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Sample records for define utility functions

  1. Defining functional dyspepsia.

    PubMed

    Mearin, Fermín; Calleja, José Luis

    2011-12-01

    Dyspepsia and functional dyspepsia represent a highly significant public health issue. A good definition of dyspepsia is key for helping us to better approach symptoms, decision making, and therapy indications.During the last few years many attempts were made at establishing a definition of dyspepsia. Results were little successful on most occasions, and clear discrepancies arose on whether symptoms should be associated with digestion, which types of symptoms were to be included, which anatomic location should symptoms have, etc.The Rome III Committee defined dyspepsia as "a symptom or set of symptoms that most physicians consider to originate from the gastroduodenal area", including the following: postprandial heaviness, early satiety, and epigastric pain or burning. Two new entities were defined: a) food-induced dyspeptic symptoms (postprandial distress syndrome); and b) epigastric pain (epigastric pain syndrome). These and other definitions have shown both strengths and weaknesses. At times they have been much too complex, at times much too simple; furthermore, they have commonly erred on the side of being inaccurate and impractical. On the other hand, some (the most recent ones) are difficult to translate into the Spanish language. In a meeting of gastroenterologists with a special interest in digestive functional disorders, the various aspects of dyspepsia definition were discussed and put to the vote, and the following conclusions were arrived at: dyspepsia is defined as a set of symptoms, either related or unrelated to food ingestion, localized on the upper half of the abdomen. They include: a) epigastric discomfort (as a category of severity) or pain; b) postprandial heaviness; and c) early satiety. Associated complaints include: nausea, belching, bloating, and epigastric burn (heartburn). All these must be scored according to severity and frequency. Furthermore, psychological factors may be involved in the origin of functional dyspepsia. On the other hand

  2. Model-based Utility Functions

    NASA Astrophysics Data System (ADS)

    Hibbard, Bill

    2012-05-01

    Orseau and Ring, as well as Dewey, have recently described problems, including self-delusion, with the behavior of agents using various definitions of utility functions. An agent's utility function is defined in terms of the agent's history of interactions with its environment. This paper argues, via two examples, that the behavior problems can be avoided by formulating the utility function in two steps: 1) inferring a model of the environment from interactions, and 2) computing utility as a function of the environment model. Basing a utility function on a model that the agent must learn implies that the utility function must initially be expressed in terms of specifications to be matched to structures in the learned model. These specifications constitute prior assumptions about the environment so this approach will not work with arbitrary environments. But the approach should work for agents designed by humans to act in the physical world. The paper also addresses the issue of self-modifying agents and shows that if provided with the possibility to modify their utility functions agents will not choose to do so, under some usual assumptions.

  3. Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma.

    PubMed

    Ceriani, Luca; Martelli, Maurizio; Zinzani, Pier Luigi; Ferreri, Andrés J M; Botto, Barbara; Stelitano, Caterina; Gotti, Manuel; Cabras, Maria Giuseppina; Rigacci, Luigi; Gargantini, Livio; Merli, Francesco; Pinotti, Graziella; Mannina, Donato; Luminari, Stefano; Stathis, Anastasios; Russo, Eleonora; Cavalli, Franco; Giovanella, Luca; Johnson, Peter W M; Zucca, Emanuele

    2015-08-20

    The International Extranodal Lymphoma Study Group (IELSG) 26 study was designed to evaluate the role of (18)F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) in the management of primary mediastinal (thymic) large B-cell lymphoma (PMBCL). We examined the prognostic impact of functional PET parameters at diagnosis. Metabolic activity defined by the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) was measured on baseline 18FDG PET/CT following a standard protocol in a prospectively enrolled cohort of 103 PMBCL patients. All received combination chemoimmunotherapy with doxorubicin- and rituximab-based regimens; 93 had consolidation radiotherapy. Cutoff values were determined using the receiver-operating characteristic curve. At a median follow-up of 36 months, progression-free survival (PFS) and overall survival (OS) were 87% and 94%, respectively. In univariate analysis, elevated MTV and TLG were significantly associated with worse PFS and OS. Only TLG retained statistical significance for both OS (P = .001) and PFS (P < .001) in multivariate analysis. At 5 years, OS was 100% for patients with low TLG vs 80% for those with high TLG (P = .0001), whereas PFS was 99% vs 64%, respectively (P < .0001). TLG on baseline PET appeared to be a powerful predictor of PMBCL outcomes and warrants further validation as a biomarker. The IELSG 26 study was registered at www.clinicaltrials.gov as #NCT00944567.

  4. Multiphoton microscopy in defining liver function

    NASA Astrophysics Data System (ADS)

    Thorling, Camilla A.; Crawford, Darrell; Burczynski, Frank J.; Liu, Xin; Liau, Ian; Roberts, Michael S.

    2014-09-01

    Multiphoton microscopy is the preferred method when in vivo deep-tissue imaging is required. This review presents the application of multiphoton microscopy in defining liver function. In particular, multiphoton microscopy is useful in imaging intracellular events, such as mitochondrial depolarization and cellular metabolism in terms of NAD(P)H changes with fluorescence lifetime imaging microscopy. The morphology of hepatocytes can be visualized without exogenously administered fluorescent dyes by utilizing their autofluorescence and second harmonic generation signal of collagen, which is useful in diagnosing liver disease. More specific imaging, such as studying drug transport in normal and diseased livers are achievable, but require exogenously administered fluorescent dyes. If these techniques can be translated into clinical use to assess liver function, it would greatly improve early diagnosis of organ viability, fibrosis, and cancer.

  5. Defining Function in the Functional Medicine Model.

    PubMed

    Bland, Jeffrey

    2017-02-01

    In the functional medicine model, the word function is aligned with the evolving understanding that disease is an endpoint and function is a process. Function can move both forward and backward. The vector of change in function through time is, in part, determined by the unique interaction of an individual's genome with their environment, diet, and lifestyle. The functional medicine model for health care is concerned less with what we call the dysfunction or disease, and more about the dynamic processes that resulted in the person's dysfunction. The previous concept of functional somatic syndromes as psychosomatic in origin has now been replaced with a new concept of function that is rooted in the emerging 21st-century understanding of systems network-enabled biology.

  6. Spaces defined by the Paley function

    SciTech Connect

    Astashkin, S V; Semenov, E M

    2013-07-31

    The paper is concerned with Haar and Rademacher series in symmetric spaces, and also with the properties of spaces defined by the Paley function. In particular, the symmetric hull of the space of functions with uniformly bounded Paley function is found. Bibliography: 27 titles.

  7. Defining personal utility in genomics: A Delphi study.

    PubMed

    Kohler, J; Turbitt, E; Lewis, K L; Wilfond, B S; Jamal, L; Peay, H L; Biesecker, L G; Biesecker, B B

    2017-02-20

    Individual genome sequencing results are valued by patients in ways distinct from clinical utility. Such outcomes have been described as components of "personal utility," a concept that broadly encompasses patient-endorsed benefits, that is operationally defined as non-clinical outcomes. No empirical delineation of these outcomes has been reported. To address this gap, we administered a Delphi survey to adult participants in a NIH clinical exome study to extract the most highly endorsed outcomes constituting personal utility. Forty research participants responded to a Delphi survey to rate 35 items identified by a systematic literature review of personal utility. Two rounds of ranking resulted in 24 items that represented 14 distinct elements of personal utility. Elements most highly endorsed by participants were: increased self-knowledge, knowledge of "the condition," altruism, and anticipated coping. Our findings represent the first systematic effort to delineate elements of personal utility that may be used to anticipate participant expectation and inform genetic counseling prior to sequencing. The 24 items reported need to be studied further in additional clinical genome sequencing studies to assess generalizability in other populations. Further research will help to understand motivations and to predict the meaning and use of results.

  8. Speciation without Pre-Defined Fitness Functions.

    PubMed

    Gras, Robin; Golestani, Abbas; Hendry, Andrew P; Cristescu, Melania E

    2015-01-01

    The forces promoting and constraining speciation are often studied in theoretical models because the process is hard to observe, replicate, and manipulate in real organisms. Most models analyzed to date include pre-defined functions influencing fitness, leaving open the question of how speciation might proceed without these built-in determinants. To consider the process of speciation without pre-defined functions, we employ the individual-based ecosystem simulation platform EcoSim. The environment is initially uniform across space, and an evolving behavioural model then determines how prey consume resources and how predators consume prey. Simulations including natural selection (i.e., an evolving behavioural model that influences survival and reproduction) frequently led to strong and distinct phenotypic/genotypic clusters between which hybridization was low. This speciation was the result of divergence between spatially-localized clusters in the behavioural model, an emergent property of evolving ecological interactions. By contrast, simulations without natural selection (i.e., behavioural model turned off) but with spatial isolation (i.e., limited dispersal) produced weaker and overlapping clusters. Simulations without natural selection or spatial isolation (i.e., behaviour model turned off and high dispersal) did not generate clusters. These results confirm the role of natural selection in speciation by showing its importance even in the absence of pre-defined fitness functions.

  9. Considerations and Challenges in Defining Optimal Iron Utilization in Hemodialysis

    PubMed Central

    Pai, Amy Barton; Chan, Christopher T.; Coyne, Daniel W.; Hung, Adriana M.; Kovesdy, Csaba P.; Fishbane, Steven

    2015-01-01

    Trials raising concerns about erythropoiesis-stimulating agents, revisions to their labeling, and changes to practice guidelines and dialysis payment systems have provided strong stimuli to decrease erythropoiesis-stimulating agent use and increase intravenous iron administration in recent years. These factors have been associated with a rise in iron utilization, particularly among hemodialysis patients, and an unprecedented increase in serum ferritin concentrations. The mean serum ferritin concentration among United States dialysis patients in 2013 exceeded 800 ng/ml, with 18% of patients exceeding 1200 ng/ml. Although these changes are broad based, the wisdom of these practices is uncertain. Herein, we examine influences on and trends in intravenous iron utilization and assess the clinical trial, epidemiologic, and experimental evidence relevant to its safety and efficacy in the setting of maintenance dialysis. These data suggest a potential for harm from increasing use of parenteral iron in dialysis-dependent patients. In the absence of well powered, randomized clinical trials, available evidence will remain inadequate for making reliable conclusions about the effect of a ubiquitous therapy on mortality or other outcomes of importance to dialysis patients. Nephrology stakeholders have an urgent obligation to initiate well designed investigations of intravenous iron in order to ensure the safety of the dialysis population. PMID:25542967

  10. Considerations and challenges in defining optimal iron utilization in hemodialysis.

    PubMed

    Charytan, David M; Pai, Amy Barton; Chan, Christopher T; Coyne, Daniel W; Hung, Adriana M; Kovesdy, Csaba P; Fishbane, Steven

    2015-06-01

    Trials raising concerns about erythropoiesis-stimulating agents, revisions to their labeling, and changes to practice guidelines and dialysis payment systems have provided strong stimuli to decrease erythropoiesis-stimulating agent use and increase intravenous iron administration in recent years. These factors have been associated with a rise in iron utilization, particularly among hemodialysis patients, and an unprecedented increase in serum ferritin concentrations. The mean serum ferritin concentration among United States dialysis patients in 2013 exceeded 800 ng/ml, with 18% of patients exceeding 1200 ng/ml. Although these changes are broad based, the wisdom of these practices is uncertain. Herein, we examine influences on and trends in intravenous iron utilization and assess the clinical trial, epidemiologic, and experimental evidence relevant to its safety and efficacy in the setting of maintenance dialysis. These data suggest a potential for harm from increasing use of parenteral iron in dialysis-dependent patients. In the absence of well powered, randomized clinical trials, available evidence will remain inadequate for making reliable conclusions about the effect of a ubiquitous therapy on mortality or other outcomes of importance to dialysis patients. Nephrology stakeholders have an urgent obligation to initiate well designed investigations of intravenous iron in order to ensure the safety of the dialysis population.

  11. Defining and characterizing drug/compound function.

    PubMed

    Kenakin, Terry; Williams, Michael

    2014-01-01

    The receptor concept, now more than century old, remains the core concept in understanding the mechanisms of disease causality and drug action. Originally formulated in the early 1900s, receptor theory has evolved in both detail and complexity as the tools of molecular biology and increasingly sophisticated research technologies have facilitated the study of drug/ligand receptor interactions at the molecular level. The result has been a more detailed and nuanced understanding of the parameters of drug action that together with knowledge of the pleotropic nature of cellular targets and associated signaling pathways has reshaped the receptor concept. Added to the basic agonist/antagonist view of drug/ligand function, concepts like allosterism, inverse agonism, biased signaling and compound residence time have provided a broader understanding of compound-target interactions to better inform drug discovery efforts. The iteration of descriptive data from pharmacological experiments to provide generic indices of affinity and efficacy can now be used to predict expected drug/compound effects in other cell/organ systems where the sensitivity of the latter to drug effects (either via expression levels of cell surface receptors or variances in the efficiency with which those receptors are coupled to cytosolic metabolic processes) can be accommodated.

  12. Functional Relationships Between Risky and Riskless Multiattribute Utility Functions.

    DTIC Science & Technology

    1979-12-01

    theory and conjoint measurement theory form two major classes of models and assessment procedures to construct multiattribute utility functions. In...conjoint measurement theory a value function v is constructed which preserves ] preferences among riskless multiattributed outcomes. The risky utility ... utility theory and conjoint measurement theory form two major classes of models and assessment procedures to construct multi-attribute utility functions

  13. Defining Predictive Probability Functions for Species Sampling Models.

    PubMed

    Lee, Jaeyong; Quintana, Fernando A; Müller, Peter; Trippa, Lorenzo

    2013-01-01

    We review the class of species sampling models (SSM). In particular, we investigate the relation between the exchangeable partition probability function (EPPF) and the predictive probability function (PPF). It is straightforward to define a PPF from an EPPF, but the converse is not necessarily true. In this paper we introduce the notion of putative PPFs and show novel conditions for a putative PPF to define an EPPF. We show that all possible PPFs in a certain class have to define (unnormalized) probabilities for cluster membership that are linear in cluster size. We give a new necessary and sufficient condition for arbitrary putative PPFs to define an EPPF. Finally, we show posterior inference for a large class of SSMs with a PPF that is not linear in cluster size and discuss a numerical method to derive its PPF.

  14. Defining mental disorder. Exploring the 'natural function' approach

    PubMed Central

    2011-01-01

    Due to several socio-political factors, to many psychiatrists only a strictly objective definition of mental disorder, free of value components, seems really acceptable. In this paper, I will explore a variant of such an objectivist approach to defining metal disorder, natural function objectivism. Proponents of this approach make recourse to the notion of natural function in order to reach a value-free definition of mental disorder. The exploration of Christopher Boorse's 'biostatistical' account of natural function (1) will be followed an investigation of the 'hybrid naturalism' approach to natural functions by Jerome Wakefield (2). In the third part, I will explore two proposals that call into question the whole attempt to define mental disorder (3). I will conclude that while 'natural function objectivism' accounts fail to provide the backdrop for a reliable definition of mental disorder, there is no compelling reason to conclude that a definition cannot be achieved. PMID:21255405

  15. Defining mental disorder. Exploring the 'natural function' approach.

    PubMed

    Varga, Somogy

    2011-01-21

    Due to several socio-political factors, to many psychiatrists only a strictly objective definition of mental disorder, free of value components, seems really acceptable. In this paper, I will explore a variant of such an objectivist approach to defining metal disorder, natural function objectivism. Proponents of this approach make recourse to the notion of natural function in order to reach a value-free definition of mental disorder. The exploration of Christopher Boorse's 'biostatistical' account of natural function (1) will be followed an investigation of the 'hybrid naturalism' approach to natural functions by Jerome Wakefield (2). In the third part, I will explore two proposals that call into question the whole attempt to define mental disorder (3). I will conclude that while 'natural function objectivism' accounts fail to provide the backdrop for a reliable definition of mental disorder, there is no compelling reason to conclude that a definition cannot be achieved.

  16. Defining Integrals Over Connections in the Discretized Gravitational Functional Integrals

    NASA Astrophysics Data System (ADS)

    Khatsymovsky, V. M.

    Integration over connection type variables in the path integral for the discrete form of the first-order formulation of general relativity theory is studied. The result (a generalized function of the rest of variables of the type of tetrad or elementary areas) can be defined through its moments, i.e. integrals of it with the area tensor monomials. In our previous paper these moments have been defined by deforming integration contours in the complex plane as if we had passed to a Euclidean-like region. In this paper we define and evaluate the moments in the genuine Minkowski region. The distribution of interest resulting from these moments in this non-positively defined region contains the divergences. We prove that the latter contribute only to the singular (δ-function like) part of this distribution with support in the non-physical region of the complex plane of area tensors while in the physical region this distribution (usual function) confirms that defined in our previous paper which decays exponentially at large areas. Besides that, we evaluate the basic integrals over which the integral over connections in the general path integral can be expanded.

  17. 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.

  18. Defining functional DNA elements in the human genome.

    PubMed

    Kellis, Manolis; Wold, Barbara; Snyder, Michael P; Bernstein, Bradley E; Kundaje, Anshul; Marinov, Georgi K; Ward, Lucas D; Birney, Ewan; Crawford, Gregory E; Dekker, Job; Dunham, Ian; Elnitski, Laura L; Farnham, Peggy J; Feingold, Elise A; Gerstein, Mark; Giddings, Morgan C; Gilbert, David M; Gingeras, Thomas R; Green, Eric D; Guigo, Roderic; Hubbard, Tim; Kent, Jim; Lieb, Jason D; Myers, Richard M; Pazin, Michael J; Ren, Bing; Stamatoyannopoulos, John A; Weng, Zhiping; White, Kevin P; Hardison, Ross C

    2014-04-29

    With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease.

  19. Defining functional DNA elements in the human genome

    PubMed Central

    Kellis, Manolis; Wold, Barbara; Snyder, Michael P.; Bernstein, Bradley E.; Kundaje, Anshul; Marinov, Georgi K.; Ward, Lucas D.; Birney, Ewan; Crawford, Gregory E.; Dekker, Job; Dunham, Ian; Elnitski, Laura L.; Farnham, Peggy J.; Feingold, Elise A.; Gerstein, Mark; Giddings, Morgan C.; Gilbert, David M.; Gingeras, Thomas R.; Green, Eric D.; Guigo, Roderic; Hubbard, Tim; Kent, Jim; Lieb, Jason D.; Myers, Richard M.; Pazin, Michael J.; Ren, Bing; Stamatoyannopoulos, John A.; Weng, Zhiping; White, Kevin P.; Hardison, Ross C.

    2014-01-01

    With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease. PMID:24753594

  20. Multi-attribute preference functions. Health Utilities Index.

    PubMed

    Torrance, G W; Furlong, W; Feeny, D; Boyle, M

    1995-06-01

    Multi-attribute utility theory, an extension of conventional utility theory, can be applied to model preference scores for health states defined by multi-attribute health status classification systems. The type of preference independence among the attributes determines the type of preference function required: additive, multiplicative or multilinear. In addition, the type of measurement instrument used determines the type of preference score obtained: value or utility. Multi-attribute utility theory has been applied to 2 recently developed multi-attribute health status classification systems, the Health Utilities Index (HUI) Mark II and Mark III systems. Results are presented for the Mark II system, and ongoing research is described for the Mark III system. The theory is also discussed in the context of other well known multi-attribute systems. The HUI system is an efficient method of determining a general public-based utility score for a specified health outcome or for the health status of an individual. In clinical populations, the scores can be used to provide a single summary measure of health-related quality of life. In cost-utility analyses, the scores can be used as quality weights for calculating quality-adjusted life years. In general populations, the measure can be used as quality weights for determining population health expectancy.

  1. Incidence of utilization- and symptom-defined COPD exacerbations in hospital- and population-recruited patients

    PubMed Central

    Erdal, Marta; Johannessen, Ane; Eagan, Tomas Mikal; Bakke, Per; Gulsvik, Amund; Grønseth, Rune

    2016-01-01

    Objectives The objectives of this study were to estimate the impact of recruitment source and outcome definition on the incidence of acute exacerbations of COPD (AECOPD) and explore possible predictors of AECOPD. Patients and methods During a 1-year follow-up, we performed a baseline visit and four telephone interviews of 81 COPD patients and 132 controls recruited from a population-based survey and 205 hospital-recruited COPD patients. Both a definition based on health care utilization and a symptom-based definition of AECOPD were applied. For multivariate analyses, we chose a negative binomial regression model. Results COPD patients from the population- and hospital-based samples experienced on average 0.4 utilization-defined and 2.9 symptom-defined versus 1.0 and 5.9 annual exacerbations, respectively. The incidence rate ratios for utilization-defined AECOPD were 2.45 (95% CI 1.22–4.95), 3.43 (95% CI 1.59–7.38), and 5.67 (95% CI 2.58–12.48) with Global Initiative on Obstructive Lung Disease spirometric stages II, III, and IV, respectively. The corresponding incidence rate ratios for the symptom-based definition were 3.08 (95% CI 1.96–4.84), 3.45 (95% CI 1.92–6.18), and 4.00 (95% CI 2.09–7.66). Maintenance therapy (regular long-acting muscarinic antagonists, long-acting beta-2 agonists, inhaled corticosteroids, or theophylline) also increased the risk of AECOPD with both exacerbation definitions (incidence rate ratios 1.65 and 1.73, respectively). The risk of AECOPD was 59%–78% higher in the hospital sample than in the population sample. Conclusion If externally valid conclusions are to be made regarding incidence and predictors of AECOPD, studies should be based on general population samples or adjustments should be made on account of a likely higher incidence in other samples. Likewise, the effect of different AECOPD definitions should be taken into consideration. PMID:27621614

  2. Proliferation status defines functional properties of endothelial cells.

    PubMed

    Lipps, Christoph; Badar, Muhammad; Butueva, Milada; Dubich, Tatyana; Singh, Vivek Vikram; Rau, Sophie; Weber, Axel; Kracht, Michael; Köster, Mario; May, Tobias; Schulz, Thomas F; Hauser, Hansjörg; Wirth, Dagmar

    2017-04-01

    Homeostasis of solid tissue is characterized by a low proliferative activity of differentiated cells while special conditions like tissue damage induce regeneration and proliferation. For some cell types it has been shown that various tissue-specific functions are missing in the proliferating state, raising the possibility that their proliferation is not compatible with a fully differentiated state. While endothelial cells are important players in regenerating tissue as well as in the vascularization of tumors, the impact of proliferation on their features remains elusive. To examine cell features in dependence of proliferation, we established human endothelial cell lines in which proliferation is tightly controlled by a doxycycline-dependent, synthetic regulatory unit. We observed that uptake of macromolecules and establishment of cell-cell contacts was more pronounced in the growth-arrested state. Tube-like structures were formed in vitro in both proliferating and non-proliferating conditions. However, functional vessel formation upon transplantation into immune-compromised mice was restricted to the proliferative state. Kaposi's sarcoma-associated herpes virus (KSHV) infection resulted in reduced expression of endothelial markers. Upon transplantation of infected cells, drastic differences were observed: proliferation arrested cells acquired a high migratory activity while the proliferating counterparts established a tumor-like phenotype, similar to Kaposi Sarcoma lesions. The study gives evidence that proliferation governs endothelial functions. This suggests that several endothelial functions are differentially expressed during angiogenesis. Moreover, since proliferation defines the functional properties of cells upon infection with KSHV, this process crucially affects the fate of virus-infected cells.

  3. Utility of cheiloscopy, rugoscopy, and dactyloscopy for human identification in a defined cohort

    PubMed Central

    Mutalik, Vimi S.; Menon, Aparna; Jayalakshmi, N.; Kamath, Asha; Raghu, A. R.

    2013-01-01

    Background: Identification is of paramount importance in any forensic investigation. Positive identification of living or deceased using distinctive traits is a cornerstone of forensic science. The uniqueness of these patterns and subtle distinction between traits has offered worthy supplemental tools in establishing the true nature of facts. Aim: The first aim of our study was to determine the most common pattern of lip prints, palatal rugae, and finger prints in the study subjects. Secondly, to determine if any specific pattern of lip print, palatal rugae, or the finger print concurs in individuals, and thereby establish a database of these prototypes for human identification from a defined cohort. Materials and Methods: The sample size comprised 100 female students of a dental college staying together in the hostel. Lip prints were recorded on a white bond sheet using lipstick, palatal rugae on dental casts, and finger prints using printer's blue ink. Results: Our observation suggested that the reticular pattern of lip print, the wavy pattern of palatal rugae, and the loop pattern of finger prints were the predominant patterns. Correlation of the three parameters did not reveal significant differences. Conclusions: This approach of human identification utilizing conventional techniques and relevant parameters is pertinent in defined groups. However, larger representative sample with robust analytical tools may provide a necessary blueprint of human identification. PMID:23960407

  4. Reconciling resource utilization and resource selection functions

    USGS Publications Warehouse

    Hooten, Mevin B.; Hanks, Ephraim M.; Johnson, Devin S.; Alldredge, Mat W.

    2013-01-01

    Summary: 1. Analyses based on utilization distributions (UDs) have been ubiquitous in animal space use studies, largely because they are computationally straightforward and relatively easy to employ. Conventional applications of resource utilization functions (RUFs) suggest that estimates of UDs can be used as response variables in a regression involving spatial covariates of interest. 2. It has been claimed that contemporary implementations of RUFs can yield inference about resource selection, although to our knowledge, an explicit connection has not been described. 3. We explore the relationships between RUFs and resource selection functions from a hueristic and simulation perspective. We investigate several sources of potential bias in the estimation of resource selection coefficients using RUFs (e.g. the spatial covariance modelling that is often used in RUF analyses). 4. Our findings illustrate that RUFs can, in fact, serve as approximations to RSFs and are capable of providing inference about resource selection, but only with some modification and under specific circumstances. 5. Using real telemetry data as an example, we provide guidance on which methods for estimating resource selection may be more appropriate and in which situations. In general, if telemetry data are assumed to arise as a point process, then RSF methods may be preferable to RUFs; however, modified RUFs may provide less biased parameter estimates when the data are subject to location error.

  5. Role of motor unit structure in defining function

    NASA Technical Reports Server (NTRS)

    Monti, R. J.; Roy, R. R.; Edgerton, V. R.

    2001-01-01

    Motor units, defined as a motoneuron and all of its associated muscle fibers, are the basic functional units of skeletal muscle. Their activity represents the final output of the central nervous system, and their role in motor control has been widely studied. However, there has been relatively little work focused on the mechanical significance of recruiting variable numbers of motor units during different motor tasks. This review focuses on factors ranging from molecular to macroanatomical components that influence the mechanical output of a motor unit in the context of the whole muscle. These factors range from the mechanical properties of different muscle fiber types to the unique morphology of the muscle fibers constituting a motor unit of a given type and to the arrangement of those motor unit fibers in three dimensions within the muscle. We suggest that as a result of the integration of multiple levels of structural and physiological levels of organization, unique mechanical properties of motor units are likely to emerge. Copyright 2001 John Wiley & Sons, Inc.

  6. Flexible associations between Pocillopora corals and Symbiodinium limit utility of symbiosis ecology in defining species

    NASA Astrophysics Data System (ADS)

    Cunning, R.; Glynn, P. W.; Baker, A. C.

    2013-09-01

    Corals in the genus Pocillopora are the primary framework builders of eastern tropical Pacific (ETP) reefs. These corals typically associate with algal symbionts (genus Symbiodinium) in clade C and/or D, with clade D associations having greater thermal tolerance and resistance to bleaching. Recently, cryptic "species" delineations within both Pocillopora and Symbiodinium have been suggested, with host-symbiont specificity used as a supporting taxonomic character in both genera. In particular, it has been suggested that three lineages of Pocillopora (types 1-3) exist in the ETP, of which type 1 is the exclusive host of heat-tolerant Symbiodinium D1. This host specificity has been used to support the species name " Symbiodinium glynni" for this symbiont. To validate these host-symbiont relationships and their taxonomic utility, we identified Pocillopora types and their associated Symbiodinium at three sites in the ETP. We found greater flexibility in host-symbiont combinations than previously reported, with both Pocillopora types 1 and 3 able to host and be dominated by Symbiodinium in clade C or D. The prevalence of certain combinations did vary among sites, showing that a gradient of specificity exists which may be mediated by evolutionary relationships and environmental disturbance history. However, these results limit the utility of apparent host-symbiont specificity (which may have been a result of undersampling) in defining species boundaries in either corals or Symbiodinium. They also suggest that a greater diversity of corals may benefit from the thermal tolerance of clade D symbionts, affirming the need to conserve Pocillopora across its entire geographic and environmental range.

  7. Distress syndromes, illness behavior, access to care and medical utilization in a defined population.

    PubMed

    Mechanic, D; Cleary, P D; Greenley, J R

    1982-04-01

    This article examines the use of general medical services in a representative sample from a defined geographic area and in a sample of persons seeking psychiatric care from the same area. Psychiatric patients made 100 per cent more general medical care visits in the retrospective period and 83 per cent more in the prospective period than persons who did not seek mental health care. The analysis focuses on the determinants in general medical care use between those who sought mental health care and those who did not. The first hypothesis is that physical symptoms and dysfunction concomitant with psychologic disorder explain the difference. The second argues that the association is a product of help-seeking orientations and illness behavior. The third focuses on variations due to differences in access. The first two types of factors are the most important. Using sex, physical symptoms and illness behavior measures, we explain 50 per cent of the differences in retrospective utilization and 40 per cent of the differences in prospective data.

  8. Defining and Applying a Functionality Approach to Intellectual Disability

    ERIC Educational Resources Information Center

    Luckasson, R.; Schalock, R. L.

    2013-01-01

    Background: The current functional models of disability do not adequately incorporate significant changes of the last three decades in our understanding of human functioning, and how the human functioning construct can be applied to clinical functions, professional practices and outcomes evaluation. Methods: The authors synthesise current…

  9. Decompositions of Multiattribute Utility Functions Based on Convex Dependence.

    DTIC Science & Technology

    1982-03-01

    Member) Multiattribute utility theory Preference models Decision analysis Approximations Convex dependence 20. 0.STRACT (Continue an reverse d.* It...DECOMPOSITIONS OF MULTIATTRIBUTE UTILITY FUNCTIONS BASED ON CONVEX DEPENDENCE Hiroyuki Tamura* and Yutaka Nakamura** *Department of Precision Engineering...Decompositions of Multiattribute Utility Technical Report Functions Based on Convex Dependence 6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(e) S. CONTRACT O

  10. Global measures: utility in defining and measuring treatment response in dementia.

    PubMed

    Reisberg, Barry

    2007-06-01

    Global measures used in treatment trials in dementia encompass two distinct categories: (1) clinician's interview-based global severity scales, and (2) clinician's interview-based global change scales. The global severity scales that have been used include: the Clinical Dementia Rating (CDR) and the related CDR-sum of boxes (CDR-SB), the Global Deterioration Scale (GDS), and the Functional Assessment Staging (FAST) procedure. The global severity scales are clearly useful in subject categorization in treatment trials, in part because they are relatively free of many of the sociocultural biases inherent in mental status and psychometric descriptors. Global severity scales can also be used to demonstrate therapeutic efficacy in terms of the general progression of the dementia process. These measures have also proven to be useful in sensitively assessing pharmacotherapeutic effects in Alzheimer's disease (AD) treatment trials. For example, in pivotal trials: (1) in Mild to Moderate AD, the GDS has shown significant change in response to medication, whereas the results on the Mini-mental State Examination (MMSE) were not significant, and (2) in Moderate to Severe AD, the FAST has shown significant pharmacotherapeutic efficacy, whereas the results using the MMSE were not significant. The global change scales employed in dementia trials differ widely in assessment methodology. Clinical Global Impressions of Change (CGIC) scales do not have defined methodologies, whereas Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) scales are much more elaborate. The CIBIC-Plus procedures require an independent clinician assessment and can provide independent, comprehensive evidence of therapeutic efficacy. The CIBIC-Plus procedure may also be useful in sensitively assessing efficacy in future prevention trials, for example in subjects with Subjective Cognitive Impairment. For Mild Cognitive Impairment (MCI), global severity scales already appear to be

  11. Collimator Magnet with Functionally Defined Profile for Ion Implantation

    SciTech Connect

    Nicolaescu, Dan; Gotoh, Yasuhito; Sakai, Shigeki; Ishikawa, Junzo

    2011-01-07

    Advanced implantation systems used for semiconductor processing should have high precision of ion beam collimation (+/-0.1 deg and better) and wide beam aperture (400 mm and more). Typical arrangements of ion implantation systems include beam scanning (BSM) and collimator magnets (CM). Standard collimator magnets have limited precision of beam collimation due to magnetic poles that have piecewise circular profile. This study proposes a novel ''constant sum angle collimator magnet''(CSACM) with non-circular magnetic pole profile. Angles of incidence {alpha}{sub i} and exit {alpha}{sub e} are defined as angles between ion trajectory and local normal to CM input/output magnetic pole edge. Profile of the CSACM is defined as having constant algebraic sum {alpha}{sub i}+{alpha}{sub e} = const for every ion trajectory of the scanned beam, in addition to ''usual'' beam collimation. An iterative procedure allows improve CSACM taking into account magnetic fringe field effects. Simulation results prove that CSACM assures precise beam collimation in two orthogonal planes. Circular approximations for CSACM magnetic poles are proposed. The model may be further developed for global design of the ion beam line (BSM+CM) and for taking into account space-charge effects.

  12. Integral Representation for Functionals Defined on SBDp in Dimension Two

    NASA Astrophysics Data System (ADS)

    Conti, Sergio; Focardi, Matteo; Iurlano, Flaviana

    2017-03-01

    We prove an integral representation result for functionals with growth conditions which give coercivity on the space {SBD^p(Ω)}, for {Ωsubset R2}, which is a bounded open Lipschitz set, and {pin(1,∞)}. The space SBD p of functions whose distributional strain is the sum of an L p part and a bounded measure supported on a set of finite H1}-dimensional measure appears naturally in the study of fracture and damage models. Our result is based on the construction of a local approximation by W 1, p functions. We also obtain a generalization of Korn's inequality in the SBD p setting.

  13. Defining the functional traits that drive bacterial decomposer community productivity.

    PubMed

    Evans, Rachael; Alessi, Anna M; Bird, Susannah; McQueen-Mason, Simon J; Bruce, Neil C; Brockhurst, Michael A

    2017-03-21

    Microbial communities are essential to a wide range of ecologically and industrially important processes. To control or predict how these communities function, we require a better understanding of the factors which influence microbial community productivity. Here, we combine functional resource use assays with a biodiversity-ecosystem functioning (BEF) experiment to determine whether the functional traits of constituent species can be used to predict community productivity. We quantified the abilities of 12 bacterial species to metabolise components of lignocellulose and then assembled these species into communities of varying diversity and composition to measure their productivity growing on lignocellulose, a complex natural substrate. A positive relationship between diversity and community productivity was caused by a selection effect whereby more diverse communities were more likely to contain two species that significantly improved community productivity. Analysis of functional traits revealed that the observed selection effect was primarily driven by the abilities of these species to degrade β-glucan. Our results indicate that by identifying the key functional traits underlying microbial community productivity we could improve industrial bioprocessing of complex natural substrates.The ISME Journal advance online publication, 21 March 2017; doi:10.1038/ismej.2017.22.

  14. Defining inhibitory neurone function in respiratory circuits: opportunities with optogenetics?

    PubMed

    Abdala, Ana Paula; Paton, Julian F R; Smith, Jeffrey C

    2015-07-15

    Pharmacological and mathematical modelling studies support the view that synaptic inhibition in mammalian brainstem respiratory circuits is essential for generating normal and stable breathing movements. GABAergic and glycinergic neurones are known components of these circuits but their precise functional roles have not been established, especially within key microcircuits of the respiratory pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes involved in phasic control of respiratory pump and airway muscles. Here, we review briefly current concepts of relevant complexities of inhibitory synapses and the importance of synaptic inhibition in the operation of these microcircuits. We highlight results and limitations of classical pharmacological studies that have suggested critical functions of synaptic inhibition. We then explore the potential opportunities for optogenetic strategies that represent a promising new approach for interrogating function of inhibitory circuits, including a hypothetical wish list for optogenetic approaches to allow expedient application of this technology. We conclude that recent technical advances in optogenetics should provide a means to understand the role of functionally select and regionally confined subsets of inhibitory neurones in key respiratory circuits such as those in the pre-BötC and BötC.

  15. Defining an olfactory receptor function in airway smooth muscle cells

    PubMed Central

    Aisenberg, William H.; Huang, Jessie; Zhu, Wanqu; Rajkumar, Premraj; Cruz, Randy; Santhanam, Lakshmi; Natarajan, Niranjana; Yong, Hwan Mee; De Santiago, Breann; Oh, Jung Jin; Yoon, A-Rum; Panettieri, Reynold A.; Homann, Oliver; Sullivan, John K.; Liggett, Stephen B.; Pluznick, Jennifer L.; An, Steven S.

    2016-01-01

    Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells. In a heterologous expression system, OR51E2 trafficked readily to the cell surface and showed ligand selectivity and sensitivity to the short chain fatty acids (SCFAs) acetate and propionate. These endogenous metabolic byproducts of the gut microbiota slowed the rate of cytoskeletal remodeling, as well as the proliferation of human ASM cells. These cellular responses in vitro were found in ASM from non-asthmatics and asthmatics, and were absent in OR51E2-deleted primary human ASM. These results demonstrate a novel chemo-mechanical signaling network in the ASM and serve as a proof-of-concept that a specific receptor of the gut-lung axis can be targeted to treat airflow obstruction in asthma. PMID:27905542

  16. Defining an olfactory receptor function in airway smooth muscle cells.

    PubMed

    Aisenberg, William H; Huang, Jessie; Zhu, Wanqu; Rajkumar, Premraj; Cruz, Randy; Santhanam, Lakshmi; Natarajan, Niranjana; Yong, Hwan Mee; De Santiago, Breann; Oh, Jung Jin; Yoon, A-Rum; Panettieri, Reynold A; Homann, Oliver; Sullivan, John K; Liggett, Stephen B; Pluznick, Jennifer L; An, Steven S

    2016-12-01

    Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells. In a heterologous expression system, OR51E2 trafficked readily to the cell surface and showed ligand selectivity and sensitivity to the short chain fatty acids (SCFAs) acetate and propionate. These endogenous metabolic byproducts of the gut microbiota slowed the rate of cytoskeletal remodeling, as well as the proliferation of human ASM cells. These cellular responses in vitro were found in ASM from non-asthmatics and asthmatics, and were absent in OR51E2-deleted primary human ASM. These results demonstrate a novel chemo-mechanical signaling network in the ASM and serve as a proof-of-concept that a specific receptor of the gut-lung axis can be targeted to treat airflow obstruction in asthma.

  17. Mutations defining functional regions of the superantigen staphylococcal enterotoxin B

    PubMed Central

    1992-01-01

    Staphylococcal enterotoxin B (SEB) is both a superantigen and toxin. As a superantigen, SEB can bind to major histocompatibility complex (MHC) class II molecules to form a ligand for alpha/beta T cell receptors bearing particular V beta elements. As a toxin, SEB causes rapid weight loss in mice sometimes leading to death. We show here that both of these functions map to the NH2-terminal portion of the toxin. Three regions were identified: one important in MHC class II binding, one in T cell recognition, and one in both functions. These results support the conclusion that the toxicity of SEB is related to massive T cell stimulation and release of cytokine mediators and show that the residues interacting with MHC and the T cell receptor are intertwined. PMID:1370682

  18. Intestinal anastomotic injury alters spatially defined microbiome composition and function

    PubMed Central

    2014-01-01

    Background When diseased intestine (i.e., from colon cancer, diverticulitis) requires resection, its reconnection (termed anastomosis) can be complicated by non-healing of the newly joined intestine resulting in spillage of intestinal contents into the abdominal cavity (termed anastomotic leakage). While it is suspected that the intestinal microbiota have the capacity to both accelerate and complicate anastomotic healing, the associated genotypes and functions have not been characterized. Results Using 16S rRNA amplicon sequencing of samples collected on the day of surgery (postoperative day 0 (POD0)) and the 6th day following surgery (postoperative day 0 (POD6)), we analyzed the changes in luminal versus tissue-associated microbiota at anastomotic sites created in the colon of rats. Results indicated that anastomotic injury induced significant changes in the anastomotic tissue-associated microbiota with minimal differences in the luminal microbiota. The most striking difference was a 500-fold and 200-fold increase in the relative abundance of Enterococcus and Escherichia/Shigella, respectively. Functional profiling predicted the predominance of bacterial virulence-associated pathways in post-anastomotic tissues, including production of hemolysin, cytolethal toxins, fimbriae, invasins, cytotoxic necrotizing factors, and coccolysin. Conclusion Taken together, our results suggest that compositional and functional changes accompany anastomotic tissues and may potentially accelerate or complicate anastomotic healing. PMID:25250176

  19. Defining functional interactions during biogenesis of epithelial junctions

    PubMed Central

    Erasmus, J. C.; Bruche, S.; Pizarro, L.; Maimari, N.; Pogglioli, T.; Tomlinson, C.; Lees, J.; Zalivina, I.; Wheeler, A.; Alberts, A.; Russo, A.; Braga, V. M. M.

    2016-01-01

    In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell–cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases. PMID:27922008

  20. Lacunary strongly (A, φ)I-convergent sequences defined by a modulus function

    NASA Astrophysics Data System (ADS)

    Gumus, Hafize; Savas, Ekrem

    2013-10-01

    In this paper we introduce and study some new sequences of lacunary strongly (A, φ)I-convergent sequences defined by a modulus function. They are defined using by a φ-function, a A = (ank) real matrix and an ideal I of positive integers. We define Nθ(A,φ,f)I and Sθ(A,φ)I spaces and study their relation.

  1. Defining the boundaries: structure and function of LOB domain proteins.

    PubMed

    Majer, Christine; Hochholdinger, Frank

    2011-01-01

    The plant-specific LBD (Lateral Organ Boundaries Domain) gene family is essential in the regulation of plant lateral organ development and is involved in the regulation of anthocyanin and nitrogen metabolism. LBD proteins contain a characteristic LOB domain composed of a C-motif required for DNA-binding, a conserved glycine residue, and a leucine-zipper-like sequence required for protein-protein interactions. Recently, several LBD genes associated with mutant phenotypes related to almost all aspects of plant development, including embryo, root, leaf, and inflorescence development have been functionally characterized. These novel insights contribute to a better understanding of the molecular definition of boundaries between organs or boundaries between organs and meristems and the regulation of these processes by environmental cues and phytohormones.

  2. Validation and Error in Multiplicative Utility Functions

    DTIC Science & Technology

    1978-12-01

    main effect plans for asynnetrlcal factorial experiments. Technometrtcs, 1962, 4^, 21-46. Anderson, N. H. Information integration theory : a brief...an environment in which graduate students may receive training in research theory , design and methodology through active participation with senior...multlattribute utility model. The methods are a Keeney-Raiffa (1976) procedure, SMART (Edwards, 1977), a social judgment theory (SJT) based regression

  3. Defining functional biomes and monitoring their change globally.

    PubMed

    Higgins, Steven I; Buitenwerf, Robert; Moncrieff, Glenn R

    2016-11-01

    Biomes are important constructs for organizing understanding of how the worlds' major terrestrial ecosystems differ from one another and for monitoring change in these ecosystems. Yet existing biome classification schemes have been criticized for being overly subjective and for explicitly or implicitly invoking climate. We propose a new biome map and classification scheme that uses information on (i) an index of vegetation productivity, (ii) whether the minimum of vegetation activity is in the driest or coldest part of the year, and (iii) vegetation height. Although biomes produced on the basis of this classification show a strong spatial coherence, they show little congruence with existing biome classification schemes. Our biome map provides an alternative classification scheme for comparing the biogeochemical rates of terrestrial ecosystems. We use this new biome classification scheme to analyse the patterns of biome change observed over recent decades. Overall, 13% to 14% of analysed pixels shifted in biome state over the 30-year study period. A wide range of biome transitions were observed. For example, biomes with tall vegetation and minimum vegetation activity in the cold season shifted to higher productivity biome states. Biomes with short vegetation and low seasonality shifted to seasonally moisture-limited biome states. Our findings and method provide a new source of data for rigorously monitoring global vegetation change, analysing drivers of vegetation change and for benchmarking models of terrestrial ecosystem function.

  4. Formation of Well-Defined, Functional Nanotubes via Osmotically Induced Shape Transformation of Biodegradable Polymersomes

    PubMed Central

    2016-01-01

    Polymersomes are robust, versatile nanostructures that can be tailored by varying the chemical structure of copolymeric building blocks, giving control over their size, shape, surface chemistry, and membrane permeability. In particular, the generation of nonspherical nanostructures has attracted much attention recently, as it has been demonstrated that shape affects function in a biomedical context. Until now, nonspherical polymersomes have only been constructed from nondegradable building blocks, hampering a detailed investigation of shape effects in nanomedicine for this category of nanostructures. Herein, we demonstrate the spontaneous elongation of spherical polymersomes comprising the biodegradable copolymer poly(ethylene glycol)-b-poly(d,l-lactide) into well-defined nanotubes. The size of these tubes is osmotically controlled using dialysis, which makes them very easy to prepare. To confirm their utility for biomedical applications, we have demonstrated that, alongside drug loading, functional proteins can be tethered to the surface utilizing bio-orthogonal “click” chemistry. In this way the present findings establish a novel platform for the creation of biocompatible, high-aspect ratio nanoparticles for biomedical research. PMID:27374777

  5. The Use of More Realistic Utility Functions in Educational Applications.

    ERIC Educational Resources Information Center

    Novick, Melvin R.; Lindley, Dennis V.

    1978-01-01

    The use of some very simple loss or utility functions in educational evaluation has recently been advocated by Gross and Su, Petersen and Novick, and Petersen. This paper demonstrates that more realistic utility functions can easily be used and may be preferable in some applications. (Author/CTM)

  6. An Empirical Assessment of the Form of Utility Functions

    ERIC Educational Resources Information Center

    Kirby, Kris N.

    2011-01-01

    Utility functions, which relate subjective value to physical attributes of experience, are fundamental to most decision theories. Seven experiments were conducted to test predictions of the most widely assumed mathematical forms of utility (power, log, and negative exponential), and a function proposed by Rachlin (1992). For pairs of gambles for…

  7. Stability Analysis and Stabilization of Nonlinear Systems via Locally Defined Density Functions

    NASA Astrophysics Data System (ADS)

    Masubuchi, Izumi

    This paper considers local stability analysis of nonlinear systems with deriving a positively invariant set based on the Rantzer's stability theory by using density functions. We define a notion of locally defined density functions around an equilibrium that give monotonously increasing positive measures near the equilibrium of a nonlinear system. Under certain assumptions, it is shown that some level set of a locally defined density function is a positively invariant set where almost all of the system trajectories converge to the equilibrium. We also mention an SOS (sum-of-squares) formulation for synthesis of a nonlinear gain via locally defined density functions.

  8. Defining core issues in utilizing information technology to improve access: evaluation and research agenda.

    PubMed

    Jackson, George L; Krein, Sarah L; Alverson, Dale C; Darkins, Adam W; Gunnar, William; Harada, Nancy D; Helfrich, Christian D; Houston, Thomas K; Klobucar, Thomas F; Nazi, Kim M; Poropatich, Ronald K; Ralston, James D; Bosworth, Hayden B

    2011-11-01

    The Department of Veterans Affairs (VA) has been at the vanguard of information technology (IT) and use of comprehensive electronic health records. Despite the widespread use of health IT in the VA, there are still a variety of key questions that need to be answered in order to maximize the utility of IT to improve patient access to quality services. This paper summarizes the potential of IT to enhance healthcare access, key gaps in current evidence linking IT and access, and methodologic challenges for related research. We also highlight four key issues to be addressed when implementing and evaluating the impact of IT interventions on improving access to quality care: 1) Understanding broader needs/perceptions of the Veteran population and their caregivers regarding use of IT to access healthcare services and related information. 2) Understanding individual provider/clinician needs/perceptions regarding use of IT for patient access to healthcare. 3) System/Organizational issues within the VA and other organizations related to the use of IT to improve access. 4) IT integration and information flow with non-VA entities. While the VA is used as an example, the issues are salient for healthcare systems that are beginning to take advantage of IT solutions.

  9. Functional bioassays utilizing zooplankton: A comparison

    SciTech Connect

    McNaught, D.C.

    1989-01-01

    Functional zooplankton bioassays based on ingestion, reproduction and respiration are described, with methods for a new ingestion bioassay included. All bioassays are compared using three indices, including the variability of controls, the range of experimental responses, and a listing of contaminants causing inhibition/stimulation of response. The ingestion bioassay showed the greatest range of response, and was sensitive to pesticides, PCBs and heavy metals. It was also commonly characterized by a hormesis response. The reproduction bioassay showed the lowest variability, illustrated a reduced range of response, and was sensitive to nutrients and heavy metals. In one study, the respiration bioassay was sensitive only to PCBs.

  10. Defining a Model for Mitochondrial Function in mESC Differentiation

    EPA Science Inventory

    Defining a Model for Mitochondrial Function in mESC DifferentiationDefining a Model for Mitochondrial Function in mESC Differentiation Differentiating embryonic stem cells (ESCs) undergo mitochondrial maturation leading to a switch from a system dependent upon glycolysis to a re...

  11. Exploring utility function in utility management: an evaluating method of library preservation.

    PubMed

    Yan, Bin; Shi, Feng; Yu, Rui-Qiang

    2013-12-01

    In order to seek a new method of book evaluation and realize book resources sharing among the regional university libraries, we think that library should collect books of the high utility value in the case of limited funds. We proposed a changing Bellman equation as a utility function and used the explicit functions of the book usage factor and the book usage half-life derived from the utility function as an evaluating method of the collecting books. The results from empirical data given some conclusions such as the varieties diversity, the collected risk, the tendencies of reading varieties, species continuity and so on and a librarian can use the utility management to supplement the collections management.

  12. Optimal Wonderful Life Utility Functions in Multi-Agent Systems

    NASA Technical Reports Server (NTRS)

    Wolpert, David H.; Tumer, Kagan; Swanson, Keith (Technical Monitor)

    2000-01-01

    The mathematics of Collective Intelligence (COINs) is concerned with the design of multi-agent systems so as to optimize an overall global utility function when those systems lack centralized communication and control. Typically in COINs each agent runs a distinct Reinforcement Learning (RL) algorithm, so that much of the design problem reduces to how best to initialize/update each agent's private utility function, as far as the ensuing value of the global utility is concerned. Traditional team game solutions to this problem assign to each agent the global utility as its private utility function. In previous work we used the COIN framework to derive the alternative Wonderful Life Utility (WLU), and experimentally established that having the agents use it induces global utility performance up to orders of magnitude superior to that induced by use of the team game utility. The WLU has a free parameter (the clamping parameter) which we simply set to zero in that previous work. Here we derive the optimal value of the clamping parameter, and demonstrate experimentally that using that optimal value can result in significantly improved performance over that of clamping to zero, over and above the improvement beyond traditional approaches.

  13. The evolution of utility functions and psychological altruism.

    PubMed

    Clavien, Christine; Chapuisat, Michel

    2016-04-01

    Numerous studies show that humans tend to be more cooperative than expected given the assumption that they are rational maximizers of personal gain. As a result, theoreticians have proposed elaborated formal representations of human decision-making, in which utility functions including "altruistic" or "moral" preferences replace the purely self-oriented "Homo economicus" function. Here we review mathematical approaches that provide insights into the mathematical stability of alternative utility functions. Candidate utility functions may be evaluated with help of game theory, classical modeling of social evolution that focuses on behavioral strategies, and modeling of social evolution that focuses directly on utility functions. We present the advantages of the latter form of investigation and discuss one surprisingly precise result: "Homo economicus" as well as "altruistic" utility functions are less stable than a function containing a preference for the common welfare that is only expressed in social contexts composed of individuals with similar preferences. We discuss the contribution of mathematical models to our understanding of human other-oriented behavior, with a focus on the classical debate over psychological altruism. We conclude that human can be psychologically altruistic, but that psychological altruism evolved because it was generally expressed towards individuals that contributed to the actor's fitness, such as own children, romantic partners and long term reciprocators.

  14. Differential Item Functioning Detection across Two Methods of Defining Group Comparisons: Pairwise and Composite Group Comparisons

    ERIC Educational Resources Information Center

    Sari, Halil Ibrahim; Huggins, Anne Corinne

    2015-01-01

    This study compares two methods of defining groups for the detection of differential item functioning (DIF): (a) pairwise comparisons and (b) composite group comparisons. We aim to emphasize and empirically support the notion that the choice of pairwise versus composite group definitions in DIF is a reflection of how one defines fairness in DIF…

  15. Controlled Covalent Functionalization of Thermally Reduced Graphene Oxide To Generate Defined Bifunctional 2D Nanomaterials

    PubMed Central

    Faghani, Abbas; Donskyi, Ievgen S.; Fardin Gholami, Mohammad; Ziem, Benjamin; Lippitz, Andreas; Unger, Wolfgang E. S.; Böttcher, Christoph; Rabe, Jürgen P.

    2017-01-01

    Abstract A controlled, reproducible, gram‐scale method is reported for the covalent functionalization of graphene sheets by a one‐pot nitrene [2+1] cycloaddition reaction under mild conditions. The reaction between commercially available 2,4,6‐trichloro‐1,3,5‐triazine and sodium azide with thermally reduced graphene oxide (TRGO) results in defined dichlorotriazine‐functionalized sheets. The different reactivities of the chlorine substituents on the functionalized graphene allow stepwise post‐modification by manipulating the temperature. This new method provides unique access to defined bifunctional 2D nanomaterials, as exemplified by chiral surfaces and multifunctional hybrid architectures. PMID:28165179

  16. A Review of Functional Motifs Utilized by Viruses

    PubMed Central

    Sobhy, Haitham

    2016-01-01

    Short linear motifs (SLiM) are short peptides that facilitate protein function and protein-protein interactions. Viruses utilize these motifs to enter into the host, interact with cellular proteins, or egress from host cells. Studying functional motifs may help to predict protein characteristics, interactions, or the putative cellular role of a protein. In virology, it may reveal aspects of the virus tropism and help find antiviral therapeutics. This review highlights the recent understanding of functional motifs utilized by viruses. Special attention was paid to the function of proteins harboring these motifs, and viruses encoding these proteins. The review highlights motifs involved in (i) immune response and post-translational modifications (e.g., ubiquitylation, SUMOylation or ISGylation); (ii) virus-host cell interactions, including virus attachment, entry, fusion, egress and nuclear trafficking; (iii) virulence and antiviral activities; (iv) virion structure; and (v) low-complexity regions (LCRs) or motifs enriched with residues (Xaa-rich motifs). PMID:28248213

  17. Illustrating Consumer Theory with the CES Utility Function

    ERIC Educational Resources Information Center

    Tohamy, Soumaya M.; Mixon, J. Wilson, Jr.

    2004-01-01

    The authors use Microsoft Excel to derive compensated and uncompensated demand curves. They use a constant elasticity of substitution (CES) utility function to show how changes in a good's price or income affect the quantities demanded of that good and of the other composite good, using Excel's Solver. They provide three contributions. First, they…

  18. Assessing the Utility of a Demand Assessment for Functional Analysis

    ERIC Educational Resources Information Center

    Roscoe, Eileen M.; Rooker, Griffin W.; Pence, Sacha T.; Longworth, Lynlea J.

    2009-01-01

    We evaluated the utility of an assessment for identifying tasks for the functional analysis demand condition with 4 individuals who had been diagnosed with autism. During the demand assessment, a therapist presented a variety of tasks, and observers measured problem behavior and compliance to identify demands associated with low levels of…

  19. A Novel Utility Function for Energy-Efficient Power Control Game in Cognitive Radio Networks

    PubMed Central

    Al-Gumaei, Yousef Ali; Noordin, Kamarul Ariffin; Reza, Ahmed Wasif; Dimyati, Kaharudin

    2015-01-01

    Spectrum scarcity is a major challenge in wireless communications systems requiring efficient usage and utilization. Cognitive radio network (CRN) is found as a promising technique to solve this problem of spectrum scarcity. It allows licensed and unlicensed users to share the same licensed spectrum band. Interference resulting from cognitive radios (CRs) has undesirable effects on quality of service (QoS) of both licensed and unlicensed systems where it causes degradation in received signal-to-noise ratio (SIR) of users. Power control is one of the most important techniques that can be used to mitigate interference and guarantee QoS in both systems. In this paper, we develop a new approach of a distributed power control for CRN based on utility and pricing. QoS of CR user is presented as a utility function via pricing and a distributed power control as a non-cooperative game in which users maximize their net utility (utility-price). We define the price as a real function of transmit power to increase pricing charge of the farthest CR users. We prove that the power control game proposed in this study has Nash Equilibrium as well as it is unique. The obtained results show that the proposed power control algorithm based on a new utility function has a significant reduction in transmit power consumption and high improvement in speed of convergence. PMID:26258522

  20. A novel utility function for energy-efficient power control game in cognitive radio networks.

    PubMed

    Al-Gumaei, Yousef Ali; Noordin, Kamarul Ariffin; Reza, Ahmed Wasif; Dimyati, Kaharudin

    2015-01-01

    Spectrum scarcity is a major challenge in wireless communications systems requiring efficient usage and utilization. Cognitive radio network (CRN) is found as a promising technique to solve this problem of spectrum scarcity. It allows licensed and unlicensed users to share the same licensed spectrum band. Interference resulting from cognitive radios (CRs) has undesirable effects on quality of service (QoS) of both licensed and unlicensed systems where it causes degradation in received signal-to-noise ratio (SIR) of users. Power control is one of the most important techniques that can be used to mitigate interference and guarantee QoS in both systems. In this paper, we develop a new approach of a distributed power control for CRN based on utility and pricing. QoS of CR user is presented as a utility function via pricing and a distributed power control as a non-cooperative game in which users maximize their net utility (utility-price). We define the price as a real function of transmit power to increase pricing charge of the farthest CR users. We prove that the power control game proposed in this study has Nash Equilibrium as well as it is unique. The obtained results show that the proposed power control algorithm based on a new utility function has a significant reduction in transmit power consumption and high improvement in speed of convergence.

  1. Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

    NASA Astrophysics Data System (ADS)

    Zydziak, Nicolas; Konrad, Waldemar; Feist, Florian; Afonin, Sergii; Weidner, Steffen; Barner-Kowollik, Christopher

    2016-11-01

    Designing artificial macromolecules with absolute sequence order represents a considerable challenge. Here we report an advanced light-induced avenue to monodisperse sequence-defined functional linear macromolecules up to decamers via a unique photochemical approach. The versatility of the synthetic strategy--combining sequential and modular concepts--enables the synthesis of perfect macromolecules varying in chemical constitution and topology. Specific functions are placed at arbitrary positions along the chain via the successive addition of monomer units and blocks, leading to a library of functional homopolymers, alternating copolymers and block copolymers. The in-depth characterization of each sequence-defined chain confirms the precision nature of the macromolecules. Decoding of the functional information contained in the molecular structure is achieved via tandem mass spectrometry without recourse to their synthetic history, showing that the sequence information can be read. We submit that the presented photochemical strategy is a viable and advanced concept for coding individual monomer units along a macromolecular chain.

  2. Mechanisms by Which Different Functional States of Mitochondria Define Yeast Longevity

    PubMed Central

    Beach, Adam; Leonov, Anna; Arlia-Ciommo, Anthony; Svistkova, Veronika; Lutchman, Vicky; Titorenko, Vladimir I.

    2015-01-01

    Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research. PMID:25768339

  3. Utilization of alkyne bioconjugations to modulate protein function.

    PubMed

    Maza, Johnathan C; Howard, Christina A; Vipani, Megha A; Travis, Christopher R; Young, Douglas D

    2017-01-01

    The ability to introduce or modify protein function has widespread application to multiple scientific disciplines. The introduction of unique unnatural amino acids represents an excellent mechanism to incorporate new functionality; however, this approach is limited by ability of the translational machinery to recognize and incorporate the chemical moiety. To overcome this potential limitation, we aimed to exploit the functionality of existing unnatural amino acids to perform bioorthogonal reactions to introduce the desired protein modification, altering its function. Specifically, via the introduction of a terminal alkyne containing unnatural amino acid, we demonstrated chemically programmable protein modification through the Glaser-Hay coupling to other terminal alkynes, altering the function of a protein. In a proof-of-concept experiment, this approach has been utilized to modify the fluorescence spectrum of green fluorescent protein.

  4. Deriving a Utility Function For the U.S. Economy

    DTIC Science & Technology

    1988-04-01

    the urn. 1 The authors wish to thank Kenneth Arrow, Gerard Debreu , Robert Dorfman, Dale Jorgenson , and Lawrence J. Lau for their helpful comments...conditions 1121 4 that must be satisfied at the point which maximizes ’ie utility function, are quite analogous to the Arrow- Debreu conditions [1,5...formulation of the multi-period model is along the classical lines of an Arrow- Debreu (1,51 or Scarf [171 equilibrium model, with no surprises except perhaps

  5. ASSESSING THE UTILITY OF A DEMAND ASSESSMENT FOR FUNCTIONAL ANALYSIS

    PubMed Central

    Roscoe, Eileen M; Rooker, Griffin W; Pence, Sacha T; Longworth, Lynlea J

    2009-01-01

    We evaluated the utility of an assessment for identifying tasks for the functional analysis demand condition with 4 individuals who had been diagnosed with autism. During the demand assessment, a therapist presented a variety of tasks, and observers measured problem behavior and compliance to identify demands associated with low levels of compliance or high levels of problem behavior (low-probability demands) and demands associated with high levels of compliance or low levels of problem behavior (high-probability demands). Results showed that clearer functional analysis outcomes were obtained for 3 of the 4 participants when low-probability rather than high-probability demands were used. PMID:20514188

  6. Assessing the utility of a demand assessment for functional analysis.

    PubMed

    Roscoe, Eileen M; Rooker, Griffin W; Pence, Sacha T; Longworth, Lynlea J

    2009-01-01

    We evaluated the utility of an assessment for identifying tasks for the functional analysis demand condition with 4 individuals who had been diagnosed with autism. During the demand assessment, a therapist presented a variety of tasks, and observers measured problem behavior and compliance to identify demands associated with low levels of compliance or high levels of problem behavior (low-probability demands) and demands associated with high levels of compliance or low levels of problem behavior (high-probability demands). Results showed that clearer functional analysis outcomes were obtained for 3 of the 4 participants when low-probability rather than high-probability demands were used.

  7. Functional neuroimaging of traumatic brain injury: advances and clinical utility

    PubMed Central

    Irimia, Andrei; Van Horn, John Darrell

    2015-01-01

    Functional deficits due to traumatic brain injury (TBI) can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimaging studies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. PMID:26396520

  8. Green fluorescent protein nanopolygons as monodisperse supramolecular assemblies of functional proteins with defined valency

    NASA Astrophysics Data System (ADS)

    Kim, Young Eun; Kim, Yu-Na; Kim, Jung A.; Kim, Ho Min; Jung, Yongwon

    2015-05-01

    Supramolecular protein assemblies offer novel nanoscale architectures with molecular precision and unparalleled functional diversity. A key challenge, however, is to create precise nano-assemblies of functional proteins with both defined structures and a controlled number of protein-building blocks. Here we report a series of supramolecular green fluorescent protein oligomers that are assembled in precise polygonal geometries and prepared in a monodisperse population. Green fluorescent protein is engineered to be self-assembled in cells into oligomeric assemblies that are natively separated in a single-protein resolution by surface charge manipulation, affording monodisperse protein (nano)polygons from dimer to decamer. Several functional proteins are multivalently displayed on the oligomers with controlled orientations. Spatial arrangements of protein oligomers and displayed functional proteins are directly visualized by a transmission electron microscope. By employing our functional protein assemblies, we provide experimental insight into multivalent protein-protein interactions and tools to manipulate receptor clustering on live cell surfaces.

  9. National Survey of Geriatricians to Define Functional Decline in Elderly People with Minor Trauma

    PubMed Central

    Abdulaziz, Kasim; Perry, Jeffrey J.; Taljaard, Monica; Émond, Marcel; Lee, Jacques S.; Wilding, Laura; Sirois, Marie-Josée; Brehaut, Jamie

    2016-01-01

    Background This study was designed to determine a clinically significant point drop in function to define functional decline and the required sensitivity for a clinical decision tool to identify elderly patients at high risk of functional decline following a minor injury. Methods After a rigorous development process, a survey questionnaire was administered to a random sample of 178 geriatricians selected from those registered in a national medical directory. The surveys were distributed using a modified Dillman technique. Results We obtained a satisfactory response rate of 70.5%. Ninety percent of the geriatricians required a sensitivity of 90% or less for a clinical decision tool to identify injured seniors at high risk of functional decline 6 months post injury. Our results indicate that 90% of the respondents considered a drop in function of at least 2 points in activities of daily living (ADL) as clinically significant when considering all 14 ADL items. Considering only the 7 basic ADL items, 90% of physicians considered a 1 point drop as clinically significant. Conclusions A tool with a sensitivity of 90% to detect patients at risk of functional decline at 6 months post minor injury would meet or exceed the sensitivity required by 90% of geriatric specialists. These findings clearly define what is a clinically significant decline following a “minor injury.” PMID:27076859

  10. Definability of semifields of continuous positive functions by the lattices of their subalgebras

    NASA Astrophysics Data System (ADS)

    Sidorov, V. V.

    2016-09-01

    We consider the lattice {A}(U(X)) of subalgebras of a semifield U(X) of continuous positive functions on an arbitrary topological space X and its sublattice {A}_1(U(X)) of subalgebras with unity. The main result of the paper is the proof of the definability of any semifield U(X) both by the lattice {A}(U(X)) and by its sublattice {A}_1(U(X)). Bibliography: 12 titles.

  11. Wetting properties of model interphases coated with defined organic functional groups

    NASA Astrophysics Data System (ADS)

    Woche, Susanne K.; Goebel, Marc-O.; Guggenberger, Georg; Tunega, Daniel; Bachmann, Joerg

    2013-04-01

    Surface properties of soil particles are of particular interest regarding transport of water and sorption of solutes, especially hazardous xenobiotic species. Wetting properties (e.g. determined by contact angle, CA), governed by the functional groups exposed, are crucial to understand sorption processes in water repellent soils as well as for the geometry of water films sustaining microbial processes on the pore scale. Natural soil particle surfaces are characterized by a wide variety of mineralogical and chemical compounds. Their composition is almost impossible to identify in full. Hence, in order to get a better understanding about surface properties, an option is the usage of defined model surfaces, whereas the created surface should be comparable to natural soil interphases. We exposed smooth glass surfaces to different silane compounds, resulting in a coating covalently bound to the surface and exhibiting defined organic functional groups towards the pore space. The wetting properties as evaluated by CA and the surface free energy (SFE), calculated according to the Acid-Base Theory, were found to be a function of the specific functional group. Specifically, the treated surfaces showed a large variation of CA and SFE as function of chain length and polarity of the organic functional group. The study of wetting properties was accompanied by XPS analysis for selective detection of chemical compounds of the interphase. As the reaction mechanism of the coating process is known, the resulting interphase structure can be modeled based on energetic considerations. A next step is to use same coatings for the defined modification of the pore surfaces of porous media to study transport and sorption processes in complex three phase systems.

  12. Loss-of-function analyses defines vital and redundant functions of the Plasmodium rhomboid protease family.

    PubMed

    Lin, Jing-Wen; Meireles, Patrícia; Prudêncio, Miguel; Engelmann, Sabine; Annoura, Takeshi; Sajid, Mohammed; Chevalley-Maurel, Séverine; Ramesar, Jai; Nahar, Carolin; Avramut, Cristina M C; Koster, Abraham J; Matuschewski, Kai; Waters, Andrew P; Janse, Chris J; Mair, Gunnar R; Khan, Shahid M

    2013-04-01

    Rhomboid-like proteases cleave membrane-anchored proteins within their transmembrane domains. In apicomplexan parasites substrates include molecules that function in parasite motility and host cell invasion. While two Plasmodium rhomboids, ROM1 and ROM4, have been examined, the roles of the remaining six rhomboids during the malaria parasite's life cycle are unknown. We present systematic gene deletion analyses of all eight Plasmodium rhomboid-like proteins as a means to discover stage-specific phenotypes and potential functions in the rodent malaria model, P. berghei. Four rhomboids (ROM4, 6, 7 and 8) are refractory to gene deletion, suggesting an essential role during asexual blood stage development. In contrast ROM1, 3, 9 and 10 were dispensable for blood stage development and exhibited no, subtle or severe defects in mosquito or liver development. Parasites lacking ROM9 and ROM10 showed no major phenotypic defects. Parasites lacking ROM1 presented a delay in blood stage patency following liver infection, but in contrast to a previous study blood stage parasites had similar growth and virulence characteristics as wild type parasites. Parasites lacking ROM3 in mosquitoes readily established oocysts but failed to produce sporozoites. ROM3 is the first apicomplexan rhomboid identified to play a vital role in sporogony.

  13. Well-Defined Polymers Bearing Pendent Alkene Functionalities via Selective RAFT Polymerization

    PubMed Central

    Ma, Jun; Cheng, Chong; Sun, Guorong; Wooley, Karen L.

    2009-01-01

    A facile synthetic approach for the preparation of well-defined (co)polymers bearing pendent alkene functionalities was established by selective reversible addition-fragmentation chain transfer (RAFT) (co)polymerization. A divinyl monomer 4-(3′-buten-1′-oxy)-2,3,5,6-tetrafluorostyrene (1) with a styrenyl group and a pendent alkene group was synthesized. Due to a very high reactivity of the styrenyl group relative to the alkene group in 1, functional fluoro(co)polymers with both well-defined structures and pendent alkene groups were prepared by RAFT polymerizations of 1 and copolymerization of 1 with pentafluorostyrene (PFS). Alkene-functionalized diblock copolymers were also prepared by RAFT copolymerization of 1 with PFS or styrene, extending from a poly(styrene-alt-maleic anhydride) macro-chain transfer agent. Hydrolysis and ammonolysis of these copolymers resulted in amphiphilic diblock fluorocopolymers with alkene-functionalized hydrophobic segments, which were shown to form internally-functionalized micelles in THF-water. PMID:20640195

  14. Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

    PubMed Central

    Zydziak, Nicolas; Konrad, Waldemar; Feist, Florian; Afonin, Sergii; Weidner, Steffen; Barner-Kowollik, Christopher

    2016-01-01

    Designing artificial macromolecules with absolute sequence order represents a considerable challenge. Here we report an advanced light-induced avenue to monodisperse sequence-defined functional linear macromolecules up to decamers via a unique photochemical approach. The versatility of the synthetic strategy—combining sequential and modular concepts—enables the synthesis of perfect macromolecules varying in chemical constitution and topology. Specific functions are placed at arbitrary positions along the chain via the successive addition of monomer units and blocks, leading to a library of functional homopolymers, alternating copolymers and block copolymers. The in-depth characterization of each sequence-defined chain confirms the precision nature of the macromolecules. Decoding of the functional information contained in the molecular structure is achieved via tandem mass spectrometry without recourse to their synthetic history, showing that the sequence information can be read. We submit that the presented photochemical strategy is a viable and advanced concept for coding individual monomer units along a macromolecular chain. PMID:27901024

  15. The theta-syllable: a unit of speech information defined by cortical function.

    PubMed

    Ghitza, Oded

    2013-01-01

    A RECENT COMMENTARY (OSCILLATORS AND SYLLABLES: a cautionary note. Cummins, 2012) questions the validity of a class of speech perception models inspired by the possible role of neuronal oscillations in decoding speech (e.g., Ghitza, 2011; Giraud and Poeppel, 2012). In arguing against the approach, Cummins raises a cautionary flag "from a phonetician's point of view." Here we respond to his arguments from an auditory processing viewpoint, referring to a phenomenological model of Ghitza (2011) taken as a representative of the criticized approach. We shall conclude by proposing the theta-syllable as an information unit defined by cortical function-an alternative to the conventional, ambiguously defined syllable. In the large context, the resulting discussion debate should be viewed as a subtext of acoustic and auditory phonetics vs. articulatory and motor theories of speech reception.

  16. Defining modulatory inputs into CNS neuronal subclasses by functional pharmacological profiling

    PubMed Central

    Raghuraman, Shrinivasan; Garcia, Alfredo J.; Anderson, Tatiana M.; Twede, Vernon D.; Curtice, Kigen J.; Chase, Kevin; Ramirez, Jan-Marino; Olivera, Baldomero M.; Teichert, Russell W.

    2014-01-01

    Previously we defined neuronal subclasses within the mouse peripheral nervous system using an experimental strategy called “constellation pharmacology.” Here we demonstrate the broad applicability of constellation pharmacology by extending it to the CNS and specifically to the ventral respiratory column (VRC) of mouse brainstem, a region containing the neuronal network controlling respiratory rhythm. Analysis of dissociated cells from this locus revealed three major cell classes, each encompassing multiple subclasses. We broadly analyzed the combinations (constellations) of receptors and ion channels expressed within VRC cell classes and subclasses. These were strikingly different from the constellations of receptors and ion channels found in subclasses of peripheral neurons from mouse dorsal root ganglia. Within the VRC cell population, a subset of dissociated neurons responded to substance P, putatively corresponding to inspiratory pre-Bötzinger complex (preBötC) neurons. Using constellation pharmacology, we found that these substance P-responsive neurons also responded to histamine, and about half responded to bradykinin. Electrophysiological studies conducted in brainstem slices confirmed that preBötC neurons responsive to substance P exhibited similar responsiveness to bradykinin and histamine. The results demonstrate the predictive utility of constellation pharmacology for defining modulatory inputs into specific neuronal subclasses within central neuronal networks. PMID:24733934

  17. Utilization of Skills in the Care of the Patient with Common, Well-Defined Health Deviations I (NS 217): Competency-Based Course Syllabus.

    ERIC Educational Resources Information Center

    Green, Elizabeth G.; Yates, Laura H.

    "Utilization of Skills in the Care of the Patient with Common, Well-Defined Health Deviations I" (NS 217) is an associate degree nursing course offered at Chattanooga State Technical Community College to help students develop new competencies necessary for the care of patients with deviations of the cardiovascular, endocrine, integumentary, and…

  18. Software defined radio based multi-carrier multi-function waveform for cognitive radio

    NASA Astrophysics Data System (ADS)

    Zhou, Ruolin; Li, Xue; Chakravarthy, Vasu; Wu, Zhiqiang

    2010-04-01

    In this paper, we demonstrate an adaptive multicarrier multi-function waveform generator for cognitive radio via software defined radio. Using a USRP (universal software radio peripheral) software defined radio boards and GNU radio software, we implement a multi-carrier waveform generator which can generate multi-function waveforms such as OFDM, NC-OFDM, MC-CDMA, NC-MC-CDMA, CI/MC-CDMA, NCCI/ MC-CDMA, TDCS for cognitive radio. Additionally, we demonstrate a portable overlay cognitive radio using this multicarrier multi-function waveform generator. This cognitive radio is capable of detecting primary users in real time and adaptively adjusting its transmission parameters to avoid interference to primary users. More importantly, this cognitive radio can take advantage of multiple spectrum holes by employing non-contiguous multi-carrier transmission technologies. Additionally, we demonstrate that when the primary user transmission changes, the cognitive radio dynamically adjusts its transmission accordingly. We also demonstrate seamless real time video transmission between two cognitive radio nodes, while avoiding interference from primary users and interference to primary users operating in the same spectrum.

  19. Experimental Approaches for Defining Functional Roles of Microbes in the Human Gut

    PubMed Central

    Dantas, Gautam; Sommer, Morten O.A.; Degnan, Patrick H.; Goodman, Andrew L.

    2016-01-01

    The complex and intimate relationship between humans and their gut microbial communities is becoming less obscure, due in part to large-scale gut microbial genome-sequencing projects and culture-independent surveys of the composition and gene content of these communities. These studies build upon, and are complemented by, experimental efforts to define underlying mechanisms of host-microbe interactions in simplified model systems. This review highlights the intersection of these approaches. Experimental studies now leverage the advances in high-throughput DNA sequencing that have driven the explosion of microbial genome and community profiling projects, and the loss-of-function and gain-of-function strategies long employed in model organisms are now being extended to microbial genes, species, and communities from the human gut. These developments promise to deepen our understanding of human gut host–microbiota relationships and are readily applicable to other host-associated and free-living microbial communities. PMID:24024637

  20. Neurocognitive Function in HIV-Infected Patients: Comparison of Two Methods to Define Impairment

    PubMed Central

    Arenas-Pinto, Alejandro; Winston, Alan; Stöhr, Wolfgang; Day, John; Wiggins, Rebecca; Quah, Say Pheng; Ainsworth, Jonathan; Fleck, Sue; Dunn, David; Accoroni, Alex; Paton, Nicholas I.

    2014-01-01

    Objective To compare two definitions of neurocognitive impairment (NCI) in a large clinical trial of effectively-treated HIV-infected adults at baseline. Methods Hopkins Verbal Learning test-Revised (HVLT-R), Colour Trail (CTT) and Grooved Pegboard (GPT) tests were applied exploring five cognitive domains. Raw scores were transformed into Z-scores and NCI defined as summary NPZ-5 score one standard deviation below the mean of the normative dataset (i.e. <−1SD) or Z-scores <−1SD in at least two individual domains (categorical scale). Principal component analysis (PCA) was performed to explore the contribution of individual tests to the total variance. Results Mean NPZ-5 score was −0.72 (SD 0.98) and 178/548 (32%) participants had NPZ-5 scores <−1SD. When impairment was defined as <−1SD in at least two individual tests, 283 (52%) patients were impaired. Strong correlations between the two components of the HVLT-R test (learning/recall) (r = 0.73), and the CTT and (attention/executive functioning) (r = 0.66) were observed. PCA showed a clustering with three components accounting for 88% of the total variance. When patients who scored <−1SD only in two correlated tests were considered as not impaired, prevalence of NCI was 43%. When correlated test scores were averaged, 36% of participants had NPZ-3 scores <−1SD and 32% underperformed in at least two individual tests. Conclusion Controlling for differential contribution of individual test-scores on the overall performance and the level of correlation between components of the test battery used appear to be important when testing cognitive function. These two factors are likely to affect both summary scores and categorical scales in defining cognitive impairment. Trial registration EUDRACT: 2007-006448-23 and ISRCTN04857074. PMID:25078406

  1. Performance verification of network function virtualization in software defined optical transport networks

    NASA Astrophysics Data System (ADS)

    Zhao, Yongli; Hu, Liyazhou; Wang, Wei; Li, Yajie; Zhang, Jie

    2017-01-01

    With the continuous opening of resource acquisition and application, there are a large variety of network hardware appliances deployed as the communication infrastructure. To lunch a new network application always implies to replace the obsolete devices and needs the related space and power to accommodate it, which will increase the energy and capital investment. Network function virtualization1 (NFV) aims to address these problems by consolidating many network equipment onto industry standard elements such as servers, switches and storage. Many types of IT resources have been deployed to run Virtual Network Functions (vNFs), such as virtual switches and routers. Then how to deploy NFV in optical transport networks is a of great importance problem. This paper focuses on this problem, and gives an implementation architecture of NFV-enabled optical transport networks based on Software Defined Optical Networking (SDON) with the procedure of vNFs call and return. Especially, an implementation solution of NFV-enabled optical transport node is designed, and a parallel processing method for NFV-enabled OTN nodes is proposed. To verify the performance of NFV-enabled SDON, the protocol interaction procedures of control function virtualization and node function virtualization are demonstrated on SDON testbed. Finally, the benefits and challenges of the parallel processing method for NFV-enabled OTN nodes are simulated and analyzed.

  2. Self-defining future projections: exploring the identity function of thinking about the future.

    PubMed

    D'Argembeau, Arnaud; Lardi, Claudia; Van der Linden, Martial

    2012-01-01

    The act of projecting oneself into meaningful future events may significantly contribute to a person's sense of self and identity. Yet if the role of memories, in particular self-defining memories (SDMs), in grounding the self is now well established, the identity function of anticipated future events has received comparatively little attention. This article introduces the construct of self-defining future projection (SDFP) to address this issue. Two studies show that people can readily identify significant future events that they frequently think about and that convey core information about who they are as individuals. Furthermore, a person's particular style of constructing SDMs is similarly manifested in SDFPs, suggesting that both types of events can be used to ground the self. Notably, people who display a stronger tendency to extract meaning from their past experiences also reflect more about the potential implications of imagined future events. The results further demonstrate that SDMs and SDFPs both give rise to a strong sense of personal continuity over time and are meaningfully related to self-esteem. Together these findings lend support to the idea that a person's sense of self and identity is in part nourished by the anticipation of significant future events.

  3. The actin cytoskeleton in myofibroblast differentiation: Ultrastructure defining form and driving function

    PubMed Central

    Sandbo, Nathan; Dulin, Nickolai

    2011-01-01

    Myofibroblasts are modified fibroblasts, characterized by the presence of a well-developed contractile apparatus, and the formation of robust actin stress fibers. These mechanically active cells are thought to orchestrate extracellular matrix remodeling during normal wound healing in response to tissue injury, and in aberrant tissue remodeling found in fibrosing disorders. This review surveys the understanding of the role of actin stress fibers in myofibroblast biology. From its original description as a defining ultrastructural and morphologic feature, to well-accepted observations demonstrating its participation in contraction, focal adhesion maturation, and extracellular matrix reorganization, and finally to more recent observations demonstrating its role in transducing mechanical force into biochemical signals, transcriptional control of genes involved in locomotion, contraction, and matrix reorganization, and the localized regulation of mRNA translation. This breadth of functionality of the actin stress fiber serves to reinforce and amplify its mechanical function, via induced expression of proteins that themselves augment contraction, focal adhesion formation, and matrix remodeling. In composite, the functions of the actin cytoskeleton are most often aligned, allowing for the integration and amplification of signals promoting both myofibroblast differentiation and matrix remodeling during fibrogenesis. PMID:21925115

  4. Defining the players in higher-order networks: predictive modeling for reverse engineering functional influence networks.

    PubMed

    McDermott, Jason E; Archuleta, Michelle; Stevens, Susan L; Stenzel-Poore, Mary P; Sanfilippo, Antonio

    2011-01-01

    Determining biological network dependencies that can help predict the behavior of a system given prior observations from high-throughput data is a very valuable but difficult task, especially in the light of the ever-increasing volume of experimental data. Such an endeavor can be greatly enhanced by considering regulatory influences on co-expressed groups of genes representing functional modules, thus constraining the number of parameters in the system. This allows development of network models that are predictive of system dynamics. We first develop a predictive network model of the transcriptomics of whole blood from a mouse model of neuroprotection in ischemic stroke, and show that it can accurately predict system behavior under novel conditions. We then use a network topology approach to expand the set of regulators considered and show that addition of topological bottlenecks improves the performance of the predictive model. Finally, we explore how improvements in definition of functional modules may be achieved through an integration of inferred network relationships and functional relationships defined using Gene Ontology similarity. We show that appropriate integration of these two types of relationships can result in models with improved performance.

  5. Correlation of Theory and Function in Well-Defined Bimetallic Electrocatalysts - Final Report

    SciTech Connect

    Crooks, Richard M.

    2014-06-05

    The objective of this research proposal was to correlate the structure of nanoparticles that are comprised of ~100-200 atoms to their electrocatalytic function. This objective was based on the growing body of evidence suggesting that catalytic properties can be tailored through controlled synthesis of nanoparticles. What has been missing from many of these studies, and what we are contributing, is a model catalyst that is sufficiently small, structurally well-defined, and well-characterized that its function can be directly predicted by theory. Specifically, our work seeks to develop a fundamental and detailed understanding of the relationship between the structure of nanoscopic oxygen-reduction catalysts and their function. We assembled a team with expertise in theory, synthesis, and advanced characterization methods to address the primary objective of this project. We anticipated the outcomes of the study to be: (1) a better theoretical understanding of how nanoparticle structure affects catalytic properties; (2) the development of advanced, in-situ and ex-situ, atomic-scale characterization methods that are appropriate for particles containing about 100 atoms; and (3) improved synthetic methods that produce unique nanoparticle structures that can be used to test theoretical predictions. During the project period, we have made excellent progress on all three fronts.

  6. The C. elegans Connectome Consists of Homogenous Circuits with Defined Functional Roles

    PubMed Central

    Azulay, Aharon; Zaslaver, Alon

    2016-01-01

    A major goal of systems neuroscience is to decipher the structure-function relationship in neural networks. Here we study network functionality in light of the common-neighbor-rule (CNR) in which a pair of neurons is more likely to be connected the more common neighbors it shares. Focusing on the fully-mapped neural network of C. elegans worms, we establish that the CNR is an emerging property in this connectome. Moreover, sets of common neighbors form homogenous structures that appear in defined layers of the network. Simulations of signal propagation reveal their potential functional roles: signal amplification and short-term memory at the sensory/inter-neuron layer, and synchronized activity at the motoneuron layer supporting coordinated movement. A coarse-grained view of the neural network based on homogenous connected sets alone reveals a simple modular network architecture that is intuitive to understand. These findings provide a novel framework for analyzing larger, more complex, connectomes once these become available. PMID:27606684

  7. Defining functioning categories in axial Spondyloarthritis: the role of the ASAS Health Index.

    PubMed

    Di Carlo, Marco; Lato, Valentina; Di Matteo, Andrea; Carotti, Marina; Salaffi, Fausto

    2017-01-06

    The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is an inclusive questionnaire, able to describe the total impairments and restrictions due to axial spondyloarthritis (axSpA). Considering the relationship between ASAS HI and the Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, the aim of this study is to establish the ASAS HI cut-off values for functioning categories employing the ASDAS-CRP disease activity states in axSpA patients. ASAS HI and ASDAS-CPR were obtained from 140 consecutive axSpA patients, divided in the four ASDAS-CRP disease activity categories. High and very high disease activity were considered together. The ASAS HI cut-offs were obtained from the arithmetic mean, rounded off to the closest whole number, of the 75th percentile mean value of a lower rank and the 25th percentile mean value of the adjacent higher rank. This approach was applied in the transition from inactive disease and moderate disease activity, and in the transition from moderate disease activity and high/very high disease activity. Twenty-three patients were classified as having inactive disease, 36 were classified as having moderate disease activity, and 81 were in a high/very high disease activity state. Using the approach of the 75th-25th percentile mean values of adjacent disease activity states, the ASAS HI cut-offs resulted: ≤4 to dinstinguish a normal functioning, >4 and ≤8 to distinguish a moderate impairment of functioning, and >8 to distinguish a severe impairment of functioning. ASAS HI seems a reliable tool to define functioning categories in patients with axSpA.

  8. A Constrained Genetic Algorithm with Adaptively Defined Fitness Function in MRS Quantification

    NASA Astrophysics Data System (ADS)

    Papakostas, G. A.; Karras, D. A.; Mertzios, B. G.; Graveron-Demilly, D.; van Ormondt, D.

    MRS Signal quantification is a rather involved procedure and has attracted the interest of the medical engineering community, regarding the development of computationally efficient methodologies. Significant contributions based on Computational Intelligence tools, such as Neural Networks (NNs), demonstrated a good performance but not without drawbacks already discussed by the authors. On the other hand preliminary application of Genetic Algorithms (GA) has already been reported in the literature by the authors regarding the peak detection problem encountered in MRS quantification using the Voigt line shape model. This paper investigates a novel constrained genetic algorithm involving a generic and adaptively defined fitness function which extends the simple genetic algorithm methodology in case of noisy signals. The applicability of this new algorithm is scrutinized through experimentation in artificial MRS signals interleaved with noise, regarding its signal fitting capabilities. Although extensive experiments with real world MRS signals are necessary, the herein shown performance illustrates the method's potential to be established as a generic MRS metabolites quantification procedure.

  9. Neisseria gonorrhoeae O-linked pilin glycosylation: functional analyses define both the biosynthetic pathway and glycan structure

    PubMed Central

    Aas, Finn Erik; Vik, Åshild; Vedde, John; Koomey, Michael; Egge-Jacobsen, Wolfgang

    2007-01-01

    Neisseria gonorrhoeae expresses an O-linked protein glycosylation pathway that targets PilE, the major pilin subunit protein of the Type IV pilus colonization factor. Efforts to define glycan structure and thus the functions of pilin glycosylation (Pgl) components at the molecular level have been hindered by the lack of sensitive methodologies. Here, we utilized a ‘top-down’ mass spectrometric approach to characterize glycan status using intact pilin protein from isogenic mutants. These structural data enabled us to directly infer the function of six components required for pilin glycosylation and to define the glycan repertoire of strain N400. Additionally, we found that the N. gonorrhoeae pilin glycan is O-acetylated, and identified an enzyme essential for this unique modification. We also identified the N. gonorrhoeae pilin oligosaccharyltransferase using bioinformatics and confirmed its role in pilin glycosylation by directed mutagenesis. Finally, we examined the effects of expressing the PglA glycosyltransferase from the Campylobacter jejuni N-linked glycosylation system that adds N-acetylgalactosamine onto undecaprenylpyrophosphate-linked bacillosamine. The results indicate that the C. jejuni and N. gonorrhoeae pathways can interact in the synthesis of O-linked di- and trisaccharides, and therefore provide the first experimental evidence that biosynthesis of the N. gonorrhoeae pilin glycan involves a lipid-linked oligosaccharide precursor. Together, these findings underpin more detailed studies of pilin glycosylation biology in both N. gonorrhoeae and N. meningitidis, and demonstrate how components of bacterial O- and N-linked pathways can be combined in novel glycoengineering strategies. PMID:17608667

  10. Applying Utility Functions to Adaptation Planning for Home Automation Applications

    NASA Astrophysics Data System (ADS)

    Bratskas, Pyrros; Paspallis, Nearchos; Kakousis, Konstantinos; Papadopoulos, George A.

    A pervasive computing environment typically comprises multiple embedded devices that may interact together and with mobile users. These users are part of the environment, and they experience it through a variety of devices embedded in the environment. This perception involves technologies which may be heterogeneous, pervasive, and dynamic. Due to the highly dynamic properties of such environments, the software systems running on them have to face problems such as user mobility, service failures, or resource and goal changes which may happen in an unpredictable manner. To cope with these problems, such systems must be autonomous and self-managed. In this chapter we deal with a special kind of a ubiquitous environment, a smart home environment, and introduce a user-preference-based model for adaptation planning. The model, which dynamically forms a set of configuration plans for resources, reasons automatically and autonomously, based on utility functions, on which plan is likely to best achieve the user's goals with respect to resource availability and user needs.

  11. In vitro Differentiation of Functional Human Skeletal Myotubes in a Defined System.

    PubMed

    Guo, Xiufang; Greene, Keshel; Akanda, Nesar; Smith, Alec; Stancescu, Maria; Lambert, Stephen; Vandenburgh, Herman; Hickman, James

    2014-01-01

    In vitro human skeletal muscle systems are valuable tools for the study of human muscular development, disease and treatment. However, published in vitro human muscle systems have so far only demonstrated limited differentiation capacities. Advanced differentiation features such as cross-striations and contractility have only been observed in co-cultures with motoneurons. Furthermore, it is commonly regarded that cultured human myotubes do not spontaneously contract, and any contraction has been considered to originate from innervation. This study developed a serum-free culture system in which human skeletal myotubes demonstrated advanced differentiation. Characterization by immunocytochemistry, electrophysiology and analysis of contractile function revealed these major features: A) well defined sarcomeric development, as demonstrated by the presence of cross-striations. B) finely developed excitation-contraction coupling apparatus characterized by the close apposition of dihydropyridine receptors on T-tubules and Ryanodine receptors on sarcoplasmic reticulum membranes. C) spontaneous and electrically controlled contractility. This report not only demonstrates an improved level of differentiation of cultured human skeletal myotubes, but also provides the first published evidence that such myotubes are capable of spontaneous contraction. Use of this functional in vitro human skeletal muscle system would advance studies concerning human skeletal muscle development and physiology, as well as muscle-related disease and therapy.

  12. Regulating Biocompatibility of Carbon Spheres via Defined Nanoscale Chemistry and a Careful Selection of Surface Functionalities

    PubMed Central

    Misra, Santosh K.; Chang, Huei-Huei; Mukherjee, Prabuddha; Tiwari, Saumya; Ohoka, Ayako; Pan, Dipanjan

    2015-01-01

    A plethora of nanoarchitectures have been evaluated preclincially for applications in early detection and treatment of diseases at molecular and cellular levels resulted in limited success of their clinical translation. It is important to identify the factors that directly or indirectly affect their use in human. We bring a fundamental understanding of how to adjust the biocompatibility of carbon based spherical nanoparticles (CNPs) through defined chemistry and a vigilant choice of surface functionalities. CNPs of various size are designed by tweaking size (2–250 nm), surface chemistries (positive, or negatively charged), molecular chemistries (linear, dendritic, hyperbranched) and the molecular weight of the coating agents (MW 400–20 kDa). A combination of in vitro assays as tools were performed to determine the critical parameters that may trigger toxicity. Results indicated that hydrodynamic sizes are potentially not a risk factor for triggering cellular and systemic toxicity, whereas the presence of a highly positive surface charge and increasing molecular weight enhance the chance of inducing complement activation. Bare and carboxyl-terminated CNPs did present some toxicity at the cellular level which, however, is not comparable to those caused by positively charged CNPs. Similarly, negatively charged CNPs with hydroxyl and carboxylic functionalities did not cause any hemolysis. PMID:26462751

  13. In vitro Differentiation of Functional Human Skeletal Myotubes in a Defined System

    PubMed Central

    Guo, Xiufang; Greene, Keshel; Akanda, Nesar; Smith, Alec; Stancescu, Maria; Lambert, Stephen; Vandenburgh, Herman; Hickman, James

    2013-01-01

    In vitro human skeletal muscle systems are valuable tools for the study of human muscular development, disease and treatment. However, published in vitro human muscle systems have so far only demonstrated limited differentiation capacities. Advanced differentiation features such as cross-striations and contractility have only been observed in co-cultures with motoneurons. Furthermore, it is commonly regarded that cultured human myotubes do not spontaneously contract, and any contraction has been considered to originate from innervation. This study developed a serum-free culture system in which human skeletal myotubes demonstrated advanced differentiation. Characterization by immunocytochemistry, electrophysiology and analysis of contractile function revealed these major features: A) well defined sarcomeric development, as demonstrated by the presence of cross-striations. B) finely developed excitation-contraction coupling apparatus characterized by the close apposition of dihydropyridine receptors on T-tubules and Ryanodine receptors on sarcoplasmic reticulum membranes. C) spontaneous and electrically controlled contractility. This report not only demonstrates an improved level of differentiation of cultured human skeletal myotubes, but also provides the first published evidence that such myotubes are capable of spontaneous contraction. Use of this functional in vitro human skeletal muscle system would advance studies concerning human skeletal muscle development and physiology, as well as muscle-related disease and therapy. PMID:24516722

  14. Empirically defining rapid response to intensive treatment to maximize prognostic utility for bulimia nervosa and purging disorder.

    PubMed

    MacDonald, Danielle E; Trottier, Kathryn; McFarlane, Traci; Olmsted, Marion P

    2015-05-01

    Rapid response (RR) to eating disorder treatment has been reliably identified as a predictor of post-treatment and sustained remission, but its definition has varied widely. Although signal detection methods have been used to empirically define RR thresholds in outpatient settings, RR to intensive treatment has not been investigated. This study investigated the optimal definition of RR to day hospital treatment for bulimia nervosa and purging disorder. Participants were 158 patients who completed ≥6 weeks of day hospital treatment. Receiver operating characteristic (ROC) analysis was used to create four definitions of RR that could differentiate between remission and nonremission at the end of treatment. Definitions were based on binge/vomit episode frequency or percent reduction from pre-treatment, during either the first four or first two weeks of treatment. All definitions were associated with higher remission rates in rapid compared to nonrapid responders. Only one definition (i.e., ≤3 episodes in the first four weeks of treatment) predicted sustained remission (versus relapse) at 6- and 12-month follow-up. These findings provide an empirically derived definition of RR to intensive eating disorder treatment, and provide further evidence that early change is an important prognostic indicator.

  15. Requirements for Defining Utility Drive Cycles: An Exploratory Analysis of Grid Frequency Regulation Data for Establishing Battery Performance Testing Standards

    SciTech Connect

    Hafen, Ryan P.; Vishwanathan, Vilanyur V.; Subbarao, Krishnappa; Kintner-Meyer, Michael CW

    2011-10-19

    Battery testing procedures are important for understanding battery performance, including degradation over the life of the battery. Standards are important to provide clear rules and uniformity to an industry. The work described in this report addresses the need for standard battery testing procedures that reflect real-world applications of energy storage systems to provide regulation services to grid operators. This work was motivated by the need to develop Vehicle-to-Grid (V2G) testing procedures, or V2G drive cycles. Likewise, the stationary energy storage community is equally interested in standardized testing protocols that reflect real-world grid applications for providing regulation services. As the first of several steps toward standardizing battery testing cycles, this work focused on a statistical analysis of frequency regulation signals from the Pennsylvania-New Jersey-Maryland Interconnect with the goal to identify patterns in the regulation signal that would be representative of the entire signal as a typical regulation data set. Results from an extensive time-series analysis are discussed, and the results are explained from both the statistical and the battery-testing perspectives. The results then are interpreted in the context of defining a small set of V2G drive cycles for standardization, offering some recommendations for the next steps toward standardizing testing protocols.

  16. Exploring the cost–utility of stratified primary care management for low back pain compared with current best practice within risk-defined subgroups

    PubMed Central

    Whitehurst, David G T; Bryan, Stirling; Lewis, Martyn; Hill, Jonathan; Hay, Elaine M

    2012-01-01

    Objectives Stratified management for low back pain according to patients' prognosis and matched care pathways has been shown to be an effective treatment approach in primary care. The aim of this within-trial study was to determine the economic implications of providing such an intervention, compared with non-stratified current best practice, within specific risk-defined subgroups (low-risk, medium-risk and high-risk). Methods Within a cost–utility framework, the base-case analysis estimated the incremental healthcare cost per additional quality-adjusted life year (QALY), using the EQ-5D to generate QALYs, for each risk-defined subgroup. Uncertainty was explored with cost–utility planes and acceptability curves. Sensitivity analyses were performed to consider alternative costing methodologies, including the assessment of societal loss relating to work absence and the incorporation of generic (ie, non-back pain) healthcare utilisation. Results The stratified management approach was a cost-effective treatment strategy compared with current best practice within each risk-defined subgroup, exhibiting dominance (greater benefit and lower costs) for medium-risk patients and acceptable incremental cost to utility ratios for low-risk and high-risk patients. The likelihood that stratified care provides a cost-effective use of resources exceeds 90% at willingness-to-pay thresholds of £4000 (≈ 4500; $6500) per additional QALY for the medium-risk and high-risk groups. Patients receiving stratified care also reported fewer back pain-related days off work in all three subgroups. Conclusions Compared with current best practice, stratified primary care management for low back pain provides a highly cost-effective use of resources across all risk-defined subgroups. PMID:22492783

  17. Utilizing Combined Methodologies to Define the Role of Plasma Membrane Delivery During Axon Branching and Neuronal Morphogenesis.

    PubMed

    Winkle, Cortney C; Hanlin, Christopher C; Gupton, Stephanie L

    2016-03-16

    During neural development, growing axons extend to multiple synaptic partners by elaborating axonal branches. Axon branching is promoted by extracellular guidance cues like netrin-1 and results in dramatic increases to the surface area of the axonal plasma membrane. Netrin-1-dependent axon branching likely involves temporal and spatial control of plasma membrane expansion, the components of which are supplied through exocytic vesicle fusion. These fusion events are preceded by formation of SNARE complexes, comprising a v-SNARE, such as VAMP2 (vesicle-associated membrane protein 2), and plasma membrane t-SNAREs, syntaxin-1 and SNAP25 (synaptosomal-associated protein 25). Detailed herein isa multi-pronged approach used to examine the role of SNARE mediated exocytosis in axon branching. The strength of the combined approach is data acquisition at a range of spatial and temporal resolutions, spanning from the dynamics of single vesicle fusion events in individual neurons to SNARE complex formation and axon branching in populations of cultured neurons. This protocol takes advantage of established biochemical approaches to assay levels of endogenous SNARE complexes and Total Internal Reflection Fluorescence (TIRF) microscopy of cortical neurons expressing VAMP2 tagged with a pH-sensitive GFP (VAMP2-pHlourin) to identify netrin-1 dependent changes in exocytic activity in individual neurons. To elucidate the timing of netrin-1-dependent branching, time-lapse differential interference contrast (DIC) microscopy of single neurons over the order of hours is utilized. Fixed cell immunofluorescence paired with botulinum neurotoxins that cleave SNARE machinery and block exocytosis demonstrates that netrin-1 dependent axon branching requires SNARE-mediated exocytic activity.

  18. Utilizing Combined Methodologies to Define the Role of Plasma Membrane Delivery During Axon Branching and Neuronal Morphogenesis

    PubMed Central

    Winkle, Cortney C.; Hanlin, Christopher C.; Gupton, Stephanie L.

    2016-01-01

    During neural development, growing axons extend to multiple synaptic partners by elaborating axonal branches. Axon branching is promoted by extracellular guidance cues like netrin-1 and results in dramatic increases to the surface area of the axonal plasma membrane. Netrin-1-dependent axon branching likely involves temporal and spatial control of plasma membrane expansion, the components of which are supplied through exocytic vesicle fusion. These fusion events are preceded by formation of SNARE complexes, comprising a v-SNARE, such as VAMP2 (vesicle-associated membrane protein 2), and plasma membrane t-SNAREs, syntaxin-1 and SNAP25 (synaptosomal-associated protein 25). Detailed herein is a multi-pronged approach used to examine the role of SNARE mediated exocytosis in axon branching. The strength of the combined approach is data acquisition at a range of spatial and temporal resolutions, spanning from the dynamics of single vesicle fusion events in individual neurons to SNARE complex formation and axon branching in populations of cultured neurons. This protocol takes advantage of established biochemical approaches to assay levels of endogenous SNARE complexes and Total Internal Reflection Fluorescence (TIRF) microscopy of cortical neurons expressing VAMP2 tagged with a pH-sensitive GFP (VAMP2-pHlourin) to identify netrin-1 dependent changes in exocytic activity in individual neurons. To elucidate the timing of netrin-1-dependent branching, time-lapse differential interference contrast (DIC) microscopy of single neurons over the order of hours is utilized. Fixed cell immunofluorescence paired with botulinum neurotoxins that cleave SNARE machinery and block exocytosis demonstrates that netrin-1 dependent axon branching requires SNARE-mediated exocytic activity. PMID:27023471

  19. MeV gamma-ray observation with a well-defined point spread function based on electron tracking

    NASA Astrophysics Data System (ADS)

    Takada, A.; Tanimori, T.; Kubo, H.; Mizumoto, T.; Mizumura, Y.; Komura, S.; Kishimoto, T.; Takemura, T.; Yoshikawa, K.; Nakamasu, Y.; Matsuoka, Y.; Oda, M.; Miyamoto, S.; Sonoda, S.; Tomono, D.; Miuchi, K.; Kurosawa, S.; Sawano, T.

    2016-07-01

    The field of MeV gamma-ray astronomy has not opened up until recently owing to imaging difficulties. Compton telescopes and coded-aperture imaging cameras are used as conventional MeV gamma-ray telescopes; however their observations are obstructed by huge background, leading to uncertainty of the point spread function (PSF). Conventional MeV gamma-ray telescopes imaging utilize optimizing algorithms such as the ML-EM method, making it difficult to define the correct PSF, which is the uncertainty of a gamma-ray image on the celestial sphere. Recently, we have defined and evaluated the PSF of an electron-tracking Compton camera (ETCC) and a conventional Compton telescope, and thereby obtained an important result: The PSF strongly depends on the precision of the recoil direction of electron (scatter plane deviation, SPD) and is not equal to the angular resolution measure (ARM). Now, we are constructing a 30 cm-cubic ETCC for a second balloon experiment, Sub-MeV gamma ray Imaging Loaded-on-balloon Experiment: SMILE-II. The current ETCC has an effective area of 1 cm2 at 300 keV, a PSF of 10° at FWHM for 662 keV, and a large field of view of 3 sr. We will upgrade this ETCC to have an effective area of several cm2 and a PSF of 5° using a CF4-based gas. Using the upgraded ETCC, our observation plan for SMILE-II is to map of the electron-positron annihilation line and the 1.8 MeV line from 26Al. In this paper, we will report on the current performance of the ETCC and on our observation plan.

  20. VgrG and PAAR Proteins Define Distinct Versions of a Functional Type VI Secretion System

    PubMed Central

    Cianfanelli, Francesca R.; Alcoforado Diniz, Juliana; Guo, Manman; De Cesare, Virginia; Trost, Matthias; Coulthurst, Sarah J.

    2016-01-01

    The Type VI secretion system (T6SS) is widespread among bacterial pathogens and acts as an effective weapon against competitor bacteria and eukaryotic hosts by delivering toxic effector proteins directly into target cells. The T6SS utilises a bacteriophage-like contractile machinery to expel a puncturing device based on a tube of Hcp topped with a VgrG spike, which can be extended by a final tip from a PAAR domain-containing protein. Effector proteins are believed to be delivered by specifically associating with particular Hcp, VgrG or PAAR proteins, either covalently (‘specialised’) or non-covalently (‘cargo’ effectors). Here we used the T6SS of the opportunistic pathogen Serratia marcescens, together with integratecd genetic, proteomic and biochemical approaches, to elucidate the role of specific VgrG and PAAR homologues in T6SS function and effector specificity, revealing new aspects and unexpected subtleties in effector delivery by the T6SS. We identified effectors, both cargo and specialised, absolutely dependent on a particular VgrG for delivery to target cells, and discovered that other cargo effectors can show a preference for a particular VgrG. The presence of at least one PAAR protein was found to be essential for T6SS function, consistent with designation as a ‘core’ T6SS component. We showed that specific VgrG-PAAR combinations are required to assemble a functional T6SS and that the three distinct VgrG-PAAR assemblies in S. marcescens exhibit distinct effector specificity and efficiency. Unexpectedly, we discovered that two different PAAR-containing Rhs proteins can functionally pair with the same VgrG protein. Showing that accessory EagR proteins are involved in these interactions, native VgrG-Rhs-EagR complexes were isolated and specific interactions between EagR and cognate Rhs proteins identified. This study defines an essential yet flexible role for PAAR proteins in the T6SS and highlights the existence of distinct versions of the

  1. Contrast sensitivity functions to stimuli defined in Cartesian, polar and hyperbolic coordinates.

    PubMed

    Zana, Y; Cavalcanti, A C G T

    2005-01-01

    Recent electrophysiological studies indicate that cells in the LGN, V1, V2, and V4 areas in monkeys are specifically sensitive to Cartesian, polar and hyperbolic stimuli. We have characterized the contrast sensitivity functions (CSF) to stimuli defined in these coordinates with the two-alternatives forced-choice paradigm. CSFs to Cartesian, concentric, and hyperbolic stimuli have had similar shapes, with peak sensitivity at approximately 3 c/deg. However, the Cartesian CSF peak sensitivity has been at least 0.1 log units higher than that to stimuli in any other coordinate system. The concentric-Bessel CSF has a low-pass shape, peaking at 1.5 c/deg or below. The radial CSF has a bell shape with maximum sensitivity at 8 c/360 degrees. Only the concentric-Bessel CSF could be explained in terms of the components of maximum amplitude of the Fourier transform. Neural models, which in previous studies predicted the responses to Cartesian and polar Glass patterns, failed to account for the full CSFs data.

  2. Structure-function relationship of anticoagulant and antithrombotic well-defined sulfated polysaccharides from marine invertebrates.

    PubMed

    Pomin, Vitor H

    2012-01-01

    Marine sulfated polysaccharides (MSPs), such as sulfated fucans (SFs), sulfated galactans (SGs), and glycosaminoglycans (GAGs) isolated from invertebrate animals, are highly anionic polysaccharides capable of interacting with certain cationic proteins, such as (co)-factors of the coagulation cascade during clotting-inhibition process. Primarily, these molecular complexes between MSPs and coagulation-related proteins seem to be driven mostly by electrostatic interactions. However, through a systematic comparison using several novel well-defined sulfated polysaccharides composed of repetitive oligosaccharides with clear sulfation patterns, it was proved that those molecular interactions are essentially regulated by the stereochemistry of the glycans (which depends on a conjunction of anomeric configurations, sugar types, conformational preferences, glycosylation, and sulfation sites), rather than just a mere consequence of the electronegative density charges (mainly from number of sulfate groups). Here, we present an overview about the structure-function relationship of the invertebrate MSPs with regular structures as potential anticoagulant and antithrombotic agents, as pathologies related to the cardiovascular system are one of the major causes of mortality in the world.

  3. Direct conversion of human fibroblasts into functional osteoblasts by defined factors.

    PubMed

    Yamamoto, Kenta; Kishida, Tsunao; Sato, Yoshiki; Nishioka, Keisuke; Ejima, Akika; Fujiwara, Hiroyoshi; Kubo, Toshikazu; Yamamoto, Toshiro; Kanamura, Narisato; Mazda, Osam

    2015-05-12

    Osteoblasts produce calcified bone matrix and contribute to bone formation and remodeling. In this study, we established a procedure to directly convert human fibroblasts into osteoblasts by transducing some defined factors and culturing in osteogenic medium. Osteoblast-specific transcription factors, Runt-related transcription factor 2 (Runx2), and Osterix, in combination with Octamer-binding transcription factor 3/4 (Oct4) and L-Myc (RXOL) transduction, converted ∼ 80% of the fibroblasts into osteocalcin-producing cells. The directly converted osteoblasts (dOBs) induced by RXOL displayed a similar gene expression profile as normal human osteoblasts and contributed to bone repair after transplantation into immunodeficient mice at artificial bone defect lesions. The dOBs expressed endogenous Runx2 and Osterix, and did not require continuous expression of the exogenous genes to maintain their phenotype. Another combination, Oct4 plus L-Myc (OL), also induced fibroblasts to produce bone matrix, but the OL-transduced cells did not express Osterix and exhibited a more distant gene expression profile to osteoblasts compared with RXOL-transduced cells. These findings strongly suggest successful direct reprogramming of fibroblasts into functional osteoblasts by RXOL, a technology that may provide bone regeneration therapy against bone disorders.

  4. Dynamic functional imaging of brain glucose utilization using fPET-FDG

    SciTech Connect

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; Catana, Ciprian; Polimeni, Jonathan R.; Sander, Christin Y.; Zürcher, Nicole R.; Chonde, Daniel B.; Fowler, Joanna S.; Rosen, Bruce R.; Hooker, Jacob M.

    2014-06-14

    We report that glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. Ultimately, this new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.

  5. Dynamic functional imaging of brain glucose utilization using fPET-FDG

    DOE PAGES

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; ...

    2014-06-14

    We report that glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits themore » utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. Ultimately, this new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.« less

  6. Dynamic Functional Imaging of Brain Glucose Utilization using fPET-FDG

    PubMed Central

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; Catana, Ciprian; Polimeni, Jonathan R.; Sander, Christin Y.; Zürcher, Nicole R.; Chonde, Daniel B.; Fowler, Joanna S.; Rosen, Bruce R.; Hooker, Jacob M.

    2014-01-01

    Glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. This new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis is straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism. PMID:24936683

  7. Dynamic functional imaging of brain glucose utilization using fPET-FDG.

    PubMed

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B; Catana, Ciprian; Polimeni, Jonathan R; Sander, Christin Y; Zürcher, Nicole R; Chonde, Daniel B; Fowler, Joanna S; Rosen, Bruce R; Hooker, Jacob M

    2014-10-15

    Glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[(18)F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. This new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.

  8. A Prospective Cohort Study Defining Utilities Using Time Trade-Offs and the Euroqol-5D to Assess the Impact of Cancer-Related Lymphedema

    PubMed Central

    Cheville, Andrea L.; Almoza, Mously; Courmier, Janice N.; Basford, Jeffrey R.

    2013-01-01

    BACKGROUND The devastating impact of lymphedema on cancer survivors’ quality of life has prompted consideration of several changes in medical and surgical care. Unfortunately, our understanding of the benefits gained from these approaches relative to their cost remains limited. This study was designed to estimate utilities for lymphedema and characterize how utilities differ between subgroups defined by lymphedema etiology and distribution. METHODS A consecutive sample of 236 subjects with lymphedema seen at a lymphedema clinic completed both a time trade-off (TTO) exercise and the Euroqol 5D. Responses were adjusted in multivariate regression models for demographic factors, comorbidities, and lymphedema severity/location. RESULTS Most participants (167 of 236, 71%) had lymphedema as a consequence of cancer treatment; 123 with breast cancer and upper extremity involvement. Mean TTO utility estimates were consistently higher than Euroqol 5D estimates. Unadjusted TTO (0.85; standard deviation [SD], 0.21) and Euroqol 5D (0.76; SD, 0.18) scores diminished with increasing lymphedema stage and patient body mass index (BMI). Adjusted utility scores were lowest in patients with cancer-related lower extremity lymphedema (TTO=0.82; SD, 0.04 and Euroqol 5D=0.80; SD, 0.03). Breast cancer patients also had lower adjusted Euroqol 5D scores (0.80; SD, 0.02). CONCLUSIONS Lymphedema-associated utilities are in the range of 0.80. Lower utilities are observed for patients with higher lymphedema stages, elevated BMI, and cancer-related lymphedema. Greater expenditures for the prevention and treatment of cancer-related lymphedema are warranted. PMID:20564063

  9. Utility of shallow-water ATRIS images in defining biogeologic processes and self-similarity in skeletal scleractinia, Florida reefs

    USGS Publications Warehouse

    Lidz, B.H.; Brock, J.C.; Nagle, D.B.

    2008-01-01

    A recently developed remote-sensing instrument acquires high-quality digital photographs in shallow-marine settings within water depths of 15 m. The technology, known as the Along-Track Reef-Imaging System, provides remarkably clear, georeferenced imagery that allows visual interpretation of benthic class (substrates, organisms) for mapping coral reef habitats, as intended. Unforeseen, however, are functions new to the initial technologic purpose: interpr??table evidence for real-time biogeologic processes and for perception of scaled-up skeletal self-similarity of scleractinian microstructure. Florida reef sea trials lacked the grid structure required to map contiguous habitat and submarine topography. Thus, only general observations could be made relative to times and sites of imagery. Degradation of corals was nearly universal; absence of reef fish was profound. However, ???1% of more than 23,600 sea-trial images examined provided visual evidence for local environs and processes. Clarity in many images was so exceptional that small tracks left by organisms traversing fine-grained carbonate sand were visible. Other images revealed a compelling sense, not yet fully understood, of the microscopic wall structure characteristic of scleractinian corals. Conclusions drawn from classifiable images are that demersal marine animals, where imaged, are oblivious to the equipment and that the technology has strong capabilities beyond mapping habitat. Imagery acquired along predetermined transects that cross a variety of geomorphic features within depth limits will ( 1) facilitate construction of accurate contour maps of habitat and bathymetry without need for ground-truthing, (2) contain a strong geologic component of interpreted real-time processes as they relate to imaged topography and regional geomorphology, and (3) allow cost-effective monitoring of regional- and local-scale changes in an ecosystem by use of existing-image global-positioning system coordinates to re

  10. Role of Utility and Inference in the Evolution of Functional Information

    PubMed Central

    Sharov, Alexei A.

    2009-01-01

    Functional information means an encoded network of functions in living organisms from molecular signaling pathways to an organism’s behavior. It is represented by two components: code and an interpretation system, which together form a self-sustaining semantic closure. Semantic closure allows some freedom between components because small variations of the code are still interpretable. The interpretation system consists of inference rules that control the correspondence between the code and the function (phenotype) and determines the shape of the fitness landscape. The utility factor operates at multiple time scales: short-term selection drives evolution towards higher survival and reproduction rate within a given fitness landscape, and long-term selection favors those fitness landscapes that support adaptability and lead to evolutionary expansion of certain lineages. Inference rules make short-term selection possible by shaping the fitness landscape and defining possible directions of evolution, but they are under control of the long-term selection of lineages. Communication normally occurs within a set of agents with compatible interpretation systems, which I call communication system. Functional information cannot be directly transferred between communication systems with incompatible inference rules. Each biological species is a genetic communication system that carries unique functional information together with inference rules that determine evolutionary directions and constraints. This view of the relation between utility and inference can resolve the conflict between realism/positivism and pragmatism. Realism overemphasizes the role of inference in evolution of human knowledge because it assumes that logic is embedded in reality. Pragmatism substitutes usefulness for truth and therefore ignores the advantage of inference. The proposed concept of evolutionary pragmatism rejects the idea that logic is embedded in reality; instead, inference rules are

  11. Defining function of lipopolysaccharide O-antigen ligase WaaL using chemoenzymatically synthesized substrates.

    PubMed

    Han, Weiqing; Wu, Baolin; Li, Lei; Zhao, Guohui; Woodward, Robert; Pettit, Nicholas; Cai, Li; Thon, Vireak; Wang, Peng G

    2012-02-17

    The WaaL-mediated ligation of O-antigen onto the core region of the lipid A-core block is an important step in the lipopolysaccharide (LPS) biosynthetic pathway. Although the LPS biosynthesis has been largely characterized, only a limited amount of in vitro biochemical evidence has been established for the ligation reaction. Such limitations have primarily resulted from the barriers in purifying WaaL homologues and obtaining chemically defined substrates. Accordingly, we describe herein a chemical biology approach that enabled the reconstitution of this ligation reaction. The O-antigen repeating unit (O-unit) of Escherichia coli O86 was first enzymatically assembled via sequential enzymatic glycosylation of a chemically synthesized GalNAc-pyrophosphate-undecaprenyl precursor. Subsequent expression of WaaL through use of a chaperone co-expression system then enabled the demonstration of the in vitro ligation between the synthesized donor (O-unit-pyrophosphate-undecaprenyl) and the isolated lipid A-core acceptor. The previously reported ATP and divalent metal cation dependence were not observed using this system. Further analyses of other donor substrates revealed that WaaL possesses a highly relaxed specificity toward both the lipid moiety and the glycan moiety of the donor. Lastly, three conserved amino acid residues identified by sequence alignment were found essential for the WaaL activity. Taken together, the present work represents an in vitro systematic investigation of the WaaL function using a chemical biology approach, providing a system that could facilitate the elucidation of the mechanism of WaaL-catalyzed ligation reaction.

  12. Urodynamic Investigation: A Valid Tool to Define Normal Lower Urinary Tract Function?

    PubMed Central

    Sammer, Ulla; Knüpfer, Stephanie C.; Mehnert, Ulrich; Kessler, Thomas M.

    2016-01-01

    Objectives To evaluate whether urodynamic investigation (UDI), the gold standard to assess refractory lower urinary tract symptoms (LUTS), is appropriate to select healthy volunteers with apparent normal lower urinary tract function as control subjects for comparative studies. Subjects and Methods 42 healthy subjects (22 women, mean age 32±10 years; 20 men, mean age 37±12 years) without LUTS were included into this prospective single-centre cohort study. All subjects recorded a 3-day bladder diary, completed validated questionnaires regarding LUTS, and underwent neuro-urological assessment as well as free uroflowmetry. Same session repeat UDI was performed according to “Good Urodynamic Practice” recommended by the International Continence Society, but using an air-charged instead of a water-filled catheter, and evaluated by a blinded investigator. Results All 3-day bladder diaries, LUTS questionnaires, neuro-urological assessments and free uroflowmetries were within normal limits. Overall (either during the first or second UDI), same session repeat UDI revealed pathological findings in 71% (30/42): Detrusor overactivity was detected in 14% (3/22) and 30% (6/20), post void residual >100mL in 14% (3/22) and 25% (5/20), bladder outlet obstruction in 9% (2/22) and 20% (4/20) and detrusor sphincter dyssynergia in 77% (17/22) and 65% (13/20) of our women and men, respectively. Repeatability of detrusor overactivity (κ = 0.78, 95% CI: 0.54–1.02) and detrusor sphincter dyssynergia (κ = 0.77, 95% CI: 0.55–0.98) showed substantial agreement between both UDIs. All other assessed urodynamic parameters had wide 95% limits of agreement for differences in the parameters indicating poor repeatability. Conclusions More than 70% of our healthy subjects showed pathological urodynamic findings. Although UDI is the gold standard to assess refractory LUTS, it seems not to be applicable in healthy subjects to define normal lower urinary tract function. Therefore, we do not

  13. Utilization of Peanut Skin Extracts as Functional Food Ingredients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peanut skins are a by-product of the blanching industry that have not been utilized to their full potential. They have been found to contain significant quantities of compounds containing phenolic moieties such as catechins, procyanidins, and other polyphenols that have positive associations with h...

  14. Learning and Recovering Additive and Multiplicative Value Functions: A Criterion Validation of Multiattribute Utility Techniques

    DTIC Science & Technology

    1982-12-01

    multiattribute value functions. Operations Research, 1979, 27, 810-822. Fishburn, P. Utility theory for decision making. New York: Wiley, 1970...Psychology, 1980, 21, 66-82. v. Winterfeldt, D. and Fischer, G.W. Multiattribute utility theory : models and assessment procedres. In D. Wendt and...plicative value functions: A criterion _____________ validation of multiattribute utility 6. 7EPPORMING ONG. RgPeR? NUgMBER techn iclues 82-1 AijWOR*JS

  15. Recent advances in tomato functional genomics: utilization of VIGS.

    PubMed

    Sahu, Pranav Pankaj; Puranik, Swati; Khan, Moinuddin; Prasad, Manoj

    2012-10-01

    Tomato unquestionably occupies a significant position in world vegetable production owing to its world-wide consumption. The tomato genome sequencing efforts being recently concluded, it becomes more imperative to recognize important functional genes from this treasure of generated information for improving tomato yield. While much progress has been made in conventional tomato breeding, post-transcriptional gene silencing (PTGS) offers an alternative approach for advancement of tomato functional genomics. In particular, virus-induced gene silencing (VIGS) is increasingly being used as rapid, reliable, and lucrative screening strategy to elucidate gene function. In this review, we focus on the recent advancement made through exploiting the potential of this technique for manipulating different agronomically important traits in tomato by discussing several case studies.

  16. The theta-syllable: a unit of speech information defined by cortical function

    PubMed Central

    Ghitza, Oded

    2013-01-01

    A recent commentary (Oscillators and syllables: a cautionary note. Cummins, 2012) questions the validity of a class of speech perception models inspired by the possible role of neuronal oscillations in decoding speech (e.g., Ghitza, 2011; Giraud and Poeppel, 2012). In arguing against the approach, Cummins raises a cautionary flag “from a phonetician's point of view.” Here we respond to his arguments from an auditory processing viewpoint, referring to a phenomenological model of Ghitza (2011) taken as a representative of the criticized approach. We shall conclude by proposing the theta-syllable as an information unit defined by cortical function—an alternative to the conventional, ambiguously defined syllable. In the large context, the resulting discussion debate should be viewed as a subtext of acoustic and auditory phonetics vs. articulatory and motor theories of speech reception. PMID:23519170

  17. Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle

    PubMed Central

    Littlejohn, Mathew D.; Henty, Kristen M.; Tiplady, Kathryn; Johnson, Thomas; Harland, Chad; Lopdell, Thomas; Sherlock, Richard G.; Li, Wanbo; Lukefahr, Steven D.; Shanks, Bruce C.; Garrick, Dorian J.; Snell, Russell G.; Spelman, Richard J.; Davis, Stephen R.

    2014-01-01

    Lactation, hair development and homeothermy are characteristic evolutionary features that define mammals from other vertebrate species. Here we describe the discovery of two autosomal dominant mutations with antagonistic, pleiotropic effects on all three of these biological processes, mediated through the prolactin signalling pathway. Most conspicuously, mutations in prolactin (PRL) and its receptor (PRLR) have an impact on thermoregulation and hair morphology phenotypes, giving prominence to this pathway outside of its classical roles in lactation. PMID:25519203

  18. Performance evaluation of multi-stratum resources integration based on network function virtualization in software defined elastic data center optical interconnect.

    PubMed

    Yang, Hui; Zhang, Jie; Ji, Yuefeng; Tian, Rui; Han, Jianrui; Lee, Young

    2015-11-30

    Data center interconnect with elastic optical network is a promising scenario to meet the high burstiness and high-bandwidth requirements of data center services. In our previous work, we implemented multi-stratum resilience between IP and elastic optical networks that allows to accommodate data center services. In view of this, this study extends to consider the resource integration by breaking the limit of network device, which can enhance the resource utilization. We propose a novel multi-stratum resources integration (MSRI) architecture based on network function virtualization in software defined elastic data center optical interconnect. A resource integrated mapping (RIM) scheme for MSRI is introduced in the proposed architecture. The MSRI can accommodate the data center services with resources integration when the single function or resource is relatively scarce to provision the services, and enhance globally integrated optimization of optical network and application resources. The overall feasibility and efficiency of the proposed architecture are experimentally verified on the control plane of OpenFlow-based enhanced software defined networking (eSDN) testbed. The performance of RIM scheme under heavy traffic load scenario is also quantitatively evaluated based on MSRI architecture in terms of path blocking probability, provisioning latency and resource utilization, compared with other provisioning schemes.

  19. Defining the Physiological Factors that Contribute to Postflight Changes in Functional Performance

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Arzeno, N.; Buxton, R.; Feiveson, A. H.; Kofman, I.; Lawrence, E.; Lee, S. M. C.; Mulavara, A. P.; Peters, B. T.; Platts, S. H.; Ploutz-Snyder, L.; Reschke, M. F.; Ryder, J.; Spiering, B. A.; Stenger, M. B.; Wood, S.

    2009-01-01

    Astronauts experience alterations in multiple physiological systems due to exposure to the microgravity conditions of space flight. These physiological changes include sensorimotor disturbances, cardiovascular deconditioning and loss of muscle mass and strength. These changes might affect the ability of crewmembers to perform critical mission tasks immediately after landing on lunar and Martian surfaces. To date, changes in functional performance have not been systematically studied or correlated with physiological changes. To understand how changes in physiological function impact functional performance an interdisciplinary pre/postflight testing regimen (Functional Task Test, FTT) has been developed that systematically evaluates both astronaut postflight functional performance and related physiological changes. The overall objective of the FTT is to identify the key underlying physiological factors that contribute to performance of functional tests that are representative of critical mission tasks. This study will identify which physiological systems contribute the most to impaired performance on each functional test. This will allow us to identify the physiological systems that play the largest role in decrement in functional performance. Using this information we can then design and implement countermeasures that specifically target the physiological systems most responsible for the altered functional performance associated with space flight. The functional test battery was designed to address high priority tasks identified by the Constellation program as critical for mission success. The set of functional tests making up the FTT include the: 1) Seat Egress and Walk Test, 2) Ladder Climb Test, 3) Recovery from Fall/Stand Test, 4) Rock Translation Test, 5) Jump Down Test, 6) Torque Generation Test, and 7) Construction Activity Board Test. Corresponding physiological measures include assessments of postural and gait control, dynamic visual acuity, fine motor

  20. Ecological function as a target for ecosystem-based management: Defining when change matters in decision making

    EPA Science Inventory

    Ecosystem-based management (EBM) accounts for both direct and indirect drivers of ecological change for decision making. Just as with direct management of a resource, EBM requires a definition of management thresholds that define when change in function is sufficient to merit ma...

  1. New method for fMRI investigations of language: defining ROIs functionally in individual subjects.

    PubMed

    Fedorenko, Evelina; Hsieh, Po-Jang; Nieto-Castañón, Alfonso; Whitfield-Gabrieli, Susan; Kanwisher, Nancy

    2010-08-01

    Previous neuroimaging research has identified a number of brain regions sensitive to different aspects of linguistic processing, but precise functional characterization of these regions has proven challenging. We hypothesize that clearer functional specificity may emerge if candidate language-sensitive regions are identified functionally within each subject individually, a method that has revealed striking functional specificity in visual cortex but that has rarely been applied to neuroimaging studies of language. This method enables pooling of data from corresponding functional regions across subjects rather than from corresponding locations in stereotaxic space (which may differ functionally because of the anatomical variability across subjects). However, it is far from obvious a priori that this method will work as it requires that multiple stringent conditions be met. Specifically, candidate language-sensitive brain regions must be identifiable functionally within individual subjects in a short scan, must be replicable within subjects and have clear correspondence across subjects, and must manifest key signatures of language processing (e.g., a higher response to sentences than nonword strings, whether visual or auditory). We show here that this method does indeed work: we identify 13 candidate language-sensitive regions that meet these criteria, each present in >or=80% of subjects individually. The selectivity of these regions is stronger using our method than when standard group analyses are conducted on the same data, suggesting that the future application of this method may reveal clearer functional specificity than has been evident in prior neuroimaging research on language.

  2. Defining the multivalent functions of CTCF from chromatin state and three-dimensional chromatin interactions.

    PubMed

    Lu, Yiming; Shan, Guangyu; Xue, Jiguo; Chen, Changsheng; Zhang, Chenggang

    2016-07-27

    CCCTC-binding factor (CTCF) is a multi-functional protein that is assigned various, even contradictory roles in the genome. High-throughput sequencing-based technologies such as ChIP-seq and Hi-C provided us the opportunity to assess the multivalent functions of CTCF in the human genome. The location of CTCF-binding sites with respect to genomic features provides insights into the possible roles of this protein. Here we present the first genome-wide survey and characterization of three important functions of CTCF: enhancer insulator, chromatin barrier and enhancer linker. We developed a novel computational framework to discover the multivalent functions of CTCF based on chromatin state and three-dimensional chromatin architecture. We applied our method to five human cell lines and identified ∼46 000 non-redundant CTCF sites related to the three functions. Disparate effects of these functions on gene expression were found and distinct genomic features of these CTCF sites were characterized in GM12878 cells. Finally, we investigated the cell-type specificities of CTCF sites related to these functions across five cell types. Our study provides new insights into the multivalent functions of CTCF in the human genome.

  3. Estimating Moho depth utilizing S-wave receiver functions

    NASA Astrophysics Data System (ADS)

    Ceylan, S.; Rychert, C.; Harmon, N.

    2014-12-01

    H-k stacking method [Zhu and Kanamori, 2000] is a widely used grid search technique for estimating the Moho depth (H) and Vp/Vs (k) beneath a given station. The H-k surface reaches a maximum when the optimum H and k values are used, which is assumed to be the average crustal structure beneath the seismic station. In general, the method is employed in conjunction with P-wave receiver functions. Here, we investigate the usability of H-k stacking method with S-to-P (Sp) conversions and S-wave reverberations within the crust, employing an extended multi-taper deconvolution. We apply the method to southern California, using data recorded between 1990-2011. We compare results with those of prior studies that used P-to-S (Ps) conversions [Zhu and Kanamori, 2000; Yan and Clayton, 2007], applying a smoothing length of 0.5 degrees to reflect lateral Sp sensitivity. P-waves have better potential to resolve lateral variations in Moho depth owing to the higher frequency content and the geometry of Ps ray path. Our results from Sp conversions are in broad agreement with those from Ps, affirming that S-wave receiver functions can be used in conjunction with the H-k stacking method. Consistent with the P-wave receiver function results, crust is thinner beneath the central Transverse Range (30 km) with respect to eastern Transverse Range (33 km) and Peninsular Region (35 km). Our Moho depth observations (35 km) are more compatible with those of Yan and Clayton [2007] (~35 km) than Zhu and Kanamori [2000] (~30 km) beneath Sierra Nevada, most probably due to a larger data set this study and Yan and Clayton [2007] use. Also, results from this study are deeper than those from Ps for the Salton Trough (30-35 km vs. 25 km). In this case, broad receiver function waveform characteristics suggest a more gradual impedance change across the Moho discontinuity and/or a multi-layered crust. We suggest that a combination of P- and S-wave receiver functions can yield more robust crustal thickness

  4. Highly reflective polymeric substrates functionalized utilizing atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Zuzuarregui, Ana; Coto, Borja; Rodríguez, Jorge; Gregorczyk, Keith E.; Ruiz de Gopegui, Unai; Barriga, Javier; Knez, Mato

    2015-08-01

    Reflective surfaces are one of the key elements of solar plants to concentrate energy in the receivers of solar thermal electricity plants. Polymeric substrates are being considered as an alternative to the widely used glass mirrors due to their intrinsic and processing advantages, but optimizing both the reflectance and the physical stability of polymeric mirrors still poses technological difficulties. In this work, polymeric surfaces have been functionalized with ceramic thin-films by atomic layer deposition. The characterization and optimization of the parameters involved in the process resulted in surfaces with a reflection index of 97%, turning polymers into a real alternative to glass substrates. The solution we present here can be easily applied in further technological areas where seemingly incompatible combinations of polymeric substrates and ceramic coatings occur.

  5. Highly reflective polymeric substrates functionalized utilizing atomic layer deposition

    SciTech Connect

    Zuzuarregui, Ana Gregorczyk, Keith E.; Coto, Borja; Ruiz de Gopegui, Unai; Barriga, Javier; Rodríguez, Jorge; Knez, Mato

    2015-08-10

    Reflective surfaces are one of the key elements of solar plants to concentrate energy in the receivers of solar thermal electricity plants. Polymeric substrates are being considered as an alternative to the widely used glass mirrors due to their intrinsic and processing advantages, but optimizing both the reflectance and the physical stability of polymeric mirrors still poses technological difficulties. In this work, polymeric surfaces have been functionalized with ceramic thin-films by atomic layer deposition. The characterization and optimization of the parameters involved in the process resulted in surfaces with a reflection index of 97%, turning polymers into a real alternative to glass substrates. The solution we present here can be easily applied in further technological areas where seemingly incompatible combinations of polymeric substrates and ceramic coatings occur.

  6. Fronto-striatal organization: Defining functional and microstructural substrates of behavioural flexibility

    PubMed Central

    Morris, Laurel S.; Kundu, Prantik; Dowell, Nicholas; Mechelmans, Daisy J.; Favre, Pauline; Irvine, Michael A.; Robbins, Trevor W.; Daw, Nathaniel; Bullmore, Edward T.; Harrison, Neil A.; Voon, Valerie

    2016-01-01

    Discrete yet overlapping frontal-striatal circuits mediate broadly dissociable cognitive and behavioural processes. Using a recently developed multi-echo resting-state functional MRI (magnetic resonance imaging) sequence with greatly enhanced signal compared to noise ratios, we map frontal cortical functional projections to the striatum and striatal projections through the direct and indirect basal ganglia circuit. We demonstrate distinct limbic (ventromedial prefrontal regions, ventral striatum – VS, ventral tegmental area – VTA), motor (supplementary motor areas – SMAs, putamen, substantia nigra) and cognitive (lateral prefrontal and caudate) functional connectivity. We confirm the functional nature of the cortico-striatal connections, demonstrating correlates of well-established goal-directed behaviour (involving medial orbitofrontal cortex – mOFC and VS), probabilistic reversal learning (lateral orbitofrontal cortex – lOFC and VS) and attentional shifting (dorsolateral prefrontal cortex – dlPFC and VS) while assessing habitual model-free (SMA and putamen) behaviours on an exploratory basis. We further use neurite orientation dispersion and density imaging (NODDI) to show that more goal-directed model-based learning (MBc) is also associated with higher mOFC neurite density and habitual model-free learning (MFc) implicates neurite complexity in the putamen. This data highlights similarities between a computational account of MFc and conventional measures of habit learning. We highlight the intrinsic functional and structural architecture of parallel systems of behavioural control. PMID:26673945

  7. A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays

    PubMed Central

    Patel, Asha K.; Celiz, Adam D.; Rajamohan, Divya; Anderson, Daniel G.; Langer, Robert; Davies, Martyn C.

    2016-01-01

    Cardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components such as the substrate on which cells adhere to are important variables controlling the biological activity of cells. Using a combinatorial materials approach we develop a synthetic, chemically defined cellular niche for the support of functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) in a serum-free fully defined culture system. Almost 700 polymers were synthesized and evaluated for their utility as growth substrates. From this group, 20 polymers were identified that supported cardiomyocyte adhesion and spreading. The most promising 3 polymers were scaled up for extended culture of hESC-CMs for 15 days and were characterized using patch clamp electrophysiology and myofibril analysis to find that functional and structural phenotype was maintained on these synthetic substrates without the need for coating with extracellular matrix protein. In addition, we found that hESC-CMs cultured on a co-polymer of isobornyl methacrylate and tert-butylamino-ethyl methacrylate exhibited significantly longer sarcomeres relative to gelatin control. The potential utility of increased structural integrity was demonstrated in an in vitro toxicity assay that found an increase in detection sensitivity of myofibril disruption by the anti-cancer drug doxorubicin at a concentration of 0.05 µM in cardiomyocytes cultured on the co-polymer compared to 0.5 µM on gelatin. The chemical moieties identified in this large-scale screen provide chemically defined conditions for the culture and manipulation of hESC-CMs, as well as a framework for the rational design of superior biomaterials. PMID:26005764

  8. TU-F-12A-04: Differential Radiation Avoidance of Functional Liver Regions Defined by 99mTc-Sulfur Colloid SPECT/CT with Proton Therapy

    SciTech Connect

    Bowen, S; Miyaoka, R; Kinahan, P; Sandison, G; Vesselle, H; Nyflot, M; Apisarnthanarax, S; Saini, J; Wong, T

    2014-06-15

    Purpose: Radiotherapy for hepatocellular carcinoma patients is conventionally planned without consideration of spatial heterogeneity in hepatic function, which may increase risk of radiation-induced liver disease. Pencil beam scanning (PBS) proton radiotherapy (pRT) plans were generated to differentially decrease dose to functional liver volumes (FLV) defined on [{sup 99m}Tc]sulfur colloid (SC) SPECT/CT images (functional avoidance plans) and compared against conventional pRT plans. Methods: Three HCC patients underwent SC SPECT/CT scans for pRT planning acquired 15 min post injection over 24 min. Images were reconstructed with OSEM following scatter, collimator, and exhale CT attenuation correction. Functional liver volumes (FLV) were defined by liver:spleen uptake ratio thresholds (43% to 90% maximum). Planning objectives to FLV were based on mean SC SPECT uptake ratio relative to GTV-subtracted liver and inversely scaled to mean liver dose of 20 Gy. PTV target coverage (V{sub 95}) was matched between conventional and functional avoidance plans. PBS pRT plans were optimized in RayStation for single field uniform dose (SFUD) and systematically perturbed to verify robustness to uncertainty in range, setup, and motion. Relative differences in FLV DVH and target dose heterogeneity (D{sub 2}-D{sub 98})/D50 were assessed. Results: For similar liver dose between functional avoidance and conventional PBS pRT plans (D{sub mean}≤5% difference, V{sub 18Gy}≤1% difference), dose to functional liver volumes were lower in avoidance plans but varied in magnitude across patients (FLV{sub 70%max} D{sub mean}≤26% difference, V{sub 18Gy}≤8% difference). Higher PTV dose heterogeneity in avoidance plans was associated with lower functional liver dose, particularly for the largest lesion [(D{sub 2}-D{sub 98})/D{sub 50}=13%, FLV{sub 90%max}=50% difference]. Conclusion: Differential avoidance of functional liver regions defined on sulfur colloid SPECT/CT is feasible with proton

  9. Curcumin-functionalized silk biomaterials for anti-aging utility.

    PubMed

    Yang, Lei; Zheng, Zhaozhu; Qian, Cheng; Wu, Jianbing; Liu, Yawen; Guo, Shaozhe; Li, Gang; Liu, Meng; Wang, Xiaoqin; Kaplan, David L

    2017-02-02

    Curcumin is a natural antioxidant that is isolated from turmeric (Curcuma longa) and exhibits strong free radical scavenging activity, thus functional for anti-aging. However, poor stability and low solubility of curcumin in aqueous conditions limit its biomedical applications. Previous studies have shown that the anti-oxidation activity of curcumin embedded in silk fibroin films could be well preserved, resulting in the promoted adipogenesis from human mesenchymal stem cells (hMSCs) cultured on the surface of the films. In the present study, curcumin was encapsulated in both silk fibroin films (silk/cur films) and nanoparticles (silk/cur NPs), and their anti-aging effects were compared with free curcumin in solution, with an aim to elucidate the mechanism of anti-aging of silk-associated curcumin and to better serve biomedical applications in the future. The morphology and structure of silk/cur film and silk/cur NP were characterized using SEM, FTIR and DSC, indicating characteristic stable beta-sheet structure formation in the materials. Strong binding of curcumin molecules to the beta-sheet domains of silk fibroin resulted in the slow release of curcumin with well-preserved activity from the materials. For cell aging studies, rat bone marrow mesenchymal stem cells (rBMSCs) were cultured in the presence of free curcumin (FC), silk/cur film and silk/cur NP, and cell proliferation and markers of aging (P53, P16, HSP70 gene expression and β-Galactosidase activity) were examined. The results indicated that cell aging was retarded in all FC, silk/cur NP and silk/cur film samples, with the silk-associated curcumin superior to the FC.

  10. Defining functional changes in the brain caused by targeted stereotaxic radiosurgery.

    PubMed

    Parihar, Vipan K; Acharya, Munjal M; Roa, Dante E; Bosch, Omar; Christie, Lori-Ann; Limoli, Charles L

    2014-04-01

    Brain tumor patients routinely undergo cranial radiotherapy, and while beneficial, this treatment often results in debilitating cognitive dysfunction. This serious and unresolved problem has at present, no clinical recourse, and has driven our efforts to more clearly define the consequences of different brain irradiation paradigms on specific indices of cognitive performance and on the underlying cellular mechanisms believed to affect these processes. To accomplish this we have developed the capability to deliver highly focused X-ray beams to small and precisely defined volumes of the athymic rat brain, thereby providing more realistic simulations of clinical irradiation scenarios. Using this technique, termed stereotaxic radiosurgery, we evaluated the cognitive consequences of irradiation targeted to the hippocampus in one or both hemispheres of the brain, and compared that to whole brain irradiation. While whole brain irradiation was found to elicit significant deficits in novel place recognition and fear conditioning, standard platforms for quantifying hippocampal and non-hippocampal decrements, irradiation targeted to both hippocampi was only found to elicit deficits in fear conditioning. Cognitive decrements were more difficult to demonstrate in animals subjected to unilateral hippocampal ablation. Immunohistochemical staining for newly born immature (doublecortin positive) and mature (NeuN positive) neurons confirmed our capability to target irradiation to the neurogenic regions of the hippocampus. Stereotaxic radiosurgery (SRS) of the ipsilateral hemisphere reduced significantly the number of doublecortin and NeuN positive neurons by 80% and 27% respectively. Interestingly, neurogenesis on the contralateral side was upregulated in response to stereotaxic radiosurgery, where the number of doublecortin and NeuN positive neurons increased by 22% and 36% respectively. Neuroinflammation measured by immunostaining for activated microglia (ED1 positive cells) was

  11. Using siRNA to define functional interactions between melanopsin and multiple G Protein partners.

    PubMed

    Hughes, Steven; Jagannath, Aarti; Hickey, Doron; Gatti, Silvia; Wood, Matthew; Peirson, Stuart N; Foster, Russell G; Hankins, Mark W

    2015-01-01

    Melanopsin expressing photosensitive retinal ganglion cells (pRGCs) represent a third class of ocular photoreceptors and mediate a range of non-image forming responses to light. Melanopsin is a G protein coupled receptor (GPCR) and existing data suggest that it employs a membrane bound signalling cascade involving Gnaq/11 type G proteins. However, to date the precise identity of the Gα subunits involved in melanopsin phototransduction remains poorly defined. Here we show that Gnaq, Gna11 and Gna14 are highly co-expressed in pRGCs of the mouse retina. Furthermore, using RNAi based gene silencing we show that melanopsin can signal via Gnaq, Gna11 or Gna14 in vitro, and demonstrate that multiple members of the Gnaq/11 subfamily, including Gna14 and at least Gnaq or Gna11, can participate in melanopsin phototransduction in vivo and contribute to the pupillary light responses of mice lacking rod and cone photoreceptors. This diversity of G protein interactions suggests additional complexity in the melanopsin phototransduction cascade and may provide a basis for generating the diversity of light responses observed from pRGC subtypes.

  12. Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA.

    PubMed

    Kobielak, Krzysztof; Pasolli, H Amalia; Alonso, Laura; Polak, Lisa; Fuchs, Elaine

    2003-11-10

    Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/beta-catenin-regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated beta-catenin. This places the block downstream from Lef1 expression but upstream from beta-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized beta-catenin to activate the hair specific keratin genes and generate the hair shaft.

  13. Conservation defines functional motifs in the squint/nodal-related 1 RNA dorsal localization element

    PubMed Central

    Gilligan, Patrick C.; Kumari, Pooja; Lim, Shimin; Cheong, Albert; Chang, Alex; Sampath, Karuna

    2011-01-01

    RNA localization is emerging as a general principle of sub-cellular protein localization and cellular organization. However, the sequence and structural requirements in many RNA localization elements remain poorly understood. Whereas transcription factor-binding sites in DNA can be recognized as short degenerate motifs, and consensus binding sites readily inferred, protein-binding sites in RNA often contain structural features, and can be difficult to infer. We previously showed that zebrafish squint/nodal-related 1 (sqt/ndr1) RNA localizes to the future dorsal side of the embryo. Interestingly, mammalian nodal RNA can also localize to dorsal when injected into zebrafish embryos, suggesting that the sequence motif(s) may be conserved, even though the fish and mammal UTRs cannot be aligned. To define potential sequence and structural features, we obtained ndr1 3′-UTR sequences from approximately 50 fishes that are closely, or distantly, related to zebrafish, for high-resolution phylogenetic footprinting. We identify conserved sequence and structural motifs within the zebrafish/carp family and catfish. We find that two novel motifs, a single-stranded AGCAC motif and a small stem-loop, are required for efficient sqt RNA localization. These findings show that comparative sequencing in the zebrafish/carp family is an efficient approach for identifying weak consensus binding sites for RNA regulatory proteins. PMID:21149265

  14. Structural Waters Define a Functional Channel Mediating Activation of the GPCR, rhodopsin

    SciTech Connect

    Angel, T.; Gupta, S; Jastrzebska, B; Palczewski, K; Chance, M

    2009-01-01

    Structural water molecules may act as prosthetic groups indispensable for proper protein function. In the case of allosteric activation of G protein-coupled receptors (GPCRs), water likely imparts structural plasticity required for agonist-induced signal transmission. Inspection of structures of GPCR superfamily members reveals the presence of conserved embedded water molecules likely important to GPCR function. Coupling radiolytic hydroxyl radical labeling with rapid H2O18 solvent mixing, we observed no exchange of these structural waters with bulk solvent in either ground state or for the Meta II or opsin states. However, the radiolysis approach permitted labeling of selected side chain residues within the transmembrane helices and revealed activation-induced changes in local structural constraints likely mediated by dynamics of both water and protein. These results suggest both a possible general mechanism for water-dependent communication in family A GPCRs based on structural conservation, and a strategy for probing membrane protein structure.

  15. Rapid assembly of structurally defined and highly functionalized conjugated dienes via tethered enyne metathesis.

    PubMed

    Yao, Q

    2001-06-28

    [reaction: see text] Conjugated dienes are versatile building blocks in organic synthesis, and the development of new methods for their synthesis remains an important topic in modern synthetic organic chemistry. We describe here an expedient synthesis of highly functionalized conjugated dienes through sequential silicon-tethered ring-closing enyne metathesis mediated by Grubbs' Ru carbene catalysts and Tamao oxidation. Notable attributes of this methodology include short synthetic manipulations and the structural complexity it confers on the resulting diene moiety.

  16. Efficient generation of functional Schwann cells from adipose-derived stem cells in defined conditions.

    PubMed

    Xie, Songtao; Lu, Fan; Han, Juntao; Tao, Ke; Wang, Hongtao; Simental, Alfred; Hu, Dahai; Yang, Hao

    2017-03-15

    Schwann cells (SCs) are hitherto regarded as the most promising candidates for viable cell-based therapy to peripheral nervous system (PNS) injuries or degenerative diseases. However, the extreme drawbacks of transplanting autologous SCs for clinical applications still represent a significant bottleneck in neural regenerative medicine, mainly owing to the need of sacrificing a functional nerve to generate autologous SCs and the nature of slow expansion of the SCs. Thus, it is of great importance to establish an alternative cell system for the generation of sufficient SCs. Here, we demonstrated that adipose-derived stem cells (ADSCs) of rat robustly give rise to morphological, phenotypic and functional SCs using an optimized protocol. After undergoing a 3-week in vitro differentiation, almost all of treated ADSCs exhibited spindle shaped morphology similar to genuine SCs and expressed SC markers GFAP and S100. Most importantly, apart from acquisition of SC antigenic and biochemical features, the ADSC-derived SCs were functionally identical to native SCs as they possess a potential ability to form myelin, and secret nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glia-derived neurotrophic factor (GDNF). The current study may provide an ideal strategy for harvesting sufficient SCs for cell-based treatment of various peripheral nerve injuries or disorders.

  17. Utility of the modified ATP III defined metabolic syndrome and severe obesity as predictors of insulin resistance in overweight children and adolescents: a cross-sectional study

    PubMed Central

    Dhuper, Sarita; Cohen, Hillel W; Daniel, Josephine; Gumidyala, Padmasree; Agarwalla, Vipin; St Victor, Rosemarie; Dhuper, Sunil

    2007-01-01

    Background The rising prevalence of obesity and metabolic syndrome (MetS) has received increased attention since both place individuals at risk for Type II diabetes and cardiovascular disease. Insulin resistance (IR) has been implicated in the pathogenesis of obesity and MetS in both children and adults and is a known independent cardiovascular risk factor. However measures of IR are not routinely performed in children while MetS or severe obesity when present, are considered as clinical markers for IR. Objective The study was undertaken to assess the utility of ATPIII defined metabolic syndrome (MetS) and severe obesity as predictors of insulin resistance (IR) in a group of 576 overweight children and adolescents attending a pediatric obesity clinic in Brooklyn. Methods Inclusion criteria were children ages 3–19, and body mass index > 95th percentile for age. MetS was defined using ATP III criteria, modified for age. IR was defined as upper tertile of homeostasis model assessment (HOMA) within 3 age groups (3–8, n = 122; 9–11, n = 164; 12–19, n = 290). Sensitivity, specificity, positive predictive values and odds ratios (OR) with 95% confidence intervals (CI) were calculated within age groups for predicting IR using MetS and severe obesity respectively. Results MetS was present in 45%, 48% and 42% of the respective age groups and significantly predicted IR only in the oldest group (OR = 2.0, 95% CI 1.2, 3.4; p = .006). Sensitivities were <55%; specificities <63% and positive predictive values ≤ 42% in all groups. Severe obesity was significantly associated with IR in both the 9–11 (p = .002) and 12–18 (p = .01) groups but positive predictive values were nonetheless ≤ 51% for all groups. Conclusion The expression of IR in overweight children and adolescents is heterogeneous and MetS or severe obesity may not be sufficiently sensitive and specific indicators of insulin resistance. In addition to screening for MetS in overweight children markers for

  18. Defining conservation priorities for freshwater fishes according to taxonomic, functional, and phylogenetic diversity

    USGS Publications Warehouse

    Strecker, Angela; Olden, Julian D.; Whittier, Joanna B.; Paukert, Craig P.

    2011-01-01

    To date, the predominant use of systematic conservation planning has been to evaluate and conserve areas of high terrestrial biodiversity. Although studies in freshwater ecosystems have received recent attention, research has rarely considered the potential trade-offs between protecting different dimensions of biodiversity and the ecological processes that maintain diversity. We provide the first systematic prioritization for freshwaters (focusing on the highly threatened and globally distinct fish fauna of the Lower Colorado River Basin, USA) simultaneously considering scenarios of: taxonomic, functional, and phylogenetic diversity; contemporary threats to biodiversity (including interactions with nonnative species); and future climate change and human population growth. There was 75% congruence between areas of highest conservation priority for different aspects of biodiversity, suggesting that conservation efforts can concurrently achieve strong complementarity among all types of diversity. However, sizable fractions of the landscape were incongruent across conservation priorities for different diversity scenarios, underscoring the importance of considering multiple dimensions of biodiversity and highlighting catchments that contribute disproportionately to taxonomic, functional, and phylogenetic diversity in the region. Regions of projected human population growth were not concordant with conservation priorities; however, higher human population abundance will likely have indirect effects on native biodiversity by increasing demand for water. This will come in direct conflict with projected reductions in precipitation and warmer temperatures, which have substantial overlap with regions of high contemporary diversity. Native and endemic fishes in arid ecosystems are critically endangered by both current and future threats, but our results highlight the use of systematic conservation planning for the optimal allocation of limited resources that incorporates

  19. Defining conservation priorities for freshwater fishes according to taxonomic, functional, and phylogenetic diversity

    USGS Publications Warehouse

    Strecker, A.L.; Olden, J.D.; Whittier, Joanna B.; Paukert, C.P.

    2011-01-01

    To date, the predominant use of systematic conservation planning has been to evaluate and conserve areas of high terrestrial biodiversity. Although studies in freshwater ecosystems have received recent attention, research has rarely considered the potential tradeoffs between protecting different dimensions of biodiversity and the ecological processes that maintain diversity. We provide the first systematic prioritization for freshwaters (focusing on the highly threatened and globally distinct fish fauna of the Lower Colorado River Basin, USA) simultaneously considering scenarios of: taxonomic, functional, and phylogenetic diversity;contemporary threats to biodiversity (including interactions with nonnative species);and future climate change and human population growth. There was 75% congruence between areas of highest conservation priority for different aspects of biodiversity, suggesting that conservation efforts can concurrently achieve strong complementarity among all types of diversity. However, sizable fractions of the landscape were incongruent across conservation priorities for different diversity scenarios, underscoring the importance of considering multiple dimensions of biodiversity and highlighting catchments that contribute disproportionately to taxonomic, functional, and phylogenetic diversity in the region. Regions of projected human population growth were not concordant with conservation priorities;however, higher human population abundance will likely have indirect effects on native biodiversity by increasing demand for water. This will come in direct conflict with projected reductions in precipitation and warmer temperatures, which have substantial overlap with regions of high contemporary diversity. Native and endemic fishes in arid ecosystems are critically endangered by both current and future threats, but our results highlight the use of systematic conservation planning for the optimal allocation of limited resources that incorporates multiple

  20. The Hidden World within Plants: Ecological and Evolutionary Considerations for Defining Functioning of Microbial Endophytes

    PubMed Central

    van Overbeek, Leonard S.; Berg, Gabriele; Pirttilä, Anna Maria; Compant, Stéphane; Campisano, Andrea; Döring, Matthias; Sessitsch, Angela

    2015-01-01

    SUMMARY All plants are inhabited internally by diverse microbial communities comprising bacterial, archaeal, fungal, and protistic taxa. These microorganisms showing endophytic lifestyles play crucial roles in plant development, growth, fitness, and diversification. The increasing awareness of and information on endophytes provide insight into the complexity of the plant microbiome. The nature of plant-endophyte interactions ranges from mutualism to pathogenicity. This depends on a set of abiotic and biotic factors, including the genotypes of plants and microbes, environmental conditions, and the dynamic network of interactions within the plant biome. In this review, we address the concept of endophytism, considering the latest insights into evolution, plant ecosystem functioning, and multipartite interactions. PMID:26136581

  1. Determination of human DNA polymerase utilization for the repair of a model ionizing radiation-induced DNA strand break lesion in a defined vector substrate

    NASA Technical Reports Server (NTRS)

    Winters, T. A.; Russell, P. S.; Kohli, M.; Dar, M. E.; Neumann, R. D.; Jorgensen, T. J.

    1999-01-01

    Human DNA polymerase and DNA ligase utilization for the repair of a major class of ionizing radiation-induced DNA lesion [DNA single-strand breaks containing 3'-phosphoglycolate (3'-PG)] was examined using a novel, chemically defined vector substrate containing a single, site-specific 3'-PG single-strand break lesion. In addition, the major human AP endonuclease, HAP1 (also known as APE1, APEX, Ref-1), was tested to determine if it was involved in initiating repair of 3'-PG-containing single-strand break lesions. DNA polymerase beta was found to be the primary polymerase responsible for nucleotide incorporation at the lesion site following excision of the 3'-PG blocking group. However, DNA polymerase delta/straightepsilon was also capable of nucleotide incorporation at the lesion site following 3'-PG excision. In addition, repair reactions catalyzed by DNA polymerase beta were found to be most effective in the presence of DNA ligase III, while those catalyzed by DNA polymerase delta/straightepsilon appeared to be more effective in the presence of DNA ligase I. Also, it was demonstrated that the repair initiating 3'-PG excision reaction was not dependent upon HAP1 activity, as judged by inhibition of HAP1 with neutralizing HAP1-specific polyclonal antibody.

  2. CNTF variants with increased biological potency and receptor selectivity define a functional site of receptor interaction.

    PubMed Central

    Saggio, I; Gloaguen, I; Poiana, G; Laufer, R

    1995-01-01

    Human CNTF is a neurocytokine that elicits potent neurotrophic effects by activating a receptor complex composed of the ligand-specific alpha-receptor subunit (CNTFR alpha) and two signal transducing proteins, which together constitute a receptor for leukemia inhibitory factor (LIFR). At high concentrations, CNTF can also activate the LIFR and possibly other cross-reactive cytokine receptors in the absence of CNTFR alpha. To gain a better understanding of its structure-function relationships and to develop analogs with increased receptor specificity, the cytokine was submitted to affinity maturation using phage display technology. Variants with greatly increased CNTFR alpha affinity were selected from a phage-displayed library of CNTF variants carrying random amino acid substitutions in the putative D helix. Selected variants contained substitutions of the wild-type Gln167 residue, either alone or in combination with neighboring mutations. These results provide evidence for an important functional role of the mutagenized region in CNTFR alpha binding. Affinity enhancing mutations conferred to CNTF increased potency to trigger biological effects mediated by CNTFR alpha and enhanced neurotrophic activity on chicken ciliary neurons. In contrast, the same mutations did not potentiate the CNTFR alpha-independent receptor actions of CNTF. These CNTF analogs thus represent receptor-specific superagonists, which should help to elucidate the mechanisms underlying the pleiotropic actions of the neurocytokine. PMID:7621819

  3. Defining the structure and function of acyl-homoserine lactone autoinducers.

    PubMed

    Churchill, Mair E A; Sibhatu, Hiruy M; Uhlson, Charis L

    2011-01-01

    Quorum sensing plays a central role in regulating many community-derived symbiotic and pathogenic relationships of bacteria, and as such has attracted much attention in recent years. Acyl-homoserine lactones (AHLs) are important signaling molecules in the quorum sensing gene-regulatory processes found in numerous gram-negative species of bacteria that interact with eukaryotic organisms. AHLs are produced by acyl-homoserine lactone synthases. Bacteria can have multiple genes for AHL synthase enzymes, and such species are likely to produce several different types of AHLs. Determination of the types and the relative amounts of AHLs produced by AHL synthases in bacteria under varied conditions provides important insights into the mechanism of AHL synthase function and the regulation of transcriptional cascades initiated by quorum sensing signaling. This chapter describes a mass spectrometry method for determining the types and relative amounts of AHLs present in a sample.

  4. Defining the structure and function of acyl-homoserine lactone autoinducers

    PubMed Central

    Churchill, Mair E.A.; Sibhatu, Hiruy M.; Uhlson, Charis L.

    2012-01-01

    Quorum sensing plays a central role in regulating many community derived symbiotic and pathogenic relationships of bacteria, and as such has attracted much attention in recent years. Acyl-homoserine lactones (AHLs) are important signaling molecules in the quorum sensing gene regulatory processes found in numerous gram-negative species of bacteria that interact with eukaryotic organisms. AHLs are produced by acyl-homoserine lactone synthases. Bacteria can have multiple genes for AHL synthase enzymes, and such species are likely to produce several different types of AHLs. Determination of the types and the relative amounts of AHLs produced by AHL synthases in bacteria under varied conditions provides important insights into the mechanism of AHL synthase function and the regulation of transcriptional cascades initiated by quorum sensing signaling. This chapter describes a mass spectrometry method for determining the types and relative amounts of AHLs present in a sample. PMID:21031311

  5. zif-1 translational repression defines a second, mutually exclusive OMA function in germline transcriptional repression.

    PubMed

    Guven-Ozkan, Tugba; Robertson, Scott M; Nishi, Yuichi; Lin, Rueyling

    2010-10-01

    Specification of primordial germ cells requires global repression of transcription. In C. elegans, primordial germ cells are generated through four rounds of asymmetric divisions, starting from the zygote P0, each producing a transcriptionally repressed germline blastomere (P1-P4). Repression in P2-P4 requires PIE-1, which is provided maternally in oocytes and segregated to all germline blastomeres. We have shown previously that OMA-1 and OMA-2 repress global transcription in P0 and P1 by sequestering TAF-4, an essential component of TFIID. Soon after the first mitotic cycle, OMA proteins undergo developmentally regulated degradation. Here, we show that OMA proteins also repress transcription in P2-P4 indirectly, through a completely different mechanism that operates in oocytes. OMA proteins bind to both the 3' UTR of the zif-1 transcript and the eIF4E-binding protein, SPN-2, repressing translation of zif-1 mRNA in oocytes. zif-1 encodes the substrate-binding subunit of the E3 ligase for PIE-1 degradation. Inhibition of zif-1 translation in oocytes ensures high PIE-1 levels in oocytes and germline blastomeres. The two OMA protein functions are strictly regulated in both space and time by MBK-2, a kinase activated following fertilization. Phosphorylation by MBK-2 facilitates the binding of OMA proteins to TAF-4 and simultaneously inactivates their function in repressing zif-1 translation. Phosphorylation of OMA proteins displaces SPN-2 from the zif-1 3' UTR, releasing translational repression. We propose that MBK-2 phosphorylation serves as a developmental switch, converting OMA proteins from specific translational repressors in oocytes to global transcriptional repressors in embryos, together effectively repressing transcription in all germline blastomeres.

  6. DEFINING THE PLAYERS IN HIGHER-ORDER NETWORKS: PREDICTIVE MODELING FOR REVERSE ENGINEERING FUNCTIONAL INFLUENCE NETWORKS

    SciTech Connect

    McDermott, Jason E.; Costa, Michelle N.; Stevens, S.L.; Stenzel-Poore, Mary; Sanfilippo, Antonio P.

    2011-01-20

    A difficult problem that is currently growing rapidly due to the sharp increase in the amount of high-throughput data available for many systems is that of determining useful and informative causative influence networks. These networks can be used to predict behavior given observation of a small number of components, predict behavior at a future time point, or identify components that are critical to the functioning of the system under particular conditions. In these endeavors incorporating observations of systems from a wide variety of viewpoints can be particularly beneficial, but has often been undertaken with the objective of inferring networks that are generally applicable. The focus of the current work is to integrate both general observations and measurements taken for a particular pathology, that of ischemic stroke, to provide improved ability to produce useful predictions of systems behavior. A number of hybrid approaches have recently been proposed for network generation in which the Gene Ontology is used to filter or enrich network links inferred from gene expression data through reverse engineering methods. These approaches have been shown to improve the biological plausibility of the inferred relationships determined, but still treat knowledge-based and machine-learning inferences as incommensurable inputs. In this paper, we explore how further improvements may be achieved through a full integration of network inference insights achieved through application of the Gene Ontology and reverse engineering methods with specific reference to the construction of dynamic models of transcriptional regulatory networks. We show that integrating two approaches to network construction, one based on reverse-engineering from conditional transcriptional data, one based on reverse-engineering from in situ hybridization data, and another based on functional associations derived from Gene Ontology, using probabilities can improve results of clustering as evaluated by a

  7. Functional Analysis Helps to Define KCNC3 Mutational Spectrum in Dutch Ataxia Cases

    PubMed Central

    Fokkens, Michiel R.; Meijer, Michel; Boerrigter, Melissa; Verschuuren-Bemelmans, Corien C.; Kremer, Berry P. H.; van de Warrenburg, Bart P.; Dooijes, Dennis; Boddeke, Erik; Sinke, Richard J.; Verbeek, Dineke S.

    2015-01-01

    Spinocerebellar ataxia type 13 (SCA13) is an autosomal dominantly inherited neurodegenerative disorder of the cerebellum caused by mutations in the voltage gated potassium channel KCNC3. To identify novel pathogenic SCA13 mutations in KCNC3 and to gain insights into the disease prevalence in the Netherlands, we sequenced the entire coding region of KCNC3 in 848 Dutch cerebellar ataxia patients with familial or sporadic origin. We evaluated the pathogenicity of the identified variants by co-segregation analysis and in silico prediction followed by biochemical and electrophysiological studies. We identified 19 variants in KCNC3 including 2 non-coding, 11 missense and 6 synonymous variants. Two missense variants did not co-segregate with the disease and were excluded as potentially disease-causing mutations. We also identified the previously reported p.R420H and p.R423H mutations in our cohort. Of the remaining 7 missense variants, functional analysis revealed that 2 missense variants shifted Kv3.3 channel activation to more negative voltages. These variations were associated with early disease onset and mild intellectual disability. Additionally, one other missense variant shifted channel activation to more positive voltages and was associated with spastic ataxic gait. Whereas, the remaining missense variants did not change any of the channel characteristics. Of these three functional variants, only one variant was in silico predicted to be damaging and segregated with disease. The other two variants were in silico predicted to be benign and co-segregation analysis was not optimal or could only be partially confirmed. Therefore, we conclude that we have identified at least one novel pathogenic mutation in KCNC3 that cause SCA13 and two additionally potential SCA13 mutations. This leads to an estimate of SCA13 prevalence in the Netherlands to be between 0.6% and 1.3%. PMID:25756792

  8. Defining the Accuracy of Secretin Pancreatic Function Testing in Patients With Suspected Early Chronic Pancreatitis

    PubMed Central

    Ketwaroo, Gyanprakash; Brown, Alphonso; Young, Benjamin; Kheraj, Rakhi; Sawhney, Mandeep; Mortele, Koenraad J.; Najarian, Robert; Tewani, Sumeet; Dasilva, Deborah; Freedman, Steven; Sheth, Sunil

    2017-01-01

    OBJECTIVES The diagnosis of chronic pancreatitis in patients with characteristic symptoms but normal pancreatic imaging is challenging. Assessment of pancreatic function through secretin pancreatic function testing (SPFT) has been advocated in this setting, but its diagnostic accuracy is not fully known. METHODS This was a retrospective review of patients who received SPFT at our tertiary care institution between January 1995 and December 2008 for suspected chronic pancreatitis. For all patients, medical records were reviewed for evidence of subsequent development of chronic pancreatitis by imaging and/or pathology. Patients were then categorized as “true positive” or “true negative” for chronic pancreatitis based on follow-up imaging or histologic evidence. RESULTS In all, 116 patients underwent SPFT. Of the 27 patients who tested positive, 7 were lost to follow-up. Of the remaining 20 SPFT-positive patients, 9 (45 %) developed radiologic or histologic evidence of chronic pancreatitis after a median of 4 years (1–11 years). Of the 89 patients who had negative SPFT testing, 19 were lost to follow-up. Of the remaining 70 patients, 2 were eventually diagnosed with chronic pancreatitis based on subsequent imaging/histology after a median follow-up period of 7 years (3–11 years). The sensitivity of the SPFT in diagnosing chronic pancreatitis was 82 % with a specificity of 86 %. The positive predictive value (PPV) of chronic pancreatitis was 45 % with a negative predictive value (NPV) of 97 %. CONCLUSIONS In patients with suspected early chronic pancreatitis and normal pancreatic imaging, SPFT is highly accurate at ruling out early chronic pancreatitis with a NPV of 97 %. PMID:23711627

  9. Defining the functional boundaries of the murine α1,3-fucosyltransferase Fut7 reveals a remarkably compact locus.

    PubMed

    Ebel, Mark E; Kansas, Geoffrey S

    2014-03-07

    Fut7 encodes an α1,3-fucosyltransferase critical for biosynthesis of glycan ligands for all three selectins. Consistent with this function, Fut7 expression is limited to hematopoietic cells and high endothelial cells which express selectin ligands. Mechanisms that govern Fut7 expression are poorly defined. To begin to understand the molecular genetic basis for transcriptional regulation of Fut7, a transgenic, gain-of-function, genetic complementation approach in mice was used to define the "functional boundaries" of the murine Fut7 locus, defined here as any uninterupted stretch of genomic DNA that contains all cis-acting genetic elements essential for accurate physiologic expression. A 12.7-kb contiguous genomic interval, which lies completely between the highly conserved flanking Npdc1 and Abca2 loci on chromosome 2 and which contains the complete transcriptional unit plus ∼7.4 kb upstream of the transcriptional start site and ∼2 kb downstream of the transcriptional termination and polyadenylation sites, was used as a transgene (Tg) on a Fut7 null background. Tg+ mice exhibited restoration of Fut7 gene expression and physiologic levels of selectin ligand expression and function on neutrophils, activated T cells, and high endothelial cells and corrected the functional defects in these cells found in Fut7 null mice without leading to detectable expression of Fut7 in normally non-expressing tissues. These results demonstrate that all genetic information essential for appropriate and selective expression of Fut7 in diverse cell types and in response to distinct developmental signals is contained within this comparatively small genetic region.

  10. Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer.

    PubMed

    Maxfield, Kimberly E; Taus, Patrick J; Corcoran, Kathleen; Wooten, Joshua; Macion, Jennifer; Zhou, Yunyun; Borromeo, Mark; Kollipara, Rahul K; Yan, Jingsheng; Xie, Yang; Xie, Xian-Jin; Whitehurst, Angelique W

    2015-11-16

    Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer-testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology.

  11. Comprehensive functional characterization of cancer–testis antigens defines obligate participation in multiple hallmarks of cancer

    PubMed Central

    Maxfield, Kimberly E.; Taus, Patrick J.; Corcoran, Kathleen; Wooten, Joshua; Macion, Jennifer; Zhou, Yunyun; Borromeo, Mark; Kollipara, Rahul K.; Yan, Jingsheng; Xie, Yang; Xie, Xian-Jin; Whitehurst, Angelique W.

    2015-01-01

    Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer–testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology. PMID:26567849

  12. Functional analysis via standardized whole-blood stimulation systems defines the boundaries of a healthy immune response to complex stimuli.

    PubMed

    Duffy, Darragh; Rouilly, Vincent; Libri, Valentina; Hasan, Milena; Beitz, Benoit; David, Mikael; Urrutia, Alejandra; Bisiaux, Aurélie; Labrie, Samuel T; Dubois, Annick; Boneca, Ivo G; Delval, Cécile; Thomas, Stéphanie; Rogge, Lars; Schmolz, Manfred; Quintana-Murci, Lluis; Albert, Matthew L

    2014-03-20

    Standardization of immunophenotyping procedures has become a high priority. We have developed a suite of whole-blood, syringe-based assay systems that can be used to reproducibly assess induced innate or adaptive immune responses. By eliminating preanalytical errors associated with immune monitoring, we have defined the protein signatures induced by (1) medically relevant bacteria, fungi, and viruses; (2) agonists specific for defined host sensors; (3) clinically employed cytokines; and (4) activators of T cell immunity. Our results provide an initial assessment of healthy donor reference values for induced cytokines and chemokines and we report the failure to release interleukin-1α as a common immunological phenotype. The observed naturally occurring variation of the immune response may help to explain differential susceptibility to disease or response to therapeutic intervention. The implementation of a general solution for assessment of functional immune responses will help support harmonization of clinical studies and data sharing.

  13. Maintenance of Hepatic Functions in Primary Human Hepatocytes Cultured on Xeno-Free and Chemical Defined Human Recombinant Laminins.

    PubMed

    Watanabe, Masaaki; Zemack, Helen; Johansson, Helene; Hagbard, Louise; Jorns, Carl; Li, Meng; Ellis, Ewa

    2016-01-01

    Refined methods for maintaining specific functions of isolated hepatocytes under xeno-free and chemical defined conditions is of great importance for the development of hepatocyte research and regenerative therapy. Laminins, a large family of heterotrimeric basement membrane adhesion proteins, are highly cell and tissue type specific components of the extracellular matrix and strongly influence the behavior and function of associated cells and/or tissues. However, detailed biological functions of many laminin isoforms are still to be evaluated. In this study, we determined the distribution of laminin isoforms in human liver tissue and isolated primary human hepatocytes by western blot analysis, and investigated the efficacy of different human recombinant laminin isoforms on hepatic functions during culture. Protein expressions of laminin-chain α2, α3, α4, β1, β3, γ1, and γ2 were detected in both isolated human hepatocytes and liver tissue. No α1 and α5 expression could be detected in liver tissue or hepatocytes. Hepatocytes were isolated from five different individual livers, and cultured on human recombinant laminin isoforms -111, -211, -221, -332, -411, -421, -511, and -521 (Biolamina AB), matrigel (extracted from Engelbreth-Holm-Swarm sarcoma), or collagen type IV (Collagen). Hepatocytes cultured on laminin showed characteristic hexagonal shape in a flat cell monolayer. Viability, double stranded DNA concentration, and Ki67 expression for hepatocytes cultured for six days on laminin were comparable to those cultured on EHS and Collagen. Hepatocytes cultured on laminin also displayed production of human albumin, alpha-1-antitrypsin, bile acids, and gene expression of liver-enriched factors, such as hepatocyte nuclear factor 4 alpha, glucose-6-phosphate, cytochrome P450 3A4, and multidrug resistance-associated protein 2. We conclude that all forms of human recombinant laminin tested maintain cell viability and liver-specific functions of primary human

  14. Changes in citric acid cycle flux and anaplerosis antedate the functional decline in isolated rat hearts utilizing acetoacetate.

    PubMed Central

    Russell, R R; Taegtmeyer, H

    1991-01-01

    To determine the temporal relationship between changes in contractile performance and flux through the citric acid cycle in hearts oxidizing acetoacetate, we perfused isolated working rat hearts with either glucose or acetoacetate (both 5 mM) and freeze-clamped the tissue at defined times. After 60 min of perfusion, hearts utilizing acetoacetate exhibited lower systolic and diastolic pressures and lower cardiac outputs. The oxidation of acetoacetate increased the tissue content of 2-oxoglutarate and glutamate and decreased the content of succinyl-CoA suggesting inhibition of citric acid cycle flux through 2-oxoglutarate dehydrogenase. Whereas hearts perfused with either acetoacetate or glucose were similar with respect to their function for the first 20 min, changes in tissue metabolites were already observed within 5 min of perfusion at near-physiological workloads. The addition of lactate or propionate, but not acetate, to hearts oxidizing acetoacetate improved contractile performance, although inhibition of 2-oxoglutarate dehydrogenase was probably not diminished. If lactate or propionate were added, malate and citrate accumulated indicating utilization of anaplerotic pathways for the citric acid cycle. We conclude that a decreased rate of flux through 2-oxoglutarate dehydrogenase in hearts oxidizing acetoacetate precedes, and may be responsible for, contractile failure and is not the result of decreased cardiac work. Further, anaplerosis play an important role in the maintenance of contractile function in hearts utilizing acetoacetate. Images PMID:1671390

  15. Utility of Urinary Biomarkers in Predicting Loss of Residual Renal Function: The balANZ Trial

    PubMed Central

    Cho, Yeoungjee; Johnson, David W.; Vesey, David A.; Hawley, Carmel M.; Clarke, Margaret; Topley, Nicholas

    2015-01-01

    ♦ Background: The ability of urinary biomarkers to predict residual renal function (RRF) decline in peritoneal dialysis (PD) patients has not been defined. The present study aimed to explore the utility of established biomarkers from kidney injury models for predicting loss of RRF in incident PD patients, and to evaluate the impact on RRF of using neutral-pH PD solution low in glucose degradation products. ♦ Methods: The study included 50 randomly selected participants from the balANZ trial who had completed 24 months of follow-up. A change in glomerular filtration rate (GFR) was used as the primary clinical outcome measure. In a mixed-effects general linear model, baseline measurements of 18 novel urinary biomarkers and albumin were used to predict GFR change. The model was further used to evaluate the impact of biocompatible PD solution on RRF, adjusted for each biomarker. ♦ Results: Baseline albuminuria was not a useful predictor of change in RRF in PD patients (p = 0.84). Only clusterin was a significant predictor of GFR decline in the whole population (p = 0.04, adjusted for baseline GFR and albuminuria). However, the relationship was no longer apparent when albuminuria was removed from the model (p = 0.31). When the effect of the administered PD solutions was examined using a model adjusted for PD solution type, baseline albuminuria, and GFR, higher baseline urinary concentrations of trefoil factor 3 (TFF3, p = 0.02), kidney injury molecule 1 (KIM-1, p = 0.04), and interferon γ-induced protein 10 (IP-10, p = 0.03) were associated with more rapid decline of RRF in patients receiving conventional PD solution compared with biocompatible PD solution. ♦ Conclusions: Higher urinary levels of kidney injury biomarkers (TFF3, KIM-1, IP-10) at baseline predicted significantly slower RRF decline in patients receiving biocompatible PD solutions. Findings from the present investigation should help to guide future studies to validate the utility of urinary

  16. Association of tissue lineage and gene expression: conservatively and differentially expressed genes define common and special functions of tissues

    PubMed Central

    2010-01-01

    Background Embryogenesis is the process by which the embryo is formed, develops, and establishes developmental hierarchies of tissues. The recent advance in microarray technology made it possible to investigate the tissue specific patterns of gene expression and their relationship with tissue lineages. This study is focused on how tissue specific functions, tissue lineage, and cell differentiation are correlated, which is essential to understand embryonic development and organism complexity. Results We performed individual gene and gene set based analysis on multiple tissue expression data, in association with the classic topology of mammalian fate maps of embryogenesis. For each sub-group of tissues on the fate map, conservatively, differentially and correlatively expressed genes or gene sets were identified. Tissue distance was found to correlate with gene expression divergence. Tissues of the ectoderm or mesoderm origins from the same segments on the fate map shared more similar expression pattern than those from different origins. Conservatively expressed genes or gene sets define common functions in a tissue group and are related to tissue specific diseases, which is supported by results from Gene Ontology and KEGG pathway analysis. Gene expression divergence is larger in certain human tissues than in the mouse homologous tissues. Conclusion The results from tissue lineage and gene expression analysis indicate that common function features of neighbor tissue groups were defined by the conservatively expressed genes and were related to tissue specific diseases, and differentially expressed genes contribute to the functional divergence of tissues. The difference of gene expression divergence in human and mouse homologous tissues reflected the organism complexity, i.e. distinct neural development levels and different body sizes. PMID:21172044

  17. Defining an Abrasion Index for Lunar Surface Systems as a Function of Dust Interaction Modes and Variable Concentration Zones

    NASA Technical Reports Server (NTRS)

    Kobrick, Ryan L.; Klaus, David M.; Street, Kenneth W., Jr.

    2010-01-01

    Unexpected issues were encountered during the Apollo era of lunar exploration due to detrimental abrasion of materials upon exposure to the fine-grained, irregular shaped dust on the surface of the Moon. For critical design features involving contact with the lunar surface and for astronaut safety concerns, operational concepts and dust tolerance must be considered in the early phases of mission planning. To systematically define material selection criteria, dust interaction can be characterized by two-body or three-body abrasion testing, and subcategorically by physical interactions of compression, rolling, sliding and bending representing specific applications within the system. Two-body abrasion occurs when a single particle or asperity slides across a given surface removing or displacing material. Three-body abrasion occurs when multiple particles interact with a solid surface, or in between two surfaces, allowing the abrasives to freely rotate and interact with the material(s), leading to removal or displacement of mass. Different modes of interaction are described in this paper along with corresponding types of tests that can be utilized to evaluate each configuration. In addition to differential modes of abrasion, variable concentrations of dust in different zones can also be considered for a given system design and operational protocol. These zones include: (1) outside the habitat where extensive dust exposure occurs, (2) in a transitional zone such as an airlock or suitport, and (3) inside the habitat or spacesuit with a low particle count. These zones can be used to help define dust interaction frequencies, and corresponding risks to the systems and/or crew can be addressed by appropriate mitigation strategies. An abrasion index is introduced that includes the level of risk, R, the hardness of the mineralogy, H, the severity of the abrasion mode, S, and the frequency of particle interactions, F.

  18. Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus

    PubMed Central

    Graham, Robert R.; Kyogoku, Chieko; Sigurdsson, Snaevar; Vlasova, Irina A.; Davies, Leela R. L.; Baechler, Emily C.; Plenge, Robert M.; Koeuth, Thearith; Ortmann, Ward A.; Hom, Geoffrey; Bauer, Jason W.; Gillett, Clarence; Burtt, Noel; Cunninghame Graham, Deborah S.; Onofrio, Robert; Petri, Michelle; Gunnarsson, Iva; Svenungsson, Elisabet; Rönnblom, Lars; Nordmark, Gunnel; Gregersen, Peter K.; Moser, Kathy; Gaffney, Patrick M.; Criswell, Lindsey A.; Vyse, Timothy J.; Syvänen, Ann-Christine; Bohjanen, Paul R.; Daly, Mark J.; Behrens, Timothy W.; Altshuler, David

    2007-01-01

    Systematic genome-wide studies to map genomic regions associated with human diseases are becoming more practical. Increasingly, efforts will be focused on the identification of the specific functional variants responsible for the disease. The challenges of identifying causal variants include the need for complete ascertainment of genetic variants and the need to consider the possibility of multiple causal alleles. We recently reported that risk of systemic lupus erythematosus (SLE) is strongly associated with a common SNP in IFN regulatory factor 5 (IRF5), and that this variant altered spicing in a way that might provide a functional explanation for the reproducible association to SLE risk. Here, by resequencing and genotyping in patients with SLE, we find evidence for three functional alleles of IRF5: the previously described exon 1B splice site variant, a 30-bp in-frame insertion/deletion variant of exon 6 that alters a proline-, glutamic acid-, serine- and threonine-rich domain region, and a variant in a conserved polyA+ signal sequence that alters the length of the 3′ UTR and stability of IRF5 mRNAs. Haplotypes of these three variants define at least three distinct levels of risk to SLE. Understanding how combinations of variants influence IRF5 function may offer etiological and therapeutic insights in SLE; more generally, IRF5 and SLE illustrates how multiple common variants of the same gene can together influence risk of common disease. PMID:17412832

  19. From patenting genes to proteins: the search for utility via function.

    PubMed

    Ilag, Lawrence L; Ilag, Leodegario M; Ilag, Leodevico L

    2002-05-01

    The debate regarding the patenting of genes has extended into the post-genome era. With only approximately 35000 genes deduced from the draft sequence of the human genome, there are fears that a few companies have already gained monopoly on the potential benefits from this knowledge. Nevertheless, it is accepted that proteins determine gene function and function is not readily predicted from gene sequence. Furthermore, genes can encode multiple proteins and a single protein can have multiple functions. Here, we argue that unraveling the intrinsic complexity of proteins and their functions is the key towards determining the utility requirement for patenting protein inventions and consider the possible socioeconomic impact.

  20. Cross-study analysis of genomic data defines the ciliate multigenic epiplasmin family: strategies for functional analysis in Paramecium tetraurelia

    PubMed Central

    Damaj, Raghida; Pomel, Sébastien; Bricheux, Geneviève; Coffe, Gérard; Viguès, Bernard; Ravet, Viviane; Bouchard, Philippe

    2009-01-01

    Background The sub-membranous skeleton of the ciliate Paramecium, the epiplasm, is composed of hundreds of epiplasmic scales centered on basal bodies, and presents a complex set of proteins, epiplasmins, which belong to a multigenic family. The repeated duplications observed in the P. tetraurelia genome present an interesting model of the organization and evolution of a multigenic family within a single cell. Results To study this multigenic family, we used phylogenetic, structural, and analytical transcriptional approaches. The phylogenetic method defines 5 groups of epiplasmins in the multigenic family. A refined analysis by Hydrophobic Cluster Analysis (HCA) identifies structural characteristics of 51 epiplasmins, defining five separate groups, and three classes. Depending on the sequential arrangement of their structural domains, the epiplasmins are defined as symmetric, asymmetric or atypical. The EST data aid in this classification, in the identification of putative regulating sequences such as TATA or CAAT boxes. When specific RNAi experiments were conducted using sequences from either symmetric or asymmetric classes, phenotypes were drastic. Local effects show either disrupted or ill-shaped epiplasmic scales. In either case, this results in aborted cell division. Using structural features, we show that 4 epiplasmins are also present in another ciliate, Tetrahymena thermophila. Their affiliation with the distinctive structural groups of Paramecium epiplasmins demonstrates an interspecific multigenic family. Conclusion The epiplasmin multigenic family illustrates the history of genomic duplication in Paramecium. This study provides a framework which can guide functional analysis of epiplasmins, the major components of the membrane skeleton in ciliates. We show that this set of proteins handles an important developmental information in Paramecium since maintenance of epiplasm organization is crucial for cell morphogenesis. PMID:19493334

  1. High-Functioning Autism and Asperger's Disorder: Utility and Meaning for Families

    ERIC Educational Resources Information Center

    Ruiz Calzada, Luisa; Pistrang, Nancy; Mandy, William P. L.

    2012-01-01

    We used framework analysis to investigate the utility of pervasive developmental disorder diagnoses, interviewing young people (aged 9-16 years) with high-functioning autistic disorder (AD) and Asperger's disorder (AsD), and their parents. Twenty two participants from ten families described both gains and costs resulting from diagnosis. Perceived…

  2. Utility of the International Classification of Functioning, Disability and Health (ICF) for Educational Psychologists' Work

    ERIC Educational Resources Information Center

    Aljunied, Mariam; Frederickson, Norah

    2014-01-01

    Despite embracing a bio-psycho-social perspective, the World Health Organization's International Classification of Functioning, Disability and Health (ICF) assessment framework has had limited application to date with children who have special educational needs (SEN). This study examines its utility for educational psychologists' work with…

  3. Surface-Directed Assembly of Sequence-Defined Synthetic Polymers into Networks of Hexagonally Patterned Nanoribbons with Controlled Functionalities.

    PubMed

    Chen, Chun-Long; Zuckermann, Ronald N; DeYoreo, James J

    2016-05-24

    The exquisite self-assembly of proteins and peptides in nature into highly ordered functional materials has inspired innovative approaches to the design and synthesis of biomimetic materials. While sequence-defined polymers hold great promise to mimic proteins and peptides for functions, controlled assembly of them on surfaces still remains underdeveloped. Here, we report the assembly of 12-mer peptoids containing alternating acidic and aromatic monomers into networks of hexagonally patterned nanoribbons on mica surfaces. Ca(2+)-carboxylate coordination creates peptoid-peptoid and peptoid-mica interactions that control self-assembly. In situ atomic force microscopy (AFM) shows that peptoids first assemble into discrete nanoparticles; these particles then transform into hexagonally patterned nanoribbons on mica surfaces. AFM-based dynamic force spectroscopy studies show that peptoid-mica interactions are much stronger than peptoid-peptoid interactions, illuminating the driving forces for mica-directed peptoid assembly. We further demonstrate the display of functional domains at the N-terminus of assembling peptoids to produce extended networks with similar hierarchical structures. This research demonstrates that surface-directed peptoid assembly can be used as a robust platform to develop biomimetic coating materials for applications.

  4. Genetic analysis of the Salmonella enterica type III secretion-associated ATPase InvC defines discrete functional domains.

    PubMed

    Akeda, Yukihiro; Galán, Jorge E

    2004-04-01

    An essential component of all type III secretion systems is a highly conserved ATPase that shares significant amino acid sequence similarity to the beta subunit of the F(0)F(1) ATPases and is thought to provide the energy for the secretion process. We have performed a genetic and functional analysis of InvC, the ATPase associated with the Salmonella enterica type III secretion system encoded within its pathogenicity island 1. Through a mutagenesis analysis, we have identified amino acid residues that are essential for specific activities of InvC, such as nucleotide hydrolysis and membrane binding. This has allowed us to define discrete domains of InvC that are specifically associated with different essential activities of this protein.

  5. Recovering functions defined on the unit sphere by integration on a special family of sub-spheres

    NASA Astrophysics Data System (ADS)

    Salman, Yehonatan

    2016-05-01

    The aim of this article is to derive a reconstruction formula for the recovery of C1 functions, defined on the unit sphere {{{S}}}^{n - 1} , given their integrals on a special family of n - 2 dimensional sub-spheres. For a fixed point overline{a} strictly inside {{{S}}}^{n - 1} , each sub-sphere in this special family is obtained by intersection of {{{S}}}^{n - 1} with a hyperplane passing through overline{a} . The case overline{a} = 0 results in an inversion formula for the special case of integration on great spheres (i.e., Funk transform). The limiting case where pin {{{S}}}^{n - 1} and overline{a}→ p results in an inversion formula for the special case of integration on spheres passing through a common point in {{{S}}}^{n - 1}.

  6. Utility functions and resource management in an oversubscribed heterogeneous computing environment

    SciTech Connect

    Khemka, Bhavesh; Friese, Ryan; Briceno, Luis Diego; Siegel, Howard Jay; Maciejewski, Anthony A.; Koenig, Gregory A.; Groer, Christopher S.; Hilton, Marcia M.; Poole, Stephen W.; Okonski, G.; Rambharos, R.

    2014-09-26

    We model an oversubscribed heterogeneous computing system where tasks arrive dynamically and a scheduler maps the tasks to machines for execution. The environment and workloads are based on those being investigated by the Extreme Scale Systems Center at Oak Ridge National Laboratory. Utility functions that are designed based on specifications from the system owner and users are used to create a metric for the performance of resource allocation heuristics. Each task has a time-varying utility (importance) that the enterprise will earn based on when the task successfully completes execution. We design multiple heuristics, which include a technique to drop low utility-earning tasks, to maximize the total utility that can be earned by completing tasks. The heuristics are evaluated using simulation experiments with two levels of oversubscription. The results show the benefit of having fast heuristics that account for the importance of a task and the heterogeneity of the environment when making allocation decisions in an oversubscribed environment. Furthermore, the ability to drop low utility-earning tasks allow the heuristics to tolerate the high oversubscription as well as earn significant utility.

  7. Utility functions and resource management in an oversubscribed heterogeneous computing environment

    DOE PAGES

    Khemka, Bhavesh; Friese, Ryan; Briceno, Luis Diego; ...

    2014-09-26

    We model an oversubscribed heterogeneous computing system where tasks arrive dynamically and a scheduler maps the tasks to machines for execution. The environment and workloads are based on those being investigated by the Extreme Scale Systems Center at Oak Ridge National Laboratory. Utility functions that are designed based on specifications from the system owner and users are used to create a metric for the performance of resource allocation heuristics. Each task has a time-varying utility (importance) that the enterprise will earn based on when the task successfully completes execution. We design multiple heuristics, which include a technique to drop lowmore » utility-earning tasks, to maximize the total utility that can be earned by completing tasks. The heuristics are evaluated using simulation experiments with two levels of oversubscription. The results show the benefit of having fast heuristics that account for the importance of a task and the heterogeneity of the environment when making allocation decisions in an oversubscribed environment. Furthermore, the ability to drop low utility-earning tasks allow the heuristics to tolerate the high oversubscription as well as earn significant utility.« less

  8. Surface-Directed Assembly of Sequence-Defined Synthetic Polymers into Networks of Hexagonally Patterned Nanoribbons with Controlled Functionalities

    SciTech Connect

    Chen, Chun-Long; Zuckermann, Ronald N.; DeYoreo, James J.

    2016-05-24

    The exquisite self-assembly of proteins and peptides in nature into highly ordered functional materials has inspired innovative approaches to biomimetic materials design and synthesis. Here we report the assembly of peptoids—a class of highly stable sequence-defined synthetic polymers—into biomimetic materials on mica surfaces. The assembling 12-mer peptoid contains alternating acidic and aromatic residues, and the presence of Ca2+ cations creates peptoid-peptoid and peptoid-mica interactions that drive assembly. In situ atomic force microscopy (AFM) shows that peptoids first assemble into discrete nanoparticles, these particles then transform into hexagonally-patterned nanoribbons on mica surfaces. AFM-based dynamic force spectroscopy (DFS) studies show that peptoid-mica interactions are much stronger than peptoidpeptoid interactions in the presence of Ca2+, illuminating the physical parameters that drive peptoid assembly. We further demonstrate the display of functional groups at the N-terminus of assembling peptoid sequence to produce biomimetic materials with similar hierarchical structures. This research demonstrates that surface-directed peptoid assembly can be used as a robust platform to develop biomimetic coating materials for applications.

  9. High-functioning autism and Asperger's disorder: utility and meaning for families.

    PubMed

    Ruiz Calzada, Luisa; Pistrang, Nancy; Mandy, William P L

    2012-02-01

    We used framework analysis to investigate the utility of pervasive developmental disorder diagnoses, interviewing young people (aged 9-16 years) with high-functioning autistic disorder (AD) and Asperger's disorder (AsD), and their parents. Twenty two participants from ten families described both gains and costs resulting from diagnosis. Perceived advantages of AD and AsD diagnosis were increased understanding and practical support, and parental empowerment. Disadvantages included the effects of stigma and concerns about validity. Participants tended to consider AsD and AD as interchangeable terms. Findings suggest that the utility of AD and AsD depends upon both their validity and how these diagnoses are received in their cultural, economic and legislative context. Improvement of post-diagnostic services will improve the utility of AD and AsD.

  10. Identifying functionally important cis-peptide containing segments in proteins and their utility in molecular function annotation.

    PubMed

    Das, Sreetama; Ramakumar, Suryanarayanarao; Pal, Debnath

    2014-12-01

    Cis-peptide embedded segments are rare in proteins but often highlight their important role in molecular function when they do occur. The high evolutionary conservation of these segments illustrates this observation almost universally, although no attempt has been made to systematically use this information for the purpose of function annotation. In the present study, we demonstrate how geometric clustering and level-specific Gene Ontology molecular-function terms (also known as annotations) can be used in a statistically significant manner to identify cis-embedded segments in a protein linked to its molecular function. The present study identifies novel cis-peptide fragments, which are subsequently used for fragment-based function annotation. Annotation recall benchmarks interpreted using the receiver-operator characteristic plot returned an area-under-curve > 0.9, corroborating the utility of the annotation method. In addition, we identified cis-peptide fragments occurring in conjunction with functionally important trans-peptide fragments, providing additional insights into molecular function. We further illustrate the applicability of our method in function annotation where homology-based annotation transfer is not possible. The findings of the present study add to the repertoire of function annotation approaches and also facilitate engineering, design and allied studies around the cis-peptide neighborhood of proteins.

  11. The Utility of Forms and Functions of Aggression in Emerging Adulthood: Association with Personality Disorder Symptomatology

    ERIC Educational Resources Information Center

    Ostrov, Jamie M.; Houston, Rebecca J.

    2008-01-01

    A sample of 679 (341 women) emerging adults (M = 18.90 years; SD = 1.11; range = 18.00-22.92) participated in a study on the utility of forms (i.e., physical and relational) and functions (i.e., proactive and reactive) of aggression. We examined the link between these four subtypes of aggression and personality pathology (i.e., psychopathic…

  12. Pathways of Polyunsaturated Fatty Acid Utilization: Implications for Brain Function in Neuropsychiatric Health and Disease

    PubMed Central

    Liu, Joanne J.; Green, Pnina; Mann, J. John; Rapoport, Stanley I.; Sublette, M. Elizabeth

    2014-01-01

    Essential polyunsaturated fatty acids (PUFAs) have profound effects on brain development and function. Abnormalities of PUFA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimer’s disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUFA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUFA utilization, highlighting their relevance to neuropsychiatric disease. PMID:25498862

  13. When mothering goes awry: Challenges and opportunities for utilizing evidence across rodent, nonhuman primate and human studies to better define the biological consequences of negative early caregiving☆

    PubMed Central

    Sánchez, Mar M.; Gonzalez, Andrea

    2016-01-01

    Across mammalian species, mothers shape socio-emotional development and serve as essential external regulators of infant physiology, brain development, behavior patterns, and emotional regulation. Caregiving quality, consistency and predictability shape the infant's underlying neurobiological processes. Although the requirements for “optimal” caregiving differ across species, the negative long-term consequences of the absence of needed caregiving (e.g. neglect) or the presence of harmful/aversive caregiving (e.g. physical abuse), are translatable across species. Recognizing the significant potential of cross species comparisons in terms of defining underlying mechanisms, effective translation requires consideration of the evolutionary, ecological, and fundamental biological and developmental differences between and among species. This review provides both an overview of several success stories of cross-species translations in relation to negative caregiving and a template for future studies seeking to most effectively define the underlying biological processes and advance research dedicated to mitigating the lasting negative health consequences of child maltreatment. PMID:26506032

  14. Comparative evaluation of mathematical functions to describe growth and efficiency of phosphorus utilization in growing pigs.

    PubMed

    Kebreab, E; Schulin-Zeuthen, M; Lopez, S; Soler, J; Dias, R S; de Lange, C F M; France, J

    2007-10-01

    Success of pig production depends on maximizing return over feed costs and addressing potential nutrient pollution to the environment. Mathematical modeling has been used to describe many important aspects of inputs and outputs of pork production. This study was undertaken to compare 4 mathematical functions for the best fit in terms of describing specific data sets on pig growth and, in a separate experiment, to compare these 4 functions for describing of P utilization for growth. Two data sets with growth data were used to conduct growth analysis and another data set was used for P efficiency analysis. All data sets were constructed from independent trials that measured BW, age, and intake. Four growth functions representing diminishing returns (monomolecular), sigmoidal with a fixed point of inflection (Gompertz), and sigmoidal with a variable point of inflection (Richards and von Bertalanffy) were used. Meta-analysis of the data was conducted to identify the most appropriate functions for growth and P utilization. Based on Bayesian information criteria, the Richards equation described the BW vs. age data best. The additional parameter of the Richards equation was necessary because the data required a lower point of inflection (138 d) than the Gompertz, with a fixed point of inflexion at 1/e times the final BW (189 d), could accommodate. Lack of flexibility in the Gompertz equation was a limitation to accurate prediction. The monomolecular equation was best at determining efficiencies of P utilization for BW gain compared with the sigmoidal functions. The parameter estimate for the rate constant in all functions decreased as available P intake increased. Average efficiencies during different stages of growth were calculated and offer insight into targeting stages where high feed (nutrient) input is required and when adjustments are needed to accommodate the loss of efficiency and the reduction of potential pollution problems. It is recommended that the Richards

  15. Utilization of Functional Exercises to Build Regional Emergency Preparedness among Rural Health Organizations in the US.

    PubMed

    Obaid, Jannah M; Bailey, Ginger; Wheeler, Heidi; Meyers, Laura; Medcalf, Sharon J; Hansen, Keith F; Sanger, Kristine K; Lowe, John J

    2017-01-30

    Rural communities face barriers to disaster preparedness and considerable risk of disasters. Emergency preparedness among rural communities has improved with funding from federal programs and implementation of a National Incident Management System. The objective of this project was to design and implement disaster exercises to test decision making by rural response partners to improve regional planning, collaboration, and readiness. Six functional exercises were developed and conducted among three rural Nebraska (USA) regions by the Center for Preparedness Education (CPE) at the University of Nebraska Medical Center (Omaha, Nebraska USA). A total of 83 command centers participated. Six functional exercises were designed to test regional response and command-level decision making, and each 3-hour exercise was followed by a 3-hour regional after action conference. Participant feedback, single agency debriefing feedback, and regional After Action Reports were analyzed. Functional exercises were able to test command-level decision making and operations at multiple agencies simultaneously with limited funding. Observations included emergency management jurisdiction barriers to utilization of unified command and establishment of joint information centers, limited utilization of documentation necessary for reimbursement, and the need to develop coordinated public messaging. Functional exercises are a key tool for testing command-level decision making and response at a higher level than what is typically achieved in tabletop or short, full-scale exercises. Functional exercises enable evaluation of command staff, identification of areas for improvement, and advancing regional collaboration among diverse response partners. Obaid JM , Bailey G , Wheeler H , Meyers L , Medcalf SJ , Hansen KF , Sanger KK , Lowe JJ . Utilization of functional exercises to build regional emergency preparedness among rural health organizations in the US. Prehosp Disaster Med. 2017;32(2):1-7.

  16. An analysis of the utilization of e-mail by physicians and patients: defining benefits, addressing concerns and forecasting implications on the doctor-patient relationship.

    PubMed

    Lang, Kirk T; Kiel, Joan M

    2008-01-01

    Though e-mail is ubiquitous in everyday life, it has not been the preferred mode of communication between physicians and patients. Several factors, including privacy and security, reimbursement and legal concerns, have been seen as barriers toward increased utilization. This article examines effect of e-mail on the doctor-patient relationship. It also addresses concerns expressed by providers and patients, and explores technology- and policy-based solutions to many of these issues.

  17. Optimum allocation of monitoring wells around a solid-waste landfill site using precursor indicators and fuzzy utility functions

    NASA Astrophysics Data System (ADS)

    Morisawa, Shinsuke; Inoue, Yoriteru

    1991-06-01

    An optimum monitoring well network (number of wells and their locations) is proposed which enables rapid, redundant and economical detection of contaminants in groundwater around a solid-waste landfill site. The procedure also guarantees detection of the contaminants given data on the probability of detection at different points in the saturated zone. The well selection is accomplished using a two-step procedure: (1) A Monte Carlo simulation of contaminant transport in the unconsolidated shallow saturated zone is conducted. In this zone hydrogeological parameters are variable but their stochastic distributions are known. Three governing equations are solved numerically using the finite-difference method to obtain the travel time distribution of each contaminant: the two-dimensional steady-state groundwater flow equation; the two-dimensional transient convective-dispersion equation for sorptive contaminants; and the sorptive-desorptive isotherm equation. (2) The procedure utilizes "fuzzy" theory, comprising of a set of newly developed mathematical techniques to deal with uncertainty in a wide range of man-machine interface issues, to assist in the design of a monitoring well network. The procedure requires a mathematical description of a four-attribute design problem using fuzzy utility functions and fuzzy weights. An optimum monitoring well network is then defined as the network having maximum total utility, which is evaluated as a fuzzy expectation of weighted arithmetic sums of the four utilities. One result of the simulation is the definition of relationships between the contaminant of interest and precursor materials. The precursor material can then serve as an "indicator" for faster detection of contaminant leaked from solid-waste landfill site. The procedures are applied to a hypothetical solid-waste landfill site under appropriate conditions to obtain the optimum monitoring well network for detection of precursor indicators. Sensitivity analysis of the

  18. Utility of Functional Hemodynamics and Echocardiography to Aid Diagnosis and Management of Shock.

    PubMed

    McGee, William T; Raghunathan, Karthik; Adler, Adam C

    2015-12-01

    The utility of functional hemodynamics and bedside ultrasonography is increasingly recognized as advantageous for both improved diagnosis and management of shock states. In contrast to conventional "static" measures, "dynamic" hemodynamic measures and bedside imaging modalities enhance pathophysiology-based comprehensive understanding of shock states and the response to therapy. The current editions of major textbooks in the primary specialties--in which clinicians routinely encounter patients in shock--including surgery, anesthesia, emergency medicine, and internal medicine continue to incorporate traditional (conventional) descriptions of shock that use well-described (but potentially misleading) intravascular pressures to classify shock states. Reliance on such intravascular pressure measurements is not as helpful as newer "dynamic" functional measures including ultrasonography to both better assess volume responsiveness and biventricular cardiac function. This review thus emphasizes the application of current functional hemodynamics and ultrasonography to the diagnosis and management of shock as a contrast to conventional "static" pressure-based measures.

  19. The clinical utility of functional capacity evaluations: the opinion of health professionals working within occupational rehabilitation.

    PubMed

    James, Carole; MacKenzie, Lynette

    2009-01-01

    Functional Capacity Evaluations (FCE's) are used within the occupational rehabilitation arena with the aim of assessing an individual's functional abilities in relation to work tasks. Therapists use a variety of different FCE's, both standardized and non standardized. This study aimed to investigate therapists' views on the clinical utility of FCE's in general and to identify if these differed between professional groups. A cross sectional study design was used. Health professionals who conduct FCE's and who worked for WorkCover accredited rehabilitation providers in NSW were surveyed. Surveys were returned from 79 participants working for 65 different rehabilitation providers. Of those who replied, 82\\% (n=63) were occupational therapists, 13% (n=10) physiotherapists and 5% (n=5) exercise physiologists. The mean years of professional experience was 10.9 years and the mean years of FCE experience was 5.3 years. Data were analyzed using STATA [v8.0] and the clinical utility of FCE's was considered relating to: usefulness & relevance; adaptability and flexibility; therapist perceived requirements and issues in practice. No differences were found related to the clinical utility of FCE's between professional groups or years of professional experience. The results suggest consistency and similarities in how FCE's are currently used in practice across NSW (Australia). Limitations of this study and areas for further research are suggested.

  20. Analytical study of the effects of soft tissue artefacts on functional techniques to define axes of rotation.

    PubMed

    De Rosario, Helios; Page, Álvaro; Besa, Antonio

    2017-02-06

    The accurate location of the main axes of rotation (AoR) is a crucial step in many applications of human movement analysis. There are different formal methods to determine the direction and position of the AoR, whose performance varies across studies, depending on the pose and the source of errors. Most methods are based on minimizing squared differences between observed and modelled marker positions or rigid motion parameters, implicitly assuming independent and uncorrelated errors, but the largest error usually results from soft tissue artefacts (STA), which do not have such statistical properties and are not effectively cancelled out by such methods. However, with adequate methods it is possible to assume that STA only account for a small fraction of the observed motion and to obtain explicit formulas through differential analysis that relate STA components to the resulting errors in AoR parameters. In this paper such formulas are derived for three different functional calibration techniques (Geometric Fitting, mean Finite Helical Axis, and SARA), to explain why each technique behaves differently from the others, and to propose strategies to compensate for those errors. These techniques were tested with published data from a sit-to-stand activity, where the true axis was defined using bi-planar fluoroscopy. All the methods were able to estimate the direction of the AoR with an error of less than 5°, whereas there were errors in the location of the axis of 30-40mm. Such location errors could be reduced to less than 17mm by the methods based on equations that use rigid motion parameters (mean Finite Helical Axis, SARA) when the translation component was calculated using the three markers nearest to the axis.

  1. Utility of the International Classification of Functioning, Disability and Health (ICF) for educational psychologists’ work

    PubMed Central

    Aljunied, Mariam; Frederickson, Norah

    2014-01-01

    Despite embracing a bio-psycho-social perspective, the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) assessment framework has had limited application to date with children who have special educational needs (SEN). This study examines its utility for educational psychologists’ work with children who have Autism Spectrum Disorders (ASD). Mothers of 40 children with ASD aged eight to 12 years were interviewed using a structured protocol based on the ICF framework. The Diagnostic Interview for Social and Communication Disorder (DISCO) was completed with a subset of 19 mothers. Internal consistency and inter-rater reliability of the interview assessments were found to be acceptable and there was evidence for concurrent and discriminant validity. Despite some limitations, initial support for the utility of the ICF model suggests its potential value across educational, health and care fields. Further consideration of its relevance to educational psychologists in new areas of multi-agency working is warranted. PMID:26157197

  2. Microbial resource utilization traits and trade-offs: implications for community structure, functioning, and biogeochemical impacts at present and in the future

    PubMed Central

    Litchman, Elena; Edwards, Kyle F.; Klausmeier, Christopher A.

    2015-01-01

    Trait-based approaches provide a mechanistic framework to understand and predict the structure and functioning of microbial communities. Resource utilization traits and trade-offs are among key microbial traits that describe population dynamics and competition among microbes. Several important trade-offs have been identified for prokaryotic and eukaryotic microbial taxa that define contrasting ecological strategies and contribute to species coexistence and diversity. The shape, dimensionality, and hierarchy of trade-offs may determine coexistence patterns and need to be better characterized. Laboratory measured resource utilization traits can be used to explain temporal and spatial structure and dynamics of natural microbial communities and predict biogeochemical impacts. Global environmental change can alter microbial community composition through altering resource utilization by different microbes and, consequently, may modify biogeochemical impacts of microbes. PMID:25904900

  3. Utility and Limitations of Using Gene Expression Data to Identify Functional Associations

    PubMed Central

    Peng, Cheng; Shiu, Shin-Han

    2016-01-01

    Gene co-expression has been widely used to hypothesize gene function through guilt-by association. However, it is not clear to what degree co-expression is informative, whether it can be applied to genes involved in different biological processes, and how the type of dataset impacts inferences about gene functions. Here our goal is to assess the utility and limitations of using co-expression as a criterion to recover functional associations between genes. By determining the percentage of gene pairs in a metabolic pathway with significant expression correlation, we found that many genes in the same pathway do not have similar transcript profiles and the choice of dataset, annotation quality, gene function, expression similarity measure, and clustering approach significantly impacts the ability to recover functional associations between genes using Arabidopsis thaliana as an example. Some datasets are more informative in capturing coordinated expression profiles and larger data sets are not always better. In addition, to recover the maximum number of known pathways and identify candidate genes with similar functions, it is important to explore rather exhaustively multiple dataset combinations, similarity measures, clustering algorithms and parameters. Finally, we validated the biological relevance of co-expression cluster memberships with an independent phenomics dataset and found that genes that consistently cluster with leucine degradation genes tend to have similar leucine levels in mutants. This study provides a framework for obtaining gene functional associations by maximizing the information that can be obtained from gene expression datasets. PMID:27935950

  4. Hydrocephalus Defined

    MedlinePlus

    ... narrow pathways. CSF is in constant production and absorption; it has a defined pathway from the lateral ... there is an imbalance of production and/or absorption. With most types of hydrocephalus, the fluid gets ...

  5. Functionalization of plasmonic metamaterials utilizing metal-organic framework thin films

    NASA Astrophysics Data System (ADS)

    Jakšić, Zoran; Popović, Zora; Djerdj, Igor; Jaćimović, Željko K.; Radulović, Katarina

    2012-05-01

    We considered theoretically and experimentally a strategy to functionalize plasmonic metamaterials utilizing either a metal-organic framework (MOF) or inorganic-organic hybrids for application in adsorption-based gas sensing. MOFs are one-dimensional (1D), 2D or 3D crystalline compounds that simultaneously contain metal ions or ion clusters and organic moieties, forming thus porous networks ensuring an increased effective surface for adsorption. Metamaterials can enhance plasmonic sensor performance through metal-dielectric nanocompositing that simultaneously tailors the electromagnetic response and boosts adsorption of the targeted analyte through the use of nanopores. To perform functionalization, it is necessary to integrate one or several layers of MOF nanocrystals with the metamaterial scaffold. The simplest approach is to use dip or drop coating or the layer-by-layer technique. The scaffolds that we considered included freestanding, ultrathin membranes and sandwich structures with nanoaperture arrays. For this investigation, we used a non-aqueous sol-gel route to synthesize vanadium oxyanthracene carboxylate, a novel material with 1D crystal structure. Our results suggest that preferential concentration of analyte within the MOF pores may ensure improved adsorption and thus sensor sensitivity enhancement. Also, one may increase selectivity by introducing nanoparticle fillers or by utilizing other functionalizing materials such as catalysts or ligands.

  6. Utility of transcranial Doppler ultrasound for the integrative assessment of cerebrovascular function.

    PubMed

    Willie, C K; Colino, F L; Bailey, D M; Tzeng, Y C; Binsted, G; Jones, L W; Haykowsky, M J; Bellapart, J; Ogoh, S; Smith, K J; Smirl, J D; Day, T A; Lucas, S J; Eller, L K; Ainslie, P N

    2011-03-30

    There is considerable utility in the use of transcranial Doppler ultrasound (TCD) to assess cerebrovascular function. The brain is unique in its high energy and oxygen demand but limited capacity for energy storage that necessitates an effective means of regional blood delivery. The relative low cost, ease-of-use, non-invasiveness, and excellent temporal resolution of TCD make it an ideal tool for the examination of cerebrovascular function in both research and clinical settings. TCD is an efficient tool to access blood velocities within the cerebral vessels, cerebral autoregulation, cerebrovascular reactivity to CO(2), and neurovascular coupling, in both physiological states and in pathological conditions such as stroke and head trauma. In this review, we provide: (1) an overview of TCD methodology with respect to other techniques; (2) a methodological synopsis of the cerebrovascular exam using TCD; (3) an overview of the physiological mechanisms involved in regulation of the cerebral blood flow; (4) the utility of TCD for assessment of cerebrovascular pathology; and (5) recommendations for the assessment of four critical and complimentary aspects of cerebrovascular function: intra-cranial blood flow velocity, cerebral autoregulation, cerebral reactivity, and neurovascular coupling. The integration of these regulatory mechanisms from an integrated systems perspective is discussed, and future research directions are explored.

  7. Pseudomonas aeruginosa Cif defines a distinct class of α/β epoxide hydrolases utilizing a His/Tyr ring-opening pair.

    PubMed

    Bahl, Christopher D; Madden, Dean R

    2012-02-01

    The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that secretes a multitude of virulence factors during the course of infection. Among these is Cif, an epoxide hydrolase (EH) that reduces the functional localization of the cystic fibrosis transmembrane conductance regulator in epithelial cells. In addition to being the first reported EH virulence factor, Cif possesses unique sequence deviations from canonical EH motifs. Foremost among these is the substitution of a histidine for the first epoxide ring-opening tyrosine in the active site. To test the functional equivalence of Tyr and His side chains at this position, we have generated the mutant Cif-H177Y. Structural analysis confirms that both the WT His and mutant Tyr side chains can be accommodated without large-scale conformational changes. However, the Tyr mutant is functionally inactive. Based on a detailed analysis of the structure of the Tyr mutant, it appears that Cif's main-chain conformation imposes a functional requirement for a His at this position. Comparison with canonical EH structures reveals additional conformational differences, which are coupled to divergent sequence characteristics. When used to probe the genomes of other opportunistic pathogens, these sequence-structure criteria uncover candidate sequences that appear to form a distinct subfamily of Cif-like epoxide hydrolases characterized by a conserved His/Tyr ring-opening pair.

  8. Optimization of the dressing parameters in cylindrical grinding based on a generalized utility function

    NASA Astrophysics Data System (ADS)

    Aleksandrova, Irina

    2016-01-01

    The existing studies, concerning the dressing process, focus on the major influence of the dressing conditions on the grinding response variables. However, the choice of the dressing conditions is often made, based on the experience of the qualified staff or using data from reference books. The optimal dressing parameters, which are only valid for the particular methods and dressing and grinding conditions, are also used. The paper presents a methodology for optimization of the dressing parameters in cylindrical grinding. The generalized utility function has been chosen as an optimization parameter. It is a complex indicator determining the economic, dynamic and manufacturing characteristics of the grinding process. The developed methodology is implemented for the dressing of aluminium oxide grinding wheels by using experimental diamond roller dressers with different grit sizes made of medium- and high-strength synthetic diamonds type ??32 and ??80. To solve the optimization problem, a model of the generalized utility function is created which reflects the complex impact of dressing parameters. The model is built based on the results from the conducted complex study and modeling of the grinding wheel lifetime, cutting ability, production rate and cutting forces during grinding. They are closely related to the dressing conditions (dressing speed ratio, radial in-feed of the diamond roller dresser and dress-out time), the diamond roller dresser grit size/grinding wheel grit size ratio, the type of synthetic diamonds and the direction of dressing. Some dressing parameters are determined for which the generalized utility function has a maximum and which guarantee an optimum combination of the following: the lifetime and cutting ability of the abrasive wheels, the tangential cutting force magnitude and the production rate of the grinding process. The results obtained prove the possibility of control and optimization of grinding by selecting particular dressing

  9. Organization of Artificial Superlattices Utilizing Nanosheets as a Building Block and Exploration of Their Advanced Functions

    NASA Astrophysics Data System (ADS)

    Ma, Renzhi; Sasaki, Takayoshi

    2015-07-01

    This review covers some of the latest developments in the organization of artificial superlattice assemblies utilizing colloidal oxide or hydroxide nanosheets bearing a negative or positive charge, respectively. Various solution-based procedures, e.g., flocculation, electrostatic sequential adsorption, and Langmuir-Blodgett deposition, have been introduced for the self-assembly of 2D nanosheets. Superlattice composites or films integrated with different nanosheets may yield concerted or synergistic modulation, e.g., soft coupling or new electronic states at interfaces. This behavior offers an unprecedented opportunity for the exploration of high-performance devices, as well as advanced or novel functions that cannot be achieved with a single-component material.

  10. Estimation of a valuation function for a diabetes mellitus-specific preference-based measure of health: the Diabetes Utility Index.

    PubMed

    Sundaram, Murali; Smith, Michael J; Revicki, Dennis A; Miller, Lesley-Ann; Madhavan, Suresh; Hobbs, Gerry

    2010-01-01

    Preference-based measures of health (PBMH) provide 'preference' or 'utility' weights that enable the calculation of QALYs for the economic evaluations of interventions. The Diabetes Utility Index (DUI) was developed as a brief, self-administered, diabetes mellitus-specific PBMH that can efficiently estimate patient-derived health state utilities. To describe the development of the valuation function for the DUI, and to report the validation results of the valuation function. Multi-Attribute Utility Theory (MAUT) was used as the framework to develop a valuation function for the DUI. Twenty of 768 possible health states of the DUI classified as anchor states, single-attribute level states including corner states, and marker states were selected and described for preference elicitation interviews. Visual analogue scale and standard gamble (SG) exercises were used to measure preferences from individuals with diabetes recruited from primary care and community settings in and around Morgantown, WV, USA for the 20 health states defined by combinations of DUI attributes and severity levels. Data collected in the interviews were used to develop a valuation function that calculates utilities for the DUI health states and calculates attribute-level utilities. A validation survey of the valuation function was conducted in collaboration with the West Virginia University (WVU) Diabetes Institute. A total of 100 individuals with diabetes were interviewed and their preferences for various DUI health states measured. From data generated in the interviews, a DUI valuation function was developed on a scale where 1.00 = perfect health (PH) and 0.00 = the all worse 'pits' state, and adjusted to yield utilities on the conventional scale 1.00 = PH and 0.00 = dead. A total of 396 patients with diabetes who received care at WVU clinics completed a DUI mail validation survey (response rate = 33%). Clinical data consisting of International Classification of Diseases, 9th edition, diagnosis

  11. Utilization of functional near infrared spectroscopy for non-invasive evaluation

    NASA Astrophysics Data System (ADS)

    Halim, A. A. A.; Laili, M. H.; Aziz, N. A.; Laili, A. R.; Salikin, M. S.; Rusop, M.

    2016-07-01

    The goal of this brief review is to report the techniques of functional near infrared spectroscopy for non-invasive evaluation in human study. The development of functional near infrared spectroscopy (fNIRS) technologies has advanced quantification signal using multiple wavelength and detector to solve the propagation of light inside the tissues including the absorption, scattering coefficient and to define the light penetration into tissues multilayers. There are a lot of studies that demonstrate signal from fNIRS which can be used to evaluate the changes of oxygenation level and measure the limitation of muscle performance in human brain and muscle tissues. Comprehensive reviews of diffuse reflectance based on beer lambert law theory were presented in this paper. The principle and development of fNIRS instrumentation is reported in detail.

  12. Toad heart utilizes exclusively slow skeletal muscle troponin T: an evolutionary adaptation with potential functional benefits.

    PubMed

    Feng, Han-Zhong; Chen, Xuequn; Hossain, M Moazzem; Jin, Jian-Ping

    2012-08-24

    The three isoforms of vertebrate troponin T (TnT) are normally expressed in a muscle type-specific manner. Here we report an exception that the cardiac muscle of toad (Bufo) expresses exclusively slow skeletal muscle TnT (ssTnT) together with cardiac forms of troponin I and myosin as determined using immunoblotting, cDNA cloning, and/or LC-MS/MS. Using RT-PCR and 3'- and 5'-rapid amplification of cDNA ends on toad cardiac mRNA, we cloned full-length cDNAs encoding two alternatively spliced variants of ssTnT. Expression of the cloned cDNAs in Escherichia coli confirmed that the toad cardiac muscle expresses solely ssTnT, predominantly the low molecular weight variant with the exon 5-encoded NH(2)-terminal segment spliced out. Functional studies were performed in ex vivo working toad hearts and compared with the frog (Rana) hearts. The results showed that toad hearts had higher contractile and relaxation velocities and were able to work against a significantly higher afterload than that of frog hearts. Therefore, the unique evolutionary adaptation of utilizing exclusively ssTnT in toad cardiac muscle corresponded to a fitness value from improving systolic function of the heart. The data demonstrated a physiological importance of the functional diversity of TnT isoforms. The structure-function relationship of TnT may be explored for the development of new treatment of heart failure.

  13. Utility of wireless motility capsule and lactulose breath testing in the evaluation of patients with chronic functional bloating

    PubMed Central

    Triadafilopoulos, George

    2016-01-01

    Background The precise aetiology of chronic bloating remains poorly understood and underlying gastroparesis, small bowel bacterial overgrowth and colonic inertia may, individually or collectively, play a role. Aims In this retrospective cohort analysis of symptomatic patients with chronic persistent bloating, we determined the clinical utility of wireless motility capsule and lactulose breath test in further defining the underlying aetiology for functional bloating. Methods Consecutive patients with chronic bloating underwent clinical assessment, wireless motility capsule testing and lactulose breath testing using standard protocols. Results 52 patients qualified for inclusion in this analysis, fulfilling Rome III criteria for functional bloating. Most patients (54%) had an abnormal wireless motility capsule study; of those, 11.5% had evidence of gastroparesis, 7.7% had small bowel transit delay, 15.8% had colonic inertia, 3.8% had delayed gastric and small bowel transit, 5.6% had combined gastric and colonic transit delay, 3.8% had delayed small bowel and colonic transit, and 5.6% had delayed gastric, small bowel and colon transit times. Using clinical questionnaires the median scores for bloating, constipation and eructation were not significantly different. Neither constipation nor eructation was specific to gastroparesis or colonic inertia but bloating was numerically more prevalent and severe in patients with delayed small bowel transit. 40% of patients had positive lactulose breath test but had no distinguishing clinical characteristics. Conclusions Chronic functional bloating may reflect underlying gastroparesis, small intestinal bacterial overgrowth or colonic inertia. Wireless motility capsule and lactulose breath test are useful in the assessment of patients with bloating and should be considered during evaluation. PMID:27648298

  14. Parametrically defined differential equations

    NASA Astrophysics Data System (ADS)

    Polyanin, A. D.; Zhurov, A. I.

    2017-01-01

    The paper deals with nonlinear ordinary differential equations defined parametrically by two relations. It proposes techniques to reduce such equations, of the first or second order, to standard systems of ordinary differential equations. It obtains the general solution to some classes of nonlinear parametrically defined ODEs dependent on arbitrary functions. It outlines procedures for the numerical solution of the Cauchy problem for parametrically defined differential equations.

  15. ZBED evolution: repeated utilization of DNA transposons as regulators of diverse host functions.

    PubMed

    Hayward, Alexander; Ghazal, Awaisa; Andersson, Göran; Andersson, Leif; Jern, Patric

    2013-01-01

    ZBED genes originate from domesticated hAT DNA transposons and encode regulatory proteins of diverse function in vertebrates. Here we reveal the evolutionary relationship between ZBED genes and demonstrate that they are derived from at least two independent domestication events in jawed vertebrate ancestors. We show that ZBEDs form two monophyletic clades, one of which has expanded through several independent duplications in host lineages. Subsequent diversification of ZBED genes has facilitated regulation of multiple diverse fundamental functions. In contrast to known examples of transposable element exaptation, our results demonstrate a novel unprecedented capacity for the repeated utilization of a family of transposable element-derived protein domains sequestered as regulators during the evolution of diverse host gene functions in vertebrates. Specifically, ZBEDs have contributed to vertebrate regulatory innovation through the donation of modular DNA and protein interacting domains. We identify that C7ORF29, ZBED2, 3, 4, and ZBEDX form a monophyletic group together with ZBED6, that is distinct from ZBED1 genes. Furthermore, we show that ZBED5 is related to Buster DNA transposons and is phylogenetically separate from other ZBEDs. Our results offer new insights into the evolution of regulatory pathways, and suggest that DNA transposons have contributed to regulatory complexity during genome evolution in vertebrates.

  16. Mean-variance portfolio optimization by using time series approaches based on logarithmic utility function

    NASA Astrophysics Data System (ADS)

    Soeryana, E.; Fadhlina, N.; Sukono; Rusyaman, E.; Supian, S.

    2017-01-01

    Investments in stocks investors are also faced with the issue of risk, due to daily price of stock also fluctuate. For minimize the level of risk, investors usually forming an investment portfolio. Establishment of a portfolio consisting of several stocks are intended to get the optimal composition of the investment portfolio. This paper discussed about optimizing investment portfolio of Mean-Variance to stocks by using mean and volatility is not constant based on logarithmic utility function. Non constant mean analysed using models Autoregressive Moving Average (ARMA), while non constant volatility models are analysed using the Generalized Autoregressive Conditional heteroscedastic (GARCH). Optimization process is performed by using the Lagrangian multiplier technique. As a numerical illustration, the method is used to analyse some Islamic stocks in Indonesia. The expected result is to get the proportion of investment in each Islamic stock analysed.

  17. A national critical loads framework for atmospheric deposition effects assessment: II. Defining assessment end points, indicators, and functional subregions

    NASA Astrophysics Data System (ADS)

    Hunsaker, Carolyn; Graham, Robin; Turner, Robert S.; Ringold, Paul L.; Holdren, George R.; Strickland, Timothy C.

    1993-05-01

    The United States Environmental Protection Agency, with support from the US Department of Energy and the National Oceanographic and Atmospheric Administration, has been evaluating the feasibility of an effects-based (critical loads) approach to atmospheric pollutant regulation and abatement. The rationale used to develop three of the six steps in a flexible assessment framework (Strickland and others, 1992) is presented along with a discussion of a variety of implementation approaches and their ramifications. The rationale proposes that it is necessary to provide an explicit statement of the condition of the resource that is considered valuable (assessment end point) because: (1) individual ecosystem components may be more or less sensitive to deposition, (2) it is necessary to select indicators of ecosystem condition that can be objectively measured and that reflect changes in the quality of the assessment end point, and (3) acceptable status (i.e., value of indicator and quality of assessment end point at critical load) must be defined. The rationale also stresses the importance of defining the assessment regions and subregions to improve the analysis and understanding of the indicator response to deposition. Subregional definition can be based on a variety of criteria, including informed judgment or quantitative procedures. It also depends on the geographic scale at which exposure and effects models are accurate and on data availability, resolution, and quality.

  18. Functional VEGFA knockdown with artificial 3′-tailed mirtrons defined by 5′ splice site and branch point

    PubMed Central

    Kock, Kian Hong; Kong, Kiat Whye; Hoon, Shawn; Seow, Yiqi

    2015-01-01

    Mirtrons are introns that form pre-miRNA hairpins after splicing to produce RNA interference (RNAi) effectors distinct from Drosha-dependent intronic miRNAs, and will be especially useful for co-delivery of coding genes and RNAi. A specific family of mirtrons – 3′-tailed mirtrons – has hairpins precisely defined on the 5′ end by the 5′ splice site and 3′ end by the branch point. Here, we present design principles for artificial 3′-tailed mirtrons and demonstrate, for the first time, efficient gene knockdown with tailed mirtrons within eGFP coding region. These artificial tailed mirtrons, unlike canonical mirtrons, have very few sequence design restrictions. Tailed mirtrons targeted against VEGFA mRNA, the misregulation of which is causative of several disorders including cancer, achieved significant levels of gene knockdown. Tailed mirtron-mediated knockdown was further shown to be splicing-dependent, and at least as effective as equivalent artificial intronic miRNAs, with the added advantage of very defined cleavage sites for generation of mature miRNA guide strands. Further development and exploitation of this unique mirtron biogenesis pathway for therapeutic RNAi coupled into protein-expressing genes can potentially enable the development of precisely controlled combinatorial gene therapy. PMID:26089392

  19. Bayesian analysis versus discriminant function analysis: their relative utility in the diagnosis of coronary disease.

    PubMed

    Detrano, R; Leatherman, J; Salcedo, E E; Yiannikas, J; Williams, G

    1986-05-01

    Both Bayesian analysis assuming independence and discriminant function analysis have been used to estimate probabilities of coronary disease. To compare their relative accuracy, we submitted 303 subjects referred for coronary angiography to stress electrocardiography, thallium scintigraphy, and cine fluoroscopy. Severe angiographic disease was defined as at least one greater than 50% occlusion of a major vessel. Four calculations were done: (1) Bayesian analysis using literature estimates of pretest probabilities, sensitivities, and specificities was applied to the clinical and test data of a randomly selected subgroup (group I, 151 patients) to calculate posttest probabilities. (2) Bayesian analysis using literature estimates of pretest probabilities (but with sensitivities and specificities derived from the remaining 152 subjects [group II]) was applied to group I data to estimate posttest probabilities. (3) A discriminant function with logistic regression coefficients derived from the clinical and test variables of group II was used to calculate posttest probabilities of group I. (4) A discriminant function derived with the use of test results from group II and pretest probabilities from the literature was used to calculate posttest probabilities of group I. Receiver operating characteristic curve analysis showed that all four calculations could equivalently rank the disease probabilities for our patients. A goodness-of-fit analysis suggested the following relationship between the accuracies of the four calculations: (1) less than (2) approximately equal to (4) less than (3). Our results suggest that data-based discriminant functions are more accurate than literature-based Bayesian analysis assuming independence in predicting severe coronary disease based on clinical and noninvasive test results.

  20. Extraction of physical Schottky parameters using the Lambert function in Ni/AlGaN/GaN HEMT devices with defined conduction phenomena

    NASA Astrophysics Data System (ADS)

    Latry, O.; Divay, A.; Fadil, D.; Dherbécourt, P.

    2017-01-01

    Electrical characterization analyses are proposed in this work using the Lambert function on Schottky junctions in GaN wide band gap semiconductor devices for extraction of physical parameters. The Lambert function is used to give an explicit expression of the current in the Schottky junction. This function is applied with defined conduction phenomena, whereas other work presented arbitrary (or undefined) conduction mechanisms in such parameters’ extractions. Based upon AlGaN/GaN HEMT structures, extractions of parameters are undergone in order to provide physical characteristics. This work highlights a new expression of current with defined conduction phenomena in order to quantify the physical properties of Schottky contacts in AlGaN/GaN HEMT transistors. Project supported by the French Department of Defense (DGA).

  1. Defining chaos

    SciTech Connect

    Hunt, Brian R.; Ott, Edward

    2015-09-15

    In this paper, we propose, discuss, and illustrate a computationally feasible definition of chaos which can be applied very generally to situations that are commonly encountered, including attractors, repellers, and non-periodically forced systems. This definition is based on an entropy-like quantity, which we call “expansion entropy,” and we define chaos as occurring when this quantity is positive. We relate and compare expansion entropy to the well-known concept of topological entropy to which it is equivalent under appropriate conditions. We also present example illustrations, discuss computational implementations, and point out issues arising from attempts at giving definitions of chaos that are not entropy-based.

  2. Increasing the utility of the Functional Assessment for Burns Score: Not just for major burns.

    PubMed

    Smailes, Sarah T; Engelsman, Kayleen; Rodgers, Louise; Upson, Clara

    2016-02-01

    The Functional Assessment for Burns (FAB) score is established as an objective measure of physical function that predicts discharge outcome in adult patients with major burn. However, its validity in patients with minor and moderate burn is unknown. This is a multi-centre evaluation of the predictive validity of the FAB score for discharge outcome in adult inpatients with minor and moderate burns. FAB assessments were undertaken within 48 h of admission to (FAB 1), and within 48 h of discharge (FAB 2) from burn wards in 115 patients. Median age was 45 years and median burn size 4%. There were significant improvements in the patients' FAB scores (p<0.0001), 98 patients were discharged home (no social care) and 17 patients discharged to further inpatient rehabilitation or home with social care. FAB 1 score (≤ 14) is strongly associated with discharge to inpatient rehabilitation or home with social care (p=0.0001) and as such can be used to facilitate early discharge planning. FAB 2 (≤ 30) independently predicts discharge outcome to inpatient rehabilitation or home with social care (p<0.0001), increasing its utility to patients with minor and moderate burns.

  3. Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

    PubMed Central

    Morrison, Eamonn; Wai, Patty; Leonidou, Andri; Bland, Philip; Khalique, Saira; Farnie, Gillian; Daley, Frances; Peck, Barrie; Natrajan, Rachael

    2016-01-01

    The identification of functional driver events in cancer is central to furthering our understanding of cancer biology and indispensable for the discovery of the next generation of novel drug targets. It is becoming apparent that more complex models of cancer are required to fully appreciate the contributing factors that drive tumorigenesis in vivo and increase the efficacy of novel therapies that make the transition from pre-clinical models to clinical trials. Here we present a methodology for generating uniform and reproducible tumor spheroids that can be subjected to siRNA functional screening. These spheroids display many characteristics that are found in solid tumors that are not present in traditional two-dimension culture. We show that several commonly used breast cancer cell lines are amenable to this protocol. Furthermore, we provide proof-of-principle data utilizing the breast cancer cell line BT474, confirming their dependency on amplification of the epidermal growth factor receptor HER2 and mutation of phosphatidylinositol-4,5-biphosphate 3-kinase (PIK3CA) when grown as tumor spheroids. Finally, we are able to further investigate and confirm the spatial impact of these dependencies using immunohistochemistry. PMID:28060271

  4. Relations between Brain Structure and Attentional Function in Spina Bifida: Utilization of Robust Statistical Approaches

    PubMed Central

    Kulesz, Paulina A.; Tian, Siva; Juranek, Jenifer; Fletcher, Jack M.; Francis, David J.

    2015-01-01

    Objective Weak structure-function relations for brain and behavior may stem from problems in estimating these relations in small clinical samples with frequently occurring outliers. In the current project, we focused on the utility of using alternative statistics to estimate these relations. Method Fifty-four children with spina bifida meningomyelocele performed attention tasks and received MRI of the brain. Using a bootstrap sampling process, the Pearson product moment correlation was compared with four robust correlations: the percentage bend correlation, the Winsorized correlation, the skipped correlation using the Donoho-Gasko median, and the skipped correlation using the minimum volume ellipsoid estimator Results All methods yielded similar estimates of the relations between measures of brain volume and attention performance. The similarity of estimates across correlation methods suggested that the weak structure-function relations previously found in many studies are not readily attributable to the presence of outlying observations and other factors that violate the assumptions behind the Pearson correlation. Conclusions Given the difficulty of assembling large samples for brain-behavior studies, estimating correlations using multiple, robust methods may enhance the statistical conclusion validity of studies yielding small, but often clinically significant, correlations. PMID:25495830

  5. Towards spatially smart abatement of human pharmaceuticals in surface waters: Defining impact of sewage treatment plants on susceptible functions.

    PubMed

    Coppens, Lieke J C; van Gils, Jos A G; Ter Laak, Thomas L; Raterman, Bernard W; van Wezel, Annemarie P

    2015-09-15

    For human pharmaceuticals, sewage treatment plants (STPs) are a major point of entry to surface waters. The receiving waters provide vital functions. Modeling the impact of STPs on susceptible functions of the surface water system allows for a spatially smart implementation of abatement options at, or in the service area of, STPs. This study was performed on a nation-wide scale for the Netherlands. Point source emissions included were 345 Dutch STPs and nine rivers from neighboring countries. The Dutch surface waters were represented by 2511 surface water units. Modeling was performed for two extreme discharge conditions. Monitoring data of 7 locations along the rivers Rhine and Meuse fall mostly within the range of modeled concentrations. Half of the abstracted volumes of raw water for drinking water production, and a quarter of the Natura 2000 areas (European Union nature protection areas) hosted by the surface waters, are influenced by STPs at low discharge. The vast majority of the total impact of all Dutch STPs during both discharge conditions can be attributed to only 19% of the STPs with regard to the drinking water function, and to 39% of the STPs with regard to the Natura 2000 function. Attributing water treatment technologies to STPs as one of the possible measures to improve water quality and protect susceptible functions can be done in a spatially smart and cost-effective way, using consumption-based detailed hydrological and water quality modeling.

  6. An in vivo analysis of the vestigial gene in Drosophila melanogaster defines the domains required for Vg function.

    PubMed

    MacKay, Julie O; Soanes, Kelly H; Srivastava, Ajay; Simmonds, Andrew; Brook, William J; Bell, John B

    2003-04-01

    Considerable evidence indicates an obligate partnership of the Drosophila melanogaster Vestigial (VG) and Scalloped (SD) proteins within the context of wing development. These two proteins interact physically and a 56-amino-acid motif within VG is necessary and sufficient for this binding. While the importance of this SD-binding domain has been clearly demonstrated both in vitro and in vivo, the remaining portions of VG have not been examined for in vivo function. Herein, additional regions within VG were tested for possible in vivo functions. The results identify two additional domains that must be present for optimal VG function as measured by the loss of ability to rescue vg mutants, to induce ectopic sd expression, and to perform other normal VG functions when they are deleted. An in vivo study such as this one is fundamentally important because it identifies domains of VG that are necessary in the cellular context in which wing development actually occurs. The results also indicate that an additional large portion of VG, outside of these two domains and the SD-binding domain, is dispensable in the execution of these normal VG functions.

  7. Identification and functional analysis of the gene cluster for L-arabinose utilization in Corynebacterium glutamicum.

    PubMed

    Kawaguchi, Hideo; Sasaki, Miho; Vertès, Alain A; Inui, Masayuki; Yukawa, Hideaki

    2009-06-01

    Corynebacterium glutamicum ATCC 31831 grew on l-arabinose as the sole carbon source at a specific growth rate that was twice that on d-glucose. The gene cluster responsible for l-arabinose utilization comprised a six-cistron transcriptional unit with a total length of 7.8 kb. Three l-arabinose-catabolizing genes, araA (encoding l-arabinose isomerase), araB (l-ribulokinase), and araD (l-ribulose-5-phosphate 4-epimerase), comprised the araBDA operon, upstream of which three other genes, araR (LacI-type transcriptional regulator), araE (l-arabinose transporter), and galM (putative aldose 1-epimerase), were present in the opposite direction. Inactivation of the araA, araB, or araD gene eliminated growth on l-arabinose, and each of the gene products was functionally homologous to its Escherichia coli counterpart. Moreover, compared to the wild-type strain, an araE disruptant exhibited a >80% decrease in the growth rate at a lower concentration of l-arabinose (3.6 g liter(-1)) but not at a higher concentration of l-arabinose (40 g liter(-1)). The expression of the araBDA operon and the araE gene was l-arabinose inducible and negatively regulated by the transcriptional regulator AraR. Disruption of araR eliminated the repression in the absence of l-arabinose. Expression of the regulon was not repressed by d-glucose, and simultaneous utilization of l-arabinose and d-glucose was observed in aerobically growing wild-type and araR deletion mutant cells. The regulatory mechanism of the l-arabinose regulon is, therefore, distinct from the carbon catabolite repression mechanism in other bacteria.

  8. Evaluation of a black-footed ferret resource utilization function model

    USGS Publications Warehouse

    Eads, D.A.; Millspaugh, J.J.; Biggins, D.E.; Jachowski, D.S.; Livieri, T.M.

    2011-01-01

    Resource utilization function (RUF) models permit evaluation of potential habitat for endangered species; ideally such models should be evaluated before use in management decision-making. We evaluated the predictive capabilities of a previously developed black-footed ferret (Mustela nigripes) RUF. Using the population-level RUF, generated from ferret observations at an adjacent yet distinct colony, we predicted the distribution of ferrets within a black-tailed prairie dog (Cynomys ludovicianus) colony in the Conata Basin, South Dakota, USA. We evaluated model performance, using data collected during post-breeding spotlight surveys (2007-2008) by assessing model agreement via weighted compositional analysis and count-metrics. Compositional analysis of home range use and colony-level availability, and core area use and home range availability, demonstrated ferret selection of the predicted Very high and High occurrence categories in 2007 and 2008. Simple count-metrics corroborated these findings and suggested selection of the Very high category in 2007 and the Very high and High categories in 2008. Collectively, these results suggested that the RUF was useful in predicting occurrence and intensity of space use of ferrets at our study site, the 2 objectives of the RUF. Application of this validated RUF would increase the resolution of habitat evaluations, permitting prediction of the distribution of ferrets within distinct colonies. Additional model evaluation at other sites, on other black-tailed prairie dog colonies of varying resource configuration and size, would increase understanding of influences upon model performance and the general utility of the RUF. ?? 2011 The Wildlife Society.

  9. Using expert knowledge and modeling to define mangrove composition, functioning, and threats and estimate time frame for recovery

    PubMed Central

    Mukherjee, Nibedita; Sutherland, William J; Khan, Md Nabiul I; Berger, Uta; Schmitz, Nele; Dahdouh-Guebas, Farid; Koedam, Nico

    2014-01-01

    Mangroves are threatened worldwide, and their loss or degradation could impact functioning of the ecosystem. Our aim was to investigate three aspects of mangroves at a global scale: (1) their constituents (2) their indispensable ecological functions, and (3) the maintenance of their constituents and functions in degraded mangroves. We focused on answering two questions: “What is a mangrove ecosystem” and “How vulnerable are mangrove ecosystems to different impacts”? We invited 106 mangrove experts globally to participate in a survey based on the Delphi technique and provide inputs on the three aspects. The outputs from the Delphi technique for the third aspect, i.e. maintenance of constituents and functions were incorporated in a modeling approach to simulate the time frame for recovery. Presented here for the first time are the consensus definition of the mangrove ecosystem and the list of mangrove plant species. In this study, experts considered even monospecific (tree) stands to be a mangrove ecosystem as long as there was adequate tidal exchange, propagule dispersal, and faunal interactions. We provide a ranking of the important ecological functions, faunal groups, and impacts on mangroves. Degradation due to development was identified as having the largest impact on mangroves globally in terms of spatial scale, intensity, and time needed for restoration. The results indicate that mangroves are ecologically unique even though they may be species poor (from the vegetation perspective). The consensus list of mangrove species and the ranking of the mangrove ecological functions could be a useful tool for restoration and management of mangroves. While there is ample literature on the destruction of mangroves due to aquaculture in the past decade, this study clearly shows that more attention must go to avoiding and mitigating mangrove loss due to coastal development (such as building of roads, ports, or harbors). PMID:25360265

  10. Using expert knowledge and modeling to define mangrove composition, functioning, and threats and estimate time frame for recovery.

    PubMed

    Mukherjee, Nibedita; Sutherland, William J; Khan, Md Nabiul I; Berger, Uta; Schmitz, Nele; Dahdouh-Guebas, Farid; Koedam, Nico

    2014-06-01

    Mangroves are threatened worldwide, and their loss or degradation could impact functioning of the ecosystem. Our aim was to investigate three aspects of mangroves at a global scale: (1) their constituents (2) their indispensable ecological functions, and (3) the maintenance of their constituents and functions in degraded mangroves. We focused on answering two questions: "What is a mangrove ecosystem" and "How vulnerable are mangrove ecosystems to different impacts"? We invited 106 mangrove experts globally to participate in a survey based on the Delphi technique and provide inputs on the three aspects. The outputs from the Delphi technique for the third aspect, i.e. maintenance of constituents and functions were incorporated in a modeling approach to simulate the time frame for recovery. Presented here for the first time are the consensus definition of the mangrove ecosystem and the list of mangrove plant species. In this study, experts considered even monospecific (tree) stands to be a mangrove ecosystem as long as there was adequate tidal exchange, propagule dispersal, and faunal interactions. We provide a ranking of the important ecological functions, faunal groups, and impacts on mangroves. Degradation due to development was identified as having the largest impact on mangroves globally in terms of spatial scale, intensity, and time needed for restoration. The results indicate that mangroves are ecologically unique even though they may be species poor (from the vegetation perspective). The consensus list of mangrove species and the ranking of the mangrove ecological functions could be a useful tool for restoration and management of mangroves. While there is ample literature on the destruction of mangroves due to aquaculture in the past decade, this study clearly shows that more attention must go to avoiding and mitigating mangrove loss due to coastal development (such as building of roads, ports, or harbors).

  11. Assessment of Global Functioning in Adolescents with Autism Spectrum Disorders: Utility of the Developmental Disability-Child Global Assessment Scale

    ERIC Educational Resources Information Center

    White, Susan W.; Smith, Laura A.; Schry, Amie R.

    2014-01-01

    Assessment of global functioning is an important consideration in treatment outcome research; yet, there is little guidance on its evidence-based assessment for children with autism spectrum disorders. This study investigated the utility and validity of clinician-rated global functioning using the Developmental Disability-Child Global Assessment…

  12. Review: Dietary fiber utilization and its effects on physiological functions and gut health of swine.

    PubMed

    Jha, R; Berrocoso, J D

    2015-09-01

    Although dietary fiber (DF) negatively affects energy and nutrient digestibility, there is growing interest for the inclusion of its fermentable fraction in pig diets due to their functional properties and potential health benefits beyond supplying energy to the animals. This paper reviews some of the relevant information available on the role of different types of DF on digestion of nutrients in different sections of the gut, the fermentation process and its influence on gut environment, especially production and utilization of metabolites, microbial community and gut health of swine. Focus has been given on DF from feed ingredients (grains and coproducts) commonly used in pig diets. Some information on the role DF in purified form in comparison with DF in whole matrix of feed ingredients is also presented. First, composition and fractions of DF in different feed ingredients are briefly reviewed. Then, roles of different fractions of DF on digestion characteristics and physiological functions in the gastrointestinal tract (GIT) are presented. Specific roles of different fractions of DF on fermentation characteristics and their effects on production and utilization of metabolites in the GIT have been discussed. In addition, roles of DF fermentation on metabolic activity and microbial community in the intestine and their effects on intestinal health are reviewed and discussed. Evidence presented in this review indicates that there is wide variation in the composition and content of DF among feed ingredients, thereby their physico-chemical properties in the GIT of swine. These variations, in turn, affect the digestion and fermentation characteristics in the GIT of swine. Digestibility of DF from different feed ingredients is more variable and lower than that of other nutrients like starch, sugars, fat and CP. Soluble fractions of DF are fermented faster, produce higher amounts of volatile fatty acid than insoluble fractions, and favors growth of beneficial microbiota

  13. Well-defined, size-tunable, multi-functional micelles for efficient paclitaxel delivery for cancer treatment

    PubMed Central

    Luo, Juntao; Xiao, Kai; Li, Yuanpei; Lee, Joyce S.; Shi, Lifang; Tan, Yih-Horng; Xing, Li; Cheng, R. Holland; Liu, Gang-Yu; Lam, Kit S.

    2010-01-01

    We have developed a well-defined and biocompatible amphiphilic telodendrimer system (PEG-b-dendritic oligo-cholic acid) which can self-assemble into multifunctional micelles in aqueous solution for efficient delivery of hydrophobic drugs such as paclitaxel. In this telodendrimer system, cholic acid is essential for the formation of stable micelles with high drug loading capacity, owing to its facial amphiphilicity. A series of telodendrimers with variable length of PEG chain and number of cholic acid in the dendritic blocks were synthesized. The structure and molecular weight of each of these telodendrimers were characterized, and their critical micellization concentration (CMC), drug-loading properties, particle sizes and cytotoxicity were examined and evaluated for further optimization for anticancer drug delivery. The sizes of the micelles, with and without paclitaxel loading, could be tuned from 11.5 to 21 nm and from 15 to 141 nm, respectively. Optical imaging studies in xenograft models demonstrated preferential uptakes of the smaller paclitaxel-loaded micelles (17–60 nm) by the tumor, and the larger micelles (150 nm) by the liver and lung. The toxicity and anti-tumor efficacy profiles of these paclitaxel-loaded micelles in xenograft models were found to be superior to those of Taxol® and Abraxane®. PMID:20536174

  14. Defining The Neighborhoods That Escort The Oocyte Through Its Early Life Events And Into A Functional Follicle

    PubMed Central

    Jorgensen, Joan S.

    2014-01-01

    The ovary functions to chaperone the most precious cargo for female individuals, the oocyte, to allow the passage of genetic material to subsequent generations. Within the ovary, single oocytes are surrounded by a legion of granulosa cells inside each follicle. These two cell types depend upon one another to support follicle formation and oocyte survival. The infrastructure and events that work together to ultimately form these functional follicles within the ovary are unprecedented, given that the oocyte is fated like all other neighboring cells within the embryo prior to gastrulation. This review discusses the journey of the germ cell in the context of the developing female mouse embryo, with a focus on specific signaling events and cell-cell interactions that escort the primordial germ cell as it is specified into the germ-cell fate, migrates through the hindgut into the gonad, differentiates into an oocyte, and culminates upon formation of the primordial and then primary follicle. PMID:24105719

  15. The IMMUTANS variegation locus of Arabidopsis defines a mitochondrial alternative oxidase homolog that functions during early chloroplast biogenesis.

    PubMed Central

    Wu, D; Wright, D A; Wetzel, C; Voytas, D F; Rodermel, S

    1999-01-01

    Nuclear gene-induced variegation mutants provide a powerful system to dissect interactions between the genetic systems of the nucleus-cytoplasm, the chloroplast, and the mitochondrion. The immutans (im) variegation mutation of Arabidopsis is nuclear and recessive and results in the production of green- and white-sectored leaves. The green sectors contain cells with normal chloroplasts, whereas the white sectors are heteroplastidic and contain cells with abnormal, pigment-deficient plastids as well as some normal chloroplasts. White sector formation can be promoted by enhanced light intensities, but sectoring becomes irreversible early in leaf development. The white sectors accumulate the carotenoid precursor phytoene. We have positionally cloned IM and found that the gene encodes a 40.5-kD protein with sequence motifs characteristic of alternative oxidase, a mitochondrial protein that functions as a terminal oxidase in the respiratory chains of all plants. However, phylogenetic analyses revealed that the IM protein is only distantly related to these other alternative oxidases, suggesting that IM is a novel member of this protein class. We sequenced three alleles of im, and all are predicted to be null. Our data suggest a model of variegation in which the IM protein functions early in chloroplast biogenesis as a component of a redox chain responsible for phytoene desaturation but that a redundant electron transfer function is capable of compensating for IM activity in some plastids and cells. PMID:9878631

  16. Structural and Function Correlation of Cone Packing Utilizing Adaptive Optics and Microperimetry

    PubMed Central

    Supriya, Dabir; Shwetha, Mangalesh; Kiran Anupama, Kumar; Kummelil Mathew, Kurian; Berendschot, Tos T. J. M.; Schouten, Jan S. A. G.; Bharamshetter, Roopa; Naresh, Yadav K.; Rohit, Shetty; Hegde, Bharath

    2015-01-01

    Aim. To assess the functional aspects of cone mosaic and correlate cone packing with retinal sensitivity utilizing microperimetry in emmetropes at different eccentricities. Methods. Twenty-four healthy volunteers underwent microperimetry (MAIA Centervue, Italy) and assessment of photoreceptors using adaptive optics retinal camera, rtx1 (Imagine Eyes, Orsay, France), at 2 and 3 degrees from the foveal centre in 4 quadrants: superior, inferior, temporal, and nasal. Data was analyzed using SPSS version 17 (IBM). Spearman's correlation tests were used to establish correlation between mean cone packing density and retinal sensitivity at different quadrants. Results. Thirteen females and 11 males (age range 20–40 years) were included. The cone density was found to be significantly different among all quadrants (temporal = 25786.68/mm2 ± 4367.07/mm2, superior = 23009.35/mm2 ± 5415.81/mm2, nasal = 22838.09/mm2 ± 4166.22/mm2, and inferior = 21097.53/mm2 ± 4235.84/mm2). A statistical significance (P < 0.008) was found between orthogonal meridians, that is, temporal, nasal (48624.77/mm2)> superior, inferior (44106.88/mm2). A drop in retinal sensitivity was observed as the eccentricity increased (P < 0.05). It was also found that as cone packing density decreased retinal sensitivity also decreased (P < 0.05) in all quadrants. This was observed at both 2 and 3 degrees. Conclusion. It is of crucial importance to establish normative variations in cone structure-function correlation. This may help in detection of subtle pathology and its early intervention. PMID:26167509

  17. High Performance Nonvolatile Transistor Memories Utilizing Functional Polyimide-Based Supramolecular Electrets.

    PubMed

    Tung, Wei-Yao; Li, Meng-Hsien; Wu, Hung-Chin; Liu, Hsin-Yu; Hsieh, Yun-Ting; Chen, Wen-Chang

    2016-05-20

    We report pentacene-based organic field-effect transistor memory devices utilizing supramolecular electrets, consisting of a polyimide, PI(6FOH-ODPA), containing hydroxyl groups for hydrogen bonding with amine functionalized aromatic rings (AM) of 1-aniline (AM1), 2-naphthylamine (AM2), 2-aminoanthracene (AM3), and 1-aminopyrene (AM4). The effect of the phenyl ring size and composition of AM1-AM4 on the hole-trapping capability of the fabricated devices was investigated systematically. Under an operating voltage under ±40 V, the prepared devices using the electrets of 100 % AM1-AM4/PI ratios exhibited a memory window of 0, 8.59, 25.97, and 29.95 V, respectively, suggesting that the hole-trapping capability increased with enhancing phenyl ring size. The memory window was enhanced as the amount of AM in PI increased. Furthermore, the devices showed a long charge-retention time of 10(4)  s with an ON/OFF current ratio of around 10(3) -10(4) and multiple switching stability over 100 cycles. This study demonstrated that the electrical characteristics of the OFET memory devices could be manipulated through the chemical compositions of the supramolecular electrets.

  18. Quality traits of Indian peanut cultivars and their utility as nutritional and functional food.

    PubMed

    Bishi, S K; Lokesh, Kumar; Mahatma, M K; Khatediya, N; Chauhan, S M; Misra, J B

    2015-01-15

    Peanut (Arachis hypogaea L.) is considered as a highly nutritious foodstuff. Of late, the importance of peanut as a functional food has been growing. Kernels of forty-one Indian peanut cultivars were analyzed for their oil, fatty acid profiles, sucrose, raffinose family oligosaccharides (RFOs); phenolics, and free amino acids contents along with antioxidant capacity. The range and the mean value (given in parenthesis) for each of the traits analysed were, oil: 44.1-53.8% (50.1%), O/L ratio: 0.9-2.8 (1.4), sucrose: 2.61-6.5% (4.63%), RFOs: 0.12-0.76% (0.47%), phenolics: 0.14-0.39% (0.23%), free amino acids: 0.052-0.19% (0.12%) and antioxidant capacity: 1.05-6.97 (3.40) μmol TEg(-1). The significant correlation between phenol content and antioxidant capacity suggests phenol content as an easy marker for rapid screening of genotypes for their antioxidant capacity. A few cultivars with desirable traits and their prospective utility were identified which would be useful for future breeding programme to develop nutritional superior peanuts.

  19. Investigating the Function of an Arabinan Utilization Locus Isolated from a Termite Gut Community

    PubMed Central

    Arnal, Grégory; Bastien, Géraldine; Monties, Nelly; Abot, Anne; Anton Leberre, Véronique; Bozonnet, Sophie; O'Donohue, Michael

    2014-01-01

    Biocatalysts are essential for the development of bioprocesses efficient for plant biomass degradation. Previously, a metagenomic clone containing DNA from termite gut microbiota was pinpointed in a functional screening that revealed the presence of arabinofuranosidase activity. Subsequent genetic and bioinformatic analysis revealed that the DNA fragment belonged to a member of the genus Bacteroides and encoded 19 open reading frames (ORFs), and annotation suggested the presence of hypothetical transporter and regulator proteins and others involved in the catabolism of pentose sugar. In this respect and considering the phenotype of the metagenomic clone, it was noted that among the ORFs, there are four putative arabinose-specific glycoside hydrolases, two from family GH43 and two from GH51. In this study, a thorough bioinformatics analysis of the metagenomic clone gene cluster has been performed and the four aforementioned glycoside hydrolases have been characterized. Together, the results provide evidence that the gene cluster is a polysaccharide utilization locus dedicated to the breakdown of the arabinan component in pectin and related substrates. Characterization of the two GH43 and the two GH51 glycoside hydrolases has revealed that each of these enzymes displays specific catalytic capabilities and that when these are combined the enzymes act synergistically, increasing the efficiency of arabinan degradation. PMID:25304507

  20. Numerical information processing under the global rule expressed by the Euler-Riemann ζ function defined in the complex plane

    NASA Astrophysics Data System (ADS)

    Chatelin, Françoise

    2010-09-01

    When nonzero, the ζ function is intimately connected with numerical information processing. Two other functions play a key role, namely, η(s )=∑n ≥1(-1)n +1/ns and λ(s )=∑n ≥01/(2n+1)s. The paper opens on a survey of some of the seminal work of Euler [Mémoires Acad. Sci., Berlin 1768, 83 (1749)] and of the amazing theorem by Voronin [Math. USSR, Izv. 9, 443 (1975)] Then, as a follow-up of Chatelin [Qualitative Computing. A Computational Journey into Nonlinearity (World Scientific, Singapore, in press)], we present a fresh look at the triple (η ,ζ,λ) which suggests an elementary analysis based on the distances of the three complex numbers z, z /2, and 2/z to 0 and 1. This metric approach is used to contextualize any nonlinear computation when it is observed at a point describing a complex plane. The results applied to ζ, η, and λ shed a new epistemological light about the critical line. The suggested interpretation related to ζ carries computational significance.

  1. The Structure of the Human RNase H2 Complex Defines Key Interaction Interfaces Relevant to Enzyme Function and Human Disease*

    PubMed Central

    Reijns, Martin A. M.; Bubeck, Doryen; Gibson, Lucien C. D.; Graham, Stephen C.; Baillie, George S.; Jones, E. Yvonne; Jackson, Andrew P.

    2011-01-01

    Ribonuclease H2 (RNase H2) is the major nuclear enzyme involved in the degradation of RNA/DNA hybrids and removal of ribonucleotides misincorporated in genomic DNA. Mutations in each of the three RNase H2 subunits have been implicated in a human auto-inflammatory disorder, Aicardi-Goutières Syndrome (AGS). To understand how mutations impact on RNase H2 function we determined the crystal structure of the human heterotrimer. In doing so, we correct several key regions of the previously reported murine RNase H2 atomic model and provide biochemical validation for our structural model. Our results provide new insights into how the subunits are arranged to form an enzymatically active complex. In particular, we establish that the RNASEH2A C terminus is a eukaryotic adaptation for binding the two accessory subunits, with residues within it required for enzymatic activity. This C-terminal extension interacts with the RNASEH2C C terminus and both are necessary to form a stable, enzymatically active heterotrimer. Disease mutations cluster at this interface between all three subunits, destabilizing the complex and/or impairing enzyme activity. Altogether, we locate 25 out of 29 residues mutated in AGS patients, establishing a firm basis for future investigations into disease pathogenesis and function of the RNase H2 enzyme. PMID:21177854

  2. Synthesis of end-functionalized polyacetylenes that contain polar groups by employing well-defined palladium catalysts.

    PubMed

    Rodriguez Castanon, Jesus; Kuwata, Keiko; Shiotsuki, Masashi; Sanda, Fumio

    2012-10-29

    A series of [(dppf)PdBr(R)]-type complexes (dppf=1,1'-bis(diphenylphosphino)ferrocene; R=p-cyanophenyl (1 a), o-hydroxymethylphenyl (1 b), and triphenylvinyl (1 c)), in combination with silver trifluoromethanesulfonate (AgOTf), were demonstrated to be active for the polymerization of monosubstituted polar acetylene monomers HC≡CCONHC(4)H(9) (2), HC≡CCO(2)C(8)H(17) (3), HC≡CCH(2)OCONHC(6)H(13) (4), HC≡CCH(2)OCO(2)C(6)H(13) (5), and HC≡CCH(CH(3))OH (6). The yields and molecular weights of the polymers depended on the combination of the Pd catalyst and monomer that was employed. Matrix-assisted laser-desorption/ionization-time of flight (MALDI-TOF) mass spectrometric analysis indicated the formation of polymers that contained the "R" and "H" groups at the chain ends. IR spectroscopic analysis supported the R-end-functionalization of the polymers. NMR spectroscopy and MS identified the presence of species that were formed by single, double, and triple insertion of the monomers into the Pd-C(6)H(4)-p-CN bond, thereby giving solid evidence for an insertion mechanism for the present system. Density functional theory (DFT) calculations suggested the preference for 1,2-insertion of the monomer compared to 2,1-insertion.

  3. Epigenetics and Preeclampsia: Defining Functional Epimutations in the Preeclamptic Placenta Related to the TGF-β Pathway

    PubMed Central

    Martin, Elizabeth; Ray, Paul D.; Smeester, Lisa; Grace, Matthew R.; Boggess, Kim; Fry, Rebecca C.

    2015-01-01

    Preeclampsia is a potentially fatal pregnancy disorder affecting millions of women around the globe. Dysregulation in gene and protein expression within key biological pathways controlling angiogenesis has been implicated in the development of preeclampsia. Altered CpG methylation, a type of epimutation, may underlie this pathway dysregulation. In the present study, placental tissue from preeclamptic cases and normotensive controls was analyzed for genome-wide differential CpG methylation and concomitant changes in gene expression. A set of 123 genes, representing 19.9% of all genes with altered CpG methylation, was associated with functional changes in transcript levels. Underscoring the complex relationships between CpG methylation and gene expression, here hypermethylation was never associated with gene silencing, nor was hypomethylation always associated with gene activation. Moreover, the genomic region of the CpG mark was important in predicting the relationship between CpG methylation and gene expression. The 123 genes were enriched for their involvement in the transforming growth factor beta (TGF-β) signaling pathway, a known regulator of placental trophoblast invasion and migration. This is the first study to identify CpG hypomethylation as an activator of TGF-β-associated gene expression in the preeclamptic placenta. The results suggest functional epimutations are associated with preeclampsia disease status and the identified genes may represent novel biomarkers of disease. PMID:26510177

  4. FURTHER DEFINING SPECTRAL TYPE 'Y' AND EXPLORING THE LOW-MASS END OF THE FIELD BROWN DWARF MASS FUNCTION

    SciTech Connect

    Davy Kirkpatrick, J.; Gelino, Christopher R.; Griffith, Roger L.; Marsh, Kenneth A.; Cushing, Michael C.; Mace, Gregory N.; Wright, Edward L.; McLean, Ian S.; Skrutskie, Michael F.; Eisenhardt, Peter R.; Mainzer, Amanda K.; Burgasser, Adam J.; Tinney, C. G.; Parker, Stephen; Salter, Graeme

    2012-07-10

    We present the discovery of another seven Y dwarfs from the Wide-field Infrared Survey Explorer (WISE). Using these objects, as well as the first six WISE Y dwarf discoveries from Cushing et al., we further explore the transition between spectral types T and Y. We find that the T/Y boundary roughly coincides with the spot where the J - H colors of brown dwarfs, as predicted by models, turn back to the red. Moreover, we use preliminary trigonometric parallax measurements to show that the T/Y boundary may also correspond to the point at which the absolute H (1.6 {mu}m) and W2 (4.6 {mu}m) magnitudes plummet. We use these discoveries and their preliminary distances to place them in the larger context of the solar neighborhood. We present a table that updates the entire stellar and substellar constituency within 8 pc of the Sun, and we show that the current census has hydrogen-burning stars outnumbering brown dwarfs by roughly a factor of six. This factor will decrease with time as more brown dwarfs are identified within this volume, but unless there is a vast reservoir of cold brown dwarfs invisible to WISE, the final space density of brown dwarfs is still expected to fall well below that of stars. We also use these new Y dwarf discoveries, along with newly discovered T dwarfs from WISE, to investigate the field substellar mass function. We find that the overall space density of late-T and early-Y dwarfs matches that from simulations describing the mass function as a power law with slope -0.5 < {alpha} < 0.0; however, a power law may provide a poor fit to the observed object counts as a function of spectral type because there are tantalizing hints that the number of brown dwarfs continues to rise from late-T to early-Y. More detailed monitoring and characterization of these Y dwarfs, along with dedicated searches aimed at identifying more examples, are certainly required.

  5. Health and functional status and utilization of health care services among holocaust survivors and their counterparts in Israel.

    PubMed

    Iecovich, Esther; Carmel, Sara

    2010-01-01

    To examine differences in health and functional status and in utilization of health services between holocaust survivors and their counterparts; and (b) to investigate if holocaust survivor status is a significant predictor of health status, functional status, and utilization of health services. The study included 1255 respondents of whom 272 were holocaust survivors. Interviews were conducted face-to-face at the respondents' homes. Participants were asked about their health (self-rated health and comorbidity) and functional (ADL and IADL) status, utilization of inpatient and outpatient health care services, age, gender, education, marital status, length of residence in Israel, and if they were holocaust survivors. Holocaust survivors, who were frailer and more chronically ill compared to their counterparts, visited their family physician and the nurse at the health care clinic more often than their counterparts did, and received more homecare services. Yet, there were no differences between them in the utilization of other health care services such as visits to specialists, emergency department, and hospitalizations. Holocaust survivors are more homebound due to more morbidity and functional limitations and therefore receive more health home care services that offset the utilization of other health services.

  6. Utility of preoperative in vitro platelet function tests for predicting bleeding risk in patients undergoing functional endoscopic sinus surgery

    PubMed Central

    Lee, A-Jin; Kim, Sang-Gyung

    2016-01-01

    Background It is necessary to predict the bleeding risk in patients undergoing functional endoscopic sinus surgery (FESS). To evaluate the adequacy of primary hemostasis, preoperative hemostatic screening tests are used. In the present study, we determined whether there is a positive correlation between prolonged closure time (CT) with collagen/epinephrine (CT-epi), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT) and bleeding during FESS. Patients and methods We reviewed the medical records of 90 patients without bleeding histories who had undergone FESS from March 2013 to June 2014. More than 200 mL of blood loss was defined as moderate bleeding during surgery. With respect to bleeding during surgery, we determined the sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of CT-epi, PT, INR and aPTT. Results Of the 90 patients, 17 (18.9%) patients had preoperative prolonged CT values and three (17.6%) patients had bleeding. In comparison, five (6.8%) of the 73 (81.1%) patients who had undergone FESS with preoperative normal PFA values experienced bleeding (P=0.171). On the other hand, patients with prolonged PT values (2, 2.2%), prolonged INR values (3, 3.3%) or prolonged PTT values (1, 1.1%) had no bleeding episode. Preoperative CT had low sensitivity (44.4%) and PPV (23.5%). Conclusion During preoperative period, the hemostatic screening may not be helpful to detect the bleeding tendency in adult patients undergoing FESS. Routine measurement of CT-epi, PT, INR and aPTT for preoperative screening may not be recommended for FESS patients. PMID:27799837

  7. Defined amino acids in the gag proteins of human immunodeficiency virus type 1 are functionally active during virus assembly.

    PubMed

    Kattenbeck, B; Rohrhofer, A; Niedrig, M; Wolf, H; Modrow, S

    1996-01-01

    A structurally highly ordered arrangement of the polyprotein precursor, Pr55gag is a necessary prerequisite for assembly, budding and maturation of the human immunodeficiency virus type 1 (HIV-1). In particular, distinct regions of the matrix protein (p17) and the capsid protein (p24) contained within Pr55gag are functionally active during these processes. In order to determine such regions we exchanged amino acid triplets within p17 (amino acids 46-61) and p24 (amino acids 341-352) for alanine residues and deleted the whole regions. Synthetic peptides derived from these regions had been shown previously to inhibit the production of infectious virus. The effect of the mutations on the release of viral particles was investigated by using recombinant baculoviruses for the expression of mutated Pr55gag as virus-like particles and by use of the respective HI proviruses for monitoring the production of infectious particles.

  8. Labview utilities

    SciTech Connect

    Persaud, Arun

    2011-09-30

    The software package provides several utilities written in LabView. These utilities don't form independent programs, but rather can be used as a library or controls in other labview programs. The utilities include several new controls (xcontrols), VIs for input and output routines, as well as other 'helper'-functions not provided in the standard LabView environment.

  9. Postthymic expansion in human CD4 naive T cells defined by expression of functional high-affinity IL-2 receptors.

    PubMed

    Pekalski, Marcin L; Ferreira, Ricardo C; Coulson, Richard M R; Cutler, Antony J; Guo, Hui; Smyth, Deborah J; Downes, Kate; Dendrou, Calliope A; Castro Dopico, Xaquin; Esposito, Laura; Coleman, Gillian; Stevens, Helen E; Nutland, Sarah; Walker, Neil M; Guy, Catherine; Dunger, David B; Wallace, Chris; Tree, Timothy I M; Todd, John A; Wicker, Linda S

    2013-03-15

    As the thymus involutes with age, the maintenance of peripheral naive T cells in humans becomes strongly dependent on peripheral cell division. However, mechanisms that orchestrate homeostatic division remain unclear. In this study we present evidence that the frequency of naive CD4 T cells that express CD25 (IL-2 receptor α-chain) increases with age on subsets of both CD31(+) and CD31(-) naive CD4 T cells. Analyses of TCR excision circles from sorted subsets indicate that CD25(+) naive CD4 T cells have undergone more rounds of homeostatic proliferation than their CD25(-) counterparts in both the CD31(+) and CD31(-) subsets, indicating that CD25 is a marker of naive CD4 T cells that have preferentially responded to survival signals from self-Ags or cytokines. CD25 expression on CD25(-) naive CD4 T cells can be induced by IL-7 in vitro in the absence of TCR activation. Although CD25(+) naive T cells respond to lower concentrations of IL-2 as compared with their CD25(-) counterparts, IL-2 responsiveness is further increased in CD31(-) naive T cells by their expression of the signaling IL-2 receptor β-chain CD122, forming with common γ-chain functional high-affinity IL-2 receptors. CD25 plays a role during activation: CD25(+) naive T cells stimulated in an APC-dependent manner were shown to produce increased levels of IL-2 as compared with their CD25(-) counterparts. This study establishes CD25(+) naive CD4 T cells, which are further delineated by CD31 expression, as a major functionally distinct immune cell subset in humans that warrants further characterization in health and disease.

  10. Social Service Utilization, Sense of Community, Family Functioning and the Mental Health of New Immigrant Women in Hong Kong

    PubMed Central

    Wu, Qiaobing; Chow, Julian Chun-Chung

    2013-01-01

    Drawing upon a sample of 296 new immigrant women in Hong Kong, this study investigated how social service utilization, family functioning, and sense of community influenced the depressive symptoms of new immigrant women. Results of the structural equation modeling suggested that family functioning and sense of community were both significantly and negatively associated with the depression of new immigrant women. Utilization of community services also influenced the depression of immigrant women indirectly through the mediating effect of sense of community. Implications of the research findings for mental health intervention were discussed. PMID:23629592

  11. Fetal glucose uptake and utilization as functions of maternal glucose concentration.

    PubMed

    Hay, W W; Sparks, J W; Wilkening, R B; Battaglia, F C; Meschia, G

    1984-03-01

    Seventeen studies were performed in 12 pregnant sheep to examine the relationship among simultaneously measured glucose uptake via the umbilical circulation, fetal glucose utilization (mg X min-1 X kg-1), and maternal arterial glucose (Gm, mg/dl). Fetal glucose utilization was measured by means of tracer glucose infused into the fetus or both mother and fetus. By fasting the ewe, Gm was varied in the 62-22 range. A decrease in Gm was accompanied by a significant (P less than 0.001) decrease in umbilical uptake (uptake = 0.09 Gm - 0.96, r = 0.82) and in fetal utilization, measured either by [U-14C]glucose (utilization = 0.062 Gm + 0.91, r = 0.90) or [6-3H]glucose (utilization = 0.065 Gm + 0.51, r = 0.91). At uptake greater than 3 mg X min-1 X kg-1, utilization and uptake were not significantly different. At lower uptakes, utilization did not decline as much as uptake. The results demonstrate that maternal fasting decreases both the umbilical uptake and the fetal utilization of glucose and suggest that fetal glucogenesis increases when the availability of exogenous glucose is markedly reduced.

  12. How do you (estimate you will) like them apples? Integration as a defining trait of orbitofrontal function.

    PubMed

    Schoenbaum, Geoffrey; Esber, Guillem R

    2010-04-01

    The past 15 years have seen a rapid increase in our understanding of orbitofrontal function. Today this region is the focus of an enormous amount of research, including work on such complex phenomena as regret, ambiguity, and willingness to pay. The orbitofrontal cortex is also credited as a major player in a host of neuropsychiatric diseases. This transformation arguably began with the application of concepts derived from animal learning theory. We will review data from studies emphasizing these approaches to argue that the orbitofrontal cortex forms a crucial part of a network of structures that signals information about expected outcomes. Further we will suggest that, within this network, the orbitofrontal cortex provides the critical ability to integrate information in real-time to make what amounts to actionable predictions or estimates about future outcomes. As we will show, the influence of these estimates can be demonstrated experimentally in appropriate behavioral settings, and their operation can also readily explain the role of orbitofrontal cortex in much more complex phenomena such as those cited above.

  13. Extensive Ex Vivo Expansion of Functional Human Erythroid Precursors Established From Umbilical Cord Blood Cells by Defined Factors

    PubMed Central

    Huang, Xiaosong; Shah, Siddharth; Wang, Jing; Ye, Zhaohui; Dowey, Sarah N; Tsang, Kit Man; Mendelsohn, Laurel G; Kato, Gregory J; Kickler, Thomas S; Cheng, Linzhao

    2014-01-01

    There is a constant shortage of red blood cells (RBCs) from sufficiently matched donors for patients who need chronic transfusion. Ex vivo expansion and maturation of human erythroid precursors (erythroblasts) from the patients or optimally matched donors could represent a potential solution. Proliferating erythroblasts can be expanded from umbilical cord blood mononuclear cells (CB MNCs) ex vivo for 106–107-fold (in ~50 days) before proliferation arrest and reaching sufficient number for broad application. Here, we report that ectopic expression of three genetic factors (Sox2, c-Myc, and an shRNA against TP53 gene) associated with iPSC derivation enables CB-derived erythroblasts to undergo extended expansion (~1068-fold in ~12 months) in a serum-free culture condition without change of cell identity or function. These expanding erythroblasts maintain immature erythroblast phenotypes and morphology, a normal diploid karyotype and dependence on a specific combination of growth factors for proliferation throughout expansion period. When being switched to a terminal differentiation condition, these immortalized erythroblasts gradually exit cell cycle, decrease cell size, accumulate hemoglobin, condense nuclei and eventually give rise to enucleated hemoglobin-containing erythrocytes that can bind and release oxygen. Our result may ultimately lead to an alternative approach to generate unlimited numbers of RBCs for personalized transfusion medicine. PMID:24002691

  14. CD49a Expression Defines Tissue-Resident CD8(+) T Cells Poised for Cytotoxic Function in Human Skin.

    PubMed

    Cheuk, Stanley; Schlums, Heinrich; Gallais Sérézal, Irène; Martini, Elisa; Chiang, Samuel C; Marquardt, Nicole; Gibbs, Anna; Detlofsson, Ebba; Introini, Andrea; Forkel, Marianne; Höög, Charlotte; Tjernlund, Annelie; Michaëlsson, Jakob; Folkersen, Lasse; Mjösberg, Jenny; Blomqvist, Lennart; Ehrström, Marcus; Ståhle, Mona; Bryceson, Yenan T; Eidsmo, Liv

    2017-02-21

    Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8(+)CD49a(+) Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8(+)CD49a(-) Trm cells from psoriasis lesions predominantly generated IL-17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8(+) Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases.

  15. Regulatory function of a malleable protein matrix as a novel fermented whey product on features defining the metabolic syndrome.

    PubMed

    Beaulieu, J; Millette, E; Trottier, E; Précourt, L-P; Dupont, C; Lemieux, P

    2010-06-01

    Previously, we reported that a malleable protein matrix (MPM), composed of whey fermented by a proprietary Lactobacillus kefiranofaciens strain, has immunomodulatory and anti-inflammatory properties. MPM consumption leads to a considerable reduction in the cytokine and chemokine production (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6), thus lowering chronic inflammation or metaflammation. Inhibition of metaflammation should provide positive impact, particularly in the context of dyslipidemia, insulin resistance, and hypertension. In this study, we investigated whether short-term MPM supplementation ameliorates those features of metabolic syndrome (MetS). The ability of MPM to potentially regulate triglyceride level, cholesterol level, blood glucose level, and hypertension was evaluated in different animal models. MPM lowers triglyceride level by 37% (P < .05) in a poloxamer 407 dyslipidemia-induced rat model. It also reduces total cholesterol by 18% (P < .05) and low-density lipoprotein-cholesterol level by 32% (P < .05) and raises high-density lipoprotein-cholesterol level by 17% (P < .01) in Syrian Golden hamsters fed a high fat/high cholesterol diet for 2 weeks. MPM reestablishes the fasting glucose insulin ratio index to normal levels (P = .07) in this latter model and lowers the plasma glucose level area under the curve (-10%, P = .09) in fructose-fed rats after 2 weeks of treatment. In spontaneously hypertensive rats, MPM-treated animals showed a reduction of SBP by at least 13% (P < .05) for 4 weeks. Results from this study suggest that MPM is a functional ingredient with beneficial effects on lipid metabolism, blood glucose control, and hypertension that might contribute to the management of MetS and thus reducing the risk of cardiovascular diseases.

  16. Graded functional diffusion map-defined characteristics of apparent diffusion coefficients predict overall survival in recurrent glioblastoma treated with bevacizumab.

    PubMed

    Ellingson, Benjamin M; Cloughesy, Timothy F; Lai, Albert; Mischel, Paul S; Nghiemphu, Phioanh L; Lalezari, Shadi; Schmainda, Kathleen M; Pope, Whitney B

    2011-10-01

    Diffusion imaging has shown promise as a predictive and prognostic biomarker in glioma. We assessed the ability of graded functional diffusion maps (fDMs) and apparent diffusion coefficient (ADC) characteristics to predict overall survival (OS) in recurrent glioblastoma multiforme (GBM) patients treated with bevacizumab. Seventy-seven patients with recurrent GBMs were retrospectively examined. MRI scans were obtained before and approximately 6 weeks after treatment with bevacizumab. Graded fDMs were created by registering datasets to each patient's pretreatment scan and then performing voxel-wise subtraction between post- and pretreatment ADC maps. Voxels were categorized according to the degree of change in ADC within pretreatment fluid-attenuated inversion recovery (FLAIR) and contrast-enhancing regions of interest (ROIs). We found that the volume of tissue showing decreased ADC within both FLAIR and contrast-enhancing regions stratified OS (log-rank, P < .05). fDMs applied to contrast-enhancing ROIs more accurately predicted OS compared with fDMs applied to FLAIR ROIs. Graded fDMs (showing voxels with decreased ADC between 0.25 and 0.4 µm(2)/ms) were more predictive of OS than traditional (single threshold) fDMs, and the predictive ability of graded fDMs could be enhanced even further by adding the ADC characteristics from the fDM-classified voxels to the analysis (log-rank, P < .001). These results demonstrate that spatially resolved diffusion-based tumor metrics are a powerful imaging biomarker of survival in patients with recurrent GBM treated with bevacizumab.

  17. The utility of pulmonary function testing in predicting outcomes following liver transplantation.

    PubMed

    Kia, Leila; Cuttica, Michael J; Yang, Amy; Donnan, Erica N; Whitsett, Maureen; Singhvi, Ajay; Lemmer, Alexander; Levitsky, Josh

    2016-06-01

    Although pulmonary function tests (PFTs) are routinely performed in patients during the evaluation period before liver transplantation (LT), their utility in predicting post-LT mortality and morbidity outcomes is not known. The aim of this study was to determine the impact of obstructive and/or restrictive lung disease on post-LT outcomes. We conducted a retrospective analysis of patients who had pre-LT PFTs and underwent a subsequent LT (2007-2013). We used statistical analyses to determine independent associations between PFT parameters and outcomes (graft/patient survival, time on ventilator, and hospital/intensive care unit [ICU] length of stay [LOS]). A total of 415 LT recipients with available PFT data were included: 65% of patients had normal PFTs; 8% had obstructive lung disease; and 27% had restrictive lung disease. There was no difference in patient and graft survival between patients with normal, obstructive, and restrictive lung disease. However, restrictive lung disease was associated with longer post-LT time on ventilator and both ICU and hospital LOS (P < 0.05). More specific PFT parameters (diffusing capacity of the lungs for carbon monoxide, total lung capacity, and residual volume) were all significant predictors of ventilator time and both ICU and hospital LOS (P < 0.05). Although pre-LT PFT parameters may not predict post-LT mortality, restrictive abnormalities correlate with prolonged post-LT ventilation and LOS. Efforts to identify and minimize the impact of restrictive abnormalities on PFTs might improve such outcomes. Liver Transplantation 22 805-811 2016 AASLD.

  18. Hierarchical decomposition of burn body diagram based on cutaneous functional units and its utility.

    PubMed

    Richard, Reg; Jones, John A; Parshley, Philip

    2015-01-01

    A burn body diagram (BBD) is a common feature used in the delivery of burn care for estimating the TBSA burn as well as calculating fluid resuscitation and nutritional requirements, wound healing, and rehabilitation intervention. However, little change has occurred for over seven decades in the configuration of the BBD. The purpose of this project was to develop a computerized model using hierarchical decomposition (HD) to more precisely determine the percentage burn within a BBD based on cutaneous functional units (CFUs). HD is a process by which a system is degraded into smaller parts that are more precise in their use. CFUs were previously identified fields of the skin involved in the range of motion. A standard Lund/Browder (LB) BBD template was used as the starting point to apply the CFU segments. LB body divisions were parceled down into smaller body area divisions through a HD process based on the CFU concept. A numerical pattern schema was used to label the various segments in a cephalo/caudal, anterior/posterior, medial/lateral manner. Hand/fingers were divided based on anatomical landmarks and known cutaneokinematic function. The face was considered using aesthetic units. Computer code was written to apply the numeric hierarchical schema to CFUs and applied within the context of the surface area graphic evaluation BBD program. Each segmented CFU was coded to express 100% of itself. The CFU/HD method refined the standard LB diagram from 13 body segments and 33 subdivisions into 182 isolated CFUs. Associated CFUs were reconstituted into 219 various surface area combinations totaling 401 possible surface segments. The CFU/HD schema of the body surface mapping is applicable to measuring and calculating percent wound healing in a more precise manner. It eliminates subjective assessment of the percentage wound healing and the need for additional devices such as planimetry. The development of CFU/HD body mapping schema has rendered a technologically advanced

  19. Defining the functional domain of programmed cell death 10 through its interactions with phosphatidylinositol-3,4,5-trisphosphate.

    PubMed

    Dibble, Christopher F; Horst, Jeremy A; Malone, Michael H; Park, Kun; Temple, Brenda; Cheeseman, Holly; Barbaro, Justin R; Johnson, Gary L; Bencharit, Sompop

    2010-07-23

    Cerebral cavernous malformations (CCM) are vascular abnormalities of the central nervous system predisposing blood vessels to leakage, leading to hemorrhagic stroke. Three genes, Krit1 (CCM1), OSM (CCM2), and PDCD10 (CCM3) are involved in CCM development. PDCD10 binds specifically to PtdIns(3,4,5)P3 and OSM. Using threading analysis and multi-template modeling, we constructed a three-dimensional model of PDCD10. PDCD10 appears to be a six-helical-bundle protein formed by two heptad-repeat-hairpin structures (alpha1-3 and alpha4-6) sharing the closest 3D homology with the bacterial phosphate transporter, PhoU. We identified a stretch of five lysines forming an amphipathic helix, a potential PtdIns(3,4,5)P3 binding site, in the alpha5 helix. We generated a recombinant wild-type (WT) and three PDCD10 mutants that have two (Delta2KA), three (Delta3KA), and five (Delta5KA) K to A mutations. Delta2KA and Delta3KA mutants hypothetically lack binding residues to PtdIns(3,4,5)P3 at the beginning and the end of predicted helix, while Delta5KA completely lacks all predicted binding residues. The WT, Delta2KA, and Delta3KA mutants maintain their binding to PtdIns(3,4,5)P3. Only the Delta5KA abolishes binding to PtdIns(3,4,5)P3. Both Delta5KA and WT show similar secondary and tertiary structures; however, Delta5KA does not bind to OSM. When WT and Delta5KA are co-expressed with membrane-bound constitutively-active PI3 kinase (p110-CAAX), the majority of the WT is co-localized with p110-CAAX at the plasma membrane where PtdIns(3,4,5)P3 is presumably abundant. In contrast, the Delta5KA remains in the cytoplasm and is not present in the plasma membrane. Combining computational modeling and biological data, we propose that the CCM protein complex functions in the PI3K signaling pathway through the interaction between PDCD10 and PtdIns(3,4,5)P3.

  20. Generation of Functional Human Retinal Ganglion Cells with Target Specificity from Pluripotent Stem Cells by Chemically Defined Recapitulation of Developmental Mechanism.

    PubMed

    Teotia, Pooja; Chopra, Divyan A; Dravid, Shashank Manohar; Van Hook, Matthew J; Qiu, Fang; Morrison, John; Rizzino, Angie; Ahmad, Iqbal

    2017-03-01

    Glaucoma is a complex group of diseases wherein a selective degeneration of retinal ganglion cells (RGCs) lead to irreversible loss of vision. A comprehensive approach to glaucomatous RGC degeneration may include stem cells to functionally replace dead neurons through transplantation and understand RGCs vulnerability using a disease in a dish stem cell model. Both approaches require the directed generation of stable, functional, and target-specific RGCs from renewable sources of cells, that is, the embryonic stem cells and induced pluripotent stem cells. Here, we demonstrate a rapid and safe, stage-specific, chemically defined protocol that selectively generates RGCs across species, including human, by recapitulating the developmental mechanism. The de novo generated RGCs from pluripotent cells are similar to native RGCs at the molecular, biochemical, functional levels. They also express axon guidance molecules, and discriminate between specific and nonspecific targets, and are nontumorigenic. Stem Cells 2017;35:572-585.

  1. The Utility of the MMPI-2 Malingering Discriminant Function Index in the Detection of Malingering: A Study of Criminal Defendants

    ERIC Educational Resources Information Center

    Toomey, Joseph A.; Kucharski, L. Thomas; Duncan, Scott

    2009-01-01

    This study examined the utility of the Minnesota Multiphasic Personality Inventory-2's (MMPI-2) malingering discriminant function index (M-DFI), recently developed by Bacchiochi and Bagby, in the detection of malingering in a forensic sample. Criminal defendants were divided into "malingering" and "not malingering" groups using…

  2. Assessment of Postflight Locomotor Performance Utilizing a Test of Functional Mobility: Strategic and Adaptive Responses

    NASA Technical Reports Server (NTRS)

    Warren, L. E.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Ruttley, T. M.; Bloomberg, J. J.

    2006-01-01

    /16 crewmembers exhibited significant strategic motor learning patterns in their micro curves, as defined by m > 1 in the equation of the line y=m*LN(x) +b. These data indicate that postflight recovery in locomotor function involves both strategic and adaptive mechanisms. Future countermeasures will be designed to enhance both recovery processes.

  3. Structure-function analysis of 2-keto-3-deoxy-D-glycero-D-galactonononate-9-phosphate phosphatase defines specificity elements in type C0 haloalkanoate dehalogenase family members.

    PubMed

    Lu, Zhibing; Wang, Liangbing; Dunaway-Mariano, Debra; Allen, Karen N

    2009-01-09

    The phosphotransferases of the haloalkanoate dehalogenase superfamily (HADSF) act upon a wide range of metabolites in all eukaryotes and prokaryotes and thus constitute a significant force in cell function. The challenge posed for biochemical function assignment of HADSF members is the identification of the structural determinants that target a specific metabolite. The "8KDOP" subfamily of the HADSF is defined by the known structure and catalytic activity of 2-keto-3-deoxy-8-phospho-d-manno-octulosonic acid (KDO-8-P) phosphatase. Homologues of this enzyme have been uniformly annotated as KDO-8-P phosphatase. One such gene, BT1713, from the Bacteroides thetaiotaomicron genome was recently found to encode the enzyme 2-keto-3-deoxy-d-glycero-d-galacto-9-phosphonononic acid (KDN-9-P) phosphatase in the biosynthetic pathway of the 9-carbon alpha-keto acid, 2-keto-3-deoxy-d-glycero-d-galactonononic acid (KDN). To find the structural elements that provide substrate-specific interactions and to allow identification of genomic sequence markers, the x-ray crystal structures of BT1713 liganded to the cofactor Mg(2+)and complexed with tungstate or VO(3)(-)/Neu5Ac were determined to 1.1, 1.85, and 1.63 A resolution, respectively. The structures define the active site to be at the subunit interface and, as confirmed by steady-state kinetics and site-directed mutagenesis, reveal Arg-64(*), Lys-67(*), and Glu-56 to be the key residues involved in sugar binding that are essential for BT1713 catalytic function. Bioinformatic analyses of the differentially conserved residues between BT1713 and KDO-8-P phosphatase homologues guided by the knowledge of the structure-based specificity determinants define Glu-56 and Lys-67(*) to be the key residues that can be used in future annotations.

  4. Structure-Function Analysis of 2-Keto-3-Deoxy-D-Glycero-D-Galacto-Nononate-9-Phosphate Phosphatase Defines Specificity Elements in Type C0 had Family Members

    SciTech Connect

    Lu, Z.; Wang, L; Dunaway-Mariano, D; Allen, K

    2009-01-01

    The phosphotransferases of the haloalkanoate dehalogenase superfamily (HADSF) act upon a wide range of metabolites in all eukaryotes and prokaryotes and thus constitute a significant force in cell function. The challenge posed for biochemical function assignment of HADSF members is the identification of the structural determinants that target a specific metabolite. The '8KDOP' subfamily of the HADSF is defined by the known structure and catalytic activity of 2-keto-3-deoxy-8-phospho-d-manno-octulosonic acid (KDO-8-P) phosphatase. Homologues of this enzyme have been uniformly annotated as KDO-8-P phosphatase. One such gene, BT1713, from the Bacteroides thetaiotaomicron genome was recently found to encode the enzyme 2-keto-3-deoxy-d-glycero-d-galacto-9-phosphonononic acid (KDN-9-P) phosphatase in the biosynthetic pathway of the 9-carbon ?-keto acid, 2-keto-3-deoxy-d-glycero-d-galactonononic acid (KDN). To find the structural elements that provide substrate-specific interactions and to allow identification of genomic sequence markers, the x-ray crystal structures of BT1713 liganded to the cofactor Mg2+and complexed with tungstate or Formula/Neu5Ac were determined to 1.1, 1.85, and 1.63 A resolution, respectively. The structures define the active site to be at the subunit interface and, as confirmed by steady-state kinetics and site-directed mutagenesis, reveal Arg-64*, Lys-67*, and Glu-56 to be the key residues involved in sugar binding that are essential for BT1713 catalytic function. Bioinformatic analyses of the differentially conserved residues between BT1713 and KDO-8-P phosphatase homologues guided by the knowledge of the structure-based specificity determinants define Glu-56 and Lys-67* to be the key residues that can be used in future annotations.

  5. Defining Platelet Function During Polytrauma

    DTIC Science & Technology

    2013-02-01

    Dosage of any hemostatic agents administered including activated Factor VII.  Dosage of any anticoagulants including subcutaneous heparin for deep...Intentional self-inflicted injury  Recent (within 2 weeks) use of anticoagulants including heparins, aspirin, clopidogrel, prasugrel, or...admission use of aspirin, non-steroidal anti-inflammatory medications, warfarin, heparins, or specific antiplatelet drugs.  Major injuries as identified by

  6. Function and Aesthetics: Defining Craftsmanship

    ERIC Educational Resources Information Center

    MacEachren, Zabe

    2004-01-01

    Many experiential education programs are developed on pillars promoting craftsmanship. Changing cultural situations have altered both our definition of, and the experiences offered to, participants that influence their concept of craftsmanship. By using Kurt Hahn's educational ideas, various experiences are explored and critiqued to determine what…

  7. Defining Platelet Function During Polytrauma

    DTIC Science & Technology

    2014-04-01

    NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b . ABSTRACT U c. THIS PAGE U UU 772 19b. TELEPHONE NUMBER (include area code) 2 Table of...al by our k by base ata stratifie nd injuries er groups. ry and sho evere shoc ck severity s injury an ee betwee re shock g f subjects b creased wit...s when stra preselected ed by pro definition excess < - d by ISS a and seve Blood pr ck. There k groups ( b are given d shock c n mild and

  8. Evaluation of the utility of a discrete-trial functional analysis in early intervention classrooms.

    PubMed

    Kodak, Tiffany; Fisher, Wayne W; Paden, Amber; Dickes, Nitasha

    2013-01-01

    We evaluated a discrete-trial functional analysis implemented by regular classroom staff in a classroom setting. The results suggest that the discrete-trial functional analysis identified a social function for each participant and may require fewer staff than standard functional analysis procedures.

  9. Evaluation of the Utility of a Discrete-Trial Functional Analysis in Early Intervention Classrooms

    ERIC Educational Resources Information Center

    Kodak, Tiffany; Fisher, Wayne W.; Paden, Amber; Dickes, Nitasha

    2013-01-01

    We evaluated a discrete-trial functional analysis implemented by regular classroom staff in a classroom setting. The results suggest that the discrete-trial functional analysis identified a social function for each participant and may require fewer staff than standard functional analysis procedures.

  10. Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions

    NASA Astrophysics Data System (ADS)

    Kutikhin, Anton G.; Velikanova, Elena A.; Mukhamadiyarov, Rinat A.; Glushkova, Tatiana V.; Borisov, Vadim V.; Matveeva, Vera G.; Antonova, Larisa V.; Filip’Ev, Dmitriy E.; Golovkin, Alexey S.; Shishkova, Daria K.; Burago, Andrey Yu.; Frolov, Alexey V.; Dolgov, Viktor Yu.; Efimova, Olga S.; Popova, Anna N.; Malysheva, Valentina Yu.; Vladimirov, Alexandr A.; Sozinov, Sergey A.; Ismagilov, Zinfer R.; Russakov, Dmitriy M.; Lomzov, Alexander A.; Pyshnyi, Dmitriy V.; Gutakovsky, Anton K.; Zhivodkov, Yuriy A.; Demidov, Evgeniy A.; Peltek, Sergey E.; Dolganyuk, Viatcheslav F.; Babich, Olga O.; Grigoriev, Evgeniy V.; Brusina, Elena B.; Barbarash, Olga L.; Yuzhalin, Arseniy E.

    2016-06-01

    Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease.

  11. Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions

    PubMed Central

    Kutikhin, Anton G.; Velikanova, Elena A.; Mukhamadiyarov, Rinat A.; Glushkova, Tatiana V.; Borisov, Vadim V.; Matveeva, Vera G.; Antonova, Larisa V.; Filip’ev, Dmitriy E.; Golovkin, Alexey S.; Shishkova, Daria K.; Burago, Andrey Yu.; Frolov, Alexey V.; Dolgov, Viktor Yu.; Efimova, Olga S.; Popova, Anna N.; Malysheva, Valentina Yu.; Vladimirov, Alexandr A.; Sozinov, Sergey A.; Ismagilov, Zinfer R.; Russakov, Dmitriy M.; Lomzov, Alexander A.; Pyshnyi, Dmitriy V.; Gutakovsky, Anton K.; Zhivodkov, Yuriy A.; Demidov, Evgeniy A.; Peltek, Sergey E.; Dolganyuk, Viatcheslav F.; Babich, Olga O.; Grigoriev, Evgeniy V.; Brusina, Elena B.; Barbarash, Olga L.; Yuzhalin, Arseniy E.

    2016-01-01

    Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease. PMID:27251104

  12. Hardening Software Defined Networks

    DTIC Science & Technology

    2014-07-01

    Utilizing this inflection point requires security technologies that have two characteristics. First, security technologies must be incentive-aligned...for initial adoption. Securing SDN requires designing technologies that provide immediate returns for the early adopters. Compare with BGPSEC, which... technologies must function without complete adoption. And of course, third, these must be resilient against attack. Compare with egress filtering, which

  13. Meta-Analyses of Ethnic Match as a Predictor of Dropout, Utilization, and Level of Functioning.

    ERIC Educational Resources Information Center

    Maramba, Gloria Gia; Hall, Gordon C. Nagayama

    2002-01-01

    Meta-analyses were performed on seven studies of ethnic match and psychotherapy. Results reveal a small dropout and utilization effect sizes, indicating that ethnic match is not a significant clinical predictor of decreasing dropout after the first session or increasing number of sessions attended. (Contains references and tables.) (GCP)

  14. [An oral function improvement program utilizing health behavior theories ameliorates oral functions and oral hygienic conditions of pre-frail elderly persons].

    PubMed

    Sakaguchi, Hideo

    2014-06-01

    Oral function improvement programs utilizing health behavior theories are considered to be effective in preventing the need for long-term social care. In the present study, an oral function improvement program based upon health behavior theories was designed, and its utility was assessed in 102 pre-frail elderly persons (33 males, 69 females, mean age: 76.9 +/- 5.7) considered to be in potential need of long-term social care and attending a long-term care prevention class in Sayama City, Saitama Prefecture, Japan. The degree of improvement in oral functions (7 items) and oral hygienic conditions (3 items) was assessed by comparing oral health before and after participation in the program. The results showed statistically significant improvements in the following oral functions: (1) lip functions (oral diadochokinesis, measured by the regularity of the repetition of the syllable "Pa"), (2) tongue functions, (3) tongue root motor skills (oral diadochokinesis, measured by the regularity of the repetition of the syllables "Ta" and "Ka"), (4) tongue extension/retraction, (5) side-to-side tongue movement functions, (6) cheek motor skills, and (7) repetitive saliva swallowing test (RSST). The following measures of oral hygiene also showed a statistically significant improvement: (1) debris on dentures or teeth, (2) coated tongue, and (3) frequency of oral cleaning. These findings demonstrated that an improvement program informed by health behavior theories is useful in improving oral functions and oral hygiene conditions.

  15. Benchmarking the performance of density functional theory based Green's function formalism utilizing different self-energy models in calculating electronic transmission through molecular systems.

    PubMed

    Prociuk, Alexander; Van Kuiken, Ben; Dunietz, Barry D

    2006-11-28

    Electronic transmission through a metal-molecule-metal system is calculated by employing a Green's function formalism in the scattering based scheme. Self-energy models representing the bulk and the potential bias are used to describe electron transport through the molecular system. Different self-energies can be defined by varying the partition between device and bulk regions of the metal-molecule-metal model system. In addition, the self-energies are calculated with different representations of the bulk through its Green's function. In this work, the dependence of the calculated transmission on varying the self-energy subspaces is benchmarked. The calculated transmission is monitored with respect to the different choices defining the self-energy model. In this report, we focus on one-dimensional model systems with electronic structures calculated at the density functional level of theory.

  16. The importance of chemistry in creating well-defined nanoscopic embedded therapeutics: devices capable of the dual functions of imaging and therapy.

    PubMed

    Nyström, Andreas M; Wooley, Karen L

    2011-10-18

    Nanomedicine is a rapidly evolving field, for which polymer building blocks are proving useful for the construction of sophisticated devices that provide enhanced diagnostic imaging and treatment of disease, known as theranostics. These well-defined nanoscopic objects have high loading capacities, can protect embedded therapeutic cargo, and offer control over the conditions and rates of release. Theranostics also offer external surface area for the conjugation of ligands to impart stealth characteristics and/or direct their interactions with biological receptors and provide a framework for conjugation of imaging agents to track delivery to diseased site(s). The nanoscopic dimensions allow for extensive biological circulation. The incorporation of such multiple functions is complicated, requiring exquisite chemical control during production and rigorous characterization studies to confirm the compositions, structures, properties, and performance. We are particularly interested in the study of nanoscopic objects designed for treatment of lung infections and acute lung injury, urinary tract infections, and cancer. This Account highlights our work over several years to tune the assembly of unique nanostructures. We provide examples of how the composition, structure, dimensions, and morphology of theranostic devices can tune their performance as drug delivery agents for the treatment of infectious diseases and cancer. The evolution of nanostructured materials from relatively simple overall shapes and internal morphologies to those of increasing complexity is driving the development of synthetic methodologies for the preparation of increasingly complex nanomedicine devices. Our nanomedicine devices are derived from macromolecules that have well-defined compositions, structures, and topologies, which provide a framework for their programmed assembly into nanostructures with controlled sizes, shapes, and morphologies. The inclusion of functional units within selective

  17. The phylogenetic utility and functional constraint of microRNA flanking sequences

    PubMed Central

    Kenny, Nathan J.; Sin, Yung Wa; Hayward, Alexander; Paps, Jordi; Chu, Ka Hou; Hui, Jerome H. L.

    2015-01-01

    MicroRNAs (miRNAs) have recently risen to prominence as novel factors responsible for post-transcriptional regulation of gene expression. miRNA genes have been posited as highly conserved in the clades in which they exist. Consequently, miRNAs have been used as rare genome change characters to estimate phylogeny by tracking their gain and loss. However, their short length (21–23 bp) has limited their perceived utility in sequenced-based phylogenetic inference. Here, using reference taxa with established phylogenetic relationships, we demonstrate that miRNA sequences are of high utility in quantitative, rather than in qualitative, phylogenetic analysis. The clear orthology among miRNA genes from different species makes it straightforward to identify and align these sequences from even fragmentary datasets. We also identify significant sequence conservation in the regions directly flanking miRNA genes, and show that this too is of utility in phylogenetic analysis, as well as highlighting conserved regions that will be of interest to other fields. Employing miRNA sequences from 12 sequenced drosophilid genomes, together with a Tribolium castaneum outgroup, we demonstrate that this approach is robust using Bayesian and maximum-likelihood methods. The utility of these characters is further demonstrated in the rhabditid nematodes and primates. As next-generation sequencing makes it more cost-effective to sequence genomes and small RNA libraries, this methodology provides an alternative data source for phylogenetic analysis. The approach allows rapid resolution of relationships between both closely related and rapidly evolving species, and provides an additional tool for investigation of relationships within the tree of life. PMID:25694624

  18. Determining firms׳ utility functions and competitive roles from data on market shares using Lotka-Volterra models.

    PubMed

    Marasco, A; Picucci, A; Romano, A

    2016-06-01

    In this article, we include data on historical and estimated market shares of two markets. In particular, we include annual data on the market shares of the Japanese beer market (1963-2000) and biannual data on the market shares of the mobile phones market in Greece (1998-2007). In addition, we estimate monthly data on market shares for both markets. We show how this data can be used to derive firms' utility functions and their competitive roles.

  19. Morphological and functional characterization of human induced pluripotent stem cell-derived neurons (iCell Neurons) in defined culture systems.

    PubMed

    Berry, Bonnie J; Akanda, Nesar; Smith, Alec S T; Long, Christopher J; Schnepper, Mark T; Guo, Xiufang; Hickman, James J

    2015-01-01

    Pre-clinical testing of drug candidates in animal models is expensive, time-consuming, and often fails to predict drug effects in humans. Industry and academia alike are working to build human-based in vitro test beds and advanced high throughput screening systems to improve the translation of preclinical results to human drug trials. Human neurons derived from induced pluripotent stems cells (hiPSCs) are readily available for use within these test-beds and high throughput screens, but there remains a need to robustly evaluate cellular behavior prior to their incorporation in such systems. This study reports on the characterization of one source of commercially available hiPSC-derived neurons, iCell(®) Neurons, for their long-term viability and functional performance to assess their suitability for integration within advanced in vitro platforms. The purity, morphology, survival, identity, and functional maturation of the cells utilizing different culture substrates and medium combinations were evaluated over 28 days in vitro (DIV). Patch-clamp electrophysiological data demonstrated increased capacity for repetitive firing of action potentials across all culture conditions. Significant differences in cellular maturity, morphology, and functional performance were observed in the different conditions, highlighting the importance of evaluating different surface types and growth medium compositions for application in specific in vitro protocols.

  20. Treatment Utility of Functional versus Empiric Assessment within Consultation for Reading Problems

    ERIC Educational Resources Information Center

    Beavers, Karen F.; Kratochwill, Thomas R.; Braden, Jeffery P.

    2004-01-01

    In this study, 18 teachers and 32 of their students who had reading difficulties were randomly assigned to one of two assessment conditions. In the functional assessment condition, consultants identified functional relationships among environmental events and targeted reading behaviors to develop an intervention plan. In the empiric condition,…

  1. The Utility of CDOM for Improving the Resolution of Riverine DOM Fluxes and Biogeochemical Function

    NASA Astrophysics Data System (ADS)

    Spencer, R. G.; Aiken, G.; Mann, P. J.; Holmes, R. M.; Niggemann, J.; Dittmar, T.; Hernes, P.; Stubbins, A.

    2014-12-01

    A major historical limitation to geochemical studies assessing fluvial fluxes of dissolved organic matter (DOM) has been the issue of both temporal and spatial scaling. Examples will be presented from watersheds around the world highlighting how chromophoric dissolved organic matter (CDOM) measurements can be utilized as proxies for more intensive and expensive analytical analyses (e.g. molecular-level organic biomarkers). Utilizing these refined CDOM loads for terrigenous biomarkers results in improved temporal resolution and a significant change in flux estimates. Examining CDOM and dissolved organic carbon (DOC) flux data from an assortment of terrestrial biomes we establish a robust relationship between CDOM and DOC loads. The application of this relationship allows future studies to derive DOC loads from CDOM utilizing emerging in-situ or remote sensing technologies and thus refine river-to-ocean DOC fluxes, as well as exploit historic imagery to examine how fluxes may have changed. Calculated CDOM yields from a range of rivers are correlated to watershed percent wetland and highlight the importance of certain regions with respect to CDOM flux to the coastal ocean. This approach indicates that future studies might predict CDOM and DOC yields for different watershed types that could then be readily converted to loads providing for the estimation of CDOM and DOC export from ungauged watersheds. Examination of CDOM yields also highlights important geographical regions for future study with respect to the role of terrigenous CDOM in ocean color budgets and CDOM's role in biogeochemical processes. Finally, examples will be presented linking CDOM parameters to DOM composition and biogeochemical properties with the aim of providing measurements to improve the spatial and especially temporal resolution of the role DOM plays in fluvial networks.

  2. The Utility of the HSAB Principle via the Fukui Function in Biological Systems

    PubMed Central

    Faver, John; Merz, Kenneth M.

    2010-01-01

    The hard/soft acid-base principle has long been known to be an excellent predictor of chemical reactivity. The Fukui function, a reactivity descriptor from conceptual density functional theory, has been shown to be related to the local softness of a system. The usefulness of the Fukui function is explored and demonstrated herein for three common biological problems: ligand docking, active site detection, and protein folding. In each type of study, a scoring function is developed based on the local HSAB principle using atomic Fukui indices. Even with necessary approximations for its use in large systems, the Fukui function remains a useful descriptor for predicting chemical reactivity and understanding chemical systems. PMID:20369029

  3. Method for utilizing properties of the sinc(x) function for phase retrieval on nyquist-under-sampled data

    NASA Technical Reports Server (NTRS)

    Dean, Bruce H. (Inventor); Smith, Jeffrey Scott (Inventor); Aronstein, David L. (Inventor)

    2012-01-01

    Disclosed herein are systems, methods, and non-transitory computer-readable storage media for simulating propagation of an electromagnetic field, performing phase retrieval, or sampling a band-limited function. A system practicing the method generates transformed data using a discrete Fourier transform which samples a band-limited function f(x) without interpolating or modifying received data associated with the function f(x), wherein an interval between repeated copies in a periodic extension of the function f(x) obtained from the discrete Fourier transform is associated with a sampling ratio Q, defined as a ratio of a sampling frequency to a band-limited frequency, and wherein Q is assigned a value between 1 and 2 such that substantially no aliasing occurs in the transformed data, and retrieves a phase in the received data based on the transformed data, wherein the phase is used as feedback to an optical system.

  4. Functional genomics screening utilizing mutant mouse embryonic stem cells identifies novel radiation-response genes.

    PubMed

    Loesch, Kimberly; Galaviz, Stacy; Hamoui, Zaher; Clanton, Ryan; Akabani, Gamal; Deveau, Michael; DeJesus, Michael; Ioerger, Thomas; Sacchettini, James C; Wallis, Deeann

    2015-01-01

    Elucidating the genetic determinants of radiation response is crucial to optimizing and individualizing radiotherapy for cancer patients. In order to identify genes that are involved in enhanced sensitivity or resistance to radiation, a library of stable mutant murine embryonic stem cells (ESCs), each with a defined mutation, was screened for cell viability and gene expression in response to radiation exposure. We focused on a cancer-relevant subset of over 500 mutant ESC lines. We identified 13 genes; 7 genes that have been previously implicated in radiation response and 6 other genes that have never been implicated in radiation response. After screening, proteomic analysis showed enrichment for genes involved in cellular component disassembly (e.g. Dstn and Pex14) and regulation of growth (e.g. Adnp2, Epc1, and Ing4). Overall, the best targets with the highest potential for sensitizing cancer cells to radiation were Dstn and Map2k6, and the best targets for enhancing resistance to radiation were Iqgap and Vcan. Hence, we provide compelling evidence that screening mutant ESCs is a powerful approach to identify genes that alter radiation response. Ultimately, this knowledge can be used to define genetic variants or therapeutic targets that will enhance clinical therapy.

  5. Identification and functional analysis of the gene cluster for fructan utilization in Prevotella intermedia.

    PubMed

    Fuse, Haruka; Fukamachi, Haruka; Inoue, Mitsuko; Igarashi, Takeshi

    2013-02-25

    Fructanase enzymes hydrolyze the β-2,6 and β-2,1 linkages of levan and inulin fructans, respectively. We analyzed the influence of fructan on the growth of Prevotella intermedia. The growth of P. intermedia was enhanced by addition of inulin, implying that P. intermedia could also use inulin. Based on this finding, we identified and analyzed the genes encoding a putative fructanase (FruA), sugar transporter (FruB), and fructokinase (FruK) in the genome of strain ATCC25611. Transcript analysis by RT-PCR showed that the fruABK genes were co-transcribed as a single mRNA and semi-quantitative analysis confirmed that the fruA gene was induced in response to fructose and inulin. Recombinant FruA and FruK were purified and characterized biochemically. FruA strongly hydrolyzed inulin, with slight degradation of levan via an exo-type mechanism, revealing that FruA is an exo-β-d-fructanase. FruK converted fructose to fructose-6-phosphate in the presence of ATP, confirming that FruK is an ATP-dependent fructokinase. These results suggest that P. intermedia can utilize fructan as a carbon source for growth, and that the fructanase, sugar transporter, and fructokinase proteins we identified are involved in this fructan utilization.

  6. Kidney function assessment and its role in drug development, review and utilization.

    PubMed

    Tortorici, Michael A; Nolin, Thomas D

    2014-07-01

    A key regulatory requirement pertaining to drug development is characterization of the role of kidney function in drug disposition and response, along with provision of corresponding renal dose adjustment recommendations. Traditionally, this information has been derived from Phase I pharmacokinetic studies in which regulatory guidance exists for pharmaceutical manufacturers on the design, conduct, analysis, and interpretation of data. Categorization and stratification of subjects into kidney function groups and dosing recommendations have historically been based on creatinine clearance estimates using the Cockcroft-Gault equation. As new estimating equations have emerged, the choice of equation for assessment of kidney function has become an area of debate. This review highlights these equations and provides recent examples of the use of quantitative models, incorporating efficacy and safety to make rational dose recommendations in subjects with impaired kidney function.

  7. Hybrid diversity method utilizing adaptive diversity function for recovering unknown aberrations in an optical system

    NASA Technical Reports Server (NTRS)

    Dean, Bruce H. (Inventor)

    2009-01-01

    A method of recovering unknown aberrations in an optical system includes collecting intensity data produced by the optical system, generating an initial estimate of a phase of the optical system, iteratively performing a phase retrieval on the intensity data to generate a phase estimate using an initial diversity function corresponding to the intensity data, generating a phase map from the phase retrieval phase estimate, decomposing the phase map to generate a decomposition vector, generating an updated diversity function by combining the initial diversity function with the decomposition vector, generating an updated estimate of the phase of the optical system by removing the initial diversity function from the phase map. The method may further include repeating the process beginning with iteratively performing a phase retrieval on the intensity data using the updated estimate of the phase of the optical system in place of the initial estimate of the phase of the optical system, and using the updated diversity function in place of the initial diversity function, until a predetermined convergence is achieved.

  8. Impairment in Occupational Functioning and Adult ADHD: The Predictive Utility of Executive Function (EF) Ratings Versus EF Tests

    PubMed Central

    Barkley, Russell A.; Murphy, Kevin R.

    2010-01-01

    Attention deficit hyperactivity disorder (ADHD) is associated with deficits in executive functioning (EF). ADHD in adults is also associated with impairments in major life activities, particularly occupational functioning. We investigated the extent to which EF deficits assessed by both tests and self-ratings contributed to the degree of impairment in 11 measures involving self-reported occupational problems, employer reported workplace adjustment, and clinician rated occupational adjustment. Three groups of adults were recruited as a function of their severity of ADHD: ADHD diagnosis (n = 146), clinical controls self-referring for ADHD but not diagnosed with it (n = 97), and community controls (n = 109). Groups were combined and regression analyses revealed that self-ratings of EF were significantly predictive of impairments in all 11 measures of occupational adjustment. Although several tests of EF also did so, they contributed substantially less than did the EF ratings, particularly when analyzed jointly with the ratings. We conclude that EF deficits contribute to the impairments in occupational functioning that occur in conjunction with adult ADHD. Ratings of EF in daily life contribute more to such impairments than do EF tests, perhaps because, as we hypothesize, each assesses a different level in the hierarchical organization of EF as a meta-construct. PMID:20197297

  9. THE CLINICAL UTILITY OF FUNCTIONAL PERFORMANCE TESTS WITHIN ONE-YEAR POST-ACL RECONSTRUCTION: A SYSTEMATIC REVIEW

    PubMed Central

    Narducci, Elizabeth; Waltz, Amanda; Gorski, Katheryn; Leppla, Lucas

    2011-01-01

    Introduction: A tear of the anterior cruciate ligament (ACL) represents a significant injury for an athlete that requires substantial time away from sport, and significant rehabilitation after reconstruction. The physical therapist is responsible to determine when a patient is capable of tolerating the physical demands of daily activities and to attempt to prevent re-injury. Physical or functional performance tests (FPTs) are one mechanism used to evaluate the athlete's physical skills and capabilities prior to returning to sports participation. The purpose of this systematic review is to critically examine the clinical utility of functional performance tests used with patients less than or equal to one year post ACL reconstruction. Methods: A systematic review of the relevant literature was performed using PRISMA guidelines. A total of twelve studies were included for analysis. Results: Two independent blinded reviewers then analyzed and rated the final included articles (n=12) utilizing the Newcastle-Ottawa Scale (NOS). Percent overall agreement between raters for the NOS was 88% with a fixed-marginal kappa (κ) of 0.80. Of the 12 included articles, the FPTs were utilized as an outcome measure within the study design (41.7%) or studied as a measure of function (58.3%). Among those studies that used FPTs as a “measure of function” 71.4% studied a battery of FPTs, while 28.6% studied a single test. None of the studies utilized FPTs as a measure to determine readiness to return to sport. Discussion: FPTs are being utilized with patients, less than or equal to one year post ACL reconstruction, either as an assessment of functional performance or as an outcome measure. No studies identified a FPT or test battery that has construct or predictive validity for “return to sport” in athletic population one-year post-ACL reconstruction. The identification of the critical elements within the return to sport construct may allow lower extremity performance tests to be

  10. Development of a conditional Mesd (mesoderm development) allele for functional analysis of the low-density lipoprotein receptor-related family in defined tissues.

    PubMed

    Taibi, Andrew V; Lighthouse, Janet K; Grady, Richard C; Shroyer, Kenneth R; Holdener, Bernadette C

    2013-01-01

    The Low-density lipoprotein receptor-Related Protein (LRP) family members are essential for diverse processes ranging from the regulation of gastrulation to the modulation of lipid homeostasis. Receptors in this family bind and internalize a diverse array of ligands in the extracellular matrix (ECM). As a consequence, LRPs regulate a wide variety of cellular functions including, but not limited to lipid metabolism, membrane composition, cell motility, and cell signaling. Not surprisingly, mutations in single human LRPs are associated with defects in cholesterol metabolism and development of atherosclerosis, abnormalities in bone density, or aberrant eye vasculature, and may be a contributing factor in development of Alzheimer's disease. Often, members of this diverse family of receptors perform overlapping roles in the same tissues, complicating the analysis of their function through conventional targeted mutagenesis. Here, we describe development of a mouse Mesd (Mesoderm Development) conditional knockout allele, and demonstrate that ubiquitous deletion of Mesd using Cre-recombinase blocks gastrulation, as observed in the traditional knockout and albino-deletion phenotypes. This conditional allele will serve as an excellent tool for future characterization of the cumulative contribution of LRP members in defined tissues.

  11. Utilization of Microscale Silicon Cantilevers to Assess Cellular Contractile Function In Vitro

    PubMed Central

    Smith, Alec S.T.; Long, Christopher J.; McAleer, Christopher; Bobbitt, Nathaniel; Srinivasan, Balaji; Hickman, James J.

    2014-01-01

    The development of more predictive and biologically relevant in vitro assays is predicated on the advancement of versatile cell culture systems which facilitate the functional assessment of the seeded cells. To that end, microscale cantilever technology offers a platform with which to measure the contractile functionality of a range of cell types, including skeletal, cardiac, and smooth muscle cells, through assessment of contraction induced substrate bending. Application of multiplexed cantilever arrays provides the means to develop moderate to high-throughput protocols for assessing drug efficacy and toxicity, disease phenotype and progression, as well as neuromuscular and other cell-cell interactions. This manuscript provides the details for fabricating reliable cantilever arrays for this purpose, and the methods required to successfully culture cells on these surfaces. Further description is provided on the steps necessary to perform functional analysis of contractile cell types maintained on such arrays using a novel laser and photo-detector system. The representative data provided highlights the precision and reproducible nature of the analysis of contractile function possible using this system, as well as the wide range of studies to which such technology can be applied. Successful widespread adoption of this system could provide investigators with the means to perform rapid, low cost functional studies in vitro, leading to more accurate predictions of tissue performance, disease development and response to novel therapeutic treatment. PMID:25350792

  12. Pre- and postoperative evaluation of renal function in patients with staghorn calculi utilizing quantitative renal scanning.

    PubMed

    Stage, K H; Lewis, S

    1981-01-01

    Differential quantitative renal scans using 99-technetium diethylene triaminepentaacetic acid (DTPA) or 131I Hippuran were obtained properatively on 12 patients with unilateral or bilateral staghorn calculi. Of the 14 renal units studied, 12 kidneys underwent anatrophic nephrolithotomy, pyelolithotomy, or a combination of both techniques; 2 patients underwent nephrectomy based on poor function of the affected side preoperatively. Postoperative follow-up scans were obtained on the 12 kidneys undergoing stone cleanout. Seven of 12 kidneys (58 per cent) studied pre- and postoperatively showed moderate to significant improvement in per cent contribution to total renal function. Seven of 10 kidneys (70 per cent) studied pre- and postoperatively showed improvement in glomerular filtration rate or effective renal plasma flow. The scans revelaed no dramatic difference in postoperative functional loss between pyelolithotomy and anatrophic nephrolithotomy. The computerizewd quantitative renal scan helps in selection of surgical technique and objective postoperative assessment of surgical results.

  13. Tumor functional and molecular imaging utilizing ultrasound and ultrasound-mediated optical techniques.

    PubMed

    Yuan, Baohong; Rychak, Joshua

    2013-02-01

    Tumor functional and molecular imaging has significantly contributed to cancer preclinical research and clinical applications. Among typical imaging modalities, ultrasonic and optical techniques are two commonly used methods; both share several common features such as cost efficiency, absence of ionizing radiation, relatively inexpensive contrast agents, and comparable maximum-imaging depth. Ultrasonic and optical techniques are also complementary in imaging resolution, molecular sensitivity, and imaging space (vascular and extravascular). The marriage between ultrasonic and optical techniques takes advantages of both techniques. This review introduces tumor functional and molecular imaging using microbubble-based ultrasound and ultrasound-mediated optical imaging techniques.

  14. Delineating potential epileptogenic areas utilizing resting functional magnetic resonance imaging (fMRI) in epilepsy patients.

    PubMed

    Pizarro, Ricardo; Nair, Veena; Meier, Timothy; Holdsworth, Ryan; Tunnell, Evelyn; Rutecki, Paul; Sillay, Karl; Meyerand, Mary E; Prabhakaran, Vivek

    2016-08-01

    Seizure localization includes neuroimaging like electroencephalogram, and magnetic resonance imaging (MRI) with limited ability to characterize the epileptogenic network. Temporal clustering analysis (TCA) characterizes epileptogenic network congruent with interictal epileptiform discharges by clustering together voxels with transient signals. We generated epileptogenic areas for 12 of 13 epilepsy patients with TCA, congruent with different areas of seizure onset. Resting functional MRI (fMRI) scans are noninvasive, and can be acquired quickly, in patients with different levels of severity and function. Analyzing resting fMRI data using TCA is quick and can complement clinical methods to characterize the epileptogenic network.

  15. Boundary value problem of Pontryagin's maximum principle in a two-sector economy model with an integral utility function

    NASA Astrophysics Data System (ADS)

    Kiselev, Yu. N.; Orlov, M. V.; Orlov, S. M.

    2015-11-01

    An infinite-horizon two-sector economy model with a Cobb-Douglas production function and a utility function that is an integral functional with discounting and a logarithmic integrand is investigated. The application of Pontryagin's maximum principle yields a boundary value problem with special conditions at infinity. The search for the solution of the maximum-principle boundary value problem is complicated by singular modes in its optimal solution. In the construction of the solution to the problem, they are described in analytical form. Additionally, a special version of the sweep method in continuous form is proposed, which is of interest from theoretical and computational points of view. An important result is the proof of the optimality of the extremal solution obtained by applying the maximum-principle boundary value problem.

  16. (Mal)Adaptive Psychological Functioning of Students Utilizing University Counseling Services

    PubMed Central

    Biasi, Valeria; Cerutti, Rita; Mallia, Luca; Menozzi, Francesca; Patrizi, Nazarena; Violani, Cristiano

    2017-01-01

    Background: University students confront psychological difficulties that can negatively influence their academic performance. The present study aimed to assess several areas of adaptive and maladaptive psychological functioning among university students who request counseling services. Method: One hundred eighty-four young female students seeking professional psychological help (Counseling seekers) and 185 young female students who have never asked for psychological help (Non-counseling seekers) were asked to complete the Adult Self-Report (ASR) to evaluate both their internalizing and externalizing problems through DSM-oriented scales as well as their adaptive functioning. Results: ANOVA results indicated worse psychological functioning for the students who sought counseling. They reported lower score in ASR Adaptive Functioning Scales (i.e., friends, jobs, family, education), and higher scores in DSM-oriented scales (i.e., Depressive, Anxiety, Somatic, Avoidant Personality, Attention Deficit/Hyperactivity symptoms) than the students who never asked psychological help. Furthermore, discriminant analysis successfully discriminated between the two groups of students on the basis of the ASR’s adaptive and DSM-oriented scales. Conclusion: The study findings could be useful to guide university counseling services in their screening activities as well as useful for clinical practice. PMID:28360880

  17. Athletes and Sedentary Individuals: An Intergroup Comparison Utilizing a Pulmonary Function Ratio Obtained During Submaximal Exercise.

    ERIC Educational Resources Information Center

    Maud, Peter J.

    A pulmonary function ratio describing oxygen extraction from alveolar ventilation was used for an intergroup comparison between three groups of athletes (rugby, basketball, and football players) and one group of sedentary subjects during steady-state submaximal exercise. The ratio and its component parts are determined from only three gas…

  18. The Utilization of Social Policy Research: An Empirical Analysis of Its Structure and Functions.

    ERIC Educational Resources Information Center

    van de Vall, Mark; Bolas, Cheryl

    Results of a study to determine the impact of social policy research upon organizational decisions are reported. Studies of 120 projects in the Netherlands were drawn from three areas of social policy making: industrial and labor relations, regional and urban planning, and social welfare and public health. Three functions of social policy research…

  19. The Utility of the Lambert Function W[a exp(a - bt)] in Chemical Kinetics

    ERIC Educational Resources Information Center

    Williams, Brian Wesley

    2010-01-01

    The mathematical Lambert function W[a exp(a - bt)] is used to find integrated rate laws for several examples, including simple enzyme and Lindemann-Christiansen-Hinshelwood (LCH) unimolecular decay kinetics. The results derived here for the well-known LCH mechanism as well as for a dimer-monomer reaction mechanism appear to be novel. A nonlinear…

  20. Prekindergarten Children's Executive Functioning Skills and Achievement Gains: The Utility of Direct Assessments and Teacher Ratings

    ERIC Educational Resources Information Center

    Fuhs, Mary Wagner; Farran, Dale Clark; Nesbitt, Kimberly Turner

    2015-01-01

    An accumulating body of evidence suggests that young children who exhibit greater executive functioning (EF) skills in early childhood also achieve more academically. The goal of the present study was to examine the unique contributions of direct assessments and teacher ratings of children's EF skills at the beginning of prekindergarten (pre-k) to…

  1. nanoCAGE reveals 5′ UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAs

    PubMed Central

    Gandin, Valentina; Masvidal, Laia; Hulea, Laura; Gravel, Simon-Pierre; Cargnello, Marie; McLaughlan, Shannon; Cai, Yutian; Balanathan, Preetika; Morita, Masahiro; Rajakumar, Arjuna; Furic, Luc; Pollak, Michael; Porco, John A.; St-Pierre, Julie; Pelletier, Jerry; Larsson, Ola; Topisirovic, Ivan

    2016-01-01

    The diversity of MTOR-regulated mRNA translation remains unresolved. Whereas ribosome-profiling suggested that MTOR almost exclusively stimulates translation of the TOP (terminal oligopyrimidine motif) and TOP-like mRNAs, polysome-profiling indicated that MTOR also modulates translation of mRNAs without the 5′ TOP motif (non-TOP mRNAs). We demonstrate that in ribosome-profiling studies, detection of MTOR-dependent changes in non-TOP mRNA translation was obscured by low sensitivity and methodology biases. Transcription start site profiling using nano-cap analysis of gene expression (nanoCAGE) revealed that not only do many MTOR-sensitive mRNAs lack the 5′ TOP motif but that 5′ UTR features distinguish two functionally and translationally distinct subsets of MTOR-sensitive mRNAs: (1) mRNAs with short 5′ UTRs enriched for mitochondrial functions, which require EIF4E but are less EIF4A1-sensitive; and (2) long 5′ UTR mRNAs encoding proliferation- and survival-promoting proteins, which are both EIF4E- and EIF4A1-sensitive. Selective inhibition of translation of mRNAs harboring long 5′ UTRs via EIF4A1 suppression leads to sustained expression of proteins involved in respiration but concomitant loss of those protecting mitochondrial structural integrity, resulting in apoptosis. Conversely, simultaneous suppression of translation of both long and short 5′ UTR mRNAs by MTOR inhibitors results in metabolic dormancy and a predominantly cytostatic effect. Thus, 5′ UTR features define different modes of MTOR-sensitive translation of functionally distinct subsets of mRNAs, which may explain the diverse impact of MTOR and EIF4A inhibitors on neoplastic cells. PMID:26984228

  2. Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data

    PubMed Central

    Joo, Seongjung; Kawabata, Hugh; Al, Maiwenn J.; Allison, Paul D.; Rutten‐van Mölken, Maureen P. M. H.; Frits, Michelle L.; Iannaccone, Christine K.; Shadick, Nancy A.; Weinblatt, Michael E.

    2016-01-01

    Objective To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. Methods Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M‐HAQ), the EuroQol 5‐domain (EQ‐5D; a quality‐of‐life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Results Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM‐HAQ −0.047; P = 0.0100) and CDAI ≤2.8 (−0.073; P = 0.0003) but not DAS28‐CRP <2.6 (−0.022; P = 0.1735). Target attainment was associated with significantly improved EQ‐5D (0.022–0.096; P < 0.0030 versus LDA, MDA, or SDA). Patients achieving guideline‐recommended disease targets were 36–45% less likely to be hospitalized (P < 0.0500) and 23–45% less likely to utilize DME (P < 0.0100). Conclusion Attaining recommended target disease‐activity measures was associated with enhanced physical functioning and health‐related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients. PMID:26238974

  3. The effect of education on regional brain metabolism and its functional connectivity in an aged population utilizing positron emission tomography.

    PubMed

    Kim, Jaeik; Chey, Jeanyung; Kim, Sang-Eun; Kim, Hoyoung

    2015-05-01

    Education involves learning new information and acquiring cognitive skills. These require various cognitive processes including learning, memory, and language. Since cognitive processes activate associated brain areas, we proposed that the brains of elderly people with longer education periods would show traces of repeated activation as increased synaptic connectivity and capillary in brain areas involved in learning, memory, and language. Utilizing positron emission topography (PET), this study examined the effect of education in the human brain utilizing the regional cerebral glucose metabolism rates (rCMRglcs). 26 elderly women with high-level education (HEG) and 26 with low-level education (LEG) were compared with regard to their regional brain activation and association between the regions. Further, graphical theoretical analysis using rCMRglcs was applied to examine differences in the functional network properties of the brain. The results showed that the HEG had higher rCMRglc in the ventral cerebral regions that are mainly involved in memory, language, and neurogenesis, while the LEG had higher rCMRglc in apical areas of the cerebrum mainly involved in motor and somatosensory functions. Functional connectivity investigated with graph theoretical analysis illustrated that the brain of the HEG compared to those of the LEG were overall more efficient, more resilient, and characterized by small-worldness. This may be one of the brain's mechanisms mediating the reserve effects found in people with higher education.

  4. Functional Analysis of the Fructooligosaccharide Utilization Operon in Lactobacillus paracasei 1195▿

    PubMed Central

    Goh, Yong Jun; Lee, Jong-Hwa; Hutkins, Robert W.

    2007-01-01

    The fosABCDXE operon encodes components of a putative fructose/mannose phosphoenolpyruvate-dependent phosphotransferase system and a β-fructosidase precursor (FosE) that are involved in the fructooligosaccharide (FOS) utilization pathway of Lactobacillus paracasei 1195. The presence of an N-terminal signal peptide sequence and an LPQAG cell wall anchor motif in the C-terminal region of the deduced FosE precursor amino acid sequence predicted that the enzyme is cell wall associated, indicating that FOS may be hydrolyzed extracellularly. In this study, cell fractionation experiments demonstrated that the FOS hydrolysis activity was present exclusively in the cell wall extract of L. paracasei previously grown on FOS. In contrast, no measurable FOS hydrolysis activity was detected in the cell wall extract from the isogenic fosE mutant. Induction of β-fructosidase activity was observed when cells were grown on FOS, inulin, sucrose, or fructose but not when cells were grown on glucose. A diauxic growth pattern was observed when cells were grown on FOS in the presence of limiting glucose (0.1%). Analysis of the culture supernatant revealed that glucose was consumed first, followed by the longer-chain FOS species. Transcription analysis further showed that the fos operon was expressed only after glucose was depleted in the medium. Expression of fosE in a non-FOS-fermenting strain, Lactobacillus rhamnosus GG, enabled the recombinant strain to metabolize FOS, inulin, sucrose, and levan. PMID:17644636

  5. Functional and comparative genomic analyses of an operon involved in fructooligosaccharide utilization by Lactobacillus acidophilus

    PubMed Central

    Barrangou, Rodolphe; Altermann, Eric; Hutkins, Robert; Cano, Raul; Klaenhammer, Todd R.

    2003-01-01

    Lactobacillus acidophilus is a probiotic organism that displays the ability to use prebiotic compounds such as fructooligosaccharides (FOS), which stimulate the growth of beneficial commensals in the gastrointestinal tract. However, little is known about the mechanisms and genes involved in FOS utilization by Lactobacillus species. Analysis of the L. acidophilus NCFM genome revealed an msm locus composed of a transcriptional regulator of the LacI family, a four-component ATP-binding cassette (ABC) transport system, a fructosidase, and a sucrose phosphorylase. Transcriptional analysis of this operon demonstrated that gene expression was induced by sucrose and FOS but not by glucose or fructose, suggesting some specificity for nonreadily fermentable sugars. Additionally, expression was repressed by glucose but not by fructose, suggesting catabolite repression via two cre-like sequences identified in the promoter–operator region. Insertional inactivation of the genes encoding the ABC transporter substrate-binding protein and the fructosidase reduced the ability of the mutants to grow on FOS. Comparative analysis of gene architecture within this cluster revealed a high degree of synteny with operons in Streptococcus mutans and Streptococcus pneumoniae. However, the association between a fructosidase and an ABC transporter is unusual and may be specific to L. acidophilus. This is a description of a previously undescribed gene locus involved in transport and catabolism of FOS compounds, which can promote competition of beneficial microorganisms in the human gastrointestinal tract. PMID:12847288

  6. Reaching unanimous agreements within agent-based negotiation teams with linear and monotonic utility functions.

    PubMed

    Sanchez-Anguix, Victor; Julian, Vicente; Botti, Vicente; García-Fornes, Ana

    2012-06-01

    In this article, an agent-based negotiation model for negotiation teams that negotiate a deal with an opponent is presented. Agent-based negotiation teams are groups of agents that join together as a single negotiation party because they share an interest that is related to the negotiation process. The model relies on a trusted mediator that coordinates and helps team members in the decisions that they have to take during the negotiation process: which offer is sent to the opponent, and whether the offers received from the opponent are accepted. The main strength of the proposed negotiation model is the fact that it guarantees unanimity within team decisions since decisions report a utility to team members that is greater than or equal to their aspiration levels at each negotiation round. This work analyzes how unanimous decisions are taken within the team and the robustness of the model against different types of manipulations. An empirical evaluation is also performed to study the impact of the different parameters of the model.

  7. The Nutraceutical Properties of Ovotransferrin and Its Potential Utilization as a Functional Food

    PubMed Central

    Giansanti, Francesco; Leboffe, Loris; Angelucci, Francesco; Antonini, Giovanni

    2015-01-01

    Ovotransferrin or conalbumin belong to the transferrin protein family and is endowed with both iron-transfer and protective activities. In addition to its well-known antibacterial properties, ovotransferrin displays other protective roles similar to those already ascertained for the homologous mammalian lactoferrin. These additional functions, in many cases not directly related to iron binding, are also displayed by the peptides derived from partial hydrolysis of ovotransferrin, suggesting a direct relationship between egg consumption and human health. PMID:26556366

  8. The Nutraceutical Properties of Ovotransferrin and Its Potential Utilization as a Functional Food.

    PubMed

    Giansanti, Francesco; Leboffe, Loris; Angelucci, Francesco; Antonini, Giovanni

    2015-11-04

    Ovotransferrin or conalbumin belong to the transferrin protein family and is endowed with both iron-transfer and protective activities. In addition to its well-known antibacterial properties, ovotransferrin displays other protective roles similar to those already ascertained for the homologous mammalian lactoferrin. These additional functions, in many cases not directly related to iron binding, are also displayed by the peptides derived from partial hydrolysis of ovotransferrin, suggesting a direct relationship between egg consumption and human health.

  9. Eddy current nondestructive testing device for measuring variable characteristics of a sample utilizing Walsh functions

    DOEpatents

    Libby, Hugo L.; Hildebrand, Bernard P.

    1978-01-01

    An eddy current testing device for measuring variable characteristics of a sample generates a signal which varies with variations in such characteristics. A signal expander samples at least a portion of this generated signal and expands the sampled signal on a selected basis of square waves or Walsh functions to produce a plurality of signal components representative of the sampled signal. A network combines these components to provide a display of at least one of the characteristics of the sample.

  10. Utilizing Probability Distribution Functions and Ensembles to Forecast lonospheric and Thermosphere Space Weather

    DTIC Science & Technology

    2016-04-26

    Functions and Ensembles to Forecast lonospheric and Thermosphere Space Weather 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-12-1-0265 5c. PROGRAM...Wind Velocity, Ionosphere, Thermosphere, Space Weather 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER OF PAGES 10 19a...and realistic. • The ability of an ensemble-driven ionosphere-thermosphere model to “predict” space weather needs to be proven. This will be done

  11. Utilization of Food Processing By-products as Dietary, Functional, and Novel Fiber: A Review.

    PubMed

    Sharma, Satish Kumar; Bansal, Sangita; Mangal, Manisha; Dixit, Anil Kumar; Gupta, Ram K; Mangal, A K

    2016-07-26

    Fast growing food processing industry in most countries across the world, generates huge quantity of by-products, including pomace, hull, husk, pods, peel, shells, seeds, stems, stalks, bran, washings, pulp refuse, press cakes, etc., which have less use and create considerable environmental pollution. With growing interest in health promoting functional foods, the demand of natural bioactives has increased and exploration for new sources is on the way. Many of the food processing industrial by-products are rich sources of dietary, functional, and novel fibers. These by-products can be directly (or after certain modifications for isolation or purification of fiber) used for the manufacture of various foods, i.e. bread, buns, cake, pasta, noodles, biscuit, ice creams, yogurts, cheese, beverages, milk shakes, instant breakfasts, ice tea, juices, sports drinks, wine, powdered drink, fermented milk products, meat products and meat analogues, synthetic meat, etc. A comprehensive literature survey has been carried on this topic to give an overview in the field dietary fiber from food by-products. In this article, the developments in the definition of fiber, fiber classification, potential sources of dietary fibers in food processing by-products, their uses, functional properties, caloric content, energy values and the labelling regulations have been discussed.

  12. A multi-functional apparatus for α and β spectroscopy utilizing a permanent ring-magnet β spectrometer

    NASA Astrophysics Data System (ADS)

    Becchetti, F. D.; Febbraro, M.; Riggins, J.; Torres-Isea, R. O.

    2016-11-01

    A multi-functional teaching apparatus has been developed for α and β spectroscopy utilizing a solid-state detector and associated electronics. The possible experiments include conventional measurements to determine α and β decay energies, half lives, characteristic energy loss of nuclear particles in matter, and limits on the β-neutrino mass set from endpoints in β-decay spectra. In addition, the relativistic mass increase of β particles is verified using a high-efficiency, axially symmetric permanent ring-magnet β spectrometer. The basic apparatus also can be adapted for experiments in Rutherford scattering and other nuclear measurements.

  13. Functional Annotation Analytics of Bacillus Genomes Reveals Stress Responsive Acetate Utilization and Sulfate Uptake in the Biotechnologically Relevant Bacillus megaterium.

    PubMed

    Williams, Baraka S; Isokpehi, Raphael D; Mbah, Andreas N; Hollman, Antoinesha L; Bernard, Christina O; Simmons, Shaneka S; Ayensu, Wellington K; Garner, Bianca L

    2012-01-01

    Bacillus species form an heterogeneous group of Gram-positive bacteria that include members that are disease-causing, biotechnologically-relevant, and can serve as biological research tools. A common feature of Bacillus species is their ability to survive in harsh environmental conditions by formation of resistant endospores. Genes encoding the universal stress protein (USP) domain confer cellular and organismal survival during unfavorable conditions such as nutrient depletion. As of February 2012, the genome sequences and a variety of functional annotations for at least 123 Bacillus isolates including 45 Bacillus cereus isolates were available in public domain bioinformatics resources. Additionally, the genome sequencing status of 10 of the B. cereus isolates were annotated as finished with each genome encoded 3 USP genes. The conservation of gene neighborhood of the 140 aa universal stress protein in the B. cereus genomes led to the identification of a predicted plasmid-encoded transcriptional unit that includes a USP gene and a sulfate uptake gene in the soil-inhabiting Bacillus megaterium. Gene neighborhood analysis combined with visual analytics of chemical ligand binding sites data provided knowledge-building biological insights on possible cellular functions of B. megaterium universal stress proteins. These functions include sulfate and potassium uptake, acid extrusion, cellular energy-level sensing, survival in high oxygen conditions and acetate utilization. Of particular interest was a two-gene transcriptional unit that consisted of genes for a universal stress protein and a sirtuin Sir2 (deacetylase enzyme for NAD+-dependent acetate utilization). The predicted transcriptional units for stress responsive inorganic sulfate uptake and acetate utilization could explain biological mechanisms for survival of soil-inhabiting Bacillus species in sulfate and acetate limiting conditions. Considering the key role of sirtuins in mammalian physiology additional

  14. Functional Annotation Analytics of Bacillus Genomes Reveals Stress Responsive Acetate Utilization and Sulfate Uptake in the Biotechnologically Relevant Bacillus megaterium

    PubMed Central

    Williams, Baraka S.; Isokpehi, Raphael D.; Mbah, Andreas N.; Hollman, Antoinesha L.; Bernard, Christina O.; Simmons, Shaneka S.; Ayensu, Wellington K.; Garner, Bianca L.

    2012-01-01

    Bacillus species form an heterogeneous group of Gram-positive bacteria that include members that are disease-causing, biotechnologically-relevant, and can serve as biological research tools. A common feature of Bacillus species is their ability to survive in harsh environmental conditions by formation of resistant endospores. Genes encoding the universal stress protein (USP) domain confer cellular and organismal survival during unfavorable conditions such as nutrient depletion. As of February 2012, the genome sequences and a variety of functional annotations for at least 123 Bacillus isolates including 45 Bacillus cereus isolates were available in public domain bioinformatics resources. Additionally, the genome sequencing status of 10 of the B. cereus isolates were annotated as finished with each genome encoded 3 USP genes. The conservation of gene neighborhood of the 140 aa universal stress protein in the B. cereus genomes led to the identification of a predicted plasmid-encoded transcriptional unit that includes a USP gene and a sulfate uptake gene in the soil-inhabiting Bacillus megaterium. Gene neighborhood analysis combined with visual analytics of chemical ligand binding sites data provided knowledge-building biological insights on possible cellular functions of B. megaterium universal stress proteins. These functions include sulfate and potassium uptake, acid extrusion, cellular energy-level sensing, survival in high oxygen conditions and acetate utilization. Of particular interest was a two-gene transcriptional unit that consisted of genes for a universal stress protein and a sirtuin Sir2 (deacetylase enzyme for NAD+-dependent acetate utilization). The predicted transcriptional units for stress responsive inorganic sulfate uptake and acetate utilization could explain biological mechanisms for survival of soil-inhabiting Bacillus species in sulfate and acetate limiting conditions. Considering the key role of sirtuins in mammalian physiology additional

  15. Real-time Periodic Processing of RT-middleware Utilizing Linux Standard Functionalities

    NASA Astrophysics Data System (ADS)

    Shimizu, Masaharu; Toda, Kengo; Hayashibara, Yasuo; Yamato, Hideaki; Furuta, Takayuki

    A new methodology of real-time periodic processing on RT-middleware based on the Linux standard functionalities is presented in this paper. The central of discussion is on the realization of real-time processing while keeping the reusability of software modules ensured by the RT-middleware framework as well as the portability provided by the Linux development mainstream. In order to show the validity of the proposed approach, two robot systems, including an omnidirectional electric wheelchair steered by haptic joystick, are presented and the discussion about the evaluation result follows from the view point of practicality.

  16. The Acquisition and Utilization of Spatial and Functional Knowledge for Imagery Analysis

    DTIC Science & Technology

    1991-03-01

    Mathematical and Information Sciences Dist Avai Id David M. McKeown, Jr. A-i f Principal Investigator Digital Mapping Laboratory School of Computer Science...5.2.1. Focusing Functional-Areas 23 5.2.2. Ambiguous Interpretations 25 5.2.3. Relative Shape Constraints 25 5.3. Results for Model Generation 26 5.3.1...tool allows the user to graphically display ground truth data, SPAM interpretations and consistency information , as well as permitting the user to invoke

  17. Improvement in Empirical Potential Functions for Increasing the Utility of Molecular Dynamics Simulations

    NASA Astrophysics Data System (ADS)

    Yamashita, Takefumi

    Accurate modeling of potential functions is critical for realistic molecular dynamics (MD) simulations. In this study, improvement in potential functions is discussed by revisiting the multistate empirical valence bond (MS-EVB) method and the FUJI force field. The MS-EVB method enables simulation of dynamic chemical reactions in various situations. In this study, excess protons in water under shear were investigated by combining the MS-EVB method with the non-equilibrium MD technique. It was found that the orientation of the hydronium-like moiety is considerably more anisotropic under shear than that of the water molecule. Separately, the FUJI force field includes main-chain torsional parameters carefully derived on the basis of high-level ab initio calculations. To further demonstrate that the use of the FUJI force field improves the accuracy of MD results beyond previously reported examples, the conformational distribution of the Ala dipeptide was investigated. The results obtained using the FUJI force field agreed more closely with the experimental results than those obtained using other standard force fields. Interestingly, the MD trajectories with the FUJI force field undergo the Y conformation more frequently than those with other popular force fields. Furthermore, it was found that the choice of force field affects the structures of an antigen-antibody complex obtained using MD simulations. These improvements in the force fields essentially extend the range of applications for the MD simulation method.

  18. CHARACTERISTICS OF BORDERLINE PERSONALITY DISORDER IN A COMMUNITY SAMPLE: COMORBIDITY, TREATMENT UTILIZATION, AND GENERAL FUNCTIONING

    PubMed Central

    Tomko, Rachel L.; Trull, Timothy J.; Wood, Phillip K.; Sher, Kenneth J.

    2013-01-01

    This study provides estimates of the prevalence and demographic features of borderline personality disorder (BPD) in a community sample as well as BPD comorbidity rates with Axis I and II disorders. In addition, the authors provide data on general functioning and treatment seeking among individuals with BPD. Data from 34,481 participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were analyzed. Results suggest that 2.7% of adults in the United States meet diagnostic criteria for BPD, with slightly higher rates of the disorder in females, people in lower income brackets, people younger than 30, and individuals who are separated or divorced. Racial/ethnic differences were evident, with Native Americans (5.0%) and Blacks (3.5%) having significantly higher rates of the disorder, on average, and Asians having significantly lower rates (1.2%). Individuals with a BPD diagnosis were likely to have co-occurring lifetime mood disorders, anxiety disorders, substance use disorders, and other personality disorders. Specifically, 84.8% of individuals with BPD also had a lifetime anxiety disorder, 82.7% had a lifetime mood disorder/episode, and 78.2% were diagnosed with a lifetime substance use disorder. Individuals with BPD showed significant impairment in functioning and were highly likely to seek therapy or receive medication for mental health concerns. PMID:25248122

  19. Cognitive Modules Utilized for Narrative Comprehension in Children: A Functional Magnetic Resonance Imaging Study

    PubMed Central

    Schmithorst, Vincent J.; Holland, Scott K.; Plante, Elena

    2005-01-01

    The ability to comprehend narratives constitutes an important component of human development and experience. The neural correlates of auditory narrative comprehension in children were investigated in a large-scale functional magnetic resonance imaging (fMRI) study involving 313 subjects ages 5–18. Using group Independent Component Analysis (ICA), bilateral task-related components were found comprising the primary auditory cortex, the mid-superior temporal gyrus, the hippocampus, the angular gyrus and medial aspect of the parietal lobule (precuneus/posterior cingulate). In addition, a right-lateralized component was found involving the most posterior aspect of the superior temporal gyrus, and a left-lateralized component was found comprising the inferior frontal gyrus (including Broca’s area), the inferior parietal lobule, and the medial temporal gyrus. Using a novel data-driven analysis technique, increased task-related activity related to age was found in the components comprising the mid-superior temporal gyrus (Wernicke’s area) and the posterior aspect of the superior temporal gyrus, while decreased activity related to age was found in the component comprising the angular gyrus. The results are discussed in light of recent hypotheses involving the functional segregation of Wernicke’s area and the specific role of the mid-superior temporal gyrus in speech comprehension. PMID:16109491

  20. The Predictive Utility of Early Childhood Disruptive Behaviors for School-Age Social Functioning

    PubMed Central

    Shaw, Daniel S.; Dishion, Thomas J.; Wilson, Melvin N.

    2016-01-01

    Research suggests that school-age children with disruptive behavior (DB) problems frequently demonstrate impaired social skills and experience rejection from peers, which plays a crucial role in the pathway to more serious antisocial behavior. A critical question is which DB problems in early childhood are prognostic of impaired social functioning in school-age children. This study examines the hypothesis that aggression in early childhood will be the more consistent predictor of compromised social functioning than inattentive, hyperactive-impulsive, or oppositional behavior. Participants included an ethnically diverse sample of 725 high-risk children from 3 geographically distinct areas followed from ages 2 to 8.5. Four latent growth models of DB from child ages 2 to 5, and potential interactions between dimensions, were used to predict latent parent and teacher ratings of school-age social dysfunction. Analyses were conducted in a multi-group format to examine potential differences between intervention and control group participants. Results showed that age 2 aggression was the DB problem most consistently associated with both parent- and teacher-rated social dysfunction for both groups. Early starting aggressive behavior may be particularly important for the early identification of children at risk for school-age social difficulties. PMID:25526865

  1. The Predictive Utility of Early Childhood Disruptive Behaviors for School-Age Social Functioning.

    PubMed

    Brennan, Lauretta M; Shaw, Daniel S; Dishion, Thomas J; Wilson, Melvin N

    2015-08-01

    Research suggests that school-age children with disruptive behavior (DB) problems frequently demonstrate impaired social skills and experience rejection from peers, which plays a crucial role in the pathway to more serious antisocial behavior. A critical question is which DB problems in early childhood are prognostic of impaired social functioning in school-age children. This study examines the hypothesis that aggression in early childhood will be the more consistent predictor of compromised social functioning than inattentive, hyperactive-impulsive, or oppositional behavior. Participants included an ethnically diverse sample of 725 high-risk children from 3 geographically distinct areas followed from ages 2 to 8.5. Four latent growth models of DB from child ages 2 to 5, and potential interactions between dimensions, were used to predict latent parent and teacher ratings of school-age social dysfunction. Analyses were conducted in a multi-group format to examine potential differences between intervention and control group participants. Results showed that age 2 aggression was the DB problem most consistently associated with both parent- and teacher-rated social dysfunction for both groups. Early starting aggressive behavior may be particularly important for the early identification of children at risk for school-age social difficulties.

  2. Utilization of carboxylic functional groups generated during purification of carbon nanotube fiber for its strength improvement

    NASA Astrophysics Data System (ADS)

    Im, Yong-O.; Lee, Sung-Hyun; Kim, Teawon; Park, Junbeom; Lee, Jaegeun; Lee, Kun-Hong

    2017-01-01

    One of the most promising method to produce carbon nanotube (CNT) fiber is directly spinning CNT fiber from CNT aerogel. Despite the advantage of this method in terms of productivity, the CNTs thus produced include impurities such as amorphous carbon and residual catalysts. To remove these unwanted materials, the CNT fiber is usually subjected to acid treatment. At the same time, however, the acid treatment damages the CNT wall, creating functional groups on it. In this work, specific tensile strength of CNT fibers was increased by introducing cross-links between the individual CNTs using carboxylic functional groups which were inevitably generated during the acid treatment of CNT fibers. The esterification of the carboxylic acid with 1,5-pentanediol as a linker resulted in cross-links in between the CNTs, thereby increasing the specific strength of the CNT fiber from 0.43 to 1.12 N/tex and Young's modulus from 30.70 to 47.57 N/tex. Supporting weak shear interactions of untreated CNT fiber by adding covalent bonding through the cross-linking reaction led to the improvement of mechanical properties of the CNT fiber. Elimination of impurities and narrowed interspacing between CNT bundles caused by acid treatment was also confirmed, which additionally contributed to enhancing the mechanical properties of CNT fiber.

  3. World Climate Classification and Search: Data Mining Approach Utilizing Dynamic Time Warping Similarity Function

    NASA Astrophysics Data System (ADS)

    Stepinski, T. F.; Netzel, P.; Jasiewicz, J.

    2014-12-01

    We have developed a novel method for classification and search of climate over the global land surface excluding Antarctica. Our method classifies climate on the basis of the outcome of time series segmentation and clustering. We use WorldClim 30 arc sec. (approx. 1 km) resolution grid data which is based on 50 years of climatic observations. Each cell in a grid is assigned a 12 month series consisting of 50-years monthly averages of mean, maximum, and minimum temperatures as well as the total precipitation. The presented method introduces several innovations with comparison to existing data-driven methods of world climate classifications. First, it uses only climatic rather than bioclimatic data. Second, it employs object-oriented methodology - the grid is first segmented before climatic segments are classified. Third, and most importantly, the similarity between climates in two given cells is performed using the dynamic time warping (DTW) measure instead of the Euclidean distance. The DTW is known to be superior to Euclidean distance for time series, but has not been utilized before in classification of global climate. To account for computational expense of DTW we use highly efficient GeoPAT software (http://sil.uc.edu/gitlist/) that, in the first step, segments the grid into local regions of uniform climate. In the second step, the segments are classified. We also introduce a climate search - a GeoWeb-based method for interactive presentation of global climate information in the form of query-and-retrieval. A user selects a geographical location and the system returns a global map indicating level of similarity between local climates and a climate in the selected location. The results of the search for location: "University of Cincinnati, Main Campus" are presented on attached map. The results of the search for location: "University of Cincinnati, Main Campus" are presented on the map. We have compared the results of our method to Koeppen classification scheme

  4. Graphene-coated meshes for electroactive flow control devices utilizing two antagonistic functions of repellency and permeability

    PubMed Central

    Tabassian, Rassoul; Oh, Jung-Hwan; Kim, Sooyeun; Kim, Donggyu; Ryu, Seunghwa; Cho, Seung-Min; Koratkar, Nikhil; Oh, Il-Kwon

    2016-01-01

    The wettability of graphene on various substrates has been intensively investigated for practical applications including surgical and medical tools, textiles, water harvesting, self-cleaning, oil spill removal and microfluidic devices. However, most previous studies have been limited to investigating the intrinsic and passive wettability of graphene and graphene hybrid composites. Here, we report the electrowetting of graphene-coated metal meshes for use as electroactive flow control devices, utilizing two antagonistic functions, hydrophobic repellency versus liquid permeability. Graphene coating was able to prevent the thermal oxidation and corrosion problems that plague unprotected metal meshes, while also maintaining its hydrophobicity. The shapes of liquid droplets and the degree of water penetration through the graphene-coated meshes were controlled by electrical stimuli based on the functional control of hydrophobic repellency and liquid permeability. Furthermore, using the graphene-coated metal meshes, we developed two active flow devices demonstrating the dynamic locomotion of water droplets and electroactive flow switching. PMID:27796291

  5. Graphene-coated meshes for electroactive flow control devices utilizing two antagonistic functions of repellency and permeability.

    PubMed

    Tabassian, Rassoul; Oh, Jung-Hwan; Kim, Sooyeun; Kim, Donggyu; Ryu, Seunghwa; Cho, Seung-Min; Koratkar, Nikhil; Oh, Il-Kwon

    2016-10-31

    The wettability of graphene on various substrates has been intensively investigated for practical applications including surgical and medical tools, textiles, water harvesting, self-cleaning, oil spill removal and microfluidic devices. However, most previous studies have been limited to investigating the intrinsic and passive wettability of graphene and graphene hybrid composites. Here, we report the electrowetting of graphene-coated metal meshes for use as electroactive flow control devices, utilizing two antagonistic functions, hydrophobic repellency versus liquid permeability. Graphene coating was able to prevent the thermal oxidation and corrosion problems that plague unprotected metal meshes, while also maintaining its hydrophobicity. The shapes of liquid droplets and the degree of water penetration through the graphene-coated meshes were controlled by electrical stimuli based on the functional control of hydrophobic repellency and liquid permeability. Furthermore, using the graphene-coated metal meshes, we developed two active flow devices demonstrating the dynamic locomotion of water droplets and electroactive flow switching.

  6. Graphene-coated meshes for electroactive flow control devices utilizing two antagonistic functions of repellency and permeability

    NASA Astrophysics Data System (ADS)

    Tabassian, Rassoul; Oh, Jung-Hwan; Kim, Sooyeun; Kim, Donggyu; Ryu, Seunghwa; Cho, Seung-Min; Koratkar, Nikhil; Oh, Il-Kwon

    2016-10-01

    The wettability of graphene on various substrates has been intensively investigated for practical applications including surgical and medical tools, textiles, water harvesting, self-cleaning, oil spill removal and microfluidic devices. However, most previous studies have been limited to investigating the intrinsic and passive wettability of graphene and graphene hybrid composites. Here, we report the electrowetting of graphene-coated metal meshes for use as electroactive flow control devices, utilizing two antagonistic functions, hydrophobic repellency versus liquid permeability. Graphene coating was able to prevent the thermal oxidation and corrosion problems that plague unprotected metal meshes, while also maintaining its hydrophobicity. The shapes of liquid droplets and the degree of water penetration through the graphene-coated meshes were controlled by electrical stimuli based on the functional control of hydrophobic repellency and liquid permeability. Furthermore, using the graphene-coated metal meshes, we developed two active flow devices demonstrating the dynamic locomotion of water droplets and electroactive flow switching.

  7. Utilization of Modified NFL Combine Testing to Identify Functional Deficits in Athletes Following ACL Reconstruction

    PubMed Central

    MYER, GREGORY D.; SCHMITT, LAURA C.; BRENT, JENSEN L.; FORD, KEVIN R.; BARBER FOSS, KIM D.; SCHERER, BRADLEY J.; HEIDT, ROBERT S.; DIVINE, JON G.; HEWETT, TIMOTHY E.

    2012-01-01

    STUDY DESIGN Case control. OBJECTIVES To use modified NFL Combine testing methodology to test for functional deficits in athletes following anterior cruciate ligament (ACL) reconstruction following return to sport. BACKGROUND There is a need to develop objective, performance-based, on-field assessment methods designed to identify potential lower extremity performance deficits and related impairments in this population. METHODS Eighteen patients (mean ± SD age, 16.9 ± 2.1 years; height, 170.0 ± 8.7 cm; body mass, 71.9 ± 21.8 kg) who returned to their sport within a year following ACL reconstruction (95% CI: 7.8 to 11.9 months from surgery) participated (ACLR group). These individuals were asked to bring 1 or 2 teammates to serve as control participants, who were matched for sex, sport, and age (n = 20; mean ± SD age, 16.9 ± 1.1 years; height, 169.7 ± 8.4 cm; body mass, 70.1 ± 20.7 kg). Functional performance was tested using the broad jump, vertical jump, modified long shuttle, modified pro shuttle, modified agility T-test, timed hop, triple hop, single hop, and crossover hop tests. A 1-way multivariate analysis of variance (MANOVA) was used to evaluate group differences for dependent performance variables. RESULTS The functional performance measurements of skills requiring bilateral involvement of both lower extremities showed no group differences between the ACLR and control groups (P>.05). An overall group difference (P = .006) was observed for the combined limb symmetry index (LSI) measures. However, the modified double-limb performance tasks (long shuttle, modified agility T-test, and pro shuttle) were not, independently, sufficiently sensitive to detect limb deficits in individuals with ACL reconstruction. Conversely, the LSI on the distance measures of the single-limb performance tasks all provided moderate to large effect sizes to differentiate between the ACLR and control groups, as the individuals who had ACL reconstruction demonstrated involved

  8. Production of D-tagatose, a functional sweetener, utilizing alginate immobilized Lactobacillus fermentum CGMCC2921 cells.

    PubMed

    Xu, Zheng; Li, Sha; Fu, Fenggen; Li, Guixiang; Feng, Xiaohai; Xu, Hong; Ouyang, Pingkai

    2012-02-01

    D-tagatose is a ketohexose that can be used as a novel functional sweetener in foods, beverages, and dietary supplements. This study was aimed at developing a high-yielding D-tagatose production process using alginate immobilized Lactobacillus fermentum CGMCC2921 cells. For the isomerization from D-galactose into D-tagatose, the immobilized cells showed optimum temperature and pH at 65 °C and 6.5, respectively. The alginate beads exhibited a good stability after glutaraldehyde treatment and retained 90% of the enzyme activity after eight cycles (192 h at 65 °C) of batch conversion. The addition of borate with a molar ratio of 1.0 to D-galactose led to a significant enhancement in the D-tagatose yield. Using commercial β-galactosidase and immobilized L. fermentum cells, D-tagatose was successfully obtained from lactose after a two-step biotransformation. The relatively high conversion rate and productivity from D-galactose to D-tagatose of 60% and 11.1 g l⁻¹ h⁻¹ were achieved in a packed-bed bioreactor. Moreover, lactobacilli have been approved as generally recognized as safe organisms, which makes this L. fermentum strain an attracting substitute for recombinant Escherichia coli cells among D-tagatose production progresses.

  9. Reducing the effects of dredged material levees on coastal marsh function: sediment deposition and nekton utilization.

    PubMed

    Reed, Denise J; Peterson, Mark S; Lezina, Brian J

    2006-05-01

    Dredged material levees in coastal Louisiana are normally associated with pipeline canals or, more frequently, canals dredged through the wetlands to allow access to drilling locations for mineral extraction. The hydrologic impact on marshes behind the levee is of concern to coastal resource managers because of the potential impact on sediment transport and deposition, and the effect on estuarine organism access to valuable nursery habitat. This study examined the effects of gaps in dredged material levees, compared to continuous levees and natural channel banks, on these two aspects of marsh function. Field studies for sediment deposition were conducted biweekly for a year, and nekton samples were collected in spring and fall. Variation in nekton density among study areas and landscape types was great in part because of the inherent sampling gear issues and in part because of differences in characteristics among areas. Nekton densities were generally greater in natural compared to leveed and gapped landscapes. Differences in landscape type did not explain patterns in sediment deposition. The gaps examined appear to be too restrictive of marsh flooding to provide efficient movements of floodwaters onto the marsh during moderate flooding events. The "trapping" effect of the levees increases sediment deposition during extreme events. Gapping material levees may be an effective method of partially restoring upper marsh connection to nekton, but this method may work best in lower elevation marshes where nekton use is greater.

  10. Digestive function of lysozyme in synanthropic acaridid mites enables utilization of bacteria as a food source.

    PubMed

    Erban, Tomas; Hubert, Jan

    2008-03-01

    The activity of lysozyme, the enzyme that hydrolyzes peptidoglycan in G(+) bacterial cell walls, was detected in whole mite extracts (WME) and in spent growth medium extracts (SGME) of 14 species of synanthropic mites (Acari: Acaridida). The adaptation of lysozyme for digestive activity and bacteriophagy was based on: (i) high lysozyme activity in SGME, and (ii) the correlation of maximum lysozyme activity at acidic pH values, corresponding to pH in the ventriculus and caeca. We show that the digestion of fluorescein-labeled Micrococcus lysodeikticus cells began in ventriculus and continued during the passage of a food bolus through the gut. The fluorescein was absorbed by midgut cells and penetrated to parenchymal tissues. Eight species showed a higher rate of population growth on a M. lysodeikticus diet than on a control diet. The lysozyme activity in SGME was positively correlated to the standardized rate (r (s)) of population growth, although no correlation was found between r (s) and lysozyme activity in WME. The lysozyme activity in WME was negatively correlated to that in SGME. The highest activity of digestive lysozyme was found in Lepidoglyphus destructor, Chortoglyphus arcuatus and Dermatophagoides farinae. All of these findings indicate that lysozyme in acaridid mites possesses both defensive and digestive functions. The enzymatic properties of mite lysozyme are similar to those of the lysozymes present in the ruminant stomach and in the insect midgut.

  11. Development of a cell-defined siRNA microarray for analysis of gene function in human bone marrow stromal cells.

    PubMed

    Kim, Hi Chul; Kim, Gi-Hwan; Cho, Ssang-Goo; Lee, Eun Ju; Kwon, Yong-Jun

    2016-03-01

    Small interfering RNA (siRNA) screening approaches have provided useful tools for the validation of genetic functions; however, image-based siRNA screening using multiwell plates requires large numbers of cells and time, which could be the barrier in application for gene mechanisms study using human adult cells. Therefore, we developed the advanced method with the cell-defined siRNA microarray (CDSM), for functional analysis of genes in small scale within slide glass using human bone marrow stromal cells (hBMSCs). We designed cell spot system with biomaterials (sucrose, gelatin, poly-L-lysine and matrigel) to control the attachment of hBMSCs inside spot area on three-dimensional (3D) hydrogel-coated slides. The p65 expression was used as a validation standard which described our previous report. For the optimization of siRNA mixture, first, we detected five kinds of commercialized reagent (Lipofectamine 2000, RNAi-Max, Metafectine, Metafectine Pro, TurboFectin 8.0) via validation. Then, according to quantification of p65 expression, we selected 2 μl of RNAi-Max as the most effective reagent condition on our system. Using same validation standard, we optimized sucrose and gelatin concentration (80 mM and 0.13%), respectively. Next, we performed titration of siRNA quantity (2.66-5.55 μM) by reverse transfection time (24 h, 48 h, 72 h) and confirmed 3.75 μM siRNA concentration and 48 h as the best condition. To sum up the process for optimized CDSM, 3 μl of 20 μM siRNA (3.75 μM) was transferred to the 384-well V-bottom plate containing 2 μl of dH2O and 2 μl of 0.6M sucrose (80 mM). Then, 2 μl of RNAi-Max was added and incubated for 20 min at room temperature after mixing gently and centrifugation shortly. Five microliters of gelatin (0.26%) and 2 μl of growth factor reduced phenol red-free matrigel (12.5%) were added and mixed by pipetting gently. Finally, optimized siRNA mixture was printed on 3D hydrogel-coated slides and cell-defined attachment and si

  12. The impact of amino acid variability on alloreactivity defines a functional distance predictive of permissive HLA-DPB1 mismatches in hematopoietic stem cell transplantation.

    PubMed

    Crivello, Pietro; Zito, Laura; Sizzano, Federico; Zino, Elisabetta; Maiers, Martin; Mulder, Arend; Toffalori, Cristina; Naldini, Luigi; Ciceri, Fabio; Vago, Luca; Fleischhauer, Katharina

    2015-02-01

    A major challenge in unrelated hematopoietic stem cell transplantation (HSCT) is the prediction of permissive HLA mismatches, ie, those associated with lower clinical risks compared to their nonpermissive counterparts. For HLA-DPB1, a clinically prognostic model has been shown to be matching for T cell epitope (TCE) groups assigned by cross reactivity of T cells alloreactive to HLA-DPB1∗09:01; however, the molecular basis of this observation is not fully understood. Here, we have mutated amino acids (aa) in 10 positions of HLA-DPB1∗09:01 to other naturally occurring variants, expressed them by lentiviral vectors in B cell lines, and quantitatively measured allorecognition by 17 CD4(+) T cell effectors from 6 unrelated individuals. A significant impact on the median alloresponse was observed for peptide contact positions 9, 11, 35, 55, 69, 76, and 84, but not for positions 8, 56, and 57 pointing away from the groove. A score for the "functional distance" (FD) from HLA-DPB1∗09:01 was defined as the sum of the median impact of polymorphic aa in a given HLA-DPB1 allele on T cell alloreactivity. Established TCE group assignment of 23 alleles correlated with FD scores of ≤0.5, 0.6 to 1.9 and ≥2 for TCE groups 1, 2, and 3, respectively. Based on this, prediction of TCE group assignment will be possible for any given HLA-DPB1 allele, including currently 367 alleles encoding distinct proteins for which T cell cross reactivity patterns are unknown. Experimental confirmation of the in silico TCE group classification was successfully performed for 7 of 7 of these alleles. Our findings have practical implications for the applicability of TCE group matching in unrelated HSCT and provide new insights into the molecular mechanisms underlying this model. The innovative concept of FD opens new potential avenues for risk prediction in unrelated HSCT.

  13. Utility of the wireless motility capsule and lactulose breath testing in the evaluation of patients with Parkinson's disease who present with functional gastrointestinal symptoms

    PubMed Central

    Su, Andrew; Gandhy, Rita; Barlow, Carrolee; Triadafilopoulos, George

    2017-01-01

    Background The aetiology and origin of gastrointestinal symptoms in Parkinson's disease (PD) remains poorly understood. Gastroparesis, small bowel transit delay and bacterial overgrowth may, individually or collectively, play a role. Aims In patients with PD and functional gastrointestinal symptoms, we aimed to determine the utility of the wireless motility capsule and lactulose breath tests in further defining their symptoms' aetiology. Methods In this retrospective cohort study, consecutive patients with PD and functional gastrointestinal symptoms underwent clinical assessment, as well as wireless motility capsule and lactulose breath testing using standard protocols. Results We studied 65 patients with PD and various gastrointestinal symptoms. 35% exhibited gastroparesis by the wireless motility capsule study, 20% small bowel transit delay, while 8% had combined transit abnormalities, suggestive of overlapping gastric and small bowel dysmotility. Small bowel bacterial overgrowth was seen in 34% of cases. Symptoms of abdominal pain, regurgitation, bloating, nausea, vomiting, belching and weight loss could not distinguish between patients with or without gastroparesis, although bloating was significantly more prominent (p<0.001) overall and specifically more so in patients with slow small bowel transit (p<0.01). There was no relationship between delayed small bowel transit time and bacterial overgrowth (p=0.5); PD scores and duration were not correlated with either the transit findings or small bowel bacterial overgrowth. Conclusions Functional gastrointestinal symptoms in patients with PD may reflect gastroparesis, small bowel transit delay or both, suggesting motor and/or autonomic dysfunction, and may be associated with small bowel bacterial overgrowth. The wireless motility capsule and lactulose breath testing are non-invasive and useful in the assessment of these patients. PMID:28321329

  14. Defining periodontal health

    PubMed Central

    2015-01-01

    Assessment of the periodontium has relied exclusively on a variety of physical measurements (e.g., attachment level, probing depth, bone loss, mobility, recession, degree of inflammation, etc.) in relation to various case definitions of periodontal disease. Periodontal health was often an afterthought and was simply defined as the absence of the signs and symptoms of a periodontal disease. Accordingly, these strict and sometimes disparate definitions of periodontal disease have resulted in an idealistic requirement of a pristine periodontium for periodontal health, which makes us all diseased in one way or another. Furthermore, the consequence of not having a realistic definition of health has resulted in potentially questionable recommendations. The aim of this manuscript was to assess the biological, environmental, sociological, economic, educational and psychological relationships that are germane to constructing a paradigm that defines periodontal health using a modified wellness model. The paradigm includes four cardinal characteristics, i.e., 1) a functional dentition, 2) the painless function of a dentition, 3) the stability of the periodontal attachment apparatus, and 4) the psychological and social well-being of the individual. Finally, strategies and policies that advocate periodontal health were appraised. I'm not sick but I'm not well, and it's a sin to live so well. Flagpole Sitta, Harvey Danger PMID:26390888

  15. Functional definition of BirA suggests a biotin utilization pathway in the zoonotic pathogen Streptococcus suis

    PubMed Central

    Ye, Huiyan; Cai, Mingzhu; Zhang, Huimin; Li, Zhencui; Wen, Ronghui; Feng, Youjun

    2016-01-01

    Biotin protein ligase is universal in three domains of life. The paradigm version of BPL is the Escherichia coli BirA that is also a repressor for the biotin biosynthesis pathway. Streptococcus suis, a leading bacterial agent for swine diseases, seems to be an increasingly-important opportunistic human pathogen. Unlike the scenario in E. coli, S. suis lacks the de novo biotin biosynthesis pathway. In contrast, it retains a bioY, a biotin transporter-encoding gene, indicating an alternative survival strategy for S. suis to scavenge biotin from its inhabiting niche. Here we report functional definition of S. suis birA homologue. The in vivo functions of the birA paralogue with only 23.6% identity to the counterpart of E. coli, was judged by its ability to complement the conditional lethal mutants of E. coli birA. The recombinant BirA protein of S. suis was overexpressed in E. coli, purified to homogeneity and verified with MS. Both cellulose TLC and MALDI-TOFF-MS assays demonstrated that the S. suis BirA protein catalyzed the biotinylation reaction of its acceptor biotin carboxyl carrier protein. EMSA assays confirmed binding of the bioY gene to the S. suis BirA. The data defined the first example of the bifunctional BirA ligase/repressor in Streptococcus. PMID:27217336

  16. Oral intake of encapsulated dried ginger root powder hardly affects human thermoregulatory function, but appears to facilitate fat utilization

    NASA Astrophysics Data System (ADS)

    Miyamoto, Mayumi; Matsuzaki, Kentaro; Katakura, Masanori; Hara, Toshiko; Tanabe, Yoko; Shido, Osamu

    2015-10-01

    The present study investigated the impact of a single oral ingestion of ginger on thermoregulatory function and fat oxidation in humans. Morning and afternoon oral intake of 1.0 g dried ginger root powder did not alter rectal temperature, skin blood flow, O2 consumption, CO2 production, and thermal sensation and comfort, or induce sweating at an ambient temperature of 28 °C. Ginger ingestion had no effect on threshold temperatures for skin blood flow or thermal sweating. Serum levels of free fatty acids were significantly elevated at 120 min after ginger ingestion in both the morning and afternoon. Morning ginger intake significantly reduced respiratory exchange ratios and elevated fat oxidation by 13.5 % at 120 min after ingestion. This was not the case in the afternoon. These results suggest that the effect of a single oral ginger administration on the peripheral and central thermoregulatory function is miniscule, but does facilitate fat utilization although the timing of the administration may be relevant.

  17. Oral intake of encapsulated dried ginger root powder hardly affects human thermoregulatory function, but appears to facilitate fat utilization.

    PubMed

    Miyamoto, Mayumi; Matsuzaki, Kentaro; Katakura, Masanori; Hara, Toshiko; Tanabe, Yoko; Shido, Osamu

    2015-10-01

    The present study investigated the impact of a single oral ingestion of ginger on thermoregulatory function and fat oxidation in humans. Morning and afternoon oral intake of 1.0 g dried ginger root powder did not alter rectal temperature, skin blood flow, O2 consumption, CO2 production, and thermal sensation and comfort, or induce sweating at an ambient temperature of 28 °C. Ginger ingestion had no effect on threshold temperatures for skin blood flow or thermal sweating. Serum levels of free fatty acids were significantly elevated at 120 min after ginger ingestion in both the morning and afternoon. Morning ginger intake significantly reduced respiratory exchange ratios and elevated fat oxidation by 13.5 % at 120 min after ingestion. This was not the case in the afternoon. These results suggest that the effect of a single oral ginger administration on the peripheral and central thermoregulatory function is miniscule, but does facilitate fat utilization although the timing of the administration may be relevant.

  18. A new approach for the preparation of well-defined Rh and Pt nanoparticles stabilized by phosphine-functionalized silica for selective hydrogenation reactions.

    PubMed

    Llop Castelbou, J; Szeto, K C; Barakat, W; Merle, N; Godard, C; Taoufik, M; Claver, C

    2017-03-18

    In this work, a new methodology for the synthesis of well-defined metallic nanoparticles supported on silica is described. This methodology is based on the surface control provided by SOMC. The nanoparticles are formed via the organometallic approach and are catalytically active in the hydrogenation of p-xylene, 3-hexyne, 4-phenyl-2 butanone, benzaldehyde, and furfural.

  19. Drinking Levels Defined

    MedlinePlus

    ... Is A Standard Drink? Drinking Levels Defined Drinking Levels Defined Moderate alcohol consumption: According to the "Dietary ... of drinking that brings blood alcohol concentration (BAC) levels to 0.08 g/dL. This typically occurs ...

  20. Japanese plan for SSF utilization

    NASA Technical Reports Server (NTRS)

    Mizuno, Toshio

    1992-01-01

    The Japanese Experiment Module (JEM) program has made significant progress. The JEM preliminary design review was completed in July 1992; construction of JEM operation facilities has begun; and the micro-G airplane, drop shaft, and micro-G experiment rocket are all operational. The national policy for JEM utilization was also established. The Space Experiment Laboratory (SEL) opened in June '92 and will function as a user support center. Eight JEM multiuser facilities are in phase B, and scientific requirements are being defined for 17 candidate multiuser facilities. The National Joint Research Program is about to start. Precursor missions and early Space Station utilization activities are being defined. This paper summarizes the program in outline and graphic form.

  1. Highly efficient SO2 absorption/activation and subsequent utilization by polyethylene glycol-functionalized Lewis basic ionic liquids.

    PubMed

    Yang, Zhen-Zhen; He, Liang-Nian; Song, Qing-Wen; Chen, Kai-Hong; Liu, An-Hua; Liu, Xiang-Ming

    2012-12-05

    Up to now, flue-gas desulfurization (FGD) is one of the most effective techniques to control SO(2) emission from the combustion of fossil fuels. The conventional technology for FGD poses serious inherent drawbacks such as formation of byproducts and volatilization of solvents. In this work, polyethylene glycol (PEG)-functionalized Lewis basic ionic liquids (ILs) derived from DABCO were proved to be highly efficient absorbents for FGD due to its specific features such as high thermal stability, negligible vapor pressure, high loading capacity. Notably, PEG(150)MeDABCONTf(2) gave an extremely high SO(2) capacity (4.38 mol mol(-1) IL), even under 0.1 bar SO(2) partial pressure (1.01 mol mol(-1) IL), presumably owing to the strong SO(2)-philic characterization of the PEG chain. Furthermore, the absorbed SO(2) could be easy to release by just bubbling N(2) at room temperature, greatly reducing energy requirement for SO(2) desorption. In addition, SO(2)/CO(2) selectivity (110) of PEG(150)MeDABCONTf(2) is two times larger than the non-functionalized imidazolium IL (45). On the other hand, through activation of SO(2) with the tertiary nitrogen in the cation, Lewis basic ILs such as PEG(150)MeDABCOBr proved to be efficient catalysts for the conversion of SO(2) to some value-added chemicals such as cyclic sulfites without utilization of any organic solvent or additive. Thus, this protocol would pave the way for the development of technological innovation towards efficient and low energy demanded practical process for SO(2) absorption and subsequent transformation.

  2. Assistive Technology Needs, Functional Difficulties, and Services Utilization and Coordination of Children with Developmental Disabilities in the United States.

    PubMed

    Lin, Sue C; Gold, Robert S

    2017-01-31

    Assistive technology (AT) enhances the ability of individuals with disabilities to be fully engaged in activities at home, at school, and within their communities-especially for children with developmental disabilities (DD) with physical, sensory, learning, and/or communication impairments. The prevalence of children with DD in the United States has risen from 12.84% in 1997 to 15.04% in 2008. Thus, it is important to monitor the status of their AT needs, functional difficulties, services utilization, and coordination. Using data from the 2009-2010 National Survey on Children with Special Health Care Needs (NS-CSHCN), we conducted bivariate and multivariate statistical analysis, which found that 90% or more of parents of both children with DD and other CSHCN reported that their child's AT needs were met for vision, hearing, mobility, communication, and durable medical equipment; furthermore, children with DD had lower odds of AT needs met for vision and hearing and increased odds for meeting AT needs in mobility and communication. Our findings outline the current AT needs of children with DD nationally. Fulfilling these needs has the potential to engender positive lifelong effects on the child's disabilities, sense of independence, self-confidence, and productivity.

  3. Development of a functional assay to detect inhibitors of Plasmodium falciparum glutathione reductase utilizing liquid chromatography-mass spectrometry.

    PubMed

    Burkard, Lexi; Scheuermann, Alexis; Simithy, Johayra; Calderón, Angela I

    2016-04-01

    Plasmodium falciparum (Pf) like most other organisms, has a sophisticated antioxidant system, part of which includes glutathione reductase (GR). GR works by recycling toxic glutathione disulfide to glutathione, thereby reducing reactive oxygen species and making a form of glutathione (GSH) the parasite can use. Inhibition of this enzyme in Pf impedes parasite growth. In addition, it has been confirmed that PfGR is not identical to human GR. Thus, PfGR is an excellent target for antimalarial drug development. A functional assay utilizing liquid chromatography-mass spectrometry was developed to specifically identify and evaluate inhibitors of PfGR. Using recombinant PfGR enzyme and 1,4-naphthoquinone (1) as a reference compound and 4-nitrobenzothiadiazole (2) and methylene blue (3) as additional compounds, we quantified the concentration of GSH produced compared with a control to determine the inhibitory effect of these compounds. Our results coincide with that presented in literature: compounds 1-3 inhibit PfGR with IC50 values of 2.71, 8.38, and 19.23 µm, respectively. Good precision for this assay was exhibited by low values of intraday and interday coefficient of variation (3.1 and 2.4%, respectively). Thus, this assay can be used to screen for other potential inhibitors of PfGR quickly and accurately.

  4. Orbiter electrical equipment utilization baseline

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The baseline for utilization of Orbiter electrical equipment in both electrical and Environmental Control and Life Support System (ECLSS) thermal analyses is established. It is a composite catalog of Space Shuttle equipment, as defined in the Shuttle Operational Data Book. The major functions and expected usage of each component type are described. Functional descriptions are designed to provide a fundamental understanding of the Orbiter electrical equipment, to insure correlation of equipment usage within nominal analyses, and to aid analysts in the formulation of off-nominal, contingency analyses.

  5. Estimation of an image derived input function with MR-defined carotid arteries in FDG-PET human studies using a novel partial volume correction method.

    PubMed

    Sari, Hasan; Erlandsson, Kjell; Law, Ian; Larsson, Henrik Bw; Ourselin, Sebastien; Arridge, Simon; Atkinson, David; Hutton, Brian F

    2017-04-01

    Kinetic analysis of (18)F-fluorodeoxyglucose positron emission tomography data requires an accurate knowledge the arterial input function. The gold standard method to measure the arterial input function requires collection of arterial blood samples and is an invasive method. Measuring an image derived input function is a non-invasive alternative but is challenging due to partial volume effects caused by the limited spatial resolution of the positron emission tomography scanners. In this work, a practical image derived input function extraction method is presented, which only requires segmentation of the carotid arteries from MR images. The simulation study results showed that at least 92% of the true intensity could be recovered after the partial volume correction. Results from 19 subjects showed that the mean cerebral metabolic rate of glucose calculated using arterial samples and partial volume corrected image derived input function were 26.9 and 25.4 mg/min/100 g, respectively, for the grey matter and 7.2 and 6.7 mg/min/100 g for the white matter. No significant difference in the estimated cerebral metabolic rate of glucose values was observed between arterial samples and corrected image derived input function (p > 0.12 for grey matter and white matter). Hence, the presented image derived input function extraction method can be a practical alternative to noninvasively analyze dynamic (18)F-fluorodeoxyglucose data without the need for blood sampling.

  6. Defining the Interactions of Cellobiohydrolase with Substrate through Structure Function Studies: Cooperative Research and Development Final Report, CRADA Number CRD-10-409

    SciTech Connect

    Beckham, G. T.; Himmel, M. E.

    2013-07-01

    NREL researchers will use their expertise and skilled resources in numerical computational modeling to generate structure-function relationships for improved cellulase variant enzymes to support the development of cellulases with improved performance in biomass conversion.

  7. Defining the nociceptor transcriptome

    PubMed Central

    Thakur, Matthew; Crow, Megan; Richards, Natalie; Davey, Gareth I. J.; Levine, Emma; Kelleher, Jayne H.; Agley, Chibeza C.; Denk, Franziska; Harridge, Stephen D. R.; McMahon, Stephen B.

    2014-01-01

    Unbiased “omics” techniques, such as next generation RNA-sequencing, can provide entirely novel insights into biological systems. However, cellular heterogeneity presents a significant barrier to analysis and interpretation of these datasets. The neurons of the dorsal root ganglia (DRG) are an important model for studies of neuronal injury, regeneration and pain. The majority of investigators utilize a dissociated preparation of whole ganglia when studying cellular and molecular function. We demonstrate that the standard methods for producing these preparations gives a 10%-neuronal mixture of cells, with the remainder of cells constituting satellite glia and other non-neuronal cell types. Using a novel application of magnetic purification, we consistently obtain over 95% pure, viable neurons from adult tissue, significantly enriched for small diameter nociceptors expressing the voltage gated ion channel Nav1.8. Using genome-wide RNA-sequencing we compare the currently used (10% neuronal) and pure (95% nociceptor) preparations and find 920 genes enriched. This gives an unprecedented insight into the molecular composition of small nociceptive neurons in the DRG, potentially altering the interpretation of previous studies performed at the tissue level, and indicating a number of novel markers of this widely-studied population of cells. We anticipate that the ease of use, affordability and speed of this technique will see it become widely adopted, delivering a greatly improved capacity to study the roles of nociceptors in health and disease. PMID:25426020

  8. Structural and Functional Analysis of a Lytic Polysaccharide Monooxygenase Important for Efficient Utilization of Chitin in Cellvibrio japonicus.

    PubMed

    Forsberg, Zarah; Nelson, Cassandra E; Dalhus, Bjørn; Mekasha, Sophanit; Loose, Jennifer S M; Crouch, Lucy I; Røhr, Åsmund K; Gardner, Jeffrey G; Eijsink, Vincent G H; Vaaje-Kolstad, Gustav

    2016-04-01

    Cellvibrio japonicusis a Gram-negative soil bacterium that is primarily known for its ability to degrade plant cell wall polysaccharides through utilization of an extensive repertoire of carbohydrate-active enzymes. Several putative chitin-degrading enzymes are also found among these carbohydrate-active enzymes, such as chitinases, chitobiases, and lytic polysaccharide monooxygenases (LPMOs). In this study, we have characterized the chitin-active LPMO,CjLPMO10A, a tri-modular enzyme containing a catalytic family AA10 LPMO module, a family 5 chitin-binding module, and a C-terminal unclassified module of unknown function. Characterization of the latter module revealed tight and specific binding to chitin, thereby unraveling a new family of chitin-binding modules (classified as CBM73). X-ray crystallographic elucidation of theCjLPMO10A catalytic module revealed that the active site of the enzyme combines structural features previously only observed in either cellulose or chitin-active LPMO10s. Analysis of the copper-binding site by EPR showed a signal signature more similar to those observed for cellulose-cleaving LPMOs. The full-length LPMO shows no activity toward cellulose but is able to bind and cleave both α- and β-chitin. Removal of the chitin-binding modules reduced LPMO activity toward α-chitin compared with the full-length enzyme. Interestingly, the full-length enzyme and the individual catalytic LPMO module boosted the activity of an endochitinase equally well, also yielding similar amounts of oxidized products. Finally, gene deletion studies show thatCjLPMO10A is needed byC. japonicusto obtain efficient growth on both purified chitin and crab shell particles.

  9. Structural and Functional Analysis of a Lytic Polysaccharide Monooxygenase Important for Efficient Utilization of Chitin in Cellvibrio japonicus*

    PubMed Central

    Forsberg, Zarah; Nelson, Cassandra E.; Dalhus, Bjørn; Mekasha, Sophanit; Loose, Jennifer S. M.; Crouch, Lucy I.; Røhr, Åsmund K.; Gardner, Jeffrey G.; Eijsink, Vincent G. H.; Vaaje-Kolstad, Gustav

    2016-01-01

    Cellvibrio japonicus is a Gram-negative soil bacterium that is primarily known for its ability to degrade plant cell wall polysaccharides through utilization of an extensive repertoire of carbohydrate-active enzymes. Several putative chitin-degrading enzymes are also found among these carbohydrate-active enzymes, such as chitinases, chitobiases, and lytic polysaccharide monooxygenases (LPMOs). In this study, we have characterized the chitin-active LPMO, CjLPMO10A, a tri-modular enzyme containing a catalytic family AA10 LPMO module, a family 5 chitin-binding module, and a C-terminal unclassified module of unknown function. Characterization of the latter module revealed tight and specific binding to chitin, thereby unraveling a new family of chitin-binding modules (classified as CBM73). X-ray crystallographic elucidation of the CjLPMO10A catalytic module revealed that the active site of the enzyme combines structural features previously only observed in either cellulose or chitin-active LPMO10s. Analysis of the copper-binding site by EPR showed a signal signature more similar to those observed for cellulose-cleaving LPMOs. The full-length LPMO shows no activity toward cellulose but is able to bind and cleave both α- and β-chitin. Removal of the chitin-binding modules reduced LPMO activity toward α-chitin compared with the full-length enzyme. Interestingly, the full-length enzyme and the individual catalytic LPMO module boosted the activity of an endochitinase equally well, also yielding similar amounts of oxidized products. Finally, gene deletion studies show that CjLPMO10A is needed by C. japonicus to obtain efficient growth on both purified chitin and crab shell particles. PMID:26858252

  10. Synthesis and functions of well-defined polymer-drug conjugates as efficient nanocarriers for intravesical chemotherapy of bladder cancer(a).

    PubMed

    Yu, Qingsong; Zhang, Jiajing; Zhang, Guan; Gan, Zhihua

    2015-04-01

    Novel poly(ethylene glycol) and poly(N-(2-hydroxypropyl)methacrylamide) block copolymer (PEG-b-PHPMA) with well-defined composition was synthesized by RAFT polymerization. Folate and doxorubicin (DOX) were quantitatively introduced into the copolymer. The influences of folate content and pH value on folate receptor (FR) mediated cell endocytosis and pH-responsive DOX release were studied. It has been demonstrated that minimum folate content is needed for the enrichment of hydrophobic folate on the hydrophilic part of polymer conjugates. The cytotoxicity of targetable polymer drug conjugates was much higher than that of non-targetable ones and free DOX. It could be concluded that the folate plays a significant role in targeting and internalization of the conjugates against bladder cancer cells.

  11. Structural and Functional Characterization of a Ruminal β-Glycosidase Defines a Novel Subfamily of Glycoside Hydrolase Family 3 with Permuted Domain Topology*

    PubMed Central

    Ramírez-Escudero, Mercedes; del Pozo, Mercedes V.; Marín-Navarro, Julia; González, Beatriz; Golyshin, Peter N.; Polaina, Julio; Ferrer, Manuel; Sanz-Aparicio, Julia

    2016-01-01

    Metagenomics has opened up a vast pool of genes for putative, yet uncharacterized, enzymes. It widens our knowledge on the enzyme diversity world and discloses new families for which a clear classification is still needed, as is exemplified by glycoside hydrolase family-3 (GH3) proteins. Herein, we describe a GH3 enzyme (GlyA1) from resident microbial communities in strained ruminal fluid. The enzyme is a β-glucosidase/β-xylosidase that also shows β-galactosidase, β-fucosidase, α-arabinofuranosidase, and α-arabinopyranosidase activities. Short cello- and xylo-oligosaccharides, sophorose and gentibiose, are among the preferred substrates, with the large polysaccharide lichenan also being hydrolyzed by GlyA1. The determination of the crystal structure of the enzyme in combination with deletion and site-directed mutagenesis allowed identification of its unusual domain composition and the active site architecture. Complexes of GlyA1 with glucose, galactose, and xylose allowed picturing the catalytic pocket and illustrated the molecular basis of the substrate specificity. A hydrophobic platform defined by residues Trp-711 and Trp-106, located in a highly mobile loop, appears able to allocate differently β-linked bioses. GlyA1 includes an additional C-terminal domain previously unobserved in GH3 members, but crystallization of the full-length enzyme was unsuccessful. Therefore, small angle x-ray experiments have been performed to investigate the molecular flexibility and overall putative shape. This study provided evidence that GlyA1 defines a new subfamily of GH3 proteins with a novel permuted domain topology. Phylogenetic analysis indicates that this topology is associated with microbes inhabiting the digestive tracts of ruminants and other animals, feeding on chemically diverse plant polymeric materials. PMID:27679487

  12. Analysis of the Yersinia enterocolitica PspBC proteins defines functional domains, essential amino acids and new roles within the phage-shock-protein response.

    PubMed

    Gueguen, Erwan; Savitzky, Diana C; Darwin, Andrew J

    2009-11-01

    The Yersinia enterocolitica phage-shock-protein (Psp) stress response system is activated by mislocalized outer-membrane secretin components of protein export systems and is essential for virulence. The cytoplasmic membrane proteins PspB and PspC were proposed to be dual function components of the system, acting both as positive regulators of psp gene expression and to support survival during secretin-induced stress. In this study we have uncoupled the regulatory and physiological functions of PspBC and discovered unexpected new roles, functional domains and essential amino acids. First, we showed that PspB controls PspC concentration by both pre- and post-transcriptional mechanisms. We then screened for PspBC mutants with altered transcriptional regulatory function. Unexpectedly, we identified PspB and PspC mutants that activated psp gene expression in the absence of secretin-induced stress. Together with a subsequent truncation analysis, this revealed that the PspC cytoplasmic domain plays an unforeseen role in negatively regulating psp gene expression. Conversely, mutations within the PspC periplasmic domain abolished its ability to activate psp gene expression. Significantly, PspC mutants unable to activate psp gene expression retained their ability to support survival during secretin-induced stress. These data provide compelling support for the proposal that these two functions are independent.

  13. SPO14 separation-of-function mutations define unique roles for phospholipase D in secretion and cellular differentiation in Saccharomyces cerevisiae.

    PubMed Central

    Rudge, S A; Pettitt, T R; Zhou, C; Wakelam, M J; Engebrecht, J A

    2001-01-01

    In Saccharomyces cerevisiae, phospholipase D (PLD), encoded by the SPO14 gene, catalyzes the hydrolysis of phosphatidylcholine, producing choline and phosphatidic acid. SPO14 is essential for cellular differentiation during meiosis and is required for Golgi function when the normal secretory apparatus is perturbed (Sec14-independent secretion). We isolated specific alleles of SPO14 that support Sec14-independent secretion but not sporulation. Identification of these separation-of-function alleles indicates that the role of PLD in these two physiological processes is distinct. Analyses of the mutants reveal that the corresponding proteins are stable, phosphorylated, catalytically active in vitro, and can localize properly within the cell during meiosis. Surprisingly, the separation-of-function mutations map to the conserved catalytic region of the PLD protein. Choline and phosphatidic acid molecular species profiles during Sec14-independent secretion and meiosis reveal that while strains harboring one of these alleles, spo14S-11, hydrolyze phosphatidylcholine in Sec14-independent secretion, they fail to do so during sporulation or normal vegetative growth. These results demonstrate that Spo14 PLD catalytic activity and cellular function can be differentially regulated at the level of phosphatidylcholine hydrolysis. PMID:11514437

  14. Eliciting and Combining Decision Criteria Using a Limited Palette of Utility Functions and Uncertainty Distributions: Illustrated by Application to Pest Risk Analysis.

    PubMed

    Holt, Johnson; Leach, Adrian W; Schrader, Gritta; Petter, Françoise; MacLeod, Alan; van der Gaag, Dirk Jan; Baker, Richard H A; Mumford, John D

    2014-01-01

    Utility functions in the form of tables or matrices have often been used to combine discretely rated decision-making criteria. Matrix elements are usually specified individually, so no one rule or principle can be easily stated for the utility function as a whole. A series of five matrices are presented that aggregate criteria two at a time using simple rules that express a varying degree of constraint of the lower rating over the higher. A further nine possible matrices were obtained by using a different rule either side of the main axis of the matrix to describe situations where the criteria have a differential influence on the outcome. Uncertainties in the criteria are represented by three alternative frequency distributions from which the assessors select the most appropriate. The output of the utility function is a distribution of rating frequencies that is dependent on the distributions of the input criteria. In pest risk analysis (PRA), seven of these utility functions were required to mimic the logic by which assessors for the European and Mediterranean Plant Protection Organization arrive at an overall rating of pest risk. The framework enables the development of PRAs that are consistent and easy to understand, criticize, compare, and change. When tested in workshops, PRA practitioners thought that the approach accorded with both the logic and the level of resolution that they used in the risk assessments.

  15. Defining the Metabolic Functions and Roles in Virulence of the rpoN1 and rpoN2 Genes in Ralstonia solanacearum GMI1000.

    PubMed

    Lundgren, Benjamin R; Connolly, Morgan P; Choudhary, Pratibha; Brookins-Little, Tiffany S; Chatterjee, Snigdha; Raina, Ramesh; Nomura, Christopher T

    2015-01-01

    The alternative sigma factor RpoN is a unique regulator found among bacteria. It controls numerous processes that range from basic metabolism to more complex functions such as motility and nitrogen fixation. Our current understanding of RpoN function is largely derived from studies on prototypical bacteria such as Escherichia coli. Bacillus subtilis and Pseudomonas putida. Although the extent and necessity of RpoN-dependent functions differ radically between these model organisms, each bacterium depends on a single chromosomal rpoN gene to meet the cellular demands of RpoN regulation. The bacterium Ralstonia solanacearum is often recognized for being the causative agent of wilt disease in crops, including banana, peanut and potato. However, this plant pathogen is also one of the few bacterial species whose genome possesses dual rpoN genes. To determine if the rpoN genes in this bacterium are genetically redundant and interchangeable, we constructed and characterized ΔrpoN1, ΔrpoN2 and ΔrpoN1 ΔrpoN2 mutants of R. solanacearum GMI1000. It was found that growth on a small range of metabolites, including dicarboxylates, ethanol, nitrate, ornithine, proline and xanthine, were dependent on only the rpoN1 gene. Furthermore, the rpoN1 gene was required for wilt disease on tomato whereas rpoN2 had no observable role in virulence or metabolism in R. solanacearum GMI1000. Interestingly, plasmid-based expression of rpoN2 did not fully rescue the metabolic deficiencies of the ΔrpoN1 mutants; full recovery was specific to rpoN1. In comparison, only rpoN2 was able to genetically complement a ΔrpoN E. coli mutant. These results demonstrate that the RpoN1 and RpoN2 proteins are not functionally equivalent or interchangeable in R. solanacearum GMI1000.

  16. Defining the Metabolic Functions and Roles in Virulence of the rpoN1 and rpoN2 Genes in Ralstonia solanacearum GMI1000

    PubMed Central

    Lundgren, Benjamin R.; Connolly, Morgan P.; Choudhary, Pratibha; Brookins-Little, Tiffany S.; Chatterjee, Snigdha; Raina, Ramesh; Nomura, Christopher T.

    2015-01-01

    The alternative sigma factor RpoN is a unique regulator found among bacteria. It controls numerous processes that range from basic metabolism to more complex functions such as motility and nitrogen fixation. Our current understanding of RpoN function is largely derived from studies on prototypical bacteria such as Escherichia coli. Bacillus subtilis and Pseudomonas putida. Although the extent and necessity of RpoN-dependent functions differ radically between these model organisms, each bacterium depends on a single chromosomal rpoN gene to meet the cellular demands of RpoN regulation. The bacterium Ralstonia solanacearum is often recognized for being the causative agent of wilt disease in crops, including banana, peanut and potato. However, this plant pathogen is also one of the few bacterial species whose genome possesses dual rpoN genes. To determine if the rpoN genes in this bacterium are genetically redundant and interchangeable, we constructed and characterized ΔrpoN1, ΔrpoN2 and ΔrpoN1 ΔrpoN2 mutants of R. solanacearum GMI1000. It was found that growth on a small range of metabolites, including dicarboxylates, ethanol, nitrate, ornithine, proline and xanthine, were dependent on only the rpoN1 gene. Furthermore, the rpoN1 gene was required for wilt disease on tomato whereas rpoN2 had no observable role in virulence or metabolism in R. solanacearum GMI1000. Interestingly, plasmid-based expression of rpoN2 did not fully rescue the metabolic deficiencies of the ΔrpoN1 mutants; full recovery was specific to rpoN1. In comparison, only rpoN2 was able to genetically complement a ΔrpoN E. coli mutant. These results demonstrate that the RpoN1 and RpoN2 proteins are not functionally equivalent or interchangeable in R. solanacearum GMI1000. PMID:26659655

  17. Associations of Electrocardiographic P-wave Characteristics with Left Atrial Structure, Function and Diffuse Left Ventricular Fibrosis Defined by Cardiac Magnetic Resonance: the PRIMERI Study

    PubMed Central

    Win, Theingi Tiffany; Venkatesh, Bharath Ambale; Volpe, Gustavo J; Mewton, Nathan; Rizzi, Patricia; Sharma, Ravi K.; Strauss, David G.; Lima, Joao A.; Tereshchenko, Larisa G.

    2014-01-01

    Background Abnormal P-terminal force in V1 (PTFV1) is associated with an increased risk of heart failure, stroke, atrial fibrillation (AF) and death. Objective Our goal was to explore associations of left ventricular (LV) diffuse fibrosis with left atrium (LA) function and ECG measures of LA electrical activity. Methods AF-free patients (n=91, mean age 59.5, 61.5% men, 65.9% Caucasian) with structural heart disease (wide spatial QRS-T angle≥105° ± Selvester QRS score≥5 on ECG) but LV ejection fraction >35% underwent clinical evaluation, cardiac magnetic resonance and resting ECG. LA function indices were obtained by multimodality tissue tracking using 2 and 4-chamber long-axis images. T1 mapping and late gadolinium enhancement were used to assess diffuse LV fibrosis and presence of scar. P-prime in V1 amplitude (PPaV1) and duration (PPdV1), averaged P-duration, PR interval and P-axis were automatically measured using 12SL TM algorithm. PTFV1 was calculated as product of PPaV1 by PPdV1. Results In linear regression after adjustment for demographic, body mass index, LA volumemax index, presence of scar and LV mass index, each decile increase in LV interstitial fibrosis was associated with 0.76mV*ms increase in negative abnormal PTFV1 [(95%CI −1.42 to −0.09), P=0.025], 15.3ms prolongation in PPdV1 [(95%CI 6.9 to 23.8), P=0.001], and 5.4ms widening in averaged P-duration [(95%CI 0.9 to 10.0), P=0.020]. LV fibrosis did not affect LA function. PPaV1 and PTFV1 were associated with an increase in LA volumes, decrease in LAEF and LA reservoir function. Conclusion LV interstitial fibrosis is associated with abnormal PTFV1, prolonged PPdV1 and P-duration, but does not affect LA function. PMID:25267584

  18. Upper Limb Evaluation in Duchenne Muscular Dystrophy: Fat-Water Quantification by MRI, Muscle Force and Function Define Endpoints for Clinical Trials

    PubMed Central

    Ricotti, Valeria; Evans, Matthew R. B.; Sinclair, Christopher D. J.; Butler, Jordan W.; Ridout, Deborah A.; Hogrel, Jean-Yves; Emira, Ahmed; Morrow, Jasper M.; Reilly, Mary M.; Hanna, Michael G.; Janiczek, Robert L.; Matthews, Paul M.; Yousry, Tarek A.; Muntoni, Francesco; Thornton, John S.

    2016-01-01

    Objective A number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function. Methods 15 non-ambulant DMD boys (mean age 13.3 y) and 10 age-gender matched healthy controls (mean age 14.6 y) were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.). Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation. Results Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (p<0.001). A progressive f.f. increase was observed in DMD over 12 months, reaching significance from 6 months (p<0.001, n = 7), accompanied by a significant loss in pinch strength at 6 months (p<0.001, n = 9) and a loss of upper limb function and grip force observed over 12 months (p<0.001, n = 8). Conclusions These results support the use of MRI muscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and function. PMID

  19. A refined model for the TSG-6 link module in complex with hyaluronan: use of defined oligosaccharides to probe structure and function.

    PubMed

    Higman, Victoria A; Briggs, David C; Mahoney, David J; Blundell, Charles D; Sattelle, Benedict M; Dyer, Douglas P; Green, Dixy E; DeAngelis, Paul L; Almond, Andrew; Milner, Caroline M; Day, Anthony J

    2014-02-28

    Tumor necrosis factor-stimulated gene-6 (TSG-6) is an inflammation-associated hyaluronan (HA)-binding protein that contributes to remodeling of HA-rich extracellular matrices during inflammatory processes and ovulation. The HA-binding domain of TSG-6 consists solely of a Link module, making it a prototypical member of the superfamily of proteins that interacts with this high molecular weight polysaccharide composed of repeating disaccharides of D-glucuronic acid and N-acetyl-D-glucosamine (GlcNAc). Previously we modeled a complex of the TSG-6 Link module in association with an HA octasaccharide based on the structure of the domain in its HA-bound conformation. Here we have generated a refined model for a HA/Link module complex using novel restraints identified from NMR spectroscopy of the protein in the presence of 10 distinct HA oligosaccharides (from 4- to 8-mers); the model was then tested using unique sugar reagents, i.e. chondroitin/HA hybrid oligomers and an octasaccharide in which a single sugar ring was (13)C-labeled. The HA chain was found to make more extensive contacts with the TSG-6 surface than thought previously, such that a D-glucuronic acid ring makes stacking and ionic interactions with a histidine and lysine, respectively. Importantly, this causes the HA to bend around two faces of the Link module (resembling the way that HA binds to CD44), potentially providing a mechanism for how TSG-6 can reorganize HA during inflammation. However, the HA-binding site defined here may not play a role in TSG-6-mediated transfer of heavy chains from inter-α-inhibitor onto HA, a process known to be essential for ovulation.

  20. Multi-attribute utility function or statistical inference models: a comparison of health state valuation models using the HUI2 health state classification system.

    PubMed

    Stevens, Katherine; McCabe, Christopher; Brazier, John; Roberts, Jennifer

    2007-09-01

    A key issue in health state valuation modelling is the choice of functional form. The two most frequently used preference based instruments adopt different approaches; one based on multi-attribute utility theory (MAUT), the other on statistical analysis. There has been no comparison of these alternative approaches in the context of health economics. We report a comparison of these approaches for the health utilities index mark 2. The statistical inference model predicts more accurately than the one based on MAUT. We discuss possible explanations for the differences in performance, the importance of the findings, and implications for future research.

  1. Symbiotic specificity, association patterns, and function determine community responses to global changes: defining critical research areas for coral-Symbiodinium symbioses.

    PubMed

    Fabina, Nicholas S; Putnam, Hollie M; Franklin, Erik C; Stat, Michael; Gates, Ruth D

    2013-11-01

    Climate change-driven stressors threaten the persistence of coral reefs worldwide. Symbiotic relationships between scleractinian corals and photosynthetic endosymbionts (genus Symbiodinium) are the foundation of reef ecosystems, and these associations are differentially impacted by stress. Here, we couple empirical data from the coral reefs of Moorea, French Polynesia, and a network theoretic modeling approach to evaluate how patterns in coral-Symbiodinium associations influence community stability under climate change. To introduce the effect of climate perturbations, we simulate local 'extinctions' that represent either the loss of coral species or the ability to engage in symbiotic interactions. Community stability is measured by determining the duration and number of species that persist through the simulated extinctions. Our results suggest that four factors greatly increase coral-Symbiodinium community stability in response to global changes: (i) the survival of generalist hosts and symbionts maximizes potential symbiotic unions; (ii) elevated symbiont diversity provides redundant or complementary symbiotic functions; (iii) compatible symbiotic assemblages create the potential for local recolonization; and (iv) the persistence of certain traits associate with symbiotic diversity and redundancy. Symbiodinium may facilitate coral persistence through novel environmental regimes, but this capacity is mediated by symbiotic specificity, association patterns, and the functional performance of the symbionts. Our model-based approach identifies general trends and testable hypotheses in coral-Symbiodinium community responses. Future studies should consider similar methods when community size and/or environmental complexity preclude experimental approaches.

  2. WW domains of Rsp5p define different functions: determination of roles in fluid phase and uracil permease endocytosis in Saccharomyces cerevisiae.

    PubMed

    Gajewska, B; Kamińska, J; Jesionowska, A; Martin, N C; Hopper, A K; Zoładek, T

    2001-01-01

    Rsp5p, ubiquitin-protein ligase, an enzyme of the ubiquitination pathway, contains three WW domains that mediate protein-protein interactions. To determine if these domains adapt Rsp5p to a subset of substrates involved in numerous cellular processes, we generated mutations in individual or combinations of the WW domains. The rsp5-w1, rsp5-w2, and rsp5-w3 mutant alleles complement RSP5 deletions at 30 degrees. Thus, individual WW domains are not essential. Each rsp5-w mutation caused temperature-sensitive growth. Among variants with mutations in multiple WW domains, only rsp5-w1w2 complemented the deletion. Thus, the WW3 domain is sufficient for Rsp5p essential functions. To determine whether rsp5-w mutations affect endocytosis, fluid phase and uracil permease (Fur4p) endocytosis was examined. The WW3 domain is important for both processes. WW2 appears not to be important for fluid phase endocytosis whereas it is important for Fur4p endocytosis. In contrast, the WW1 domain affects fluid phase endocytosis, but it does not appear to function in Fur4p endocytosis. Thus, various WW domains play different roles in the endocytosis of these two substrates. Rsp5p is located in the cytoplasm in a punctate pattern that does not change during the cell cycle. Altering WW domains does not change the location of Rsp5p.

  3. In vivo genetic mutations define predominant functions of the human T-cell leukemia/lymphoma virus p12I protein.

    PubMed

    Fukumoto, Risaku; Andresen, Vibeke; Bialuk, Izabela; Cecchinato, Valentina; Walser, Jean-Claude; Valeri, Valerio W; Nauroth, Julie M; Gessain, Antoine; Nicot, Christophe; Franchini, Genoveffa

    2009-04-16

    The human T-cell leukemia/lymphoma virus type 1 (HTLV-1) ORF-I encodes a 99-amino acid hydrophobic membrane protein, p12(I), that affects receptors in different cellular compartments. We report here that proteolytic cleavage dictates different cellular localization and functions of p12(I). The removal of a noncanonical endoplasmic reticulum (ER) retention/retrieval signal within the amino terminus of p12(I) is necessary for trafficking to the Golgi apparatus and generation of a completely cleaved 8-kDa protein. The 8-kDa protein in turn traffics to the cell surface, is recruited to the immunologic synapse following T-cell receptor (TCR) ligation, and down-regulates TCR proximal signaling. The uncleaved 12-kDa form of p12(I) resides in the ER and interacts with the beta and gamma(c) chains of the interleukin-2 receptor (IL-2R), the heavy chain of the major histocompatibility complex (MHC) class I, as well as calreticulin and calnexin. Genetic analysis of ORF-I from ex vivo samples of HTLV-1-infected patients reveals predominant amino acid substitutions within ORF-I that affect proteolytic cleavage, suggesting that ER-associated functions of p12(I) may contribute to the survival and proliferation of the infected T cells in the host.

  4. Dimerization and thiol sensitivity of the salicylic acid binding thimet oligopeptidases TOP1 and TOP2 define their functions in redox-sensitive cellular pathways

    PubMed Central

    Westlake, Timothy J.; Ricci, William A.; Popescu, George V.; Popescu, Sorina C.

    2015-01-01

    A long-term goal in plant research is to understand how plants integrate signals from multiple environmental stressors. The importance of salicylic acid (SA) in plant response to biotic and abiotic stress is known, yet the molecular details of the SA-mediated pathways are insufficiently understood. Our recent work identified the peptidases TOP1 and TOP2 as critical components in plant response to pathogens and programmed cell death (PCD). In this study, we investigated the characteristics of TOPs related to the regulation of their enzymatic activity and function in oxidative stress response. We determined that TOP1 and TOP2 interact with themselves and each other and their ability to associate in dimers is influenced by SA and the thiol-based reductant DTT. Biochemical characterization of TOP1 and TOP2 indicated distinct sensitivities to DTT and similarly robust activity under a range of pH values. Treatments of top mutants with Methyl Viologen (MV) revealed TOP1 and TOP2 as a modulators of the plant tolerance to MV, and that exogenous SA alleviates the toxicity of MV in top background. Finally, we generated a TOP-centered computational model of a plant cell whose simulation outputs replicate experimental findings and predict novel functions of TOP1 and TOP2. Altogether, our work indicates that TOP1 and TOP2 mediate plant responses to oxidative stress through spatially separated pathways and positions proteolysis in a network for plant response to diverse stressors. PMID:26042129

  5. Cerebral blood flow with [15O]water PET studies using an image-derived input function and MR-defined carotid centerlines

    NASA Astrophysics Data System (ADS)

    Fung, Edward K.; Carson, Richard E.

    2013-03-01

    Full quantitative analysis of brain PET data requires knowledge of the arterial input function into the brain. Such data are normally acquired by arterial sampling with corrections for delay and dispersion to account for the distant sampling site. Several attempts have been made to extract an image-derived input function (IDIF) directly from the internal carotid arteries that supply the brain and are often visible in brain PET images. We have devised a method of delineating the internal carotids in co-registered magnetic resonance (MR) images using the level-set method and applying the segmentations to PET images using a novel centerline approach. Centerlines of the segmented carotids were modeled as cubic splines and re-registered in PET images summed over the early portion of the scan. Using information from the anatomical center of the vessel should minimize partial volume and spillover effects. Centerline time-activity curves were taken as the mean of the values for points along the centerline interpolated from neighboring voxels. A scale factor correction was derived from calculation of cerebral blood flow (CBF) using gold standard arterial blood measurements. We have applied the method to human subject data from multiple injections of [15O]water on the HRRT. The method was assessed by calculating the area under the curve (AUC) of the IDIF and the CBF, and comparing these to values computed using the gold standard arterial input curve. The average ratio of IDIF to arterial AUC (apparent recovery coefficient: aRC) across 9 subjects with multiple (n = 69) injections was 0.49 ± 0.09 at 0-30 s post tracer arrival, 0.45 ± 0.09 at 30-60 s, and 0.46 ± 0.09 at 60-90 s. Gray and white matter CBF values were 61.4 ± 11.0 and 15.6 ± 3.0 mL/min/100 g tissue using sampled blood data. Using IDIF centerlines scaled by the average aRC over each subjects’ injections, gray and white matter CBF values were 61.3 ± 13.5 and 15.5 ± 3.4 mL/min/100 g tissue. Using global

  6. Defining the Functional Potential and Active Community Members of a Sediment Microbial Community in a High-Arctic Hypersaline Subzero Spring

    PubMed Central

    Lay, Chih-Ying; Mykytczuk, Nadia C. S.; Yergeau, Étienne; Lamarche-Gagnon, Guillaume; Greer, Charles W.

    2013-01-01

    The Lost Hammer (LH) Spring is the coldest and saltiest terrestrial spring discovered to date and is characterized by perennial discharges at subzero temperatures (−5°C), hypersalinity (salinity, 24%), and reducing (≈−165 mV), microoxic, and oligotrophic conditions. It is rich in sulfates (10.0%, wt/wt), dissolved H2S/sulfides (up to 25 ppm), ammonia (≈381 μM), and methane (11.1 g day−1). To determine its total functional and genetic potential and to identify its active microbial components, we performed metagenomic analyses of the LH Spring outlet microbial community and pyrosequencing analyses of the cDNA of its 16S rRNA genes. Reads related to Cyanobacteria (19.7%), Bacteroidetes (13.3%), and Proteobacteria (6.6%) represented the dominant phyla identified among the classified sequences. Reconstruction of the enzyme pathways responsible for bacterial nitrification/denitrification/ammonification and sulfate reduction appeared nearly complete in the metagenomic data set. In the cDNA profile of the LH Spring active community, ammonia oxidizers (Thaumarchaeota), denitrifiers (Pseudomonas spp.), sulfate reducers (Desulfobulbus spp.), and other sulfur oxidizers (Thermoprotei) were present, highlighting their involvement in nitrogen and sulfur cycling. Stress response genes for adapting to cold, osmotic stress, and oxidative stress were also abundant in the metagenome. Comparison of the composition of the functional community of the LH Spring to metagenomes from other saline/subzero environments revealed a close association between the LH Spring and another Canadian high-Arctic permafrost environment, particularly in genes related to sulfur metabolism and dormancy. Overall, this study provides insights into the metabolic potential and the active microbial populations that exist in this hypersaline cryoenvironment and contributes to our understanding of microbial ecology in extreme environments. PMID:23563939

  7. Burn patients' return to daily activities and participation as defined by the International Classification of Functioning, Disability and Health: A systematic review.

    PubMed

    Osborne, Candice L; Meyer, Walter J; Ottenbacher, Kenneth J; Arcari, Christine M

    2016-12-29

    The World Health Organization's International Classification of Functioning, Disability and Health (ICF) is a universal classification system of health and health-related domains. The ICF has been successfully applied to a wide range of health conditions and diseases; however, its application in the field of burn recovery has been minimal. This systematic review uses the domains of the ICF component 'activities and participation' to explore: (1) the extent to which return to daily activities and community participation after burn has been examined in the pediatric population, (2) the most common assessments used to determine activity and participation outcomes, and (3) what activity and participation areas are most affected in the pediatric burn population after discharge from acute care. Results determined that it is difficult to draw overarching conclusions in the area of return to 'activities and participation' for children with burn based on the paucity of current evidence. Of the studies conducted, few examined the same subtopics or used similar measurements. This suggests a need for more robust studies in this area in order to inform and improve burn rehabilitation practices to meet the potential needs of burn patients beyond an acute care setting.

  8. RING finger-dependent ubiquitination by PRAJA is dependent on TGF-beta and potentially defines the functional status of the tumor suppressor ELF.

    PubMed

    Saha, T; Vardhini, D; Tang, Y; Katuri, V; Jogunoori, W; Volpe, E A; Haines, D; Sidawy, A; Zhou, X; Gallicano, I; Schlegel, R; Mishra, B; Mishra, L

    2006-02-02

    In gastrointestinal cells, biological signals for transforming growth factor-beta (TGF-beta) are transduced through transmembrane serine/threonine kinase receptors that signal to Smad proteins. Smad4, a tumor suppressor, is often mutated in human gastrointestinal cancers. The mechanism of Smad4 inactivation, however, remains uncertain and could be through E3-mediated ubiquitination of Smad4/adaptor protein complexes. Disruption of ELF (embryonic liver fodrin), a Smad4 adaptor protein, modulates TGF-beta signaling. We have found that PRAJA, a RING-H2 protein, interacts with ELF in a TGF-beta-dependent manner, with a fivefold increase of PRAJA expression and a subsequent decrease in ELF and Smad4 expression, in gastrointestinal cancer cell lines (P < 0.05). Strikingly, PRAJA manifests substantial E3-dependent ubiquitination of ELF and Smad3, but not Smad4. Delta-PRAJA, which has a deleted RING finger domain at the C terminus, abolishes ubiquitination of ELF. A stable cell line that overexpresses PRAJA exhibits low levels of ELF in comparison to a Delta-PRAJA stable cell line, where ELF expression is high compared to normal controls. The alteration of ELF and/or Smad4 expression and/or function in the TGF-beta signaling pathway may be induced by enhancement of ELF degradation, which is mediated by a high-level expression of PRAJA in gastrointestinal cancers. In hepatocytes, half-life (t(1/2)) and rate constant for degradation (k(D)) of ELF is 1.91 h and 21.72 min(-1) when coupled with ectopic expression of PRAJA in cells stimulated by TGF-beta, compared to PRAJA-transfected unstimulated cells (t(1/2) = 4.33 h and k(D) = 9.6 min(-1)). These studies reveal a mechanism for tumorigenesis whereby defects in adaptor proteins for Smads, such as ELF, can undergo degradation by PRAJA, through the ubiquitin-mediated pathway.

  9. Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

    PubMed Central

    Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin; Manning, Alisa; Rivas, Manuel A.; Highland, Heather M.; Locke, Adam E.; Grarup, Niels; Im, Hae Kyung; Cingolani, Pablo; Flannick, Jason; Fontanillas, Pierre; Fuchsberger, Christian; Gaulton, Kyle J.; Teslovich, Tanya M.; Rayner, N. William; Robertson, Neil R.; Beer, Nicola L.; Rundle, Jana K.; Bork-Jensen, Jette; Ladenvall, Claes; Blancher, Christine; Buck, David; Buck, Gemma; Burtt, Noël P.; Gabriel, Stacey; Gjesing, Anette P.; Groves, Christopher J.; Hollensted, Mette; Huyghe, Jeroen R.; Jackson, Anne U.; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S.; Stringham, Heather M.; Syvänen, Ann-Christine; Trakalo, Joseph; Abecasis, Goncalo; Bell, Graeme I.; Blangero, John; Cox, Nancy J.; Duggirala, Ravindranath; Hanis, Craig L.; Seielstad, Mark; Wilson, James G.; Christensen, Cramer; Brandslund, Ivan; Rauramaa, Rainer; Surdulescu, Gabriela L.; Doney, Alex S. F.; Lannfelt, Lars; Linneberg, Allan; Isomaa, Bo; Tuomi, Tiinamaija; Jørgensen, Marit E.; Jørgensen, Torben; Kuusisto, Johanna; Uusitupa, Matti; Salomaa, Veikko; Spector, Timothy D.; Morris, Andrew D.; Palmer, Colin N. A.; Collins, Francis S.; Mohlke, Karen L.; Bergman, Richard N.; Ingelsson, Erik; Lind, Lars; Tuomilehto, Jaakko; Hansen, Torben; Watanabe, Richard M.; Prokopenko, Inga; Dupuis, Josee; Karpe, Fredrik; Groop, Leif; Laakso, Markku; Pedersen, Oluf; Florez, Jose C.; Morris, Andrew P.; Altshuler, David; Meigs, James B.; Boehnke, Michael; McCarthy, Mark I.; Lindgren, Cecilia M.; Gloyn, Anna L.

    2015-01-01

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights. PMID:25625282

  10. The functional importance of a cap site-proximal region of the human prointerleukin 1 beta gene is defined by viral protein trans-activation.

    PubMed Central

    Hunninghake, G W; Monks, B G; Geist, L J; Monick, M M; Monroy, M A; Stinski, M F; Webb, A C; Dayer, J M; Auron, P E; Fenton, M J

    1992-01-01

    Prointerleukin 1 beta (IL-1 beta) is a cytokine that mediates a broad range of biological activities. Genomic sequences that regulate IL-1 beta transcription include both inducible regulatory elements located more than 2,700 bp upstream of the transcriptional start site (cap site) and proximal elements located near the TATA box of this gene. In this study, we focused on the identification and characterization of trans-acting nuclear regulatory proteins that bind to the cap site-proximal region of the human IL-1 beta gene. We identified a protein, termed NFIL-1 beta A (NF beta A), that binds to a highly conserved 12-bp DNA sequence (-49 to -38) located upstream of the TATA box motif in both the human and murine IL-1 beta genes. The IL-1 alpha gene, which lacks a TATA motif, does not possess an NF beta A-binding sequence within the promoter region, suggesting that NF beta A may selectively regulate IL-1 beta expression. Using electrophoretic mobility shift assays, we identified several distinct DNA-protein complexes that are expressed in a cell-type-specific manner. In monocytic cell lines, the relative abundance of these complexes varies rapidly following stimulation of the cells with phorbol esters or lipopolysaccharide. UV cross-linking analysis identified two distinct DNA-binding polypeptides that comprise distinct complexes. The functional role of NF beta A was assessed in transient transfection assays. These data indicate that NF beta A is required for both basal and inducible promoter activity in monocytic cells. Furthermore, the human cytomegalovirus immediate-early 1 gene product requires the presence of NF beta A in order to trans-activate the proximal IL-1 beta promoter in a monocytic cell line. We propose that NF beta A is a factor that mediates either direct or indirect activation by the immediate-early 1 gene product. The proximity of this essential factor to the TATA motif suggests a possible role in transcriptional initiation. Images PMID:1630455

  11. Consortium for health and military performance and American College of Sports Medicine Summit: utility of functional movement assessment in identifying musculoskeletal injury risk.

    PubMed

    Teyhen, Deydre; Bergeron, Michael F; Deuster, Patricia; Baumgartner, Neal; Beutler, Anthony I; de la Motte, Sarah J; Jones, Bruce H; Lisman, Peter; Padua, Darin A; Pendergrass, Timothy L; Pyne, Scott W; Schoomaker, Eric; Sell, Timothy C; O'Connor, Francis

    2014-01-01

    Prevention of musculoskeletal injuries (MSKI) is critical in both civilian and military populations to enhance physical performance, optimize health, and minimize health care expenses. Developing a more unified approach through addressing identified movement impairments could result in improved dynamic balance, trunk stability, and functional movement quality while potentially minimizing the risk of incurring such injuries. Although the evidence supporting the utility of injury prediction and return-to-activity readiness screening tools is encouraging, considerable additional research is needed regarding improving sensitivity, specificity, and outcomes, and especially the implementation challenges and barriers in a military setting. If selected current functional movement assessments can be administered in an efficient and cost-effective manner, utilization of the existing tools may be a beneficial first step in decreasing the burden of MSKI, with a subsequent focus on secondary and tertiary prevention via further assessments on those with prior injury history.

  12. Defining the Human Microbiome

    PubMed Central

    Ursell, Luke K; Metcalf, Jessica L; Parfrey, Laura Wegener; Knight, Rob

    2012-01-01

    Rapidly developing sequencing methods and analytical techniques are enhancing our ability to understand the human microbiome, and, indeed, how we define the microbiome and its constituents. In this review we highlight recent research that expands our ability to understand the human microbiome on different spatial and temporal scales, including daily timeseries datasets spanning months. Furthermore, we discuss emerging concepts related to defining operational taxonomic units, diversity indices, core versus transient microbiomes and the possibility of enterotypes. Additional advances in sequencing technology and in our understanding of the microbiome will provide exciting prospects for exploiting the microbiota for personalized medicine. PMID:22861806

  13. Defining Mathematical Giftedness

    ERIC Educational Resources Information Center

    Parish, Linda

    2014-01-01

    This theoretical paper outlines the process of defining "mathematical giftedness" for a present study on how primary school teaching shapes the mindsets of children who are mathematically gifted. Mathematical giftedness is not a badge of honour or some special value attributed to a child who has achieved something exceptional.…

  14. Defined by Limitations

    ERIC Educational Resources Information Center

    Arriola, Sonya; Murphy, Katy

    2010-01-01

    Undocumented students are a population defined by limitations. Their lack of legal residency and any supporting paperwork (e.g., Social Security number, government issued identification) renders them essentially invisible to the American and state governments. They cannot legally work. In many states, they cannot legally drive. After the age of…

  15. Defining the Language Arts.

    ERIC Educational Resources Information Center

    Barth, Patte, Ed.

    1994-01-01

    This issue of "Basic Education" presents articles that discuss, respectively, defining the language arts, an agenda for English, the benefits of two languages, a new teacher (presently teaching English in a foreign country) looking ahead, and the Shaker Fellowships awarded by the school district in Shaker Heights, Ohio. Articles in the…

  16. On Defining Mass

    ERIC Educational Resources Information Center

    Hecht, Eugene

    2011-01-01

    Though central to any pedagogical development of physics, the concept of mass is still not well understood. Properly defining mass has proven to be far more daunting than contemporary textbooks would have us believe. And yet today the origin of mass is one of the most aggressively pursued areas of research in all of physics. Much of the excitement…

  17. Transition Coordinators: Define Yourselves.

    ERIC Educational Resources Information Center

    Asselin, Susan B.; Todd-Allen, Mary; deFur, Sharon

    1998-01-01

    Describes a technique that was used successfully to identify the changing roles and responsibilities of special educators as transition coordinators. The Developing a Curriculum (DACUM) model uses people who are currently working in the occupation to define job responsibilities. The duties of a transition coordinator are identified. (CR)

  18. Defining in Classroom Activities.

    ERIC Educational Resources Information Center

    Mariotti, Maria Alessandra; Fischbein, Efraim

    1997-01-01

    Discusses some aspects of the defining process in geometrical context in the reference frame of the theory of "figural concepts." Presents analysis of some examples taken from a teaching experiment at the sixth-grade level. Contains 30 references. (Author/ASK)

  19. Impact of nutrition on immune function and the inflammatory response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The review utilizes data on three micronutrients (vitamin A, zinc and iron), anthropometrically defined undernutrition (stunting, wasting and underweight) and obesity to evaluate the effect on immune function, recovery of immune function in response to nutritional interventions, related health outco...

  20. Modeling of a 3DTV service in the software-defined networking architecture

    NASA Astrophysics Data System (ADS)

    Wilczewski, Grzegorz

    2014-11-01

    In this article a newly developed concept towards modeling of a multimedia service offering stereoscopic motion imagery is presented. Proposed model is based on the approach of utilization of Software-defined Networking or Software Defined Networks architecture (SDN). The definition of 3D television service spanning SDN concept is identified, exposing basic characteristic of a 3DTV service in a modern networking organization layout. Furthermore, exemplary functionalities of the proposed 3DTV model are depicted. It is indicated that modeling of a 3DTV service in the Software-defined Networking architecture leads to multiplicity of improvements, especially towards flexibility of a service supporting heterogeneity of end user devices.

  1. Strain energy release rate as a function of temperature and preloading history utilizing the edge delamination fatique test method

    NASA Technical Reports Server (NTRS)

    Zimmerman, Richard S.; Adams, Donald F.

    1989-01-01

    Static laminate and tension-tension fatigue tests of IM7/8551-7 composite materials was performed. The Edge Delamination Test (EDT) was utilized to evaluate the temperature and preloading history effect on the critical strain energy release rate. Static and fatigue testing was performed at room temperature and 180 F (82 C). Three preloading schemes were used to precondition fatigue test specimens prior to performing the normal tension-tension fatigue EDT testing. Computer software was written to perform all fatigue testing while monitoring the dynamic modulus to detect the onset of delamination and record the test information for later retrieval and reduction.

  2. Defining Dynamic Route Structure

    NASA Technical Reports Server (NTRS)

    Zelinski, Shannon; Jastrzebski, Michael

    2011-01-01

    This poster describes a method for defining route structure from flight tracks. Dynamically generated route structures could be useful in guiding dynamic airspace configuration and helping controllers retain situational awareness under dynamically changing traffic conditions. Individual merge and diverge intersections between pairs of flights are identified, clustered, and grouped into nodes of a route structure network. Links are placed between nodes to represent major traffic flows. A parametric analysis determined the algorithm input parameters producing route structures of current day flight plans that are closest to todays airway structure. These parameters are then used to define and analyze the dynamic route structure over the course of a day for current day flight paths. Route structures are also compared between current day flight paths and more user preferred paths such as great circle and weather avoidance routing.

  3. Defining and Diagnosing Sepsis.

    PubMed

    Scott, Michael C

    2017-02-01

    Sepsis is a heterogeneous clinical syndrome that encompasses infections of many different types and severity. Not surprisingly, it has confounded most attempts to apply a single definition, which has also limited the ability to develop a set of reliable diagnostic criteria. It is perhaps best defined as the different clinical syndromes produced by an immune response to infection that causes harm to the body beyond that of the local effects of the infection.

  4. Expression and functional roles of Bradyrhizobium japonicum genes involved in the utilization of inorganic and organic sulfur compounds in free-living and symbiotic conditions.

    PubMed

    Sugawara, Masayuki; Shah, Gopit R; Sadowsky, Michael J; Paliy, Oleg; Speck, Justin; Vail, Andrew W; Gyaneshwar, Prasad

    2011-04-01

    Strains of Bradyrhizobium spp. form nitrogen-fixing symbioses with many legumes, including soybean. Although inorganic sulfur is preferred by bacteria in laboratory conditions, sulfur in agricultural soil is mainly present as sulfonates and sulfur esters. Here, we show that Bradyrhizobium japonicum and B. elkanii strains were able to utilize sulfate, cysteine, sulfonates, and sulfur-ester compounds as sole sulfur sources for growth. Expression and functional analysis revealed that two sets of gene clusters (bll6449 to bll6455 or bll7007 to bll7011) are important for utilization of sulfonates sulfur source. The bll6451 or bll7010 genes are also expressed in the symbiotic nodules. However, B. japonicum mutants defective in either of the sulfonate utilization operons were not affected for symbiosis with soybean, indicating the functional redundancy or availability of other sulfur sources in planta. In accordance, B. japonicum bacteroids possessed significant sulfatase activity. These results indicate that strains of Bradyrhizobium spp. likely use organosulfur compounds for growth and survival in soils, as well as for legume nodulation and nitrogen fixation.

  5. Human chimera-type galectin-3: defining the critical tail length for high-affinity glycoprotein/cell surface binding and functional competition with galectin-1 in neuroblastoma cell growth regulation.

    PubMed

    Kopitz, Jürgen; Vértesy, Sabine; André, Sabine; Fiedler, Sabine; Schnölzer, Martina; Gabius, Hans-Joachim

    2014-09-01

    Many human proteins have a modular design with receptor and structural domains. Using adhesion/growth-regulatory galectin-3 as model, we describe an interdisciplinary strategy to define the functional significance of its tail established by nine non-triple helical collagen-like repeats (I-IX) and the N-terminal peptide. Genetic engineering with sophisticated mass spectrometric product analysis provided the tools for biotesting, i.e. eight protein variants with different degrees of tail truncation. Evidently,various aspects of galectin-3 activity (cis binding and cell bridging) are affected by tail shortening in a different manner. Thus, this combined approach reveals an unsuspected complexity of structure-function relationship, encouraging further application beyond this chimera-type galectin.

  6. Utilization of near-source video and ground motion in the assessment of seismic source functions from mining explosions

    SciTech Connect

    Anderson, D.P.; Stump, B.W.

    1994-09-01

    Identification of seismic events detected under a Comprehensive Test Ban Treaty requires a clear physical understanding of the different types of seismic sources including mining explosions, rock bursts, mine collapse and small, shallow earthquakes. Constraint of the operative physical processes in the source region and linkage to the generation of seismic waveforms with particular emphasis on regional seismograms is needed. In order to properly address the multi-dimensional aspect of data sets designed to constrain these sources, we are investigating a number of modern visualization tools that have only recently become available with new, high-speed graphical computers that can utilize relatively large data sets. The results of this study will provide a basis for identifying important processes in the source region that contribute to regional seismograms.

  7. Performance of density functional theory for 3d transition metal-containing complexes: utilization of the correlation consistent basis sets.

    PubMed

    Tekarli, Sammer M; Drummond, Michael L; Williams, T Gavin; Cundari, Thomas R; Wilson, Angela K

    2009-07-30

    The performance of 44 density functionals used in conjunction with the correlation consistent basis sets (cc-pVnZ where n = T and Q) has been assessed for the gas-phase enthalpies of formation at 298.15 K of 3d transition metal (TM) containing systems. Nineteen molecules were examined: ScS, VO, VO(2), Cr(CO)(6), MnS, MnCl(2), Mn(CO)(5)Cl, FeCl(3), Fe(CO)(5), CoH(CO)(4), NiCl(2), Ni(CO)(4), CuH, CuF, CuCl, ZnH, ZnO, ZnCl, and Zn(CH(3))(2). Of the functionals examined, the functionals that resulted in the smallest mean absolute deviation (MAD, in parentheses, kcal mol(-1)) from experiment were B97-1 (6.9), PBE1KCIS (8.1), TPSS1KCIS (9.6), B97-2 (9.7), and B98 (10.7). All five of these functionals include some degree of Hartree-Fock (HF) exchange. The impact of increasing the basis set from cc-pVTZ to cc-pVQZ was found to be slight for the generalized gradient approximation (GGA) and meta-GGA (MGGA) functionals studied, indicating basis set saturation at the triple-zeta level. By contrast, for most of the generalized gradient exchange (GGE), hybrid GGA (HGGA), and hybrid meta-GGA (HMGGA) functionals considered, improvements in the average MAD of 2-3 kcal mol(-1) were seen upon progressing to a quadruple-zeta level basis set. Overall, it was found that the functionals that include Hartree-Fock exchange performed best overall, but those with greater than 40% HF exchange exhibit significantly poor performance for the prediction of enthalpies of formation for 3d TM complexes. Carbonyl-containing complexes, a mainstay in organometallic TM chemistry, are demonstrated to be exceedingly difficult to describe accurately with all but 2 of the 44 functionals considered. The most accurate functional, for both CO-containing and CO-free compounds, is B97-1/cc-pVQZ, which is shown to be capable of yielding results within 1 kcal mol(-1) of high-level ab initio composite methodologies.

  8. What can water utilities do to improve risk management within their business functions? An improved tool and application of process benchmarking.

    PubMed

    MacGillivray, Brian H; Pollard, Simon J T

    2008-11-01

    We present a model for benchmarking risk analysis and risk based decision making practice within organisations. It draws on behavioural and normative risk research, the principles of capability maturity modelling and our empirical observations. It codifies the processes of risk analysis and risk based decision making within a framework that distinguishes between different levels of maturity. Application of the model is detailed within the selected business functions of a water and wastewater utility. Observed risk analysis and risk based decision making practices are discussed, together with their maturity of implementation. The findings provide academics, utility professionals, and regulators a deeper understanding of the practical and theoretical underpinnings of risk management, and how distinctions can be made between organisational capabilities in this essential business process.

  9. A surface work function measurement technique utilizing constant deflected grazing electron trajectories: oxygen uptake on Cu(001).

    PubMed

    Ermakov, A V; Ciftlikli, E Z; Syssoev, S E; Shuttleworth, I G; Hinch, B J

    2010-10-01

    We report on the application of a novel nondestructive in-vacuum technique for relative work function measurements, employing a grazing incidence electron deflection above a sample with a planar surface. Two deflected electron beam detectors are used as a position sensitive detector to control feedback to the sample potential as the sample work function changes. With feedback the sample potential exactly follows the surface sample-size averaged work function variation, so that the deflected beam trajectory remains stable. We also discuss methods to optimize the initial electron trajectories for this method, so as to minimize unwanted effects such as from uncontrolled external magnetic fields. As the electron beam does not impinge on the surface in this new technique electron induced desorption, ionization, dissociation, and/or decomposition is not induced at the interface. Importantly also the technique allows for free access to the surfaces enabling simultaneous deposition/evaporation and/or application of other surface characterization methods. We demonstrate its application in concurrent measurements of helium atom reflectivity and work function changes taking place during molecular oxygen exposure of a Cu(001) surface. A work function measurement sensitivity and stability is demonstrated at ∼10 mV at a sampling rate of 1 Hz and after application of an ∼7 s smoothing routine. In comparison to the helium atom reflectivity measurements, the work function measurements are more sensitive to the initial O uptake, and less so to the final coverage variations and possible surface reordering at higher O coverages.

  10. Improved gut barrier function via increased threonine utilization may explain enhanced resistance to necrotizing enterocolitis in preterm pigs fed colostrum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Threonine is an essential amino acid necessary for synthesis of gut mucins that form the protective intestinal mucous layer. In premature infants, this function might be compromised leading to necrotizing enterocolitis (NEC). We hypothesized that enteral feeding with colostrum, relative to infant fo...

  11. The clinical utility and specificity of parent report of executive function among children with prenatal alcohol exposure.

    PubMed

    Nguyen, Tanya T; Glass, Leila; Coles, Claire D; Kable, Julie A; May, Philip A; Kalberg, Wendy O; Sowell, Elizabeth R; Jones, Kenneth L; Riley, Edward P; Mattson, Sarah N

    2014-08-01

    Prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) result in behavioral issues related to poor executive function (EF). This overlap may hinder clinical identification of alcohol-exposed children. This study examined the relation between parent and neuropsychological measures of EF and whether parent ratings aid in differential diagnosis. Neuropsychological measures of EF, including the Delis-Kaplan Executive Function System (D-KEFS), were administered to four groups of children (8-16 years): alcohol-exposed with ADHD (AE+, n=80), alcohol-exposed without ADHD (AE-, n=36), non-exposed with ADHD (ADHD, n=93), and controls (CON, n=167). Primary caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF). For parent ratings, multivariate analyses of variance revealed main effects of Exposure and ADHD and an interaction between these factors, with significant differences between all groups on nearly all BRIEF scales. For neuropsychological measures, results indicated main effects of Exposure and ADHD, but no interaction. Discriminant function analysis indicated the BRIEF accurately classifies groups. These findings confirm compounded behavioral, but not neuropsychological, effects in the AE+ group over the other clinical groups. Parent-report was not correlated with neuropsychological performance in the clinical groups and may provide unique information about neurobehavior. Parent-report measures are clinically useful in predicting alcohol exposure regardless of ADHD. Results contribute to a neurobehavioral profile of prenatal alcohol exposure.

  12. Utilization of high resolution computed tomography to visualize the three dimensional structure and function of plant vasculature

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High resolution x-ray computed tomography (HRCT) is a non-destructive diagnostic imaging technique with sub-micron resolution capability that is now being used to evaluate the structure and function of plant xylem network in three dimensions (3D). HRCT imaging is based on the same principles as medi...

  13. [Measures to prevent patient identification errors in blood collection/physiological function testing utilizing a laboratory information system].

    PubMed

    Shimazu, Chisato; Hoshino, Satoshi; Furukawa, Taiji

    2013-08-01

    We constructed an integrated personal identification workflow chart using both bar code reading and an all in-one laboratory information system. The information system not only handles test data but also the information needed for patient guidance in the laboratory department. The reception terminals at the entrance, displays for patient guidance and patient identification tools at blood-sampling booths are all controlled by the information system. The number of patient identification errors was greatly reduced by the system. However, identification errors have not been abolished in the ultrasound department. After re-evaluation of the patient identification process in this department, we recognized that the major reason for the errors came from excessive identification workflow. Ordinarily, an ultrasound test requires patient identification 3 times, because 3 different systems are required during the entire test process, i.e. ultrasound modality system, laboratory information system and a system for producing reports. We are trying to connect the 3 different systems to develop a one-time identification workflow, but it is not a simple task and has not been completed yet. Utilization of the laboratory information system is effective, but is not yet perfect for patient identification. The most fundamental procedure for patient identification is to ask a person's name even today. Everyday checks in the ordinary workflow and everyone's participation in safety-management activity are important for the prevention of patient identification errors.

  14. Reliability, validity, and clinical utility of the Executive Function Performance Test: a measure of executive function in a sample of people with stroke.

    PubMed

    Baum, Carolyn M; Connor, Lisa Tabor; Morrison, Tracy; Hahn, Michelle; Dromerick, Alexander W; Edwards, Dorothy F

    2008-01-01

    This study examined the reliability and validity of the Executive Function Performance Test (EFPT). The EFPT assesses executive function deficits in the performance of real-world tasks. It uses a structured cueing and scoring system to assess higher-level cognitive functions, specifically initiation, organization, sequencing safety and judgment, and task completion. Seventy-three participants with mild to moderate stroke and 22 age- and education-matched controls completed the 4 EFPT tasks (cooking, using the telephone, managing medications, and paying bills). Significant differences were found between participants with mild and moderate stroke and healthy control participants. The EFPT can help occupational therapists determine the level of support needed by people with cognitive impairments to perform complex instrumental tasks. Objective information derived from this assessment is an essential part of the process of determining whether the person can live independently and helping families understand how to support the performance of their family members at home.

  15. Preload dependence of new Doppler techniques limits their utility for left ventricular diastolic function assessment in hemodialysis patients.

    PubMed

    Ie, Eric H Y; Vletter, Wim B; ten Cate, Folkert J; Nette, Robert W; Weimar, Willem; Roelandt, Jos R T C; Zietse, Robert

    2003-07-01

    Left ventricular (LV) hypertrophy leads to diastolic dysfunction. Standard Doppler transmitral and pulmonary vein (PV) flow velocity measurements are preload dependent. New techniques such as mitral annulus velocity by Doppler tissue imaging (DTI) and LV inflow propagation velocity measured from color M-mode have been proposed as relatively preload-independent measurements of diastolic function. These parameters were studied before and after hemodialysis (HD) with ultrafiltration to test their potential advantage for LV diastolic function assessment in HD patients. Ten patients (seven with LV hypertrophy) underwent Doppler echocardiography 1 h before, 1 h after, and 1 d after HD. Early (E) and atrial (A) peak transmitral flow velocities, peak PV systolic (s) and diastolic (d) flow velocities, peak e and a mitral annulus velocities in DTI, and early diastolic LV flow propagation velocity (V(p)) were measured. In all patients, the E/A ratio after HD (0.54; 0.37 to 1.02) was lower (P < 0.01) than before HD (0.77; 0.60 to 1.34). E decreased (P < 0.01), whereas A did not. PV s/d after HD (2.15; 1.08 to 3.90) was higher (P < 0.01) than before HD (1.80; 1.25 to 2.68). Tissue e/a after HD (0.40; 0.26 to 0.96) was lower (P < 0.01) than before HD (0.56; 0.40 to 1.05). Tissue e decreased (P < 0.02), whereas a did not. V(p) after HD (30 cm/s; 16 to 47 cm/s) was lower (P < 0.01) than before HD (45 cm/s; 32 to 60 cm/s). Twenty-four hours after the initial measurements values for E/A (0.59; 0.37 to 1.23), PV s/d (1.85; 1.07 to 3.38), e/a (0.41; 0.27 to 1.06), and V(p) (28 cm/s; 23 to 33 cm/s) were similar as those taken 1 h after HD. It is concluded that, even when using the newer Doppler techniques DTI and color M-mode, pseudonormalization, which was due to volume overload before HD, resulted in underestimation of the degree of diastolic dysfunction. Therefore, the advantage of these techniques over conventional parameters for the assessment of LV diastolic function in HD

  16. An optically detectable CO2 sensor utilizing polyethylenimine and starch functionalized InGaN/GaN multiple quantum wells

    NASA Astrophysics Data System (ADS)

    Chen, Y. C.; Shih, H. Y.; Chen, J. Y.; Tan, W. J.; Chen, Y. F.

    2013-07-01

    An optically detectable gas sensor based on the high surface sensitivity of functionalized polyethylenimine/starch In0.15Ga0.85N/GaN strained semiconductor multiple quantum wells (MQWs) has been developed. Due to the excellent piezoelectricity of the MQWs, the change of surface charges caused by chemical interaction can introduce a strain and induce an internal field. In turn, it tilts the energy levels of the MQWs and modifies the optical properties. Through the measurement of the changes in photoluminescence as well as Raman scattering spectra under different concentrations of carbon dioxide gas, we demonstrate the feasibility and high sensitivity of the sensors derived from our methodology.

  17. Orbital flight simulation utility software unit specifications

    NASA Technical Reports Server (NTRS)

    Wilson, S. W.

    1986-01-01

    The HP PASCAL source code contained in pages 6 through 104 was developed for the Mission Planning and Analysis Division (MPAD) and takes the place of detailed flow charts defining the specifications for a Utility Software Unit designed to support orbital flight simulators such as MANHANDLE and GREAS (General Research and Engineering Analysis Simulator). Besides providing basic input/output, mathematical, vector, matrix, quaternion, and statistical routines for such simulators, one of the primary functions of the Utility Software Unit is to isolate all system-dependent code in one well-defined compartment, thereby facilitating transportation of the simulations from one computer to another. Directives to the PASCAL compilers of the HP-9000 Series 200 PASCAL 3.0 operating system and the HP-9000 Series 500 HP-UX 5.0 operations systems are also provided.

  18. New functionally dioecious bush tomato from northwestern Australia, Solanum ossicruentum, may utilize “trample burr” dispersal

    PubMed Central

    Martine, Christopher T.; Cantley, Jason T.; Frawley, Emma S.; Butler, Alice R.; Jordon-Thaden, Ingrid E.

    2016-01-01

    Abstract A new Australian species of functionally dioecious bush tomato of Solanum subgenus Leptostemonum is described. Solanum ossicruentum Martine & J.Cantley, sp. nov., is thought to be allied with members of the problematic “Dioicum Complex” lineage, but differs in its short silvery indumentum, long calyx lobes, larger stature, and an unusual fruit morphology that may represent “trample burr” seed dispersal. The species occurs in a range extending from the eastern Kimberley in Western Australia to far northwestern Northern Territory and has been recognized for decades as a variant of Solanum dioicum W.Fitzg. Specimens of this species were previously referred to by D.E. Symon and others as Solanum dioicum ‘Tanami.’ Ex situ crossing studies and SEM images of inaperturate pollen grains produced in morphologically hermaphrodite flowers indicate that this taxon is functionally dioecious. The scientific name was chosen with the help of 150 seventh grade life science students from Pennsylvania, USA. PMID:27489475

  19. Facilitation and restoration of cognitive function in primate prefrontal cortex by a neuroprosthesis that utilizes minicolumn-specific neural firing

    NASA Astrophysics Data System (ADS)

    Hampson, Robert E.; Gerhardt, Greg A.; Marmarelis, Vasilis; Song, Dong; Opris, Ioan; Santos, Lucas; Berger, Theodore W.; Deadwyler, Sam A.

    2012-10-01

    Objective. Maintenance of cognitive control is a major concern for many human disease conditions; therefore, a major goal of human neuroprosthetics is to facilitate and/or recover the cognitive function when such circumstances impair appropriate decision making. Approach. Minicolumnar activity from the prefrontal cortex (PFC) was recorded from nonhuman primates trained to perform a delayed match to sample (DMS), via custom-designed conformal multielectrode arrays that provided inter-laminar recordings from neurons in the PFC layer 2/3 and layer 5. Such recordings were analyzed via a previously demonstrated nonlinear multi-input-multi-output (MIMO) neuroprosthesis in rodents, which extracted and characterized multicolumnar firing patterns during DMS performance. Main results. The MIMO model verified that the conformal recorded individual PFC minicolumns responded to entrained target selections in patterns critical for successful DMS performance. This allowed the substitution of task-related layer 5 neuron firing patterns with electrical stimulation in the same recording regions during columnar transmission from layer 2/3 at the time of target selection. Such stimulation improved normal task performance, but more importantly, recovered performance when applied as a neuroprosthesis following the pharmacological disruption of decision making in the same task. Significance. These findings provide the first successful application of neuroprosthesis in the primate brain designed specifically to restore or repair the disrupted cognitive function.

  20. Defining the Anthropocene

    NASA Astrophysics Data System (ADS)

    Lewis, Simon; Maslin, Mark

    2016-04-01

    Time is divided by geologists according to marked shifts in Earth's state. Recent global environmental changes suggest that Earth may have entered a new human-dominated geological epoch, the Anthropocene. Should the Anthropocene - the idea that human activity is a force acting upon the Earth system in ways that mean that Earth will be altered for millions of years - be defined as a geological time-unit at the level of an Epoch? Here we appraise the data to assess such claims, first in terms of changes to the Earth system, with particular focus on very long-lived impacts, as Epochs typically last millions of years. Can Earth really be said to be in transition from one state to another? Secondly, we then consider the formal criteria used to define geological time-units and move forward through time examining whether currently available evidence passes typical geological time-unit evidence thresholds. We suggest two time periods likely fit the criteria (1) the aftermath of the interlinking of the Old and New Worlds, which moved species across continents and ocean basins worldwide, a geologically unprecedented and permanent change, which is also the globally synchronous coolest part of the Little Ice Age (in Earth system terms), and the beginning of global trade and a new socio-economic "world system" (in historical terms), marked as a golden spike by a temporary drop in atmospheric CO2, centred on 1610 CE; and (2) the aftermath of the Second World War, when many global environmental changes accelerated and novel long-lived materials were increasingly manufactured, known as the Great Acceleration (in Earth system terms) and the beginning of the Cold War (in historical terms), marked as a golden spike by the peak in radionuclide fallout in 1964. We finish by noting that the Anthropocene debate is politically loaded, thus transparency in the presentation of evidence is essential if a formal definition of the Anthropocene is to avoid becoming a debate about bias. The

  1. The biological function and clinical utilization of CD147 in human diseases: a review of the current scientific literature.

    PubMed

    Xiong, Lijuan; Edwards, Carl K; Zhou, Lijun

    2014-09-29

    CD147 or EMMPRIN is a member of the immunoglobulin superfamily in humans. It is widely expressed in human tumors and plays a central role in the progression of many cancers by stimulating the secretion of matrix metalloproteinases (MMPs) and cytokines. CD147 regulates cell proliferation, apoptosis, and tumor cell migration, metastasis and differentiation, especially under hypoxic conditions. CD147 is also important to many organ systems. This review will provide a detailed overview of the discovery, characterization, molecular structure, diverse biological functions and regulatory mechanisms of CD147 in human physiological and pathological processes. In particular, recent studies have demonstrated the potential application of CD147 not only as a phenotypic marker of activated regulatory T cells but also as a potential diagnostic marker for early-stage disease. Moreover, CD147 is recognized as an effective therapeutic target for hepatocellular carcinoma (HCC) and other cancers, and exciting clinical progress has been made in HCC treatment using CD147-directed monoclonal antibodies.

  2. Analysis of the metabolic utilization of carbon sources and potential functional diversity of the bacterial community in lab-scale horizontal subsurface-flow constructed wetlands.

    PubMed

    Deng, Huanhuan; Ge, Liyun; Xu, Tan; Zhang, Minghua; Wang, Xuedong; Zhang, Yalei; Peng, Hong

    2011-01-01

    Microorganisms are an integral part of the biogeochemical processes in wetlands. To improve the performance of constructed wetlands, it is very important to know the metabolic properties and functional diversity of the microbial communities. The purpose of this study is to analyze the metabolic properties and functional diversity of the microbial community in a horizontal subsurface-flow constructed wetland (CW) in a laboratory study through the sole-carbon-source utilization profiles using Biolog-ECO microplates. The technique has advantages over traditional cell culture techniques, such as molecular-level techniques-RNA amplification, which are time-consuming, expensive, and only applicable to the small number of species that may be cultured. This CW was designed to treat rural eutrophic water in China, using the plant L. This study showed that the metabolic activities of upper front substrate microorganisms (UF) were greater than those of the lower back substrate microorganisms (LB) in the CW. Integrated areas under average well color development (AWCD) curves of substrate microorganisms in the UF were 131.9, 4.8, and 99.3% higher than in the lower front part (LF), the upper back part (UB), and the LB part of the CW, respectively. Principal components analysis showed significant differences in both community structure and metabolic utilization of carbon sources between substrate microorganisms from different sampling sites. Carbon source utilization of polymers, carbohydrates, carboxylic acids, and amino acids was higher in UF than in LF, but that of amines and phenolic compounds was very similar in UF and LF. The richness, evenness, and diversity of upper substrate microbial communities were significantly higher than those of lower substrate. The LF substrate microbial communities had lower evenness than the other sampling plots, and the lowest richness of substrate microbial community was found in the LB part of the CW.

  3. Defining equity in health

    PubMed Central

    Braveman, P; Gruskin, S

    2003-01-01

    Study objective: To propose a definition of health equity to guide operationalisation and measurement, and to discuss the practical importance of clarity in defining this concept. Design: Conceptual discussion. Setting, Patients/Participants, and Main results: not applicable. Conclusions: For the purposes of measurement and operationalisation, equity in health is the absence of systematic disparities in health (or in the major social determinants of health) between groups with different levels of underlying social advantage/disadvantage—that is, wealth, power, or prestige. Inequities in health systematically put groups of people who are already socially disadvantaged (for example, by virtue of being poor, female, and/or members of a disenfranchised racial, ethnic, or religious group) at further disadvantage with respect to their health; health is essential to wellbeing and to overcoming other effects of social disadvantage. Equity is an ethical principle; it also is consonant with and closely related to human rights principles. The proposed definition of equity supports operationalisation of the right to the highest attainable standard of health as indicated by the health status of the most socially advantaged group. Assessing health equity requires comparing health and its social determinants between more and less advantaged social groups. These comparisons are essential to assess whether national and international policies are leading toward or away from greater social justice in health. PMID:12646539

  4. Defining Neonatal Sepsis

    PubMed Central

    Wynn, James L.

    2016-01-01

    Purpose of the review Although infection rates have modestly decreased in the neonatal intensive care unit (NICU) as a result of ongoing quality improvement measures, neonatal sepsis remains a frequent and devastating problem among hospitalized preterm neonates. Despite multiple attempts to address this unmet need, there have been minimal advances in clinical management, outcomes, and accuracy of diagnostic testing options over the last three decades. One strong contributor to a lack of medical progress is a variable case definition of disease. The inability to agree on a precise definition greatly reduces the likelihood of aligning findings from epidemiologists, clinicians, and researchers, which, in turn, severely hinders progress towards improving outcomes. Recent findings Pediatric consensus definitions for sepsis are not accurate in term infants and are not appropriate for preterm infants. In contrast to the defined multi-stage criteria for other devastating diseases encountered in the NICU (e.g., bronchopulmonary dysplasia), there is significant variability in the criteria used by investigators to substantiate the diagnosis of neonatal sepsis. Summary The lack of an accepted consensus definition for neonatal sepsis impedes our efforts towards improved diagnostic and prognostic options as well as accurate outcomes information for this vulnerable population. PMID:26766602

  5. Defining hypercalciuria in nephrolithiasis

    PubMed Central

    Pak, Charles Y.C.; Sakhaee, Khashayar; Moe, Orson W.; Poindexter, John; Adams-Huet, Beverley

    2014-01-01

    The classic definition of hypercalciuria, an upper normal limit of 200 mg/day, is based on a constant diet restricted in calcium, sodium, and animal protein; however, random diet data challenge this. Here our retrospective study determined the validity of the classic definition of hypercalciuria by comparing data from 39 publications analyzing urinary calcium excretion on a constant restricted diet and testing whether hypercalciuria could be defined when extraneous dietary influences were controlled. These papers encompassed 300 non-stone-forming patients, 208 patients with absorptive hypercalciuria type I (presumed due to high intestinal calcium absorption), and 234 stone formers without absorptive hypercalciuria; all evaluated on a constant restricted diet. In non-stone formers, the mean urinary calcium was well below 200 mg/day, and the mean for all patients was 127±46 mg/day with an upper limit of 219 mg/day. In absorptive hypercalciuria type I, the mean urinary calcium significantly exceeded 200 mg/day in all studies with a combined mean of 259±55 mg/day. Receiver operating characteristic curve analysis showed the optimal cutoff point for urinary calcium excretion was 172 mg/day on a restricted diet, a value that approximates the traditional limit of 200 mg/day. Thus, on a restricted diet, a clear demarcation was seen between urinary calcium excretion of kidney stone formers with absorptive hypercalciuria type I and normal individuals. When dietary variables are controlled, the classic definition of hypercalciuria of nephrolithiasis appears valid. PMID:21775970

  6. Heightened clinical utility of smartphone versus body-worn inertial system for shoulder function B-B score

    PubMed Central

    Aminian, Kamiar; Ancey, Céline; Jaccard, Hervé; Lécureux, Estelle; Duc, Cyntia; Farron, Alain; Jolles, Brigitte M.; Gleeson, Nigel

    2017-01-01

    Background The B-B Score is a straightforward kinematic shoulder function score including only two movements (hand to the Back + lift hand as to change a Bulb) that demonstrated sound measurement properties for patients for various shoulder pathologies. However, the B-B Score results using a smartphone or a reference system have not yet been compared. Provided that the measurement properties are comparable, the use of a smartphone would offer substantial practical advantages. This study investigated the concurrent validity of a smartphone and a reference inertial system for the measurement of the kinematic shoulder function B-B Score. Methods Sixty-five patients with shoulder conditions (with rotator cuff conditions, adhesive capsulitis and proximal humerus fracture) and 20 healthy participants were evaluated using a smartphone and a reference inertial system. Measurements were performed twice, alternating between two evaluators. The B-B Score differences between groups, differences between devices, relationship between devices, intra- and inter-evaluator reproducibility were analysed. Results The smartphone mean scores (SD) were 94.1 (11.1) for controls and 54.1 (18.3) for patients (P < 0.01). The difference between devices was non-significant for the control (P = 0.16) and the patient group (P = 0.81). The analysis of the relationship between devices showed 0.97 ICC, −0.6 bias and −13.2 to 12.0 limits of agreement (LOA). The smartphone intra-evaluator ICC was 0.92, the bias 1.5 and the LOA −17.4 to 20.3. The smartphone inter-evaluator ICC was 0.92, the bias 1.5 and the LOA −16.9 to 20.0. Conclusions The B-B Score results measured with a smartphone were comparable to those of an inertial system. While single measurements diverged in some cases, the intra- and inter-evaluator reproducibility was excellent and was equivalent between devices. The B-B score measured with a smartphone is straightforward and as efficient as a reference inertial system

  7. Behavior and space utilization of two common fishes within Caribbean mangroves: implications for the protective function of mangrove habitats

    NASA Astrophysics Data System (ADS)

    MacDonald, J. A.; Shahrestani, S.; Weis, J. S.

    2009-09-01

    Behaviors, activity budgets, and spatial locations of reef-associated schoolmaster snapper ( Lutjanus apodus) and non-reef-associated checkered puffer ( Sphoeroides testudineus) were cataloged in mangrove forests in Caribbean Honduras to see how and where they spent their time and whether this changed as they grew. For schoolmasters, swimming was the most common behavior, while checkered puffers spent the majority of their time resting. Both remained completely within (as opposed to outside) the mangrove roots and in the lower half of the water column most of the time. However, as the size of the fish increased there was a clear decrease in the time spent both within the root system and closer to the substrate; the larger fish spent more time higher up in the water column and outside the root system. This was observed in both the schoolmaster and the puffer; the schoolmaster subsequently moves to reefs while the puffer does not. Coupled with limited feeding, the results suggest a primarily protective function for mangroves.

  8. Ataxin1L is a regulator of HSC function highlighting the utility of cross-tissue comparisons for gene discovery.

    PubMed

    Kahle, Juliette J; Souroullas, George P; Yu, Peng; Zohren, Fabian; Lee, Yoontae; Shaw, Chad A; Zoghbi, Huda Y; Goodell, Margaret A

    2013-03-01

    Hematopoietic stem cells (HSCs) are rare quiescent cells that continuously replenish the cellular components of the peripheral blood. Observing that the ataxia-associated gene Ataxin-1-like (Atxn1L) was highly expressed in HSCs, we examined its role in HSC function through in vitro and in vivo assays. Mice lacking Atxn1L had greater numbers of HSCs that regenerated the blood more quickly than their wild-type counterparts. Molecular analyses indicated Atxn1L null HSCs had gene expression changes that regulate a program consistent with their higher level of proliferation, suggesting that Atxn1L is a novel regulator of HSC quiescence. To determine if additional brain-associated genes were candidates for hematologic regulation, we examined genes encoding proteins from autism- and ataxia-associated protein-protein interaction networks for their representation in hematopoietic cell populations. The interactomes were found to be highly enriched for proteins encoded by genes specifically expressed in HSCs relative to their differentiated progeny. Our data suggest a heretofore unappreciated similarity between regulatory modules in the brain and HSCs, offering a new strategy for novel gene discovery in both systems.

  9. The utility of regression-based norms in interpreting the minimal assessment of cognitive function in multiple sclerosis (MACFIMS).

    PubMed

    Parmenter, Brett A; Testa, S Marc; Schretlen, David J; Weinstock-Guttman, Bianca; Benedict, Ralph H B

    2010-01-01

    The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is a consensus neuropsychological battery with established reliability and validity. One of the difficulties in implementing the MACFIMS in clinical settings is the reliance on manualized norms from disparate sources. In this study, we derived regression-based norms for the MACFIMS, using a unique data set to control for standard demographic variables (i.e., age, age2, sex, education). Multiple sclerosis (MS) patients (n = 395) and healthy volunteers (n = 100) did not differ in age, level of education, sex, or race. Multiple regression analyses were conducted on the performance of the healthy adults, and the resulting models were used to predict MS performance on the MACFIMS battery. This regression-based approach identified higher rates of impairment than manualized norms for many of the MACFIMS measures. These findings suggest that there are advantages to developing new norms from a single sample using the regression-based approach. We conclude that the regression-based norms presented here provide a valid alternative to identifying cognitive impairment as measured by the MACFIMS.

  10. Utilization of wheat straw for the preparation of coated controlled-release fertilizer with the function of water retention.

    PubMed

    Xie, Lihua; Liu, Mingzhu; Ni, Boli; Wang, Yanfang

    2012-07-18

    With the aim of improving fertilizer use efficiency and minimizing the negative impact on the environment, a new coated controlled-release fertilizer with the function of water retention was prepared. A novel low water solubility macromolecular fertilizer, poly(dimethylourea phosphate) (PDUP), was "designed" and formulated from N,N'-dimethylolurea (DMU) and potassium dihydrogen phosphate. Simultaneously, an eco-friendly superabsorbent composite based on wheat straw (WS), acrylic acid (AA), 2-acryloylamino-2-methyl-1-propanesulfonic acid (AMPS), and N-hydroxymethyl acrylamide (NHMAAm) was synthesized and used as the coating to control the release of nutrient. The nitrogen release profile and water retention capacity of the product were also investigated. The degradation of the coating material in soil solution was studied. Meanwhile, the impact of the content of N-hydroxymethyl acrylamide on the degradation extent was examined. The experimental data showed that the product with good water retention and controlled-release capacities, being economical and eco-friendly, could be promising for applications in agriculture and horticulture.

  11. TEMPO-functionalized zinc phthalocyanine: synthesis, magnetic properties, and its utility for electrochemical sensing of ascorbic acid.

    PubMed

    Korkut, Sibel Eken; Akyüz, Duygu; Özdoğan, Kemal; Yerli, Yusuf; Koca, Atıf; Şener, M Kasım

    2016-02-21

    Zinc(ii) phthalocyanine (TEMPO-ZnPc), peripherally functionalized with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) radicals is synthesized and its magneto structural and electrochemical behaviors are investigated. TEMPO-ZnPc shows multi-electron ring based reduction reactions and a TEMPO based oxidation reaction. Spectroelectrochemical measurements support these peak assignments. TEMPO-ZnPc is tested as a homogeneous and heterogeneous ascorbic acid (AA) sensor. Disappearance of TEMPO-ZnPc based reduction processes and the observation of new waves at around 0 and 1.20 V with respect to increasing AA concentration indicate the interaction of TEMPO-ZnPc with AA and usability of the complex as an electrochemical AA sensor. For practical usage as heterogeneous electrocatalysts for AA sensing, a glassy carbon electrode (GCE) is coated with TEMPO-ZnPc (GCE/TEMPO-ZnPc) and this modified electrode is tested as a heterogeneous AA sensor. The redox peak of GCE/TEMPO-ZnPc at 0.81 V decreases the peak current while a new wave is observed at 0.65 V during the titration of the electrolyte with AA. GCE/TEMPO-ZnPc sense AA with 1.75 × 10(-6) mol dm(-3) LOD with a sensitivity of 1.89 × 10(3) A cm mol(-1).

  12. Defining Contract Terms

    DTIC Science & Technology

    1992-09-01

    grass roots estimate as an estivate developed by requesting and collecting estimates from functional organizations within a conpany or agency for a...provides the definition under "engineering cost estimate" and lists the term "’grass roots’ estivate " as a synonym of that term) (12:72; 19:43). The Pricer’s...of the effort. Synonym: none Antonym: none Estivate to Coplete (ETC) Those necessary and reasonable costs that in the estimator’s judgement are

  13. Utility of Echocardiography in the Assessment of Left Ventricular Diastolic Function and Restrictive Physiology in Children and Young Adults with Restrictive Cardiomyopathy: A Comparative Echocardiography-Catheterization Study.

    PubMed

    Ryan, Thomas D; Madueme, Peace C; Jefferies, John L; Michelfelder, Erik C; Towbin, Jeffrey A; Woo, Jessica G; Sahay, Rashmi D; King, Eileen C; Brown, Roberta; Moore, Ryan A; Grenier, Michelle A; Goldstein, Bryan H

    2017-02-01

    The aim of the study is to determine the utility of echocardiography in the assessment of diastolic function in children and young adults with restrictive cardiomyopathy (RCM). RCM is a rare disease with high mortality requiring frequent surveillance. Accurate, noninvasive echocardiographic measures of diastolic function may reduce the need for invasive catheterization. Single-center, prospective, observational study of pediatric and young adult RCM patients undergoing assessment of diastolic parameters by simultaneous transthoracic echocardiogram (TTE) and invasive catheterization. Twenty-one studies in 15 subjects [median (IQR) = 13.8 years (7.0-19.2), 60% female] were acquired with median left ventricular end-diastolic pressure (LVEDP) 21 (IQR 18-25) mmHg. TTE parameters of diastolic function, including pulmonary vein A wave duration (r s  = 0.79) and indexed left atrial volume (r s  = 0.49), demonstrated significant positive correlation, while mitral valve A (r s  = -0.44), lateral e' (r s  = -0.61) and lateral a' (r s  = -0.61) velocities showed significant negative correlation with LVEDP. Lateral a' velocity (≤0.042 m/s) and pulmonary vein A wave duration (≥156 m/s) both had sensitivity and specificity ≥80% for LVEDP ≥ 20 mmHg. In pediatric and young adult patients with RCM, lateral a' velocity and pulmonary vein A wave duration predicted elevated LVEDP with high sensitivity and specificity; however, due to technical limitations the latter was reliably measured in 12/21 patients. These noninvasive parameters may have utility in identifying patients that require further assessment with invasive testing. These findings require validation in a multicenter prospective cohort prior to widespread clinical implementation.

  14. Identification of BDNF Sensitive Electrophysiological Markers of Synaptic Activity and Their Structural Correlates in Healthy Subjects Using a Genetic Approach Utilizing the Functional BDNF Val66Met Polymorphism

    PubMed Central

    Soltész, Fruzsina; Suckling, John; Lawrence, Phil; Tait, Roger; Ooi, Cinly; Bentley, Graham; Dodds, Chris M.; Miller, Sam R.; Wille, David R.; Byrne, Misha; McHugh, Simon M.; Bellgrove, Mark A.; Croft, Rodney J.; Lu, Bai; Bullmore, Edward T.; Nathan, Pradeep J.

    2014-01-01

    Increasing evidence suggests that synaptic dysfunction is a core pathophysiological hallmark of neurodegenerative disorders. Brain-derived neurotropic factor (BDNF) is key synaptogenic molecule and targeting synaptic repair through modulation of BDNF signalling has been suggested as a potential drug discovery strategy. The development of such “synaptogenic” therapies depend on the availability of BDNF sensitive markers of synaptic function that could be utilized as biomarkers for examining target engagement or drug efficacy in humans. Here we have utilized the BDNF Val66Met genetic polymorphism to examine the effect of the polymorphism and genetic load (i.e. Met allele load) on electrophysiological (EEG) markers of synaptic activity and their structural (MRI) correlates. Sixty healthy adults were prospectively recruited into the three genetic groups (Val/Val, Val/Met, Met/Met). Subjects also underwent fMRI, tDCS/TMS, and cognitive assessments as part of a larger study. Overall, some of the EEG markers of synaptic activity and brain structure measured with MRI were the most sensitive markers of the polymorphism. Met carriers showed decreased oscillatory activity and synchrony in the neural network subserving error-processing, as measured during a flanker task (ERN); and showed increased slow-wave activity during resting. There was no evidence for a Met load effect on the EEG measures and the polymorphism had no effects on MMN and P300. Met carriers also showed reduced grey matter volume in the anterior cingulate and in the (left) prefrontal cortex. Furthermore, anterior cingulate grey matter volume, and oscillatory EEG power during the flanker task predicted subsequent behavioural adaptation, indicating a BDNF dependent link between brain structure, function and behaviour associated with error processing and monitoring. These findings suggest that EEG markers such as ERN and resting EEG could be used as BDNF sensitive functional markers in early clinical

  15. Utilizing repetitive transcranial magnetic stimulation to improve language function in stroke patients with chronic non-fluent aphasia.

    PubMed

    Garcia, Gabriella; Norise, Catherine; Faseyitan, Olufunsho; Naeser, Margaret A; Hamilton, Roy H

    2013-07-02

    Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia(1). In this experiment, we demonstrate the administration of low-frequency repetitive TMS (rTMS) to an optimal stimulation site in the right hemisphere in patients with chronic non-fluent aphasia. A battery of standardized language measures is administered in order to assess baseline performance. Patients are subsequently randomized to either receive real rTMS or initial sham stimulation. Patients in the real stimulation undergo a site-finding phase, comprised of a series of six rTMS sessions administered over five days; stimulation is delivered to a different site in the right frontal lobe during each of these sessions. Each site-finding session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture-naming task. By comparing the degree of transient change in naming ability elicited by stimulation of candidate sites, we are able to locate the area of optimal response for each individual patient. We then administer rTMS to this site during the treatment phase. During treatment, patients undergo a total of ten days of stimulation over the span of two weeks; each session is comprised of 20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is paired with an fMRI-naming task on the first and last days of treatment. After the treatment phase is complete, the language battery obtained at baseline is repeated two and six months following stimulation in order to identify rTMS-induced changes in performance. The fMRI-naming task is also repeated two and six months following treatment. Patients who are randomized to the sham arm of the study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat language testing two months after completing sham treatment. Sham patients then cross over into the real stimulation arm, completing real site-finding, real treatment, fMRI, and two- and six

  16. Will anticipated future climatic conditions affect belowground C utilization? - Insights into the role of microbial functional groups in a temperate heath/grassland.

    NASA Astrophysics Data System (ADS)

    Reinsch, Sabine; Michelsen, Anders; Sárossy, Zsuzsa; Egsgaard, Helge; Kappel Schmidt, Inger; Jakobsen, Iver; Ambus, Per

    2013-04-01

    The global terrestrial soil organic matter stock is the biggest terrestrial carbon pool (1500 Pg C) of which about 4 % is turned over annually. Thus, terrestrial ecosystems have the potential to accelerate or diminish atmospheric climate change effects via belowground carbon processes. We investigated the effect of elevated CO2 (510 ppm), prolonged spring/summer droughts and increased temperature (1 ˚C) on belowground carbon allocation and on the recovery of carbon by the soil microbial community. An in-situ 13C-carbon pulse-labeling experiment was carried out in a temperate heath/grassland (Denmark) in May 2011. Recently assimilated 13C-carbon was traced into roots, soil and microbial biomass 1, 2 and 8 days after pulse-labeling. The importance of the microbial community in C utilization was investigated using 13C enrichment patterns in microbial functional groups on the basis of phospholipid fatty acids (PLFAs) in roots. Gram-negative and gram-positive bacteria were distinguished from the decomposer groups of actinomycetes (belonging to the group of gram-positive bacteria) and saprophytic fungi. Mycorrhizal fungi specific PLFAs were not detected probably due to limited sample size in combination with restricted sensitivity of the used GC-c-IRMS setup. Climate treatments did not affect 13C allocation into roots, soil and microbial biomass carbon and also the total microbial biomass size stayed unchanged as frequently observed. However, climate treatments changed the composition of the microbial community: elevated CO2 significantly reduced the abundance of gram-negative bacteria (17:0cy) but did not affect the abundance of decomposers. Drought favored the bacterial community whereas increased temperatures showed reduced abundance of gram-negative bacteria (19:0cy) and changed the actinomycetes community (10Me16:0, 10Me18:0). However, not only the microbial community composition was affected by the applied climatic conditions, but also the activity of microbial

  17. Utilization of specific and non-specific peptide interactions with inorganic nanomaterials on the surface of bacteriophage M13: Methodologies towards phage supported bi-functional materials

    NASA Astrophysics Data System (ADS)

    Avery, Kendra Nicole

    Many types of organisms create a variety of nano and micro scale materials from precursors available in their surrounding environments by a process called biomineralization. As scientists begin to understand how these organisms utilize specific and non-specific interactions with a variety of biopolymers such as chitin, peptides, proteins and nucleic acids with these precursors to create inorganic/organic composite materials, they have begun to wonder about the synthesis of other types of non-biologically templated synthetic techniques that might be possible. Bioengineered organisms and biopolymers have begun to be used for these types of studies. A variety of selection techniques exist for discovering biopolymers with an affinity for a target material, however, one of the most notable is a technique called peptide phage display. This is a technique that utilizes a commercially available randomized peptide library attached at the tip of the filamentous bacteriophage M13. In this dissertation capabilities of bacteriophage M13 are explored in regard to the creation of bi-functional nano materials by exploiting both specific peptide interactions as well as non-specific peptide interactions on the surface of the organism. Chapter 2 focuses on utilizing the specific peptide interactions of the randomized library at pIII in order to discover peptides with high binding affinity for a variety of nanomaterials. Selection studies called biopanning are performed on a variety of nanomaterials such as CaMoO4, allotropes of Ni, Fe2O3 and Fe3O4, and Rh and Pt with the fcc type crystal structure. Similarities and differences between peptides discovered for these materials are discussed. Chapter 3 focuses on utilizing the non-specific peptide interactions on the long axis of M13 called pVIII. The pVIII region consists of 2700 copies of the same 50 amino acid protein which as a negatively charged domain which is exposed to solution. The pVIII region therefore provides the surface of

  18. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial

    SciTech Connect

    Sclafani, Francesco; Peckitt, Clare; Cunningham, David; Tait, Diana; Giralt, Jordi; Glimelius, Bengt; Keränen, Susana Roselló; Bateman, Andrew; Hickish, Tamas; Tabernero, Josep; Thomas, Janet; Brown, Gina; Oates, Jacqueline; Chau, Ian

    2015-10-01

    Objective: Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials: QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire. Results: Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery. Conclusions: Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term.

  19. Functional Characterization of Sodium-dependent Multivitamin Transporter (SMVT) in MDCK-MDR1 cells and its Utilization as a Target for Drug Delivery

    PubMed Central

    Luo, Shuanghui; Kansara, Viral S.; Zhu, Xiaodong; Pal, Dhananjay; Mitra, Ashim. K.

    2008-01-01

    The objective of this research is to characterize a sodium-dependent multivitamin transporter (SMVT) in MDCK-MDR1 cells (Madin-Darby canine kidney cells transfected with the human MDR1 gene) and to investigate the feasibility of utilizing MDCK-MDR1 cell line as an in vitro model to study the permeability of biotin-conjugated prodrugs of anti-HIV protease inhibitors. Mechanism of [3H] biotin uptake and transport was delineated. Transepithelial permeability of the biotin conjugated prodrug i.e. biotin-saquinavir was also studied. Reverse transcription-polymerase chain reaction (RT-PCR) was carried out to confirm the existence of SMVT in MDCK-MDR1 cells. Biotin uptake was Na+, pH, and temperature dependent, but energyindependent. Transepithelial transport studies of biotin-saquinavir in MDCK-MDR1, wild type MDCK, and Caco-2 cells revealed that permeability of biotin-saquinavir was similar in all three cell lines. A band of SMVT mRNA at 862 bp was identified by RT-PCR. A sodium-dependent multivitamin transporter, SMVT, responsible for biotin uptake and transport, was identified and functionally characterized in MDCK-MDR1 cells. Therefore, MDCK-MDR1 cell line may be utilized as an in vitro model to study the permeability of biotin conjugated prodrugs such as HIV protease inhibitors. PMID:16749865

  20. Expression of the T-cell surface molecule CD2 and an epitope-loss CD2 mutant to define the role of lymphocyte function-associated antigen 3 (LFA-3) in T-cell activation.

    PubMed Central

    Bierer, B E; Peterson, A; Barbosa, J; Seed, B; Burakoff, S J

    1988-01-01

    To define the role of the CD2-lymphocyte function-associated antigen 3 (LFA-3) interaction in T-cell activation, we have expressed a cDNA encoding the human CD2 molecule in a murine antigen-specific T-cell hybridoma. Expression of the CD2 molecule greatly enhances T-cell responsiveness to antigen; this enhancement is inhibited by anti-CD2 and anti-LFA-3 monoclonal antibodies (mAbs). CD2+ hybridomas produce interleukin 2 in response to combinations of anti-CD2 mAbs 9.6 and 9-1 and, in the presence of mAb 9-1, to sheep erythrocytes or to the LFA-3 antigen. Furthermore, hybridomas expressing a mutant CD2 molecule that has lost mAb 9.6 binding do not exhibit the enhanced response to antigen or the ability to respond to LFA-3 plus mAb 9-1, but these hybridomas retain the ability to respond to combinations of anti-CD2 mAbs. The role of the CD2-LFA-3 interaction in T-cell activation and the potential for other physiologic ligands for CD2 are discussed. PMID:2448792

  1. A Classroom Mathematics Utility.

    ERIC Educational Resources Information Center

    Williams, Michael

    1984-01-01

    Reviews CATUSPLOT, a mathematics utility aimed at high school algebra through college-level calculus. Basic program capabilities include plotting, tabulating, integrating, and locating of intersections of functions composed of combinations of polynomial, trigonometric, and exponential functions. Rated excellent on all areas examined…

  2. Biochemical characterization, mitochondrial localization, expression, and potential functions for an Arabidopsis γ-aminobutyrate transaminase that utilizes both pyruvate and glyoxylate

    PubMed Central

    Clark, Shawn M.; Di Leo, Rosa; Dhanoa, Preetinder K.; Van Cauwenberghe, Owen R.; Mullen, Robert T.; Shelp, Barry J.

    2009-01-01

    γ-Aminobutyrate transaminase (GABA-T) catalyses the breakdown of GABA to succinic semialdehyde. In this report, the previously identified Arabidopsis thaliana (L.) Heyhn GABA-T (AtGABA-T) was characterized in more detail. Full-length AtGABA-T contains an N-terminal 36 amino acid long targeting pre-sequence (36 amino acids) that is both sufficient and necessary for targeting the enzyme to mitochondria. Removal of the pre-sequence encoding this N-terminal targeting domain and co-expression of the resulting truncated AtGABA-T cDNA with the GroES/EL molecular chaperone complex in Escherichia coli yielded good recovery of the soluble recombinant proteins. Activity assays indicated that purified recombinant GABA-T has both pyruvate- and glyoxylate-dependent activities, but cannot utilize 2-oxoglutarate as amino acceptor. Kinetic parameters for glyoxylate- and pyruvate-dependent GABA-T activities were similar, with physiologically relevant affinities. Assays of GABA-T activity in cell-free leaf extracts from wild-type Arabidopsis and two knockout mutants in different genetic backgrounds confirmed that the native enzyme possesses both pyruvate- and glyoxylate-dependent activities. The GABA-T transcript was present throughout the plant, but its expression was highest in roots and increased as a function of leaf development. A GABA-T with dual functions suggests the potential for interaction between GABA metabolism and photorespiratory glyoxylate production. PMID:19264755

  3. 16 CFR 238.0 - Bait advertising defined. 1

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Bait advertising defined. 1 238.0 Section... BAIT ADVERTISING § 238.0 Bait advertising defined. 1 1 For the purpose of this part “advertising” includes any form of public notice however disseminated or utilized. Bait advertising is an alluring...

  4. 16 CFR 238.0 - Bait advertising defined. 1

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Bait advertising defined. 1 238.0 Section... BAIT ADVERTISING § 238.0 Bait advertising defined. 1 1 For the purpose of this part “advertising” includes any form of public notice however disseminated or utilized. Bait advertising is an alluring...

  5. 16 CFR 238.0 - Bait advertising defined. 1

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Bait advertising defined. 1 238.0 Section... BAIT ADVERTISING § 238.0 Bait advertising defined. 1 1 For the purpose of this part “advertising” includes any form of public notice however disseminated or utilized. Bait advertising is an alluring...

  6. 16 CFR 238.0 - Bait advertising defined. 1

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Bait advertising defined. 1 238.0 Section... BAIT ADVERTISING § 238.0 Bait advertising defined. 1 1 For the purpose of this part “advertising” includes any form of public notice however disseminated or utilized. Bait advertising is an alluring...

  7. 16 CFR 238.0 - Bait advertising defined. 1

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Bait advertising defined. 1 238.0 Section... BAIT ADVERTISING § 238.0 Bait advertising defined. 1 1 For the purpose of this part “advertising” includes any form of public notice however disseminated or utilized. Bait advertising is an alluring...

  8. Utility straight sections

    SciTech Connect

    Leemann, B.; Peggs, S.; Peterson, J.

    1985-10-01

    Utility straight sections are insertions in the SSC lattice to provide relatively free space to facilitate various beam manipulations. These uses include beam-abort, injection (and conceivably ejection), space for the rf system, and collimation. A typical utility straight section is 1500 meters in overall length (ranging from 500 to 1200 meters). It has zero dispersion and high values of the beta functions. The betatron phase shift across the insertion is about 90{degrees} in each plane.

  9. Evaluation of sexual function outcomes in women undergoing vaginal rejuvenation/vaginoplasty procedures for symptoms of vaginal laxity/decreased vaginal sensation utilizing validated sexual function questionnaire (PISQ-12).

    PubMed

    Moore, Robert D; Miklos, John R; Chinthakanan, Orawee

    2014-03-01

    Sexual function outcomes were analyzed in a group of women (n = 78) presenting for vaginal rejuvenation/vaginoplasty procedure for a chief complaint of vaginal laxity and decreased sensation with intercourse. Outcomes were analyzed utilizing the validated Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) before and at least 6 months after repair with vaginal rejuvenation/vaginoplasty procedure (VR). Mean age was 43.6 ± 7.9 (range 25-62), and 19 patients (24.3%) were found to have prolapse at time of initial exam and underwent vaginal vault suspension in addition to VR. Compared preoperatively and postoperatively, the overall sexual function (Total PISQ-12) statistically improved (30.3 ± 6.6 vs. 38.2 ± 5.2, P < 0.001). All individual scores statistically improved except in 3 categories in which there was no change (Q1-desire, Q5-pain, and Q11- partner premature ejaculation). Overall sexual satisfaction improved as well as subcategories of increased sexual excitement during intercourse and overall increase in intensity of orgasms. Pain with intercourse subscores were found to be no different from preoperatively to postoperatively. Previous studies have shown that sexual function improves with repair of prolapse; however, this is the first study to show improved function using a validated questionnaire in patients undergoing VR for laxity.

  10. Utilization of Electrically Reduced Neutral Red by Actinobacillus succinogenes: Physiological Function of Neutral Red in Membrane-Driven Fumarate Reduction and Energy Conservation

    PubMed Central

    Park, D. H.; Zeikus, J. G.

    1999-01-01

    Neutral red (NR) functioned as an electronophore or electron channel enabling either cells or membranes purified from Actinobacillus succinogenes to drive electron transfer and proton translocation by coupling fumarate reduction to succinate production. Electrically reduced NR, unlike methyl or benzyl viologen, bound to cell membranes, was not toxic, and chemically reduced NAD. The cell membrane of A. succinogenes contained high levels of benzyl viologen-linked hydrogenase (12.2 U), fumarate reductase (13.1 U), and diaphorase (109.7 U) activities. Fumarate reductase (24.5 U) displayed the highest activity with NR as the electron carrier, whereas hydrogenase (1.1 U) and diaphorase (0.8 U) did not. Proton translocation by whole cells was dependent on either electrically reduced NR or H2 as the electron donor and on the fumarate concentration. During the growth of Actinobacillus on glucose plus electrically reduced NR in an electrochemical bioreactor system versus on glucose alone, electrically reduced NR enhanced glucose consumption, growth, and succinate production by about 20% while it decreased acetate production by about 50%. The rate of fumarate reduction to succinate by purified membranes was twofold higher with electrically reduced NR than with hydrogen as the electron donor. The addition of 2-(n-heptyl)-4-hydroxyquinoline N-oxide to whole cells or purified membranes inhibited succinate production from H2 plus fumarate but not from electrically reduced NR plus fumarate. Thus, NR appears to replace the function of menaquinone in the fumarate reductase complex, and it enables A. succinogenes to utilize electricity as a significant source of metabolic reducing power. PMID:10198002

  11. Advanced Power Electronic Interfaces for Distributed Energy Systems, Part 2: Modeling, Development, and Experimental Evaluation of Advanced Control Functions for Single-Phase Utility-Connected Inverter

    SciTech Connect

    Chakraborty, S.; Kroposki, B.; Kramer, W.

    2008-11-01

    Integrating renewable energy and distributed generations into the Smart Grid architecture requires power electronic (PE) for energy conversion. The key to reaching successful Smart Grid implementation is to develop interoperable, intelligent, and advanced PE technology that improves and accelerates the use of distributed energy resource systems. This report describes the simulation, design, and testing of a single-phase DC-to-AC inverter developed to operate in both islanded and utility-connected mode. It provides results on both the simulations and the experiments conducted, demonstrating the ability of the inverter to provide advanced control functions such as power flow and VAR/voltage regulation. This report also analyzes two different techniques used for digital signal processor (DSP) code generation. Initially, the DSP code was written in C programming language using Texas Instrument's Code Composer Studio. In a later stage of the research, the Simulink DSP toolbox was used to self-generate code for the DSP. The successful tests using Simulink self-generated DSP codes show promise for fast prototyping of PE controls.

  12. Clarifying and Defining Library Services.

    ERIC Educational Resources Information Center

    Shubert, Joseph F., Ed.; Josey, E. J., Ed.

    1991-01-01

    This issue presents articles which, in some way, help to clarify and define library services. It is hoped that this clarification in library service will serve to secure the resources libraries need to serve the people of New York. The following articles are presented: (1) Introduction: "Clarifying and Defining Library Services" (Joseph…

  13. Paleontological evidence for defining the Anthropocene

    NASA Astrophysics Data System (ADS)

    Barnosky, A. D.

    2012-12-01

    Paleontological criteria formed the basis for defining most of the geological eras, periods, epochs, and ages that are commonly recognized. By the same token, the Anthropocene can be defined by paleontological distinctiveness in accordance with commonly accepted biostratigraphic and biochronologic practice. Here I focus on the utility of defining the Anthropocene by the distinctive fossils (or potential fossils of the future) that have accumulated and are accumulating in the sedimentary record. I discuss what kinds of biostratrigraphic criteria would be of most use in recognizing the Anthropocene's base and temporal extent, including pros and cons of definitions based on range zones, interval zones, lineage zones, assemblage zones, and abundance zones, as well as implications for potential reference sections. Key paleontological criteria useful in formally defining the Anthropocene as a geological epoch include (1) anthropogenic trace fossils such as buildings, roads, plastics, etc; (2) abundance zones based on remains of domesticated species and humans; and (3) assemblage zones based on species transported around the globe by people. The magnitude of paleontologically-recognizable changes that have occurred since humans became the dominant species on Earth is at least as great as the paleontological differences that distinguish other Cenozoic epochs, and supports recognition of the Anthropocene as a formal stratigraphic unit.

  14. Utilization management in microbiology.

    PubMed

    Branda, John A; Lewandrowski, Kent

    2014-01-01

    The available literature concerning utilization management in the clinical microbiology laboratory is relatively limited compared with that for high-volume, automated testing in the central Core Laboratory. However, the same strategies employed elsewhere in the clinical laboratory operation can be applied to utilization management challenges in microbiology, including decision support systems, application of evidence-based medicine, screening algorithms and gatekeeper functions. The results of testing in the microbiology laboratory have significant effects on the cost of clinical care, especially costs related to antimicrobial agents and infection control practices. Consequently many of the successful utilization management interventions described in clinical microbiology have targeted not just the volume of tests performed in the laboratory, but also the downstream costs of care. This article will review utilization management strategies in clinical microbiology, including specific examples from our institution and other healthcare organizations.

  15. SPAR data handling utilities

    NASA Technical Reports Server (NTRS)

    Giles, G. L.; Haftka, R. T.

    1978-01-01

    The SPAR computer software system is a collection of processors that perform particular steps in the finite-element structural analysis procedure. The data generated by each processor are stored on a data base complex residing on an auxiliary storage device, and these data are then used by subsequent processors. The SPAR data handling utilities use routines to transfer data between the processors and the data base complex. A detailed description of the data base complex organization is presented. A discussion of how these SPAR data handling utilities are used in an application program to perform desired user functions is given with the steps necessary to convert an existing program to a SPAR processor by incorporating these utilities. Finally, a sample SPAR processor is included to illustrate the use of the data handling utilities.

  16. Adaptable formations utilizing heterogeneous unmanned systems

    NASA Astrophysics Data System (ADS)

    Barnes, Laura E.; Garcia, Richard; Fields, MaryAnne; Valavanis, Kimon

    2009-05-01

    This paper addresses the problem of controlling and coordinating heterogeneous unmanned systems required to move as a group while maintaining formation. We propose a strategy to coordinate groups of unmanned ground vehicles (UGVs) with one or more unmanned aerial vehicles (UAVs). UAVs can be utilized in one of two ways: (1) as alpha robots to guide the UGVs; and (2) as beta robots to surround the UGVs and adapt accordingly. In the first approach, the UAV guides a swarm of UGVs controlling their overall formation. In the second approach, the UGVs guide the UAVs controlling their formation. The unmanned systems are brought into a formation utilizing artificial potential fields generated from normal and sigmoid functions. These functions control the overall swarm geometry. Nonlinear limiting functions are defined to provide tighter swarm control by modifying and adjusting a set of control variables forcing the swarm to behave according to set constraints. Formations derived are subsets of elliptical curves but can be generalized to any curvilinear shape. Both approaches are demonstrated in simulation and experimentally. To demonstrate the second approach in simulation, a swarm of forty UAVs is utilized in a convoy protection mission. As a convoy of UGVs travels, UAVs dynamically and intelligently adapt their formation in order to protect the convoy of vehicles as it moves. Experimental results are presented to demonstrate the approach using a fully autonomous group of three UGVs and a single UAV helicopter for coordination.

  17. Annotating user-defined abstractions for optimization

    SciTech Connect

    Quinlan, D; Schordan, M; Vuduc, R; Yi, Q

    2005-12-05

    This paper discusses the features of an annotation language that we believe to be essential for optimizing user-defined abstractions. These features should capture semantics of function, data, and object-oriented abstractions, express abstraction equivalence (e.g., a class represents an array abstraction), and permit extension of traditional compiler optimizations to user-defined abstractions. Our future work will include developing a comprehensive annotation language for describing the semantics of general object-oriented abstractions, as well as automatically verifying and inferring the annotated semantics.

  18. Burnout and health care utilization.

    PubMed

    Jackson, C N; Manning, M R

    1995-01-01

    This study explores the relationship between burnout and health care utilization of 238 employed adults. Burnout was measured by the Maslach Burnout Inventory and health care utilization by insurance company records regarding these employees' health care costs and number of times they accessed health care services over a one year period. ANOVAs were conducted using Golembiewski and Munzenrider's approach to define the burnout phase. Significant differences in health care costs were found.

  19. The Problem of Defining Intelligence.

    ERIC Educational Resources Information Center

    Lubar, David

    1981-01-01

    The major philosophical issues surrounding the concept of intelligence are reviewed with respect to the problems surrounding the process of defining and developing artificial intelligence (AI) in computers. Various current definitions and problems with these definitions are presented. (MP)

  20. Software-defined quantum communication systems

    NASA Astrophysics Data System (ADS)

    Humble, Travis S.; Sadlier, Ronald J.

    2014-08-01

    Quantum communication (QC) systems harness modern physics through state-of-the-art optical engineering to provide revolutionary capabilities. An important concern for QC engineering is designing and prototyping these systems to evaluate the proposed capabilities. We apply the paradigm of software-defined communication for engineering QC systems to facilitate rapid prototyping and prototype comparisons. We detail how to decompose QC terminals into functional layers defining hardware, software, and middleware concerns, and we describe how each layer behaves. Using the superdense coding protocol as an example, we describe implementations of both the transmitter and receiver, and we present results from numerical simulations of the behavior. We conclude that the software-defined QC provides a robust framework in which to explore the large design space offered by this new regime of communication.

  1. Defining proprioceptive behaviors for autonomous mobile robots

    NASA Astrophysics Data System (ADS)

    Overholt, James L.; Hudas, Greg R.; Gerhart, Grant R.

    2002-07-01

    Proprioception is a sense of body position and movement that supports the control of many automatic motor functions such as posture and locomotion. This concept, normally relegated to the fields of neural physiology and kinesiology, is being utilized in the field of unmanned mobile robotics. This paper looks at developing proprioceptive behaviors for use in controlling an unmanned ground vehicle. First, we will discuss the field of behavioral control of mobile robots. Next, a discussion of proprioception and the development of proprioceptive sensors will be presented. We will then focus on the development of a unique neural-fuzzy architecture that will be used to incorporate the control behaviors coming directly from the proprioceptive sensors. Finally we will present a simulation experiment where a simple multi-sensor robot, utilizing both external and proprioceptive sensors, is presented with the task of navigating an unknown terrain to a known target position. Results of the mobile robot utilizing this unique fusion methodology will be discussed.

  2. Approaches to defining deltaic sustainability in the 21st century

    NASA Astrophysics Data System (ADS)

    Day, John W.; Agboola, Julius; Chen, Zhongyuan; D'Elia, Christopher; Forbes, Donald L.; Giosan, Liviu; Kemp, Paul; Kuenzer, Claudia; Lane, Robert R.; Ramachandran, Ramesh; Syvitski, James; Yañez-Arancibia, Alejandro

    2016-12-01

    Deltas are among the most productive and economically important of global ecosystems but unfortunately they are also among the most threatened by human activities. Here we discuss deltas and human impact, several approaches to defining deltaic sustainability and present a ranking of sustainability. Delta sustainability must be considered within the context of global biophysical and socioeconomic constraints that include thermodynamic limitations, scale and embeddedness, and constraints at the level of the biosphere/geosphere. The development, functioning, and sustainability of deltas are the result of external and internal inputs of energy and materials, such as sediments and nutrients, that include delta lobe development, channel switching, crevasse formation, river floods, storms and associated waves and storm surges, and tides and other ocean currents. Modern deltas developed over the past several thousand years with relatively stable global mean sea level, predictable material inputs from drainage basins and the sea, and as extremely open systems. Human activity has changed these conditions to make deltas less sustainable, in that they are unable to persist through time structurally or functionally. Deltaic sustainability can be considered from geomorphic, ecological, and economic perspectives, with functional processes at these three levels being highly interactive. Changes in this functioning can lead to either enhanced or diminished sustainability, but most changes have been detrimental. There is a growing understanding that the trajectories of global environmental change and cost of energy will make achieving delta sustainability more challenging and limit options for management. Several delta types are identified in terms of sustainability including those in arid regions, those with high and low energy-intensive management systems, deltas below sea level, tropical deltas, and Arctic deltas. Representative deltas are ranked on a sustainability range

  3. Defined by Word and Space

    ERIC Educational Resources Information Center

    Brisco, Nicole D.

    2010-01-01

    In the author's art class, she found that many of her students in an intro art class have some technical skill, but lack the ability to think conceptually. Her goal was to create an innovative project that combined design, painting, and sculpture into a compact unit that asked students how they define themselves. In the process of answering this…

  4. Defining and Measuring Psychomotor Performance

    ERIC Educational Resources Information Center

    Autio, Ossi

    2007-01-01

    Psychomotor performance is fundamental to human existence. It is important in many real world activities and nowadays psychomotor tests are used in several fields of industry, army, and medical sciences in employee selection. This article tries to define psychomotor activity by introducing some psychomotor theories. Furthermore the…

  5. Defining "Folklore" in the Classroom.

    ERIC Educational Resources Information Center

    Falke, Anne

    Folklore, a body of traditional beliefs of a people conveyed orally or by means of custom, is very much alive, involves all people, and is not the study of popular culture. In studying folklore, the principal tasks of the folklorist have been defined as determining definition, classification, source (the folk), origin (who composed folklore),…

  6. Detectability of auditory signals presented without defined observation intervals

    NASA Technical Reports Server (NTRS)

    Watson, C. S.; Nichols, T. L.

    1976-01-01

    Ability to detect tones in noise was measured without defined observation intervals. Latency density functions were estimated for the first response following a signal and, separately, for the first response following randomly distributed instances of background noise. Detection performance was measured by the maximum separation between the cumulative latency density functions for signal-plus-noise and for noise alone. Values of the index of detectability, estimated by this procedure, were approximately those obtained with a 2-dB weaker signal and defined observation intervals. Simulation of defined- and non-defined-interval tasks with an energy detector showed that this device performs very similarly to the human listener in both cases.

  7. Evaluation of Short-Term Bioassays to Predict Functional Impairment. Development of Pulmonary Bioassays in Small Animals/Directory of Institutions/Individuals Involved in Utilization.

    DTIC Science & Technology

    1980-10-01

    PARTICLES - INHALED RADIOLABELLED FERRIC OXIDE SCANNED IN VIVO TEST SYSTEMS UTILIZED: DONKEYS COMPOUNDS TESTED: SULFURIC ACID, AMMONIUM SULFATE, SULFUR...50 ORGANIZATION: UNIVERSITY OF ROCHESTER RADIATION BIOLOGY AND BIOPHYSICS DEPARTMENT SCHOOL OF MEDICINE AND DENTISTRY ROCHESTER, NEW YORK 14642 DR...ORGANIZATION: UNIVERSITY OF UTAH SCHOOL OF MEDICINE SALT LAKE CITY, UTAH 84132 DR. SUETARO WATANABE (801) 581-7806 (CONTACT) TESTS PERFORMED

  8. Defining Our National Cyberspace Boundaries

    DTIC Science & Technology

    2010-02-17

    invention of the World Wide Web in 19 1989, the Internet Corporation for Assigned Names and Numbers ( ICANN ) (the international organization that...anonymity in cyberspace could be accomplished through the issuing of IP addresses as the Internet transitions from IPv4 to IPv6. ICANN should issue...agreement (MOA) between the U.S. Department of Commerce and ICANN . This new MOA should define which blocks of IP addresses will be used for entities

  9. How to define green adjuvants.

    PubMed

    Beck, Bert; Steurbaut, Walter; Spanoghe, Pieter

    2012-08-01

    The concept 'green adjuvants' is difficult to define. This paper formulates an answer based on two approaches. Starting from the Organisation for Economic Cooperation and Development (OECD) definition for green chemistry, production-based and environmental-impact-based definitions for green adjuvants are proposed. According to the production-based approach, adjuvants are defined as green if they are manufactured using renewable raw materials as much as possible while making efficient use of energy, preferably renewable energy. According to the environmental impact approach, adjuvants are defined as green (1) if they have a low human and environmental impact, (2) if they do not increase active ingredient environmental mobility and/or toxicity to humans and non-target organisms, (3) if they do not increase the exposure to these active substances and (4) if they lower the impact of formulated pesticides by enhancing the performance of active ingredients, thus potentially lowering the required dosage of active ingredients. Based on both approaches, a tentative definition for 'green adjuvants' is given, and future research and legislation directions are set out.

  10. Utilization of Octopine and Nopaline by Agrobacterium

    PubMed Central

    Lippincott, James A.; Beiderbeck, Rolf; Lippincott, Barbara B.

    1973-01-01

    Tests for utilization of d-octopine and nopaline in defined media containing a carbon and nitrogen source were made on 60 strains of Agrobacterium representing four species and on a representative of each of five species of Rhizobium. Among 46 virulent strains of Agrobacterium, only two strains were found which utilized neither compound, while three strains were found which could utilize both. Of the remaining virulent strains, 27 utilized octopine and 14 utilized nopaline. Each of six strains of A. rhizogenes tested utilized only octopine but at a slower rate relative to growth than most A. tumefaciens. All eight of the A. radiobacter strains failed to utilize either compound, as did four of six nonvirulent strains of A. tumefaciens. The rhizobia did not utilize octopine or, with the possible exception of R. japonicum, nopaline. Virulence in the genus Agrobacterium is concluded to be highly correlated with the ability to utilize one or both of these compounds. PMID:4745420

  11. Software-defined Quantum Communication Systems

    SciTech Connect

    Humble, Travis S; Sadlier, Ronald J

    2014-01-01

    Quantum communication systems harness modern physics through state-of-the-art optical engineering to provide revolutionary capabilities. An important concern for quantum communication engineering is designing and prototyping these systems to prototype proposed capabilities. We apply the paradigm of software-defined communica- tion for engineering quantum communication systems to facilitate rapid prototyping and prototype comparisons. We detail how to decompose quantum communication terminals into functional layers defining hardware, software, and middleware concerns, and we describe how each layer behaves. Using the super-dense coding protocol as a test case, we describe implementations of both the transmitter and receiver, and we present results from numerical simulations of the behavior. We find that while the theoretical benefits of super dense coding are maintained, there is a classical overhead associated with the full implementation.

  12. Involvement of HLA class I alleles in natural killer (NK) cell-specific functions: expression of HLA-Cw3 confers selective protection from lysis by alloreactive NK clones displaying a defined specificity (specificity 2)

    PubMed Central

    1992-01-01

    This study was designed to identify the target molecules of the natural killer (NK) cell-mediated recognition of normal allogeneic target cells. As previously shown, the gene(s) governing the first NK-defined allospecificity (specificity 1) were found to be localized in the major histocompatibility complex region between BF gene and HLA-A. In addition, the analysis of a previously described family revealed that a donor (donor 81) was heterozygous for three distinct NK-defined allospecificities (specificities 1, 2, and 5). HLA variants were derived from the B-Epstein-Barr virus cell line of donor 81 by gamma irradiation followed by negative selection using monoclonal antibodies specific for the appropriate HLA allele. Several variants were derived that lacked one or more class I antigen expressions. These variants were analyzed for the susceptibility to lysis by NK clones recognizing different allospecificities. The loss of HLA-A did not modify the phenotype (i.e., "resistance to lysis"). On the other hand, a variant lacking expression of all class I antigens became susceptible to lysis by all alloreactive clones. Variants characterized by the selective loss of class I antigens coded for by the maternal chromosome became susceptible to lysis by anti-2-specific clones. Conversely, variants selectively lacking class I antigens coded for by paternal chromosome became susceptible to lysis by anti-1 and anti-5 clones (but not by anti-2 clones). Since the Cw3 allele was lost in the variant that acquired susceptibility to lysis by anti-2 clones and, in informative families, it was found to cosegregate with the character "resistance to lysis" by anti-2 clones, we analyzed whether Cw3 could represent the element conferring selective resistance to lysis by anti-2 clones. To this end, murine P815 cells transfected with HLA Cw3 (or with other HLA class I genes) were used as target cells in a cytolytic assay in which effector cells were represented by alloreactive NK clones

  13. Defining Child Neglect Based on Child Protective Services Data

    ERIC Educational Resources Information Center

    Dubowitz, H.; Pitts, S.C.; Litrownik, A.J.; Cox, C.E.; Runyan, D.; Black, M.M.

    2005-01-01

    Objectives:: To compare neglect defined by Child Protective Services official codes with neglect defined by a review of CPS narrative data, and to examine the validity of the different neglect measures using children's functioning at age 8 years. Methods:: Data are from 740 children participating in a consortium of longitudinal studies on child…

  14. Defining life: the virus viewpoint.

    PubMed

    Forterre, Patrick

    2010-04-01

    Are viruses alive? Until very recently, answering this question was often negative and viruses were not considered in discussions on the origin and definition of life. This situation is rapidly changing, following several discoveries that have modified our vision of viruses. It has been recognized that viruses have played (and still play) a major innovative role in the evolution of cellular organisms. New definitions of viruses have been proposed and their position in the universal tree of life is actively discussed. Viruses are no more confused with their virions, but can be viewed as complex living entities that transform the infected cell into a novel organism-the virus-producing virions. I suggest here to define life (an historical process) as the mode of existence of ribosome encoding organisms (cells) and capsid encoding organisms (viruses) and their ancestors. I propose to define an organism as an ensemble of integrated organs (molecular or cellular) producing individuals evolving through natural selection. The origin of life on our planet would correspond to the establishment of the first organism corresponding to this definition.

  15. Structure-Function Dissection of Myxococcus xanthus CarD N-Terminal Domain, a Defining Member of the CarD_CdnL_TRCF Family of RNA Polymerase Interacting Proteins

    PubMed Central

    Bernal-Bernal, Diego; Gallego-García, Aránzazu; García-Martínez, Gema; García-Heras, Francisco; Jiménez, María Angeles; Padmanabhan, S.; Elías-Arnanz, Montserrat

    2015-01-01

    Two prototypes of the large CarD_CdnL_TRCF family of bacterial RNA polymerase (RNAP)-binding proteins, Myxococcus xanthus CarD and CdnL, have distinct functions whose molecular basis remain elusive. CarD, a global regulator linked to the action of several extracytoplasmic function (ECF) σ-factors, binds to the RNAP β subunit (RNAP-β) and to protein CarG via an N-terminal domain, CarDNt, and to DNA via an intrinsically unfolded C-terminal domain resembling eukaryotic high-mobility-group A (HMGA) proteins. CdnL, a CarDNt-like protein that is essential for cell viability, is implicated in σA-dependent rRNA promoter activation and interacts with RNAP-β but not with CarG. While the HMGA-like domain of CarD by itself is inactive, we find that CarDNt has low but observable ability to activate ECF σ-dependent promoters in vivo, indicating that the C-terminal DNA-binding domain is required to maximize activity. Our structure-function dissection of CarDNt reveals an N-terminal, five-stranded β -sheet Tudor-like domain, CarD1–72, whose structure and contacts with RNAP-β mimic those of CdnL. Intriguingly, and in marked contrast to CdnL, CarD mutations that disrupt its interaction with RNAP-β did not annul activity. Our data suggest that the CarDNt C-terminal segment, CarD61–179, may be structurally distinct from its CdnL counterpart, and that it houses at least two distinct and crucial function determinants: (a) CarG-binding, which is specific to CarD; and (b) a basic residue stretch, which is also conserved and functionally required in CdnL. This study highlights the evolution of shared and divergent interactions in similar protein modules that enable the distinct activities of two related members of a functionally important and widespread bacterial protein family. PMID:25811865

  16. Chloromethane Utilization Gene Cluster from Hyphomicrobium chloromethanicum Strain CM2T and Development of Functional Gene Probes To Detect Halomethane-Degrading Bacteria

    PubMed Central

    McAnulla, Craig; Woodall, Claire A.; McDonald, Ian R.; Studer, Alex; Vuilleumier, Stephane; Leisinger, Thomas; Murrell, J. Colin

    2001-01-01

    Hyphomicrobium chloromethanicum CM2T, an aerobic methylotrophic member of the α subclass of the class proteobacteria, can grow with chloromethane as the sole carbon and energy source. H. chloromethanicum possesses an inducible enzyme system for utilization of chloromethane, in which two polypeptides (67-kDa CmuA and 35-kDa CmuB) are expressed. Previously, four genes, cmuA, cmuB, cmuC, and purU, were shown to be essential for growth of Methylobacterium chloromethanicum on chloromethane. The cmuA and cmuB genes were used as probes to identify homologs in H. chloromethanicum. A cmu gene cluster (9.5 kb) in H. chloromethanicum contained 10 open reading frames: folD (partial), pduX, orf153, orf207, orf225, cmuB, cmuC, cmuA, fmdB, and paaE (partial). CmuA from H. chloromethanicum (67 kDa) showed high identity to CmuA from M. chloromethanicum and contains an N-terminal methyltransferase domain and a C-terminal corrinoid-binding domain. CmuB from H. chloromethanicum is related to a family of methyl transfer proteins and to the CmuB methyltransferase from M. chloromethanicum. CmuC from H. chloromethanicum shows identity to CmuC from M. chloromethanicum and is a putative methyltransferase. folD codes for a methylene-tetrahydrofolate cyclohydrolase, which may be involved in the C1 transfer pathway for carbon assimilation and CO2 production, and paaE codes for a putative redox active protein. Molecular analyses and some preliminary biochemical data indicated that the chloromethane utilization pathway in H. chloromethanicum is similar to the corrinoid-dependent methyl transfer system in M. chloromethanicum. PCR primers were developed for successful amplification of cmuA genes from newly isolated chloromethane utilizers and enrichment cultures. PMID:11133460

  17. A comparison of the sensitivity of EQ-5D, SF-6D and TTO utility values to changes in vision and perceived visual function in patients with primary open-angle glaucoma

    PubMed Central

    2012-01-01

    Background Economic viability of treatments for primary open-angle glaucoma (POAG) should be assessed objectively to prioritise health care interventions. This study aims to identify the methods for eliciting utility values (UVs) most sensitive to differences in visual field and visual functioning in patients with POAG. As a secondary objective, the dimensions of generic health-related and vision-related quality of life most affected by progressive vision loss will be identified. Methods A total of 132 POAG patients were recruited. Three sets of utility values (EuroQoL EQ-5D, Short Form SF-6D, Time Trade Off) and a measure of perceived visual functioning from the National Eye Institute Visual Function Questionnaire (VFQ-25) were elicited during face-to-face interviews. The sensitivity of UVs to differences in the binocular visual field, visual acuity and visual functioning measures was analysed using non-parametric statistical methods. Results Median utilities were similar across Integrated Visual Field score quartiles for EQ-5D (P = 0.08) whereas SF-6D and Time-Trade-Off UVs significantly decreased (p = 0.01 and p = 0.001, respectively). The VFQ-25 score varied across Integrated Visual Field and binocular visual acuity groups and was associated with all three UVs (P ≤ 0.001); most of its vision-specific sub-scales were associated with the vision markers. The most affected dimension was driving. A relationship with vision markers was found for the physical component of SF-36 and not for any dimension of EQ-5D. Conclusions The Time-Trade-Off was more sensitive than EQ-5D and SF-6D to changes in vision and visual functioning associated with glaucoma progression but could not measure quality of life changes in the mildest disease stages. PMID:22909264

  18. Defining Life: Synthesis and Conclusions

    NASA Astrophysics Data System (ADS)

    Gayon, Jean

    2010-04-01

    The first part of the paper offers philosophical landmarks on the general issue of defining life. §1 defends that the recognition of “life” has always been and remains primarily an intuitive process, for the scientist as for the layperson. However we should not expect, then, to be able to draw a definition from this original experience, because our cognitive apparatus has not been primarily designed for this. §2 is about definitions in general. Two kinds of definition should be carefully distinguished: lexical definitions (based upon current uses of a word), and stipulative or legislative definitions, which deliberately assign a meaning to a word, for the purpose of clarifying scientific or philosophical arguments. The present volume provides examples of these two kinds of definitions. §3 examines three traditional philosophical definitions of life, all of which have been elaborated prior to the emergence of biology as a specific scientific discipline: life as animation (Aristotle), life as mechanism, and life as organization (Kant). All three concepts constitute a common heritage that structures in depth a good deal of our cultural intuitions and vocabulary any time we try to think about “life”. The present volume offers examples of these three concepts in contemporary scientific discourse. The second part of the paper proposes a synthesis of the major debates developed in this volume. Three major questions have been discussed. A first issue (§4) is whether we should define life or not, and why. Most authors are skeptical about the possibility of defining life in a strong way, although all admit that criteria are useful in contexts such as exobiology, artificial life and the origins of life. §5 examines the possible kinds of definitions of life presented in the volume. Those authors who have explicitly defended that a definition of life is needed, can be classified into two categories. The first category (or standard view) refers to two conditions

  19. Functional genomics of commercial baker's yeasts that have different abilities for sugar utilization and high-sucrose tolerance under different sugar conditions.

    PubMed

    Tanaka-Tsuno, Fumiko; Mizukami-Murata, Satomi; Murata, Yoshinori; Nakamura, Toshihide; Ando, Akira; Takagi, Hiroshi; Shima, Jun

    2007-10-01

    In the modern baking industry, high-sucrose-tolerant (HS) and maltose-utilizing (LS) yeast were developed using breeding techniques and are now used commercially. Sugar utilization and high-sucrose tolerance differ significantly between HS and LS yeasts. We analysed the gene expression profiles of HS and LS yeasts under different sucrose conditions in order to determine their basic physiology. Two-way hierarchical clustering was performed to obtain the overall patterns of gene expression. The clustering clearly showed that the gene expression patterns of LS yeast differed from those of HS yeast. Quality threshold clustering was used to identify the gene clusters containing upregulated genes (cluster 1) and downregulated genes (cluster 2) under high-sucrose conditions. Clusters 1 and 2 contained numerous genes involved in carbon and nitrogen metabolism, respectively. The expression level of the genes involved in the metabolism of glycerol and trehalose, which are known to be osmoprotectants, in LS yeast was higher than that in HS yeast under sucrose concentrations of 5-40%. No clear correlation was found between the expression level of the genes involved in the biosynthesis of the osmoprotectants and the intracellular contents of the osmoprotectants. The present gene expression data were compared with data previously reported in a comprehensive analysis of a gene deletion strain collection. Welch's t-test for this comparison showed that the relative growth rates of the deletion strains whose deletion occurred in genes belonging to cluster 1 were significantly higher than the average growth rates of all deletion strains.

  20. Smooth Pursuit of Flicker-Defined Motion

    NASA Technical Reports Server (NTRS)

    Mulligan, Jeffrey B.; Stevenson, Scott B.

    2014-01-01

    We examined the pursuit response to stimuli defined by space-variant flicker of a dense random dot carrier pattern. On each frame, every element of the pattern could change polarity, with a probability given by a two-dimensional Gaussian distribution. A normal distribution produces a circular region of twinkle, while inverting the distribution results in a spot of static texture in a twinkling surround. In this latter case, the carrier texture could be stationary, or could move with the twinkle modulator, thereby producing first-order motion in the region of the spot. While the twinkle-defined spot produces a strong sensation of motion, the complementary stimulus defined by the absence of twinkle does not, when viewed peripherally, it appears to move in steps even when the generating distribution moves smoothly. We examined pursuit responses to these stimuli using two techniques: 1) the eye movement correlogram, obtained by cross-correlating eye velocity with the velocity of a randomly-moving stimulus; and 2) delayed visual feedback, where transient stabilization of a target can produce spontaneous oscillations of the eye, with a period empirically observed to vary linearly with the applied delay. Both techniques provide an estimate of the internal processing time, which can be as short as 100 milliseconds for a first-order target. Assessed by the correlogram method, the response to flicker-defined motion is delayed by more than 100 milliseconds, and significantly weaker (especially in the vertical dimension). When initially presented in the delayed feedback condition, purely saccadic oscillation is observed. One subject eventually developed smooth oscillations (albeit with significant saccadic intrusions), showing a period-versus-delay slope similar to that observed for first-order targets. This result is somewhat surprising, given that we interpret the slope of the period-versus-delay-function as reflecting the balance between position- and velocity

  1. Hamiltonians defined by biorthogonal sets

    NASA Astrophysics Data System (ADS)

    Bagarello, Fabio; Bellomonte, Giorgia

    2017-04-01

    In some recent papers, studies on biorthogonal Riesz bases have found renewed motivation because of their connection with pseudo-Hermitian quantum mechanics, which deals with physical systems described by Hamiltonians that are not self-adjoint but may still have real point spectra. Also, their eigenvectors may form Riesz, not necessarily orthonormal, bases for the Hilbert space in which the model is defined. Those Riesz bases allow a decomposition of the Hamiltonian, as already discussed in some previous papers. However, in many physical models, one has to deal not with orthonormal bases or with Riesz bases, but just with biorthogonal sets. Here, we consider the more general concept of G -quasi basis, and we show a series of conditions under which a definition of non-self-adjoint Hamiltonian with purely point real spectra is still possible.

  2. Defining biocultural approaches to conservation.

    PubMed

    Gavin, Michael C; McCarter, Joe; Mead, Aroha; Berkes, Fikret; Stepp, John Richard; Peterson, Debora; Tang, Ruifei

    2015-03-01

    We contend that biocultural approaches to conservation can achieve effective and just conservation outcomes while addressing erosion of both cultural and biological diversity. Here, we propose a set of guidelines for the adoption of biocultural approaches to conservation. First, we draw lessons from work on biocultural diversity and heritage, social-ecological systems theory, integrated conservation and development, co-management, and community-based conservation to define biocultural approaches to conservation. Second, we describe eight principles that characterize such approaches. Third, we discuss reasons for adopting biocultural approaches and challenges. If used well, biocultural approaches to conservation can be a powerful tool for reducing the global loss of both biological and cultural diversity.

  3. Energy Velocity Defined by Brillouin

    NASA Astrophysics Data System (ADS)

    Hosono, Hiroyuki; Hosono, Toshio

    The physical meaning of the energy velocity in lossy Lorentz media is clarified. First, two expressions for the energy velocity, one by Brillouin and another by Diener, are examined. We show that, while Diener's is disqualified, Brillouin's is acceptable as energy velocity. Secondly, we show that the signal velocity defined by Brillouin and Baerwald is exactly identical with the Brillouin's energy velocity. Thirdly, by using triangle-modulated harmonic wave, we show that the superluminal group velocity plays its role as a revelator only after the arrival of the signal traveling at the subluminal energy velocity. In short, nothing moves at the group velocity, and every frequency component of a signal propagates at its own energy velocity.

  4. Using Bayesian Population Viability Analysis to Define Relevant Conservation Objectives

    PubMed Central

    Green, Adam W.; Bailey, Larissa L.

    2015-01-01

    Adaptive management provides a useful framework for managing natural resources in the face of uncertainty. An important component of adaptive management is identifying clear, measurable conservation objectives that reflect the desired outcomes of stakeholders. A common objective is to have a sustainable population, or metapopulation, but it can be difficult to quantify a threshold above which such a population is likely to persist. We performed a Bayesian metapopulation viability analysis (BMPVA) using a dynamic occupancy model to quantify the characteristics of two wood frog (Lithobates sylvatica) metapopulations resulting in sustainable populations, and we demonstrate how the results could be used to define meaningful objectives that serve as the basis of adaptive management. We explored scenarios involving metapopulations with different numbers of patches (pools) using estimates of breeding occurrence and successful metamorphosis from two study areas to estimate the probability of quasi-extinction and calculate the proportion of vernal pools producing metamorphs. Our results suggest that ≥50 pools are required to ensure long-term persistence with approximately 16% of pools producing metamorphs in stable metapopulations. We demonstrate one way to incorporate the BMPVA results into a utility function that balances the trade-offs between ecological and financial objectives, which can be used in an adaptive management framework to make optimal, transparent decisions. Our approach provides a framework for using a standard method (i.e., PVA) and available information to inform a formal decision process to determine optimal and timely management policies. PMID:26658734

  5. Miniature EVA Software Defined Radio

    NASA Technical Reports Server (NTRS)

    Pozhidaev, Aleksey

    2012-01-01

    As NASA embarks upon developing the Next-Generation Extra Vehicular Activity (EVA) Radio for deep space exploration, the demands on EVA battery life will substantially increase. The number of modes and frequency bands required will continue to grow in order to enable efficient and complex multi-mode operations including communications, navigation, and tracking applications. Whether conducting astronaut excursions, communicating to soldiers, or first responders responding to emergency hazards, NASA has developed an innovative, affordable, miniaturized, power-efficient software defined radio that offers unprecedented power-efficient flexibility. This lightweight, programmable, S-band, multi-service, frequency- agile EVA software defined radio (SDR) supports data, telemetry, voice, and both standard and high-definition video. Features include a modular design, an easily scalable architecture, and the EVA SDR allows for both stationary and mobile battery powered handheld operations. Currently, the radio is equipped with an S-band RF section. However, its scalable architecture can accommodate multiple RF sections simultaneously to cover multiple frequency bands. The EVA SDR also supports multiple network protocols. It currently implements a Hybrid Mesh Network based on the 802.11s open standard protocol. The radio targets RF channel data rates up to 20 Mbps and can be equipped with a real-time operating system (RTOS) that can be switched off for power-aware applications. The EVA SDR's modular design permits implementation of the same hardware at all Network Nodes concept. This approach assures the portability of the same software into any radio in the system. It also brings several benefits to the entire system including reducing system maintenance, system complexity, and development cost.

  6. Benthic Habitat-Based Framework for Ecological Production Functions: Case Study for Utilization by Estuarine Birds in a Northeast Pacific Estuary

    EPA Science Inventory

    Habitat-based frameworks have been proposed for developing Ecological Production Functions (EPFs) to describe the spatial distribution of ecosystem services. As proof of concept, we generated EPFs that compared bird use patterns among intertidal benthic habitats for Yaquina estu...

  7. Greater Utilization of Neural-Circuits Related to Executive Functions is Associated with Better Reading: A Longitudinal fMRI Study Using the Verb Generation Task

    PubMed Central

    Horowitz-Kraus, Tzipi; Vannest, Jennifer J.; Gozdas, Elveda; Holland, Scott K.

    2014-01-01

    Introduction: Reading is an acquired-developmental ability that relies on intact language and executive function skills. Verbal fluency tasks (such as verb generation) also engage language and executive function skills. Performance of such tasks matures with normal language development, and is independent of reading proficiency. In this longitudinal fMRI study, we aim to examine the association between maturation of neural-circuits supporting both executive functions and language (assessed using verb generation) with reading proficiency achieved in adolescence with a focus on left-lateralization typical for language proficiency. Methods: Normalized fMRI data from the verb generation task was collected from 16 healthy children at ages 7, 11, and 17 years and was correlated with reading scores at 17 years of age. Lateralization indices were calculated in key language, reading, and executive function-related regions in all age groups. Results: Typical development was associated with (i) increasingly left-lateralized patterns in language regions (ii) more profound left-lateralized activation for reading and executive function-related regions when correlating with reading scores, (iii) greater involvement of frontal and parietal regions (in older children), and of the anterior frontal cortex (in younger children). Conclusion: We suggest that reading and verb generation share mutual neural-circuits during development with major reliance on regions related to executive functions and reading. The results are discussed in the context of the dual-networks architecture model. PMID:24999322

  8. Frequency analysis of functional immunoglobulin C- and V-gene expression by mitogen-reactive B cells in germfree mice fed chemically defined ultra-filtered "antigen-free" diet.

    PubMed

    Hooijkaas, H; van der Linde-Preesman, A A; Bitter, W M; Benner, R; Pleasants, J R; Wostmann, B S

    1985-04-01

    The frequencies of lipopolysaccharide (LPS)-reactive B cells and their antibody specificity repertoire have been determined in the spleen and bone marrow (BM) of conventional (CV) and "antigen-free" C3H/HeCr mice of various ages. The antigen-free mice were germfree (GF)-raised and were fed an ultrafiltered solution of chemically defined (CD) low m.w. nutrients, and were thus devoid of exogenous antigenic stimulation. Spleen and BM cells were grown in a limiting dilution culture system that allows the growth and development of every newly formed LPS-reactive B cell into a clone of IgM-secreting cells which are capable of switching to other immunoglobulin (Ig) heavy chain isotypes (C-gene expression). The secretion of IgM and IgG1 was determined in the protein A plaque assay, whereas specific IgM antibody-secreting cells (V-gene expression) were detected in plaque assays specific for various heterologous erythrocytes and sheep red blood cells (SRBC) coupled with a number of different haptens. The absolute frequency of LPS-reactive B cells and their capacity to switch to IgG1-secretion was not significantly different in 8- to 12-wk-old and 52-wk-old GF-CD mice and their age-matched CV controls. Moreover, no differences were observed in the frequencies of antigen-specific B cells within the pool of LPS reactive B cells. These frequencies ranged from 1 in 20 to 1 in 50 for NIP4-SRBC and NNP2-SRBC, from 1 in 100 to 1 in 150 for NIP0.4-SRBC, from 1 in 50 to 1 in 100 for TNP30-SRBC, and from 1 in 1000 to 1 in 2000 for SRBC and horse red blood cells. Within the limitations of having determined the switching capacity of IgM to IgG1 only and having assessed only a minor fraction of the total B cell antibody-specificity repertoire, the data indicate that young and old GF-CD mice, although devoid of exogenous antigenic and/or mitogenic stimulation, generate B cells with a similar switching capacity and a similar IgM antibody specificity repertoire as CV mice.

  9. Utility of Language Comprehension Tests for Unintelligible or Non-Speaking Children with Cerebral Palsy: A Systematic Review

    ERIC Educational Resources Information Center

    Geytenbeek, Joke; Harlaar, Laurike; Stam, Marloes; Ket, Hans; Becher, Jules G.; Oostrom, Kim; Vermeulen, Jeroen

    2010-01-01

    Aim: To identify the use and utility of language comprehension tests for unintelligible or non-speaking children with severe cerebral palsy (CP). Method: Severe CP was defined as severe dysarthria (unintelligible speech) or anarthria (absence of speech) combined with severe limited mobility, corresponding to Gross Motor Function Classification…

  10. Functional Analysis of Two l-Arabinose Transporters from Filamentous Fungi Reveals Promising Characteristics for Improved Pentose Utilization in Saccharomyces cerevisiae.

    PubMed

    Li, Jingen; Xu, Jing; Cai, Pengli; Wang, Bang; Ma, Yanhe; Benz, J Philipp; Tian, Chaoguang

    2015-06-15

    Limited uptake is one of the bottlenecks for l-arabinose fermentation from lignocellulosic hydrolysates in engineered Saccharomyces cerevisiae. This study characterized two novel l-arabinose transporters, LAT-1 from Neurospora crassa and MtLAT-1 from Myceliophthora thermophila. Although the two proteins share high identity (about 83%), they display different substrate specificities. Sugar transport assays using the S. cerevisiae strain EBY.VW4000 indicated that LAT-1 accepts a broad substrate spectrum. In contrast, MtLAT-1 appeared much more specific for l-arabinose. Determination of the kinetic properties of both transporters revealed that the Km values of LAT-1 and MtLAT-1 for l-arabinose were 58.12 ± 4.06 mM and 29.39 ± 3.60 mM, respectively, with corresponding Vmax values of 116.7 ± 3.0 mmol/h/g dry cell weight (DCW) and 10.29 ± 0.35 mmol/h/g DCW, respectively. In addition, both transporters were found to use a proton-coupled symport mechanism and showed only partial inhibition by d-glucose during l-arabinose uptake. Moreover, LAT-1 and MtLAT-1 were expressed in the S. cerevisiae strain BSW2AP containing an l-arabinose metabolic pathway. Both recombinant strains exhibited much faster l-arabinose utilization, greater biomass accumulation, and higher ethanol production than the control strain. In conclusion, because of higher maximum velocities and reduced inhibition by d-glucose, the genes for the two characterized transporters are promising targets for improved l-arabinose utilization and fermentation in S. cerevisiae.

  11. Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes.

    PubMed

    Maranzana, Andrea; Giordana, Anna; Indarto, Antonius; Tonachini, Glauco; Barone, Vincenzo; Causà, Mauro; Pavone, Michele

    2013-12-28

    Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔEAB. Counterpoise-corrected interaction energies ΔEAB are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A-B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [EMP2/CBS] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔECC-MP, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔEAB with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting deviation from the computational

  12. Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes

    SciTech Connect

    Maranzana, Andrea E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it Giordana, Anna E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it Indarto, Antonius Tonachini, Glauco; Barone, Vincenzo E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it; Causà, Mauro E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it; Pavone, Michele E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it

    2013-12-28

    Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔE{sub AB}. Counterpoise-corrected interaction energies ΔE{sub AB} are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A−B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [E{sub MP2/CBS}] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔE{sub CC-MP}, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔE{sub AB} with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting

  13. Symptomatic improvement in function and disease activity in a patient with ankylosing spondylitis utilizing a course of chiropractic therapy: a prospective case study

    PubMed Central

    Rutherford, Susan M; Nicolson, Cameron F; Crowther, Edward R

    2005-01-01

    Background There is limited outcome measure support for chiropractic manipulative therapy in the management of ankylosing spondylitis. An improvement in specific indices for both function and disease activity during chiropractic therapy for ankylosing spondylitis has not previously been reported. Objective To measure changes in function and disease activity in a patient with ankylosing spondylitis during a course of chiropractic therapy. The clinical management of ankylosing spondylitis, including chiropractic manipulative therapy and the implications of this case study are discussed. Clinical Features A 34-year-old male with a 10 year diagnosis of ankylosing spondylitis sought chiropractic treatment for spinal pain and stiffness. His advanced radiographic signs included an increased atlantodental interspace and cervical vertebral ankylosis. Intervention and outcome The Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), finger-tip-to-floor distance and chest expansion were assessed during an 18 week course of chiropractic spinal manipulation and mobilization therapy. There was a 90% improvement in the disease activity index and an 85% improvement in the functional index from the pre-treatment baseline, as measured by the BASDAI and BASFI respectively. Spinal flexibility and chest expansion also improved. Conclusion To the authors knowledge this is the first study to incorporate ankylosing spondylitis specific indices, for both disease activity and function, to objectively support the use of chiropractic manipulative therapy in the management of ankylosing spondylitis. More intensive research is suggested. PMID:17549197

  14. Defining risk in aerospace medical unconsciousness research.

    PubMed

    Whinnery, J E

    1989-07-01

    The maneuverability envelopes of current and future fighter/attack aircraft exceed unprotected human tolerance to environmental stress. Human exposure to unconsciousness therefore can result not only inflight, but in research and training laboratories which endeavor to provide methods of enhanced protection for aircrew. Solving the problem of unconsciousness requires a thorough understanding of the phenomenon itself. This can only be accomplished by defining the psychophysiologic aspects of unconsciousness and techniques to prevent its occurrence or enhance recovery, should it occur. The safety of experimental human exposure to G-LOC however, remains of some concern. A framework for discussing the relative insult to the central nervous system may be constructed from what is currently known about G-LOC. The results of animal experimentation allow an estimation of the central nervous system tolerance to hypoxia without permanent alteration of tissue integrity. Clinical medicine documentation of syncope and fainting episodes, coupled with a long history of uncomplicated G-LOC episodes suggests that a certain window of safe exposure exists. Utilization of G-LOC as an endpoint included exposure of very large numbers of humans to unconsciousness without significant complication. Animal experimentation suggests that 180 s of central nervous system hypoxia is associated with uncomplicated recovery. Human exposure as long as 100 s has also been safely accomplished. Centrifuge G-LOC exposure typically results in only 15-20 s of central nervous system hypoxia. As long as G-LOC experimentation using humans is performed within well defined limits, it may be accomplished within an acceptable risk envelope.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Coming utility squeeze play

    SciTech Connect

    Stoiaken, L.N.

    1988-02-01

    Like a sleeping giant, utilities are waking up and preparing to participate in the increasingly competitive power production industry. Some are establishing subsidiaries to participate in join venture deals with independents. Others are competing by offering lucrative discount or deferral rates to important industrial and commercial customers considering cogeneration. And now, a third approach is beginning to shape up- the disaggregation of generation assets into a separate generation company, or genco. This article briefly discusses these three and also devotes brief sections to functional segmentation and The regulatory arena.

  16. Classical subjective expected utility

    PubMed Central

    Cerreia-Vioglio, Simone; Maccheroni, Fabio; Marinacci, Massimo; Montrucchio, Luigi

    2013-01-01

    We consider decision makers who know that payoff-relevant observations are generated by a process that belongs to a given class M, as postulated in Wald [Wald A (1950) Statistical Decision Functions (Wiley, New York)]. We incorporate this Waldean piece of objective information within an otherwise subjective setting à la Savage [Savage LJ (1954) The Foundations of Statistics (Wiley, New York)] and show that this leads to a two-stage subjective expected utility model that accounts for both state and model uncertainty. PMID:23559375

  17. Defining the Stimulus - A Memoir

    PubMed Central

    Terrace, Herbert

    2010-01-01

    The eminent psychophysicist, S. S. Stevens, once remarked that, “the basic problem of psychology was the definition of the stimulus” (Stevens, 1951, p. 46). By expanding the traditional definition of the stimulus, the study of animal learning has metamorphosed into animal cognition. The main impetus for that change was the recognition that it is often necessary to postulate a representation between the traditional S and R of learning theory. Representations allow a subject to re-present a stimulus it learned previously that is currently absent. Thus, in delayed-matching-to-sample, one has to assume that a subject responds to a representation of the sample during test if it responds correctly. Other examples, to name but a few, include concept formation, spatial memory, serial memory, learning a numerical rule, imitation and metacognition. Whereas a representation used to be regarded as a mentalistic phenomenon that was unworthy of scientific inquiry, it can now be operationally defined. To accommodate representations, the traditional discriminative stimulus has to be expanded to allow for the role of representations. The resulting composite can account for a significantly larger portion of the variance of performance measures than the exteroceptive stimulus could by itself. PMID:19969047

  18. Defining reclaimed water potability requirements

    NASA Technical Reports Server (NTRS)

    Janik, D. S.

    1986-01-01

    Water used during previous space missions has been either carried or made aloft. Future human space endeavors will probably have to utilize some form of water reclamation and recycling. There is little applied experience in either the US or foreign space programs with this technology. Water reclamation and recycling constitutes an engineering challenge of the broadest nature and will require an intensive research and development effort if this technology is to mature in time for practical use on the proposed US spacestation. In order for this to happen, reclaimed/recycled water specification will need to be devised to guide engineering development. Perhaps the most strigent specifications will involve water to be consumed. NASA's present Potable Water Specifications are not applicable to reclaimed or recycled potable water. No specifications for reclaimed or recycled potable water presently exist either inside or outside NASA. NASA's past experience with potable water systems is reviewed, limitations of the present Potable Water Specifications are examined, present world expertise with potable water reclamation/recycling systems and system analogs is reviewed, and an approach to developing pertinent Reclaimed/Recycled Potable Water Specifications for spacecraft is presented.

  19. PF1: an A-T hook-containing DNA binding protein from rice that interacts with a functionally defined d(AT)-rich element in the oat phytochrome A3 gene promoter.

    PubMed Central

    Nieto-Sotelo, J; Ichida, A; Quail, P H

    1994-01-01

    Phytochrome-imposed down-regulation of the expression of its own phytochrome A gene (PHYA) is one of the fastest light-induced effects on transcription reported in plants to date. Functional analysis of the oat PHYA3 promoter in a transfection assay has revealed two positive elements, PE1 and PE3, that function synergistically to support high levels of transcription in the absence of light. We have isolated a rice cDNA clone (pR4) encoding a DNA binding protein that binds to the AT-rich PE1 element. We tested the selectivity of the pR4-encoded DNA binding activity using linker substitution mutations of PE1 that are known to disrupt positive expression supported by the PHYA3 promoter in vivo. Binding to these linker substitution mutants was one to two orders of magnitude less than to the native PE1 element. Because this is the behavior expected of positive factor 1 (PF1), the presumptive nuclear transcription factor that acts in trans at the PE1 element in vivo, the data support the conclusion that the protein encoded by pR4 is in fact rice PF1. The PF1 polypeptide encoded by pR4 is 213 amino acids long and contains four repeats of the A-T hook DNA binding motif found in high-mobility group I-Y (HMGI-Y) proteins. In addition, PF1 contains an 11-amino acid-long hydrophobic region characteristic of HMG I proteins, its N-terminal region shows strong similarities to a pea H1 histone sequence and a short peptide sequence from wheat HMGa, and it shows a high degree of similarity along its entire length to the HMG Y-like protein encoded by a soybean cDNA, SB16. In vitro footprinting and quantitative gel shift analyses showed that PF1 binds preferentially to the PE1 element but also at lower affinity to two other AT-rich regions upstream of PE1. This feature is consistent with the binding characteristics of HMG I-Y proteins that are known to bind to most runs of six or more AT base pairs. Taken together, the properties of PF1 suggest that it belongs to a newly described

  20. Number series of atoms, interatomic bonds and interface bonds defining zinc-blende nanocrystals as function of size, shape and surface orientation: Analytic tools to interpret solid state spectroscopy data

    NASA Astrophysics Data System (ADS)

    König, Dirk

    2016-08-01

    Semiconductor nanocrystals (NCs) experience stress and charge transfer by embedding materials or ligands and impurity atoms. In return, the environment of NCs experiences a NC stress response which may lead to matrix deformation and propagated strain. Up to now, there is no universal gauge to evaluate the stress impact on NCs and their response as a function of NC size dNC. I deduce geometrical number series as analytical tools to obtain the number of NC atoms NNC(dNC[i]), bonds between NC atoms Nbnd(dNC[i]) and interface bonds NIF(dNC[i]) for seven high symmetry zinc-blende (zb) NCs with low-index faceting: {001} cubes, {111} octahedra, {110} dodecahedra, {001}-{111} pyramids, {111} tetrahedra, {111}-{001} quatrodecahedra and {001}-{111} quadrodecahedra. The fundamental insights into NC structures revealed here allow for major advancements in data interpretation and understanding of zb- and diamond-lattice based nanomaterials. The analytical number series can serve as a standard procedure for stress evaluation in solid state spectroscopy due to their deterministic nature, easy use and general applicability over a wide range of spectroscopy methods as well as NC sizes, forms and materials.

  1. Health-Related Quality of Life and Cognitive Functioning from the Perspective of Parents of School-Aged Children with Asperger's Syndrome Utilizing the PedsQL[TM

    ERIC Educational Resources Information Center

    Limbers, Christine A.; Heffer, Robert W.; Varni, James W.

    2009-01-01

    HRQOL as a multidimensional construct has not been previously investigated in children with Asperger's Syndrome. The objective of the present study was to examine the initial feasibility, reliability, and validity of the PedsQL[TM] 4.0 Generic Core Scales and PedsQL[TM] Cognitive Functioning Scale parent proxy-report versions in school-aged…

  2. Study of the thickness effect on the dielectric functions by utilizing a wedge-shaped Ti film sample with continuously varied thickness

    NASA Astrophysics Data System (ADS)

    Hu, Er-Tao; Zhang, Rong-Jun; Cai, Qing-Yuan; Wang, Zi-Yi; Xu, Ji-Ping; Zheng, Yu-Xiang; Wang, Song-You; Wei, Yan-Feng; Huang, Ren-Zhong; Chen, Liang-Yao

    2015-09-01

    The dielectric functions of direct-current-sputtered wedge-shaped ultrathin titanium (Ti) film on K9 glass were investigated in this paper. The wedge-shaped Ti thin film was deposited under the identical conditions with continuously varied thickness. Atomic force microscope revealed that the thin film surface was very smooth with the surface roughness of about 0.5 nm. The dielectric functions of the wedge-shaped films in the wavelength range of 300-1200 nm were obtained by a focused-beam ellipsometer with the beam size on the sample about 200 μm. Results show that ɛ 1, the real part of the dielectric function, is negative almost in the whole spectrum region, proving that the film at the measured area is continuous and shows metallic behavior. On the other hand, ɛ 1 decreases with the increase in the film thickness, while ɛ 2, the imaginary part of the dielectric function, has the opposite variation tendency. The changing of ɛ 1 with film thickness is due to the reduced electron-electron interactions and enhanced metallic behavior. While for ɛ 2, it gets larger with the increase in the film thickness, which is mainly owing to the decrease in the tensile stress in the film.

  3. Exploring the Utility of Background and Cognitive Variables in Explaining Latent Differential Item Functioning: An Example of the PISA 2009 Reading Assessment

    ERIC Educational Resources Information Center

    Chen, Ying-Fang; Jiao, Hong

    2014-01-01

    Differential item functioning (DIF) may be caused by an interaction of multiple manifest grouping variables or unexplored manifest variables, which cannot be detected by conventional DIF detection methods that are based on a single manifest grouping variable. Such DIF may be detected by a latent approach using the mixture item response theory…

  4. Defining the mammalian CArGome

    PubMed Central

    Sun, Qiang; Chen, Guang; Streb, Jeffrey W.; Long, Xiaochun; Yang, Yumei; Stoeckert, Christian J.; Miano, Joseph M.

    2006-01-01

    Serum response factor (SRF) binds a 1216-fold degenerate cis element known as the CArG box. CArG boxes are found primarily in muscle- and growth-factor-associated genes although the full spectrum of functional CArG elements in the genome (the CArGome) has yet to be defined. Here we describe a genome-wide screen to further define the functional mammalian CArGome. A computational approach involving comparative genomic analyses of human and mouse orthologous genes uncovered >100 hypothetical SRF-dependent genes, including 10 previously identified SRF targets, harboring a conserved CArG element within 4000 bp of the annotated transcription start site (TSS). We PCR-cloned 89 hypothetical SRF targets and subjected each of them to at least two of several validations including luciferase reporter, gel shift, chromatin immunoprecipitation, and mRNA expression following RNAi knockdown of SRF; 60/89 (67%) of the targets were validated. Interestingly, 26 of the validated SRF target genes encode for cytoskeletal/contractile or adhesion proteins. RNAi knockdown of SRF diminishes expression of several SRF-dependent cytoskeletal genes and elicits an attending perturbation in the cytoarchitecture of both human and rodent cells. These data illustrate the power of integrating existing algorithms to interrogate the genome in a relatively unbiased fashion for cis-regulatory element discovery. In this manner, we have further expanded the mammalian CArGome with the discovery of an array of cyto-contractile genes that coordinate normal cytoskeletal homeostasis. We suggest one function of SRF is that of an ancient master regulator of the actin cytoskeleton. PMID:16365378

  5. c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction

    PubMed Central

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.

    2015-01-01

    Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction (TAC; n = 7/group). Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes. PMID:26266538

  6. The molecular basis of color vision in colorful fish: Four Long Wave-Sensitive (LWS) opsins in guppies (Poecilia reticulata) are defined by amino acid substitutions at key functional sites

    PubMed Central

    2008-01-01

    Background Comparisons of functionally important changes at the molecular level in model systems have identified key adaptations driving isolation and speciation. In cichlids, for example, long wavelength-sensitive (LWS) opsins appear to play a role in mate choice and male color variation within and among species. To test the hypothesis that the evolution of elaborate coloration in male guppies (Poecilia reticulata) is also associated with opsin gene diversity, we sequenced long wavelength-sensitive (LWS) opsin genes in six species of the family Poeciliidae. Results Sequences of four LWS opsin genes were amplified from the guppy genome and from mRNA isolated from adult guppy eyes. Variation in expression was quantified using qPCR. Three of the four genes encode opsins predicted to be most sensitive to different wavelengths of light because they vary at key amino acid positions. This family of LWS opsin genes was produced by a diversity of duplication events. One, an intronless gene, was produced prior to the divergence of families Fundulidae and Poeciliidae. Between-gene PCR and DNA sequencing show that two of the guppy LWS opsins are linked in an inverted orientation. This inverted tandem duplication event occurred near the base of the poeciliid tree in the common ancestor of Poecilia and Xiphophorus. The fourth sequence has been uncovered only in the genus Poecilia. In the guppies surveyed here, this sequence is a hybrid, with the 5' end most similar to one of the tandem duplicates and the 3' end identical to the other. Conclusion Enhanced wavelength discrimination, a possible consequence of opsin gene duplication and divergence, might have been an evolutionary prerequisite for color-based sexual selection and have led to the extraordinary coloration now observed in male guppies and in many other poeciliids. PMID:18638376

  7. Defining disability: metaphysical not political.

    PubMed

    Riddle, Christopher A

    2013-08-01

    social model, unlike an interactional approach, is unable to provide a realistic account of the experience of disability, and subsequently, unable to be properly utilized to ensure justice for people with disabilities.

  8. Utility of hesperidinase for food function research: enzymatic digestion of botanical extracts alters cellular antioxidant capacities and anti-inflammatory properties.

    PubMed

    Yu, Lu; Huang, Haiqiu; Yu, Liangli Lucy; Wang, Thomas T Y

    2014-08-27

    Food-derived phytochemicals, many known for their health beneficial effects, often exist in conjugated forms containing sugar moieties such as glucose or rhamnose in foods. The uptake of these compounds requires colonic bacterial cleavage of sugar moieties. However, most studies involved in screening extracts for biological activities do not take this process into account. This study seeks to determine the utility of commercially available hesperidinase to mimic colonic digestion and to test the effects of this treatment on the biological properties of extracts. Using hesperidinase resulted in efficient hydrolysis of Engelhardia roxburghiana Wall. extract containing rhamnose conjugates. Enzymatic digestion enhanced the extract's cellular antioxidant ability by 2-fold in HepG2/C3A and the anti-inflammatory effect on lipopolysaccharide-induced interleukin (IL)-1β and IL-6 expression in mouse macrophage J774A.1 and human monocyte THP-1 cells. Enzymatic digestion also efficiently processed extracts with mixed rhamnose and glucose conjugates and altered their biological activities. Results of the present study supported the importance of considering enzymatic digestion during the biological activity studies of botanicals.

  9. Assessing change in cognitive function in dementia: the relative utilities of the Alzheimer's Disease Assessment Scale-Cognitive Subscale and the Cognitive Drug Research system.

    PubMed

    Wesnes, Keith A

    2008-01-01

    This paper considers the suitability of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) as the gold standard in registration trials of treatments for Alzheimer's disease. Working groups have recommended replacing the ADAS-cog if suitable automated alternatives can be found. This paper makes the case for the Cognitive Drug Research (CDR) computerised cognitive assessment system, as an example of a suitable instrument to replace the ADAS-cog. The CDR system has been widely used in dementia work for 20 years and shows good correlations to the ADAS-cog, while additionally assessing the domains of attention, working memory, information processing and retrieval speed of information held in memory. The utility of the system in evaluating and differentiating the major dementias will be described, as well as its ability to track deterioration over time. Its validation as a core measure of cognitive dysfunction in the dementias will be described, as will work showing that various CDR measures relate closely to activities of daily living. The sensitivity of the CDR system to anticholinesterases will be described in Alzheimer's disease, dementia with Lewy bodies and Parkinson's dementia. Finally, the CDR system has a large normative database which allows treatment effects in dementia to be put into an unambiguous clinical perspective.

  10. Functional EpoR Pathway Utilization Is Not Detected in Primary Tumor Cells Isolated from Human Breast, Non-Small Cell Lung, Colorectal, and Ovarian Tumor Tissues

    PubMed Central

    Patterson, Scott D.; Rossi, John M.; Paweletz, Katherine L.; Fitzpatrick, V. Dan; Begley, C. Glenn; Busse, Leigh; Elliott, Steve; McCaffery, Ian

    2015-01-01

    Several clinical trials in oncology have reported increased mortality or disease progression associated with erythropoiesis-stimulating agents. One hypothesis proposes that erythropoiesis-stimulating agents directly stimulate tumor proliferation and/or survival through cell-surface receptors. To test this hypothesis and examine if human tumors utilize the erythropoietin receptor pathway, the response of tumor cells to human recombinant erythropoietin was investigated in disaggregated tumor cells obtained from 186 patients with colorectal, breast, lung, ovarian, head and neck, and other tumors. A cocktail of well characterized tumor growth factors (EGF, HGF, and IGF-1) were analyzed in parallel as a positive control to determine whether freshly-isolated tumor cells were able to respond to growth factor activation ex vivo. Exposing tumor cells to the growth factor cocktail resulted in stimulation of survival and proliferation pathways as measured by an increase in phosphorylation of the downstream signaling proteins AKT and ERK. In contrast, no activation by human recombinant erythropoietin was observed in isolated tumor cells. Though tumor samples exhibited a broad range of cell-surface expression of EGFR, c-Met, and IGF-1R, no cell-surface erythropoietin receptor was detected in tumor cells from the 186 tumors examined (by flow cytometry or Western blot). Erythropoiesis-stimulating agents did not act directly upon isolated tumor cells to stimulate pathways known to promote proliferation or survival of human tumor cells isolated from primary and metastatic tumor tissues. PMID:25807104

  11. Functional Characterization of a Marine Bacillus Esterase and its Utilization in the Stereo-Selective Production of D-Methyl Lactate.

    PubMed

    Huang, Jinlong; Zhang, Yun; Hu, Yunfeng

    2016-12-01

    Chiral lactic acid and its ester derivatives are crucial building blocks and platforms in the generation of high value-added drugs, fine chemicals and functional materials. Optically pure D-lactic acid and its ester derivatives cannot be directly generated from fermentation and are quite expensive. Herein, we identified, heterologously expressed and functionally characterized one Bacillus esterase BSE01701 from the deep sea of the Indian Ocean. Esterase BSE01701 could enzymatically resolve inexpensive racemic methyl lactate and generate chiral D-methyl lactate. The enantiomeric excess of desired chiral D-methyl lactate and the substrate conversion could reach over 99 % and 60 %, respectively, after process optimization. Notably, the addition of 60 % (v/v) organic co-solvent heptane could greatly improve both the enantiomeric excess of D-methyl lactate and the conversion. BSE01701 was a very promising marine microbial esterase in the generation of chiral chemicals in industry.

  12. Health-related quality of life and cognitive functioning from the perspective of parents of school-aged children with Asperger's Syndrome utilizing the PedsQL.

    PubMed

    Limbers, Christine A; Heffer, Robert W; Varni, James W

    2009-11-01

    HRQOL as a multidimensional construct has not been previously investigated in children with Asperger's Syndrome. The objective of the present study was to examine the initial feasibility, reliability, and validity of the PedsQL 4.0 Generic Core Scales and PedsQL Cognitive Functioning Scale parent proxy-report versions in school-aged children with Asperger's Syndrome. The PedsQL evidenced no missing responses (0.0%), achieved excellent reliability for the Generic Core Total Scale score (alpha = 0.82) and Cognitive Functioning Scale (alpha = 0.92), distinguished between children with Asperger's Syndrome and a matched sample of healthy children, and was related to similar constructs on the Asperger Syndrome Diagnostic Scale. The results demonstrate the initial measurement properties of the PedsQL in school-aged children with Asperger's Syndrome.

  13. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

    SciTech Connect

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.; Bertrand, Luc

    2015-08-12

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.

  14. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

    DOE PAGES

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; ...

    2015-08-12

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.« less

  15. Defining a Standard Metric for Electricity Savings

    SciTech Connect

    Brown, Marilyn; Akbari, Hashem; Blumstein, Carl; Koomey, Jonathan; Brown, Richard; Calwell, Chris; Carter, Sheryl; Cavanagh, Ralph; Chang, Audrey; Claridge, David; Craig, Paul; Diamond, Rick; Eto, Joseph H.; Fulkerson, William; Gadgil, Ashok; Geller, Howard; Goldemberg, Jose; Goldman, Chuck; Goldstein, David B.; Greenberg, Steve; Hafemeister, David; Harris, Jeff; Harvey, Hal; Heitz, Eric; Hirst, Eric; Hummel, Holmes; Kammen, Dan; Kelly, Henry; Laitner, Skip; Levine, Mark; Lovins, Amory; Masters, Gil; McMahon, James E.; Meier, Alan; Messenger, Michael; Millhone, John; Mills, Evan; Nadel, Steve; Nordman, Bruce; Price, Lynn; Romm, Joe; Ross, Marc; Rufo, Michael; Sathaye, Jayant; Schipper, Lee; Schneider, Stephen H; Sweeney, James L; Verdict, Malcolm; Vorsatz, Diana; Wang, Devra; Weinberg, Carl; Wilk, Richard; Wilson, John; Worrell, Ernst

    2009-03-01

    The growing investment by governments and electric utilities in energy efficiency programs highlights the need for simple tools to help assess and explain the size of the potential resource. One technique that is commonly used in this effort is to characterize electricity savings in terms of avoided power plants, because it is easier for people to visualize a power plant than it is to understand an abstraction such as billions of kilowatt-hours. Unfortunately, there is no standardization around the characteristics of such power plants. In this letter we define parameters for a standard avoided power plant that have physical meaning and intuitive plausibility, for use in back-of-the-envelope calculations. For the prototypical plant this article settles on a 500 MW existing coal plant operating at a 70percent capacity factor with 7percent T&D losses. Displacing such a plant for one year would save 3 billion kW h per year at the meter and reduce emissions by 3 million metric tons of CO2 per year. The proposed name for this metric is the Rosenfeld, in keeping with the tradition among scientists of naming units in honor of the person most responsible for the discovery and widespread adoption of the underlying scientific principle in question--Dr. Arthur H. Rosenfeld.

  16. Structural and functional characterization of an orphan ATP-binding cassette ATPase involved in manganese utilization and tolerance in Leptospira spp.

    PubMed

    Benaroudj, Nadia; Saul, Frederick; Bellalou, Jacques; Miras, Isabelle; Weber, Patrick; Bondet, Vincent; Murray, Gerald L; Adler, Ben; Ristow, Paula; Louvel, Hélène; Haouz, Ahmed; Picardeau, Mathieu

    2013-12-01

    Pathogenic Leptospira species are the etiological agents of the widespread zoonotic disease leptospirosis. Most organisms, including Leptospira, require divalent cations for proper growth, but because of their high reactivity, these metals are toxic at high concentrations. Therefore, bacteria have acquired strategies to maintain metal homeostasis, such as metal import and efflux. By screening Leptospira biflexa transposon mutants for their ability to use Mn(2+), we have identified a gene encoding a putative orphan ATP-binding cassette (ABC) ATPase of unknown function. Inactivation of this gene in both L. biflexa and L. interrogans strains led to mutants unable to grow in medium in which iron was replaced by Mn(2+), suggesting an involvement of this ABC ATPase in divalent cation uptake. A mutation in this ATPase-coding gene increased susceptibility to Mn(2+) toxicity. Recombinant ABC ATPase of the pathogen L. interrogans exhibited Mg(2+)-dependent ATPase activity involving a P-loop motif. The structure of this ATPase was solved from a crystal containing two monomers in the asymmetric unit. Each monomer adopted a canonical two-subdomain organization of the ABC ATPase fold with an α/β subdomain containing the Walker motifs and an α subdomain containing the ABC signature motif (LSSGE). The two monomers were arranged in a head-to-tail orientation, forming a V-shaped particle with all the conserved ABC motifs at the dimer interface, similar to functional ABC ATPases. These results provide the first structural and functional characterization of a leptospiral ABC ATPase.

  17. Evolutionary Conserved Positions Define Protein Conformational Diversity

    PubMed Central

    Saldaño, Tadeo E.; Monzon, Alexander M.; Parisi, Gustavo; Fernandez-Alberti, Sebastian

    2016-01-01

    Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix. PMID:27008419

  18. The Health Utilities Index (HUI): concepts, measurement properties and applications.

    PubMed

    Horsman, John; Furlong, William; Feeny, David; Torrance, George

    2003-10-16

    This is a review of the Health Utilities Index (HUI) multi-attribute health-status classification systems, and single- and multi-attribute utility scoring systems. HUI refers to both HUI Mark 2 (HUI2) and HUI Mark 3 (HUI3) instruments. The classification systems provide compact but comprehensive frameworks within which to describe health status. The multi-attribute utility functions provide all the information required to calculate single-summary scores of health-related quality of life (HRQL) for each health state defined by the classification systems. The use of HUI in clinical studies for a wide variety of conditions in a large number of countries is illustrated. HUI provides comprehensive, reliable, responsive and valid measures of health status and HRQL for subjects in clinical studies. Utility scores of overall HRQL for patients are also used in cost-utility and cost-effectiveness analyses. Population norm data are available from numerous large general population surveys. The widespread use of HUI facilitates the interpretation of results and permits comparisons of disease and treatment outcomes, and comparisons of long-term sequelae at the local, national and international levels.

  19. Reconfigurable, Cognitive Software-Defined Radio

    NASA Technical Reports Server (NTRS)

    Bhat, Arvind

    2015-01-01

    Software-defined radio (SDR) technology allows radios to be reconfigured to perform different communication functions without using multiple radios to accomplish each task. Intelligent Automation, Inc., has developed SDR platforms that switch adaptively between different operation modes. The innovation works by modifying both transmit waveforms and receiver signal processing tasks. In Phase I of the project, the company developed SDR cognitive capabilities, including adaptive modulation and coding (AMC), automatic modulation recognition (AMR), and spectrum sensing. In Phase II, these capabilities were integrated into SDR platforms. The reconfigurable transceiver design employs high-speed field-programmable gate arrays, enabling multimode operation and scalable architecture. Designs are based on commercial off-the-shelf (COTS) components and are modular in nature, making it easier to upgrade individual components rather than redesigning the entire SDR platform as technology advances.

  20. Utility of the Late Life Function and Disability Instrument as an Outcome Measure in Patients Participating in Outpatient Cardiac Rehabilitation: A Preliminary Study

    PubMed Central

    2012-01-01

    ABSTRACT Purpose: The purpose of this study was to examine the concurrent validity of the Late Life Function and Disability Instrument (LLFDI) in patients with coronary heart disease (CHD) and to evaluate the accuracy of information obtained through self-report questionnaire versus interview formats. Methods: The study included 29 patients older than 60 years attending an outpatient cardiac rehabilitation program. Participants completed the LLFDI, three additional self-report criterion measures, and six performance-based tests; they completed the LLFDI a second time via interview. We used descriptive statistics, correlations, and t-tests to analyze the data. Results: All LLFDI components were correlated (rs=0.36–0.83) with the self-report criterion measures. The Function Component of the LLFDI was moderately correlated with the 6-Minute Walk Test (r=0.62), timed up-and-go (r=−0.58), walking speed (r=−0.57), and timed sit-to-stand (r=−0.56) scores. The LLFDI demonstrated a ceiling effect (10%) only in the Disability Limitation component. All LLFDI component scores obtained via self-report questionnaire were correlated with scores obtained via interview; except in a single subcategory, there was no difference between LLFDI scores obtained through self-report questionnaire and those obtained through interview. Conclusions: Results indicate that the LLFDI has appropriate validity for older patients (>60 years) with CHD and can be completed independently by patients rather than administered by clinicians. PMID:23277685

  1. Prognostic utility of right ventricular systolic functions assessed by tissue doppler imaging in dilated cardiomyopathy and its correlation with plasma NT-pro-BNP levels.

    PubMed

    Tigen, Kursat; Karaahmet, Tansu; Cevik, Cihan; Gurel, Emre; Pala, Selcuk; Mutlu, Bulent; Basaran, Yelda

    2009-01-01

    The authors invesitgated the impact of right ventricular systolic function measured by tissue Doppler imaging on clinical end points and its correlation with plasma NT-pro-BNP levels in 75 patients with nonischemic dilated cardiomyopathy. Echocardiographic peak systolic velocities of tricuspid lateral annulus by tissue Doppler imaging and plasma pro-B-type natriuretic peptide (NT-pro-BNP) levels were measured. Forty patients had clinical end points in 29+/-16 months. They were found to have higher plasma NT-pro-BNP levels and lower tricuspid lateral annulus and interventricular septum tissue Doppler peak systolic velocities than patients without clinical end points. Cut-off level of plasma NT-pro-BNP levels for predicting clinical end points was 1700 pg/mL (sensitivity and specificity, 82% and 75%, respectively). Cut-off level of tricuspid lateral annulus tissue Doppler peak systolic velocities for predicting clinical end points was 6.25 cm/sec (sensitivity and specificity, 80% and 57%, respectively). In conclusion, plasma NT-pro-BNP levels and tissue Doppler-derived right ventricular systolic functional parameters are helpful in determining prognosis in dilated cardiomyopathy.

  2. Process Model for Defining Space Sensing and Situational Awareness Requirements

    DTIC Science & Technology

    2006-04-01

    process model for defining systems for space sensing and space situational awareness is presented. The paper concentrates on eight steps for determining the requirements to include: decision maker needs, system requirements, exploitation methods and vulnerabilities, critical capabilities, and identify attack scenarios. Utilization of the USAF anti-tamper (AT) implementation process as a process model departure point for the space sensing and situational awareness (SSSA...is presented. The AT implementation process model , as an

  3. Utilities` business plans include outsourcing

    SciTech Connect

    1995-11-01

    A panel discussion on the benefits and drawbacks of outsourcing information system functions and telecommunications operations drew much interest at the UTC (the Telecommunications Association) Annual Conference and Exhibition, held here in late summer. A panel, consisting of executives from utilities that have outsourced these services discussed this controversial business management trend. {open_quotes}Outsourcing decisions should be a balance between corporate functional requirements and cost reduction,{close_quotes} said panelist Richard Kubica, Northeast Utilities Service Co.`s manager of network planning and engineering.

  4. Functional Characterization of a Novel Marine Microbial Esterase and its Utilization in the Enantioselective Preparation of (R)-Methyl 2-Chloropropionate.

    PubMed

    Cao, Yingying; Deng, Dun; Sun, Aijun; Zhang, Yun; Hu, Yunfeng

    2016-09-01

    Chiral 2-chloropropanoic acids and their ester derivatives are crucial intermediates in the synthesis of many chemicals, especially herbicides. The enzymatic synthesis of chiral 2-chloropropanoic acids and their ester derivatives by esterases was not easily achieved, because the structural difference between the two enantiomers was too small to be recognized by esterases. Herein, we report the expression and functional characterization of one novel low temperature-resistant esterase EST12-7 identified from the genome of Pseudonocardia antitumoralis SCSIO 01299 isolated from the sediments of the South China Sea. Biocatalyst EST12-7 could hydrolyze racemic methyl 2-chloropropinate and generate optically pure (R)-methyl 2-chloropropinate with high enantiomeric excess (>99 %) and conversion (>49 %) after process optimization. Notably, the addition of different surfactants and using surfactants of different concentrations in the kinetic resolution catalyzed by EST12-7 could greatly affect the enantiomeric excess and conversion rate of product (R)-methyl 2-chloropropinate.

  5. Functional Characterization of a Robust Marine Microbial Esterase and Its Utilization in the Stereo-Selective Preparation of Ethyl (S)-3-Hydroxybutyrate.

    PubMed

    Wang, Yilong; Zhang, Yun; Hu, Yunfeng

    2016-11-01

    One novel microbial esterase PHE21 was cloned from the genome of Pseudomonas oryzihabitans HUP022 identified from the deep sea of the Western Pacific. PHE21 was heterologously expressed and functionally characterized to be a robust esterase which behaved high resistance to various metal ions, organic solvents, surfactants, and NaCl. Despite the fact that the two enantiomers of ethyl 3-hydroxybutyrate were hard to be enzymatically resolved before, we successfully resolved racemic ethyl 3-hydroxybutyrate through direct hydrolysis reactions and generated chiral ethyl (S)-3-hydroxybutyrate using esterase PHE21. After process optimization, the enantiomeric excess, the conversion rate, and the yield of desired product ethyl (S)-3-hydroxybutyrate could reach 99, 65, and 87 %, respectively. PHE21 is a novel marine microbial esterase with great potential in asymmetric synthesis as well as in other industries.

  6. Identification of rhtX and fptX, novel genes encoding proteins that show homology and function in the utilization of the siderophores rhizobactin 1021 by Sinorhizobium meliloti and pyochelin by Pseudomonas aeruginosa, respectively.

    PubMed

    Cuív, Páraic O; Clarke, Paul; Lynch, Damien; O'Connell, Michael

    2004-05-01

    Rhizobactin 1021 is a hydroxymate siderophore produced by the soil bacterium Sinorhizobium meliloti 2011. A regulon comprising rhtA, encoding the outer membrane receptor protein for the ferrisiderophore; the biosynthesis operon rhbABCDEF; and rhrA, the Ara-C-like regulator of the receptor and biosynthesis genes has been previously described. We report the discovery of a gene, located upstream of rhbA and named rhtX (for "rhizobactin transport"), which is required, in addition to rhtA, to confer the ability to utilize rhizobactin 1021 on a strain of S. meliloti that does not naturally utilize the siderophore. Rhizobactin 1021 is structurally similar to aerobactin, which is transported in Escherichia coli via the IutA outer membrane receptor and the FhuCDB inner membrane transport system. E. coli expressing iutA and fhuCDB was found to also transport rhizobactin 1021. We demonstrated that RhtX alone could substitute for FhuCDB to transport rhizobactin 1021 in E. coli. RhtX shows similarity to a number of uncharacterized proteins which are encoded proximal to genes that are either known to be or predicted to be involved in iron acquisition. Among these is PA4218 of Pseudomonas aeruginosa, which is located close to the gene cluster that functions in pyochelin biosynthesis and outer membrane transport. PA4218 was mutated by allelic replacement, and the mutant was found to have a pyochelin utilization-defective phenotype. It is proposed that PA4218 be named fptX (for "ferripyochelin transport"). RhtX and FptX appear to be members of a novel family of permeases that function as single-subunit transporters of siderophores.

  7. High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism.

    PubMed

    Griffin, Jennifer E; Gawronski, Jeffrey D; Dejesus, Michael A; Ioerger, Thomas R; Akerley, Brian J; Sassetti, Christopher M

    2011-09-01

    The pathways that comprise cellular metabolism are highly interconnected, and alterations in individual enzymes can have far-reaching effects. As a result, global profiling methods that measure gene expression are of limited value in predicting how the loss of an individual function will affect the cell. In this work, we employed a new method of global phenotypic profiling to directly define the genes required for the growth of Mycobacterium tuberculosis. A combination of high-density mutagenesis and deep-sequencing was used to characterize the composition of complex mutant libraries exposed to different conditions. This allowed the unambiguous identification of the genes that are essential for Mtb to grow in vitro, and proved to be a significant improvement over previous approaches. To further explore functions that are required for persistence in the host, we defined the pathways necessary for the utilization of cholesterol, a critical carbon source during infection. Few of the genes we identified had previously been implicated in this adaptation by transcriptional profiling, and only a fraction were encoded in the chromosomal region known to encode sterol catabolic functions. These genes comprise an unexpectedly large percentage of those previously shown to be required for bacterial growth in mouse tissue. Thus, this single nutritional change accounts for a significant fraction of the adaption to the host. This work provides the most comprehensive genetic characterization of a sterol catabolic pathway to date, suggests putative roles for uncharacterized virulence genes, and precisely maps genes encoding potential drug targets.

  8. Sociometabolic transitions defining the Anthropocene

    NASA Astrophysics Data System (ADS)

    Fischer-Kowalski, Prof; Krausmann, Prof; Pallua, Mag

    2014-05-01

    We search for a valid and quantifiable description of how and when humans acquire the ability to dominate major features of the Earth system. While common approaches (such as Kaplan et al. 2011 for example) seek to quantify the human impact upon the carbon cycle by identifying the area of land cleared by humans, we choose a more comprehensive path. Our point of departure is different human modes of subsistence, and we base our analysis on their social metabolism, in particular their energy metabolism. As a starting point, we use Ehrlich's classical IPAT formula, and give it a specific interpretation: human impact on Earth equals population size times affluence (interpreted as energy available per person) times technology - for each mode of subsistence. The overall impact (or rather human pressure) then equals the composite sum of these. We qualitatively describe the functional characteristics of hunter gatherers, agrarian and industrial modes of subsistence such as population dynamics, energy regime and the technologies by which they interact with their environment. In a 'toy' model, we translate these considerations into global numbers for the past millennia: we estimate the respective population sizes and affluence (energy), and finally also technology concerning its impact on the carbon cycle. Along this path, there are a number of findings: that it is reasonably possible to cross-check the size of pre-industrial agrarian populations from the size of urban populations; that it was in the last centuries BC that the size of agrarian populations exceeded those of hunter gatherers; that there seems to be a loglinear function of increasing average energetic metabolic rate from human basic metabolism across hunter gatherers and the agrarian mode to the industrial regime; and that from AD 1500 onwards, there is a very close relation between the urban population and fossil fuel use. We see a major historical dividing line around AD 1500: up to then, human population

  9. Manpower Planning and Personnel Management Models Based on Utility Theory,

    DTIC Science & Technology

    1980-08-01

    and Morgenstern [1947]. 2.3 Assessment of Utility Functions For decision problems with multiple objectives, multiattribute utility theory provides... multiattribute utility theory and applications. In Multiple Criteria Decision Making, M.K. Starr and M. Zelany (eds.), North Holland, Amsterdam. Fishburn...Princeton University Press, Princeton, NJ. Fishburn, P.C. (1977). Multiattribute utilities in expected utility theory . In Conflicting Objectives in

  10. Beware of Publicity! Perceived Distress of Negative Cyber Incidents and Implications for Defining Cyberbullying

    ERIC Educational Resources Information Center

    Pieschl, Stephanie; Kuhlmann, Christina; Porsch, Torsten

    2015-01-01

    Cyberbullying is usually defined by utilizing offline criteria for bullying ("repetition," "power imbalance," "intent to harm"). However, this ignores the potential relevance of cyber-specific factors ("publicity," "medium," "type" [i.e., denigration]). We compared six factors, each with…

  11. Twist1 activity thresholds define multiple functions in limb development.

    PubMed

    Krawchuk, Dayana; Weiner, Shoshana J; Chen, You-Tzung; Lu, Benson C; Costantini, Frank; Behringer, Richard R; Laufer, Ed

    2010-11-01

    The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1(-/-) embryos die at midgestation. However, studies on early limb buds found that Twist1(-/-) mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional alleles to generate a Twist1 allelic series that survives to birth. As Twist1 activity is reduced, limb skeletal defects progress from preaxial polydactyly to girdle reduction combined with hypoplasia, aplasia or mirror symmetry of all limb segments. With reduced Twist1 activity there is striking and progressive upregulation of ectopic Shh expression in the anterior of the limb, combined with an anterior shift in the posterior Shh domain, which is expressed at normal intensity, and loss of the posterior AER. Consequently limb outgrowth is initially impaired, before an ectopic anterior Shh domain expands the AER, promoting additional growth and repatterning. Reducing the dosage of FGF targets of the Etv gene family, which are known repressors of Shh expression in anterior limb mesenchyme, strongly enhances the anterior skeletal phenotype. Conversely this and other phenotypes are suppressed by reducing the dosage of the Twist1 antagonist Hand2. Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity.

  12. Genome-wide approaches to defining macrophage identity and function

    PubMed Central

    Fonseca, Gregory J; Seidman, Jason S; Glass, Christopher K

    2016-01-01

    Macrophages play essential roles in the response to injury and infection and contribute to the development and/or homeostasis of the various tissues they reside in. Conversely, macrophages also influence the pathogenesis of metabolic, neurodegenerative, and neoplastic diseases. Mechanisms that contribute to the phenotypic diversity of macrophages in health and disease remain poorly understood. Here we review the recent application of genome-wide approaches to characterize the transcriptomes and epigenetic landscapes of tissue-resident macrophages. These studies are beginning to provide insights into how distinct tissue environments are interpreted by transcriptional regulatory elements to drive specialized programs of gene expression. PMID:28087927

  13. Twist1 activity thresholds define multiple functions in limb development

    PubMed Central

    Krawchuk, Dayana; Weiner, Shoshana J.; Chen, You-Tzung; Lu, Benson; Costantini, Frank; Behringer, Richard R.; Laufer, Ed

    2010-01-01

    Summary The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1−/− embryos die at midgestation. However, studies on early limb buds found that Twist1−/− mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional alleles to generate a Twist1 allelic series that survives to birth. As Twist1 activity is reduced, limb skeletal defects progress from preaxial polydactyly to girdle reduction combined with hypoplasia, aplasia or mirror symmetry of all limb segments. With reduced Twist1 activity there is striking and progressive upregulation of ectopic Shh expression in the anterior of the limb, combined with an anterior shift in the posterior Shh domain, which is expressed at normal intensity, and loss of the posterior AER. Consequently limb outgrowth is initially impaired, before an ectopic anterior Shh domain expands the AER, promoting additional growth and repatterning. Reducing the dosage of FGF targets of the Etv gene family, which are known repressors of Shh expression in the anterior limb mesenchyme, strongly enhances the anterior skeletal phenotype. Conversely this and other phenotypes are suppressed by reducing the dosage of the Twist1 antagonist Hand2. Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity. PMID:20732316

  14. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  15. Gas utilization technologies

    SciTech Connect

    Biljetina, R.

    1994-09-01

    One of the constant challenges facing the research community is the identification of technology needs 5 to 15 years from now. A look back into history indicates that the forces driving natural gas research have changed from decade to decade. In the 1970s research was driven by concerns for adequate supply; in the 1980s research was aimed at creating new markets for natural gas. What then are the driving forces for the 1990s? Recent reports from the natural gas industry have helped define a new direction driven primarily by market demand for natural gas. A study prepared by the Interstate Natural Gas Association of America Foundation entitled ``Survey of Natural Research, Development, and Demonstration RD&D Priorities`` indicated that in the 1990s the highest research priority should be for natural gas utilization and that technology development efforts should not only address efficiency and cost, but environmental and regulatory issues as well. This study and others, such as the report by the American Gas Association (A.G.A.) entitled ``Strategic Vision for Natural Gas Through the Year 2000,`` clearly identify the market sectors driving today`s technology development needs. The biggest driver is the power generation market followed by the industrial, transportation, appliance, and gas cooling markets. This is best illustrated by the GRI 1994 Baseline Projection on market growth in various sectors between the year 1992 and 2010. This paper highlights some of the recent technology developments in each one of these sectors.

  16. Improving the diagnostic criteria for primary liver graft non-function in adults utilizing standard and transportable laboratory parameters. An outcome based analysis.

    PubMed

    Al-Freah, Mohammad A B; McPhail, Mark J W; Dionigi, Elena; Foxton, Matthew R; Auzinger, Georg; Rela, Mohamed; Wendon, Julia A; O'Grady, John G; Heneghan, Michael A; Heaton, Nigel D; Bernal, William

    2017-02-15

    Current diagnostic criteria for primary non-function (PNF) of liver grafts are based on clinical experience rather than statistical methods. A retrospective, single centre study was conducted of all adults (n=1,286) who underwent primary liver transplant 2000-2008 in our centre. Laboratory variable during the first post-liver transplant week were analysed. Forty two patients (3.7%) had 2-week graft failure. Transplant albumin, day-1 AST, day-1 lactate, day-3 bilirubin, day-3 INR and day-7 AST were independently associated with PNF on multivariate logistic regression. PNF score =(0.000280*D1AST)+(0.361*D1 Lactate)+(0.00884*D3 Bilirubin)+(0.940*D 3 INR)+(0.00153*D7 AST)-(0.0972*TxAlbumin)-4.5503. ROC analysis showed the model AUROC of 0.912 (0.889 -0.932) was superior to the current United Kingdom (UK) PNF criteria of 0.669 (0.634-0.704, p<0.0001). When applied to a validation cohort (n=386, 34.4% patients) the model had AUROC of 0.831 (0.789 -0.867) compared to the UK EGD criteria of 0.674 (0.624-0.721). The new model performed well after exclusion of patients with marginal grafts and when modified to include variables from the first three post-LT days only (AUROC of 0.818, 0.776-0.856, p=0.001). This model is superior to the current UK PNF criteria and is based on statistical methods. The model is also applicable to recipients of all types of grafts (marginal and non-marginal). This article is protected by copyright. All rights reserved.

  17. The laboratory test utilization management toolbox

    PubMed Central

    Baird, Geoffrey

    2014-01-01

    Efficiently managing laboratory test utilization requires both ensuring adequate utilization of needed tests in some patients and discouraging superfluous tests in other patients. After the difficult clinical decision is made to define the patients that do and do not need a test, a wealth of interventions are available to the clinician and laboratorian to help guide appropriate utilization. These interventions are collectively referred to here as the utilization management toolbox. Experience has shown that some tools in the toolbox are weak and other are strong, and that tools are most effective when many are used simultaneously. While the outcomes of utilization management studies are not always as concrete as may be desired, what data is available in the literature indicate that strong utilization management interventions are safe and effective measures to improve patient health and reduce waste in an era of increasing financial pressure. PMID:24969916

  18. An analysis of the lack of donor pancreas utilization from younger adult organ donors.

    PubMed

    Wiseman, Alexander C; Wainright, Jennifer L; Sleeman, Elizabeth; McBride, Maureen A; Baker, Tim; Samana, Ciara; Stock, Peter

    2010-09-15

    Donor pancreas utilization rates for whole organ transplant have remained low and have decreased over time. To identify the reasons for nonuse of pancreas from donors who meet common baseline acceptance criteria, we examined Organ Procurement and Transplantation Network data from 2005 to 2007 and identified a subgroup of 1763 "potential pancreas donors" defined by age (19-40 years), body mass index (<30 kg/m), successful liver donation, and negative viral serology testing, which were not used. We characterize this cohort of potential donors including reasons for refusal, factors that may contribute to pancreas acceptance and function, and potential explanations for the lack of growth in pancreas organ utilization.

  19. Defining moments in leadership character development.

    PubMed

    Bleich, Michael R

    2015-06-01

    Critical moments in life define one's character and clarify true values. Reflective leadership is espoused as an important practice for transformational leaders. Professional development educators can help surface and explore defining moments, strengthen leadership behavior with defining moments as a catalyst for change, and create safe spaces for leaders to expand their leadership capacity.

  20. Limitations to oxygen transport and utilization during sprint exercise in humans: evidence for a functional reserve in muscle O2 diffusing capacity.

    PubMed

    Calbet, José A L; Losa-Reyna, José; Torres-Peralta, Rafael; Rasmussen, Peter; Ponce-González, Jesús Gustavo; Sheel, A William; de la Calle-Herrero, Jaime; Guadalupe-Grau, Amelia; Morales-Alamo, David; Fuentes, Teresa; Rodríguez-García, Lorena; Siebenmann, Christoph; Boushel, Robert; Lundby, Carsten

    2015-10-15

    To determine the contribution of convective and diffusive limitations to V̇(O2peak) during exercise in humans, oxygen transport and haemodynamics were measured in 11 men (22 ± 2 years) during incremental (IE) and 30 s all-out cycling sprints (Wingate test, WgT), in normoxia (Nx, P(IO2): 143 mmHg) and hypoxia (Hyp, P(IO2): 73 mmHg). Carboxyhaemoglobin (COHb) was increased to 6-7% before both WgTs to left-shift the oxyhaemoglobin dissociation curve. Leg V̇(O2) was measured by the Fick method and leg blood flow (BF) with thermodilution, and muscle O2 diffusing capacity (D(MO2)) was calculated. In the WgT mean power output, leg BF, leg O2 delivery and leg V̇(O2) were 7, 5, 28 and 23% lower in Hyp than Nx (P < 0.05); however, peak WgT D(MO2) was higher in Hyp (51.5 ± 9.7) than Nx (20.5 ± 3.0 ml min(-1) mmHg(-1), P < 0.05). Despite a similar P(aO2) (33.3 ± 2.4 and 34.1 ± 3.3 mmHg), mean capillary P(O2) (16.7 ± 1.2 and 17.1 ± 1.6 mmHg), and peak perfusion during IE and WgT in Hyp, D(MO2) and leg V̇(O2) were 12 and 14% higher, respectively, during WgT than IE in Hyp (both P < 0.05). D(MO2) was insensitive to COHb (COHb: 0.7 vs. 7%, in IE Hyp and WgT Hyp). At exhaustion, the Y equilibration index was well above 1.0 in both conditions, reflecting greater convective than diffusive limitation to the O2 transfer in both Nx and Hyp. In conclusion, muscle V̇(O2) during sprint exercise is not limited by O2 delivery, O2 offloading from haemoglobin or structure-dependent diffusion constraints in the skeletal muscle. These findings reveal a remarkable functional reserve in muscle O2 diffusing capacity.