between these bands is given by Xmax. The determination of Xma is complicated by the fact that the two-dimensional spectral power...eddy which results depends critically on the choice of the indicator function (Marht and Frank, 1988). This is due to the fact that the measurement

Applying Wave (registered trademark) to Build an Air Force Community of Interest Shared Space

DTIC Science & Technology

2007-08-01

Performance. It is essential that an inverse transform be defined for every transform, or else the query mediator must be smart enough to figure out how...to invert it. Without an inverse transform , if an incoming query constrains on the transformed attribute, the query mediator might generate a query...plan that is horribly inefficient. If you must code a custom transformation function, you must also code the inverse transform . Putting the

A Fuzzy Logic Optimal Control Law Solution to the CMMCA Tracking Problem

DTIC Science & Technology

1993-03-01

or from a transfer function. Many times, however, the resulting algorithms are so complex as to be completely or essentially useless. Applications...implemented in a nearly real time computer simulation. Located within the LQ framework are all the performance data for both the ClMCA and the CX...repuired nor desired. 34 - / k more general and less exacting framework was used. In order to concentrate on tho theory and problem solution, it was

Inorganic versus organic selenium supplementation: a review.

PubMed

Mahima; Verma, Amit Kumar; Kumar, Amit; Rahal, Anu; Kumar, Vinod; Roy, Debashis

2012-05-01

Selenium is an essential trace element in the diets which is required for maintenance of health, growth and biochemical-physiological functions. The area covered in this review has been rapidly unfolding in recent years and has already acquired a vast spread. This study presents a concise introductory overview of the effect of organic and inorganic selenium on growth performance, carcass traits, daily egg production, egg quality, Se uptake in various tissues and plasma and plasma glutathione peroxidase activity in animals.

Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual blood-stage lifecycle

PubMed Central

Stallmach, Robert; Kavishwar, Manoli; Withers-Martinez, Chrislaine; Hackett, Fiona; Collins, Christine R; Howell, Steven A; Yeoh, Sharon; Knuepfer, Ellen; Atid, Avshalom J; Holder, Anthony A; Blackman, Michael J

2015-01-01

The malaria parasite Plasmodium falciparum replicates in an intraerythrocytic parasitophorous vacuole (PV). The most abundant P. falciparum PV protein, called SERA5, is essential in blood stages and possesses a papain-like domain, prompting speculation that it functions as a proteolytic enzyme. Unusually however, SERA5 possesses a Ser residue (Ser596) at the position of the canonical catalytic Cys of papain-like proteases, and the function of SERA5 or whether it performs an enzymatic role is unknown. In this study, we failed to detect proteolytic activity associated with the Ser596-containing parasite-derived or recombinant protein. However, substitution of Ser596 with a Cys residue produced an active recombinant enzyme with characteristics of a cysteine protease, demonstrating that SERA5 can bind peptides. Using targeted homologous recombination in P. falciparum, we substituted Ser596 with Ala with no phenotypic consequences, proving that SERA5 does not perform an essential enzymatic role in the parasite. We could also replace an internal segment of SERA5 with an affinity-purification tag. In contrast, using almost identical targeting constructs, we could not truncate or C-terminally tag the SERA5 gene, or replace Ser596 with a bulky Arg residue. Our findings show that SERA5 plays an indispensable but non-enzymatic role in the P. falciparum blood-stage life cycle. PMID:25599609

B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review

PubMed Central

Kennedy, David O.

2016-01-01

The B-vitamins comprise a group of eight water soluble vitamins that perform essential, closely inter-related roles in cellular functioning, acting as co-enzymes in a vast array of catabolic and anabolic enzymatic reactions. Their collective effects are particularly prevalent to numerous aspects of brain function, including energy production, DNA/RNA synthesis/repair, genomic and non-genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules. However, human epidemiological and controlled trial investigations, and the resultant scientific commentary, have focused almost exclusively on the small sub-set of vitamins (B9/B12/B6) that are the most prominent (but not the exclusive) B-vitamins involved in homocysteine metabolism. Scant regard has been paid to the other B vitamins. This review describes the closely inter-related functions of the eight B-vitamins and marshals evidence suggesting that adequate levels of all members of this group of micronutrients are essential for optimal physiological and neurological functioning. Furthermore, evidence from human research clearly shows both that a significant proportion of the populations of developed countries suffer from deficiencies or insufficiencies in one or more of this group of vitamins, and that, in the absence of an optimal diet, administration of the entire B-vitamin group, rather than a small sub-set, at doses greatly in excess of the current governmental recommendations, would be a rational approach for preserving brain health. PMID:26828517

B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review.

PubMed

Kennedy, David O

2016-01-27

The B-vitamins comprise a group of eight water soluble vitamins that perform essential, closely inter-related roles in cellular functioning, acting as co-enzymes in a vast array of catabolic and anabolic enzymatic reactions. Their collective effects are particularly prevalent to numerous aspects of brain function, including energy production, DNA/RNA synthesis/repair, genomic and non-genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules. However, human epidemiological and controlled trial investigations, and the resultant scientific commentary, have focused almost exclusively on the small sub-set of vitamins (B9/B12/B6) that are the most prominent (but not the exclusive) B-vitamins involved in homocysteine metabolism. Scant regard has been paid to the other B vitamins. This review describes the closely inter-related functions of the eight B-vitamins and marshals evidence suggesting that adequate levels of all members of this group of micronutrients are essential for optimal physiological and neurological functioning. Furthermore, evidence from human research clearly shows both that a significant proportion of the populations of developed countries suffer from deficiencies or insufficiencies in one or more of this group of vitamins, and that, in the absence of an optimal diet, administration of the entire B-vitamin group, rather than a small sub-set, at doses greatly in excess of the current governmental recommendations, would be a rational approach for preserving brain health.

Non-coding stem-bulge RNAs are required for cell proliferation and embryonic development in C. elegans

PubMed Central

Kowalski, Madzia P.; Baylis, Howard A.; Krude, Torsten

2015-01-01

ABSTRACT Stem bulge RNAs (sbRNAs) are a family of small non-coding stem-loop RNAs present in Caenorhabditis elegans and other nematodes, the function of which is unknown. Here, we report the first functional characterisation of nematode sbRNAs. We demonstrate that sbRNAs from a range of nematode species are able to reconstitute the initiation of chromosomal DNA replication in the presence of replication proteins in vitro, and that conserved nucleotide sequence motifs are essential for this function. By functionally inactivating sbRNAs with antisense morpholino oligonucleotides, we show that sbRNAs are required for S phase progression, early embryonic development and the viability of C. elegans in vivo. Thus, we demonstrate a new and essential role for sbRNAs during the early development of C. elegans. sbRNAs show limited nucleotide sequence similarity to vertebrate Y RNAs, which are also essential for the initiation of DNA replication. Our results therefore establish that the essential function of small non-coding stem-loop RNAs during DNA replication extends beyond vertebrates. PMID:25908866

Computer Modeling of the Earliest Cellular Structures and Functions

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Chipot, Christophe; Schweighofer, Karl

2000-01-01

In the absence of extinct or extant record of protocells (the earliest ancestors of contemporary cells). the most direct way to test our understanding of the origin of cellular life is to construct laboratory models of protocells. Such efforts are currently underway in the NASA Astrobiology Program. They are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures and developing designs for molecules that perform proto-cellular functions. Many of these functions, such as import of nutrients, capture and storage of energy. and response to changes in the environment are carried out by proteins bound to membrane< We will discuss a series of large-scale, molecular-level computer simulations which demonstrate (a) how small proteins (peptides) organize themselves into ordered structures at water-membrane interfaces and insert into membranes, (b) how these peptides aggregate to form membrane-spanning structures (eg. channels), and (c) by what mechanisms such aggregates perform essential proto-cellular functions, such as proton transport of protons across cell walls, a key step in cellular bioenergetics. The simulations were performed using the molecular dynamics method, in which Newton's equations of motion for each item in the system are solved iteratively. The problems of interest required simulations on multi-nanosecond time scales, which corresponded to 10(exp 6)-10(exp 8) time steps.

Rubber closures for freeze-dried products.

PubMed

Hopkins, G H

1976-10-01

Once a biological product has been developed to perform its required medical or pharmaceutical function, it is essential that a container-closure system by chosen which will preserve the efficacy of the product up to the point of administration. The general requirements applicable to proper closure function will be reviewed and the suitability of natural and synthetic elastomers to perform these functions will be discussed. The specialized application of elastomeric materials as closures for freeze-dried products presents additional requirements which are superimposed upon those previously discussed. The first of these unique considerations relates to the proper physical design which will permit the outgassing of water vapor during the sublimation step in the lyophilizing chamber. During this outgassing the design must also permit the closure to remain affixed in the neck while only partially inserted. Since these preparations are lyophilized because they are unstable in aqueous solutions, the elastomer used must constitute an effective barrier to the transmission of moisture vapor through the closure. The MVT and gas transmission properties of elastomers will be discussed. Special consideration will be given to the extremely low temperatures used in the sublimation, stoppering, and storage before use of lyophilized products. The phenomenon of glass transition points with different elastomers will be explained as its relation to satisfactory performance of the closure function at low temperatures.

The Americans with Disabilities Act: Using Job Analysis To Meet New Challenges.

ERIC Educational Resources Information Center

Lozada-Larsen, Susana R.

This paper focuses on the role that job analysis plays under the Americans with Disabilities Act (ADA). The most obvious use of job analysis data is in defining the essential functions of each job. The job analysis technique used should: list the functions of the job, define which functions are essential rather than marginal, and offer proof of…

Performance of a Miniaturized Arcjet

NASA Technical Reports Server (NTRS)

Sankovic, John M.; Jacobson, David T.

1995-01-01

Performance measurements were obtained and life-limiting mechanisms were identified on a laboratory-model arcjet thruster designed to operate at a nominal power level of 300 W. The design employed a supersonic-arc-attachment concept and was operated from 200 to 400 W on hydrogen/nitrogen mixtures in ratios simulating fully decomposed hydrazine and ammonia. Power was provided by breadboard power processor. Performance was found to be a strong function of propellant flow rate. Anode losses were essentially constant for the range of mass flow rates tested. It is believed that the performance is dominated by viscous effects. Significantly improved performance was noted with simulated ammonia operation. At 300 W the specific impulse on simulated ammonia was 410 s with an efficiency of 0.34, while simulated hydrazine provided 370 s specific impulse at an efficiency of 0.27.

Analysis of the functional domains of the mismatch repair homologue Msh1p and its role in mitochondrial genome maintenance.

PubMed

Mookerjee, Shona A; Lyon, Hiram D; Sia, Elaine A

2005-02-01

Mitochondrial DNA (mtDNA) repair occurs in all eukaryotic organisms and is essential for the maintenance of mitochondrial function. Evidence from both humans and yeast suggests that mismatch repair is one of the pathways that functions in overall mtDNA stability. In the mitochondria of the yeast Saccharomyces cerevisiae, the presence of a homologue to the bacterial MutS mismatch repair protein, MSH1, has long been known to be essential for mitochondrial function. The mechanisms for which it is essential are unclear, however. Here, we analyze the effects of two point mutations, msh1-F105A and msh1-G776D, both predicted to be defective in mismatch repair; and we show that they are both able to maintain partial mitochondrial function. Moreover, there are significant differences in the severity of mitochondrial disruption between the two mutants that suggest multiple roles for Msh1p in addition to mismatch repair. Our overall findings suggest that these additional predicted functions of Msh1p, including recombination surveillance and heteroduplex rejection, may be primarily responsible for its essential role in mtDNA stability.

Lipid-Antigen Presentation by CD1d+ B Cells Is Essential for the Maintenance of Invariant Natural Killer T Cells

PubMed Central

Bosma, Anneleen; Abdel-Gadir, Azza; Isenberg, David A.; Jury, Elizabeth C.; Mauri, Claudia

2012-01-01

Summary B cells perform many immunological functions, including presenting lipid antigen to CD1d-restricted invariant natural killer T (iNKT) cells, known to contribute to maintaining tolerance in autoimmunity. Patients with systemic lupus erythematous (SLE) display dysregulated B cell responses and reduced peripheral iNKT cell frequencies. The significance of these defects and how they relate to SLE pathogenesis remain elusive. We report that B cells are essential for iNKT cell expansion and activation in healthy donors but fail to exert a similar effect in SLE patients. Defective B cell-mediated stimulation of iNKT cells in SLE patients was associated with altered CD1d recycling, a defect recapitulated in B cells from healthy donors after stimulation with interferon-α (IFN-α) and anti-immunoglobulin (Ig). iNKT cell number and function were restored in SLE patients responding to anti-CD20 treatment upon normalization of CD1d expression exclusively in repopulated immature B cells. We propose that healthy B cells are pivotal for iNKT cell homeostasis. PMID:22406267

A coarse-grained model of microtubule self-assembly

NASA Astrophysics Data System (ADS)

Regmi, Chola; Cheng, Shengfeng

Microtubules play critical roles in cell structures and functions. They also serve as a model system to stimulate the next-generation smart, dynamic materials. A deep understanding of their self-assembly process and biomechanical properties will not only help elucidate how microtubules perform biological functions, but also lead to exciting insight on how microtubule dynamics can be altered or even controlled for specific purposes such as suppressing the division of cancer cells. Combining all-atom molecular dynamics (MD) simulations and the essential dynamics coarse-graining method, we construct a coarse-grained (CG) model of the tubulin protein, which is the building block of microtubules. In the CG model a tubulin dimer is represented as an elastic network of CG sites, the locations of which are determined by examining the protein dynamics of the tubulin and identifying the essential dynamic domains. Atomistic MD modeling is employed to directly compute the tubulin bond energies in the surface lattice of a microtubule, which are used to parameterize the interactions between CG building blocks. The CG model is then used to study the self-assembly pathways, kinetics, dynamics, and nanomechanics of microtubules.

Gamma power and cognition in patients with schizophrenia and their first-degree relatives.

PubMed

Díez, Álvaro; Suazo, Vanessa; Casado, Pilar; Martín-Loeches, Manuel; Molina, Vicente

2014-01-01

Gamma oscillations are essential for functional neural assembly formation underlying higher cerebral functions. Previous studies concerning gamma band power in schizophrenia have yielded diverse results. In this study, we assessed gamma band power in minimally treated patients with schizophrenia, their first-degree relatives and healthy controls during an oddball paradigm performance, as well as the relation between gamma power and cognitive performance. We found a higher gamma power in the patient group than in the healthy controls at the P3, P4, Fz, Pz and T5 sites. Compared with their relatives, gamma power in the patients was only marginally higher over P3 and P4. We found a nearly significant inverse association between gamma power at F4 and Tower of London performance in the patients, as well as a significant inverse association between gamma power at T5 and verbal memory and working memory scores in the relatives. These results support higher total gamma power in association with schizophrenia and its inverse association with cognitive performance in patients and their first-degree relatives.

Consumer diversity across kingdoms supports multiple functions in a coastal ecosystem

PubMed Central

Hensel, Marc J. S.; Silliman, Brian R.

2013-01-01

The global biodiversity crisis impairs the valuable benefits ecosystems provide humans. These nature-generated benefits are defined by a multitude of different ecosystem functions that operate simultaneously. Although several studies have simulated species loss in communities and tracked the response of single functions such as productivity or nutrient cycling, these studies have involved relatively similar taxa, and seldom are strikingly different functions examined. With the exception of highly managed ecosystems such as agricultural fields, rarely are we interested in only one function being performed well. Instead, we rely on ecosystems to deliver several different functions at the same time. Here, we experimentally investigated the extinction impacts of dominant consumers in a salt marsh. These consumers are remarkably phylogenetically diverse, spanning two kingdoms (i.e., Animalia and Fungi). Our field studies reveal that a diverse consumer assemblage significantly enhances simultaneous functioning of disparate ecosystem processes (i.e., productivity, decomposition, and infiltration). Extreme functional and phylogenetic differences among consumers underlie this relationship. Each marsh consumer affected at least one different ecosystem function, and each individual function was affected by no more than two consumers. The implications of these findings are profound: If we want ecosystems to perform many different functions well, it is not just number of species that matter. Rather, the presence of species representing markedly different ecologies and biology is also essential to maximizing multiple functions. Moreover, this work emphasizes the need to incorporate both microcomponents and macrocomponents of food webs to accurately predict biodiversity declines on integrated-ecosystem functioning. PMID:24297926

Expansion of a physical function item bank and development of an abbreviated form for clinical research.

PubMed

Bode, Rita K; Lai, Jin-shei; Dineen, Kelly; Heinemann, Allen W; Shevrin, Daniel; Von Roenn, Jamie; Cella, David

2006-01-01

We expanded an existing 33-item physical function (PF) item bank with a sufficient number of items to enable computerized adaptive testing (CAT). Ten items were written to expand the bank and the new item pool was administered to 295 people with cancer. For this analysis of the new pool, seven poorly performing items were identified for further examination. This resulted in a bank with items that define an essentially unidimensional PF construct, cover a wide range of that construct, reliably measure the PF of persons with cancer, and distinguish differences in self-reported functional performance levels. We also developed a 5-item (static) assessment form ("BriefPF") that can be used in clinical research to express scores on the same metric as the overall bank. The BriefPF was compared to the PF-10 from the Medical Outcomes Study SF-36. Both short forms significantly differentiated persons across functional performance levels. While the entire bank was more precise across the PF continuum than either short form, there were differences in the area of the continuum in which each short form was more precise: the BriefPF was more precise than the PF-10 at the lower functional levels and the PF-10 was more precise than the BriefPF at the higher levels. Future research on this bank will include the development of a CAT version, the PF-CAT.

Exascale computing and big data

DOE PAGES

Reed, Daniel A.; Dongarra, Jack

2015-06-25

Scientific discovery and engineering innovation requires unifying traditionally separated high-performance computing and big data analytics. The tools and cultures of high-performance computing and big data analytics have diverged, to the detriment of both; unification is essential to address a spectrum of major research domains. The challenges of scale tax our ability to transmit data, compute complicated functions on that data, or store a substantial part of it; new approaches are required to meet these challenges. Finally, the international nature of science demands further development of advanced computer architectures and global standards for processing data, even as international competition complicates themore » openness of the scientific process.« less

Exascale computing and big data

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

Reed, Daniel A.; Dongarra, Jack

Scientific discovery and engineering innovation requires unifying traditionally separated high-performance computing and big data analytics. The tools and cultures of high-performance computing and big data analytics have diverged, to the detriment of both; unification is essential to address a spectrum of major research domains. The challenges of scale tax our ability to transmit data, compute complicated functions on that data, or store a substantial part of it; new approaches are required to meet these challenges. Finally, the international nature of science demands further development of advanced computer architectures and global standards for processing data, even as international competition complicates themore » openness of the scientific process.« less

Sensor performance analysis

NASA Technical Reports Server (NTRS)

Montgomery, H. E.; Ostrow, H.; Ressler, G. M.

1990-01-01

The theory is described and the equations required to design are developed and the performance of electro-optical sensor systems that operate from the visible through the thermal infrared spectral regions are analyzed. Methods to compute essential optical and detector parameters, signal-to-noise ratio, MTF, and figures of merit such as NE delta rho and NE delta T are developed. A set of atmospheric tables are provided to determine scene radiance in the visible spectral region. The Planck function is used to determine radiance in the infrared. The equations developed were incorporated in a spreadsheet so that a wide variety of sensor studies can be rapidly and efficiently conducted.

Neyman-Pearson biometric score fusion as an extension of the sum rule

NASA Astrophysics Data System (ADS)

Hube, Jens Peter

2007-04-01

We define the biometric performance invariance under strictly monotonic functions on match scores as normalization symmetry. We use this symmetry to clarify the essential difference between the standard score-level fusion approaches of sum rule and Neyman-Pearson. We then express Neyman-Pearson fusion assuming match scores defined using false acceptance rates on a logarithmic scale. We show that by stating Neyman-Pearson in this form, it reduces to sum rule fusion for ROC curves with logarithmic slope. We also introduce a one parameter model of biometric performance and use it to express Neyman-Pearson fusion as a weighted sum rule.

Brazilian Normative Data on Letter and Category Fluency Tasks: Effects of Gender, Age, and Geopolitical Region

PubMed Central

Hazin, Izabel; Leite, Gilmara; Oliveira, Rosinda M.; Alencar, João C.; Fichman, Helenice C.; Marques, Priscila d. N.; de Mello, Claudia Berlim

2016-01-01

Verbal fluency is a basic function of language that refers to the ability to produce fluent speech. Despite being an essentially linguistic function, its measurements are also used to evaluate executive aspects of verbal behavior. Performance in verbal fluency (VF) tasks varies according to age, education, and cognitive development. Neurodevelopmental disorders that affect the functioning of frontal areas tend to cause lower performance in VF tasks. Despite the relative consensus that has been reached in terms of the use of VF tasks for the diagnosis of dyslexia and attention-deficit/hyperactivity disorder, few studies have considered regional variations in Brazil. The present study sought to provide normative data on VF tasks in children by considering gender, age, education, and geopolitical region of origin with auxiliary purposes in neuropsychological diagnosis of disorders that occur with executive changes The study included 298 participants, 7–10 years of age of both genders, who performed three letter fluency tasks and three category fluency tasks. The data were subjected to correlational and variance analyses, with age and gender as factors. No effect of gender on the children's performance was found. However, significant differences between age groups were observed, with better performance in letter tasks in older children and better performance in letter tasks compared with category tasks. Significant regional differences in performance on the letter VF task were observed. These results reinforce the importance of regional normative data in countries with high regional cultural variations, such as Brazil. PMID:27242598

Iron nutrition and premenopausal women: effects of poor iron status on physical and neuropsychological performance.

PubMed

McClung, James P; Murray-Kolb, Laura E

2013-01-01

Iron is a nutritionally essential trace element that functions through incorporation into proteins and enzymes, many of which contribute to physical and neuropsychological performance. Poor iron status, including iron deficiency (ID; diminished iron stores) and iron deficiency anemia (IDA; poor iron stores and diminished hemoglobin), affects billions of people worldwide. This review focuses on physical and neuropsychological outcomes associated with ID and IDA in premenopausal women, as the prevalence of ID and IDA is often greater in premenopausal women than other population demographics. Recent studies addressing the physiological effects of poor iron status on physical performance, including work productivity, voluntary activity, and athletic performance, are addressed. Similarly, the effects of iron status on neurological performance, including cognition, affect, and behavior, are summarized. Nutritional countermeasures for the prevention of poor iron status and the restoration of decrements in performance outcomes are described.

Adaptive Working Memory Training Reduces the Negative Impact of Anxiety on Competitive Motor Performance.

PubMed

Ducrocq, Emmanuel; Wilson, Mark; Smith, Tim J; Derakshan, Nazanin

2017-12-01

Optimum levels of attentional control are essential to prevent athletes from experiencing performance breakdowns under pressure. The current study explored whether training attentional control using the adaptive dual n-back paradigm, designed to directly target processing efficiency of the main executive functions of working memory (WM), would result in transferrable effects on sports performance outcomes. A total of 30 tennis players were allocated to an adaptive WM training or active control group and underwent 10 days of training. Measures of WM capacity as well as performance and objective gaze indices of attentional control in a tennis volley task were assessed in low- and high-pressure posttraining conditions. Results revealed significant benefits of training on WM capacity, quiet eye offset, and tennis performance in the high-pressure condition. Our results confirm and extend previous findings supporting the transfer of cognitive training benefits to objective measures of sports performance under pressure.

Hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry for highly rapid and sensitive analysis of underivatized amino acids in functional foods.

PubMed

Zhou, Guisheng; Pang, Hanqing; Tang, Yuping; Yao, Xin; Mo, Xuan; Zhu, Shaoqing; Guo, Sheng; Qian, Dawei; Qian, Yefei; Su, Shulan; Zhang, Li; Jin, Chun; Qin, Yong; Duan, Jin-ao

2013-05-01

This work presented a new analytical methodology based on hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry in multiple-reaction monitoring mode for analysis of 24 underivatized free amino acids (FAAs) in functional foods. The proposed method was first reported and validated by assessing the matrix effects, linearity, limit of detections and limit of quantifications, precision, repeatability, stability and recovery of all target compounds, and it was used to determine the nutritional substances of FAAs in ginkgo seeds and further elucidate the nutritional value of this functional food. The result showed that ginkgo seed turned out to be a good source of FAAs with high levels of several essential FAAs and to have a good nutritional value. Furthermore, the principal component analysis was performed to classify the ginkgo seed samples on the basis of 24 FAAs. As a result, the samples could be mainly clustered into three groups, which were similar to areas classification. Overall, the presented method would be useful for the investigation of amino acids in edible plants and agricultural products.

The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation.

PubMed

Suzuki, K; Kirisako, T; Kamada, Y; Mizushima, N; Noda, T; Ohsumi, Y

2001-11-01

Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Apg proteins coordinate the formation of autophagosomes. Several key reactions performed by these proteins have been described, but a comprehensive understanding of the overall network is still lacking. Based on Apg protein localization, we have identified a novel structure that functions in autophagosome formation. This pre-autophagosomal structure, containing at least five Apg proteins, i.e. Apg1p, Apg2p, Apg5p, Aut7p/Apg8p and Apg16p, is localized in the vicinity of the vacuole. Analysis of apg mutants revealed that the formation of both a phosphatidylethanolamine-conjugated Aut7p and an Apg12p- Apg5p conjugate is essential for the localization of Aut7p to the pre-autophagosomal structure. Vps30p/Apg6p and Apg14p, components of an autophagy- specific phosphatidylinositol 3-kinase complex, Apg9p and Apg16p are all required for the localization of Apg5p and Aut7p to the structure. The Apg1p protein kinase complex functions in the late stage of autophagosome formation. Here, we present the classification of Apg proteins into three groups that reflect each step of autophagosome formation.

The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation

PubMed Central

Suzuki, Kuninori; Kirisako, Takayoshi; Kamada, Yoshiaki; Mizushima, Noboru; Noda, Takeshi; Ohsumi, Yoshinori

2001-01-01

Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Apg proteins coordinate the formation of autophagosomes. Several key reactions performed by these proteins have been described, but a comprehensive understanding of the overall network is still lacking. Based on Apg protein localization, we have identified a novel structure that functions in autophagosome formation. This pre-autophagosomal structure, containing at least five Apg proteins, i.e. Apg1p, Apg2p, Apg5p, Aut7p/Apg8p and Apg16p, is localized in the vicinity of the vacuole. Analysis of apg mutants revealed that the formation of both a phosphatidylethanolamine-conjugated Aut7p and an Apg12p– Apg5p conjugate is essential for the localization of Aut7p to the pre-autophagosomal structure. Vps30p/Apg6p and Apg14p, components of an autophagy- specific phosphatidylinositol 3-kinase complex, Apg9p and Apg16p are all required for the localization of Apg5p and Aut7p to the structure. The Apg1p protein kinase complex functions in the late stage of autophagosome formation. Here, we present the classification of Apg proteins into three groups that reflect each step of autophagosome formation. PMID:11689437

Nanoprocess and nanoscale surface functionalization on cathode materials for advanced lithium-ion batteries.

PubMed

Alaboina, Pankaj Kumar; Uddin, Md-Jamal; Cho, Sung-Jin

2017-10-26

Nanotechnology-driven development of cathode materials is an essential part to revolutionize the evolution of the next generation lithium ion batteries. With the progress of nanoprocess and nanoscale surface modification investigations on cathode materials in recent years, the advanced battery technology future seems very promising - Thanks to nanotechnology. In this review, an overview of promising nanoscale surface deposition methods and their significance in surface functionalization on cathodes is extensively summarized. Surface modified cathodes are provided with a protective layer to overcome the electrochemical performance limitations related to side reactions with electrolytes, reduce self-discharge reactions, improve thermal and structural stability, and further enhance the overall battery performance. The review addresses the importance of nanoscale surface modification on battery cathodes and concludes with a comparison of the different nanoprocess techniques discussed to provide a direction in the race to build advanced lithium-ion batteries.

pH-programmable DNA logic arrays powered by modular DNAzyme libraries.

PubMed

Elbaz, Johann; Wang, Fuan; Remacle, Francoise; Willner, Itamar

2012-12-12

Nature performs complex information processing circuits, such the programmed transformations of versatile stem cells into targeted functional cells. Man-made molecular circuits are, however, unable to mimic such sophisticated biomachineries. To reach these goals, it is essential to construct programmable modular components that can be triggered by environmental stimuli to perform different logic circuits. We report on the unprecedented design of artificial pH-programmable DNA logic arrays, constructed by modular libraries of Mg(2+)- and UO(2)(2+)-dependent DNAzyme subunits and their substrates. By the appropriate modular design of the DNA computation units, pH-programmable logic arrays of various complexities are realized, and the arrays can be erased, reused, and/or reprogrammed. Such systems may be implemented in the near future for nanomedical applications by pH-controlled regulation of cellular functions or may be used to control biotransformations stimulated by bacteria.

Evaluation and Validation of Organic Materials for Advanced Stirling Convertors (ASCs): Overview

NASA Technical Reports Server (NTRS)

Shin, Euy-Sik Eugene

2015-01-01

Various organic materials are used as essential parts in Stirling Convertors for their unique properties and functionalities such as bonding, potting, sealing, thread locking, insulation, and lubrication. More efficient Advanced Stirling Convertors (ASC) are being developed for future space applications especially with a long mission cycle, sometimes up to 17 years, such as deep space exploration or lunar surface power or Mars rovers, and others. Thus, performance, durability, and reliability of those organics should be critically evaluated in every possible material-process-fabrication-service environment relations based on their mission specifications. In general, thermal stability, radiation hardness, outgassing, and material compatibility of the selected organics have been systematically evaluated while their process and fabrication conditions and procedures were being optimized. Service environment-simulated long term aging tests up to 4 years were performed as a function of temperature for durability assessment of the most critical organic material systems.

The Est3 protein associates with yeast telomerase through an OB-fold domain

PubMed Central

Lee, Jaesung S.; Mandell, Edward K.; Tucey, Timothy M.; Morris, Danna K.; Victoria, Lundblad

2009-01-01

The Est3 protein is a small regulatory subunit of yeast telomerase which is dispensable for enzyme catalysis but essential for telomere replication in vivo. Using structure prediction combined with in vivo characterization, we show here that Est3 consists of a predicted OB (oligo-saccharide/oligo-nucleotide binding) fold. Mutagenesis of predicted surface residues was used to generate a functional map of one surface of Est3, which identified a site that mediates association with the telomerase complex. Surprisingly, the predicted OB-fold of Est3 is structurally similar to the OB-fold of the mammalian TPP1 protein, despite the fact that Est3 and TPP1, as components of telomerase and a telomere capping complex, respectively, perform functionally distinct tasks at chromosome ends. The analysis performed on Est3 may be instructive in generating comparable missense mutations on the surface of the OB-fold domain of TPP1. PMID:19172754

Utility of Space Transportation System to Space Communication Community

NASA Technical Reports Server (NTRS)

Bronstein, L. M.

1975-01-01

A potentially cost effective technique was investigated of launching operational satellites into synchronous orbit using the space transportation system (STS). This technique uses an unguided spinning solid rocket motor as the means for boosting a satellite from a low altitude shuttle parking orbit into a synchronous transfer orbit. The spacecraft is then injected into a geosynchronous orbit by an apogee kick motor fired at transfer orbit apogee. The approach is essentially that used on all Delta and Atlas-Centaur launches of synchronous satellites with the shuttle orbiter performing the function of the first two stages of the Delta three stage launch vehicle and the perigee kick motor performing the function of the Delta third state. It is concluded that the STS can be useful to the space communication community as well as to other geostationary satellite system users if the recommended actions are implemented.

Centralized and Decentralized Control for Demand Response

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

Lu, Shuai; Samaan, Nader A.; Diao, Ruisheng

2011-04-29

Demand response has been recognized as an essential element of the smart grid. Frequency response, regulation and contingency reserve functions performed traditionally by generation resources are now starting to involve demand side resources. Additional benefits from demand response include peak reduction and load shifting, which will defer new infrastructure investment and improve generator operation efficiency. Technical approaches designed to realize these functionalities can be categorized into centralized control and decentralized control, depending on where the response decision is made. This paper discusses these two control philosophies and compares their relative advantages and disadvantages in terms of delay time, predictability, complexity,more » and reliability. A distribution system model with detailed household loads and controls is built to demonstrate the characteristics of the two approaches. The conclusion is that the promptness and reliability of decentralized control should be combined with the predictability and simplicity of centralized control to achieve the best performance of the smart grid.« less

Analytical functions to predict cosmic-ray neutron spectra in the atmosphere.

PubMed

Sato, Tatsuhiko; Niita, Koji

2006-09-01

Estimation of cosmic-ray neutron spectra in the atmosphere has been an essential issue in the evaluation of the aircrew doses and the soft-error rates of semiconductor devices. We therefore performed Monte Carlo simulations for estimating neutron spectra using the PHITS code in adopting the nuclear data library JENDL-High-Energy file. Excellent agreements were observed between the calculated and measured spectra for a wide altitude range even at the ground level. Based on a comprehensive analysis of the simulation results, we propose analytical functions that can predict the cosmic-ray neutron spectra for any location in the atmosphere at altitudes below 20 km, considering the influences of local geometries such as ground and aircraft on the spectra. The accuracy of the analytical functions was well verified by various experimental data.

Facial anatomy.

PubMed

Marur, Tania; Tuna, Yakup; Demirci, Selman

2014-01-01

Dermatologic problems of the face affect both function and aesthetics, which are based on complex anatomical features. Treating dermatologic problems while preserving the aesthetics and functions of the face requires knowledge of normal anatomy. When performing successfully invasive procedures of the face, it is essential to understand its underlying topographic anatomy. This chapter presents the anatomy of the facial musculature and neurovascular structures in a systematic way with some clinically important aspects. We describe the attachments of the mimetic and masticatory muscles and emphasize their functions and nerve supply. We highlight clinically relevant facial topographic anatomy by explaining the course and location of the sensory and motor nerves of the face and facial vasculature with their relations. Additionally, this chapter reviews the recent nomenclature of the branching pattern of the facial artery. © 2013 Elsevier Inc. All rights reserved.

Team Training for Dynamic Cross-Functional Teams in Aviation: Behavioral, Cognitive, and Performance Outcomes.

PubMed

Littlepage, Glenn E; Hein, Michael B; Moffett, Richard G; Craig, Paul A; Georgiou, Andrea M

2016-12-01

This study evaluates the effectiveness of a training program designed to improve cross-functional coordination in airline operations. Teamwork across professional specializations is essential for safe and efficient airline operations, but aviation education primarily emphasizes positional knowledge and skill. Although crew resource management training is commonly used to provide some degree of teamwork training, it is generally focused on specific specializations, and little training is provided in coordination across specializations. The current study describes and evaluates a multifaceted training program designed to enhance teamwork and team performance of cross-functional teams within a simulated airline flight operations center. The training included a variety of components: orientation training, position-specific declarative knowledge training, position-specific procedural knowledge training, a series of high-fidelity team simulations, and a series of after-action reviews. Following training, participants demonstrated more effective teamwork, development of transactive memory, and more effective team performance. Multifaceted team training that incorporates positional training and team interaction in complex realistic situations and followed by after-action reviews can facilitate teamwork and team performance. Team training programs, such as the one described here, have potential to improve the training of aviation professionals. These techniques can be applied to other contexts where multidisciplinary teams and multiteam systems work to perform highly interdependent activities. © 2016, Human Factors and Ergonomics Society.

Noradrenaline transporter blockade increases fronto-parietal functional connectivity relevant for working memory.

PubMed

Hernaus, Dennis; Casales Santa, Marta Ma; Offermann, Jan Stefan; Van Amelsvoort, Thérèse

2017-04-01

Experimental animal work has demonstrated that dopamine and noradrenaline play an essential role in modulating prefrontal cortex-mediated networks underlying working memory performance. Studies of functional connectivity have been instrumental in extending such notions to humans but, so far, have almost exclusively focussed on pharmacological agents with a predominant dopaminergic mechanism of action. Here, we investigate the effect of a single dose of atomoxetine 60mg, a noradrenaline transporter inhibitor, on working memory performance and associated functional connectivity during an n-back task in 19 healthy male volunteers. Atomoxetine increased functional connectivity between right anterior insula and dorsolateral prefrontal cortex, precentral gyrus, posterior parietal cortex and precuneus during the high-working memory load condition of the n-back task. Increased atomoxetine-induced insula-dorsolateral prefrontal cortex functional connectivity during this condition correlated with decreased reaction time variability and was furthermore predicted by working memory capacity. These results show for the first time that noradrenaline transporter blockade-induced increases in cortical catecholamines accentuate fronto-parietal working memory-related network integrity. The observation of significant inter-subject variability in response to atomoxetine has implications for inverted-U frameworks of dopamine and noradrenaline function, which could be useful to predict drug effects in clinical disorders with variable treatment response. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Linking Inter-Individual Variability in Functional Brain Connectivity to Cognitive Ability in Elderly Individuals

PubMed Central

Li, Rui; Yin, Shufei; Zhu, Xinyi; Ren, Weicong; Yu, Jing; Wang, Pengyun; Zheng, Zhiwei; Niu, Ya-Nan; Huang, Xin; Li, Juan

2017-01-01

Increasing evidence suggests that functional brain connectivity is an important determinant of cognitive aging. However, the fundamental concept of inter-individual variations in functional connectivity in older individuals is not yet completely understood. It is essential to evaluate the extent to which inter-individual variability in connectivity impacts cognitive performance at an older age. In the current study, we aimed to characterize individual variability of functional connectivity in the elderly and to examine its significance to individual cognition. We mapped inter-individual variability of functional connectivity by analyzing whole-brain functional connectivity magnetic resonance imaging data obtained from a large sample of cognitively normal older adults. Our results demonstrated a gradual increase in variability in primary regions of the visual, sensorimotor, and auditory networks to specific subcortical structures, particularly the hippocampal formation, and the prefrontal and parietal cortices, which largely constitute the default mode and fronto-parietal networks, to the cerebellum. Further, the inter-individual variability of the functional connectivity correlated significantly with the degree of cognitive relevance. Regions with greater connectivity variability demonstrated more connections that correlated with cognitive performance. These results also underscored the crucial function of the long-range and inter-network connections in individual cognition. Thus, individual connectivity–cognition variability mapping findings may provide important information for future research on cognitive aging and neurocognitive diseases. PMID:29209203

The quality of clinical maternal and neonatal healthcare - a strategy for identifying 'routine care signal functions'.

PubMed

Brenner, Stephan; De Allegri, Manuela; Gabrysch, Sabine; Chinkhumba, Jobiba; Sarker, Malabika; Muula, Adamson S

2015-01-01

A variety of clinical process indicators exists to measure the quality of care provided by maternal and neonatal health (MNH) programs. To allow comparison across MNH programs in low- and middle-income countries (LMICs), a core set of essential process indicators is needed. Although such a core set is available for emergency obstetric care (EmOC), the 'EmOC signal functions', a similar approach is currently missing for MNH routine care evaluation. We describe a strategy for identifying core process indicators for routine care and illustrate their usefulness in a field example. We first developed an indicator selection strategy by combining epidemiological and programmatic aspects relevant to MNH in LMICs. We then identified routine care process indicators meeting our selection criteria by reviewing existing quality of care assessment protocols. We grouped these indicators into three categories based on their main function in addressing risk factors of maternal or neonatal complications. We then tested this indicator set in a study assessing MNH quality of clinical care in 33 health facilities in Malawi. Our strategy identified 51 routine care processes: 23 related to initial patient risk assessment, 17 to risk monitoring, 11 to risk prevention. During the clinical performance assessment a total of 82 cases were observed. Birth attendants' adherence to clinical standards was lowest in relation to risk monitoring processes. In relation to major complications, routine care processes addressing fetal and newborn distress were performed relatively consistently, but there were major gaps in the performance of routine care processes addressing bleeding, infection, and pre-eclampsia risks. The identified set of process indicators could identify major gaps in the quality of obstetric and neonatal care provided during the intra- and immediate postpartum period. We hope our suggested indicators for essential routine care processes will contribute to streamlining MNH program evaluations in LMICs.

Genome-wide identification of microRNA targets in the neglected disease pathogens of the genus Echinococcus.

PubMed

Macchiaroli, Natalia; Maldonado, Lucas L; Zarowiecki, Magdalena; Cucher, Marcela; Gismondi, María Inés; Kamenetzky, Laura; Rosenzvit, Mara Cecilia

2017-06-01

MicroRNAs (miRNAs), a class of small non-coding RNAs, are key regulators of gene expression at post-transcriptional level and play essential roles in biological processes such as development. MiRNAs silence target mRNAs by binding to complementary sequences in the 3'untranslated regions (3'UTRs). The parasitic helminths of the genus Echinococcus are the causative agents of echinococcosis, a zoonotic neglected disease. In previous work, we performed a comprehensive identification and characterization of Echinococcus miRNAs. However, current knowledge about their targets is limited. Since target prediction algorithms rely on complementarity between 3'UTRs and miRNA sequences, a major limitation is the lack of accurate sequence information of 3'UTR for most species including parasitic helminths. We performed RNA-seq and developed a pipeline that integrates the transcriptomic data with available genomic data of this parasite in order to identify 3'UTRs of Echinococcus canadensis. The high confidence set of 3'UTRs obtained allowed the prediction of miRNA targets in Echinococcus through a bioinformatic approach. We performed for the first time a comparative analysis of miRNA targets in Echinococcus and Taenia. We found that many evolutionarily conserved target sites in Echinococcus and Taenia may be functional and under selective pressure. Signaling pathways such as MAPK and Wnt were among the most represented pathways indicating miRNA roles in parasite growth and development. Genome-wide identification and characterization of miRNA target genes in Echinococcus provide valuable information to guide experimental studies in order to understand miRNA functions in the parasites biology. miRNAs involved in essential functions, especially those being absent in the host or showing sequence divergence with respect to host orthologs, might be considered as novel therapeutic targets for echinococcosis control. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and manufacture of visor for helmet-mounted display

NASA Astrophysics Data System (ADS)

Krevor, David H.; McNelly, Gregg; Skubon, John; Speirs, Robert

2004-01-01

The manufacturing design and process development for the Visor for the JHMCS (Joint Helmet Mounted Cueing System) are discussed. The JHMCS system is a Helmet Mounted Display (HMD) system currently flying on the F-15, F-16 and F/A-18 aircraft. The Visor manufacturing processes are essential to both system performance and economy. The Visor functions both as the system optical combiner and personal protective equipment for the pilot. The Visor material is optical polycarbonate. For a military HMD system, the mechanical and environmental properties of the Visor are as necessary as the optical properties. The visor must meet stringent dimensional requirements to assure adequate system optical performance. Injection molding can provide dimensional fidelity to the requirements, if done properly. Concurrent design of the visor and the tool (i.e., the injection mold) is essential. The concurrent design necessarily considers manufacturing operations and the use environment of the Visor. Computer modeling of the molding process is a necessary input to the mold design. With proper attention to product design and tool development, it is possible to improve upon published standard dimensional tolerances for molded polycarbonate articles.

Guidelines for reporting and using prediction tools for genetic variation analysis.

PubMed

Vihinen, Mauno

2013-02-01

Computational prediction methods are widely used for the analysis of human genome sequence variants and their effects on gene/protein function, splice site aberration, pathogenicity, and disease risk. New methods are frequently developed. We believe that guidelines are essential for those writing articles about new prediction methods, as well as for those applying these tools in their research, so that the necessary details are reported. This will enable readers to gain the full picture of technical information, performance, and interpretation of results, and to facilitate comparisons of related methods. Here, we provide instructions on how to describe new methods, report datasets, and assess the performance of predictive tools. We also discuss what details of predictor implementation are essential for authors to understand. Similarly, these guidelines for the use of predictors provide instructions on what needs to be delineated in the text, as well as how researchers can avoid unwarranted conclusions. They are applicable to most prediction methods currently utilized. By applying these guidelines, authors will help reviewers, editors, and readers to more fully comprehend prediction methods and their use. © 2012 Wiley Periodicals, Inc.

Novel Rhizosphere Soil Alleles for the Enzyme 1-Aminocyclopropane-1-Carboxylate Deaminase Queried for Function with an In Vivo Competition Assay

PubMed Central

Jin, Zhao; Di Rienzi, Sara C.; Janzon, Anders; Werner, Jeff J.; Angenent, Largus T.; Dangl, Jeffrey L.; Fowler, Douglas M.

2015-01-01

Metagenomes derived from environmental microbiota encode a vast diversity of protein homologs. How this diversity impacts protein function can be explored through selection assays aimed to optimize function. While artificially generated gene sequence pools are typically used in selection assays, their usage may be limited because of technical or ethical reasons. Here, we investigate an alternative strategy, the use of soil microbial DNA as a starting point. We demonstrate this approach by optimizing the function of a widely occurring soil bacterial enzyme, 1-aminocyclopropane-1-carboxylate (ACC) deaminase. We identified a specific ACC deaminase domain region (ACCD-DR) that, when PCR amplified from the soil, produced a variant pool that we could swap into functional plasmids carrying ACC deaminase-encoding genes. Functional clones of ACC deaminase were selected for in a competition assay based on their capacity to provide nitrogen to Escherichia coli in vitro. The most successful ACCD-DR variants were identified after multiple rounds of selection by sequence analysis. We observed that previously identified essential active-site residues were fixed in the original unselected library and that additional residues went to fixation after selection. We identified a divergent essential residue whose presence hints at the possible use of alternative substrates and a cluster of neutral residues that did not influence ACCD performance. Using an artificial ACCD-DR variant library generated by DNA oligomer synthesis, we validated the same fixation patterns. Our study demonstrates that soil metagenomes are useful starting pools of protein-coding-gene diversity that can be utilized for protein optimization and functional characterization when synthetic libraries are not appropriate. PMID:26637602

Accelerator tube construction and characterization for a tandem-electrostatic-quadrupole for accelerator-based boron neutron capture therapy.

PubMed

Cartelli, D; Vento, V Thatar; Castell, W; Di Paolo, H; Kesque, J M; Bergueiro, J; Valda, A A; Erhardt, J; Kreiner, A J

2011-12-01

The accelerator tubes are essential components of the accelerator. Their function is to transport and accelerate a very intense proton or deuteron beam through the machine, from the ion source to the neutron production target, without significant losses. In this contribution, we discuss materials selected for the tube construction, the procedures used for their assembly and the testing performed to meet the stringent requirements to which it is subjected. Copyright © 2011 Elsevier Ltd. All rights reserved.

Separating essentials from incidentals: an execution architecture for real-time control systems

NASA Technical Reports Server (NTRS)

Dvorak, Daniel; Reinholtz, Kirk

2004-01-01

This paper describes an execution architecture that makes such systems far more analyzable and verifiable by aggressive separation of concerns. The architecture separates two key software concerns: transformations of global state, as defined in pure functions; and sequencing/timing of transformations, as performed by an engine that enforces four prime invariants. The important advantage of this architecture, besides facilitating verification, is that it encourages formal specification of systems in a vocabulary that brings systems engineering closer to software engineering.

Molecular dynamics on diffusive time scales from the phase-field-crystal equation.

PubMed

Chan, Pak Yuen; Goldenfeld, Nigel; Dantzig, Jon

2009-03-01

We extend the phase-field-crystal model to accommodate exact atomic configurations and vacancies by requiring the order parameter to be non-negative. The resulting theory dictates the number of atoms and describes the motion of each of them. By solving the dynamical equation of the model, which is a partial differential equation, we are essentially performing molecular dynamics simulations on diffusive time scales. To illustrate this approach, we calculate the two-point correlation function of a fluid.

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

Jose Reyes

In recent years it has been recognized that the application of passive safety systems (i.e., those whose operation takes advantage of natural forces such as convection and gravity), can contribute to simplification and potentially to improved economics of new nuclear power plant designs. In 1991 the IAEA Conference on ''The Safety of Nuclear Power: Strategy for the Future'' noted that for new plants the use of passive safety features is a desirable method of achieving simplification and increasing the reliability of the performance of essential safety functions, and should be used wherever appropriate''.

IT Infrastructure Projects: A Framework for Analysis. ECAR Research Bulletin

ERIC Educational Resources Information Center

Grochow, Jerrold M.

2014-01-01

Just as maintaining a healthy infrastructure of water delivery and roads is essential to the functioning of cities and towns, maintaining a healthy infrastructure of information technology is essential to the functioning of universities. Deterioration in IT infrastructure can lead to deterioration in research, teaching, and administration. Given…

System control of an autonomous planetary mobile spacecraft

NASA Technical Reports Server (NTRS)

Dias, William C.; Zimmerman, Barbara A.

1990-01-01

The goal is to suggest the scheduling and control functions necessary for accomplishing mission objectives of a fairly autonomous interplanetary mobile spacecraft, while maximizing reliability. Goals are to provide an extensible, reliable system conservative in its use of on-board resources, while getting full value from subsystem autonomy, and avoiding the lure of ground micromanagement. A functional layout consisting of four basic elements is proposed: GROUND and SYSTEM EXECUTIVE system functions and RESOURCE CONTROL and ACTIVITY MANAGER subsystem functions. The system executive includes six subfunctions: SYSTEM MANAGER, SYSTEM FAULT PROTECTION, PLANNER, SCHEDULE ADAPTER, EVENT MONITOR and RESOURCE MONITOR. The full configuration is needed for autonomous operation on Moon or Mars, whereas a reduced version without the planning, schedule adaption and event monitoring functions could be appropriate for lower-autonomy use on the Moon. An implementation concept is suggested which is conservative in use of system resources and consists of modules combined with a network communications fabric. A language concept termed a scheduling calculus for rapidly performing essential on-board schedule adaption functions is introduced.

Observation uncertainty in reversible Markov chains.

PubMed

Metzner, Philipp; Weber, Marcus; Schütte, Christof

2010-09-01

In many applications one is interested in finding a simplified model which captures the essential dynamical behavior of a real life process. If the essential dynamics can be assumed to be (approximately) memoryless then a reasonable choice for a model is a Markov model whose parameters are estimated by means of Bayesian inference from an observed time series. We propose an efficient Monte Carlo Markov chain framework to assess the uncertainty of the Markov model and related observables. The derived Gibbs sampler allows for sampling distributions of transition matrices subject to reversibility and/or sparsity constraints. The performance of the suggested sampling scheme is demonstrated and discussed for a variety of model examples. The uncertainty analysis of functions of the Markov model under investigation is discussed in application to the identification of conformations of the trialanine molecule via Robust Perron Cluster Analysis (PCCA+) .

Institutional and Economic Determinants of Public Health System Performance

PubMed Central

Mays, Glen P.; McHugh, Megan C.; Shim, Kyumin; Perry, Natalie; Lenaway, Dennis; Halverson, Paul K.; Moonesinghe, Ramal

2006-01-01

Objectives. Although a growing body of evidence demonstrates that availability and quality of essential public health services vary widely across communities, relatively little is known about the factors that give rise to these variations. We examined the association of institutional, financial, and community characteristics of local public health delivery systems and the performance of essential services. Methods. Performance measures were collected from local public health systems in 7 states and combined with secondary data sources. Multivariate, linear, and nonlinear regression models were used to estimate associations between system characteristics and the performance of essential services. Results. Performance varied significantly with the size, financial resources, and organizational structure of local public health systems, with some public health services appearing more sensitive to these characteristics than others. Staffing levels and community characteristics also appeared to be related to the performance of selected services. Conclusions. Reconfiguring the organization and financing of public health systems in some communities—such as through consolidation and enhanced intergovernmental coordination—may hold promise for improving the performance of essential services. PMID:16449584

Design and synthesis of a series of serine derivatives as small molecule inhibitors of the SARS coronavirus 3CL protease.

PubMed

Konno, Hiroyuki; Wakabayashi, Masaki; Takanuma, Daiki; Saito, Yota; Akaji, Kenichi

2016-03-15

Synthesis of serine derivatives having the essential functional groups for the inhibitor of SARS 3CL protease and evaluation of their inhibitory activities using SARS 3CL R188I mutant protease are described. The lead compounds, functionalized serine derivatives, were designed based on the tetrapeptide aldehyde and Bai's cinnamoly inhibitor, and additionally performed with simulation on GOLD softwear. Structure activity relationship studies of the candidate compounds were given reasonable inhibitors ent-3 and ent-7k against SARS 3CL R188I mutant protease. These inhibitors showed protease selectivity and no cytotoxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens.

PubMed

Pan, Joshua; Meyers, Robin M; Michel, Brittany C; Mashtalir, Nazar; Sizemore, Ann E; Wells, Jonathan N; Cassel, Seth H; Vazquez, Francisca; Weir, Barbara A; Hahn, William C; Marsh, Joseph A; Tsherniak, Aviad; Kadoch, Cigall

2018-05-23

Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks that recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex. Finally, by integrating functional networks with large protein-protein interaction networks, we discovered novel protein complexes involving recently evolved genes of unknown function. Taken together, these findings demonstrate the utility of genetic perturbation screens alone, and in combination with large-scale biophysical data, to enhance our understanding of mammalian protein complexes in normal and disease states. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Age-related changes in the activation of the intraparietal sulcus during nonsymbolic magnitude processing: an event-related functional magnetic resonance imaging study.

PubMed

Ansari, Daniel; Dhital, Bibek

2006-11-01

Numerical magnitude processing is an essential everyday skill. Functional brain imaging studies with human adults have repeatedly revealed that bilateral regions of the intraparietal sulcus are correlated with various numerical and mathematical skills. Surprisingly little, however, is known about the development of these brain representations. In the present study, we used functional neuroimaging to compare the neural correlates of nonsymbolic magnitude judgments between children and adults. Although behavioral performance was similar across groups, in comparison to the group of children the adult participants exhibited greater effects of numerical distance on the left intraparietal sulcus. Our findings are the first to reveal that even the most basic aspects of numerical cognition are subject to age-related changes in functional neuroanatomy. We propose that developmental impairments of number may be associated with atypical specialization of cortical regions underlying magnitude processing.

An integrative machine learning strategy for improved prediction of essential genes in Escherichia coli metabolism using flux-coupled features.

PubMed

Nandi, Sutanu; Subramanian, Abhishek; Sarkar, Ram Rup

2017-07-25

Prediction of essential genes helps to identify a minimal set of genes that are absolutely required for the appropriate functioning and survival of a cell. The available machine learning techniques for essential gene prediction have inherent problems, like imbalanced provision of training datasets, biased choice of the best model for a given balanced dataset, choice of a complex machine learning algorithm, and data-based automated selection of biologically relevant features for classification. Here, we propose a simple support vector machine-based learning strategy for the prediction of essential genes in Escherichia coli K-12 MG1655 metabolism that integrates a non-conventional combination of an appropriate sample balanced training set, a unique organism-specific genotype, phenotype attributes that characterize essential genes, and optimal parameters of the learning algorithm to generate the best machine learning model (the model with the highest accuracy among all the models trained for different sample training sets). For the first time, we also introduce flux-coupled metabolic subnetwork-based features for enhancing the classification performance. Our strategy proves to be superior as compared to previous SVM-based strategies in obtaining a biologically relevant classification of genes with high sensitivity and specificity. This methodology was also trained with datasets of other recent supervised classification techniques for essential gene classification and tested using reported test datasets. The testing accuracy was always high as compared to the known techniques, proving that our method outperforms known methods. Observations from our study indicate that essential genes are conserved among homologous bacterial species, demonstrate high codon usage bias, GC content and gene expression, and predominantly possess a tendency to form physiological flux modules in metabolism.

Determination of the Core of a Minimal Bacterial Gene Set†

PubMed Central

Gil, Rosario; Silva, Francisco J.; Peretó, Juli; Moya, Andrés

2004-01-01

The availability of a large number of complete genome sequences raises the question of how many genes are essential for cellular life. Trying to reconstruct the core of the protein-coding gene set for a hypothetical minimal bacterial cell, we have performed a computational comparative analysis of eight bacterial genomes. Six of the analyzed genomes are very small due to a dramatic genome size reduction process, while the other two, corresponding to free-living relatives, are larger. The available data from several systematic experimental approaches to define all the essential genes in some completely sequenced bacterial genomes were also considered, and a reconstruction of a minimal metabolic machinery necessary to sustain life was carried out. The proposed minimal genome contains 206 protein-coding genes with all the genetic information necessary for self-maintenance and reproduction in the presence of a full complement of essential nutrients and in the absence of environmental stress. The main features of such a minimal gene set, as well as the metabolic functions that must be present in the hypothetical minimal cell, are discussed. PMID:15353568

DiffSLC: A graph centrality method to detect essential proteins of a protein-protein interaction network.

PubMed

Mistry, Divya; Wise, Roger P; Dickerson, Julie A

2017-01-01

Identification of central genes and proteins in biomolecular networks provides credible candidates for pathway analysis, functional analysis, and essentiality prediction. The DiffSLC centrality measure predicts central and essential genes and proteins using a protein-protein interaction network. Network centrality measures prioritize nodes and edges based on their importance to the network topology. These measures helped identify critical genes and proteins in biomolecular networks. The proposed centrality measure, DiffSLC, combines the number of interactions of a protein and the gene coexpression values of genes from which those proteins were translated, as a weighting factor to bias the identification of essential proteins in a protein interaction network. Potentially essential proteins with low node degree are promoted through eigenvector centrality. Thus, the gene coexpression values are used in conjunction with the eigenvector of the network's adjacency matrix and edge clustering coefficient to improve essentiality prediction. The outcome of this prediction is shown using three variations: (1) inclusion or exclusion of gene co-expression data, (2) impact of different coexpression measures, and (3) impact of different gene expression data sets. For a total of seven networks, DiffSLC is compared to other centrality measures using Saccharomyces cerevisiae protein interaction networks and gene expression data. Comparisons are also performed for the top ranked proteins against the known essential genes from the Saccharomyces Gene Deletion Project, which show that DiffSLC detects more essential proteins and has a higher area under the ROC curve than other compared methods. This makes DiffSLC a stronger alternative to other centrality methods for detecting essential genes using a protein-protein interaction network that obeys centrality-lethality principle. DiffSLC is implemented using the igraph package in R, and networkx package in Python. The python package can be obtained from git.io/diffslcpy. The R implementation and code to reproduce the analysis is available via git.io/diffslc.

Effects of dietary supplementation of red pepper (Schinus terebinthifolius Raddi) essential oil on performance, small intestinal morphology and microbial counts of weanling pigs.

PubMed

Cairo, Pedro Leon Gomes; Gois, Franz Dias; Sbardella, Maicon; Silveira, Hebert; de Oliveira, Roberto Maciel; Allaman, Ivan Bezerra; Cantarelli, Vinicius Souza; Costa, Leandro Batista

2018-01-01

Many strategies, such as the antibiotic growth promoters, have been developed to improve intestinal health and performance of newly weaned piglets. Natural products such as essential oils have been scientifically recognized as growth enhancer feed additives for weanling pigs, replacing the antibiotics. Therefore, it has been hypothesized that Brazilian red pepper could replace performance-enhancing antibiotics also in weanling pig diets. However, one experiment was conducted to determine the effects of dietary Brazilian red pepper essential oil or antimicrobial growth promoter on intestinal health and growth performance of weanling pigs. No effects of treatments were observed on performance and organ weights (P > 0.05). Overall, both additives [red pepper essential oil (RPEO) or antibiotic (ANT)] increased gut Lactobacillus counts compared to negative control, as well as reduced villi density (P < 0.05). Animals fed diets containing 1.5 g kg -1 RPEO presented the lowest incidence of diarrhea (P < 0.05). Our findings suggested that essential oil from Brazilian red pepper or chlorohydroxyquinoline added in weanling pig diets affect gut microbiota and histology without affecting performance and organ weights. In addition, there was an indication that high doses of essential oil could reduce the incidence of diarrhea. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Persistence of Functional Protein Domains in Mycoplasma Species and their Role in Host Specificity and Synthetic Minimal Life.

PubMed

Kamminga, Tjerko; Koehorst, Jasper J; Vermeij, Paul; Slagman, Simen-Jan; Martins Dos Santos, Vitor A P; Bijlsma, Jetta J E; Schaap, Peter J

2017-01-01

Mycoplasmas are the smallest self-replicating organisms and obligate parasites of a specific vertebrate host. An in-depth analysis of the functional capabilities of mycoplasma species is fundamental to understand how some of simplest forms of life on Earth succeeded in subverting complex hosts with highly sophisticated immune systems. In this study we present a genome-scale comparison, focused on identification of functional protein domains, of 80 publically available mycoplasma genomes which were consistently re-annotated using a standardized annotation pipeline embedded in a semantic framework to keep track of the data provenance. We examined the pan- and core-domainome and studied predicted functional capability in relation to host specificity and phylogenetic distance. We show that the pan- and core-domainome of mycoplasma species is closed. A comparison with the proteome of the "minimal" synthetic bacterium JCVI-Syn3.0 allowed us to classify domains and proteins essential for minimal life. Many of those essential protein domains, essential Domains of Unknown Function (DUFs) and essential hypothetical proteins are not persistent across mycoplasma genomes suggesting that mycoplasma species support alternative domain configurations that bypass their essentiality. Based on the protein domain composition, we could separate mycoplasma species infecting blood and tissue. For selected genomes of tissue infecting mycoplasmas, we could also predict whether the host is ruminant, pig or human. Functionally closely related mycoplasma species, which have a highly similar protein domain repertoire, but different hosts could not be separated. This study provides a concise overview of the functional capabilities of mycoplasma species, which can be used as a basis to further understand host-pathogen interaction or to design synthetic minimal life.

Persistence of Functional Protein Domains in Mycoplasma Species and their Role in Host Specificity and Synthetic Minimal Life

PubMed Central

Kamminga, Tjerko; Koehorst, Jasper J.; Vermeij, Paul; Slagman, Simen-Jan; Martins dos Santos, Vitor A. P.; Bijlsma, Jetta J. E.; Schaap, Peter J.

2017-01-01

Mycoplasmas are the smallest self-replicating organisms and obligate parasites of a specific vertebrate host. An in-depth analysis of the functional capabilities of mycoplasma species is fundamental to understand how some of simplest forms of life on Earth succeeded in subverting complex hosts with highly sophisticated immune systems. In this study we present a genome-scale comparison, focused on identification of functional protein domains, of 80 publically available mycoplasma genomes which were consistently re-annotated using a standardized annotation pipeline embedded in a semantic framework to keep track of the data provenance. We examined the pan- and core-domainome and studied predicted functional capability in relation to host specificity and phylogenetic distance. We show that the pan- and core-domainome of mycoplasma species is closed. A comparison with the proteome of the “minimal” synthetic bacterium JCVI-Syn3.0 allowed us to classify domains and proteins essential for minimal life. Many of those essential protein domains, essential Domains of Unknown Function (DUFs) and essential hypothetical proteins are not persistent across mycoplasma genomes suggesting that mycoplasma species support alternative domain configurations that bypass their essentiality. Based on the protein domain composition, we could separate mycoplasma species infecting blood and tissue. For selected genomes of tissue infecting mycoplasmas, we could also predict whether the host is ruminant, pig or human. Functionally closely related mycoplasma species, which have a highly similar protein domain repertoire, but different hosts could not be separated. This study provides a concise overview of the functional capabilities of mycoplasma species, which can be used as a basis to further understand host-pathogen interaction or to design synthetic minimal life. PMID:28224116

21 CFR 500.82 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., function, or reproduction, e.g., vitamins, essential minerals, essential amino acids, and essential fatty acids. These compounds must be supplied from external sources. FDA means the Food and Drug... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS...

21 CFR 500.82 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., function, or reproduction, e.g., vitamins, essential minerals, essential amino acids, and essential fatty acids. These compounds must be supplied from external sources. FDA means the Food and Drug... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS...

Sustaining Attention to Simple Tasks: A Meta-Analytic Review of the Neural Mechanisms of Vigilant Attention

PubMed Central

Langner, Robert; Eickhoff, Simon B.

2012-01-01

Maintaining attention for more than a few seconds is essential for mastering everyday life. Yet, our ability to stay focused on a particular task is limited, resulting in well-known performance decrements with increasing time on task. Intriguingly, such decrements are even more likely if the task is cognitively simple and repetitive. The attentional function that enables our prolonged engagement in intellectually unchallenging, uninteresting activities has been termed “vigilant attention.” Here we synthesized what we have learnt from functional neuroimaging about the mechanisms of this essential mental faculty. To this end, a quantitative meta-analysis of pertinent neuroimaging studies was performed, including supplementary analyses of moderating factors. Furthermore, we reviewed the available evidence on neural time-on-task effects, additionally considering information obtained from patients with focal brain damage. Integrating the results of both meta-analysis and review, a set of mainly right-lateralized brain regions was identified that may form the core network subserving vigilant attention in humans, including dorsomedial, mid- and ventrolateral prefrontal cortex, anterior insula, parietal areas (intraparietal sulcus, temporo-parietal junction), and subcortical structures (cerebellar vermis, thalamus, putamen, midbrain). We discuss the potential functional roles of different nodes of this network as well as implications of our findings for a theoretical account of vigilant attention. It is conjectured that sustaining attention is a multi-component, non-unitary mental faculty, involving a mixture of (i) sustained/recurrent processes subserving task-set/arousal maintenance and (ii) transient processes subserving the target-driven reorienting of attention. Finally, limitations of previous studies are considered and suggestions for future research are provided. PMID:23163491

Spectral feature design in high dimensional multispectral data

NASA Technical Reports Server (NTRS)

Chen, Chih-Chien Thomas; Landgrebe, David A.

1988-01-01

The High resolution Imaging Spectrometer (HIRIS) is designed to acquire images simultaneously in 192 spectral bands in the 0.4 to 2.5 micrometers wavelength region. It will make possible the collection of essentially continuous reflectance spectra at a spectral resolution sufficient to extract significantly enhanced amounts of information from return signals as compared to existing systems. The advantages of such high dimensional data come at a cost of increased system and data complexity. For example, since the finer the spectral resolution, the higher the data rate, it becomes impractical to design the sensor to be operated continuously. It is essential to find new ways to preprocess the data which reduce the data rate while at the same time maintaining the information content of the high dimensional signal produced. Four spectral feature design techniques are developed from the Weighted Karhunen-Loeve Transforms: (1) non-overlapping band feature selection algorithm; (2) overlapping band feature selection algorithm; (3) Walsh function approach; and (4) infinite clipped optimal function approach. The infinite clipped optimal function approach is chosen since the features are easiest to find and their classification performance is the best. After the preprocessed data has been received at the ground station, canonical analysis is further used to find the best set of features under the criterion that maximal class separability is achieved. Both 100 dimensional vegetation data and 200 dimensional soil data were used to test the spectral feature design system. It was shown that the infinite clipped versions of the first 16 optimal features had excellent classification performance. The overall probability of correct classification is over 90 percent while providing for a reduced downlink data rate by a factor of 10.

78 FR 39493 - Patient Protection and Affordable Care Act; Exchange Functions: Eligibility for Exemptions...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

...This final rule implements certain functions of the Affordable Insurance Exchanges (``Exchanges''). These specific statutory functions include determining eligibility for and granting certificates of exemption from the individual shared responsibility payment described in section 5000A of the Internal Revenue Code. Additionally, this final rule implements the responsibilities of the Secretary of Health and Human Services, in coordination with the Secretary of the Treasury, to designate other health benefits coverage as minimum essential coverage by providing that certain coverage be designated as minimum essential coverage. It also outlines substantive and procedural requirements that other types of individual coverage must fulfill in order to be certified as minimum essential coverage.

Estrogen-Related Receptor α (ERRα) and ERRγ Are Essential Coordinators of Cardiac Metabolism and Function

PubMed Central

Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B.; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M.; Patel, Vickas V.

2015-01-01

Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor α (ERRα) and ERRγ are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERRα and ERRγ together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERRα and ERRγ influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

Functional Interaction between Phosducin-like Protein 2 and Cytosolic Chaperonin Is Essential for Cytoskeletal Protein Function and Cell Cycle Progression

PubMed Central

Stirling, Peter C.; Srayko, Martin; Takhar, Karam S.; Pozniakovsky, Andrei; Hyman, Anthony A.

2007-01-01

The C haperonin Containing Tcp1 (CCT) maintains cellular protein folding homeostasis in the eukaryotic cytosol by assisting the biogenesis of many proteins, including actins, tubulins, and regulators of the cell cycle. Here, we demonstrate that the essential and conserved eukaryotic phosducin-like protein 2 (PhLP2/PLP2) physically interacts with CCT and modulates its folding activity. Consistent with this functional interaction, temperature-sensitive alleles of Saccharomyces cerevisiae PLP2 exhibit cytoskeletal and cell cycle defects. We uncovered several high-copy suppressors of the plp2 alleles, all of which are associated with G1/S cell cycle progression but which do not appreciably affect cytoskeletal protein function or fully rescue the growth defects. Our data support a model in which Plp2p modulates the biogenesis of several CCT substrates relating to cell cycle and cytoskeletal function, which together contribute to the essential function of PLP2. PMID:17429077

Perceptions on evaluative and formative functions of external supervision of Rwandan primary healthcare facilities: A qualitative study.

PubMed

Schriver, Michael; Cubaka, Vincent Kalumire; Itangishaka, Sylvere; Nyirazinyoye, Laetitia; Kallestrup, Per

2018-01-01

External supervision of primary healthcare facilities in low- and middle-income countries often has a managerial main purpose in which the role of support for professional development is unclear. To explore how Rwandan primary healthcare supervisors and providers (supervisees) perceive evaluative and formative functions of external supervision. Qualitative, exploratory study. Focus group discussions: three with supervisors, three with providers, and one mixed (n = 31). Findings were discussed with individual and groups of supervisors and providers. Evaluative activities occupied providers' understanding of supervision, including checking, correcting, marking and performance-based financing. These were presented as sources of motivation, that in self-determination theory indicate introjected regulation. Supervisors preferred to highlight their role in formative supervision, which may mask their own and providers' uncontested accounts that systematic performance evaluations predominated supervisors' work. Providers strongly requested larger focus on formative and supportive functions, voiced as well by most supervisors. Impact of performance evaluation on motivation and professional development is discussed. While external supervisors intended to support providers' professional development, our findings indicate serious problems with this in a context of frequent evaluations and performance marking. Separating the role of supporter and evaluator does not appear as the simple solution. If external supervision is to improve health care services, it is essential that supervisors and health centre managers are competent to support providers in a way that transparently accounts for various performance pressures. This includes delivery of proper formative supervision with useful feedback, maintaining an effective supervisory relationship, as well as ensuring providers are aware of the purpose and content of evaluative and formative supervision functions.

Validation of Essential Acoustic Parameters for Highly Urgent In-Vehicle Collision Warnings.

PubMed

Lewis, Bridget A; Eisert, Jesse L; Baldwin, Carryl L

2018-03-01

Objective The aim of this study was to validate the importance of key acoustic criteria for use as in-vehicle forward collision warning (FCW) systems. Background Despite recent advances in vehicle safety, automobile crashes remain one of the leading causes of death. As automation allows for more control of noncritical functions by the vehicle, the potential for disengagement and distraction from the driving task also increases. It is, therefore, as important as ever that in-vehicle safety-critical interfaces are intuitive and unambiguous, promoting effective collision avoidance responses upon first exposure even under divided-attention conditions. Method The current study used a driving simulator to assess the effectiveness of two warnings, one that met all essential acoustic parameters, one that met only some essential parameters, and a no-warning control in the context of a lead vehicle-following task in conjunction with a cognitive distractor task and collision event. Results Participants receiving an FCW comprising five essential acoustic components had improved collision avoidance responses relative to a no-warning condition and an FCW missing essential elements on their first exposure. Responses to a consistently good warning (GMU Prime) improved with subsequent exposures, whereas continued exposure to the less optimal FCW (GMU Sub-Prime) resulted in poorer performance even relative to receiving no warning at all. Conclusions This study provides support for previous warning design studies and for the validity of five key acoustic parameters essential for the design of effective in-vehicle FCWs. Application Results from this study have implications for the design of auditory FCWs and in-vehicle display design.

Emergency and trauma care in Pakistan: a cross-sectional study of healthcare levels

PubMed Central

Razzak, Junaid A; Baqir, Syed M; Khan, Uzma Rahim; Heller, David; Bhatti, Junaid; Hyder, Adnan A

2015-01-01

Background The importance of emergency medical care for the successful functioning of health systems has been increasingly recognised. This study aimed to evaluate emergency and trauma care facilities in four districts of the province of Sindh, Pakistan. Method We conducted a cross-sectional health facility survey in four districts of the province of Sindh in Pakistan using a modified version of WHO’s Guidelines for essential trauma care. 93 public health facilities (81 primary care facilities, nine secondary care hospitals, three tertiary hospitals) and 12 large private hospitals were surveyed. Interviews of healthcare providers and visual inspections of essential equipment and supplies as per guidelines were performed. A total of 141 physicians providing various levels of care were tested for their knowledge of basic emergency care using a validated instrument. Results Only 4 (44%) public secondary, 3 (25%) private secondary hospitals and all three tertiary care hospitals had designated emergency rooms. The majority of primary care health facilities had less than 60% of all essential equipments overall. Most of the secondary level public hospitals (78%) had less than 60% of essential equipments, and none had 80% or more. A fourth of private secondary care facilities and all tertiary care hospitals (n=3; 100%) had 80% or more essential equipments. The average percentage score on the physician knowledge test was 30%. None of the physicians scored above 60% correct responses. Conclusions The study findings demonstrated a gap in both essential equipment and provider knowledge necessary for effective emergency and trauma care. PMID:24157684

Differential effects of antibiotic therapy on the structure and function of human gut microbiota.

PubMed

Pérez-Cobas, Ana Elena; Artacho, Alejandro; Knecht, Henrik; Ferrús, María Loreto; Friedrichs, Anette; Ott, Stephan J; Moya, Andrés; Latorre, Amparo; Gosalbes, María José

2013-01-01

The human intestinal microbiota performs many essential functions for the host. Antimicrobial agents, such as antibiotics (AB), are also known to disturb microbial community equilibrium, thereby having an impact on human physiology. While an increasing number of studies investigate the effects of AB usage on changes in human gut microbiota biodiversity, its functional effects are still poorly understood. We performed a follow-up study to explore the effect of ABs with different modes of action on human gut microbiota composition and function. Four individuals were treated with different antibiotics and samples were taken before, during and after the AB course for all of them. Changes in the total and in the active (growing) microbiota as well as the functional changes were addressed by 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. We have found that the class of antibiotic, particularly its antimicrobial effect and mode of action, played an important role in modulating the gut microbiota composition and function. Furthermore, analysis of the resistome suggested that oscillatory dynamics are not only due to antibiotic-target resistance, but also to fluctuations in the surviving bacterial community. Our results indicated that the effect of AB on the human gut microbiota relates to the interaction of several factors, principally the properties of the antimicrobial agent, and the structure, functions and resistance genes of the microbial community.

Mapping Population-Level Spatial Access to Essential Surgical Care in Ghana Using Availability of Bellwether Procedures.

PubMed

Stewart, Barclay T; Tansley, Gavin; Gyedu, Adam; Ofosu, Anthony; Donkor, Peter; Appiah-Denkyira, Ebenezer; Quansah, Robert; Clarke, Damian L; Volmink, Jimmy; Mock, Charles

2016-08-17

Conditions that can be treated by surgery comprise more than 16% of the global disease burden. However, 5 billion people do not have access to essential surgical care. An estimated 90% of the 87 million disability-adjusted life-years incurred by surgical conditions could be averted by providing access to timely and safe surgery in low-income and middle-income countries. Population-level spatial access to essential surgery in Ghana is not known. To assess the performance of bellwether procedures (ie, open fracture repair, emergency laparotomy, and cesarean section) as a proxy for performing essential surgery more broadly, to map population-level spatial access to essential surgery, and to identify first-level referral hospitals that would most improve access to essential surgery if strengthened in Ghana. Population-based study among all households and public and private not-for-profit hospitals in Ghana. Households were represented by georeferenced census data. First-level and second-level referral hospitals managed by the Ministry of Health and all tertiary hospitals were included. Surgical data were collected from January 1 to December 31, 2014. All procedures performed at first-level referral hospitals in Ghana in 2014 were used to sort each facility into 1 of the following 3 hospital groups: those without capability to perform all 3 bellwether procedures, those that performed 1 to 11 of each procedure, and those that performed at least 12 of each procedure. Candidates for targeted capability improvement were identified by cost-distance and network analysis. Of 155 first-level referral hospitals managed by the Ghana Health Service and the Christian Health Association of Ghana, 123 (79.4%) reported surgical data. Ninety-five (77.2%) did not have the capability in 2014 to perform all 3 bellwether procedures, 24 (19.5%) performed 1 to 11 of each bellwether procedure, and 4 (3.3%) performed at least 12. The essential surgical procedure rate was greater in bellwether procedure-capable first-level referral hospitals than in noncapable hospitals (median, 638; interquartile range, 440-1418 vs 360; interquartile range, 0-896 procedures per 100 000 population; P = .03). Population-level spatial access within 2 hours to a hospital that performed 1 to 11 and at least 12 of each bellwether procedure was 83.2% (uncertainty interval [UI], 82.2%-83.4%) and 71.4% (UI, 64.4%-75.0%), respectively. Five hospitals were identified for targeted capability improvement. Almost 30% of Ghanaians cannot access essential surgery within 2 hours. Bellwether capability is a useful metric for essential surgery more broadly. Similar strategic planning exercises might be useful for other low-income and middle-income countries aiming to improve access to essential surgery.

Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice.

PubMed

Loftus, Róisín M; Assmann, Nadine; Kedia-Mehta, Nidhi; O'Brien, Katie L; Garcia, Arianne; Gillespie, Conor; Hukelmann, Jens L; Oefner, Peter J; Lamond, Angus I; Gardiner, Clair M; Dettmer, Katja; Cantrell, Doreen A; Sinclair, Linda V; Finlay, David K

2018-06-14

Natural killer (NK) cells are lymphocytes with important anti-tumour functions. Cytokine activation of NK cell glycolysis and oxidative phosphorylation (OXPHOS) are essential for robust NK cell responses. However, the mechanisms leading to this metabolic phenotype are unclear. Here we show that the transcription factor cMyc is essential for IL-2/IL-12-induced metabolic and functional responses in mice. cMyc protein levels are acutely regulated by amino acids; cMyc protein is lost rapidly when glutamine is withdrawn or when system L-amino acid transport is blocked. We identify SLC7A5 as the predominant system L-amino acid transporter in activated NK cells. Unlike other lymphocyte subsets, glutaminolysis and the tricarboxylic acid cycle do not sustain OXPHOS in activated NK cells. Glutamine withdrawal, but not the inhibition of glutaminolysis, results in the loss of cMyc protein, reduced cell growth and impaired NK cell responses. These data identify an essential role for amino acid-controlled cMyc for NK cell metabolism and function.

Grip force control in individuals with multiple sclerosis.

PubMed

Iyengar, Veena; Santos, Marcio J; Ko, Michael; Aruin, Alexander S

2009-10-01

Appropriate regulation of grip force is essential in performance of various activities of daily living such as drinking, eating, buttoning a shirt, and so on. The extent to which individuals with multiple sclerosis (MS) are able to regulate grip forces while performing elements of the activities of daily living is largely unknown. . To investigate how individuals with MS control grip force during performance of functional tasks. . This study evaluated the grip force control in selected individuals with MS (n = 9) and healthy control subjects (n = 9) while they performed the task of lifting and placing an instrumented object on a shelf and the task of lifting the object and bringing it close to the mouth to mimic drinking. The grip forces, object acceleration, force ratio, and time lag were recorded and analyzed. . The individuals with MS used significantly larger peak grip force and force ratio than control subjects while performing both tasks and for both hands. In addition, the time lag between the peaks of grip and load forces was significantly longer in individuals with MS. . The application of excessive grip force could predispose individuals with MS to additional fatigue and musculoskeletal overuse trauma. Rehabilitation protocols for the MS population may need to account for increased levels of grip force applied during the performance of functional tasks.

Minimax Estimation of Functionals of Discrete Distributions

PubMed Central

Jiao, Jiantao; Venkat, Kartik; Han, Yanjun; Weissman, Tsachy

2017-01-01

We propose a general methodology for the construction and analysis of essentially minimax estimators for a wide class of functionals of finite dimensional parameters, and elaborate on the case of discrete distributions, where the support size S is unknown and may be comparable with or even much larger than the number of observations n. We treat the respective regions where the functional is nonsmooth and smooth separately. In the nonsmooth regime, we apply an unbiased estimator for the best polynomial approximation of the functional whereas, in the smooth regime, we apply a bias-corrected version of the maximum likelihood estimator (MLE). We illustrate the merit of this approach by thoroughly analyzing the performance of the resulting schemes for estimating two important information measures: 1) the entropy H(P)=∑i=1S−pilnpi and 2) Fα(P)=∑i=1Spiα, α > 0. We obtain the minimax L2 rates for estimating these functionals. In particular, we demonstrate that our estimator achieves the optimal sample complexity n ≍ S/ln S for entropy estimation. We also demonstrate that the sample complexity for estimating Fα(P), 0 < α < 1, is n ≍ S1/α/ln S, which can be achieved by our estimator but not the MLE. For 1 < α < 3/2, we show the minimax L2 rate for estimating Fα(P) is (n ln n)−2(α−1) for infinite support size, while the maximum L2 rate for the MLE is n−2(α−1). For all the above cases, the behavior of the minimax rate-optimal estimators with n samples is essentially that of the MLE (plug-in rule) with n ln n samples, which we term “effective sample size enlargement.” We highlight the practical advantages of our schemes for the estimation of entropy and mutual information. We compare our performance with various existing approaches, and demonstrate that our approach reduces running time and boosts the accuracy. Moreover, we show that the minimax rate-optimal mutual information estimator yielded by our framework leads to significant performance boosts over the Chow–Liu algorithm in learning graphical models. The wide use of information measure estimation suggests that the insights and estimators obtained in this paper could be broadly applicable. PMID:29375152

DATMAN: A reliability data analysis program using Bayesian updating

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

Becker, M.; Feltus, M.A.

1996-12-31

Preventive maintenance (PM) techniques focus on the prevention of failures, in particular, system components that are important to plant functions. Reliability-centered maintenance (RCM) improves on the PM techniques by introducing a set of guidelines by which to evaluate the system functions. It also minimizes intrusive maintenance, labor, and equipment downtime without sacrificing system performance when its function is essential for plant safety. Both the PM and RCM approaches require that system reliability data be updated as more component failures and operation time are acquired. Systems reliability and the likelihood of component failures can be calculated by Bayesian statistical methods, whichmore » can update these data. The DATMAN computer code has been developed at Penn State to simplify the Bayesian analysis by performing tedious calculations needed for RCM reliability analysis. DATMAN reads data for updating, fits a distribution that best fits the data, and calculates component reliability. DATMAN provides a user-friendly interface menu that allows the user to choose from several common prior and posterior distributions, insert new failure data, and visually select the distribution that matches the data most accurately.« less

Reducing Recon 2 for steady-state flux analysis of HEK cell culture.

PubMed

Quek, Lake-Ee; Dietmair, Stefanie; Hanscho, Michael; Martínez, Verónica S; Borth, Nicole; Nielsen, Lars K

2014-08-20

A representative stoichiometric model is essential to perform metabolic flux analysis (MFA) using experimentally measured consumption (or production) rates as constraints. For Human Embryonic Kidney (HEK) cell culture, there is the opportunity to use an extremely well-curated and annotated human genome-scale model Recon 2 for MFA. Performing MFA using Recon 2 without any modification would have implied that cells have access to all functionality encoded by the genome, which is not realistic. The majority of intracellular fluxes are poorly determined as only extracellular exchange rates are measured. This is compounded by the fact that there is no suitable metabolic objective function to suppress non-specific fluxes. We devised a heuristic to systematically reduce Recon 2 to emphasize flux through core metabolic reactions. This implies that cells would engage these dominant metabolic pathways to grow, and any significant changes in gross metabolic phenotypes would have invoked changes in these pathways. The reduced metabolic model becomes a functionalized version of Recon 2 used for identifying significant metabolic changes in cells by flux analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

To boost or to CRUNCH? Effect of effortful encoding on episodic memory in older adults is dependent on executive functioning

PubMed Central

Fu, Li; Maes, Joseph H. R.; Kessels, Roy P. C.; Daselaar, Sander M.

2017-01-01

It is essential to develop effective interventions aimed at ameliorating age-related cognitive decline. Previous studies found that effortful encoding benefits episodic memory in older adults. However, to date it is unclear whether this benefit is different for individuals with strong versus weak executive functioning (EF). Fifty-one older adults were recruited and divided into low (N = 26) and high (N = 25) functioning groups, based on their EF capacity. All participants performed a semantic and a perceptual incidental encoding task. Each encoding task was performed under four difficulty levels to establish different effort levels. Encoding was followed by a recognition task. Results showed that the high EF group benefitted from increased effort in both tasks. However, the low EF group only showed a beneficial effect under low levels of effort. Results are consistent with the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH) and suggest that future research directed at developing efficient memory strategies to reduce negative cognitive aging effects should take individual cognitive differences among older adults into account, such as differences in EF. PMID:28328979

Flexible, phase-matched, linear receive arrays for high-field MRI in monkeys.

PubMed

Goense, Jozien; Logothetis, Nikos K; Merkle, Hellmut

2010-10-01

High signal-to-noise ratios (SNR) are essential for high-resolution anatomical and functional MRI. Phased arrays are advantageous for this but have the drawback that they often have inflexible and bulky configurations. Particularly in experiments where functional MRI is combined with simultaneous electrophysiology, space constraints can be prohibitive. To this end we developed a highly flexible multiple receive element phased array for use on anesthetized monkeys. The elements are interchangeable and different sizes and combinations of coil elements can be used, for instance, combinations of single and overlapped elements. The preamplifiers including control electronics are detachable and can serve a variety of prefabricated and phase matched arrays of different configurations, allowing the elements to always be placed in close proximity to the area of interest. Optimizing performance of the individual elements ensured high SNR at the cortical surface as well as in deeper laying structures. Performance of a variety of arrangements of gapped linear arrays was evaluated at 4.7 and 7T in high-resolution anatomical and functional MRI. Copyright © 2010 Elsevier Inc. All rights reserved.

Fast evaluation of solid harmonic Gaussian integrals for local resolution-of-the-identity methods and range-separated hybrid functionals.

PubMed

Golze, Dorothea; Benedikter, Niels; Iannuzzi, Marcella; Wilhelm, Jan; Hutter, Jürg

2017-01-21

An integral scheme for the efficient evaluation of two-center integrals over contracted solid harmonic Gaussian functions is presented. Integral expressions are derived for local operators that depend on the position vector of one of the two Gaussian centers. These expressions are then used to derive the formula for three-index overlap integrals where two of the three Gaussians are located at the same center. The efficient evaluation of the latter is essential for local resolution-of-the-identity techniques that employ an overlap metric. We compare the performance of our integral scheme to the widely used Cartesian Gaussian-based method of Obara and Saika (OS). Non-local interaction potentials such as standard Coulomb, modified Coulomb, and Gaussian-type operators, which occur in range-separated hybrid functionals, are also included in the performance tests. The speed-up with respect to the OS scheme is up to three orders of magnitude for both integrals and their derivatives. In particular, our method is increasingly efficient for large angular momenta and highly contracted basis sets.

Fast evaluation of solid harmonic Gaussian integrals for local resolution-of-the-identity methods and range-separated hybrid functionals

NASA Astrophysics Data System (ADS)

Golze, Dorothea; Benedikter, Niels; Iannuzzi, Marcella; Wilhelm, Jan; Hutter, Jürg

2017-01-01

An integral scheme for the efficient evaluation of two-center integrals over contracted solid harmonic Gaussian functions is presented. Integral expressions are derived for local operators that depend on the position vector of one of the two Gaussian centers. These expressions are then used to derive the formula for three-index overlap integrals where two of the three Gaussians are located at the same center. The efficient evaluation of the latter is essential for local resolution-of-the-identity techniques that employ an overlap metric. We compare the performance of our integral scheme to the widely used Cartesian Gaussian-based method of Obara and Saika (OS). Non-local interaction potentials such as standard Coulomb, modified Coulomb, and Gaussian-type operators, which occur in range-separated hybrid functionals, are also included in the performance tests. The speed-up with respect to the OS scheme is up to three orders of magnitude for both integrals and their derivatives. In particular, our method is increasingly efficient for large angular momenta and highly contracted basis sets.

Age effects on sensory-processing abilities and their impact on handwriting.

PubMed

Engel-Yeger, Batya; Hus, Sari; Rosenblum, Sara

2012-12-01

Sensory-processing abilities are known to deteriorate in the elderly. As a result, daily activities such as handwriting may be impaired. Yet, knowledge about sensory-processing involvement in handwriting characteristics among older persons is limited. To examine how age influences sensory-processing abilities and the impact on handwriting as a daily performance. The study participants were 118 healthy, independently functioning adults divided into four age groups: 31-45, 46-60, 61-75 and 76+ years. All participants completed the Adolescent/ Adult Sensory Profile (AASP). Handwriting process was documented using the Computerized Handwriting Penmanship Evaluation Tool (ComPET). Age significantly affects sensory processing and handwriting pressure as well as temporal and spatial measures. Both handwriting time and spatial organization of the written product were predicted by sensory seeking. When examining age contribution to the prediction of handwriting by sensory processing, sensory seeking showed a tendency for predicting handwriting pressure (p = .06), while sensory sensitivity significantly predicted handwriting velocity. Age appears to influence sensory-processing abilities and affect daily performance tasks, such as handwriting, for which sensitivity and seeking for sensations are essential. Awareness of clinicians to sensory-processing deficits among older adults and examining their impact on broader daily activities are essential to improve daily performance and quality of life.

The dual-specificity protein phosphatase DUSP9/MKP-4 is essential for placental function but is not required for normal embryonic development.

PubMed

Christie, Graham R; Williams, David J; Macisaac, Fiona; Dickinson, Robin J; Rosewell, Ian; Keyse, Stephen M

2005-09-01

To elucidate the physiological role(s) of DUSP9 (dual-specificity phosphatase 9), also known as MKP-4 (mitogen-activated protein kinase [MAPK] phosphatase 4), the gene was deleted in mice. Crossing male chimeras with wild-type females resulted in heterozygous (DUSP9(+/-)) females. However, when these animals were crossed with wild-type (DUSP9(+/y)) males none of the progeny carried the targeted DUSP9 allele, indicating that both female heterozygous and male null (DUSP9(-/y)) animals die in utero. The DUSP9 gene is on the X chromosome, and this pattern of embryonic lethality is consistent with the selective inactivation of the paternal X chromosome in the extraembryonic tissues of the mouse, suggesting that DUSP9/MKP4 performs an essential function during placental development. Examination of embryos between 8 and 10.5 days postcoitum confirmed that lethality was due to a failure of labyrinth development, and this correlates exactly with the normal expression pattern of DUSP9/MKP-4 in the trophoblast giant cells and labyrinth of the placenta. Finally, when the placental defect was rescued, male null (DUSP9(-/y)) embryos developed to term, appeared normal, and were fertile. Our results indicate that DUSP9/MKP-4 is essential for placental organogenesis but is otherwise dispensable for mammalian embryonic development and highlights the critical role of dual-specificity MAPK phosphatases in the regulation of developmental outcomes in vertebrates.

Commercially marketed supplements for bodybuilding athletes.

PubMed

Grunewald, K K; Bailey, R S

1993-02-01

We conducted a survey of 624 commercially available supplements targeted towards bodybuilding athletes. Over 800 performance claims were made for these supplements. Supplements include amino acids, boron, carnitine, choline, chromium, dibencozide, ferulic acid, gamma oryzanol, medium chain triglycerides, weight gain powders, Smilax compounds and yohimbine. Many performance claims advertised were not supported by published research studies. In some instances, we found no research to validate the claims; in other cases, research findings were extrapolated to inappropriate applications. For example, biological functions of some non-essential compounds were interpreted as performance claims for the supplements. Claims for others were based on their ability to enhance hormonal release or activity. We suggest that more research be conducted on this group of athletes and their nutritional needs. Furthermore, the effectiveness and safety of supplements merit further investigation.

Handicap discrimination considerations in treating the impaired worker: drugs, alcohol, pregnancy, and AIDS in the workplace.

PubMed

Postol, L P

1988-04-01

In dealing with applicants and employees, administrators must comply with handicap and pregnancy discrimination statutes, any union collective bargaining agreement, and any state or local statutes specifically directed at protecting certain classes of handicapped persons. The employer must make reasonable accommodations which allow the disabled worker to perform the job, although the employer need not implement accommodations which are an undue hardship. Similarly, if the impaired employee cannot safely perform the essential functions of the job, he or she need not be hired or retained. Employers must also recognize their responsibilities and liability under their health benefit plans and other liability statutes, and attempt to minimize their exposure.

Neuron-specific feeding RNAi in C. elegans and its use in a screen for essential genes required for GABA neuron function.

PubMed

Firnhaber, Christopher; Hammarlund, Marc

2013-11-01

Forward genetic screens are important tools for exploring the genetic requirements for neuronal function. However, conventional forward screens often have difficulty identifying genes whose relevant functions are masked by pleiotropy. In particular, if loss of gene function results in sterility, lethality, or other severe pleiotropy, neuronal-specific functions cannot be readily analyzed. Here we describe a method in C. elegans for generating cell-specific knockdown in neurons using feeding RNAi and its application in a screen for the role of essential genes in GABAergic neurons. We combine manipulations that increase the sensitivity of select neurons to RNAi with manipulations that block RNAi in other cells. We produce animal strains in which feeding RNAi results in restricted gene knockdown in either GABA-, acetylcholine-, dopamine-, or glutamate-releasing neurons. In these strains, we observe neuron cell-type specific behavioral changes when we knock down genes required for these neurons to function, including genes encoding the basal neurotransmission machinery. These reagents enable high-throughput, cell-specific knockdown in the nervous system, facilitating rapid dissection of the site of gene action and screening for neuronal functions of essential genes. Using the GABA-specific RNAi strain, we screened 1,320 RNAi clones targeting essential genes on chromosomes I, II, and III for their effect on GABA neuron function. We identified 48 genes whose GABA cell-specific knockdown resulted in reduced GABA motor output. This screen extends our understanding of the genetic requirements for continued neuronal function in a mature organism.

WRF-TMH: predicting transmembrane helix by fusing composition index and physicochemical properties of amino acids.

PubMed

Hayat, Maqsood; Khan, Asifullah

2013-05-01

Membrane protein is the prime constituent of a cell, which performs a role of mediator between intra and extracellular processes. The prediction of transmembrane (TM) helix and its topology provides essential information regarding the function and structure of membrane proteins. However, prediction of TM helix and its topology is a challenging issue in bioinformatics and computational biology due to experimental complexities and lack of its established structures. Therefore, the location and orientation of TM helix segments are predicted from topogenic sequences. In this regard, we propose WRF-TMH model for effectively predicting TM helix segments. In this model, information is extracted from membrane protein sequences using compositional index and physicochemical properties. The redundant and irrelevant features are eliminated through singular value decomposition. The selected features provided by these feature extraction strategies are then fused to develop a hybrid model. Weighted random forest is adopted as a classification approach. We have used two benchmark datasets including low and high-resolution datasets. tenfold cross validation is employed to assess the performance of WRF-TMH model at different levels including per protein, per segment, and per residue. The success rates of WRF-TMH model are quite promising and are the best reported so far on the same datasets. It is observed that WRF-TMH model might play a substantial role, and will provide essential information for further structural and functional studies on membrane proteins. The accompanied web predictor is accessible at http://111.68.99.218/WRF-TMH/ .

Instruction-Level Characterization of Scientific Computing Applications Using Hardware Performance Counters

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

Luo, Y.; Cameron, K.W.

1998-11-24

Workload characterization has been proven an essential tool to architecture design and performance evaluation in both scientific and commercial computing areas. Traditional workload characterization techniques include FLOPS rate, cache miss ratios, CPI (cycles per instruction or IPC, instructions per cycle) etc. With the complexity of sophisticated modern superscalar microprocessors, these traditional characterization techniques are not powerful enough to pinpoint the performance bottleneck of an application on a specific microprocessor. They are also incapable of immediately demonstrating the potential performance benefit of any architectural or functional improvement in a new processor design. To solve these problems, many people rely on simulators,more » which have substantial constraints especially on large-scale scientific computing applications. This paper presents a new technique of characterizing applications at the instruction level using hardware performance counters. It has the advantage of collecting instruction-level characteristics in a few runs virtually without overhead or slowdown. A variety of instruction counts can be utilized to calculate some average abstract workload parameters corresponding to microprocessor pipelines or functional units. Based on the microprocessor architectural constraints and these calculated abstract parameters, the architectural performance bottleneck for a specific application can be estimated. In particular, the analysis results can provide some insight to the problem that only a small percentage of processor peak performance can be achieved even for many very cache-friendly codes. Meanwhile, the bottleneck estimation can provide suggestions about viable architectural/functional improvement for certain workloads. Eventually, these abstract parameters can lead to the creation of an analytical microprocessor pipeline model and memory hierarchy model.« less

Structure and Function of the N-Terminal Domain of the Vesicular Stomatitis Virus RNA Polymerase

PubMed Central

Qiu, Shihong; Ogino, Minako; Luo, Ming

2015-01-01

ABSTRACT Viruses have various mechanisms to duplicate their genomes and produce virus-specific mRNAs. Negative-strand RNA viruses encode their own polymerases to perform each of these processes. For the nonsegmented negative-strand RNA viruses, the polymerase is comprised of the large polymerase subunit (L) and the phosphoprotein (P). L proteins from members of the Rhabdoviridae, Paramyxoviridae, and Filoviridae share sequence and predicted secondary structure homology. Here, we present the structure of the N-terminal domain (conserved region I) of the L protein from a rhabdovirus, vesicular stomatitis virus, at 1.8-Å resolution. The strictly and strongly conserved residues in this domain cluster in a single area of the protein. Serial mutation of these residues shows that many of the amino acids are essential for viral transcription but not for mRNA capping. Three-dimensional alignments show that this domain shares structural homology with polymerases from other viral families, including segmented negative-strand RNA and double-stranded RNA (dsRNA) viruses. IMPORTANCE Negative-strand RNA viruses include a diverse set of viral families that infect animals and plants, causing serious illness and economic impact. The members of this group of viruses share a set of functionally conserved proteins that are essential to their replication cycle. Among this set of proteins is the viral polymerase, which performs a unique set of reactions to produce genome- and subgenome-length RNA transcripts. In this article, we study the polymerase of vesicular stomatitis virus, a member of the rhabdoviruses, which has served in the past as a model to study negative-strand RNA virus replication. We have identified a site in the N-terminal domain of the polymerase that is essential to viral transcription and that shares sequence homology with members of the paramyxoviruses and the filoviruses. Newly identified sites such as that described here could prove to be useful targets in the design of new therapeutics against negative-strand RNA viruses. PMID:26512087

Optimization of response surface and neural network models in conjugation with desirability function for estimation of nutritional needs of methionine, lysine, and threonine in broiler chickens.

PubMed

Mehri, Mehran

2014-07-01

The optimization algorithm of a model may have significant effects on the final optimal values of nutrient requirements in poultry enterprises. In poultry nutrition, the optimal values of dietary essential nutrients are very important for feed formulation to optimize profit through minimizing feed cost and maximizing bird performance. This study was conducted to introduce a novel multi-objective algorithm, desirability function, for optimization the bird response models based on response surface methodology (RSM) and artificial neural network (ANN). The growth databases on the central composite design (CCD) were used to construct the RSM and ANN models and optimal values for 3 essential amino acids including lysine, methionine, and threonine in broiler chicks have been reevaluated using the desirable function in both analytical approaches from 3 to 16 d of age. Multi-objective optimization results showed that the most desirable function was obtained for ANN-based model (D = 0.99) where the optimal levels of digestible lysine (dLys), digestible methionine (dMet), and digestible threonine (dThr) for maximum desirability were 13.2, 5.0, and 8.3 g/kg of diet, respectively. However, the optimal levels of dLys, dMet, and dThr in the RSM-based model were estimated at 11.2, 5.4, and 7.6 g/kg of diet, respectively. This research documented that the application of ANN in the broiler chicken model along with a multi-objective optimization algorithm such as desirability function could be a useful tool for optimization of dietary amino acids in fractional factorial experiments, in which the use of the global desirability function may be able to overcome the underestimations of dietary amino acids resulting from the RSM model. © 2014 Poultry Science Association Inc.

Broadening the functionality of a J-protein/Hsp70 molecular chaperone system.

PubMed

Schilke, Brenda A; Ciesielski, Szymon J; Ziegelhoffer, Thomas; Kamiya, Erina; Tonelli, Marco; Lee, Woonghee; Cornilescu, Gabriel; Hines, Justin K; Markley, John L; Craig, Elizabeth A

2017-10-01

By binding to a multitude of polypeptide substrates, Hsp70-based molecular chaperone systems perform a range of cellular functions. All J-protein co-chaperones play the essential role, via action of their J-domains, of stimulating the ATPase activity of Hsp70, thereby stabilizing its interaction with substrate. In addition, J-proteins drive the functional diversity of Hsp70 chaperone systems through action of regions outside their J-domains. Targeting to specific locations within a cellular compartment and binding of specific substrates for delivery to Hsp70 have been identified as modes of J-protein specialization. To better understand J-protein specialization, we concentrated on Saccharomyces cerevisiae SIS1, which encodes an essential J-protein of the cytosol/nucleus. We selected suppressors that allowed cells lacking SIS1 to form colonies. Substitutions changing single residues in Ydj1, a J-protein, which, like Sis1, partners with Hsp70 Ssa1, were isolated. These gain-of-function substitutions were located at the end of the J-domain, suggesting that suppression was connected to interaction with its partner Hsp70, rather than substrate binding or subcellular localization. Reasoning that, if YDJ1 suppressors affect Ssa1 function, substitutions in Hsp70 itself might also be able to overcome the cellular requirement for Sis1, we carried out a selection for SSA1 suppressor mutations. Suppressing substitutions were isolated that altered sites in Ssa1 affecting the cycle of substrate interaction. Together, our results point to a third, additional means by which J-proteins can drive Hsp70's ability to function in a wide range of cellular processes-modulating the Hsp70-substrate interaction cycle.

Pyruvate dehydrogenase has a major role in mast cell function, and its activity is regulated by mitochondrial microphthalmia transcription factor.

PubMed

Sharkia, Israa; Hadad Erlich, Tal; Landolina, Nadine; Assayag, Miri; Motzik, Alex; Rachmin, Inbal; Kay, Gillian; Porat, Ziv; Tshori, Sagi; Berkman, Neville; Levi-Schaffer, Francesca; Razin, Ehud

2017-07-01

We have recently observed that oxidative phosphorylation-mediated ATP production is essential for mast cell function. Pyruvate dehydrogenase (PDH) is the main regulator of the Krebs cycle and is located upstream of the electron transport chain. However, the role of PDH in mast cell function has not been described. Microphthalmia transcription factor (MITF) regulates the development, number, and function of mast cells. Localization of MITF to the mitochondria and its interaction with mitochondrial proteins has not been explored. We sought to explore the role played by PDH in mast cell exocytosis and to determine whether MITF is localized in the mitochondria and involved in regulation of PDH activity. Experiments were performed in vitro by using human and mouse mast cells, as well as rat basophil leukemia cells, and in vivo in mice. The effect of PDH inhibition on mast cell function was examined. PDH interaction with MITF was measured before and after immunologic activation. Furthermore, mitochondrial localization of MITF and its effect on PDH activity were determined. PDH is essential for immunologically mediated degranulation of mast cells. After activation, PDH is serine dephosphorylated. In addition, for the first time, we show that MITF is partially located in the mitochondria and interacts with PDH. This interaction is dependent on the phosphorylation state of PDH. Furthermore, mitochondrial MITF regulates PDH activity. The association of mitochondrial MITF with PDH emerges as an important regulator of mast cell function. Our findings indicate that PDH could arise as a new target for the manipulation of allergic diseases. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Exploring N-Rich Phases in Li(x)N(y) Clusters for Hydrogen Storage at Nanoscale.

PubMed

Bhattacharya, Amrita; Bhattacharya, Saswata

2015-09-17

We have performed cascade genetic algorithm and ab initio atomistic thermodynamics under the framework of first-principles-based hybrid density functional theory to study the (meta-)stability of a wide range of Li(x)N(y) clusters. We found that hybrid xc-functional is essential to address this problem as a local/semilocal functional simply fails even to predict a qualitative prediction. Most importantly, we find that though in bulk lithium nitride, the Li-rich phase, that is, Li3N, is the stable stoichiometry; in small Li(x)N(y) clusters, N-rich phases are more stable at thermodynamic equilibrium. We further show that these N-rich clusters are promising hydrogen storage material because of their easy adsorption and desorption ability at respectively low (≤300 K) and moderately high temperature (≥600 K).

14 CFR 189.3 - Kinds of messages accepted or relayed.

Code of Federal Regulations, 2010 CFR

2010-01-01

... essential to the safety or regulatory of aircraft operation; (ii) Essential to efficient functioning of... refers, containing information required for weight and balance computation and remarks essential to the... aircraft operating agencies or their representatives that directly bear on the efficient and economic...

Who or What? Self-Replication and Function-Reproduction in the Origin of Life

NASA Technical Reports Server (NTRS)

New, Michael H.; Stassinopoulos, Dimitris; Monaco, Regina; Pohorille, Andrew; DeVincenzi, Donald (Technical Monitor)

2002-01-01

In this presentation, we will present results on the fundamental properties of two classes of replicating systems: autocatalytic replicators that reproduce exact copies of a template molecule, and function reproducers that maintain a set of essential functions without replicating the identities of the functional moieties. We will describe the stability and behavior in-the-large of autocatalytic replicators. Most importantly, we have found no sharp distinction between an autocatalytic and a non-autocatalytic domain. We will also present a new derivation of von Kiedrowski's square-root rate law. Function - reproducers are proposed as an important component of protocells and we will present theoretical results on a simple model system that incorporates known peptide biophysics. For a wide range of parameters, we have shown that this type of system can improve its overall performance, even in the absence of any method for information storage. This type of system improvement is defined to be non-genomic evolution.

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse.

PubMed

Lacagnina, Michael J; Rivera, Phillip D; Bilbo, Staci D

2017-01-01

Drugs of abuse cause persistent alterations in synaptic plasticity that may underlie addiction behaviors. Evidence suggests glial cells have an essential and underappreciated role in the development and maintenance of drug abuse by influencing neuronal and synaptic functions in multifaceted ways. Microglia and astrocytes perform critical functions in synapse formation and refinement in the developing brain, and there is growing evidence that disruptions in glial function may be implicated in numerous neurological disorders throughout the lifespan. Linking evidence of function in health and under pathological conditions, this review will outline the glial and neuroimmune mechanisms that may contribute to drug-abuse liability, exploring evidence from opioids, alcohol, and psychostimulants. Drugs of abuse can activate microglia and astrocytes through signaling at innate immune receptors, which in turn influence neuronal function not only through secretion of soluble factors (eg, cytokines and chemokines) but also potentially through direct remodeling of the synapses. In sum, this review will argue that neural-glial interactions represent an important avenue for advancing our understanding of substance abuse disorders.

Lunar Dust on Heat Rejection System Surfaces: Problems and Prospects

NASA Technical Reports Server (NTRS)

Gaier, James R.; Jaworske, Donald A.

2007-01-01

Heat rejection from power systems will be necessary for human and robotic activity on the lunar surface. Functional operation of such heat rejection systems is at risk of degradation as a consequence of dust accumulation. The Apollo astronauts encountered marked degradation of performance in heat rejection systems for the lunar roving vehicle, science packages, and other components. Although ground testing of dust mitigation concepts in support of the Apollo mission identified mitigation tools, the brush concept adopted by the Apollo astronauts proved essentially ineffective. A better understanding of the issues associated with the impact of lunar dust on the functional performance of heat rejection systems and its removal is needed as planning gets underway for human and robotic missions to the Moon. Renewed emphasis must also be placed on ground testing of pristine and dust-covered heat rejection system surfaces to quantify degradation and address mitigation concepts. This paper presents a review of the degradation in performance of heat rejection systems encountered on the lunar surface to-date, and will discuss current activities underway to evaluate the durability of candidate heat rejection system surfaces and current dust mitigation concepts.

Pretreatment neurocognitive function and self-reported symptoms in patients with newly diagnosed head and neck cancer compared with noncancer cohort.

PubMed

Bernstein, Lori J; Pond, Gregory R; Gan, Hui K; Tirona, Kattleya; Chan, Kelvin K; Hope, Andrew; Kim, John; Chen, Eric X; Siu, Lillian L; Razak, Albiruni R Abdul

2018-04-17

Newly diagnosed patients with head and neck cancer may be at risk for impaired neurocognitive function (NCF) due to disease, treatment, and lifestyle factors. Eighty pretreatment patients with head and neck cancer and 40 control patients without cancer completed assessment of NCF and self-reported cognition, fatigue, and mood. Blood samples to evaluate organ reserves, hormones, and cytokines were collected. Patients experienced worse symptoms of cognitive dysfunction, fatigue, and anxiety than controls. In contrast, NCF was equivalent for patients and controls. Using published norms as comparison, groups had similar high rates of impairment in performance (9/80 patients and 3/40 controls scored in the abnormal range). Pretreatment patients with head and neck cancer reported cognitive disturbance. The frequency of impaired performance, albeit high, was consistent with the literature demonstrating false-positive "abnormal" neuropsychological test performance is not uncommon. Inclusion of a noncancer patient control cohort is essential because using solely normative data as a comparison may foster erroneous interpretation. © 2018 Wiley Periodicals, Inc.

Seed-effect modeling improves the consistency of genome-wide loss-of-function screens and identifies synthetic lethal vulnerabilities in cancer cells.

PubMed

Jaiswal, Alok; Peddinti, Gopal; Akimov, Yevhen; Wennerberg, Krister; Kuznetsov, Sergey; Tang, Jing; Aittokallio, Tero

2017-06-01

Genome-wide loss-of-function profiling is widely used for systematic identification of genetic dependencies in cancer cells; however, the poor reproducibility of RNA interference (RNAi) screens has been a major concern due to frequent off-target effects. Currently, a detailed understanding of the key factors contributing to the sub-optimal consistency is still a lacking, especially on how to improve the reliability of future RNAi screens by controlling for factors that determine their off-target propensity. We performed a systematic, quantitative analysis of the consistency between two genome-wide shRNA screens conducted on a compendium of cancer cell lines, and also compared several gene summarization methods for inferring gene essentiality from shRNA level data. We then devised novel concepts of seed essentiality and shRNA family, based on seed region sequences of shRNAs, to study in-depth the contribution of seed-mediated off-target effects to the consistency of the two screens. We further investigated two seed-sequence properties, seed pairing stability, and target abundance in terms of their capability to minimize the off-target effects in post-screening data analysis. Finally, we applied this novel methodology to identify genetic interactions and synthetic lethal partners of cancer drivers, and confirmed differential essentiality phenotypes by detailed CRISPR/Cas9 experiments. Using the novel concepts of seed essentiality and shRNA family, we demonstrate how genome-wide loss-of-function profiling of a common set of cancer cell lines can be actually made fairly reproducible when considering seed-mediated off-target effects. Importantly, by excluding shRNAs having higher propensity for off-target effects, based on their seed-sequence properties, one can remove noise from the genome-wide shRNA datasets. As a translational application case, we demonstrate enhanced reproducibility of genetic interaction partners of common cancer drivers, as well as identify novel synthetic lethal partners of a major oncogenic driver, PIK3CA, supported by a complementary CRISPR/Cas9 experiment. We provide practical guidelines for improved design and analysis of genome-wide loss-of-function profiling and demonstrate how this novel strategy can be applied towards improved mapping of genetic dependencies of cancer cells to aid development of targeted anticancer treatments.

The role of executive functioning in memory performance in pediatric focal epilepsy

PubMed Central

Sepeta, Leigh N.; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D.; Berl, Madison M.

2016-01-01

Objective Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Methods Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (WASI/DAS), as well as visual (CMS Dot Locations) and verbal episodic memory (WRAML Story Memory and CVLT-C). Executive functioning was measured directly (WISC-IV Digit Span Backward; CELF-IV Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function (BRIEF)). Results Children with focal epilepsy had lower delayed free recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η2 = .12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η2 = .03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η2 = .08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9–19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9–10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extra-temporal, frontal vs. extra-frontal). Significance Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval. PMID:28111742

From Green to Blue: Site-Directed Mutagenesis of the Green Fluorescent Protein to Teach Protein Structure-Function Relationships

ERIC Educational Resources Information Center

Giron, Maria D.; Salto, Rafael

2011-01-01

Structure-function relationship studies in proteins are essential in modern Cell Biology. Laboratory exercises that allow students to familiarize themselves with basic mutagenesis techniques are essential in all Genetic Engineering courses to teach the relevance of protein structure. We have implemented a laboratory course based on the…

Marketing audit reveals holes and opportunities.

PubMed

Pearson, E

1990-07-01

The marketing department is an essential function of the hospital. But do you know if your marketing efforts are meeting your institution's objectives? An audit of the department is as essential as any other part of the marketing plan. The author tells you "how" and "why" you should seek the services of an auditor to examine your marketing function.

Delivery of Essential Medicines to Primary Care Institutions and its Association with Procurement Volume and Price: A Case Study in Hubei Province, China.

PubMed

Tang, Yuqing; Liu, Chaojie; Zhang, Xinping

2017-02-01

The low availability of essential medicines is a worldwide issue of concern. In 2009, China introduced a National Essential Medicines List (NEML), with NEML medicines being purchased in bulk at contracted prices established by tenders conducted at the provincial level. The availability of essential medicines in the public sector largely relies on commercial supply chains. The objectives of this paper were to analyze the delivery performance of essential medicines under NEML provincial procurement arrangements, and to determine whether the procurement volume and price of medicines are associated with the delivery performance of suppliers. We reviewed 9390 recorded orders of 1099 essential medicines in Hubei province from August 2011 to April 2012. The reliability of medicine delivery in-full and on-time (DIFOT) was considered the performance indicator, and we used Spearman correlation analyses to explore whether there were any associations between DIFOT and procurement price and volume. Quantile regressions were performed to determine such associations. The DIFOT had positive correlations with procurement price and volume. The Spearman rank correlation coefficients between price and DIFOT were 0.114, 0.34 and 0.25 for medicines with low one-third, middle one-third and high one-third procurement volumes, respectively. The quantile regression analysis revealed a positive association between price and DIFOT across all quantiles of DIFOT, and although significant positive associations between volume and DIFOT were only found at the 25th percentile of DIFOT, volume showed significant interactions with price for both the 25th and 50th percentiles of DIFOT. Higher procurement price is associated with better delivery performance of essential medicines; however, it is important to link procurement price with procurement volume. Increasing procurement volume may alleviate the negative effect of low price on delivery performance. Variation in volumes of repeated orders imposes uncertainties and may jeopardize the delivery of essential medicines.

Quantum coupled mutation finder: predicting functionally or structurally important sites in proteins using quantum Jensen-Shannon divergence and CUDA programming.

PubMed

Gültas, Mehmet; Düzgün, Güncel; Herzog, Sebastian; Jäger, Sven Joachim; Meckbach, Cornelia; Wingender, Edgar; Waack, Stephan

2014-04-03

The identification of functionally or structurally important non-conserved residue sites in protein MSAs is an important challenge for understanding the structural basis and molecular mechanism of protein functions. Despite the rich literature on compensatory mutations as well as sequence conservation analysis for the detection of those important residues, previous methods often rely on classical information-theoretic measures. However, these measures usually do not take into account dis/similarities of amino acids which are likely to be crucial for those residues. In this study, we present a new method, the Quantum Coupled Mutation Finder (QCMF) that incorporates significant dis/similar amino acid pair signals in the prediction of functionally or structurally important sites. The result of this study is twofold. First, using the essential sites of two human proteins, namely epidermal growth factor receptor (EGFR) and glucokinase (GCK), we tested the QCMF-method. The QCMF includes two metrics based on quantum Jensen-Shannon divergence to measure both sequence conservation and compensatory mutations. We found that the QCMF reaches an improved performance in identifying essential sites from MSAs of both proteins with a significantly higher Matthews correlation coefficient (MCC) value in comparison to previous methods. Second, using a data set of 153 proteins, we made a pairwise comparison between QCMF and three conventional methods. This comparison study strongly suggests that QCMF complements the conventional methods for the identification of correlated mutations in MSAs. QCMF utilizes the notion of entanglement, which is a major resource of quantum information, to model significant dissimilar and similar amino acid pair signals in the detection of functionally or structurally important sites. Our results suggest that on the one hand QCMF significantly outperforms the previous method, which mainly focuses on dissimilar amino acid signals, to detect essential sites in proteins. On the other hand, it is complementary to the existing methods for the identification of correlated mutations. The method of QCMF is computationally intensive. To ensure a feasible computation time of the QCMF's algorithm, we leveraged Compute Unified Device Architecture (CUDA).The QCMF server is freely accessible at http://qcmf.informatik.uni-goettingen.de/.

Non-Genomic Origins of Proteins and Metabolism

NASA Technical Reports Server (NTRS)

Pohorille, Andrew

2003-01-01

It is proposed that evolution of inanimate matter to cells endowed with a nucleic acid- based coding of genetic information was preceded by an evolutionary phase, in which peptides not coded by nucleic acids were able to self-organize into networks capable of evolution towards increasing metabolic complexity. Recent findings that truly different, simple peptides (Keefe and Szostak, 2001) can perform the same function (such as ATP binding) provide experimental support for this mechanism of early protobiological evolution. The central concept underlying this mechanism is that the reproduction of cellular functions alone was sufficient for self-maintenance of protocells, and that self- replication of macromolecules was not required at this stage of evolution. The precise transfer of information between successive generations of the earliest protocells was unnecessary and, possibly, undesirable. The key requirement in the initial stage of protocellular evolution was an ability to rapidly explore a large number of protein sequences in order to discover a set of molecules capable of supporting self- maintenance and growth of protocells. Undoubtedly, the essential protocellular functions were carried out by molecules not nearly as efficient or as specific as contemporary proteins. Many, potentially unrelated sequences could have performed each of these functions at an evolutionarily acceptable level. As evolution progressed, however proteins must have performed their functions with increasing efficiency and specificity. This, in turn, put additional constraints on protein sequences and the fraction of proteins capable of performing their functions at the required level decreased. At some point, the likelihood of generating a sufficiently efficient set of proteins through a non-coded synthesis was so small that further evolution was not possible without storing information about the sequences of these proteins. Beyond this point, further evolution required coupling between proteins and informational polymers that is characteristic to all known forms of life. The emergence of such coupling must be postulated in any scenario of the origin of life, no matter whether it starts with RNA or proteins. To examine the evolutionary potential of non-genomic systems, a simple, computationally tractable model, which is still capable of capturing the essential features of the real system, has been studied computationally. Both constructive and destructive processes have been introduced into the model in a stochastic manner. Instead of assuming random reaction sets, only a suite of protobiologically plausible reactions has been considered. Peptides have been explicitly considered as protoenzymes and their catalytic efficiencies have been assigned on the basis of biochemical principles and experimental estimates. Simulations have been carried out using a novel approach (The Next Reaction Method) that is appropriate even for very low concentrations of reactants. Studies have focused on global autocatalytic processes and their diversity.

Effects of Mexican oregano oil on performance, blood profile, carcass variables, and meat of broilers

USDA-ARS?s Scientific Manuscript database

Oregano essential oils (OEO) have demonstrated effects on growth performance of broilers. This study was conducted to investigate the effects of Mexican oregano essential oils (MOO) extracts from Lippia berlandieri Schauer and Poliomintha longiflora Gray on performance, blood profiles, carcass vari...

Functional analysis of UMOD gene and its effect on inflammatory cytokines in serum of essential hypertension patients.

PubMed

Jian, Liguo; Fa, Xian'en; Zhou, Zheng; Liu, Shichao

2015-01-01

The study aimed to investigate the function of uromodulin (UMOD) gene and its effect on inflammatory cytokines in serum of essential hypertension patients. The online database and software of computer were used for bioinformatics analysis on UMOD gene as well as the structure and function of its encoding proteins. Moreover, radioimmunoassay and enzyme linked immunosorbent assay was adopted to validate the content of urine UMOD protein of essential hypertension patients and their serum inflammatory cytokines. As an alkaline and hydrophilic protein, UMOD has no transmembrane region, but it does have a signal peptide sequence. It is mainly located extracellularly, belonging to a secreted protein, whose secondary structure was based mainly on Random coil which account for 58.44%. According to function prediction, it is found that the UMOD protein has stress response which may be participate in the inflammatory reaction. It has been observed from the experiment which was designed on the basis of the correlation between inflammation reaction and essential hypertension that the content of urine UMOD protein of essential hypertension patients who is in stage I was (28.71 ± 10.53) mg/24 h and when compared with the control group's content (30.15 ± 14.10 mg/24 h), the difference was not obviously; The content of urine UMOD protein of essential hypertension patients who's in stage II and III was (18.24 ± 6.12) mg/24 h and (9.43 ± 3.16) mg/24 h, respectively, which were obviously lower than that of the control group (P<0.01). Additionally, the serum inflammatory cytokines, such as TNF-α, IL-6 and IL1-α content of essential hypertension patients were all markedly higher than that of control group (P<0.05). For essential hypertension patients, there's a close relationship between the expression level of UMOD gene and inflammatory cytokines, which were manifested as the negative correlation between the level of the gene's expression and inflammatory cytokines. That has certain reference value to realize the targeted treatment for essential hypertension through regulated blood pressure conversely in the view of expression level of inflammatory cytokines.

Crude protein and essential amino acid requirements in chicks during the first week posthatch.

PubMed

Sklan, D; Noy, Y

2003-05-01

1. This study examined optimal lysine and sulphur amino acid supply in the first week posthatch in broilers and the relationship between essential amino acids and dietary crude protein during the first week posthatch on performance at 7 d and through marketing. 2. The optimal supply during the 7 d posthatch using a 230 g/kg crude protein diet for sulphur amino acids was 9.1 and for lysine was 10.3-10.8 g/kg with maximal body weight (BW) or feed efficiency as the criteria. 3. Feeding diets with crude protein content ranging from 200 to 260 g/kg with either constant amounts of essential amino acids at different crude protein levels or constant ratios of essential amino acids to crude protein resulted in enhanced performance at 7 but not at 4 d with high protein intake and proportionally increased essential amino acids. 4. Performance on diets with crude protein ranging from 160 to 280 g/kg, with constant ratios of essential amino acid to crude protein, was much enhanced with the high crude protein diets at 7 d. All chicks were transferred to standard diets after 7 d and the BW advantage due to the balanced amino acid-high crude protein diet remained through marketing. 5. Thus increasing essential amino acids in a constant ratio to crude protein enhanced performance during the 7 d posthatch.

Transcription termination factor Rho: a hub linking diverse physiological processes in bacteria.

PubMed

Grylak-Mielnicka, Aleksandra; Bidnenko, Vladimir; Bardowski, Jacek; Bidnenko, Elena

2016-03-01

Factor-dependent termination of transcription in bacteria relies on the activity of a specific RNA helicase, the termination factor Rho. Rho is nearly ubiquitous in bacteria, but the extent to which its physiological functions are conserved throughout the different phyla remains unknown. Most of our current knowledge concerning the mechanism of Rho's activity and its physiological roles comes from the model micro-organism Escherichia coli, where Rho is essential and involved in the control of several important biological processes. However, the rather comprehensive knowledge about the general mechanisms of action and activities of Rho based on the E. coli paradigm cannot be directly extrapolated to other bacteria. Recent studies performed in different species favour the view that Rho-dependent termination plays a significant role even in bacteria where Rho is not essential. Here, we summarize the current state of the ever-increasing knowledge about the various aspects of the physiological functions of Rho, such as limitation of deleterious foreign DNA expression, control of gene expression, suppression of pervasive transcription, prevention of R-loops and maintenance of chromosome integrity, focusing on similarities and differences of the activities of Rho in various bacterial species.

Operationalising emergency care delivery in sub-Saharan Africa: consensus-based recommendations for healthcare facilities.

PubMed

Calvello, Emilie J B; Tenner, Andrea G; Broccoli, Morgan C; Skog, Alexander P; Muck, Andrew E; Tupesis, Janis P; Brysiewicz, Petra; Teklu, Sisay; Wallis, Lee; Reynolds, Teri

2016-08-01

A major barrier to successful integration of acute care into health systems is the lack of consensus on the essential components of emergency care within resource-limited environments. The 2013 African Federation of Emergency Medicine Consensus Conference was convened to address the growing need for practical solutions to further implementation of emergency care in sub-Saharan Africa. Over 40 participants from 15 countries participated in the working group that focused on emergency care delivery at health facilities. Using the well-established approach developed in the WHO's Monitoring Emergency Obstetric Care, the workgroup identified the essential services delivered-signal functions-associated with each emergency care sentinel condition. Levels of emergency care were assigned based on the expected capacity of the facility to perform signal functions, and the necessary human, equipment and infrastructure resources identified. These consensus-based recommendations provide the foundation for objective facility capacity assessment in developing emergency health systems that can bolster strategic planning as well as facilitate monitoring and evaluation of service delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Essential role of the unordered VP2 n-terminal domain of the parvovirus MVM capsid in nuclear assembly and endosomal enlargement of the virion fivefold channel for cell entry

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

Sanchez-Martinez, Cristina; Grueso, Esther; Carroll, Miles

The unordered N-termini of parvovirus capsid proteins (Nt) are translocated through a channel at the icosahedral five-fold axis to serve for virus traffick. Heterologous peptides were genetically inserted at the Nt of MVM to study their functional tolerance to manipulations. Insertion of a 5T4-single-chain antibody at VP2-Nt (2Nt) yielded chimeric capsid subunits failing to enter the nucleus. The VEGFR2-binding peptide (V1) inserted at both 2Nt and VP1-Nt efficiently assembled in virions, but V1 disrupted VP1 and VP2 entry functions. The VP2 defect correlated with restricted externalization of V1-2Nt out of the coat. The specific infectivity of MVM and wtVP-pseudotyped mosaicmore » MVM-V1 virions, upon heating and/or partial 2Nt cleavage, demonstrated that some 2Nt domains become intracellularly translocated out of the virus shell and cleaved to initiate entry. The V1 insertion defines a VP2-driven endosomal enlargement of the channel as an essential structural rearrangement performed by the MVM virion to infect.« less

GPR107, a G-protein-coupled receptor essential for intoxication by Pseudomonas aeruginosa exotoxin A, localizes to the Golgi and is cleaved by furin.

PubMed

Tafesse, Fikadu G; Guimaraes, Carla P; Maruyama, Takeshi; Carette, Jan E; Lory, Stephen; Brummelkamp, Thijn R; Ploegh, Hidde L

2014-08-29

A number of toxins, including exotoxin A (PE) of Pseudomonas aeruginosa, kill cells by inhibiting protein synthesis. PE kills by ADP-ribosylation of the translation elongation factor 2, but many of the host factors required for entry, membrane translocation, and intracellular transport remain to be elucidated. A genome-wide genetic screen in human KBM7 cells was performed to uncover host factors used by PE, several of which were confirmed by CRISPR/Cas9-gene editing in a different cell type. Several proteins not previously implicated in the PE intoxication pathway were identified, including GPR107, an orphan G-protein-coupled receptor. GPR107 localizes to the trans-Golgi network and is essential for retrograde transport. It is cleaved by the endoprotease furin, and a disulfide bond connects the two cleaved fragments. Compromising this association affects the function of GPR107. The N-terminal region of GPR107 is critical for its biological function. GPR107 might be one of the long-sought receptors that associates with G-proteins to regulate intracellular vesicular transport. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Drosophila CG3303 is an essential endoribonuclease linked to TDP-43-mediated neurodegeneration

PubMed Central

Laneve, Pietro; Piacentini, Lucia; Casale, Assunta Maria; Capauto, Davide; Gioia, Ubaldo; Cappucci, Ugo; Di Carlo, Valerio; Bozzoni, Irene; Di Micco, Patrizio; Morea, Veronica; Di Franco, Carmela Antonia; Caffarelli, Elisa

2017-01-01

Endoribonucleases participate in almost every step of eukaryotic RNA metabolism, acting either as degradative or biosynthetic enzymes. We previously identified the founding member of the Eukaryotic EndoU ribonuclease family, whose components display unique biochemical features and are flexibly involved in important biological processes, such as ribosome biogenesis, tumorigenesis and viral replication. Here we report the discovery of the CG3303 gene product, which we named DendoU, as a novel family member in Drosophila. Functional characterisation revealed that DendoU is essential for Drosophila viability and nervous system activity. Pan-neuronal silencing of dendoU resulted in fly immature phenotypes, highly reduced lifespan and dramatic motor performance defects. Neuron-subtype selective silencing showed that DendoU is particularly important in cholinergic circuits. At the molecular level, we unveiled that DendoU is a positive regulator of the neurodegeneration-associated protein dTDP-43, whose downregulation recapitulates the ensemble of dendoU-dependent phenotypes. This interdisciplinary work, which comprehends in silico, in vitro and in vivo studies, unveils a relevant role for DendoU in Drosophila nervous system physio-pathology and highlights that DendoU-mediated neurotoxicity is, at least in part, contributed by dTDP-43 loss-of-function. PMID:28139767

Subsystem functional and the missing ingredient of confinement physics in density functionals.

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

Armiento, Rickard Roberto; Mattsson, Ann Elisabet; Hao, Feng

2010-08-01

The subsystem functional scheme is a promising approach recently proposed for constructing exchange-correlation density functionals. In this scheme, the physics in each part of real materials is described by mapping to a characteristic model system. The 'confinement physics,' an essential physical ingredient that has been left out in present functionals, is studied by employing the harmonic-oscillator (HO) gas model. By performing the potential {yields} density and the density {yields} exchange energy per particle mappings based on two model systems characterizing the physics in the interior (uniform electron-gas model) and surface regions (Airy gas model) of materials for the HO gases,more » we show that the confinement physics emerges when only the lowest subband of the HO gas is occupied by electrons. We examine the approximations of the exchange energy by several state-of-the-art functionals for the HO gas, and none of them produces adequate accuracy in the confinement dominated cases. A generic functional that incorporates the description of the confinement physics is needed.« less

Neurophysiologic monitoring of mental workload and fatigue during operation of a flight simulator

NASA Astrophysics Data System (ADS)

Smith, Michael E.; Gevins, Alan

2005-05-01

In one experiment, EEG recordings were made during a daytime session while 16 well-rested participants performed versions of a PC flight simulator task that were either low, moderate, or high in difficulty. In another experiment, the same subjects repeatedly performed high difficulty versions of the same task during an all night session with total sleep deprivation. Multivariate EEG metrics of cortical activation were derived for frontal brain regions essential for working memory and executive control processes that are presumably important for maintaining situational awareness, central brain regions essential for sensorimotor control, and posterior parietal and occipital regions essential for visuoperceptual processing. During the daytime session each of these regional measures displayed greater activation during the high difficulty task than during the low difficulty task, and degree of cortical activation was positively correlated with subjective workload ratings in these well-rested subjects. During the overnight session, cortical activation declined with time-on-task, and the degree of this decline over frontal regions was negatively correlated with subjective workload ratings. Since participants were already highly skilled in the task, such changes likely reflect fatigue-related diminishment of frontal executive capability rather than practice effects. These findings suggest that the success of efforts to gauge mental workload via proxy cortical activation measures in the context of adaptive automation systems will likely depend on use of user models that take both task demands and the operator"s state of alertness into account. Further methodological development of the measurement approach outlined here would be required to achieve a practical, effective objective means for monitoring transient changes in cognitive brain function during performance of complex real-world tasks.

Workflow management in large distributed systems

NASA Astrophysics Data System (ADS)

Legrand, I.; Newman, H.; Voicu, R.; Dobre, C.; Grigoras, C.

2011-12-01

The MonALISA (Monitoring Agents using a Large Integrated Services Architecture) framework provides a distributed service system capable of controlling and optimizing large-scale, data-intensive applications. An essential part of managing large-scale, distributed data-processing facilities is a monitoring system for computing facilities, storage, networks, and the very large number of applications running on these systems in near realtime. All this monitoring information gathered for all the subsystems is essential for developing the required higher-level services—the components that provide decision support and some degree of automated decisions—and for maintaining and optimizing workflow in large-scale distributed systems. These management and global optimization functions are performed by higher-level agent-based services. We present several applications of MonALISA's higher-level services including optimized dynamic routing, control, data-transfer scheduling, distributed job scheduling, dynamic allocation of storage resource to running jobs and automated management of remote services among a large set of grid facilities.

Considerations on fundamental issues in establishing a universal coverage system for health in China.

PubMed

Lei, Hai Chao

2008-11-01

This study discusses basic health services in China. In this study common sense and international experience in establishing a high-performing health system were introduced. Five components are identified: basic qualified human resources for health; basic infrastructure; essential medicines; essential technology and procedures; and basic service pathways. Recommendations were presented based upon the Chinese situation. They are: increase public financing and lower private out-of-pocket payment for services; revitalize the functions of public facilities; merge different health financing schemes; co-ordinate public fiscal and pricing policies; prioritize public financing to preventive and primary healthcare; establish and strengthen the partnership between public and private facilities and insurance schemes; and re-organize the administrative system in health-based upon the rules of simplicity, unity, and efficiency. © 2008 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

IMPDHII Protein Inhibits Toll-like Receptor 2-mediated Activation of NF-κB*

PubMed Central

Toubiana, Julie; Rossi, Anne-Lise; Grimaldi, David; Belaidouni, Nadia; Chafey, Philippe; Clary, Guilhem; Courtine, Emilie; Pene, Frederic; Mira, Jean-Paul; Claessens, Yann-Erick; Chiche, Jean-Daniel

2011-01-01

Toll-like receptor 2 (TLR2) plays an essential role in innate immunity by the recognition of a large variety of pathogen-associated molecular patterns. It induces its recruitment to lipid rafts induces the formation of a membranous activation cluster necessary to enhance, amplify, and control downstream signaling. However, the exact composition of the TLR2-mediated molecular complex is unknown. We performed a proteomic analysis in lipopeptide-stimulated THP1 and found IMPDHII protein rapidly recruited to lipid raft. Whereas IMPDHII is essential for lymphocyte proliferation, its biologic function within innate immune signal pathways has not been established yet. We report here that IMPDHII plays an important role in the negative regulation of TLR2 signaling by modulating PI3K activity. Indeed, IMPDHII increases the phosphatase activity of SHP1, which participates to the inactivation of PI3K. PMID:21460227

On-board B-ISDN fast packet switching architectures. Phase 2: Development. Proof-of-concept architecture definition report

NASA Technical Reports Server (NTRS)

Shyy, Dong-Jye; Redman, Wayne

1993-01-01

For the next-generation packet switched communications satellite system with onboard processing and spot-beam operation, a reliable onboard fast packet switch is essential to route packets from different uplink beams to different downlink beams. The rapid emergence of point-to-point services such as video distribution, and the large demand for video conference, distributed data processing, and network management makes the multicast function essential to a fast packet switch (FPS). The satellite's inherent broadcast features gives the satellite network an advantage over the terrestrial network in providing multicast services. This report evaluates alternate multicast FPS architectures for onboard baseband switching applications and selects a candidate for subsequent breadboard development. Architecture evaluation and selection will be based on the study performed in phase 1, 'Onboard B-ISDN Fast Packet Switching Architectures', and other switch architectures which have become commercially available as large scale integration (LSI) devices.

Methods for identifying an essential gene in a prokaryotic microorganism

DOEpatents

Shizuya, Hiroaki

2006-01-31

Methods are provided for the rapid identification of essential or conditionally essential DNA segments in any species of haploid cell (one copy chromosome per cell) that is capable of being transformed by artificial means and is capable of undergoing DNA recombination. This system offers an enhanced means of identifying essential function genes in diploid pathogens, such as gram-negative and gram-positive bacteria.

The Role of Auditory Evoked Potentials in the Context of Cochlear Implant Provision.

PubMed

Hoth, Sebastian; Dziemba, Oliver Christian

2017-12-01

: Auditory evoked potentials (AEP) are highly demanded during the whole process of equipping patients with cochlear implants (CI). They play an essential role in preoperative diagnostics, intraoperative testing, and postoperative monitoring of auditory performance and success. The versatility of AEP's is essentially enhanced by their property to be evokable by acoustic as well as electric stimuli. Thus, the electric responses of the auditory system following acoustic stimulation and recorded by the conventional surface technique as well as by transtympanic derivation from the promontory (Electrocochleography [ECochG]) are used for the quantitative determination of hearing loss and, additionally, electrically evoked compound actions potentials (ECAP) can be recorded with the intracochlear electrodes of the implant just adjacent to the stimulation electrode to check the functional integrity of the device and its coupling to the auditory system. The profile of ECAP thresholds is used as basis for speech processor fitting, the spread of excitation (SOE) allows the identification of electrode mislocations such as array foldover, and recovery functions may serve to optimize stimulus pulse rate. These techniques as well as those relying on scalp surface activity originating in the brainstem or the auditory cortex accompany the CI recipient during its whole life span and they offer valuable insights into functioning and possible adverse effects of the CI for clinical and scientific purposes.

Bidirectional motility of kinesin-5 motor proteins: structural determinants, cumulative functions and physiological roles.

PubMed

Singh, Sudhir Kumar; Pandey, Himanshu; Al-Bassam, Jawdat; Gheber, Larisa

2018-05-01

Mitotic kinesin-5 bipolar motor proteins perform essential functions in mitotic spindle dynamics by crosslinking and sliding antiparallel microtubules (MTs) apart within the mitotic spindle. Two recent studies have indicated that single molecules of Cin8, the Saccharomyces cerevisiae kinesin-5 homolog, are minus end-directed when moving on single MTs, yet switch directionality under certain experimental conditions (Gerson-Gurwitz et al., EMBO J 30:4942-4954, 2011; Roostalu et al., Science 332:94-99, 2011). This finding was unexpected since the Cin8 catalytic motor domain is located at the N-terminus of the protein, and such kinesins have been previously thought to be exclusively plus end-directed. In addition, the essential intracellular functions of kinesin-5 motors in separating spindle poles during mitosis can only be accomplished by plus end-directed motility during antiparallel sliding of the spindle MTs. Thus, the mechanism and possible physiological role of the minus end-directed motility of kinesin-5 motors remain unclear. Experimental and theoretical studies from several laboratories in recent years have identified additional kinesin-5 motors that are bidirectional, revealed structural determinants that regulate directionality, examined the possible mechanisms involved and have proposed physiological roles for the minus end-directed motility of kinesin-5 motors. Here, we summarize our current understanding of the remarkable ability of certain kinesin-5 motors to switch directionality when moving along MTs.

How can routine health information systems improve health systems functioning in low- and middle-income countries? Assessing the evidence base.

PubMed

Hotchkiss, David R; Diana, Mark L; Foreit, Karen G Fleischman

2012-01-01

Health system performance depends on production and use of quality health data and information. Routine health information systems (RHIS) are defined as systems that provide information at regular intervals of a year or less to meet predictable information needs. These include paper-based or electronic health records and facility- and district-level management information systems. RHIS are receiving increasing attention as an essential component of efficient, country-owned, integrated national systems. To guide investment decisions on RHIS, evidence is needed on which types of RHIS interventions work and which do not. This chapter is a systematic review of the literature on the evaluation of RHIS interventions in low- and middle-income countries, starting from the premise that investments in RHIS could be better understood and so produce greater benefits than they currently do. We describe the conceptual literature on the determinants of RHIS performance and its role in improving health systems functioning, discuss the evidence base on the effectiveness of strategies to improve RHIS performance, provide an overview of RHIS evaluation challenges, and make suggestions to improve the evidence base. The goal is to help ensure that (a) RHIS interventions are appropriately designed and implemented to improve health systems functioning and (b) resulting RHIS information is used more effectively.

A Chemical Route to Activation of Open Metal Sites in the Copper-Based Metal-Organic Framework Materials HKUST-1 and Cu-MOF-2.

PubMed

Kim, Hong Ki; Yun, Won Seok; Kim, Min-Bum; Kim, Jeung Yoon; Bae, Youn-Sang; Lee, JaeDong; Jeong, Nak Cheon

2015-08-12

Open coordination sites (OCSs) in metal-organic frameworks (MOFs) often function as key factors in the potential applications of MOFs, such as gas separation, gas sorption, and catalysis. For these applications, the activation process to remove the solvent molecules coordinated at the OCSs is an essential step that must be performed prior to use of the MOFs. To date, the thermal method performed by applying heat and vacuum has been the only method for such activation. In this report, we demonstrate that methylene chloride (MC) itself can perform the activation role: this process can serve as an alternative "chemical route" for the activation that does not require applying heat. To the best of our knowledge, no previous study has demonstrated this function of MC, although MC has been popularly used in the pretreatment step prior to the thermal activation process. On the basis of a Raman study, we propose a plausible mechanism for the chemical activation, in which the function of MC is possibly due to its coordination with the Cu(2+) center and subsequent spontaneous decoordination. Using HKUST-1 film, we further demonstrate that this chemical activation route is highly suitable for activating large-area MOF films.

Functional Performance Evaluation

NASA Technical Reports Server (NTRS)

Greenisen, Michael C.; Hayes, Judith C.; Siconolfi, Steven F.; Moore, Alan D.

1999-01-01

The Extended Duration Orbiter Medical Project (EDOMP) was established to address specific issues associated with optimizing the ability of crews to complete mission tasks deemed essential to entry, landing, and egress for spaceflights lasting up to 16 days. The main objectives of this functional performance evaluation were to investigate the physiological effects of long-duration spaceflight on skeletal muscle strength and endurance, as well as aerobic capacity and orthostatic function. Long-duration exposure to a microgravity environment may produce physiological alterations that affect crew ability to complete critical tasks such as extravehicular activity (EVA), intravehicular activity (IVA), and nominal or emergency egress. Ultimately, this information will be used to develop and verify countermeasures. The answers to three specific functional performance questions were sought: (1) What are the performance decrements resulting from missions of varying durations? (2) What are the physical requirements for successful entry, landing, and emergency egress from the Shuttle? and (3) What combination of preflight fitness training and in-flight countermeasures will minimize in-flight muscle performance decrements? To answer these questions, the Exercise Countermeasures Project looked at physiological changes associated with muscle degradation as well as orthostatic intolerance. A means of ensuring motor coordination was necessary to maintain proficiency in piloting skills, EVA, and IVA tasks. In addition, it was necessary to maintain musculoskeletal strength and function to meet the rigors associated with moderate altitude bailout and with nominal or emergency egress from the landed Orbiter. Eight investigations, referred to as Detailed Supplementary Objectives (DSOs) 475, 476, 477, 606, 608, 617, 618, and 624, were conducted to study muscle degradation and the effects of exercise on exercise capacity and orthostatic function (Table 3-1). This chapter is divided into three parts. Part 1 describes specific findings from studies of muscle strength, endurance, fiber size, and volume. Part 2 describes results from studies of how in-flight exercise affects postflight exercise capacity and orthostatic function. Part 3 focuses on the development of new noninvasive methods for assessing body composition in astronauts and how those methods can be used to correlate measures of exercise performance and changes in body composition.

A high performance scientific cloud computing environment for materials simulations

NASA Astrophysics Data System (ADS)

Jorissen, K.; Vila, F. D.; Rehr, J. J.

2012-09-01

We describe the development of a scientific cloud computing (SCC) platform that offers high performance computation capability. The platform consists of a scientific virtual machine prototype containing a UNIX operating system and several materials science codes, together with essential interface tools (an SCC toolset) that offers functionality comparable to local compute clusters. In particular, our SCC toolset provides automatic creation of virtual clusters for parallel computing, including tools for execution and monitoring performance, as well as efficient I/O utilities that enable seamless connections to and from the cloud. Our SCC platform is optimized for the Amazon Elastic Compute Cloud (EC2). We present benchmarks for prototypical scientific applications and demonstrate performance comparable to local compute clusters. To facilitate code execution and provide user-friendly access, we have also integrated cloud computing capability in a JAVA-based GUI. Our SCC platform may be an alternative to traditional HPC resources for materials science or quantum chemistry applications.

Human task animation from performance models and natural language input

NASA Technical Reports Server (NTRS)

Esakov, Jeffrey; Badler, Norman I.; Jung, Moon

1989-01-01

Graphical manipulation of human figures is essential for certain types of human factors analyses such as reach, clearance, fit, and view. In many situations, however, the animation of simulated people performing various tasks may be based on more complicated functions involving multiple simultaneous reaches, critical timing, resource availability, and human performance capabilities. One rather effective means for creating such a simulation is through a natural language description of the tasks to be carried out. Given an anthropometrically-sized figure and a geometric workplace environment, various simple actions such as reach, turn, and view can be effectively controlled from language commands or standard NASA checklist procedures. The commands may also be generated by external simulation tools. Task timing is determined from actual performance models, if available, such as strength models or Fitts' Law. The resulting action specification are animated on a Silicon Graphics Iris workstation in real-time.

Interaction of hypertension and age in visual selective attention performance.

PubMed

Madden, D J; Blumenthal, J A

1998-01-01

Previous research suggests that some aspects of cognitive performance decline as a joint function of age and hypertension. In this experiment, 51 unmedicated individuals with mild essential hypertension and 48 normotensive individuals, 18-78 years of age, performed a visual search task. The estimated time required to identify a display character and shift attention between display positions increased with age. This attention shift time did not differ significantly between hypertensive and normotensive participants, but regression analyses indicated some mediation of the age effect by blood pressure. For individuals less than 60 years of age, the error rate was greater for hypertensive than for normotensive participants. Although the present design could detect effects of only moderate to large size, the results suggest that effects of hypertension may be more evident in a relatively general measure of performance (mean error rate) than in the speed of shifting visual attention.

Discovery of Selective Inhibitors of Imidazoleglycerol-Phosphate Dehydratase from Mycobacterium tuberculosis by Virtual Screening

NASA Astrophysics Data System (ADS)

Podshivalov, D.; Mandzhieva, Yu. B.; Sidorov-Biryukov, D. D.; Timofeev, V. I.; Kuranova, I. P.

2018-01-01

Bacterial imidazoleglycerol-phosphate dehydratase from Mycobacterium tuberculosis (HisB- Mt) is a convenient target for the discovery of selective inhibitors as potential antituberculosis drugs. The virtual screening was performed to find compounds suitable for the design of selective inhibitors of HisB- Mt. The positions of four ligands, which were selected based on the docking scoring function and docked to the activesite region of the enzyme, were refined by molecular dynamics simulation. The nearest environment of the ligands was determined. These compounds selectively bind to functionally essential active-site residues, thus blocking access of substrates to the active site of the enzyme, and can be used as lead compounds for the design of selective inhibitors of HisB- M.

Justice in jeopardy: a qualitative study of institutional ethics committees in New Delhi.

PubMed

Kandhari, Rohini

2013-01-01

Protecting the safety and welfare of clinical trial subjects is the primary responsibility of the multidisciplinary ethics committee. In India, ethics committees have come under increasing criticism for functioning as "secret societies unaccountable to the public" (1). Yet, little effort has been made to undertake qualitative research on the ethics review bodies. This article describes the essential findings of a study that aimed at providing an insight into the structure and functioning of institutional ethics committees (IECs) in selected hospitals in Delhi. Importantly, the study also attempted to investigate the challenges faced by IEC members that pose barriers to IEC performance and thus jeopardise a just and effective system of protection for the human trial subject.

Functional ability assessment: guidelines for the workplace.

PubMed

Colledge, A L; Johns, R E; Thomas, M H

1999-03-01

Short- and long-term disability certification is required in all Western countries for extended time away from work. The Americans With Disabilities Act mandates that medical providers use rational thought and justifiable criteria when evaluating an employee's "fitness for duty". In order to facilitate employment/disability decisions, physicians must now serve as an advisor to the employer. Both the employer and the physician are legally obligated to carefully justify any recommendations for placement or exclusion from the workplace. We propose a uniform methodology that both physicians and employers could use together to determine the performance capability of an individual with a temporary or permanent impairment or disability in terms of essential job functions as defined under the Americans With Disabilities Act.

Examining the locus of age effects on complex span tasks.

PubMed

McCabe, Jennifer; Hartman, Marilyn

2003-09-01

To investigate the locus of age effects on complex span tasks, the authors evaluated the contributions of working memory functions and processing speed. Age differences were found in measures of storage capacity, language processing speed, and lower level speed. Statistically controlling for each of these in hierarchical regressions substantially reduced, but did not eliminate, the complex span age effect. Accounting for lower level speed and storage, however, removed essentially the entire age effect, suggesting that both functions play important and independent roles. Additional evidence for the role of storage capacity was the absence of complex span age differences with span size calibrated to individual word span performance. Explanations for age differences based on inhibition and concurrent task performamce were not supported.

Mapping Population-Level Spatial Access to Essential Surgical Care in Ghana Using Availability of Bellwether Procedures

PubMed Central

Stewart, Barclay T.; Tansley, Gavin; Gyedu, Adam; Ofosu, Anthony; Donkor, Peter; Appiah-Denkyira, Ebenezer; Quansah, Robert; Clarke, Damian L.; Volmink, Jimmy; Mock, Charles

2017-01-01

IMPORTANCE Conditions that can be treated by surgery comprise more than 16% of the global disease burden. However, 5 billion people do not have access to essential surgical care. An estimated 90% of the 87 million disability-adjusted life-years incurred by surgical conditions could be averted by providing access to timely and safe surgery in low-income and middle-income countries. Population-level spatial access to essential surgery in Ghana is not known. OBJECTIVES To assess the performance of bellwether procedures (ie, open fracture repair, emergency laparotomy, and cesarean section) as a proxy for performing essential surgery more broadly, to map population-level spatial access to essential surgery, and to identify first-level referral hospitals that would most improve access to essential surgery if strengthened in Ghana. DESIGN, SETTING, AND PARTICIPANTS Population-based study among all households and public and private not-for-profit hospitals in Ghana. Households were represented by georeferenced census data. First-level and second-level referral hospitals managed by the Ministry of Health and all tertiary hospitals were included. Surgical data were collected from January 1 to December 31, 2014. MAIN OUTCOMES AND MEASURES All procedures performed at first-level referral hospitals in Ghana in 2014 were used to sort each facility into 1 of the following 3 hospital groups: those without capability to perform all 3 bellwether procedures, those that performed 1 to 11 of each procedure, and those that performed at least 12 of each procedure. Candidates for targeted capability improvement were identified by cost-distance and network analysis. RESULTS Of 155 first-level referral hospitals managed by the Ghana Health Service and the Christian Health Association of Ghana, 123 (79.4%) reported surgical data. Ninety-five (77.2%) did not have the capability in 2014 to perform all 3 bellwether procedures, 24 (19.5%) performed 1 to 11 of each bellwether procedure, and 4 (3.3%) performed at least 12. The essential surgical procedure rate was greater in bellwether procedure–capable first-level referral hospitals than in noncapable hospitals (median, 638; interquartile range, 440–1418 vs 360; interquartile range, 0–896 procedures per 100 000 population; P = .03). Population-level spatial access within 2 hours to a hospital that performed 1 to 11 and at least 12 of each bellwether procedure was 83.2% (uncertainty interval [UI], 82.2%–83.4%) and 71.4% (UI, 64.4%–75.0%), respectively. Five hospitals were identified for targeted capability improvement. CONCLUSIONS AND RELEVANCE Almost 30% of Ghanaians cannot access essential surgery within 2 hours. Bellwether capability is a useful metric for essential surgery more broadly. Similar strategic planning exercises might be useful for other low-income and middle-income countries aiming to improve access to essential surgery. PMID:27331865

Vitamin D Insufficiency and Cognitive Function Trajectories in Older Adults: The Rancho Bernardo Study.

PubMed

Laughlin, Gail A; Kritz-Silverstein, Donna; Bergstrom, Jaclyn; Reas, Emilie T; Jassal, Simerjot K; Barrett-Connor, Elizabeth; McEvoy, Linda K

2017-01-01

Evidence of a role for vitamin D (VitD) in cognitive aging is mixed and based primarily on extreme VitD deficiency. We evaluated the association of VitD insufficiency with cognitive function in older, community-dwelling adults living in a temperate climate with year-round sunshine. A population-based longitudinal study of 1,058 adults (median age 75; 62% women) who had cognitive function assessed and serum levels of 25-hydroxyvitaminD (25OHD) measured in 1997-99 and were followed for up to three additional cognitive function assessments over a 12-year period. Overall, 14% (n = 145) of participants had VitD insufficiency defined as 25OHD <30 ng/ml. Adjusting for age, sex, education, and season, VitD insufficiency was associated with poorer baseline performance on the Mini-Mental Status Exam (MMSE) (p = 0.013), Trails Making Test B (Trails B) (p = 0.015), Category Fluency (p = 0.006), and Long Term Retrieval (p = 0.019); differences were equivalent to 5 years of age. For those with VitD insufficiency, the odds of mildly impaired performance at baseline were 38% higher for MMSE (p = 0.08), 78% higher for Trails B (p = 0.017), and 2-fold higher for Category Fluency and Long Term Retrieval (both p = 0.001). VitD insufficiency was not related to the rate of cognitive decline on any test or the risk of developing impaired performance during follow-up. In this population with little VitD deficiency, even moderately low VitD was associated with poorer performance on multiple domains of cognitive function. Low VitD did not predict 12-year cognitive decline. Clinical trials are essential to establish a causal link between VitD and cognitive well-being.

Cognitive impairment and pragmatics.

PubMed

Gutiérrez-Rexach, Javier; Schatz, Sara

2016-01-01

One of the most important ingredients of felicitous conversation exchanges is the adequate expression of illocutionary force and the achievement of perlocutionary effects, which can be considered essential to the functioning of pragmatic competence. The breakdown of illocutionary and perlocutionary functions is one of the most prominent external features of cognitive impairment in Alzheimer's Disease, with devastating psychological and social consequences for patients, their family and caregivers. The study of pragmatic functions is essential for a proper understanding of the linguistic and communicative aspects of Alzheimer's disease.

Global pediatric environmental health.

PubMed

Guidotti, Tee L; Gitterman, Benjamin A

2007-04-01

Children are uniquely vulnerable to environmental health problems. Developed countries report as the most common problems ambient (outdoor) air pollution and lead. Developing countries have a wider range of common problems, including childhood injuries, indoor air pollution, infectious disease, and poor sanitation with unsafe water. Globally, the agencies of the United Nations act to protect children and perform essential reporting and standards-setting functions. Conditions vary greatly among countries and are not always better in developing countries. Protecting the health of children requires strengthening the public health and medical systems in every country, rather than a single global agenda.

Computer-automated opponent for manned air-to-air combat simulations

NASA Technical Reports Server (NTRS)

Hankins, W. W., III

1979-01-01

Two versions of a real-time digital-computer program that operates a fighter airplane interactively against a human pilot in simulated air combat were evaluated. They function by replacing one of two pilots in the Langley differential maneuvering simulator. Both versions make maneuvering decisions from identical information and logic; they differ essentially in the aerodynamic models that they control. One is very complete, but the other is much simpler, primarily characterizing the airplane's performance (lift, drag, and thrust). Both models competed extremely well against highly trained U.S. fighter pilots.

International Infantry and Joint Services Small Arms Systems Symposium, Exhibition and Firing Demonstration

DTIC Science & Technology

2009-05-21

range performance and PHit /PKill is essential ● System prepared for additional functionalities as technology matures Aimpoint BR8 – NATO Demo Aimpoint...have been delivered to FMV (Swedish Defence Materiel Administration) ● Demonstrated for NATO in Toledo 2007- 02-15: > 65% PHit at 1.2x1.2m targets...from 100 to 250m! ● Demonstrated in Sweden 2008-10-01: > 80% PHit at different targets from 120 to 150m! ● 100 units ordered in May 2009 for use on

[The department of interdisciplinary emergency medicine: organization, structure and process optimization].

PubMed

Bernhard, Michael; Pietsch, Christian; Gries, André

2009-06-01

The essential tasks of a department of interdisciplinary emergency medicine are the initial triage and assessment of vital function as well as the subsequent organization und initiation of emergency treatment. A previously defined set of diagnostic and therapeutic measures is carried out before the patient is allocated to an in-hospital clinical service and is admitted to a ward. Moreover, diagnosis and treatment for outpatients are performed. "Time" is a critical factor to be considered for all organizational and structural aspects of a department of interdisciplinary emergency medicine.

Uncovering Common Sleep Disorders and Their Impacts on Occupational Performance.

PubMed

Judd, Sylvia R

2017-05-01

Sleep is an active process; the body undergoes restoration and regeneration. Adequate sleep is essential to health and cognitive function. Sleep is critical for cell repair, a healthy immune system, and hormonal regulation, and aids in the process of learning, memory, and emotion. Inadequate sleep can lead to multiple chronic health and mental conditions over time. The occupational health nurse can be instrumental in screening for two of the most common sleep disorders, insomnia and obstructive sleep apnea, by asking workers key questions and using simple screening tools.

Dynamic survey of mitochondria by ubiquitin

PubMed Central

Escobar-Henriques, Mafalda; Langer, Thomas

2014-01-01

Ubiquitin is a post-translational modifier with proteolytic and non-proteolytic roles in many biological processes. At mitochondria, it performs regulatory homeostatic functions and contributes to mitochondrial quality control. Ubiquitin is essential for mitochondrial fusion, regulates mitochondria-ER contacts, and participates in maternal mtDNA inheritance. Under stress, mitochondrial dysfunction induces ubiquitin-dependent responses that involve mitochondrial proteome remodeling and culminate in organelle removal by mitophagy. In addition, many ubiquitin-dependent mechanisms have been shown to regulate innate immune responses and xenophagy. Here, we review the emerging roles of ubiquitin at mitochondria. PMID:24569520

Countermeasures to Neurobehavioral Deficits from Cumulative Partial Sleep Deprivation During Space Flight

NASA Technical Reports Server (NTRS)

Dinges, David F.

1999-01-01

This project is concerned with identifying ways to prevent neurobehavioral and physical deterioration due to inadequate sleep in astronauts during long-duration manned space flight. The performance capability of astronauts during extended-duration space flight depends heavily on achieving recovery through adequate sleep. Even with appropriate circadian alignment, sleep loss can erode fundamental elements of human performance capability including vigilance, cognitive speed and accuracy, working memory, reaction time, and physiological alertness. Adequate sleep is essential during manned space flight not only to ensure high levels of safe and effective human performance, but also as a basic regulatory biology critical to healthy human functioning. There is now extensive objective evidence that astronaut sleep is frequently restricted in space flight to averages between 4 hr and 6.5 hr/day. Chronic sleep restriction during manned space flight can occur in response to endogenous disturbances of sleep (motion sickness, stress, circadian rhythms), environmental disruptions of sleep (noise, temperature, light), and curtailment of sleep due to the work demands and other activities that accompany extended space flight operations. The mechanism through which this risk emerges is the development of cumulative homeostatic pressure for sleep across consecutive days of inadequate sleep. Research has shown that the physiological sleepiness and performance deficits engendered by sleep debt can progressively worsen (i.e., accumulate) over consecutive days of sleep restriction, and that sleep limited to levels commonly experienced by astronauts (i.e., 4 - 6 hr per night) for as little as 1 week, can result in increased lapses of attention, degradation of response times, deficits in complex problem solving, reduced learning, mood disturbance, disruption of essential neuroendocrine, metabolic, and neuroimmune responses, and in some vulnerable persons, the emergence of uncontrolled sleep attacks. The prevention of cumulative performance deficits and neuroendocrine disruption from sleep restriction during extended duration space flight involves finding the most effective ways to obtain sleep in order to maintain the high-level cognitive and physical performance functions required for manned space flight. There is currently a critical deficiency in knowledge of the effects of how variations in sleep duration and timing relate to the most efficient return of performance per unit time invested in sleep during long-duration missions, and how the nature of sleep physiology (i.e., sleep stages, sleep electroencephalographic [EEG] power spectral analyses) change as a function of sleep restriction and performance degradation. The primary aim of this project is to meet these critical deficiencies through utilization of a response surface experimental paradigm, testing in a dose-response manner, varying combinations of sleep duration and timing, for the purpose of establishing how to most effectively limit the cumulative adverse effects on human performance and physiology of chronic sleep restriction in space operations.

Functional, electrophysiological recoveries of rats with sciatic nerve lesions following transplantation of elongated DRG cells.

PubMed

Dayawansa, Samantha; Zhang, Jun; Shih, Chung-Hsuan; Tharakan, Binu; Huang, Jason H

2016-04-01

Functional data are essential when confirming the efficacy of elongated dorsal root ganglia (DRG) cells as a substitute for autografting. We present the quantitative functional motor, electrophysiological findings of engineered DRG recipients for the first time. Elongated DRG neurons and autografts were transplanted to bridge 1-cm sciatic nerve lesions of Sprague Dawley (SD) rats. Motor recoveries of elongated DRG recipients (n=9), autograft recipients (n=9), unrepaired rats (n=9) and intact rats (n=6) were investigated using the angle board challenge test following 16 weeks of recovery. Electrophysiology studies were conducted to assess the functional recovery at 16 weeks. In addition, elongated DRGs were subjected to histology assessments. At threshold levels (35° angle) of the angle board challenge test, the autograft recipients', DRG recipients' and unrepaired group's performances were equal to each other and were less than the intact group (p<0.05). However, during the subthreshold (30°) angle board challenge test, the elongated DRG recipients' performance was similar to both the intact group and the autograft nerve recipients, and was better (p<0.05) than the unrepaired group. The autograft recipients' performance was similar to the unrepaired group and was significantly different (p<0.05) compared with the performance of the intact group. During electrophysiological testing, the rats with transplanted engineered DRG constructs had intact signal transmission when recorded over the lesion, while the unrepaired rats did not. It was observed that elongated DRG neurons closely resembled an autograft during histological assessments. Performances of autograft and elongated DRG construct recipients were similar. Elongated DRG neurons should be further investigated as a substitute for autografting.

Perceptions on evaluative and formative functions of external supervision of Rwandan primary healthcare facilities: A qualitative study

PubMed Central

Schriver, Michael; Cubaka, Vincent Kalumire; Itangishaka, Sylvere; Nyirazinyoye, Laetitia; Kallestrup, Per

2018-01-01

Background External supervision of primary healthcare facilities in low- and middle-income countries often has a managerial main purpose in which the role of support for professional development is unclear. Aim To explore how Rwandan primary healthcare supervisors and providers (supervisees) perceive evaluative and formative functions of external supervision. Design Qualitative, exploratory study. Data Focus group discussions: three with supervisors, three with providers, and one mixed (n = 31). Findings were discussed with individual and groups of supervisors and providers. Results Evaluative activities occupied providers’ understanding of supervision, including checking, correcting, marking and performance-based financing. These were presented as sources of motivation, that in self-determination theory indicate introjected regulation. Supervisors preferred to highlight their role in formative supervision, which may mask their own and providers’ uncontested accounts that systematic performance evaluations predominated supervisors’ work. Providers strongly requested larger focus on formative and supportive functions, voiced as well by most supervisors. Impact of performance evaluation on motivation and professional development is discussed. Conclusion While external supervisors intended to support providers’ professional development, our findings indicate serious problems with this in a context of frequent evaluations and performance marking. Separating the role of supporter and evaluator does not appear as the simple solution. If external supervision is to improve health care services, it is essential that supervisors and health centre managers are competent to support providers in a way that transparently accounts for various performance pressures. This includes delivery of proper formative supervision with useful feedback, maintaining an effective supervisory relationship, as well as ensuring providers are aware of the purpose and content of evaluative and formative supervision functions. PMID:29462144

Calculation of phonon dispersion relation using new correlation functional

NASA Astrophysics Data System (ADS)

Jitropas, Ukrit; Hsu, Chung-Hao

2017-06-01

To extend the use of Local Density Approximation (LDA), a new analytical correlation functional is introduced. Correlation energy is an essential ingredient within density functional theory and used to determine ground state energy and other properties including phonon dispersion relation. Except for high and low density limit, the general expression of correlation energy is unknown. The approximation approach is therefore required. The accuracy of the modelling system depends on the quality of correlation energy approximation. Typical correlation functionals used in LDA such as Vosko-Wilk-Nusair (VWN) and Perdew-Wang (PW) were obtained from parameterizing the near-exact quantum Monte Carlo data of Ceperley and Alder. These functionals are presented in complex form and inconvenient to implement. Alternatively, the latest published formula of Chachiyo correlation functional provides a comparable result for those much more complicated functionals. In addition, it provides more predictive power based on the first principle approach, not fitting functionals. Nevertheless, the performance of Chachiyo formula for calculating phonon dispersion relation (a key to the thermal properties of materials) has not been tested yet. Here, the implementation of new correlation functional to calculate phonon dispersion relation is initiated. The accuracy and its validity will be explored.

Are well functioning civil registration and vital statistics systems associated with better health outcomes?

PubMed

Phillips, David E; AbouZahr, Carla; Lopez, Alan D; Mikkelsen, Lene; de Savigny, Don; Lozano, Rafael; Wilmoth, John; Setel, Philip W

2015-10-03

In this Series paper, we examine whether well functioning civil registration and vital statistics (CRVS) systems are associated with improved population health outcomes. We present a conceptual model connecting CRVS to wellbeing, and describe an ecological association between CRVS and health outcomes. The conceptual model posits that the legal identity that civil registration provides to individuals is key to access entitlements and services. Vital statistics produced by CRVS systems provide essential information for public health policy and prevention. These outcomes benefit individuals and societies, including improved health. We use marginal linear models and lag-lead analysis to measure ecological associations between a composite metric of CRVS performance and three health outcomes. Results are consistent with the conceptual model: improved CRVS performance coincides with improved health outcomes worldwide in a temporally consistent manner. Investment to strengthen CRVS systems is not only an important goal for individuals and societies, but also a development imperative that is good for health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Organization and dynamics of yeast mitochondrial nucleoids

PubMed Central

MIYAKAWA, Isamu

2017-01-01

Mitochondrial DNA (mtDNA) is packaged by association with specific proteins in compact DNA-protein complexes named mitochondrial nucleoids (mt-nucleoids). The budding yeast Saccharomyces cerevisiae is able to grow either aerobically or anaerobically. Due to this characteristic, S. cerevisiae has been extensively used as a model organism to study genetics, morphology and biochemistry of mitochondria for a long time. Mitochondria of S. cerevisiae frequently fuse and divide, and perform dynamic morphological changes depending on the culture conditions and the stage of life cycle of the yeast cells. The mt-nucleoids also dynamically change their morphology, accompanying morphological changes of mitochondria. The mt-nucleoids have been isolated morphologically intact and functional analyses of mt-nucleoid proteins have been extensively performed. These studies have revealed that the functions of mt-nucleoid proteins are essential for maintenance of mtDNA. The aims of this review are to summarize the history on the research of yeast mt-nucleoids as well as recent findings on the organization of the mt-nucleoids and mitochondrial dynamics. PMID:28496055

Medical Imaging for Understanding Sleep Regulation

NASA Astrophysics Data System (ADS)

Wong, Kenneth

2011-10-01

Sleep is essential for the health of the nervous system. Lack of sleep has a profound negative effect on cognitive ability and task performance. During sustained military operations, soldiers often suffer from decreased quality and quantity of sleep, increasing their susceptibility to neurological problems and limiting their ability to perform the challenging mental tasks that their missions require. In the civilian sector, inadequate sleep and overt sleep pathology are becoming more common, with many detrimental impacts. There is a strong need for new, in vivo studies of human brains during sleep, particularly the initial descent from wakefulness. Our research team is investigating sleep using a combination of magnetic resonance imaging (MRI), positron emission tomography (PET), and electroencephalography (EEG). High resolution MRI combined with PET enables localization of biochemical processes (e.g., metabolism) to anatomical structures. MRI methods can also be used to examine functional connectivity among brain regions. Neural networks are dynamically reordered during different sleep stages, reflecting the disconnect with the waking world and the essential yet unconscious brain activity that occurs during sleep.[4pt] In collaboration with Linda Larson-Prior, Washington University; Alpay Ozcan, Virginia Tech; Seong Mun, Virginia Tech; and Zang-Hee Cho, Gachon University.

Water-Based Coating Simplifies Circuit Board Manufacturing

NASA Technical Reports Server (NTRS)

2008-01-01

The Structures and Materials Division at Glenn Research Center is devoted to developing advanced, high-temperature materials and processes for future aerospace propulsion and power generation systems. The Polymers Branch falls under this division, and it is involved in the development of high-performance materials, including polymers for high-temperature polymer matrix composites; nanocomposites for both high- and low-temperature applications; durable aerogels; purification and functionalization of carbon nanotubes and their use in composites; computational modeling of materials and biological systems and processes; and developing polymer-derived molecular sensors. Essentially, this branch creates high-performance materials to reduce the weight and boost performance of components for space missions and aircraft engine components. Under the leadership of chemical engineer, Dr. Michael Meador, the Polymers Branch boasts world-class laboratories, composite manufacturing facilities, testing stations, and some of the best scientists in the field.

[Prematurity: longitudinal analysis of executive functions].

PubMed

Sastre-Riba, S

2009-02-27

Understanding cognitive development requires an interdisciplinary and neuropsychological approach. Executive functions facilitates cognitive activity and they are related to progressive cerebral configuration during pregnancy and infancy. One of the aims of the actual neuropsychology is the ontogeny of executive functions and their capacity to explain differential and normative developmental trends, specially because of its consequences on mental flexibility, monitoring, planning and cognitive control; they are also essential for good performance at school. The incidence of developmental risk factors as prematurity could affect long-term executive functioning expressed in learning difficulties or behavioral control. We studied, comparatively and longitudinally, the individual activity on objects displayed by typical babies (n = 25), and preterm babies (n = 10) from 1.5 to 2 years-old. Applying systematic observational methodology, spontaneous babies' activity is registered. Double intra and inter-group analysis compare the data from the resolution of a non-verbal task through a multifaceted design. Results obtained show us differential pattern of early executive functioning among the groups studied. The growth of executive functioning is showed, too, through the ages studied for every group.

Functionalization of Lipid-Based Nutrient Supplement with β-Cyclodextrin Inclusions of Oregano Essential Oil.

PubMed

Gaur, Shashank; Lopez, Emely C; Ojha, Ankur; Andrade, Juan E

2018-06-01

Intestinal parasitic infection is one of the main causes of acute undernutrition in children. Oral consumption of oregano essential oil (OEO) can reduce intestinal parasitic infections, however, its addition to therapeutic and supplementary foods is hampered by its undesirable flavor. The objective of this study was to develop a functional lipid-based nutrient supplement (LNS) containing OEO, which is stable, acceptable and provides targeted intestinal delivery of bioactive. β-cyclodextrin (β-CyD) inclusion complexes of OEO (β-CyD-OEO), and carvacrol (β-CyD-CV) (1:1 molar) were prepared using slurry complexation (-20 °C) method and characterized based on encapsulation efficiency, moisture content, morphology, and 2-phase in vitro digestion stability. Carvacrol (CV) content was measured using reverse phase HPLC-UV. LNS containing β-CyD-OEO (27.2 mg encapsulate/20 g LNS) was formulated using Indian staples and ingredients. Discriminatory sensory tests (triangle) were performed with college students (n = 58) and low-income women (n = 25), with young children at home (1 to 6 years), living in Mehsana, India to evaluate differences between LNS with and without bioactive ingredient (β-CyD-OEO only). Moisture of dried complexes ranged 9.1% to 9.7% d.b., whereas water activity 0.35 to 0.412. The complex size and encapsulation efficiency of β-CyD-OEO and β-CyD-CV were 1.5 to 7 μm and 4 to 20 μm, and 86.04 ± 4.48% and 81.39 ± 3.34%, respectively. The bioactive complexes were stable through the gastric and intestinal phases. Bioaccessibility of encapsulated CV ranged 6.0% to 7.7%. Sensory tests revealed no differences (P > 0.05) in color, aroma, and taste between LNS with and without β-CyD-OEO complexes. Functionalization of LNS with β-CyD-OEO is feasible based on in vitro stability and sensory studies. Despite its antiparasitic activities, the addition of oregano essential oil into foods is limited due to its strong flavor and volatility. In this study, we evaluated the encapsulation of oregano essential oil with β-cyclodextrin and its addition into lipid-based nutrition supplements. The results revealed that complex encapsulation efficiency was above 80%. Also, the bioactive complexes were stable under in vitro gastrointestinal conditions. Sensory evaluation of LNS with and without encapsulated essential oil showed no difference in terms of color, aroma, and taste. The functional LNS can both address nutrient insufficiency as well as parasitic infection among malnourished populations in low-resource settings. © 2018 Institute of Food Technologists®.

Direct protein-protein conjugation by genetically introducing bioorthogonal functional groups into proteins.

PubMed

Kim, Sanggil; Ko, Wooseok; Sung, Bong Hyun; Kim, Sun Chang; Lee, Hyun Soo

2016-11-15

Proteins often function as complex structures in conjunction with other proteins. Because these complex structures are essential for sophisticated functions, developing protein-protein conjugates has gained research interest. In this study, site-specific protein-protein conjugation was performed by genetically incorporating an azide-containing amino acid into one protein and a bicyclononyne (BCN)-containing amino acid into the other. Three to four sites in each of the proteins were tested for conjugation efficiency, and three combinations showed excellent conjugation efficiency. The genetic incorporation of unnatural amino acids (UAAs) is technically simple and produces the mutant protein in high yield. In addition, the conjugation reaction can be conducted by simple mixing, and does not require additional reagents or linker molecules. Therefore, this method may prove very useful for generating protein-protein conjugates and protein complexes of biochemical significance. Copyright © 2016. Published by Elsevier Ltd.

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

Jackson, R.N.; Robinson, H.; Klauer, A. A.

The essential RNA helicase, Mtr4, performs a critical role in RNA processing and degradation as an activator of the nuclear exosome. The molecular basis for this vital function is not understood and detailed analysis is significantly limited by the lack of structural data. In this study, we present the crystal structure of Mtr4. The structure reveals a new arch-like domain that is specific to Mtr4 and Ski2 (the cytosolic homologue of Mtr4). In vivo and in vitro analyses demonstrate that the Mtr4 arch domain is required for proper 5.8S rRNA processing, and suggest that the arch functions independently of canonicalmore » helicase activity. In addition, extensive conservation along the face of the putative RNA exit site highlights a potential interface with the exosome. These studies provide a molecular framework for understanding fundamental aspects of helicase function in exosome activation, and more broadly define the molecular architecture of Ski2-like helicases.« less

Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

PubMed Central

Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; (Mengqiu) Xing, Malcolm; Wang, Changyong

2014-01-01

Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction. PMID:24429673

Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice.

PubMed

Takeda, K; Kamanaka, M; Tanaka, T; Kishimoto, T; Akira, S

1996-10-15

IL-13 shares many biologic responses with IL-4. In contrast to well-characterized IL-4 signaling pathways, which utilize STAT6 and 4PS/IRS2, IL-13 signaling pathways are poorly understood. Recent studies performed with STAT6-deficient mice have demonstrated that STAT6 plays an essential role in IL-4 signaling. In this study, the functions of peritoneal macrophages of STAT6-deficient mice in response to IL-13 were analyzed. In STAT6-deficient mice, neither morphologic changes nor augmentation of MHC class II expression in response to IL-13 was observed. In addition, IL-13 did not decrease the nitric oxide production by activated macrophages. Taken together, these results suggest that the macrophage functions in response to IL-13 were impaired in STAT6-deficient mice, indicating that IL-13 and IL-4 share the signaling pathway via STAT6.

Morphological analysis of dendrites and spines by hybridization of ridge detection with twin support vector machine.

PubMed

Wang, Shuihua; Chen, Mengmeng; Li, Yang; Shao, Ying; Zhang, Yudong; Du, Sidan; Wu, Jane

2016-01-01

Dendritic spines are described as neuronal protrusions. The morphology of dendritic spines and dendrites has a strong relationship to its function, as well as playing an important role in understanding brain function. Quantitative analysis of dendrites and dendritic spines is essential to an understanding of the formation and function of the nervous system. However, highly efficient tools for the quantitative analysis of dendrites and dendritic spines are currently undeveloped. In this paper we propose a novel three-step cascaded algorithm-RTSVM- which is composed of ridge detection as the curvature structure identifier for backbone extraction, boundary location based on differences in density, the Hu moment as features and Twin Support Vector Machine (TSVM) classifiers for spine classification. Our data demonstrates that this newly developed algorithm has performed better than other available techniques used to detect accuracy and false alarm rates. This algorithm will be used effectively in neuroscience research.

Chromosome ends: different sequences may provide conserved functions.

PubMed

Louis, Edward J; Vershinin, Alexander V

2005-07-01

The structures of specific chromosome regions, centromeres and telomeres, present a number of puzzles. As functions performed by these regions are ubiquitous and essential, their DNA, proteins and chromatin structure are expected to be conserved. Recent studies of centromeric DNA from human, Drosophila and plant species have demonstrated that a hidden universal centromere-specific sequence is highly unlikely. The DNA of telomeres is more conserved consisting of a tandemly repeated 6-8 bp Arabidopsis-like sequence in a majority of organisms as diverse as protozoan, fungi, mammals and plants. However, there are alternatives to short DNA repeats at the ends of chromosomes and for telomere elongation by telomerase. Here we focus on the similarities and diversity that exist among the structural elements, DNA sequences and proteins, that make up terminal domains (telomeres and subtelomeres), and how organisms use these in different ways to fulfil the functions of end-replication and end-protection. Copyright (c) 2005 Wiley Periodicals, Inc.

Brown Mycelial Mat as an Essential Morphological Structure of the Shiitake Medicinal Mushroom Lentinus edodes (Agaricomycetes).

PubMed

Vetchinkina, Elena; Gorshkov, Vladimir; Ageeva, Marina; Gogolev, Yuri; Nikitina, Valentina E

2017-01-01

We show here, to our knowledge for the first time, that the brown mycelial mat of the xylotrophic shiitake medicinal mushroom, Lentinus edodes, not only performs a protective function owing to significant changes in the ultrastructure (thickening of the cell wall, increased density, and pigmentation of the fungal hyphae) but also is a metabolically active stage in the development of the mushroom. The cells of this morphological structure exhibit repeated activation of expression of the genes lcc4, tir, exp1, chi, and exg1, coding for laccase, tyrosinase, a specific transcription factor, chitinase, and glucanase, which are required for fungal growth and morphogenesis. This study revealed the maximum activity of functionally important proteins with phenol oxidase and lectin activities, and the emergence of additional laccases, tyrosinases, and lectins, which are typical of only this stage of morphogenesis and have a regulatory function in the development and formation of fruiting bodies.

Hybrid Functional Study of Sodium and Potassium Incorporation in Cu2ZnSnS4

NASA Astrophysics Data System (ADS)

Tse, Kin Fai; Wong, Manhoi; Zhang, Yiou; Zhang, Jingzhao; Zhu, Junyi

The thermodynamics of Na and K incorporation and its effects in Cu2ZnSnS4 (CZTS) is studied using density functional theory with hybrid functional. The allowed chemical potential of Na/K in CZTS is established. Formation energy calculations shows that Na can be significantly incorporated as both substitutional defects and interstitial defects, and incorporation of K related defects are generally less favorable. Transition energy calculations is performed showing that both Na and K exhibit benign defect properties and act as a p-type dopant. The qualitative disagreement between GGA with rigid band edge shifting and HSE calculations, formation of defect complexes, and implications in experiment will also be discussed. The understandings on the defect properties of Na and K provides an essential knowledge to further understand the surfactant effects of Na and K observed in experiments. This work is supported by General Research Fund Ref. No: 14319416.

[Theoretical evaluation of the risk of decompression illness during simulated extravehicular activity].

PubMed

Nikolaev, V P

2008-01-01

Theoretical analysis of the risk of decompression illness (DI) during extravehicular activity following the Russian and NASA decompression protocols (D-R and D-US, respectively) was performed. In contrast to the tradition approach to decompression stress evaluation by the factor of tissue supersaturation with nitrogen, our probabilistic theory of decompression safety provides a completely reasoned evaluation and comparison of the levels of hazard of these decompression protocols. According to this theory, the function of cumulative DI risk is equal to the sum of functions of cumulative risk of lesion of all body tissues by gas bubbles and their supersaturation by solute gases. Based on modeling of dynamics of these functions, growth of the DI cumulative risk in the course of D-R and D-US follows essentially similar trajectories within the time-frame of up to 330 minutes. However, further extension of D-US but not D-R raises the risk of DI drastically.

Role of Ser-257 in the sliding mechanism of NADP(H) in the reaction catalyzed by the Aspergillus fumigatus flavin-dependent ornithine N5-monooxygenase SidA.

PubMed

Shirey, Carolyn; Badieyan, Somayesadat; Sobrado, Pablo

2013-11-08

SidA (siderophore A) is a flavin-dependent N-hydroxylating monooxygenase that is essential for virulence in Aspergillus fumigatus. SidA catalyzes the NADPH- and oxygen-dependent formation of N(5)-hydroxyornithine. In this reaction, NADPH reduces the flavin, and the resulting NADP(+) is the last product to be released. The presence of NADP(+) is essential for activity, as it is required for stabilization of the C4a-hydroperoxyflavin, which is the hydroxylating species. As part of our efforts to determine the molecular details of the role of NADP(H) in catalysis, we targeted Ser-257 for site-directed mutagenesis and performed extensive characterization of the S257A enzyme. Using a combination of steady-state and stopped-flow kinetic experiments, substrate analogs, and primary kinetic isotope effects, we show that the interaction between Ser-257 and NADP(H) is essential for stabilization of the C4a-hydroperoxyflavin. Molecular dynamics simulation results suggest that Ser-257 functions as a pivot point, allowing the nicotinamide of NADP(+) to slide into position for stabilization of the C4a-hydroperoxyflavin.

An enhanced genome-scale metabolic reconstruction of Streptomyces clavuligerus identifies novel strain improvement strategies.

PubMed

Toro, León; Pinilla, Laura; Avignone-Rossa, Claudio; Ríos-Estepa, Rigoberto

2018-05-01

In this work, we expanded and updated a genome-scale metabolic model of Streptomyces clavuligerus. The model includes 1021 genes and 1494 biochemical reactions; genome-reaction information was curated and new features related to clavam metabolism and to the biomass synthesis equation were incorporated. The model was validated using experimental data from the literature and simulations were performed to predict cellular growth and clavulanic acid biosynthesis. Flux balance analysis (FBA) showed that limiting concentrations of phosphate and an excess of ammonia accumulation are unfavorable for growth and clavulanic acid biosynthesis. The evaluation of different objective functions for FBA showed that maximization of ATP yields the best predictions for cellular behavior in continuous cultures, while the maximization of growth rate provides better predictions for batch cultures. Through gene essentiality analysis, 130 essential genes were found using a limited in silico media, while 100 essential genes were identified in amino acid-supplemented media. Finally, a strain design was carried out to identify candidate genes to be overexpressed or knocked out so as to maximize antibiotic biosynthesis. Interestingly, potential metabolic engineering targets, identified in this study, have not been tested experimentally.

Evolution of the Max and Mlx networks in animals.

PubMed

McFerrin, Lisa G; Atchley, William R

2011-01-01

Transcription factors (TFs) are essential for the regulation of gene expression and often form emergent complexes to perform vital roles in cellular processes. In this paper, we focus on the parallel Max and Mlx networks of TFs because of their critical involvement in cell cycle regulation, proliferation, growth, metabolism, and apoptosis. A basic-helix-loop-helix-zipper (bHLHZ) domain mediates the competitive protein dimerization and DNA binding among Max and Mlx network members to form a complex system of cell regulation. To understand the importance of these network interactions, we identified the bHLHZ domain of Max and Mlx network proteins across the animal kingdom and carried out several multivariate statistical analyses. The presence and conservation of Max and Mlx network proteins in animal lineages stemming from the divergence of Metazoa indicate that these networks have ancient and essential functions. Phylogenetic analysis of the bHLHZ domain identified clear relationships among protein families with distinct points of radiation and divergence. Multivariate discriminant analysis further isolated specific amino acid changes within the bHLHZ domain that classify proteins, families, and network configurations. These analyses on Max and Mlx network members provide a model for characterizing the evolution of TFs involved in essential networks.

Two-Step Functional Innovation of the Stem-Cell Factors WUS/WOX5 during Plant Evolution

PubMed Central

Zhang, Yuzhou; Jiao, Yue; Jiao, Hengwu

2017-01-01

WUS and WOX5, which are expressed, respectively, in the organizing center (OC) and the quiescent center (QC), are essential for shoot/root apical stem-cell maintenance in flowering plants. However, little is known about how these stem-cell factors evolved their functions in flowering plants. Here, we show that the WUS/WOX5 proteins acquired two distinct capabilities by a two-step functional innovation process in the course of plant evolution. The first-step is the apical stem-cell maintenance activity of WUS/WOX5, which originated in the common ancestor of ferns and seed plants, as evidenced by the interspecies complementation experiments, showing that ectopic expression of fern Ceratopteris richardii WUS-like (CrWUL) surrounding OC/QC, or exclusive OC-/QC-expressed gymnosperms/angiosperms WUS/WOX5 in Arabidopsis wus-1 and wox5-1 mutants, could rescue their phenotypes. The second-step is the intercellular mobility that emerged in the common ancestor of seed plants after divergence from the ferns. Evidence for this includes confocal imaging of GFP fusion proteins, showing that WUS/WOX5 from seed plants, rather than from the fern CrWUL, can migrate into cells adjacent to the OC/QC. Evolutionary analysis showed that the WUS-like gene was duplicated into two copies prior to the divergence of gymnosperms/angiosperms. Then the two gene copies (WUS and WOX5) have undergone similar levels of purifying selection, which is consistent with their conserved functions in angiosperm shoot/root stem-cell maintenance and floral organ formation. Our results highlight the critical roles and the essential prerequisites that the two-step functional innovation of these genes performs and represents in the origin of flowering plants. PMID:28053005

Extracorporeal Bioartificial Liver for Treating Acute Liver Diseases

PubMed Central

Kumar, Ashok; Tripathi, Anuj; Jain, Shivali

2011-01-01

Abstract: Liver is a vital organ of the human body performing myriad of essential functions. Liver-related ailments are often life-threatening and dramatically deteriorate the quality of life of patients. Management of acute liver diseases requires adequate support of various hepatic functions. Thus far, liver transplantation has been proven as the only effective solution for acute liver diseases. However, broader application of liver transplantation is limited by demand for lifelong immunosuppression, shortage of organ donors, relative high morbidity, and high cost. Therefore, research has been focused on attempting to develop alternative support systems to treat liver diseases. Earlier attempts have been made to use nonbiological therapies based on the use of conventional detoxification procedures such as filtration and dialysis. However, the absence of liver cells in such techniques reduced the overall survival rate of the patients and led to inadequate essential liver-specific functions. As a result, there has been growing interest in the development of biological therapy-based extracorporeal liver support systems as a bridge to liver transplantation or to support the ailing liver. A bioartificial liver support is an extracorporeal device through which plasma is circulated over living and functionally active hepatocytes packed in a bioreactor with the aim to aid the diseased liver until it regenerates or until a suitable graft for transplantation is available. This review article gives a brief overview of efficacy of various liver support systems that are currently available. Also, the development of advanced liver support systems, which has been analyzed for improving the important system component such as cell source and other culture and circulation conditions for the maintenance of the liver-specific functions, have been described. PMID:22416599

Identification and Functional Analysis of Healing Regulators in Drosophila

PubMed Central

Álvarez-Fernández, Carmen; Tamirisa, Srividya; Prada, Federico; Chernomoretz, Ariel; Podhajcer, Osvaldo; Blanco, Enrique; Martín-Blanco, Enrique

2015-01-01

Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process. However, they do allow the less understood aspects of the healing response to be explored, e.g., which signal(s) are responsible for initiating tissue remodeling? How is sealing of the epithelia achieved? Or, what inhibitory cues cancel the healing machinery upon completion? Answering these and other questions first requires the identification and functional analysis of wound specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method that is healing-permissive and that allows live imaging and biochemical analysis of cultured imaginal discs. We performed comparative genome-wide profiling between Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. Sets of potential wound-specific genes were subsequently identified. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in healing assays. This non-saturated analysis defines a relevant set of genes whose changes in expression level are functionally significant for proper tissue repair. Amongst these we identified the TCP1 chaperonin complex as a key regulator of the actin cytoskeleton essential for the wound healing response. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound healing response. PMID:25647511

Functional complementation of yeast cytosolic pyrophosphatase by bacterial and plant H+-translocating pyrophosphatases.

PubMed

Perez-Castineira, Jose R; Lopez-Marques, Rosa L; Villalba, Jose M; Losada, Manuel; Serrano, Aurelio

2002-12-10

Two types of proteins that hydrolyze inorganic pyrophosphate (PPi), very different in both amino acid sequence and structure, have been characterized to date: soluble and membrane-bound proton-pumping pyrophosphatases (sPPases and H(+)-PPases, respectively). sPPases are ubiquitous proteins that hydrolyze PPi releasing heat, whereas H+-PPases, so far unidentified in animal and fungal cells, couple the energy of PPi hydrolysis to proton movement across biological membranes. The budding yeast Saccharomyces cerevisiae has two sPPases that are located in the cytosol and in the mitochondria. Previous attempts to knock out the gene coding for a cytosolic sPPase (IPP1) have been unsuccessful, thus suggesting that this protein is essential for growth. Here, we describe the generation of a conditional S. cerevisiae mutant (named YPC-1) whose functional IPP1 gene is under the control of a galactose-dependent promoter. Thus, YPC-1 cells become growth arrested in glucose but they regain the ability to grow on this carbon source when transformed with autonomous plasmids bearing diverse foreign H+-PPase genes under the control of a yeast constitutive promoter. The heterologously expressed H+-PPases are distributed among different yeast membranes, including the plasma membrane, functional complementation by these integral membrane proteins being consistently sensitive to external pH. These results demonstrate that hydrolysis of cytosolic PPi is essential for yeast growth and that this function is not substantially affected by the intrinsic characteristics of the PPase protein that accomplishes it. Moreover, this is, to our knowledge, the first direct evidence that H+-PPases can mediate net hydrolysis of PPi in vivo. YPC-1 mutant strain constitutes a convenient expression system to perform studies aimed at the elucidation of the structure-function relationships of this type of proton pumps.

Analysis of essential gene dynamics under antibiotic stress in Streptococcus sanguinis

PubMed Central

El-Rami, Fadi; Kong, Xiangzhen; Parikh, Hardik; Zhu, Bin; Stone, Victoria; Kitten, Todd; Xu, Ping

2018-01-01

The paradoxical response of Streptococcus sanguinis to drugs prescribed for dental and clinical practices has complicated treatment guidelines and raised the need for further investigation. We conducted a high throughput study on concomitant transcriptome and proteome dynamics in a time course to assess S. sanguinis behaviour under a sub-inhibitory concentration of ampicillin. Temporal changes at the transcriptome and proteome level were monitored to cover essential genes and proteins over a physiological map of intricate pathways. Our findings revealed that translation was the functional category in S. sanguinis that was most enriched in essential proteins. Moreover, essential proteins in this category demonstrated the greatest conservation across 2774 bacterial proteomes, in comparison to other essential functional categories like cell wall biosynthesis and energy production. In comparison to non-essential proteins, essential proteins were less likely to contain ‘degradation-prone’ amino acids at their N-terminal position, suggesting a longer half-life. Despite the ampicillin-induced stress, the transcriptional up-regulation of amino acid-tRNA synthetases and proteomic elevation of amino acid biosynthesis enzymes favoured the enriched components of essential proteins revealing ‘proteomic signatures’ that can be used to bridge the genotype–phenotype gap of S. sanguinis under ampicillin stress. Furthermore, we identified a significant correlation between the levels of mRNA and protein for essential genes and detected essential protein-enriched pathways differentially regulated through a persistent stress response pattern at late time points. We propose that the current findings will help characterize a bacterial model to study the dynamics of essential genes and proteins under clinically relevant stress conditions. PMID:29393020

Application of Game Theory Approaches in Routing Protocols for Wireless Networks

NASA Astrophysics Data System (ADS)

Javidi, Mohammad M.; Aliahmadipour, Laya

2011-09-01

An important and essential issue for wireless networks is routing protocol design that is a major technical challenge due to the function of the network. Game theory is a powerful mathematical tool that analyzes the strategic interactions among multiple decision makers and the results of researches show that applied game theory in routing protocol lead to improvement the network performance through reduce overhead and motivates selfish nodes to collaborate in the network. This paper presents a review and comparison for typical representatives of routing protocols designed that applied game theory approaches for various wireless networks such as ad hoc networks, mobile ad hoc networks and sensor networks that all of them lead to improve the network performance.

In vitro and in vivo assessment of the effect of Laurus novocanariensis oil and essential oil in human skin.

PubMed

Viciolle, E; Castilho, P; Rosado, C

2012-12-01

Laurus novocanariensis is an endemic plant from the Madeira Island forest that derives a fatty oil, with a strong spicy odour, from its berries that has been used for centuries in traditional medicine to treat skin ailments. This work aimed to investigate the effect of the application of both the oil and its essential oil on normal skin, to assess their safety and potential benefits. Diffusion studies with Franz cells using human epidermal membranes were conducted. The steady-state fluxes of two model molecules through untreated skin were compared with those obtained after a 2-h pre-treatment with either the oil or the essential oil. Additionally, eleven volunteers participated in the in vivo study that was conducted on the forearm and involved daily application of the oil for 5 days. Measurements were performed every day in the treated site with bioengineering methods that measure erythema, irritation and loss of barrier function. Slightly higher steady-state fluxes were observed for both the lipophilic and the hydrophilic molecule when the epidermal membranes were pre-treated. Nevertheless, such differences had no statistical significance, which seems to confirm that neither the oil nor the essential oil impaired the epidermal barrier. Results collected with the Chromameter, the Laser Doppler Flowmeter and the visual scoring are in agreement with those established in the in vitro study. They indicate that the repeated application of the oil did not cause erythema, because the results observed in the first day of the study were maintained throughout the week. Application of the oil did not affect the skin barrier function, because the transepidermal water loss remained constant throughout the study. The stratum corneum hydration was slightly reduced on days 4 and 5. This work shows that both the oil and the essential oil were well tolerated by the skin and did not cause significant barrier impairment or irritation. © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Performance-based tests versus behavioral ratings in the assessment of executive functioning in preschoolers: associations with ADHD symptoms and reading achievement.

PubMed

Miranda, Ana; Colomer, Carla; Mercader, Jessica; Fernández, M Inmaculada; Presentación, M Jesús

2015-01-01

The early assessment of the executive processes using ecologically valid instruments is essential for identifying deficits and planning actions to deal with possible adverse consequences. The present study has two different objectives. The first objective is to analyze the relationship between preschoolers' performance on tests of Working Memory and Inhibition and parents' and teachers' ratings of these executive functions (EFs) using the Behavior Rating Inventory of Executive Function (BRIEF). The second objective consists of studying the predictive value of the different EF measures (performance-based test and rating scales) on Inattention and Hyperactivity/Impulsivity behaviors and on indicators of word reading performance. The participants in the study were 209 children in the last year of preschool, their teachers and their families. Performance-based tests of Working Memory and Inhibition were administered, as well as word reading measures (accuracy and speed). The parents and teachers filled out rating scales of the EF and typical behaviors of attention deficit hyperactivity disorder (ADHD) symptomatology. Moderate correlation values were found between the different EF assessments procedures, although the results varied depending on the different domains. Metacognition Index from the BRIEF presented stronger correlations with verbal working memory tests than with inhibition tests. Both the rating scales and the performance-based tests were significant predictors of Inattention and Hyperactivity/Impulsivity behaviors and the reading achievement measures. However, the BRIEF explained a greater percentage of variance in the case of the ADHD symptomatology, while the performance-based tests explained reading achievement to a greater degree. The implications of the findings for research and clinical practice are discussed.

Implementation of hospital governing boards: views from the field.

PubMed

McNatt, Zahirah; Thompson, Jennifer W; Mengistu, Abraham; Tatek, Dawit; Linnander, Erika; Ageze, Leulseged; Lawson, Ruth; Berhanu, Negalign; Bradley, Elizabeth H

2014-04-17

Decentralization through the establishment of hospital governing boards has been touted as an effective way to improve the quality and efficiency of hospitals in low-income countries. Although several studies have examined the process of decentralization, few have quantitatively assessed the implementation of hospital governing boards and their impact on hospital performance. Therefore, we sought to describe the functioning of governing boards and to determine the association between governing board functioning and hospital performance. We conducted a cross-sectional study with governing board chairpersons to assess board (1) structure, (2) roles and responsibilities and (3) training and orientation practices. Using bivariate analysis and multivariable regression, we examined the association between governing board functioning and hospital performance. Hospital performance indicators: 1) percent of hospital management standards met, measured with the Ethiopian Hospital Reform Implementation Guidelines and 2) patient experience, measured with the Inpatient and Outpatient Assessment of Healthcare surveys. A total of 92 boards responded to the survey (96% response rate). The average percentage of EHRIG standards met was 58.1% (standard deviation (SD) 21.7 percentage points), and the mean overall patient experience score was 7.2 (SD 2.2). Hospitals with greater hospital management standards met had governing boards that paid members, reviewed performance in several domains quarterly or more frequently, developed new revenue sources, determined services to be outsourced, reviewed patient complaints, and had members with knowledge in business and financial management (all P-values < 0.05). Hospitals with more positive patient experience had governing boards that developed new revenue sources, determined services to be outsourced, and reviewed patient complaints (all P-values < 0.05). These cross-sectional data suggest that strengthening governing boards to perform essential responsibilities may result in improved hospital performance.

Memory and multitasking performance during acute allergic inflammation in seasonal allergic rhinitis.

PubMed

Trikojat, K; Buske-Kirschbaum, A; Plessow, F; Schmitt, J; Fischer, R

2017-04-01

In previous research, patients with seasonal allergic rhinitis (SAR) showed poorer school and work performance during periods of acute allergic inflammation, supporting the idea of an impact of SAR on cognitive functions. However, the specific cognitive domains particularly vulnerable to inflammatory processes are unclear. In this study, the influence of SAR on memory and multitasking performance, as two potentially vulnerable cognitive domains essential in everyday life functioning, was investigated in patients with SAR. Non-medicated patients with SAR (n = 41) and healthy non-allergic controls (n = 42) performed a dual-task paradigm and a verbal learning and memory test during and out of symptomatic allergy periods (pollen vs. non-pollen season). Disease-related factors (e.g. symptom severity, duration of symptoms, duration of disease) and allergy-related quality of life were evaluated as potential influences of cognitive performance. During the symptomatic allergy period, patients showed (1) poorer performance in word list-based learning (P = 0.028) and (2) a general slowing in processing speed (P < 0.001) and a shift in processing strategy (P < 0.001) in multitasking. Yet, typical parameters indicating specific multitasking costs were not affected. A significant negative association was found between learning performance and duration of disease (r = -0.451, P = 0.004), whereas symptom severity (r = 0.326; P = 0.037) and quality of life (r = 0.379; P = 0.015) were positively associated with multitasking strategy. Our findings suggest that SAR has a differentiated and complex impact on cognitive functions, which should be considered in the management of SAR symptoms. They also call attention to the importance of selecting sensitive measures and carefully interpreting cognitive outcomes. © 2017 John Wiley & Sons Ltd.

Performance-based tests versus behavioral ratings in the assessment of executive functioning in preschoolers: associations with ADHD symptoms and reading achievement

PubMed Central

Miranda, Ana; Colomer, Carla; Mercader, Jessica; Fernández, M. Inmaculada; Presentación, M. Jesús

2015-01-01

The early assessment of the executive processes using ecologically valid instruments is essential for identifying deficits and planning actions to deal with possible adverse consequences. The present study has two different objectives. The first objective is to analyze the relationship between preschoolers’ performance on tests of Working Memory and Inhibition and parents’ and teachers’ ratings of these executive functions (EFs) using the Behavior Rating Inventory of Executive Function (BRIEF). The second objective consists of studying the predictive value of the different EF measures (performance-based test and rating scales) on Inattention and Hyperactivity/Impulsivity behaviors and on indicators of word reading performance. The participants in the study were 209 children in the last year of preschool, their teachers and their families. Performance-based tests of Working Memory and Inhibition were administered, as well as word reading measures (accuracy and speed). The parents and teachers filled out rating scales of the EF and typical behaviors of attention deficit hyperactivity disorder (ADHD) symptomatology. Moderate correlation values were found between the different EF assessments procedures, although the results varied depending on the different domains. Metacognition Index from the BRIEF presented stronger correlations with verbal working memory tests than with inhibition tests. Both the rating scales and the performance-based tests were significant predictors of Inattention and Hyperactivity/Impulsivity behaviors and the reading achievement measures. However, the BRIEF explained a greater percentage of variance in the case of the ADHD symptomatology, while the performance-based tests explained reading achievement to a greater degree. The implications of the findings for research and clinical practice are discussed. PMID:25972833

Integrating the Functions of Institutional Research, Institutional Effectiveness, and Information Management. Professional File. Number 126, Summer 2012

ERIC Educational Resources Information Center

Posey, James T.; Pitter, Gita Wijesinghe

2012-01-01

The objective of this paper is to identify common essential information and data needs of colleges and universities and to suggest a model to integrate these data needs into one office or department. The paper suggests there are five major data and information foundations that are essential to the effective functioning of an institution: (a)…

Insecticidal Activity of Melaleuca alternifolia Essential Oil and RNA-Seq Analysis of Sitophilus zeamais Transcriptome in Response to Oil Fumigation

PubMed Central

Liao, Min; Xiao, Jin-Jing; Zhou, Li-Jun; Liu, Yang; Wu, Xiang-Wei; Hua, Ri-Mao; Wang, Gui-Rong; Cao, Hai-Qun

2016-01-01

Background The cereal weevil, Sitophilus zeamais is one of the most destructive pests of stored cereals worldwide. Frequent use of fumigants for managing stored-product insects has led to the development of resistance in insects. Essential oils from aromatic plants including the tea oil plant, Melaleuca alternifolia may provide environmentally friendly alternatives to currently used pest control agents. However, little is known about molecular events involved in stored-product insects in response to plant essential oil fumigation. Results M. alternifolia essential oil was shown to possess the fumigant toxicity against S. zeamais. The constituent, terpinen-4-ol was the most effective compound for fumigant toxicity. M. alternifolia essential oil significantly inhibited the activity of three enzymes in S. zeamais, including two detoxifying enzymes, glutathione S-transferase (GST), and carboxylesterase (CarE), as well as a nerve conduction enzyme, acetylcholinesterase (AChE). Comparative transcriptome analysis of S. zeamais through RNA-Seq identified a total of 3,562 differentially expressed genes (DEGs), of which 2,836 and 726 were up-regulated and down-regulated in response to M. alternifolia essential oil fumigation, respectively. Based on gene ontology (GO) analysis, the majority of DEGs were involved in insecticide detoxification and mitochondrial function. Furthermore, an abundance of DEGs mapped into the metabolism pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database were associated with respiration and metabolism of xenobiotics, including cytochrome P450s, CarEs, GSTs, and ATP-binding cassette transporters (ABC transporters). Some DEGs mapped into the proteasome and phagosome pathway were found to be significantly enriched. These results led us to propose a model of insecticide action that M. alternifolia essential oil likely directly affects the hydrogen carrier to block the electron flow and interfere energy synthesis in mitochondrial respiratory chain. Conclusion This is the first study to perform a comparative transcriptome analysis of S. zeamais in response to M. alternifolia essential oil fumigation. Our results provide new insights into the insecticidal mechanism of M. alternifolia essential oil fumigation against S. zeamais and eventually contribute to the management of this important agricultural pest. PMID:27936192

Insecticidal Activity of Melaleuca alternifolia Essential Oil and RNA-Seq Analysis of Sitophilus zeamais Transcriptome in Response to Oil Fumigation.

PubMed

Liao, Min; Xiao, Jin-Jing; Zhou, Li-Jun; Liu, Yang; Wu, Xiang-Wei; Hua, Ri-Mao; Wang, Gui-Rong; Cao, Hai-Qun

2016-01-01

The cereal weevil, Sitophilus zeamais is one of the most destructive pests of stored cereals worldwide. Frequent use of fumigants for managing stored-product insects has led to the development of resistance in insects. Essential oils from aromatic plants including the tea oil plant, Melaleuca alternifolia may provide environmentally friendly alternatives to currently used pest control agents. However, little is known about molecular events involved in stored-product insects in response to plant essential oil fumigation. M. alternifolia essential oil was shown to possess the fumigant toxicity against S. zeamais. The constituent, terpinen-4-ol was the most effective compound for fumigant toxicity. M. alternifolia essential oil significantly inhibited the activity of three enzymes in S. zeamais, including two detoxifying enzymes, glutathione S-transferase (GST), and carboxylesterase (CarE), as well as a nerve conduction enzyme, acetylcholinesterase (AChE). Comparative transcriptome analysis of S. zeamais through RNA-Seq identified a total of 3,562 differentially expressed genes (DEGs), of which 2,836 and 726 were up-regulated and down-regulated in response to M. alternifolia essential oil fumigation, respectively. Based on gene ontology (GO) analysis, the majority of DEGs were involved in insecticide detoxification and mitochondrial function. Furthermore, an abundance of DEGs mapped into the metabolism pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database were associated with respiration and metabolism of xenobiotics, including cytochrome P450s, CarEs, GSTs, and ATP-binding cassette transporters (ABC transporters). Some DEGs mapped into the proteasome and phagosome pathway were found to be significantly enriched. These results led us to propose a model of insecticide action that M. alternifolia essential oil likely directly affects the hydrogen carrier to block the electron flow and interfere energy synthesis in mitochondrial respiratory chain. This is the first study to perform a comparative transcriptome analysis of S. zeamais in response to M. alternifolia essential oil fumigation. Our results provide new insights into the insecticidal mechanism of M. alternifolia essential oil fumigation against S. zeamais and eventually contribute to the management of this important agricultural pest.

Interactions between late acting proteins required for peptidoglycan synthesis during sporulation

PubMed Central

Fay, Allison; Meyer, Pablo; Dworkin, Jonathan

2010-01-01

The requirement of peptidoglycan synthesis for growth complicates the analysis of interactions between proteins involved in this pathway. In particular, the later steps that involve membrane-linked substrates have proven largely recalcitrant to in vivo analysis. Here we have taken advantage of the peptidoglycan synthesis that occurs during sporulation in Bacillus subtilis to examine the interactions between SpoVE, a non-essential, sporulation-specific homolog of the well-conserved and essential SEDS proteins, and SpoVD, a non-essential class B penicillin binding protein (PBP). We found that localization of SpoVD is dependent on SpoVE and that SpoVD protects SpoVE from in vivo proteolysis. Co-immunoprecipitations and Fluorescence Resonance Energy Transfer experiments indicated that SpoVE and SpoVD interact and co-affinity purification in E. coli demonstrated that this interaction is direct. Finally, we generated a functional protein consisting of a SpoVE-SpoVD fusion and found that a loss-of-function point mutation in either part of the fusion resulted in a loss of function of the entire fusion that was not complemented by a wild type protein. Thus, SpoVE has a direct and functional interaction with SpoVD and this conclusion will facilitate understanding the essential function SpoVE and related SEDS proteins such as FtsW and RodA play in bacterial growth and division. PMID:20417640

On the Singularity Structure of WKB Solution of the Boosted Whittaker Equation: its Relevance to Resurgent Functions with Essential Singularities

NASA Astrophysics Data System (ADS)

Kamimoto, Shingo; Kawai, Takahiro; Koike, Tatsuya

2016-12-01

Inspired by the symbol calculus of linear differential operators of infinite order applied to the Borel transformed WKB solutions of simple-pole type equation [Kamimoto et al. (RIMS Kôkyûroku Bessatsu B 52:127-146, 2014)], which is summarized in Section 1, we introduce in Section 2 the space of simple resurgent functions depending on a parameter with an infra-exponential type growth order, and then we define the assigning operator A which acts on the space and produces resurgent functions with essential singularities. In Section 3, we apply the operator A to the Borel transforms of the Voros coefficient and its exponentiation for the Whittaker equation with a large parameter so that we may find the Borel transforms of the Voros coefficient and its exponentiation for the boosted Whittaker equation with a large parameter. In Section 4, we use these results to find the explicit form of the alien derivatives of the Borel transformed WKB solutions of the boosted Whittaker equation with a large parameter. The results in this paper manifest the importance of resurgent functions with essential singularities in developing the exact WKB analysis, the WKB analysis based on the resurgent function theory. It is also worth emphasizing that the concrete form of essential singularities we encounter is expressed by the linear differential operators of infinite order.

Functional domains of the human splicing factor ASF/SF2.

PubMed Central

Zuo, P; Manley, J L

1993-01-01

The human splicing factor ASF/SF2 displays two predominant activities in in vitro splicing assays: (i) it is an essential factor apparently required for all splices and (ii) it is able to switch utilization of alternative 5' splice sites in a concentration-dependent manner. ASF/SF2 is the prototype of a family of proteins typified by the presence of one or two RNP-type RNA binding domains (RBDs) and a region highly enriched in repeating arginine-serine dipeptides (RS regions). Here we describe a functional analysis of ASF/SF2, which defines several regions essential for one, or both, of its two principal activities, and provides insights into how this type of protein functions in splicing. Two isoforms of the protein, which arise from alternative splicing, are by themselves inactive, but each can block the activity of ASF/SF2, thereby functioning as splicing repressors. Some, but not all, mutations in the RS region prevent ASF/SF2 from functioning as an essential splicing factor. However, the entire RS region can be deleted without reducing splice site switching activity, indicating that it is not absolutely required for interaction with other splicing factors. Experiments with deletion and substitution mutants reveal that the protein contains two related, but highly diverged, RBDs, and that both are essential for activity. Each RBD by itself retains the ability to bind RNA, although optimal binding requires both domains. Images PMID:8223481

NAD Kinases: Metabolic Targets Controlling Redox Co-enzymes and Reducing Power Partitioning in Plant Stress and Development

PubMed Central

Li, Bin-Bin; Wang, Xiang; Tai, Li; Ma, Tian-Tian; Shalmani, Abdullah; Liu, Wen-Ting; Li, Wen-Qiang; Chen, Kun-Ming

2018-01-01

NAD(H) and NADP(H) are essential co-enzymes which dominantly control a number of fundamental biological processes by acting as reducing power and maintaining the intracellular redox balance of all life kingdoms. As the only enzymes that catalyze NAD(H) and ATP to synthesize NADP(H), NAD Kinases (NADKs) participate in many essential metabolic reactions, redox sensitive regulation, photosynthetic performance and also reactive oxygen species (ROS) homeostasis of cells and therefore, play crucial roles in both development and stress responses of plants. NADKs are highly conserved enzymes in amino acid sequences but have multiple subcellular localization and diverse functions. They may function as monomers, dimers or multimers in cells but the enzymatic properties in plants are not well elucidated yet. The activity of plant NADK is regulated by calcium/calmodulin and plays crucial roles in photosynthesis and redox co-enzyme control. NADK genes are expressed in almost all tissues and developmental stages of plants with specificity for different members. Their transcripts can be greatly stimulated by a number of environmental factors such as pathogenic attack, irritant applications and abiotic stress treatments. Using transgenic approaches, several studies have shown that NADKs are involved in chlorophyll synthesis, photosynthetic efficiency, oxidative stress protection, hormone metabolism and signaling regulation, and therefore contribute to the growth regulation and stress tolerance of plants. In this review, the enzymatic properties and functional mechanisms of plant NADKs are thoroughly investigated based on literature and databases. The results obtained here are greatly advantageous for further exploration of NADK function in plants. PMID:29662499

Effects of Healthy Aging and Mild Cognitive Impairment on a Real-Life Decision-Making Task.

PubMed

Pertl, Marie-Theres; Benke, Thomas; Zamarian, Laura; Delazer, Margarete

2017-01-01

In this study, we investigated the effects of age and of mild cognitive impairment (MCI) on decision making under risk by adopting a task representing real-life health-related situations and involving complex numerical information. Moreover, we assessed the relationship of real-life decision making to other cognitive functions such as number processing, executive functions, language, memory, and attention. For this reason, we compared the performance of 19 healthy, relatively younger adults with that of 18 healthy older adults and the performance of the 18 healthy older adults with that of 17 patients with MCI. Results indicated difficulties in real-life decision making for the healthy older adults compared with the healthy, relatively younger adults. Difficulties of patients with MCI relative to the healthy older adults arose in particular in difficult items requiring processing of frequencies and fractions. Significant effects of age and of MCI in processing frequencies were also evident in a ratio number comparison task. Decision-making performance of healthy participants and of the patient group correlated significantly with number processing. There was a further significant correlation with executive functions for the healthy participants and with reading comprehension for the patients. Our results suggest that healthy older individuals and patients with MCI make less advantageous decisions when the information is complex and high demands are put on executive functions and numerical abilities. Moreover, we show that executive functions and numerical abilities are not only essential in laboratory gambling tasks but also in more realistic and ecological decision situations within the health context.

Native kidney function following liver transplantation using calcineurin inhibitors: single-center analysis with 20 years of follow-up.

PubMed

LaMattina, John C; Mezrich, Joshua D; Fernandez, Luis A; D'Alessandro, Anthony M; Djamali, Arjang; Musat, Alexandru I; Pirsch, John D; Foley, David P

2013-01-01

The incidence of chronic kidney disease (CKD) in liver transplant recipients has been estimated to be from 18% to 28% at 10 yr after transplantation. As outcomes from liver transplantation continue to improve, long-term native kidney function in these recipients becomes more critical to patient survival. We analyzed 1151 adult, deceased-donor, single-organ primary liver transplantations performed at our center between 7/17/84 and 12/31/07. Analysis of renal function was performed on 972 patients with liver allograft survival >1 yr. Kaplan-Meier analysis revealed that 3%, 7%, and 18% of liver transplant recipients with allograft survival >1 yr developed end-stage renal disease (ESRD) at five, 10, and 20 yr, respectively. Significant independent risk factors for ESRD included dialysis during the transplant hospitalization, the stage of CKD at one yr, hypercholesterolemia, non-Caucasian race, and hepatitis C as the primary indication for liver transplantation. The initial immunosuppression of essentially all recipients was a calcineurin inhibitor-based regimen. Close, long-term follow-up of liver transplant recipients permits optimal management of liver allograft and native renal function and can lead to excellent long-term outcomes despite a calcineurin inhibitor-based immunosuppressive regimen. © 2013 John Wiley & Sons A/S.

Risk Modeling of Interdependent Complex Systems of Systems: Theory and Practice.

PubMed

Haimes, Yacov Y

2018-01-01

The emergence of the complexity characterizing our systems of systems (SoS) requires a reevaluation of the way we model, assess, manage, communicate, and analyze the risk thereto. Current models for risk analysis of emergent complex SoS are insufficient because too often they rely on the same risk functions and models used for single systems. These models commonly fail to incorporate the complexity derived from the networks of interdependencies and interconnectedness (I-I) characterizing SoS. There is a need to reevaluate currently practiced risk analysis to respond to this reality by examining, and thus comprehending, what makes emergent SoS complex. The key to evaluating the risk to SoS lies in understanding the genesis of characterizing I-I of systems manifested through shared states and other essential entities within and among the systems that constitute SoS. The term "essential entities" includes shared decisions, resources, functions, policies, decisionmakers, stakeholders, organizational setups, and others. This undertaking can be accomplished by building on state-space theory, which is fundamental to systems engineering and process control. This article presents a theoretical and analytical framework for modeling the risk to SoS with two case studies performed with the MITRE Corporation and demonstrates the pivotal contributions made by shared states and other essential entities to modeling and analysis of the risk to complex SoS. A third case study highlights the multifarious representations of SoS, which require harmonizing the risk analysis process currently applied to single systems when applied to complex SoS. © 2017 Society for Risk Analysis.

Intrinsic disorder mediates the diverse regulatory functions of the Cdk inhibitor p21

PubMed Central

Wang, Yuefeng; Fisher, John C.; Mathew, Rose; Ou, Li; Otieno, Steve; Sublett, Jack; Xiao, Limin; Chen, Jianhan; Roussel, Martine F.; Kriwacki, Richard W.

2011-01-01

Traditionally, well-defined three-dimensional structure was thought to be essential for protein function. However, myriad biological functions are performed by highly dynamic, intrinsically disordered proteins (IDPs). IDPs often fold upon binding their biological targets and frequently exhibit “binding diversity” by targeting multiple ligands. We sought to understand the physical basis of IDP binding diversity and herein report that the cyclin-dependent kinase (Cdk) inhibitor, p21Cip1, adaptively binds to and inhibits the various Cdk/cyclin complexes that regulate eukaryotic cell division. Based on results from NMR spectroscopy, and biochemical and cellular assays, we show that structural adaptability of a helical sub-domain within p21 termed LH enables two other sub-domains termed D1 and D2 to specifically bind conserved surface features of the cyclin and Cdk subunits, respectively, within otherwise structurally distinct Cdk/cyclin complexes. Adaptive folding upon binding is likely to mediate the diverse biological functions of the thousands of IDPs present in eukaryotes. PMID:21358637

Evaluation and Design of Genome-Wide CRISPR/SpCas9 Knockout Screens

PubMed Central

Hart, Traver; Tong, Amy Hin Yan; Chan, Katie; Van Leeuwen, Jolanda; Seetharaman, Ashwin; Aregger, Michael; Chandrashekhar, Megha; Hustedt, Nicole; Seth, Sahil; Noonan, Avery; Habsid, Andrea; Sizova, Olga; Nedyalkova, Lyudmila; Climie, Ryan; Tworzyanski, Leanne; Lawson, Keith; Sartori, Maria Augusta; Alibeh, Sabriyeh; Tieu, David; Masud, Sanna; Mero, Patricia; Weiss, Alexander; Brown, Kevin R.; Usaj, Matej; Billmann, Maximilian; Rahman, Mahfuzur; Costanzo, Michael; Myers, Chad L.; Andrews, Brenda J.; Boone, Charles; Durocher, Daniel; Moffat, Jason

2017-01-01

The adaptation of CRISPR/SpCas9 technology to mammalian cell lines is transforming the study of human functional genomics. Pooled libraries of CRISPR guide RNAs (gRNAs) targeting human protein-coding genes and encoded in viral vectors have been used to systematically create gene knockouts in a variety of human cancer and immortalized cell lines, in an effort to identify whether these knockouts cause cellular fitness defects. Previous work has shown that CRISPR screens are more sensitive and specific than pooled-library shRNA screens in similar assays, but currently there exists significant variability across CRISPR library designs and experimental protocols. In this study, we reanalyze 17 genome-scale knockout screens in human cell lines from three research groups, using three different genome-scale gRNA libraries. Using the Bayesian Analysis of Gene Essentiality algorithm to identify essential genes, we refine and expand our previously defined set of human core essential genes from 360 to 684 genes. We use this expanded set of reference core essential genes, CEG2, plus empirical data from six CRISPR knockout screens to guide the design of a sequence-optimized gRNA library, the Toronto KnockOut version 3.0 (TKOv3) library. We then demonstrate the high effectiveness of the library relative to reference sets of essential and nonessential genes, as well as other screens using similar approaches. The optimized TKOv3 library, combined with the CEG2 reference set, provide an efficient, highly optimized platform for performing and assessing gene knockout screens in human cell lines. PMID:28655737

Charge requirements of lipid II flippase activity in Escherichia coli.

PubMed

Butler, Emily K; Tan, Wee Boon; Joseph, Hildy; Ruiz, Natividad

2014-12-01

Peptidoglycan (PG) is an extracytoplasmic glycopeptide matrix essential for the integrity of the envelope of most bacteria. The PG building block is a disaccharide-pentapeptide that is synthesized as a lipid-linked precursor called lipid II. The translocation of the amphipathic lipid II across the cytoplasmic membrane is required for subsequent incorporation of the disaccharide-pentapeptide into PG. In Escherichia coli, the essential inner membrane protein MurJ is the lipid II flippase. Previous studies showed that 8 charged residues in the central cavity region of MurJ are crucial for function. Here, we completed the functional analysis of all 57 charged residues in MurJ and demonstrated that the respective positive or negative charge of the 8 aforementioned residues is required for proper MurJ function. Loss of the negative charge in one of these residues, D39, causes a severe defect in MurJ biogenesis; by engineering an intragenic suppressor mutation that restores MurJ biogenesis, we found that this charge is also essential for MurJ function. Because of the low level of homology between MurJ and putative orthologs from Gram-positive bacteria, we explored the conservation of these 8 charged residues in YtgP, a homolog from Streptococcus pyogenes. We found that only 3 positive charges are similarly positioned and essential in YtgP; YtgP possesses additional charged residues within its predicted cavity that are essential for function and conserved among Gram-positive bacteria. From these data, we hypothesize that some charged residues in the cavity region of MurJ homologs are required for interaction with lipid II and/or energy coupling during transport. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Performance evaluation for pinhole collimators of small gamma camera by MTF and NNPS analysis: Monte Carlo simulation study

NASA Astrophysics Data System (ADS)

Jeon, Hosang; Kim, Hyunduk; Cha, Bo Kyung; Kim, Jong Yul; Cho, Gyuseong; Chung, Yong Hyun; Yun, Jong-Il

2009-06-01

Presently, the gamma camera system is widely used in various medical diagnostic, industrial and environmental fields. Hence, the quantitative and effective evaluation of its imaging performance is essential for design and quality assurance. The National Electrical Manufacturers Association (NEMA) standards for gamma camera evaluation are insufficient to perform sensitive evaluation. In this study, modulation transfer function (MTF) and normalized noise power spectrum (NNPS) will be suggested to evaluate the performance of small gamma camera with changeable pinhole collimators using Monte Carlo simulation. We simulated the system with a cylinder and a disk source, and seven different pinhole collimators from 1- to 4-mm-diameter pinhole with lead. The MTF and NNPS data were obtained from output images and were compared with full-width at half-maximum (FWHM), sensitivity and differential uniformity. In the result, we found that MTF and NNPS are effective and novel standards to evaluate imaging performance of gamma cameras instead of conventional NEMA standards.

Working memory network alterations in high-functioning adolescents with an autism spectrum disorder.

PubMed

Barendse, Evelien M; Schreuder, Lisanne J; Thoonen, Geert; Hendriks, Marc P H; Kessels, Roy P C; Backes, Walter H; Aldenkamp, Albert P; Jansen, Jacobus F A

2018-02-01

People with autism spectrum disorder (ASD) typically have deficits in the working memory (WM) system. WM is found to be an essential chain in successfully navigating in the social world. We hypothesize that brain networks for WM have an altered network integrity in ASD compared to controls. Thirteen adolescents (one female) with autistic disorder (n = 1), Asperger's disorder (n = 7), or pervasive developmental disorder not otherwise specified (n = 5), and 13 typically developing healthy control adolescents (one female) participated in this study. Functional magnetic resonance imaging (MRI) was performed using an n-back task and in resting state. The analysis of the behavioral data revealed deficits in WM performance in ASD, but only when tested to the limit. Adolescents with ASD showed lower binary global efficiency in the WM network than the healthy control group with n-back and resting-state data. This correlated with diagnostic scores for total problems, reciprocity, and language. Adolescents with higher-functioning autism have difficulty with the WM system, which is typically compensated. Functional MRI markers of brain network organization in ASD are related to characteristics of autism as represented in diagnostic scores. Therefore, functional MRI provides neuronal correlates for memory difficulties in adolescents with ASD. © 2017 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

Evidence against the selfish operon theory.

PubMed

Pál, Csaba; Hurst, Laurence D

2004-06-01

According to the selfish operon hypothesis, the clustering of genes and their subsequent organization into operons is beneficial for the constituent genes because it enables the horizontal gene transfer of weakly selected, functionally coupled genes. The majority of these are expected to be non-essential genes. From our analysis of the Escherichia coli genome, we conclude that the selfish operon hypothesis is unlikely to provide a general explanation for clustering nor can it account for the gene composition of operons. Contrary to expectations, essential genes with related functions have an especially strong tendency to cluster, even if they are not in operons. Moreover, essential genes are particularly abundant in operons.

Screening for Inhibitors of Essential Leishmania Glucose Transporters

DTIC Science & Technology

2012-07-01

Leishmania Glucose Transporters PRINCIPAL INVESTIGATOR: Scott M. Landfear, Ph.D. CONTRACTING ORGANIZATION: Oregon Health & Science...3. DATES COVERED 1 JUL 2011 - 30 JUN 2012 4. TITLE AND SUBTITLE Screening for Inhibitors of Essential Leishmania Glucose Transporters...function as selective inhibitors of the essential glucose transporters of the parasite Leishmania mexicana. To identify such compounds, a cell growth

77 FR 13206 - Protective Force Personnel Medical, Physical Readiness, Training, and Access Authorization Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-06

...The Department of Energy (DOE or Department) proposes to revise the regulation governing the standards for medical, physical performance, training, and access authorizations for protective force (PF) personnel employed by contractors providing security services to the Department. The existing version of this regulation was promulgated in 1993 and substantial portions of the regulation date to the mid- 1980s. Since 1993 DOE policy has placed greater reliance upon technology, vehicular response, and increased firepower and, correspondingly, has reduced its reliance upon the ability of PF personnel to perform the running tasks required in the current regulation. Furthermore, this shift in emphasis has placed a greater premium upon the retention of mature, tactically experienced, and technically sophisticated personnel, particularly since these personnel represent a considerable investment by DOE in security background investigations and training. The proposed revisions bring DOE PF medical and physical readiness requirements in line with these tactical and organizational priorities. The proposed revisions reduce the exposure of the PF population to injuries related to physical readiness testing. They would create a PF readiness classification designed specifically to encourage the retention of experienced personnel. The revisions would further ensure that PF personnel would be evaluated on a case-by-case basis on their ability to perform the essential functions of their positions without posing a direct threat to themselves or site personnel, the facility, or the general public. The proposed revisions would further ensure that reasonable accommodations would be considered before a determination is made that an individual cannot perform the essential functions of a particular position. The proposed rule also would provide for new medical review processes for PF personnel disqualified from medical certification. The proposed rule would ensure that DOE PF medical and physical readiness requirements would be compliant with the Americans with Disabilities Act (ADA) of 1990, as amended by the Americans with Disabilities Amendment Act of 2009 (ADAAA), the Privacy Act and DOE implementing regulations, and changes in DOE policy regarding PF operations made since the publication of the last version of this rule. In addition, the proposed rule would promote operational efficiency through greater emphasis on aligning training with mission-essential tasks and the increased use of simulation technologies. Finally, the proposed revision would update the regulation to reflect organizational changes in the Office of Health, Safety and Security and the creation of the National Nuclear Security Administration (NNSA).

Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

PubMed Central

Sun, Hongyu; Zhou, Jing; Huang, Zhu; Qu, Linlin; Lin, Ning; Liang, Chengxiao; Dai, Ruiwu; Tang, Lijun; Tian, Fuzhou

2017-01-01

Carbon nanotubes (CNTs) provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col) hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt%) exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future. PMID:28450785

Executive performance in older Portuguese adults with low education.

PubMed

Pavão Martins, Isabel; Maruta, Carolina; Freitas, Vanda; Mares, Inês

2013-01-01

Evaluation of executive functions is essential in clinical diagnosis, yet there are limited data regarding the performance of participants with low education. We present results on several measures of executive functions obtained in community-dwelling adults with an overall low education and study the effect of this variable in each test. A sample of 479 adults (64% female, mean age 66.4 years) was assessed by a battery comprising 13 measures of executive function (Trail Making Test; Symbol Search; Matrix reasoning; Semantic and phonemic verbal fluencies; Stroop test; and digit spans). Tests' psychometric properties and the effects of age, gender, and education were studied across education levels within each age group. Tests showed good psychometric properties. Education explained more variance than age in the majority of measures, with lower educational levels being significantly associated to worse scores. Tables are presented with mean scores, standard deviation, and the value of extreme percentiles for younger (50-65, N = 232) and older (>65 years, N = 247) × education (0-3, 4, 5-9, and >9 years) subgroups. Education-adjusted norms are necessary for an adequate interpretation of test results. The present data may be useful for clinicians caring for populations with low literacy.

A high throughput mutagenic analysis of yeast sumo structure and function

PubMed Central

Newman, Heather A.; Lu, Jian; Carson, Caryn; Boeke, Jef D.

2017-01-01

Sumoylation regulates a wide range of essential cellular functions through diverse mechanisms that remain to be fully understood. Using S. cerevisiae, a model organism with a single essential SUMO gene (SMT3), we developed a library of >250 mutant strains with single or multiple amino acid substitutions of surface or core residues in the Smt3 protein. By screening this library using plate-based assays, we have generated a comprehensive structure-function based map of Smt3, revealing essential amino acid residues and residues critical for function under a variety of genotoxic and proteotoxic stress conditions. Functionally important residues mapped to surfaces affecting Smt3 precursor processing and deconjugation from protein substrates, covalent conjugation to protein substrates, and non-covalent interactions with E3 ligases and downstream effector proteins containing SUMO-interacting motifs. Lysine residues potentially involved in formation of polymeric chains were also investigated, revealing critical roles for polymeric chains, but redundancy in specific chain linkages. Collectively, our findings provide important insights into the molecular basis of signaling through sumoylation. Moreover, the library of Smt3 mutants represents a valuable resource for further exploring the functions of sumoylation in cellular stress response and other SUMO-dependent pathways. PMID:28166236

The Prp19 WD40 Domain Contains a Conserved Protein Interaction Region Essential for its Function

PubMed Central

Vander Kooi, Craig W.; Ren, Liping; Xu, Ping; Ohi, Melanie D.; Gould, Kathleen L.; Chazin, Walter J.

2010-01-01

Summary Prp19 is a member of the WD40-repeat family of E3 ubiquitin ligases and a conserved eukaryotic RNA splicing factor essential for activation and stabilization of the spliceosome. To understand the role of the WD40 repeat domain of Prp19 we have determined its structure using X-ray crystallography. The domain has a distorted seven bladed WD40 architecture with significant asymmetry due to irregular packing of blades one and seven into the core of the WD40 domain. Structure-based mutagenesis identified a highly conserved surface centered around blade five that is required for the physical interaction between Prp19 and Cwc2, another essential splicing factor. This region is found to be required for Prp19 function and yeast viability. Experiments in vitro and in vivo demonstrate that two molecules of Cwc2 bind to the Prp19 tetramer. These coupled structural and functional studies provide a model for the functional architecture of Prp19. PMID:20462492

Effects of oregano essential oil with or without feed enzymes on growth performance, digestive enzyme, nutrient digestibility, lipid metabolism and immune response of broilers fed on wheat-soybean meal diets.

PubMed

Basmacioğlu Malayoğlu, H; Baysal, S; Misirlioğlu, Z; Polat, M; Yilmaz, H; Turan, N

2010-02-01

1. The study was conducted to determine the effects of dietary supplementation of enzyme and oregano essential oil at two levels, alone or together, on performance, digestive enzyme, nutrient digestibility, lipid metabolism and immune response of broilers fed on wheat-soybean meal based diets. 2. The following dietary treatments were used from d 0 to 21. Diet 1 (control, CONT): a commercial diet containing no enzyme or oregano essential oil, diet 2 (ENZY): supplemented with enzyme, diet 3 (EO250): supplemented with essential oil at 250 mg/kg feed, diet 4 (EO500): supplemented with essential oil at 500 mg/kg feed, diet 5 (ENZY + EO250): supplemented with enzyme and essential oil at 250 mg/kg, and diet 6 (ENZY + EO500): supplemented with enzyme and essential oil at 500 mg/kg. 3. Birds fed on diets containing ENZY, EO250 and ENZY + EO250 had significantly higher weight gain than those given CONT diet from d 0 to 7. No significant effects on feed intake, feed conversion ratio, mortality, organ weights except for jejunum weight and intestinal lengths was found with either enzyme or essential oil, alone or in combination, over the 21-d growth period. The supplementation of essential oil together with enzyme decreased jejunum weight compared with essential oil alone. 4. Supplementation with enzyme significantly decreased viscosity and increased dry matter of digesta, but did not alter pH of digesta. There was no effect of essential oil alone at either concentration on viscosity, dry matter or pH of digesta. A significant decrease in viscosity of digesta appeared when essential oil was used with together enzyme. 5. The supplementation of essential oil at both levels with or without enzyme significantly increased chymotrypsin activity in the digestive system, and improved crude protein digestibility. 6. The higher concentration of essential oil with and without enzyme significantly increased serum total cholesterol concentrations. No significant effect on immune response was found with either enzyme or essential oil, alone or together. 7. Enzymes and essential oil had different modes of actions. The supplementation of enzyme with essential oil in diets is likely more effective in view of performance, nutrient digestibility, enzyme activities and immune system.

Dynamic Network-Based Relevance Score Reveals Essential Proteins and Functional Modules in Directed Differentiation

PubMed Central

Wu, Chia-Chou; Lin, Che

2015-01-01

The induction of stem cells toward a desired differentiation direction is required for the advancement of stem cell-based therapies. Despite successful demonstrations of the control of differentiation direction, the effective use of stem cell-based therapies suffers from a lack of systematic knowledge regarding the mechanisms underlying directed differentiation. Using dynamic modeling and the temporal microarray data of three differentiation stages, three dynamic protein-protein interaction networks were constructed. The interaction difference networks derived from the constructed networks systematically delineated the evolution of interaction variations and the underlying mechanisms. A proposed relevance score identified the essential components in the directed differentiation. Inspection of well-known proteins and functional modules in the directed differentiation showed the plausibility of the proposed relevance score, with the higher scores of several proteins and function modules indicating their essential roles in the directed differentiation. During the differentiation process, the proteins and functional modules with higher relevance scores also became more specific to the neuronal identity. Ultimately, the essential components revealed by the relevance scores may play a role in controlling the direction of differentiation. In addition, these components may serve as a starting point for understanding the systematic mechanisms of directed differentiation and for increasing the efficiency of stem cell-based therapies. PMID:25977693

Fully automated multifunctional ultrahigh pressure liquid chromatography system for advanced proteome analyses

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

Lee, Jung Hwa; Hyung, Seok-Won; Mun, Dong-Gi

2012-08-03

A multi-functional liquid chromatography system that performs 1-dimensional, 2-dimensional (strong cation exchange/reverse phase liquid chromatography, or SCX/RPLC) separations, and online phosphopeptides enrichment using a single binary nano-flow pump has been developed. With a simple operation of a function selection valve, which is equipped with a SCX column and a TiO2 (titanium dioxide) column, a fully automated selection of three different experiment modes was achieved. Because the current system uses essentially the same solvent flow paths, the same trap column, and the same separation column for reverse-phase separation of 1D, 2D, and online phosphopeptides enrichment experiments, the elution time information obtainedmore » from these experiments is in excellent agreement, which facilitates correlating peptide information from different experiments.« less

Cystic fibrosis-related diabetes: a distinct condition.

PubMed

Cano Megías, Marta; González Albarrán, Olga

2015-01-01

Cystic fibrosis is the most common fatal inherited autosomal recessive disease in Caucasians, affecting approximately one out of every 2,000 births. Survival of patients with cystic fibrosis has significantly improved due to advances in respiratory and nutritional care, and their current average life expectancy is 30-40 years. Development of cystic fibrosis-related diabetes is a comorbidity that increases with age and may reach a prevalence up to 50% in adults. Its development is associated to impaired lung function and nutritional status, and early diagnosis and treatment are therefore essential to improve quality of life and performance status. Insulin therapy for diabetes and other early carbohydrate metabolism disorders may improve lung function and nutritional status of patients with cystic fibrosis. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

ATM-Mediated Transcriptional and Developmental Responses to γ-rays in Arabidopsis

PubMed Central

Renou, Jean-Pierre; Pichon, Olivier; Fochesato, Sylvain; Ortet, Philippe; Montané, Marie-Hélène

2007-01-01

ATM (Ataxia Telangiectasia Mutated) is an essential checkpoint kinase that signals DNA double-strand breaks in eukaryotes. Its depletion causes meiotic and somatic defects in Arabidopsis and progressive motor impairment accompanied by several cell deficiencies in patients with ataxia telangiectasia (AT). To obtain a comprehensive view of the ATM pathway in plants, we performed a time-course analysis of seedling responses by combining confocal laser scanning microscopy studies of root development and genome-wide expression profiling of wild-type (WT) and homozygous ATM-deficient mutants challenged with a dose of γ-rays (IR) that is sublethal for WT plants. Early morphologic defects in meristematic stem cells indicated that AtATM, an Arabidopsis homolog of the human ATM gene, is essential for maintaining the quiescent center and controlling the differentiation of initial cells after exposure to IR. Results of several microarray experiments performed with whole seedlings and roots up to 5 h post-IR were compiled in a single table, which was used to import gene information and extract gene sets. Sequence and function homology searches; import of spatio-temporal, cell cycling, and mutant-constitutive expression characteristics; and a simplified functional classification system were used to identify novel genes in all functional classes. The hundreds of radiomodulated genes identified were not a random collection, but belonged to functional pathways such as those of the cell cycle; cell death and repair; DNA replication, repair, and recombination; and transcription; translation; and signaling, indicating the strong cell reprogramming and double-strand break abrogation functions of ATM checkpoints. Accordingly, genes in all functional classes were either down or up-regulated concomitantly with downregulation of chromatin deacetylases or upregulation of acetylases and methylases, respectively. Determining the early transcriptional indicators of prolonged S-G2 phases that coincided with cell proliferation delay, or an anticipated subsequent auxin increase, accelerated cell differentiation or death, was used to link IR-regulated hallmark functions and tissue phenotypes after IR. The transcription burst was almost exclusively AtATM-dependent or weakly AtATR-dependent, and followed two major trends of expression in atm: (i)-loss or severe attenuation and delay, and (ii)-inverse and/or stochastic, as well as specific, enabling one to distinguish IR/ATM pathway constituents. Our data provide a large resource for studies on the interaction between plant checkpoints of the cell cycle, development, hormone response, and DNA repair functions, because IR-induced transcriptional changes partially overlap with the response to environmental stress. Putative connections of ATM to stem cell maintenance pathways after IR are also discussed. PMID:17487278

ATM-mediated transcriptional and developmental responses to gamma-rays in Arabidopsis.

PubMed

Ricaud, Lilian; Proux, Caroline; Renou, Jean-Pierre; Pichon, Olivier; Fochesato, Sylvain; Ortet, Philippe; Montané, Marie-Hélène

2007-05-09

ATM (Ataxia Telangiectasia Mutated) is an essential checkpoint kinase that signals DNA double-strand breaks in eukaryotes. Its depletion causes meiotic and somatic defects in Arabidopsis and progressive motor impairment accompanied by several cell deficiencies in patients with ataxia telangiectasia (AT). To obtain a comprehensive view of the ATM pathway in plants, we performed a time-course analysis of seedling responses by combining confocal laser scanning microscopy studies of root development and genome-wide expression profiling of wild-type (WT) and homozygous ATM-deficient mutants challenged with a dose of gamma-rays (IR) that is sublethal for WT plants. Early morphologic defects in meristematic stem cells indicated that AtATM, an Arabidopsis homolog of the human ATM gene, is essential for maintaining the quiescent center and controlling the differentiation of initial cells after exposure to IR. Results of several microarray experiments performed with whole seedlings and roots up to 5 h post-IR were compiled in a single table, which was used to import gene information and extract gene sets. Sequence and function homology searches; import of spatio-temporal, cell cycling, and mutant-constitutive expression characteristics; and a simplified functional classification system were used to identify novel genes in all functional classes. The hundreds of radiomodulated genes identified were not a random collection, but belonged to functional pathways such as those of the cell cycle; cell death and repair; DNA replication, repair, and recombination; and transcription; translation; and signaling, indicating the strong cell reprogramming and double-strand break abrogation functions of ATM checkpoints. Accordingly, genes in all functional classes were either down or up-regulated concomitantly with downregulation of chromatin deacetylases or upregulation of acetylases and methylases, respectively. Determining the early transcriptional indicators of prolonged S-G2 phases that coincided with cell proliferation delay, or an anticipated subsequent auxin increase, accelerated cell differentiation or death, was used to link IR-regulated hallmark functions and tissue phenotypes after IR. The transcription burst was almost exclusively AtATM-dependent or weakly AtATR-dependent, and followed two major trends of expression in atm: (i)-loss or severe attenuation and delay, and (ii)-inverse and/or stochastic, as well as specific, enabling one to distinguish IR/ATM pathway constituents. Our data provide a large resource for studies on the interaction between plant checkpoints of the cell cycle, development, hormone response, and DNA repair functions, because IR-induced transcriptional changes partially overlap with the response to environmental stress. Putative connections of ATM to stem cell maintenance pathways after IR are also discussed.

Mutational analysis of vaccinia virus E3 protein: the biological functions do not correlate with its biochemical capacity to bind double-stranded RNA.

PubMed

Dueck, Kevin J; Hu, YuanShen Sandy; Chen, Peter; Deschambault, Yvon; Lee, Jocelyn; Varga, Jessie; Cao, Jingxin

2015-05-01

Vaccinia E3 protein has the biochemical capacity of binding to double-stranded RNA (dsRNA). The best characterized biological functions of the E3 protein include its host range function, suppression of cytokine expression, and inhibition of interferon (IFN)-induced antiviral activity. Currently, the role of the dsRNA binding capacity in the biological functions of the E3 protein is not clear. To further understand the mechanism of the E3 protein biological functions, we performed alanine scanning of the entire dsRNA binding domain of the E3 protein to examine the link between its biochemical capacity of dsRNA binding and biological functions. Of the 115 mutants examined, 20 were defective in dsRNA binding. Although the majority of the mutants defective in dsRNA binding also showed defective replication in HeLa cells, nine mutants (I105A, Y125A, E138A, F148A, F159A, K171A, L182A, L183A, and I187/188A) retained the host range function to various degrees. Further examination of a set of representative E3L mutants showed that residues essential for dsRNA binding are not essential for the biological functions of E3 protein, such as inhibition of protein kinase R (PKR) activation, suppression of cytokine expression, and apoptosis. Thus, data described in this communication strongly indicate the E3 protein performs its biological functions via a novel mechanism which does not correlate with its dsRNA binding activity. dsRNAs produced during virus replication are important pathogen-associated molecular patterns (PAMPs) for inducing antiviral immune responses. One of the strategies used by many viruses to counteract such antiviral immune responses is achieved by producing dsRNA binding proteins, such as poxvirus E3 family proteins, influenza virus NS1, and Ebola virus V35 proteins. The most widely accepted model for the biological functions of this class of viral dsRNA binding proteins is that they bind to and sequester viral dsRNA PAMPs; thus, they suppress the related antiviral immune responses. However, no direct experimental data confirm such a model. In this study of vaccinia E3 protein, we found that the biological functions of the E3 protein are not necessarily linked to its biochemical capacity of dsRNA binding. Thus, our data strongly point to a new concept of virus modulation of cellular antiviral responses triggered by dsRNA PAMPs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

DIRAC File Replica and Metadata Catalog

NASA Astrophysics Data System (ADS)

Tsaregorodtsev, A.; Poss, S.

2012-12-01

File replica and metadata catalogs are essential parts of any distributed data management system, which are largely determining its functionality and performance. A new File Catalog (DFC) was developed in the framework of the DIRAC Project that combines both replica and metadata catalog functionality. The DFC design is based on the practical experience with the data management system of the LHCb Collaboration. It is optimized for the most common patterns of the catalog usage in order to achieve maximum performance from the user perspective. The DFC supports bulk operations for replica queries and allows quick analysis of the storage usage globally and for each Storage Element separately. It supports flexible ACL rules with plug-ins for various policies that can be adopted by a particular community. The DFC catalog allows to store various types of metadata associated with files and directories and to perform efficient queries for the data based on complex metadata combinations. Definition of file ancestor-descendent relation chains is also possible. The DFC catalog is implemented in the general DIRAC distributed computing framework following the standard grid security architecture. In this paper we describe the design of the DFC and its implementation details. The performance measurements are compared with other grid file catalog implementations. The experience of the DFC Catalog usage in the CLIC detector project are discussed.

Math practice and its influence on math skills and executive functions in adolescents with mild to borderline intellectual disability.

PubMed

Jansen, Brenda R J; De Lange, Eva; Van der Molen, Mariët J

2013-05-01

Adolescents with mild to borderline intellectual disability (MBID) often complete schooling without mastering basic math skills, even though basic math is essential for math-related challenges in everyday life. Limited attention to cognitive skills and low executive functioning (EF) may cause this delay. We aimed to improve math skills in an MBID-sample using computerized math training. Also, it was investigated whether EF and math performance were related and whether computerized math training had beneficial effects on EF. The sample consisted of a total of 58 adolescents (12-15 years) from special education. Participants were randomly assigned to either the experimental group or a treatment as usual (TAU) group. In the experimental condition, participants received 5 weeks of training. Math performance and EF were assessed before and after the training period. Math performance improved equally in both groups. However, frequently practicing participants improved more than participants in the control group. Visuo-spatial memory skills were positively related to addition and subtraction skills. Transfer effects from math training to EF were absent. It is concluded that math skills may increase if a reasonable effort in practicing math skills is made. The relation between visuo-spatial memory skills provides opportunities for improving math performance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Left ventricular performance in various heart diseases with or without heart failure:--an appraisal by quantitative one-plane cineangiocardiography.

PubMed

Lien, W P; Lee, Y S; Chang, F Z; Chen, J J; Shieh, W B

1978-01-01

Quantitative one-plane cineangiocardiography in right anterior oblique position for evaluation of LV performance was carried out in 62 patients with various heart diseases and in 13 subjects with normal LV. Parameters for evaluating both pump and muscle performances were derived from volume and pressure measurements. Of 31 patients with either systolic hypertension or LV myocardial diseases (coronary artery disease or idiopathic cardiomyopathy), 14 had clinical evidence of LV failure before the study. It was found that mean VCF and EF were most sensitive indicators of impaired LV performance among the various parameters. There was a close correlation between mean VCF and EF, yet discordant changes of both parameters were noted in some patients. Furthermore, wall motion abnormalities were not infrequently observed in patients with coronary artery disease or primary cardiomyopathy. Therefore, assessment of at least three ejection properties (EF, mean VCF and wall motion abnormalities) are considered to be essential for full understanding of derangement of LV function in heart disease. This is especially true of patients with coronary artery disease. LV behavior in relation to different pathological stresses or lesions, such as chronic pressure or volume load, myocardial disease and mitral stenosis, was also studied and possible cause of impaired LV myocardial function in mitral stenosis was discussed.

Importance of van der Waals interaction on structural, vibrational, and thermodynamic properties of NaCl

NASA Astrophysics Data System (ADS)

Marcondes, Michel L.; Wentzcovitch, Renata M.; Assali, Lucy V. C.

2018-05-01

Thermal equations of state (EOS) are essential in several scientific domains. However, experimental determination of EOS parameters may be limited at extreme conditions, therefore, ab initio calculations have become an important method to obtain them. Density functional theory (DFT) and its extensions with various degrees of approximations for the exchange and correlation (XC) energy is the method of choice, but large errors in the EOS parameters are still common. The alkali halides have been problematic from the onset of this field and the quest for appropriate DFT functionals for such ionic and relatively weakly bonded systems has remained an active topic of research. Here we use DFT + van der Waals functionals to calculate vibrational properties, thermal EOS, thermodynamic properties, and the B1 to B2 phase boundary of NaCl with high precision. Our results reveal a remarkable improvement over the performance of standard local density approximation and generalized gradient approximation functionals for all these properties and phase transition boundary, as well as great sensitivity of anharmonic effects on the choice of XC functional.

The role of executive functions in bilingual children with reading difficulties.

PubMed

Jalali-Moghadam, Niloufar; Kormi-Nouri, Reza

2015-06-01

To explore the joint effect of reading difficulties (RD) and bilingualism on executive functions, 190 children of four groups of 9-12 year-olds (41 bilinguals with RD, 45 monolinguals with RD, 45 bilinguals without RD, and 59 monolinguals without RD) were examined on the Concentration game, Tower of Hanoi, and Stroop as measures of executive functioning tapping into inhibitory/attentional control, working memory and planning ability. The most prominent finding was that in terms of RD, the speed of performances decreased dramatically. This general decrease was more pronounced for bilingual children with RD than for their monolingual counterparts. In conclusion, the findings suggest that while bilinguals gain more from executive functions in normal reading, they lose in terms of RD. Such an outcome confirms that executive functions are essential components of both reading and bilingualism, which depending on whether reading conditions are normal or difficult will produce cognitive advantages or disadvantages. Further, it is argued that dissimilarity between the Farsi and Swedish languages may complicate handling of such a situation. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

75 FR 32943 - Food and Drug Administration Modernization Act of 1997: Modifications to the List of Recognized...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-10

... basic safety and essential performance--Collateral standard: Electromagnetic compatibility--Requirements... standard: Electromagnetic compatibility--Requirements and tests 5-34 5-53 IEC 60601-1-2 Third edition 2007... for basic safety and essential performance--Collateral standard: Electromagnetic compatibility...

Linking Essential Tremor to the Cerebellum-Neuroimaging Evidence.

PubMed

Cerasa, Antonio; Quattrone, Aldo

2016-06-01

Essential tremor (ET) is the most common pathological tremor disorder in the world, and post-mortem evidence has shown that the cerebellum is the most consistent area of pathology in ET. In the last few years, advanced neuroimaging has tried to confirm this evidence. The aim of the present review is to discuss to what extent the evidence provided by this field of study may be generalised. We performed a systematic literature search combining the terms ET with the following keywords: MRI, VBM, MRS, DTI, fMRI, PET and SPECT. We summarised and discussed each study and placed the results in the context of existing knowledge regarding the cerebellar involvement in ET. A total of 51 neuroimaging studies met our search criteria, roughly divided into 19 structural and 32 functional studies. Despite clinical and methodological differences, both functional and structural imaging studies showed similar findings but without defining a clear topography of neurodegeneration. Indeed, the vast majority of studies found functional and structural abnormalities in several parts of the anterior and posterior cerebellar lobules, but it remains to be established to what degree these neural changes contribute to clinical symptoms of ET. Currently, advanced neuroimaging has confirmed the involvement of the cerebellum in pathophysiological processes of ET, although a high variability in results persists. For this reason, the translation of this knowledge into daily clinical practice is again partially limited, although new advanced multivariate neuroimaging approaches (machine-learning) are proving interesting changes of perspective.

PDE and cognitive processing: beyond the memory domain.

PubMed

Heckman, P R A; Blokland, A; Ramaekers, J; Prickaerts, J

2015-03-01

Phosphodiesterase inhibitors (PDE-Is) enhance cAMP and/or cGMP signaling via reducing the degradation of these cyclic nucleotides. Both cAMP and cGMP signaling are essential for a variety of cellular functions and exert their effects both pre- and post-synaptically. Either of these second messengers relays and amplifies incoming signals at receptors on the cell surface making them important elements in signal transduction cascades and essential in cellular signaling in a variety of cell functions including neurotransmitter release and neuroprotection. Consequently, these processes can be influenced by PDE-Is as they increase cAMP and/or cGMP concentrations. PDE-Is have been considered as possible therapeutic agents to treat impaired memory function linked to several brain disorders, including depression, schizophrenia and Alzheimer's disease (AD). This review will, however, focus on the possible role of phosphodiesterases (PDEs) in cognitive decline beyond the memory domain. Here we will discuss the involvement of PDEs on three related domains: attention, information filtering (sensory- and sensorimotor gating) and response inhibition (drug-induced hyperlocomotion). Currently, these are emerging cognitive domains in the field of PDE research. Here we discuss experimental studies and the potential beneficial effects of PDE-I drugs on these cognitive domains, as effects of PDE-Is on these domains could potentially influence effects on memory performance. Overall, PDE4 seems to be the most promising target for all domains discussed in this review. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognitive profile in Wilson's disease: a case series of 31 patients.

PubMed

Wenisch, E; De Tassigny, A; Trocello, J-M; Beretti, J; Girardot-Tinant, N; Woimant, F

2013-12-01

Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism. If untreated, WD, which is initially a liver disease, can turn into a multi-systemic disease with neurological involvement. Very few studies have described cognitive impairment in WD. The aim of this study is to report the cognitive profile of 31 treated WD patients. Patients were classed into two groups using the Unified Wilson Disease Rating Scale (UWDRS): WD patients without neurological signs (WD-N(-)) (n=13), and WD patients with neurological signs (WD-N(+)) (n=18). The patients participated in a neuropsychological assessment evaluating memory, executive function and visuo-spatial abilities. Both groups performed well for verbal intelligence and episodic memory skills. However, the majority of these patients exhibited altered performance for at least one cognitive test, particularly in the executive domain. The WD-N(+) group performed less well than the WD-N(-) group on cognitive tests involving rapid motor function, abstract thinking, working memory and top-down inhibitory control. Cognitive impairment in treated WD patients essentially affects executive function involving fronto-striatal circuits. Verbal intelligence and episodic memory abilities seem to be remarkably preserved. Neuropsychological assessment is a valuable tool to evaluate the presence and the consequences of these cognitive impairments in WD patients with or without neurological signs in the course of this chronic disease. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study.

PubMed

Kanayama, Gen; Rogowska, Jadwiga; Pope, Harrison G; Gruber, Staci A; Yurgelun-Todd, Deborah A

2004-11-01

Many neuropsychological studies have documented deficits in working memory among recent heavy cannabis users. However, little is known about the effects of cannabis on brain activity. We assessed brain function among recent heavy cannabis users while they performed a working memory task. Functional magnetic resonance imaging was used to examine brain activity in 12 long-term heavy cannabis users, 6-36 h after last use, and in 10 control subjects while they performed a spatial working memory task. Regional brain activation was analyzed and compared using statistical parametric mapping techniques. Compared with controls, cannabis users exhibited increased activation of brain regions typically used for spatial working memory tasks (such as prefrontal cortex and anterior cingulate). Users also recruited additional regions not typically used for spatial working memory (such as regions in the basal ganglia). These findings remained essentially unchanged when re-analyzed using subjects' ages as a covariate. Brain activation showed little or no significant correlation with subjects' years of education, verbal IQ, lifetime episodes of cannabis use, or urinary cannabinoid levels at the time of scanning. Recent cannabis users displayed greater and more widespread brain activation than normal subjects when attempting to perform a spatial working memory task. This observation suggests that recent cannabis users may experience subtle neurophysiological deficits, and that they compensate for these deficits by "working harder"-calling upon additional brain regions to meet the demands of the task.

A global interaction network maps a wiring diagram of cellular function

PubMed Central

Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N.; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D.; Pelechano, Vicent; Styles, Erin B.; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S.; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F.; Li, Sheena C.; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; Luis, Bryan-Joseph San; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W.; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G.; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M.; Moore, Claire L.; Rosebrock, Adam P.; Caudy, Amy A.; Myers, Chad L.; Andrews, Brenda; Boone, Charles

2017-01-01

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. PMID:27708008

Decentralization and health system performance - a focused review of dimensions, difficulties, and derivatives in India.

PubMed

Panda, Bhuputra; Thakur, Harshad P

2016-10-31

One of the principal goals of any health care system is to improve health through the provision of clinical and public health services. Decentralization as a reform measure aims to improve inputs, management processes and health outcomes, and has political, administrative and financial connotations. It is argued that the robustness of a health system in achieving desirable outcomes is contingent upon the width and depth of 'decision space' at the local level. Studies have used different approaches to examine one or more facets of decentralization and its effect on health system functioning; however, lack of consensus on an acceptable framework is a critical gap in determining its quantum and quality. Theorists have resorted to concepts of 'trust', 'convenience' and 'mutual benefits' to explain, define and measure components of governance in health. In the emerging 'continuum of health services' model, the challenge lies in identifying variables of performance (fiscal allocation, autonomy at local level, perception of key stakeholders, service delivery outputs, etc.) through the prism of decentralization in the first place, and in establishing directed relationships among them. This focused review paper conducted extensive web-based literature search, using PubMed and Google Scholar search engines. After screening of key words and study objectives, we retrieved 180 articles for next round of screening. One hundred and four full articles (three working papers and 101 published papers) were reviewed in totality. We attempted to summarize existing literature on decentralization and health systems performance, explain key concepts and essential variables, and develop a framework for further scientific scrutiny. Themes are presented in three separate segments of dimensions, difficulties and derivatives. Evaluation of local decision making and its effect on health system performance has been studied in a compartmentalized manner. There is sparse evidence about innovations attributable to decentralization. We observed that in India, there is very scant evaluative study on the subject. We didn't come across a single study examining the perception and experiences of local decision makers about the opportunities and challenges they faced. The existing body of evidences may be inadequate to feed into sound policy making. The principles of management hinge on measurement of inputs, processes and outputs. In the conceptual framework we propose three levels of functions (health systems functions, management functions and measurement functions) being intricately related to inputs, processes and outputs. Each level of function encompasses essential elements derived from the synthesis of information gathered through literature review and non-participant observation. We observed that it is difficult to quantify characteristics of governance at institutional, system and individual levels except through proxy means. There is an urgent need to sensitize governments and academia about how best more objective evaluation of 'shared governance' can be undertaken to benefit policy making. The future direction of enquiry should focus on context-specific evidence of its effect on the entire spectrum of health system, with special emphasis on efficiency, community participation, human resource management and quality of services.

The WRKY Transcription Factor Family in Citrus: Valuable and Useful Candidate Genes for Citrus Breeding.

PubMed

Ayadi, M; Hanana, M; Kharrat, N; Merchaoui, H; Marzoug, R Ben; Lauvergeat, V; Rebaï, A; Mzid, R

2016-10-01

WRKY transcription factors belong to a large family of plant transcriptional regulators whose members have been reported to be involved in a wide range of biological roles including plant development, adaptation to environmental constraints and response to several diseases. However, little or poor information is available about WRKY's in Citrus. The recent release of completely assembled genomes sequences of Citrus sinensis and Citrus clementina and the availability of ESTs sequences from other citrus species allowed us to perform a genome survey for Citrus WRKY proteins. In the present study, we identified 100 WRKY members from C. sinensis (51), C. clementina (48) and Citrus unshiu (1), and analyzed their chromosomal distribution, gene structure, gene duplication, syntenic relation and phylogenetic analysis. A phylogenetic tree of 100 Citrus WRKY sequences with their orthologs from Arabidopsis has distinguished seven groups. The CsWRKY genes were distributed across all ten sweet orange chromosomes. A comprehensive approach and an integrative analysis of Citrus WRKY gene expression revealed variable profiles of expression within tissues and stress conditions indicating functional diversification. Thus, candidate Citrus WRKY genes have been proposed as potentially involved in fruit acidification, essential oil biosynthesis and abiotic/biotic stress tolerance. Our results provided essential prerequisites for further WRKY genes cloning and functional analysis with an aim of citrus crop improvement.

The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

PubMed

Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

2016-05-01

Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. © 2016 John Wiley & Sons Ltd.

Essential role of the unordered VP2 n-terminal domain of the parvovirus MVM capsid in nuclear assembly and endosomal enlargement of the virion fivefold channel for cell entry.

PubMed

Sánchez-Martínez, Cristina; Grueso, Esther; Carroll, Miles; Rommelaere, Jean; Almendral, José M

2012-10-10

The unordered N-termini of parvovirus capsid proteins (Nt) are translocated through a channel at the icosahedral five-fold axis to serve for virus traffick. Heterologous peptides were genetically inserted at the Nt of MVM to study their functional tolerance to manipulations. Insertion of a 5T4-single-chain antibody at VP2-Nt (2Nt) yielded chimeric capsid subunits failing to enter the nucleus. The VEGFR2-binding peptide (V1) inserted at both 2Nt and VP1-Nt efficiently assembled in virions, but V1 disrupted VP1 and VP2 entry functions. The VP2 defect correlated with restricted externalization of V1-2Nt out of the coat. The specific infectivity of MVM and wtVP-pseudotyped mosaic MVM-V1 virions, upon heating and/or partial 2Nt cleavage, demonstrated that some 2Nt domains become intracellularly translocated out of the virus shell and cleaved to initiate entry. The V1 insertion defines a VP2-driven endosomal enlargement of the channel as an essential structural rearrangement performed by the MVM virion to infect. Copyright © 2012 Elsevier Inc. All rights reserved.

Age-dependent effect of high cholesterol diets on anxiety-like behavior in elevated plus maze test in rats.

PubMed

Hu, Xu; Wang, Tao; Luo, Jia; Liang, Shan; Li, Wei; Wu, Xiaoli; Jin, Feng; Wang, Li

2014-09-01

Cholesterol is an essential component of brain and nerve cells and is essential for maintaining the function of the nervous system. Epidemiological studies showed that patients suffering from anxiety disorders have higher serum cholesterol levels. In this study, we investigated the influence of high cholesterol diet on anxiety-like behavior in elevated plus maze in animal model and explored the relationship between cholesterol and anxiety-like behavior from the aspect of central neurochemical changes. Young (3 weeks old) and adult (20 weeks old) rats were given a high cholesterol diet for 8 weeks. The anxiety-like behavior in elevated plus maze test and changes of central neurochemical implicated in anxiety were measured. In young rats, high cholesterol diet induced anxiolytic-like behavior, decreased serum corticosterone (CORT), increased hippocampal brain-derived neurotrophic factor (BDNF), increased hippocampal mineralocorticoid receptor (MR) and decreased glucocorticoid receptor (GR). In adult rats, high cholesterol diet induced anxiety-like behavior and increase of serum CORT and decrease of hippocampal BDNF comparing with their respective control group that fed the regular diet. High cholesterol diet induced age-dependent effects on anxiety-like behavior and central neurochemical changes. High cholesterol diet might affect the central nervous system (CNS) function differently, and resulting in different behavior performance of anxiety in different age period.

Training Manual for Elements of Interface Definition and Control

NASA Technical Reports Server (NTRS)

Lalli, Vincent R. (Editor); Kastner, Robert E. (Editor); Hartt, Henry N. (Editor)

1997-01-01

The primary thrust of this manual is to ensure that the format and information needed to control interfaces between equipment are clear and understandable. The emphasis is on controlling the engineering design of the interface and not on the functional performance requirements of the system or the internal workings of the interfacing equipment. Interface control should take place, with rare exception, at the interfacing elements and no further. There are two essential sections of the manual. Chapter 2, Principles of Interface Control, discusses how interfaces are defined. It describes different types of interfaces to be considered and recommends a format for the documentation necessary for adequate interface control. Chapter 3, The Process: Through the Design Phases, provides tailored guidance for interface definition and control. This manual can be used to improve planned or existing interface control processes during system design and development. It can also be used to refresh and update the corporate knowledge base. The information presented herein will reduce the amount of paper and data required in interface definition and control processes by as much as 50 percent and will shorten the time required to prepare an interface control document. It also highlights the essential technical parameters that ensure that flight subsystems will indeed fit together and function as intended after assembly and checkout.

Bridging ultrahigh-Q devices and photonic circuits

NASA Astrophysics Data System (ADS)

Yang, Ki Youl; Oh, Dong Yoon; Lee, Seung Hoon; Yang, Qi-Fan; Yi, Xu; Shen, Boqiang; Wang, Heming; Vahala, Kerry

2018-05-01

Optical microresonators are essential to a broad range of technologies and scientific disciplines. However, many of their applications rely on discrete devices to attain challenging combinations of ultra-low-loss performance (ultrahigh Q) and resonator design requirements. This prevents access to scalable fabrication methods for photonic integration and lithographic feature control. Indeed, finding a microfabrication bridge that connects ultrahigh-Q device functions with photonic circuits is a priority of the microcavity field. Here, an integrated resonator having a record Q factor over 200 million is presented. Its ultra-low-loss and flexible cavity design brings performance to integrated systems that has been the exclusive domain of discrete silica and crystalline microcavity devices. Two distinctly different devices are demonstrated: soliton sources with electronic repetition rates and high-coherence/low-threshold Brillouin lasers. This multi-device capability and performance from a single integrated cavity platform represents a critical advance for future photonic circuits and systems.

Vitamin D, Essential Minerals, and Toxic Elements: Exploring Interactions between Nutrients and Toxicants in Clinical Medicine

PubMed Central

Schwalfenberg, Gerry K.; Genuis, Stephen J.

2015-01-01

In clinical medicine, increasing attention is being directed towards the important areas of nutritional biochemistry and toxicant bioaccumulation as they relate to human health and chronic disease. Optimal nutritional status, including healthy levels of vitamin D and essential minerals, is requisite for proper physiological function; conversely, accrual of toxic elements has the potential to impair normal physiology. It is evident that vitamin D intake can facilitate the absorption and assimilation of essential inorganic elements (such as calcium, magnesium, copper, zinc, iron, and selenium) but also the uptake of toxic elements (such as lead, arsenic, aluminum, cobalt, and strontium). Furthermore, sufficiency of essential minerals appears to resist the uptake of toxic metals. This paper explores the literature to determine a suitable clinical approach with regard to vitamin D and essential mineral intake to achieve optimal biological function and to avoid harm in order to prevent and overcome illness. It appears preferable to secure essential mineral status in conjunction with adequate vitamin D, as intake of vitamin D in the absence of mineral sufficiency may result in facilitation of toxic element absorption with potential adverse clinical outcomes. PMID:26347061

Space-based multifunctional end effector systems functional requirements and proposed designs

NASA Technical Reports Server (NTRS)

Mishkin, A. H.; Jau, B. M.

1988-01-01

The end effector is an essential element of teleoperator and telerobot systems to be employed in space in the next decade. The report defines functional requirements for end effector systems to perform operations that are currently only feasible through Extra-Vehicular Activity (EVA). Specific tasks and functions that the end effectors must be capable of performing are delineated. Required capabilities for forces and torques, clearances, compliance, and sensing are described, using current EVA requirements as guidelines where feasible. The implications of these functional requirements on the elements of potential end effector systems are discussed. The systems issues that must be considered in the design of space-based manipulator systems are identified; including impacts on subsystems tightly coupled to the end effector, i.e., control station, information processing, manipulator arm, tool and equipment stowage. Possible end effector designs are divided into three categories: single degree-of-freedom end effectors, multiple degree of freedom end effectors, and anthropomorphic hands. Specific design alternatives are suggested and analyzed within the individual categories. Two evaluations are performed: the first considers how well the individual end effectors could substitute for EVA; the second compares how manipulator systems composed of the top performers from the first evaluation would improve the space shuttle Remote Manipulator System (RMS) capabilities. The analysis concludes that the anthropomorphic hand is best-suited for EVA tasks. A left- and right-handed anthropomorphic manipulator arm configuration is suggested as appropriate to be affixed to the RMS, but could also be used as part of the Smart Front End for the Orbital Maneuvering Vehicle (OMV). The technical feasibility of the anthropomorphic hand and its control are demonstrated. An evolutionary development approach is proposed and approximate scheduling provided for implementing the suggested manipulator systems in time for space stations operations in the early 1990s.

Proceedings of a Workshop on Navy Long-Range Deep Ocean Technology: An Assessment of Current Development, Forecasts, and Research Thrusts Held at Washington, DC on September 23-24, 1982,

DTIC Science & Technology

1983-01-01

the Navy. These technologies ini- tially were reviewed in five groups; the technologies were assessed later during the workshop in four sets, two of...sulfur dioxide (LiSO2 ). The latter two systems present safety hazards after discharge.1- 7 Also these systems are already being developed exten- sively...Control The K02 life support system will supply oxygen and, at the same time, remove CO2. One chemical performs the two essential functions of the

Perioperative Care of the Liver Transplant Patient.

PubMed

Keegan, Mark T; Kramer, David J

2016-07-01

With the evolution of surgical and anesthetic techniques, liver transplantation has become "routine," allowing for modifications of practice to decrease perioperative complications and costs. There is debate over the necessity for intensive care unit admission for patients with satisfactory preoperative status and a smooth intraoperative course. Postoperative care is made easier when the liver graft performs optimally. Assessment of graft function, vigilance for complications after the major surgical insult, and optimization of multiple systems affected by liver disease are essential aspects of postoperative care. The intensivist plays a vital role in an integrated multidisciplinary transplant team. Copyright © 2016 Elsevier Inc. All rights reserved.

FBI fingerprint identification automation study: AIDS 3 evaluation report. Volume 8: Measures of effectiveness

NASA Technical Reports Server (NTRS)

Mulhall, B. D. L.

1980-01-01

The development of both quantitative criteria that were used to evaluate conceptional systems for automating the functions for the FBI Identification Division is described. Specific alternative systems for automation were compared by using these developed criteria, defined as Measures of Effectiveness (MOE), to gauge system's performance in attempting to achieve certain goals. The MOE, essentially measurement tools that were developed through the combination of suitable parameters, pertain to each conceivable area of system operation. The methods and approaches used, both in selecting the parameters and in using the resulting MOE, are described.

Shaggy aorta syndrome after acute arterial macroembolism: report of a case.

PubMed

Hayashida, Naoki; Murayama, Hirokazu; Pearce, Yoko; Asano, Souichi; Ohashi, Yukio; Kohno, Hiroki; Handa, Takemi; Matsuo, Kozo; Nakagawa, Yasutsugu; Tatsuno, Katsuhiko

2004-01-01

We report the case of a patient who underwent treatment for a macroembolism in the right lower leg, which led to shaggy aorta syndrome. Anticoagulant therapy for the macroembolism and intra-aortic catheterization exacerbated the patient's renal function and triggered another massive microembolization of the visceral arteries, with a fatal outcome. To minimize the incremental complications inherent to this syndrome, awareness and prompt diagnosis with enhanced computed tomography or intravenous digital subtraction aortography are essential. Axillo-bifemoral bypass with bilateral external iliac artery ligations, performed with optimal timing, could save patients with shaggy aorta syndrome.

Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting | Office of Cancer Genomics

Cancer.gov

The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G2 cell-cycle arrest.

CRISPRi and CRISPRa: New Functional Genomics Tools Provide Complementary Insights into Cancer Biology and Therapeutic Strategies | Office of Cancer Genomics

Cancer.gov

A central goal of research for targeted cancer therapy, or precision oncology, is to reveal the intrinsic vulnerabilities of cancer cells and exploit them as therapeutic targets. Examples of cancer cell vulnerabilities include driver oncogenes that are essential for the initiation and progression of cancer, or non-oncogene addictions resulting from the cancerous state of the cell. To identify vulnerabilities, scientists perform genetic “loss-of-function” and “gain-of-function” studies to better understand the roles of specific genes in cancer cells.

A general algorithm using finite element method for aerodynamic configurations at low speeds

NASA Technical Reports Server (NTRS)

Balasubramanian, R.

1975-01-01

A finite element algorithm for numerical simulation of two-dimensional, incompressible, viscous flows was developed. The Navier-Stokes equations are suitably modelled to facilitate direct solution for the essential flow parameters. A leap-frog time differencing and Galerkin minimization of these model equations yields the finite element algorithm. The finite elements are triangular with bicubic shape functions approximating the solution space. The finite element matrices are unsymmetrically banded to facilitate savings in storage. An unsymmetric L-U decomposition is performed on the finite element matrices to obtain the solution for the boundary value problem.

[Acute visual loss in pregnancy caused by craniopharyngioma].

PubMed

Grillo-Mallo, E; Jiménez-Benito, J; Diéz-Feijóo, E; Alonso Alonso, I; Ferrero Collado, A; Muñoz Quiñones, S

2014-04-01

A 38-year-old female, at 20-weeks gestation, experienced a sudden visual loss and visual-field abnormalities. The neuroimaging tests showed a craniopharyngioma. Surgical removal was performed with a successful outcome as regards the pregnancy and visual function. It is known that pituitary adenomas may grow during pregnancy; however this is unusual in craniopharyngiomas. They usually present with visual problems due to their suprasellar topography. Surgery is the treatment of choice, the outcome essentially depending on its complete resection. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Gradual Crossover from Subdiffusion to Normal Diffusion: A Many-Body Effect in Protein Surface Water

NASA Astrophysics Data System (ADS)

Tan, Pan; Liang, Yihao; Xu, Qin; Mamontov, Eugene; Li, Jinglai; Xing, Xiangjun; Hong, Liang

2018-06-01

Dynamics of hydration water is essential for the function of biomacromolecules. Previous studies have demonstrated that water molecules exhibit subdiffusion on the surface of biomacromolecules; yet the microscopic mechanism remains vague. Here, by performing neutron scattering, molecular dynamics simulations, and analytic modeling on hydrated perdeuterated protein powders, we found water molecules jump randomly between trapping sites on protein surfaces, whose waiting times obey a broad distribution, resulting in subdiffusion. Moreover, the subdiffusive exponent gradually increases with observation time towards normal diffusion due to a many-body volume-exclusion effect.

Empirical mode decomposition for analyzing acoustical signals

NASA Technical Reports Server (NTRS)

Huang, Norden E. (Inventor)

2005-01-01

The present invention discloses a computer implemented signal analysis method through the Hilbert-Huang Transformation (HHT) for analyzing acoustical signals, which are assumed to be nonlinear and nonstationary. The Empirical Decomposition Method (EMD) and the Hilbert Spectral Analysis (HSA) are used to obtain the HHT. Essentially, the acoustical signal will be decomposed into the Intrinsic Mode Function Components (IMFs). Once the invention decomposes the acoustic signal into its constituting components, all operations such as analyzing, identifying, and removing unwanted signals can be performed on these components. Upon transforming the IMFs into Hilbert spectrum, the acoustical signal may be compared with other acoustical signals.

The role of executive functioning in memory performance in pediatric focal epilepsy.

PubMed

Sepeta, Leigh N; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D; Berl, Madison M

2017-02-01

Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (Wechsler Abbreviated Scale of Intelligence [WASI]/Differential Ability Scales [DAS]), as well as visual Children's Memory Scale (CMS Dot Locations) and verbal episodic memory (Wide Range Assessment of Memory and Learning [WRAML] Story Memory and California Verbal Learning Test for Children [CVLT-C]). Executive functioning was measured directly (WISC-IV Digit Span Backward; Clinical Evaluation of Language Fundamentals, Fourth Edition (CELF-IV) Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function [BRIEF]). Children with focal epilepsy had lower delayed free-recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η 2 = 0.12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η 2 = 0.03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η 2 = 0.08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9-19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9-10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extratemporal, frontal vs. extrafrontal). Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Effects of ligand binding on the dynamics of rice nonspecific lipid transfer protein 1: a model from molecular simulations.

PubMed

Lai, Yen-Ting; Cheng, Chao-Sheng; Liu, Yu-Nan; Liu, Yaw-Jen; Lyu, Ping-Chiang

2008-09-01

Plant nonspecific lipid transfer proteins (nsLTPs) are small, basic proteins constituted mainly of alpha-helices and stabilized by four conserved disulfide bridges. They are characterized by the presence of a tunnel-like hydrophobic cavity, capable of transferring various lipid molecules between lipid bilayers in vitro. In this study, molecular dynamics (MD) simulations were performed at room temperature to investigate the effects of lipid binding on the dynamic properties of rice nsLTP1. Rice nsLTP1, either in the free form or complexed with one or two lipids was subjected to MD simulations. The C-terminal loop was very flexible both before and after lipid binding, as revealed by calculating the root-mean-square fluctuation. After lipid binding, the flexibility of some residues that were not in direct contact with lipid molecules increased significantly, indicating an increase of entropy in the region distal from the binding site. Essential dynamics analysis revealed clear differences in motion between unliganded and liganded rice nsLTP1s. In the free form of rice nsLTP1, loop1 exhibited the largest directional motion. This specific essential motion mode diminished after binding one or two lipid molecules. To verify the origin of the essential motion observed in the free form of rice nsLTP1, we performed multiple sequence alignments to probe the intrinsic motion encoded in the primary sequence. We found that the amino acid sequence of loop1 is highly conserved among plant nsLTP1s, thus revealing its functional importance during evolution. Furthermore, the sequence of loop1 is composed mainly of amino acids with short side chains. In this study, we show that MD simulations, together with essential dynamics analysis, can be used to determine structural and dynamic differences of rice nsLTP1 upon lipid binding. 2008 Wiley-Liss, Inc.

Enhanced tolerance to stretch-induced performance degradation of stretchable MnO2-based supercapacitors.

PubMed

Huang, Yan; Huang, Yang; Meng, Wenjun; Zhu, Minshen; Xue, Hongtao; Lee, Chun-Sing; Zhi, Chunyi

2015-02-04

The performance of many stretchable electronics, such as energy storage devices and strain sensors, is highly limited by the structural breakdown arising from the stretch imposed. In this article, we focus on a detailed study on materials matching between functional materials and their conductive substrate, as well as enhancement of the tolerance to stretch-induced performance degradation of stretchable supercapacitors, which are essential for the design of a stretchable device. It is revealed that, being widely utilized as the electrode material of the stretchable supercapacitor, metal oxides such as MnO2 nanosheets have serious strain-induced performance degradation due to their rigid structure. In comparison, with conducting polymers like a polypyrrole (PPy) film as the electrochemically active material, the performance of stretchable supercapacitors can be well preserved under strain. Therefore, a smart design is to combine PPy with MnO2 nanosheets to achieve enhanced tolerance to strain-induced performance degradation of MnO2-based supercapacitors, which is realized by fabricating an electrode of PPy-penetrated MnO2 nanosheets. The composite electrodes exhibit a remarkable enhanced tolerance to strain-induced performance degradation with well-preserved performance over 93% under strain. The detailed morphology and electrochemical impedance variations are investigated for the mechanism analyses. Our work presents a systematic investigation on the selection and matching of electrode materials for stretchable supercapacitors to achieve high performance and great tolerance to strain, which may guide the selection of functional materials and their substrate materials for the next-generation of stretchable electronics.

A global characterization and identification of multifunctional enzymes.

PubMed

Cheng, Xian-Ying; Huang, Wei-Juan; Hu, Shi-Chang; Zhang, Hai-Lei; Wang, Hao; Zhang, Jing-Xian; Lin, Hong-Huang; Chen, Yu-Zong; Zou, Quan; Ji, Zhi-Liang

2012-01-01

Multi-functional enzymes are enzymes that perform multiple physiological functions. Characterization and identification of multi-functional enzymes are critical for communication and cooperation between different functions and pathways within a complex cellular system or between cells. In present study, we collected literature-reported 6,799 multi-functional enzymes and systematically characterized them in structural, functional, and evolutionary aspects. It was found that four physiochemical properties, that is, charge, polarizability, hydrophobicity, and solvent accessibility, are important for characterization of multi-functional enzymes. Accordingly, a combinational model of support vector machine and random forest model was constructed, based on which 6,956 potential novel multi-functional enzymes were successfully identified from the ENZYME database. Moreover, it was observed that multi-functional enzymes are non-evenly distributed in species, and that Bacteria have relatively more multi-functional enzymes than Archaebacteria and Eukaryota. Comparative analysis indicated that the multi-functional enzymes experienced a fluctuation of gene gain and loss during the evolution from S. cerevisiae to H. sapiens. Further pathway analyses indicated that a majority of multi-functional enzymes were well preserved in catalyzing several essential cellular processes, for example, metabolisms of carbohydrates, nucleotides, and amino acids. What's more, a database of known multi-functional enzymes and a server for novel multi-functional enzyme prediction were also constructed for free access at http://bioinf.xmu.edu.cn/databases/MFEs/index.htm.

Prediction of essential proteins based on gene expression programming.

PubMed

Zhong, Jiancheng; Wang, Jianxin; Peng, Wei; Zhang, Zhen; Pan, Yi

2013-01-01

Essential proteins are indispensable for cell survive. Identifying essential proteins is very important for improving our understanding the way of a cell working. There are various types of features related to the essentiality of proteins. Many methods have been proposed to combine some of them to predict essential proteins. However, it is still a big challenge for designing an effective method to predict them by integrating different features, and explaining how these selected features decide the essentiality of protein. Gene expression programming (GEP) is a learning algorithm and what it learns specifically is about relationships between variables in sets of data and then builds models to explain these relationships. In this work, we propose a GEP-based method to predict essential protein by combing some biological features and topological features. We carry out experiments on S. cerevisiae data. The experimental results show that the our method achieves better prediction performance than those methods using individual features. Moreover, our method outperforms some machine learning methods and performs as well as a method which is obtained by combining the outputs of eight machine learning methods. The accuracy of predicting essential proteins can been improved by using GEP method to combine some topological features and biological features.

Functional expansion of human tRNA synthetases achieved by structural inventions

PubMed Central

Guo, Min; Schimmel, Paul; Yang, Xiang-Lei

2010-01-01

Known as an essential component of the translational apparatus, the aminoacyl-tRNA synthetase family catalyzes the first step reaction in protein synthesis, that is, to specifically attach each amino acid to its cognate tRNA. While preserving this essential role, tRNA synthetases developed other roles during evolution. Human tRNA synthetases, in particular, have diverse functions in different pathways involving angiogenesis, inflammation and apoptosis. The functional diversity is further illustrated in the association with various diseases through genetic mutations that do not affect aminoacylation or protein synthesis. Here we review the accumulated knowledge on how human tRNA synthetases used structural inventions to achieve functional expansions. PMID:19932696

Creation of a virtual cutaneous tissue bank

NASA Astrophysics Data System (ADS)

LaFramboise, William A.; Shah, Sujal; Hoy, R. W.; Letbetter, D.; Petrosko, P.; Vennare, R.; Johnson, Peter C.

2000-04-01

Cellular and non-cellular constituents of skin contain fundamental morphometric features and structural patterns that correlate with tissue function. High resolution digital image acquisitions performed using an automated system and proprietary software to assemble adjacent images and create a contiguous, lossless, digital representation of individual microscope slide specimens. Serial extraction, evaluation and statistical analysis of cutaneous feature is performed utilizing an automated analysis system, to derive normal cutaneous parameters comprising essential structural skin components. Automated digital cutaneous analysis allows for fast extraction of microanatomic dat with accuracy approximating manual measurement. The process provides rapid assessment of feature both within individual specimens and across sample populations. The images, component data, and statistical analysis comprise a bioinformatics database to serve as an architectural blueprint for skin tissue engineering and as a diagnostic standard of comparison for pathologic specimens.

Extent of hippocampal atrophy predicts degree of deficit in recall

PubMed Central

Patai, Eva Zita; Gadian, David G.; Cooper, Janine M.; Dzieciol, Anna M.; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-01-01

Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition. PMID:26417089

Extent of hippocampal atrophy predicts degree of deficit in recall.

PubMed

Patai, Eva Zita; Gadian, David G; Cooper, Janine M; Dzieciol, Anna M; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-10-13

Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition.

Recombinant human dihydroxyacetonephosphate acyl-transferase characterization as an integral monotopic membrane protein.

PubMed

Piano, Valentina; Nenci, Simone; Magnani, Francesca; Aliverti, Alessandro; Mattevi, Andrea

2016-12-02

Although the precise functions of ether phospholipids are still poorly understood, significant alterations in their physiological levels are associated either to inherited disorders or to aggressive metastatic cancer. The essential precursor, alkyl-dihydroxyacetone phosphate (DHAP), for all ether phospholipids species is synthetized in two consecutive reactions performed by two enzymes sitting on the inner side of the peroxisomal membrane. Here, we report the characterization of the recombinant human DHAP acyl-transferase, which performs the first step in alkyl-DHAP synthesis. By exploring several expression systems and designing a number of constructs, we were able to purify the enzyme in its active form and we found that it is tightly bound to the membrane through the N-terminal residues. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.