Characterizations of linear sufficient statistics

NASA Technical Reports Server (NTRS)

Peters, B. C., Jr.; Reoner, R.; Decell, H. P., Jr.

1977-01-01

A surjective bounded linear operator T from a Banach space X to a Banach space Y must be a sufficient statistic for a dominated family of probability measures defined on the Borel sets of X. These results were applied, so that they characterize linear sufficient statistics for families of the exponential type, including as special cases the Wishart and multivariate normal distributions. The latter result was used to establish precisely which procedures for sampling from a normal population had the property that the sample mean was a sufficient statistic.

Salt taste responses of the IXth nerve in Sprague-Dawley rats: lack of sensitivity to amiloride.

PubMed

Kitada, Y; Mitoh, Y; Hill, D L

1998-03-01

To explore characteristics of the salt taste function of taste receptor cells located on the posterior tongue, we recorded electrophysiological responses from the whole glossopharyngeal nerve in Sprague-Dawley (SD) rats. For all salts, relative response magnitudes increased with increased stimulus concentrations (0.2-2.0 M) of NH4+, K+, and Na+ salts. The order of effectiveness of stimulation for Cl- salts was NH4Cl > KCl > NaCl. For sodium salts, relative response magnitudes were anion dependent. Sodium salts with small anions (NaCl, NaSCN, and NaNO3) had a much stronger stimulating effect than sodium salts with large anion groups (Na2SO4, C2H3O2Na, and C6H11O7Na). The responses of the glossopharyngeal nerve to the Na+ salts of NaCl, C2H3O2Na, and C6H11O7Na were not inhibited by the lingual application of the epithelial sodium transport blocker amiloride. This is in contrast to large amiloride sensitivity of the chorda tympani nerve. Amiloride also failed to inhibit the responses to K+ salts (KCl and KC2H3O2) and to NH4Cl. These results demonstrate that taste receptors innervated by the glossopharyngeal nerve in SD rats lack amiloride sensitivity as observed in the glossopharyngeal nerve of spontaneously hypertensive and Wistar-Kyoto rats. Furthermore, the difference between the small-anion group and the large-anion group of Na+ salts in their effectiveness to produce responses in the glossopharyngeal nerve parallels the effects noted for the anion dependence in the portion of the taste response resistant to amiloride in the chorda tympani nerve. Sodium salts with the smaller anion produced the larger responses in both glossopharyngeal and chorda tympani nerves after amiloride.

A mesenchymal-like phenotype and expression of CD44 predict lack of apoptotic response to sorafenib in liver tumor cells.

PubMed

Fernando, Joan; Malfettone, Andrea; Cepeda, Edgar B; Vilarrasa-Blasi, Roser; Bertran, Esther; Raimondi, Giulia; Fabra, Àngels; Alvarez-Barrientos, Alberto; Fernández-Salguero, Pedro; Fernández-Rodríguez, Conrado M; Giannelli, Gianluigi; Sancho, Patricia; Fabregat, Isabel

2015-02-15

The multikinase inhibitor sorafenib is the only effective drug in advanced cases of hepatocellular carcinoma (HCC). However, response differs among patients and effectiveness only implies a delay. We have recently described that sorafenib sensitizes HCC cells to apoptosis. In this work, we have explored the response to this drug of six different liver tumor cell lines to define a phenotypic signature that may predict lack of response in HCC patients. Results have indicated that liver tumor cells that show a mesenchymal-like phenotype, resistance to the suppressor effects of transforming growth factor beta (TGF-β) and high expression of the stem cell marker CD44 were refractory to sorafenib-induced cell death in in vitro studies, which correlated with lack of response to sorafenib in nude mice xenograft models of human HCC. In contrast, epithelial-like cells expressing the stem-related proteins EpCAM or CD133 were sensitive to sorafenib-induced apoptosis both in vitro and in vivo. A cross-talk between the TGF-β pathway and the acquisition of a mesenchymal-like phenotype with up-regulation of CD44 expression was found in the HCC cell lines. Targeted CD44 knock-down in the mesenchymal-like cells indicated that CD44 plays an active role in protecting HCC cells from sorafenib-induced apoptosis. However, CD44 effect requires a TGF-β-induced mesenchymal background, since the only overexpression of CD44 in epithelial-like HCC cells is not sufficient to impair sorafenib-induced cell death. In conclusion, a mesenchymal profile and expression of CD44, linked to activation of the TGF-β pathway, may predict lack of response to sorafenib in HCC patients. © 2014 UICC.

Revenue Sufficiency and Reliability in a Zero Marginal Cost Future: Preprint

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

Frew, Bethany A.; Milligan, Michael; Brinkman, Greg

Features of existing wholesale electricity markets, such as administrative pricing rules and policy-based reliability standards, can distort market incentives from allowing generators sufficient opportunities to recover both fixed and variable costs. Moreover, these challenges can be amplified by other factors, including (1) inelastic demand resulting from a lack of price signal clarity, (2) low- or near-zero marginal cost generation, particularly arising from low natural gas fuel prices and variable generation (VG), such as wind and solar, and (3) the variability and uncertainty of this VG. As power systems begin to incorporate higher shares of VG, many questions arise about themore » suitability of the existing marginal-cost-based price formation, primarily within an energy-only market structure, to ensure the economic viability of resources that might be needed to provide system reliability. This article discusses these questions and provides a summary of completed and ongoing modelling-based work at the National Renewable Energy Laboratory to better understand the impacts of evolving power systems on reliability and revenue sufficiency.« less

Mice completely lacking immunoproteasomes display major alterations in antigen presentation

PubMed Central

Kincaid, Eleanor Z; Che, Jenny W; York, Ian; Escobar, Hernando; Reyes-Vargas, Eduardo; Delgado, Julio C.; Welsh, Raymond M; Karow, Margaret L.; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.; Rock, Kenneth L

2011-01-01

The importance of immunoproteasomes to antigen presentation has been unclear because animals totally lacking immunoproteasomes have not been previously developed. Here we show that dendritic cells from mice lacking the three immunoproteasome catalytic subunits display defects in presenting multiple major histocompatability (MHC) class I epitopes. During viral infection in vivo, the presentation of a majority of MHC class I epitopes is markedly reduced in immunoproteasome-deficient animals, while presentation of MHC class II peptides is unaffected. By mass spectrometry the repertoire of MHC class I-presented peptides is ~50% different and these differences are sufficient to stimulate robust transplant rejection of wild type cells in mutant mice. These results indicate that immunoproteasomes play a much more important role in antigen presentation than previously thought. PMID:22197977

Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs

PubMed Central

Choi, Kyung-Suk; Lee, Chanmi; Harfe, Brian D.

2012-01-01

The intervertebral discs, located between adjacent vertebrae, are required for stability of the spine and distributing mechanical load throughout the vertebral column. All cell types located in thes middle regions of the discs, called nuclei pulposi, are derived from the embryonic notochord. Recently, it was shown that the hedgehog signaling pathway plays an essential role during formation of nuclei pulposi. However, during the time that nuclei pulposi are forming, Shh is expressed in both the notochord and the nearby floor plate. To determine the source of SHH protein sufficient for formation of nuclei pulposi we removed Shh from either the floor plate or the notochord using tamoxifen-inducible Cre alleles. Removal of Shh from the floor plate resulted in phenotypically normal intervertebral discs, indicating that Shh expression in this tissue is not required for disc patterning. In addition, embryos that lacked Shh in the floor plate had normal vertebral columns, demonstrating that Shh expression in the notochord is sufficient for pattering the entire vertebral column. Removal of Shh from the notochord resulted in the absence of Shh in the floor plate, loss of intervertebral discs and vertebral structures. These data indicate that Shh expression in the notochord is sufficient for patterning of the intervertebral discs and the vertebral column. PMID:22841806

In vivo ultrasound visualization of non-occlusive blood clots with thrombin-sensitive contrast agents.

PubMed

Nakatsuka, Matthew A; Barback, Christopher V; Fitch, Kirsten R; Farwell, Alexander R; Esener, Sadik C; Mattrey, Robert F; Cha, Jennifer N; Goodwin, Andrew P

2013-12-01

The use of microbubbles as ultrasound contrast agents is one of the primary methods to diagnose deep venous thrombosis. However, current microbubble imaging strategies require either a clot sufficiently large to produce a circulation filling defect or a clot with sufficient vascularization to allow for targeted accumulation of contrast agents. Previously, we reported the design of a microbubble formulation that modulated its ability to generate ultrasound contrast from interaction with thrombin through incorporation of aptamer-containing DNA crosslinks in the encapsulating shell, enabling the measurement of a local chemical environment by changes in acoustic activity. However, this contrast agent lacked sufficient stability and lifetime in blood to be used as a diagnostic tool. Here we describe a PEG-stabilized, thrombin-activated microbubble (PSTA-MB) with sufficient stability to be used in vivo in circulation with no change in biomarker sensitivity. In the presence of actively clotting blood, PSTA-MBs showed a 5-fold increase in acoustic activity. Specificity for the presence of thrombin and stability under constant shear flow were demonstrated in a home-built in vitro model. Finally, PSTA-MBs were able to detect the presence of an active clot within the vena cava of a rabbit sufficiently small as to not be visible by current non-specific contrast agents. By activating in non-occlusive environments, these contrast agents will be able to detect clots not diagnosable by current contrast agents. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sufficient oxygen for animal respiration 1,400 million years ago

PubMed Central

Zhang, Shuichang; Wang, Xiaomei; Wang, Huajian; Bjerrum, Christian J.; Hammarlund, Emma U.; Costa, M. Mafalda; Connelly, James N.; Zhang, Baomin; Su, Jin; Canfield, Donald E.

2016-01-01

The Mesoproterozoic Eon [1,600–1,000 million years ago (Ma)] is emerging as a key interval in Earth history, with a unique geochemical history that might have influenced the course of biological evolution on Earth. Indeed, although this time interval is rather poorly understood, recent chromium isotope results suggest that atmospheric oxygen levels were <0.1% of present levels, sufficiently low to have inhibited the evolution of animal life. In contrast, using a different approach, we explore the distribution and enrichments of redox-sensitive trace metals in the 1,400 Ma sediments of Unit 3 of the Xiamaling Formation, North China Block. Patterns of trace metal enrichments reveal oxygenated bottom waters during deposition of the sediments, and biomarker results demonstrate the presence of green sulfur bacteria in the water column. Thus, we document an ancient oxygen minimum zone. We develop a simple, yet comprehensive, model of marine carbon−oxygen cycle dynamics to show that our geochemical results are consistent with atmospheric oxygen levels >4% of present-day levels. Therefore, in contrast to previous suggestions, we show that there was sufficient oxygen to fuel animal respiration long before the evolution of animals themselves. PMID:26729865

Lacking "Lack": A Reply to Joldersma

ERIC Educational Resources Information Center

Marshall, James D.

2007-01-01

First I would like to thank Clarence Joldersma for his review of our "Poststructuralism, Philosophy, Pedagogy" (Marshall, 2004-PPP). In particular, I would thank him for his opening sentence: "[t]his book is a response to a lack." It is the notion of a lack, noted again later in his review, which I wish to take up mainly in this response. Rather…

Obese Mice Lacking Inducible Nitric Oxide Synthase Are Sensitized to the Metabolic Actions of Peroxisome Proliferator–Activated Receptor-γ Agonism

PubMed Central

Dallaire, Patrice; Bellmann, Kerstin; Laplante, Mathieu; Gélinas, Stéphanie; Centeno-Baez, Carolina; Penfornis, Patrice; Peyot, Marie-Line; Latour, Martin G.; Lamontagne, Julien; Trujillo, Maria E.; Scherer, Philipp E.; Prentki, Marc; Deshaies, Yves; Marette, André

2008-01-01

OBJECTIVE—Synthetic ligands for peroxisome proliferator–activated receptor-γ (PPAR-γ) improve insulin sensitivity in obesity, but it is still unclear whether inflammatory signals modulate their metabolic actions. In this study, we tested whether targeted disruption of inducible nitric oxide (NO) synthase (iNOS), a key inflammatory mediator in obesity, modulates the metabolic effects of rosiglitazone in obese mice. RESEARCH DESIGN AND METHODS—iNOS−/− and iNOS+/+ were subjected to a high-fat diet or standard diet for 18 weeks and were then treated with rosiglitazone for 2 weeks. Whole-body insulin sensitivity and glucose tolerance were determined and metabolic tissues harvested to assess activation of insulin and AMP-activated protein kinase (AMPK) signaling pathways and the levels of inflammatory mediators. RESULTS—Rosiglitazone was found to similarly improve whole-body insulin sensitivity and insulin signaling to Akt/PKB in skeletal muscle of obese iNOS−/− and obese iNOS+/+ mice. However, rosiglitazone further improved glucose tolerance and liver insulin signaling only in obese mice lacking iNOS. This genotype-specific effect of rosiglitazone on glucose tolerance was linked to a markedly increased ability of the drug to raise plasma adiponectin levels. Accordingly, rosiglitazone increased AMPK activation in muscle and liver only in obese iNOS−/− mice. PPAR-γ transcriptional activity was increased in adipose tissue of iNOS−/− mice. Conversely, treatment of 3T3-L1 adipocytes with a NO donor blunted PPAR-γ activity. CONCLUSIONS—Our results identify the iNOS/NO pathway as a critical modulator of PPAR-γ activation and circulating adiponectin levels and show that invalidation of this key inflammatory mediator improves the efficacy of PPAR-γ agonism in an animal model of obesity and insulin resistance. PMID:18458147

Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs.

PubMed

Choi, Kyung-Suk; Lee, Chanmi; Harfe, Brian D

2012-01-01

The intervertebral discs, located between adjacent vertebrae, are required for stability of the spine and distributing mechanical load throughout the vertebral column. All cell types located in the middle regions of the discs, called nuclei pulposi, are derived from the embryonic notochord. Recently, it was shown that the hedgehog signaling pathway plays an essential role during formation of nuclei pulposi. However, during the time that nuclei pulposi are forming, Shh is expressed in both the notochord and the nearby floor plate. To determine the source of SHH protein sufficient for formation of nuclei pulposi we removed Shh from either the floor plate or the notochord using tamoxifen-inducible Cre alleles. Removal of Shh from the floor plate resulted in phenotypically normal intervertebral discs, indicating that Shh expression in this tissue is not required for disc patterning. In addition, embryos that lacked Shh in the floor plate had normal vertebral columns, demonstrating that Shh expression in the notochord is sufficient for pattering the entire vertebral column. Removal of Shh from the notochord resulted in the absence of Shh in the floor plate, loss of intervertebral discs and vertebral structures. These data indicate that Shh expression in the notochord is sufficient for patterning of the intervertebral discs and the vertebral column. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Mentoring Emotionally Sensitive Individuals.

ERIC Educational Resources Information Center

Shaughnessy, Michael F.; Self, Elizabeth

Mentoring individuals who are gifted, talented, and creative, but somewhat emotionally sensitive is a challenging and provocative arena. Several reasons individuals experience heightened sensitivity include: lack of nurturing, abuse, alcoholism in the family, low self-esteem, unrealistic parental expectations, and parental pressure to achieve.…

Lack of spontaneous and radiation-induced chromosome breakage at interstitial telomeric sites in murine scid cells.

PubMed

Wong, H-P; Mozdarani, H; Finnegan, C; McIlrath, J; Bryant, P E; Slijepcevic, P

2004-01-01

Interstitial telomeric sites (ITSs) in chromosomes from DNA repair-proficient mammalian cells are sensitive to both spontaneous and radiation-induced chromosome breakage. Exact mechanisms of this chromosome breakage sensitivity are not known. To investigate factors that predispose ITSs to chromosome breakage we used murine scid cells. These cells lack functional DNA-PKcs, an enzyme involved in the repair of DNA double-strand breaks. Interestingly, our results revealed lack of both spontaneous and radiation-induced chromosome breakage at ITSs found in scid chromosomes. Therefore, it is possible that increased sensitivity of ITSs to chromosome breakage is associated with the functional DNA double-strand break repair machinery. To investigate if this is the case we used scid cells in which DNA-PKcs deficiency was corrected. Our results revealed complete disappearance of ITSs in scid cells with functional DNA-PKcs, presumably through chromosome breakage at ITSs, but their unchanged frequency in positive and negative control cells. Therefore, our results indicate that the functional DNA double-strand break machinery is required for elevated sensitivity of ITSs to chromosome breakage. Interestingly, we observed significant differences in mitotic chromosome condensation between scid cells and their counterparts with restored DNA-PKcs activity suggesting that lack of functional DNA-PKcs may cause a defect in chromatin organization. Increased condensation of mitotic chromosomes in the scid background was also confirmed in vivo. Therefore, our results indicate a previously unanticipated role of DNA-PKcs in chromatin organisation, which could contribute to the lack of ITS sensitivity to chromosome breakage in murine scid cells. Copyright 2003 S. Karger AG, Basel

Visual Sensitivity of Deepwater Fishes in Lake Superior

PubMed Central

Harrington, Kelly A.; Hrabik, Thomas R.; Mensinger, Allen F.

2015-01-01

The predator-prey interactions in the offshore food web of Lake Superior have been well documented, but the sensory systems mediating these interactions remain unknown. The deepwater sculpin, (Myoxocephalus thompsoni), siscowet (Salvelinus namaycush siscowet), and kiyi (Coregonus kiyi) inhabit low light level environments. To investigate the potential role of vision in predator-prey interactions, electroretinography was used to determine visual sensitivity for each species. Spectral sensitivity curves revealed peak sensitivity at 525 nm for each species which closely corresponds to the prevalent downwelling light spectrum at depth. To determine if sufficient light was available to mediate predator-prey interactions, visual sensitivity was correlated with the intensity of downwelling light in Lake Superior to construct visual depth profiles for each species. Sufficient daytime irradiance exists for visual interactions to approximately 325 m for siscowet and kiyi and 355 m for the deepwater sculpin during summer months. Under full moon conditions, sufficient irradiance exists to elicit ERG response to light available at approximately 30 m for the siscowet and kiyi and 45 m for the deepwater sculpin. Visual interactions are therefore possible at the depths and times when these organisms overlap in the water column indicating that vision may play a far greater role at depth in deep freshwater lakes than had been previously documented. PMID:25646781

Grafting voltage and pharmacological sensitivity in potassium channels.

PubMed

Lan, Xi; Fan, Chunyan; Ji, Wei; Tian, Fuyun; Xu, Tao; Gao, Zhaobing

2016-08-01

A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7.1 channels, exhibit classical voltage sensitivity, including voltage-dependent opening and closing. Furthermore, the grafted Kv7.1 VSD transfers the potentiation activity of benzbromarone, an activator that acts on the VSDs of the donor channels, to the constructed channels. Our study indicates that one VSD is sufficient to voltage-dependently gate the pore and provides new insight into the roles of VSDs.

Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is Necessary and Sufficient for Vascular Bioactivation of Nitroglycerin.

PubMed

Opelt, Marissa; Eroglu, Emrah; Waldeck-Weiermair, Markus; Russwurm, Michael; Koesling, Doris; Malli, Roland; Graier, Wolfgang F; Fassett, John T; Schrammel, Astrid; Mayer, Bernd

2016-11-11

Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN), resulting in activation of soluble guanylate cyclase (sGC) and cGMP-mediated vasodilation. We have previously shown that a minor reaction of ALDH2-catalyzed GTN bioconversion, accounting for about 5% of the main clearance-based turnover yielding inorganic nitrite, results in direct NO formation and concluded that this minor pathway could provide the link between vascular GTN metabolism and activation of sGC. However, lack of detectable NO at therapeutically relevant GTN concentrations (≤1 μm) in vascular tissue called into question the biological significance of NO formation by purified ALDH2. We addressed this issue and used a novel, highly sensitive genetically encoded fluorescent NO probe (geNOp) to visualize intracellular NO formation at low GTN concentrations (≤1 μm) in cultured vascular smooth muscle cells (VSMC) expressing an ALDH2 mutant that reduces GTN to NO but lacks clearance-based GTN denitration activity. NO formation was compared with GTN-induced activation of sGC. The addition of 1 μm GTN to VSMC expressing either wild-type or C301S/C303S ALDH2 resulted in pronounced intracellular NO elevation, with maximal concentrations of 7 and 17 nm, respectively. Formation of GTN-derived NO correlated well with activation of purified sGC in VSMC lysates and cGMP accumulation in intact porcine aortic endothelial cells infected with wild-type or mutant ALDH2. Formation of NO and cGMP accumulation were inhibited by ALDH inhibitors chloral hydrate and daidzin. The present study demonstrates that ALDH2-catalyzed NO formation is necessary and sufficient for GTN bioactivation in VSMC. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Salivary Pepsin Lacks Sensitivity as a Diagnostic Tool to Evaluate Extraesophageal Reflux Disease.

PubMed

Dy, Fei; Amirault, Janine; Mitchell, Paul D; Rosen, Rachel

2016-10-01

To determine the sensitivity of salivary pepsin compared with multichannel intraluminal impedance with pH testing (pH-MII), endoscopy, and gastroesophageal reflux disease (GERD) questionnaires. We prospectively recruited 50 children from Boston Children's Hospital who were undergoing pH-MII to evaluate for GERD. The patients completed 24-hour pH-MII testing, completed symptom and quality of life questionnaires, and provided a saliva specimen that was analyzed using the PepTest lateral flow test. A subset of patients also underwent bronchoscopy and esophagogastroduodenoscopy. Receiver operating characteristic curve analyses were performed to determine the sensitivity of salivary pepsin compared with each reference standard. Twenty-one of the 50 patients (42%) were salivary pepsin-positive, with a median salivary pepsin concentration of 10 ng/mL (IQR, 10-55 ng/mL). There was no significant difference in the distributions of acid, nonacid, total reflux episodes, full column reflux, or any other reflux variable in patients who were pepsin-positive compared with those who were pepsin-negative (P > .50). There was no significant correlation between the number of reflux episodes and pepsin concentration (P > .10). There was no positive relationship between salivary pepsin positivity, any extraesophageal symptoms or quality of life scores, or inflammation on bronchoscopy or esophagogastroduodenoscopy (P > .30). Salivary pepsin measurement has a low sensitivity for predicting pathological gastroesophageal reflux in children. Copyright © 2016 Elsevier Inc. All rights reserved.

Decreasing Friction Sensitivity for Primary Explosives

NASA Astrophysics Data System (ADS)

Matyáš, Robert; Šelešovský, Jakub

2014-04-01

Primary explosives are a group of explosives that are widely used in various initiating devices. One of their properties is sufficient sensitivity to initiating stimuli. However, their sensitivity often introduces a safety risk during their production and subsequent handling. It is generally known that water can be used to desensitize these compounds. The most commonly used industrial primary explosives (lead azide, lead styphnate, tetrazene, and diazodinitrophenol) were mixed with water in various ratios and the sensitivity to friction was determined for all mixtures. It was found that even a small addition of water (5-10%) considerably lowered the friction sensitivity.

Self-sufficiency, free trade and safety.

PubMed

Rautonen, Jukka

2010-01-01

The relationship between free trade, self-sufficiency and safety of blood and blood components has been a perennial discussion topic in the blood service community. Traditionally, national self-sufficiency has been perceived as the ultimate goal that would also maximize safety. However, very few countries are, or can be, truly self-sufficient when self-sufficiency is understood correctly to encompass the whole value chain from the blood donor to the finished product. This is most striking when plasma derived medicines are considered. Free trade of blood products, or competition, as such can have a negative or positive effect on blood safety. Further, free trade of equipment and reagents and several plasma medicines is actually necessary to meet the domestic demand for blood and blood derivatives in most countries. Opposing free trade due to dogmatic reasons is not in the best interest of any country and will be especially harmful for the developing world. Competition between blood services in the USA has been present for decades. The more than threefold differences in blood product prices between European blood services indicate that competition is long overdue in Europe, too. This competition should be welcomed but carefully and proactively regulated to avoid putting safe and secure blood supply at risk. Copyright 2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

Anhydrobiotic engineering of bacterial and mammalian cells: is intracellular trehalose sufficient?

PubMed

Tunnacliffe, A; García de Castro, A; Manzanera, M

2001-09-01

Anhydrobiotic engineering aims to confer a high degree of desiccation tolerance on otherwise sensitive living organisms and cells by adopting the strategies of anhydrobiosis. Nonreducing disaccharides such as trehalose and sucrose are thought to play a pivotal role in resistance to desiccation stress in many microorganisms, invertebrates, and plants, and in vitro trehalose is known to confer stability on dried biomolecules and biomembranes. We have therefore tested the hypothesis that intracellular trehalose (or a similar molecule) may be not only necessary for anhydrobiosis but also sufficient. High concentrations of trehalose were produced in bacteria by osmotic preconditioning, and in mammalian cells by genetic engineering, but in neither system was desiccation tolerance similar to that seen in anhydrobiotic organisms, suggesting that trehalose alone is not sufficient for anhydrobiosis. In Escherichia coli such desiccation tolerance was achievable, but only when bacteria were dried in the presence of both extracellular trehalose and intracellular trehalose. In mouse L cells, improved osmotolerance was observed with up to 100 mM intracellular trehalose, but desiccation was invariably lethal even with extracellular trehalose present. We conclude that anhydrobiotic engineering of at least some microorganisms is achievable with present technology, but that further advances are needed for similar desiccation tolerance of mammalian cells. Copyright 2001 Elsevier Science (USA).

Working toward Self-Sufficiency.

ERIC Educational Resources Information Center

Caplan, Nathan

1985-01-01

Upon arrival in the United States, the Southeast Asian "Boat People" faced a multitude of problems that would seem to have hindered their achieving economic self-sufficiency. Nonetheless, by the time of a 1982 research study which interviewed nearly 1,400 refugee households, 25 percent of all the households in the sample had achieved…

39 CFR 491.3 - Sufficient legal form.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Sufficient legal form. 491.3 Section 491.3 Postal... AND THE POSTAL RATE COMMISSION § 491.3 Sufficient legal form. No document purporting to garnish... is legal process in the nature of garnishment; that it is issued by a court of competent jurisdiction...

39 CFR 491.3 - Sufficient legal form.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 39 Postal Service 1 2014-07-01 2014-07-01 false Sufficient legal form. 491.3 Section 491.3 Postal... AND THE POSTAL RATE COMMISSION § 491.3 Sufficient legal form. No document purporting to garnish... is legal process in the nature of garnishment; that it is issued by a court of competent jurisdiction...

27 CFR 25.174 - Bond not sufficient.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Bond not sufficient. 25.174 Section 25.174 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Tax on Beer Prepayment of Tax § 25.174 Bond not sufficient. When the...

27 CFR 25.174 - Bond not sufficient.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Bond not sufficient. 25.174 Section 25.174 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL BEER Tax on Beer Prepayment of Tax § 25.174 Bond not sufficient. When the...

27 CFR 25.174 - Bond not sufficient.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Bond not sufficient. 25.174 Section 25.174 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL BEER Tax on Beer Prepayment of Tax § 25.174 Bond not sufficient. When the...

27 CFR 25.174 - Bond not sufficient.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Bond not sufficient. 25.174 Section 25.174 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Tax on Beer Prepayment of Tax § 25.174 Bond not sufficient. When the...

27 CFR 25.174 - Bond not sufficient.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Bond not sufficient. 25.174 Section 25.174 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Tax on Beer Prepayment of Tax § 25.174 Bond not sufficient. When the...

When is Testing Sufficient

NASA Technical Reports Server (NTRS)

Rosenberg, Linda H.; Arthur, James D.; Stapko, Ruth K.; Davani, Darush

1999-01-01

The Software Assurance Technology Center (SATC) at NASA Goddard Space Flight Center has been investigating how projects can determine when sufficient testing has been completed. For most projects, schedules are underestimated, and the last phase of the software development, testing, must be decreased. Two questions are frequently asked: "To what extent is the software error-free? " and "How much time and effort is required to detect and remove the remaining errors? " Clearly, neither question can be answered with absolute certainty. Nonetheless, the ability to answer these questions with some acceptable level of confidence is highly desirable. First, knowing the extent to which a product is error-free, we can judge when it is time to terminate testing. Secondly, if errors are judged to be present, we can perform a cost/benefit trade-off analysis to estimate when the software will be ready for use and at what cost. This paper explains the efforts of the SATC to help projects determine what is sufficient testing and when is the most cost-effective time to stop testing.

Salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA.

PubMed

Gao, Qiuqiang; Liou, Liang-Chun; Ren, Qun; Bao, Xiaoming; Zhang, Zhaojie

2014-03-03

The yeast cell wall plays an important role in maintaining cell morphology, cell integrity and response to environmental stresses. Here, we report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ 0 ). Upon salt treatment, the cell wall is thickened, broken and becomes more sensitive to the cell wall-perturbing agent sodium dodecyl sulfate (SDS). Also, SCW11 mRNA levels are elevated in ρ 0 cells. Deletion of SCW11 significantly decreases the sensitivity of ρ 0 cells to SDS after salt treatment, while overexpression of SCW11 results in higher sensitivity. In addition, salt stress in ρ 0 cells induces high levels of reactive oxygen species (ROS), which further damages the cell wall, causing cells to become more sensitive towards the cell wall-perturbing agent.

Increasing intracellular trehalose is sufficient to confer desiccation tolerance to Saccharomyces cerevisiae

PubMed Central

Tapia, Hugo; Young, Lindsey; Fox, Douglas; Bertozzi, Carolyn R.; Koshland, Douglas

2015-01-01

Diverse organisms capable of surviving desiccation, termed anhydrobiotes, include species from bacteria, yeast, plants, and invertebrates. However, most organisms are sensitive to desiccation, likely due to an assortment of different stresses such as protein misfolding and aggregation, hyperosmotic stress, membrane fracturing, and changes in cell volume and shape leading to an overcrowded cytoplasm and metabolic arrest. The exact stress(es) that cause lethality in desiccation-sensitive organisms and how the lethal stresses are mitigated in desiccation-tolerant organisms remain poorly understood. The presence of trehalose in anhydrobiotes has been strongly correlated with desiccation tolerance. In the yeast Saccharomyces cerevisiae, trehalose is essential for survival after long-term desiccation. Here, we establish that the elevation of intracellular trehalose in dividing yeast by its import from the media converts yeast from extreme desiccation sensitivity to a high level of desiccation tolerance. This trehalose-induced tolerance is independent of utilization of trehalose as an energy source, de novo synthesis of other stress effectors, or the metabolic effects of trehalose biosynthetic intermediates, indicating that a chemical property of trehalose is directly responsible for desiccation tolerance. Finally, we demonstrate that elevated intracellular maltose can also make dividing yeast tolerant to short-term desiccation, indicating that other disaccharides have stress effector activity. However, trehalose is much more effective than maltose at conferring tolerance to long-term desiccation. The effectiveness and sufficiency of trehalose as an antagonizer of desiccation-induced damage in yeast emphasizes its potential to confer desiccation tolerance to otherwise sensitive organisms. PMID:25918381

Apathy in aging: are lack of interest and lack of initiative dissociable?

PubMed

Esposito, Fabienne; Rochat, Lucien; Juillerat Van der Linden, Anne-Claude; Lekeu, Françoise; Charnallet, Annik; Van der Linden, Martial

2014-01-01

Apathy is common in aging and generally defined on the basis of three dimensions: lack of initiative, lack of interest and emotional blunting. Curiously, no study until now has examined the associations and dissociations between these dimensions in elderly people (with or without dementia). These questions were addressed in two studies. In the first study, we explored the distribution of scores and the relationships between the three dimensions of apathy in 56 patients with dementia, focusing mainly on lack of initiative and lack of interest. Apathy was hetero-evaluated with the Apathy Inventory (AI), a scale widely used to assess the apathy dimensions in aging. In the second study, given the AI's limitations, we investigated in more detail the relationship between lack of initiative and interest in 115 elderly people using a new questionnaire specifically designed to assess these two dimensions. Results showed that lack of initiative was closely related to lack of interest (Study 1). Although we used a more specific questionnaire, these facets of apathy did not constitute two separable dimensions, but reflected a common main factor of apathy in aging (Study 2). Thus, the distinction between lack of initiative and lack of interest seems questionable. Only a multifactorial approach that includes the various psychological factors involved in apathy would enable one to gain a better understanding of the different manifestations of apathy and to highlight possible dissociations between them. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Comparative performance of a genetically-encoded voltage indicator and a blue voltage sensitive dye for large scale cortical voltage imaging

PubMed Central

Mutoh, Hiroki; Mishina, Yukiko; Gallero-Salas, Yasir; Knöpfel, Thomas

2015-01-01

Traditional small molecule voltage sensitive dye indicators have been a powerful tool for monitoring large scale dynamics of neuronal activities but have several limitations including the lack of cell class specific targeting, invasiveness and difficulties in conducting longitudinal studies. Recent advances in the development of genetically-encoded voltage indicators have successfully overcome these limitations. Genetically-encoded voltage indicators (GEVIs) provide sufficient sensitivity to map cortical representations of sensory information and spontaneous network activities across cortical areas and different brain states. In this study, we directly compared the performance of a prototypic GEVI, VSFP2.3, with that of a widely used small molecule voltage sensitive dye (VSD), RH1691, in terms of their ability to resolve mesoscopic scale cortical population responses. We used three synchronized CCD cameras to simultaneously record the dual emission ratiometric fluorescence signal from VSFP2.3 and RH1691 fluorescence. The results show that VSFP2.3 offers more stable and less invasive recording conditions, while the signal-to-noise level and the response dynamics to sensory inputs are comparable to RH1691 recordings. PMID:25964738

A sensitivity analysis for a thermomechanical model of the Antarctic ice sheet and ice shelves

NASA Astrophysics Data System (ADS)

Baratelli, F.; Castellani, G.; Vassena, C.; Giudici, M.

2012-04-01

The outcomes of an ice sheet model depend on a number of parameters and physical quantities which are often estimated with large uncertainty, because of lack of sufficient experimental measurements in such remote environments. Therefore, the efforts to improve the accuracy of the predictions of ice sheet models by including more physical processes and interactions with atmosphere, hydrosphere and lithosphere can be affected by the inaccuracy of the fundamental input data. A sensitivity analysis can help to understand which are the input data that most affect the different predictions of the model. In this context, a finite difference thermomechanical ice sheet model based on the Shallow-Ice Approximation (SIA) and on the Shallow-Shelf Approximation (SSA) has been developed and applied for the simulation of the evolution of the Antarctic ice sheet and ice shelves for the last 200 000 years. The sensitivity analysis of the model outcomes (e.g., the volume of the ice sheet and of the ice shelves, the basal melt rate of the ice sheet, the mean velocity of the Ross and Ronne-Filchner ice shelves, the wet area at the base of the ice sheet) with respect to the model parameters (e.g., the basal sliding coefficient, the geothermal heat flux, the present-day surface accumulation and temperature, the mean ice shelves viscosity, the melt rate at the base of the ice shelves) has been performed by computing three synthetic numerical indices: two local sensitivity indices and a global sensitivity index. Local sensitivity indices imply a linearization of the model and neglect both non-linear and joint effects of the parameters. The global variance-based sensitivity index, instead, takes into account the complete variability of the input parameters but is usually conducted with a Monte Carlo approach which is computationally very demanding for non-linear complex models. Therefore, the global sensitivity index has been computed using a development of the model outputs in a

Lack of behavioral sensitization to repeated cocaine administration from postnatal days 1 to 10.

PubMed

Meyer, J S; Yacht, A C

1993-09-01

This research determined whether sensitization (or tolerance) to the behavioral effects of cocaine in rat pups would occur following repeated cocaine administration. Rats were injected daily with 20 mg/kg of cocaine HCl s.c. from postnatal day 1 to day 10, injected with saline vehicle only, or left untreated during this period. On day 11, animals from each group were challenged with either 0, .625, 1.25, or 2.50 mg/kg of cocaine and their behavioral responses were recorded. Prior cocaine treatment did not influence the acute effects of cocaine on ultrasonic vocalizations or on any observed motor responses. In contrast, the cocaine- and saline-treated pups differed in a similar manner from the untreated control group on several behavioral measures. These results indicate that the sensitizing effects of repeated cocaine administration are not manifested during the neonatal period. However, the stimulation (stress) of handling and injection may alter the subsequent responsivity of infant rats to a cocaine challenge.

Lack of manifestations of diazoxide/5-hydroxydecanoate-sensitive KATP channel in rat brain nonsynaptosomal mitochondria.

PubMed

Brustovetsky, Tatiana; Shalbuyeva, Natalia; Brustovetsky, Nickolay

2005-10-01

Pharmacological modulation of the mitochondrial ATP-sensitive K+ channel (mitoKATP) sensitive to diazoxide and 5-hydroxydecanoate (5-HD) represents an attractive strategy to protect cells against ischaemia/reperfusion- and stroke-related injury. To re-evaluate a functional role for the mitoKATP in brain, we used Percoll-gradient-purified brain nonsynaptosomal mitochondria in a light absorbance assay, in radioisotope measurements of matrix volume, and in measurements of respiration, membrane potential (DeltaPsi) and depolarization-induced K+ efflux. The changes in mitochondrial morphology were evaluated by transmission electron microscopy (TEM). Polyclonal antibodies raised against certain fragments of known sulphonylurea receptor subunits, SUR1 and SUR2, and against different epitopes of K+ inward rectifier subunits Kir 6.1 and Kir 6.2 of the ATP-sensitive K+ channel of the plasma membrane (cellKATP), were employed to detect similar subunits in brain mitochondria. A variety of plausible blockers (ATP, 5-hydroxydecanoate, glibenclamide, tetraphenylphosphonium cation) and openers (diazoxide, pinacidil, chromakalim, minoxidil, testosterone) of the putative mitoKATP were applied to show the role of the channel in regulating matrix volume, respiration, and DeltaPsi and K+ fluxes across the inner mitochondrial membrane. None of the pharmacological agents applied to brain mitochondria in the various assays pinpointed processes that could be unequivocally associated with mitoKATP activity. In addition, immunoblotting analysis did not provide explicit evidence for the presence of the mitoKATP, similar to the cellKATP, in brain mitochondria. On the other hand, the depolarization-evoked release of K+ suppressed by ATP could be re-activated by carboxyatractyloside, an inhibitor of the adenine nucleotide translocase (ANT). Moreover, bongkrekic acid, another inhibitor of the ANT, inhibited K+ efflux similarly to ATP. These observations implicate the ANT in ATP-sensitive K

Partners in Self-Sufficiency Guidebook.

ERIC Educational Resources Information Center

Department of Housing and Urban Development, Washington, DC. Office of Policy Development and Research.

This guidebook is for community leaders who are implementing the Federal Partners in Self-Sufficiency (PS-S) program, a community-based approach to service delivery that helps families get off welfare. The program offers a comprehensive package of services including housing, education, child care, transportation, counseling, and job training and…

Detection of potentially skin sensitizing hydroperoxides of linalool in fragranced products.

PubMed

Kern, Susanne; Dkhil, Hafida; Hendarsa, Prisca; Ellis, Graham; Natsch, Andreas

2014-10-01

On prolonged exposure to air, linalool can form sensitizing hydroperoxides. Positive hydroperoxide patch tests in dermatitis patients have frequently been reported, but their relevance has not been established. Owing to a lack of analytical methods and data, it is unclear from which sources the public might be exposed to sufficient quantities of hydroperoxides for induction of sensitization to occur. To address this knowledge gap, we developed analytical methods and performed stability studies for fine fragrances and deodorants/antiperspirants. In parallel, products recalled from consumers were analysed to investigate exposure to products used in everyday life. Liquid chromatography-mass spectrometry with high mass resolution was found to be optimal for the selective and sensitive detection of the organic hydroperoxide in the complex product matrix. Linalool hydroperoxide was detected in natural linalool, but the amount was not elevated by storage in a perfume formulation exposed to air. No indication of hydroperoxide formation in fine fragrances was found in stability studies. Aged fine fragrances recalled from consumers contained a geometric mean linalool concentration of 1,888 μg/g and, corrected for matrix effects, linalool hydroperoxide at a concentration of around 14 μg/g. In antiperspirants, we detected no oxidation products. In conclusion, very low levels of linalool hydroperoxide in fragranced products may originate from raw materials, but we found no evidence for oxidation during storage of products. The levels detected are orders of magnitude below the levels inducing sensitization in experimental animals, and these results therefore do not substantiate a causal link between potential hydroperoxide formation in cosmetics and positive results of patch tests.

Adhesion to the host cell surface is sufficient to mediate Listeria monocytogenes entry into epithelial cells

PubMed Central

Ortega, Fabian E.; Rengarajan, Michelle; Chavez, Natalie; Radhakrishnan, Prathima; Gloerich, Martijn; Bianchini, Julie; Siemers, Kathleen; Luckett, William S.; Lauer, Peter; Nelson, W. James; Theriot, Julie A.

2017-01-01

The intestinal epithelium is the first physiological barrier breached by the Gram-positive facultative pathogen Listeria monocytogenes during an in vivo infection. Listeria monocytogenes binds to the epithelial host cell receptor E-cadherin, which mediates a physical link between the bacterium and filamentous actin (F-actin). However, the importance of anchoring the bacterium to F-actin through E-cadherin for bacterial invasion has not been tested directly in epithelial cells. Here we demonstrate that depleting αE-catenin, which indirectly links E-cadherin to F-actin, did not decrease L. monocytogenes invasion of epithelial cells in tissue culture. Instead, invasion increased due to increased bacterial adhesion to epithelial monolayers with compromised cell–cell junctions. Furthermore, expression of a mutant E-cadherin lacking the intracellular domain was sufficient for efficient L. monocytogenes invasion of epithelial cells. Importantly, direct biotin-mediated binding of bacteria to surface lipids in the plasma membrane of host epithelial cells was sufficient for uptake. Our results indicate that the only requirement for L. monocytogenes invasion of epithelial cells is adhesion to the host cell surface, and that E-cadherin–mediated coupling of the bacterium to F-actin is not required. PMID:28877987

Directly tailoring photon-electron coupling for sensitive photoconductance

NASA Astrophysics Data System (ADS)

Huang, Zhiming; Zhou, Wei; Huang, Jingguo; Wu, Jing; Gao, Yanqing; Qu, Yue; Chu, Junhao

2016-03-01

The coupling between photons and electrons is at the heart of many fundamental phenomena in nature. Despite tremendous advances in controlling electrons by photons in engineered energy-band systems, control over their coupling is still widely lacking. Here we demonstrate an unprecedented ability to couple photon-electron interactions in real space, in which the incident electromagnetic wave directly tailors energy bands of solid to generate carriers for sensitive photoconductance. By spatially coherent manipulation of metal-wrapped material system through anti-symmetric electric field of the irradiated electromagnetic wave, electrons in the metals are injected and accumulated in the induced potential well (EIW) produced in the solid. Respective positive and negative electric conductances are easily observed in n-type and p-type semiconductors into which electrons flow down from the two metallic sides under light irradiation. The photoconductivity is further confirmed by sweeping the injected electrons out of the semiconductor before recombination applied by sufficiently strong electric fields. Our work opens up new perspectives for tailoring energy bands of solids and is especially relevant to develop high effective photon detection, spin injection, and energy harvesting in optoelectronics and electronics.

Role of sufficient phosphorus in biodiesel production from diatom Phaeodactylum tricornutum.

PubMed

Yu, Shi-Jin; Shen, Xiao-Fei; Ge, Huo-Qing; Zheng, Hang; Chu, Fei-Fei; Hu, Hao; Zeng, Raymond J

2016-08-01

In order to study the role of sufficient phosphorus (P) in biodiesel production by microalgae, Phaeodactylum tricornutum were cultivated in six different media treatments with combination of nitrogen (N) sufficiency/deprivation and phosphorus sufficiency/limitation/deprivation. Profiles of N and P, biomass, and fatty acids (FAs) content and compositions were measured during a 7-day cultivation period. The results showed that the FA content in microalgae biomass was promoted by P deprivation. However, statistical analysis showed that FA productivity had no significant difference (p = 0.63, >0.05) under the treatments of N deprivation with P sufficiency (N-P) and N deprivation with P deprivation (N-P-), indicating P sufficiency in N deprivation medium has little effect on increasing biodiesel productivity from P. triornutum. It was also found that the P absorption in N-P medium was 1.41 times higher than that in N sufficiency and P sufficiency (NP) medium. N deprivation with P limitation (N-P-l) was the optimal treatment for producing biodiesel from P. triornutum because of both the highest FA productivity and good biodiesel quality.

Study designs for determining and comparing sensitivities of disease screening tests.

PubMed

Prorok, Philip C; Kramer, Barnett S; Miller, Anthony B

2015-12-01

To investigate the capability of various study designs to determine the sensitivity of a disease screening test. Quantities that can be calculated from these designs were derived and examined for their relationship to true sensitivity (the ability to detect unrecognized disease that would surface clinically in the absence of screening) and overdiagnosis. To examine the sensitivity of one test, the single cohort design, in which all participants receive the test, is particularly weak, providing only an upper bound on the true sensitivity, and yields no information about overdiagnosis. A randomized design, with one control arm and participants tested in the other, that includes sufficient post-screening follow-up, allows calculation of bounds on, and an approximation to, true sensitivity and also determination of overdiagnosis. Without follow-up, bounds on the true sensitivity can be calculated. To compare two tests, the single cohort paired design in which all participants receive both tests is precarious. The three arm randomized design with post screening follow-up is preferred, yielding an approximation to the true sensitivity, bounds on the true sensitivity, and the extent of overdiagnosis of each test. Without post screening follow-up, bounds on the true sensitivities can be calculated. When an unscreened control arm is not possible, the two-arm randomized design is recommended. Individual test sensitivities cannot be determined, but with sufficient post-screening follow-up, an order relationship can be established, as can the difference in overdiagnosis between the two tests. © The Author(s) 2015.

Minimal sufficient positive-operator valued measure on a separable Hilbert space

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

Kuramochi, Yui, E-mail: kuramochi.yui.22c@st.kyoto-u.ac.jp

We introduce a concept of a minimal sufficient positive-operator valued measure (POVM), which is the least redundant POVM among the POVMs that have the equivalent information about the measured quantum system. Assuming the system Hilbert space to be separable, we show that for a given POVM, a sufficient statistic called a Lehmann-Scheffé-Bahadur statistic induces a minimal sufficient POVM. We also show that every POVM has an equivalent minimal sufficient POVM and that such a minimal sufficient POVM is unique up to relabeling neglecting null sets. We apply these results to discrete POVMs and information conservation conditions proposed by the author.

Safety profile of hymenoptera venom immunotherapy (VIT) in monosensitized patients: lack of new sensitization to nontreated insect venom.

PubMed

Spoerl, D; Bircher, A J; Scherer, K

2011-01-01

Venom immunotherapy (VIT) has proven to be efficacious in reducing the severity of anaphylactic reactions following field stings in patients with Hymenoptera venom allergy. Due to sequence homologies in the allergens used in Hymenoptera vaccines, there is concern that immunotherapy could lead to sensitization to allergens to which patients were not previously sensitized. The relevance of such an undesired phenomenon is unclear. To investigate the incidence of sensitization to Hymenoptera venoms other than those to which the patients were already sensitized and to assess the overall safety profile of VIT in order to compare the risk-benefit ratio in a subpopulation of monosensitized individuals. We performed a retrospective analysis of specific immunoglobulin E (sIgE) levels in patients with no prior detectable sIgE to Hymenoptera venom other than the one for which they received VIT. We assessed the safety profile of VIT using serological and clinical parameters. Of the 56 monosensitized patients who had VIT, 3 (5%) developed sIgE to the other insect with no history of field sting to explain it. This rate was similar to the rate of new sensitization due to field stings during VIT. VIT was well-tolerated and levels of serological markers improved. No patient had a systemic anaphylactic reaction after having been stung by an insect other than the one he/she was desensitized for during follow-up. VIT seems to be safe with respect to clinically significant new sensitizations.

Lack of the purinergic receptor P2X7 results in resistance to contact hypersensitivity

PubMed Central

Weber, Felix C.; Esser, Philipp R.; Müller, Tobias; Ganesan, Jayanthi; Pellegatti, Patrizia; Simon, Markus M.; Zeiser, Robert; Idzko, Marco; Jakob, Thilo

2010-01-01

Sensitization to contact allergens requires activation of the innate immune system by endogenous danger signals. However, the mechanisms through which contact allergens activate innate signaling pathways are incompletely understood. In this study, we demonstrate that mice lacking the adenosine triphosphate (ATP) receptor P2X7 are resistant to contact hypersensitivity (CHS). P2X7-deficient dendritic cells fail to induce sensitization to contact allergens and do not release IL-1β in response to lipopolysaccharide (LPS) and ATP. These defects are restored by pretreatment with LPS and alum in an NLRP3- and ASC-dependent manner. Whereas pretreatment of wild-type mice with P2X7 antagonists, the ATP-degrading enzyme apyrase or IL-1 receptor antagonist, prevents CHS, IL-1β injection restores CHS in P2X7-deficient mice. Thus, P2X7 is a crucial receptor for extracellular ATP released in skin in response to contact allergens. The lack of P2X7 triggering prevents IL-1β release, which is an essential step in the sensitization process. Interference with P2X7 signaling may be a promising strategy for the prevention of allergic contact dermatitis. PMID:21059855

An integrated molecular docking and rescoring method for predicting the sensitivity spectrum of various serine hydrolases to organophosphorus pesticides.

PubMed

Yang, Ling-Ling; Yang, Xiao; Li, Guo-Bo; Fan, Kai-Ge; Yin, Peng-Fei; Chen, Xiang-Gui

2016-04-01

The enzymatic chemistry method is currently the most widely used method for the rapid detection of organophosphorus (OP) pesticides, but the enzymes used, such as cholinesterases, lack sufficient sensitivity to detect low concentrations of OP pesticides present in given samples. Serine hydrolase is considered an ideal enzyme source in seeking high-sensitivity enzymes used for OP pesticide detection. However, it is difficult to systematically evaluate sensitivities of various serine hydrolases to OP pesticides by in vitro experiments. This study aimed to establish an in silico method to predict the sensitivity spectrum of various serine hydrolases to OP pesticides. A serine hydrolase database containing 219 representative serine hydrolases was constructed. Based on this database, an integrated molecular docking and rescoring method was established, in which the AutoDock Vina program was used to produce the binding poses of OP pesticides to various serine hydrolases and the ID-Score method developed recently by us was adopted as a rescoring method to predict their binding affinities. In retrospective case studies, this method showed good performance in predicting the sensitivities of known serine hydrolases to two OP pesticides: paraoxon and diisopropyl fluorophosphate. The sensitivity spectrum of the 219 collected serine hydrolases to 37 commonly used OP pesticides was finally obtained using this method. Overall, this study presented a promising in silico tool to predict the sensitivity spectrum of various serine hydrolases to OP pesticides, which will help in finding high-sensitivity serine hydrolases for OP pesticide detection. © 2015 Society of Chemical Industry.

Impact of Market Behavior, Fleet Composition, and Ancillary Services on Revenue Sufficiency

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

Frew, Bethany; Gallo, Giulia; Brinkman, Gregory

work. The analysis also shows that generators face revenue sufficiency challenges in this ERCOT-like energy-only market model; net revenues provided by the market in all base markup cases and sensitivity scenarios (except when a large fraction of the existing coal fleet is retired) are not sufficient to justify investments in new capacity for thermal and nuclear power units. Overall, the work described in this paper points to the need for improved behavioral models of electricity markets to more accurately study current and potential market design issues that could arise in systems with high penetrations of renewable generation.« less

Ultra-sensitive detection using integrated waveguide technologies

USDA-ARS?s Scientific Manuscript database

There is a pressing need to detect analytes at very low concentrations, such as food- and water-borne pathogens (e.g. E. coli O157:H7) and biothreat agents (e.g., anthrax, toxins). Common fluorescence detection methods, such as 96 well plate readers, are not sufficiently sensitive for low concentra...

Improving the Perception of Self-Sufficiency towards Creative Drama

ERIC Educational Resources Information Center

Pekdogan, Serpil; Korkmaz, Halil Ibrahim

2016-01-01

The purpose of this study is to investigate the effects of a Creative Drama Based Perception of Self-sufficiency Skills Training Program on 2nd grade bachelor degree students' (who are attending a preschool teacher training program) perception of self-sufficiency. This is a quasi-experimental study. Totally 50 students were equally divided into…

Sufficient conditions for uniqueness of the weak value

NASA Astrophysics Data System (ADS)

Dressel, J.; Jordan, A. N.

2012-01-01

We review and clarify the sufficient conditions for uniquely defining the generalized weak value as the weak limit of a conditioned average using the contextual values formalism introduced in Dressel, Agarwal and Jordan (2010 Phys. Rev. Lett. 104 240401). We also respond to criticism of our work by Parrott (arXiv:1105.4188v1) concerning a proposed counter-example to the uniqueness of the definition of the generalized weak value. The counter-example does not satisfy our prescription in the case of an underspecified measurement context. We show that when the contextual values formalism is properly applied to this example, a natural interpretation of the measurement emerges and the unique definition in the weak limit holds. We also prove a theorem regarding the uniqueness of the definition under our sufficient conditions for the general case. Finally, a second proposed counter-example by Parrott (arXiv:1105.4188v6) is shown not to satisfy the sufficiency conditions for the provided theorem.

Reassessing Rogers' necessary and sufficient conditions of change.

PubMed

Watson, Jeanne C

2007-09-01

This article reviews the impact of Carl Rogers' postulate about the necessary and sufficient conditions of therapeutic change on the field of psychotherapy. It is proposed that his article (see record 2007-14630-002) made an impact in two ways; first, by acting as a spur to researchers to identify the active ingredients of therapeutic change; and, second, by providing guidelines for therapeutic practice. The role of the necessary and sufficient conditions in process-experiential therapy, an emotion-focused therapy for individuals, and their limitations in terms of research and practice are discussed. It is proposed that although the conditions are necessary and important in promoting clients' affect regulation, they do not take sufficient account of other moderating variables that affect clients' response to treatment and may need to be balanced with more structured interventions. Notwithstanding, Rogers highlighted a way of interacting with clients that is generally acknowledged as essential to effective psychotherapy practice. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Assessing sufficiency of thermal riverscapes for resilient ...

EPA Pesticide Factsheets

Resilient salmon populations require river networks that provide water temperature regimes sufficient to support a diversity of salmonid life histories across space and time. Efforts to protect, enhance and restore watershed thermal regimes for salmon may target specific locations and features within stream networks hypothesized to provide disproportionately high-value functional resilience to salmon populations. These include relatively small-scale features such as thermal refuges, and larger-scale features such as entire watersheds or aquifers that support thermal regimes buffered from local climatic conditions. Quantifying the value of both small and large scale thermal features to salmon populations has been challenged by both the difficulty of mapping thermal regimes at sufficient spatial and temporal resolutions, and integrating thermal regimes into population models. We attempt to address these challenges by using newly-available datasets and modeling approaches to link thermal regimes to salmon populations across scales. We will describe an individual-based modeling approach for assessing sufficiency of thermal refuges for migrating salmon and steelhead in large rivers, as well as a population modeling approach for assessing large-scale climate refugia for salmon in the Pacific Northwest. Many rivers and streams in the Pacific Northwest are currently listed as impaired under the Clean Water Act as a result of high summer water temperatures. Adverse effec

Self-Monitoring Artificial Red Cells with Sufficient Oxygen Supply for Enhanced Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Luo, Zhenyu; Zheng, Mingbin; Zhao, Pengfei; Chen, Ze; Siu, Fungming; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

2016-03-01

Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.

On multi-sensitivity with respect to a vector

NASA Astrophysics Data System (ADS)

Jiao, Lixin; Wang, Lidong; Li, Fengquan; Liu, Heng

2018-05-01

Consider the surjective continuous map f: X → X defined on a compact metric space X. Let 𝒦(X) be the space of all non-empty compact subsets of X equipped with the Hausdorff metric and define f¯: 𝒦(X) →𝒦(X) by f¯(A) = {f(a),a ∈ A} for any A ∈𝒦(X). In this paper, we introduce several stronger versions of sensitivities, such as multi-sensitivity with respect to a vector, 𝒩-sensitivity, strong multi-sensitivity. We obtain some basic properties of the concepts of these sensitivities and discuss the relationships with other sensitivities for continuous self-map on [0,1]. Some sufficient conditions for a dynamical system to be 𝒩-sensitive are presented. Also, it is shown that the strong multi-sensitivity of f implies that f¯ is 𝒩-sensitive. In turn, the 𝒩-sensitivity of f¯ implies that f is 𝒩-sensitive. In particular, it is proved that if f is a multi-transitive map with dense periodic sets, then f is 𝒩-sensitive. Finally, we give a multi-sensitive example which is not 𝒩-sensitive.

Epidermal jasmonate perception is sufficient for all aspects of jasmonate-mediated male fertility in Arabidopsis.

PubMed

Jewell, Jeremy B; Browse, John

2016-03-01

Jasmonate (JA) signaling is essential for several environmental responses and reproductive development in many plant species. In Arabidopsis thaliana, the most obvious phenotype of JA biosynthetic and perception mutants is profound sporophytic male sterility characterized by failure of stamen filament elongation, severe delay of anther dehiscence and pollen inviability. The site of action of JA in the context of reproductive development has been discussed, but the ideas have not been tested experimentally. To this end we used targeted expression of a COI1-YFP transgene in the coi1-1 mutant background. As COI1 is an essential component of the JA co-receptor complex, the null coi1-1 mutant is male sterile due to lack of JA perception. We show that expression of COI1-YFP in the epidermis of the stamen filament and anther in coi1 mutant plants is sufficient to rescue filament elongation, anther dehiscence and pollen viability. In contrast, filament expression alone or expression in the tapetum do not restore dehiscence and pollen viability. These results demonstrate that epidermal JA perception is sufficient for anther function and pollen viability, and suggest the presence of a JA-dependent non-autonomous signal produced in the anther epidermis to synchronize both anther dehiscence and pollen maturation. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Behavioral Interventions to Advance Self-Sufficiency

ERIC Educational Resources Information Center

MDRC, 2017

2017-01-01

As the first major effort to use a behavioral economics lens to examine human services programs that serve poor and vulnerable families in the United States, the Behavioral Interventions to Advance Self-Sufficiency (BIAS) project demonstrated the value of applying behavioral insights to improve the efficacy of human services programs. The BIAS…

Grid sensitivity for aerodynamic optimization and flow analysis

NASA Technical Reports Server (NTRS)

Sadrehaghighi, I.; Tiwari, S. N.

1993-01-01

After reviewing relevant literature, it is apparent that one aspect of aerodynamic sensitivity analysis, namely grid sensitivity, has not been investigated extensively. The grid sensitivity algorithms in most of these studies are based on structural design models. Such models, although sufficient for preliminary or conceptional design, are not acceptable for detailed design analysis. Careless grid sensitivity evaluations, would introduce gradient errors within the sensitivity module, therefore, infecting the overall optimization process. Development of an efficient and reliable grid sensitivity module with special emphasis on aerodynamic applications appear essential. The organization of this study is as follows. The physical and geometric representations of a typical model are derived in chapter 2. The grid generation algorithm and boundary grid distribution are developed in chapter 3. Chapter 4 discusses the theoretical formulation and aerodynamic sensitivity equation. The method of solution is provided in chapter 5. The results are presented and discussed in chapter 6. Finally, some concluding remarks are provided in chapter 7.

Concept analysis: lack of anonymity.

PubMed

Swan, Marilyn A; Hobbs, Barbara B

2017-05-01

To re-examine and expand understanding of the concept 'lack of anonymity' as a component of rural nursing theory. Early healthcare literature reports lack of anonymity as part of social and working environments, particularly rural nursing. Rural nursing theory included the first published concept analysis on lack of anonymity but lacked empirical referents. Workforce, societal and rural healthcare changes support an updated analysis. To further understand lack of anonymity, its present day use and applicability to diverse environments, research from multiple disciplines was reviewed. Concept analysis. A literature search using eight terms in eleven databases was conducted of literature published between 2008-2013. Walker and Avant's concept analysis methodology guided the analysis. The previous concept analysis is supported in part by current literature. The defining attributes, 'identifiable', 'establishing boundaries for public and private self and interconnectedness' in a community were updated. Updated antecedents include: (i) environmental context; (ii) opportunities to become visible; (iii) developing relationships and (iv) unconscious or limited awareness of public or personal privacy. Consequences are: (i) familiarity; (ii) visibility; (iii) awareness of privacy and (iv) manage or balance of lack of anonymity. Cases were constructed and empirical referents identified. The concept of lack of anonymity was updated; portions of the original definition remain unchanged. Empirical referents reveal the defining attributes in daily life and may guide future research on the effect of lack of anonymity on nursing practice. This analysis advances the conceptual understanding of rural nursing theory. © 2016 John Wiley & Sons Ltd.

On the topological sensitivity of cellular automata

NASA Astrophysics Data System (ADS)

Baetens, Jan M.; De Baets, Bernard

2011-06-01

Ever since the conceptualization of cellular automata (CA), much attention has been paid to the dynamical properties of these discrete dynamical systems, and, more in particular, to their sensitivity to the initial condition from which they are evolved. Yet, the sensitivity of CA to the topology upon which they are based has received only minor attention, such that a clear insight in this dependence is still lacking and, furthermore, a quantification of this so-called topological sensitivity has not yet been proposed. The lack of attention for this issue is rather surprising since CA are spatially explicit, which means that their dynamics is directly affected by their topology. To overcome these shortcomings, we propose topological Lyapunov exponents that measure the divergence of two close trajectories in phase space originating from a topological perturbation, and we relate them to a measure grasping the sensitivity of CA to their topology that relies on the concept of topological derivatives, which is introduced in this paper. The validity of the proposed methodology is illustrated for the 256 elementary CA and for a family of two-state irregular totalistic CA.

Food self-sufficiency across scales: how local can we go?

PubMed

Pradhan, Prajal; Lüdeke, Matthias K B; Reusser, Dominik E; Kropp, Juergen P

2014-08-19

This study explores the potential for regions to shift to a local food supply using food self-sufficiency (FSS) as an indicator. We considered a region food self-sufficient when its total calorie production is enough to meet its demand. For future scenarios, we considered population growth, dietary changes, improved feed conversion efficiency, climate change, and crop yield increments. Starting at the 5' resolution, we investigated FSS from the lowest administrative levels to continents. Globally, about 1.9 billion people are self-sufficient within their 5' grid, while about 1 billion people from Asia and Africa require cross-continental agricultural trade in 2000. By closing yield gaps, these regions can achieve FSS, which also reduces international trade and increases a self-sufficient population in a 5' grid to 2.9 billion. The number of people depending on international trade will vary between 1.5 and 6 billion by 2050. Climate change may increase the need for international agricultural trade by 4% to 16%.

Memory CD8+ T cells are sufficient to alleviate impaired host resistance to influenza A virus infection caused by neonatal oxygen supplementation.

PubMed

Giannandrea, Matthew; Yee, Min; O'Reilly, Michael A; Lawrence, B Paige

2012-09-01

Supplemental oxygen administered to preterm infants is an important clinical intervention, but it is associated with life-long changes in lung development and increased sensitivity to respiratory viral infections. The precise immunological changes caused by neonatal oxygen treatment remain poorly understood. We previously reported that adult mice exposed to supplemental oxygen as neonates display persistent pulmonary inflammation and enhanced mortality after a sublethal influenza A virus infection. These changes suggest that neonatal hyperoxia impairs the cytotoxic CD8(+) T cell response required to clear the virus. In this study, we show that although host resistance to several different strains of influenza A virus is reduced by neonatal hyperoxia, this treatment does not impair viral clearance, nor does it alter the magnitude of the virus-specific CD8(+) T cell response to primary infection. Moreover, memory T cells are sufficient to ameliorate the increased morbidity and mortality and alleviate the excessive lung damage observed in mice exposed to high oxygen levels as neonates, and we attribute this sufficiency principally to virus-specific memory CD8(+) T cells. Thus, we show that neonatal hyperoxia reduces host resistance to influenza virus infection without diminishing the function of cytotoxic T lymphocytes or the generation of virus-specific memory T cells and that CD8(+) memory T cells are sufficient to provide protection from negative consequences of this important life-saving intervention. Our findings suggest that vaccines that generate robust T cell memory may be efficacious at reducing the increased sensitivity to respiratory viral infections in people born prematurely.

33 CFR 115.30 - Sufficiency of State authority for bridges.

Code of Federal Regulations, 2011 CFR

2011-07-01

... for bridges. 115.30 Section 115.30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.30 Sufficiency of State authority for bridges. An opinion of the attorney general of the State as to the sufficiency of State...

33 CFR 115.30 - Sufficiency of State authority for bridges.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for bridges. 115.30 Section 115.30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.30 Sufficiency of State authority for bridges. An opinion of the attorney general of the State as to the sufficiency of State...

Making Sense of Palaeoclimate Sensitivity

NASA Technical Reports Server (NTRS)

Rohling, E. J.; Sluijs, A.; DeConto, R.; Drijfhout, S. S.; Fedorov, A.; Foster, G. L.; Ganopolski, A.; Hansen, J.; Honisch, B.; Hooghiemstra, H.;

LUCK AND HISTORY-SENSITIVE COMPATIBILISM

PubMed Central

Levy, Neil

2009-01-01

Libertarianism seems vulnerable to a serious problem concerning present luck, because it requires indeterminism somewhere in the causal chain leading to directly free action. Compatibilism, in contrast, is thought to be free of this problem, as not requiring indeterminism in the causal chain. I argue that this view is false: compatibilism is subject to a problem of present luck. This is less of a problem for compatibilism than for libertarianism. However, its effects are just as devastating for one kind of compatibilism, the kind of compatibilism which is history-sensitive, and therefore must take the problem of constitutive luck seriously. The problem of present luck confronting compatibilism is sufficient to undermine the history-sensitive compatibilist’s response to remote – constitutive – luck. PMID:19649158

High-field modulated ion-selective field-effect-transistor (FET) sensors with sensitivity higher than the ideal Nernst sensitivity.

PubMed

Chen, Yi-Ting; Sarangadharan, Indu; Sukesan, Revathi; Hseih, Ching-Yen; Lee, Geng-Yen; Chyi, Jen-Inn; Wang, Yu-Lin

2018-05-29

Lead ion selective membrane (Pb-ISM) coated AlGaN/GaN high electron mobility transistors (HEMT) was used to demonstrate a whole new methodology for ion-selective FET sensors, which can create ultra-high sensitivity (-36 mV/log [Pb 2+ ]) surpassing the limit of ideal sensitivity (-29.58 mV/log [Pb 2+ ]) in a typical Nernst equation for lead ion. The largely improved sensitivity has tremendously reduced the detection limit (10 -10  M) for several orders of magnitude of lead ion concentration compared to typical ion-selective electrode (ISE) (10 -7  M). The high sensitivity was obtained by creating a strong filed between the gate electrode and the HEMT channel. Systematical investigation was done by measuring different design of the sensor and gate bias, indicating ultra-high sensitivity and ultra-low detection limit obtained only in sufficiently strong field. Theoretical study in the sensitivity consistently agrees with the experimental finding and predicts the maximum and minimum sensitivity. The detection limit of our sensor is comparable to that of Inductively-Coupled-Plasma Mass Spectrum (ICP-MS), which also has detection limit near 10 -10  M.

High Sensitivity SPECT for Small Animals and Plants

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

Mitchell, Gregory S.

Imaging systems using single gamma-ray emitting radioisotopes typically implement collimators in order to form the images. However, a tradeoff in sensitivity is inherent in the use of collimators, and modern preclinical single-photon emission computed tomography (SPECT) systems detect a very small fraction of emitted gamma-rays (<0.3%). We have built a collimator-less system, which can reach sensitivity of 40% for 99mTc imaging, while still producing images of sufficient spatial resolution for certain applications in thin objects such as mice, small plants, and well plates used for in vitro experiments.

Quantification is Neither Necessary Nor Sufficient for Measurement

NASA Astrophysics Data System (ADS)

Mari, Luca; Maul, Andrew; Torres Irribarra, David; Wilson, Mark

2013-09-01

Being an infrastructural, widespread activity, measurement is laden with stereotypes. Some of these concern the role of measurement in the relation between quality and quantity. In particular, it is sometimes argued or assumed that quantification is necessary for measurement; it is also sometimes argued or assumed that quantification is sufficient for or synonymous with measurement. To assess the validity of these positions the concepts of measurement and quantitative evaluation should be independently defined and their relationship analyzed. We contend that the defining characteristic of measurement should be the structure of the process, not a feature of its results. Under this perspective, quantitative evaluation is neither sufficient nor necessary for measurement.

Sensitivity to Sunburn Is Associated with Susceptibility to Ultraviolet Radiation–Induced Suppression of Cutaneous Cell–Mediated Immunity

PubMed Central

Kelly, Deirdre A.; Young, Antony R.; McGregor, Jane M.; Seed, Paul T.; Potten, Christopher S.; Walker, Susan L.

2000-01-01

Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P < 0.001), and a moderate sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer. PMID:10662801

Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells.

PubMed

Kievit, Paul; Howard, Jane K; Badman, Michael K; Balthasar, Nina; Coppari, Roberto; Mori, Hiroyuki; Lee, Charlotte E; Elmquist, Joel K; Yoshimura, Akihiko; Flier, Jeffrey S

2006-08-01

Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

PPARα siRNA–Treated Expression Profiles Uncover the Causal Sufficiency Network for Compound-Induced Liver Hypertrophy

PubMed Central

Dai, Xudong; Souza, Angus T. De; Dai, Hongyue; Lewis, David L; Lee, Chang-kyu; Spencer, Andy G; Herweijer, Hans; Hagstrom, Jim E; Linsley, Peter S; Bassett, Douglas E; Ulrich, Roger G; He, Yudong D

2007-01-01

Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi) phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs) against the gene for peroxisome proliferator-activated receptor α (Ppara), our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARα-induced liver hypertrophy is supported by their ability to predict non-PPARα–induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005). Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug-induced toxicity from

Chinese nurses' perceived barriers and facilitators of ethical sensitivity.

PubMed

Huang, Fei Fei; Yang, Qing; Zhang, Jie; Khoshnood, Kaveh; Zhang, Jing Ping

2016-08-01

An overview of ethical sensitivity among Chinese registered nurses is needed to develop and optimize the education programs and interventions to cultivate and improve ethical sensitivity. The study was conducted to explore the barriers to and facilitators of ethical sensitivity among Chinese registered nurses working in hospital settings. A convergent parallel mixed-methods research design was adopted. In the cross-sectional quantitative study, the Chinese Moral Sensitivity Questionnaire-revised version was used to assess the levels of ethical sensitivity among registered nurses, and the scores were correlated with key demographics, training experiences in ethics, and workplace cultural environments (n = 306). In the qualitative study, semi-structured interviews were used to elicit the nurses' perceptions of the barriers and facilitators in nurturing ethical sensitivity (n = 15). The data were collected from February to June 2014. This study was approved by the Institutional Review Boards of Yale University and Central South University. Despite moderately high overall Chinese Moral Sensitivity Questionnaire-revised version scores, the ethical sensitivity among Chinese nurses lags in practice. Barriers to ethical sensitivity include the lack of knowledge related to ethics, lack of working experience as a nurse, the hierarchical organizational climate, and the conformist working attitude. The positive workplace cultural environments and application of ethical knowledge in practice were considered potential facilitators of ethical sensitivity. The findings of this study were compared with studies from other countries to examine the barriers and facilitators of ethical sensitivity in Chinese nurses. This mixed-methods study showed that even though the Chinese nurses have moderately high sensitivity to the ethical issues encountered in hospitals, there is still room for improvement. The barriers to and facilitators of ethical sensitivity identified here offer new and

Sensitivity of a Wave Structure to Initial Conditions

NASA Technical Reports Server (NTRS)

Duval, Walter M. B.; Duval, Walter M. B. (Technical Monitor)

2000-01-01

Microgravity experiments aimed at quantifying effects of gentler via controlled sinusoidal forcing transmitted on the interface between two miscible liquids have shown the evolution of a quasi -stationary four-mode wave structure oriented vertically. The sensitivity of the wave structure to phase angle variation is investigated computationally. We show that a slight variation of the phase angle is sufficient to cause a bifurcation to a two-mode structure. The dependence of phase angle on wave structure is attributed to sensitivity on initial conditions due to the strong nonlinearity of the coupled field equations for the parametric space of interest.

Habituation and sensitization in primary headaches

PubMed Central

2013-01-01

The phenomena of habituation and sensitization are considered most useful for studying the neuronal substrates of information processing in the CNS. Both were studied in primary headaches, that are functional disorders of the brain characterized by an abnormal responsivity to any kind of incoming innocuous or painful stimuli and it’s cycling pattern over time (interictal, pre-ictal, ictal). The present review summarizes available data on stimulus responsivity in primary headaches obtained with clinical neurophysiology. In migraine, the majority of electrophysiological studies between attacks have shown that, for a number of different sensory modalities, the brain is characterised by a lack of habituation of evoked responses to repeated stimuli. This abnormal processing of the incoming information reaches its maximum a few days before the beginning of an attack, and normalizes during the attack, at a time when sensitization may also manifest itself. An abnormal rhythmic activity between thalamus and cortex, namely thalamocortical dysrhythmia, may be the pathophysiological mechanism subtending abnormal information processing in migraine. In tension-type headache (TTH), only few signs of deficient habituation were observed only in subgroups of patients. By contrast, using grand-average responses indirect evidence for sensitization has been found in chronic TTH with increased nociceptive specific reflexes and evoked potentials. Generalized increased sensitivity to pain (lower thresholds and increased pain rating) and a dysfunction in supraspinal descending pain control systems may contribute to the development and/or maintenance of central sensitization in chronic TTH. Cluster headache patients are chrarcterized during the bout and on the headache side by a pronounced lack of habituation of the brainstem blink reflex and a general sensitization of pain processing. A better insight into the nature of these ictal/interictal electrophysiological dysfunctions in primary

Atomic magnetometer-based ultra-sensitive magnetic microscopy

NASA Astrophysics Data System (ADS)

Kim, Young Jin; Savukov, Igor

2016-03-01

An atomic magnetometer (AM) based on lasers and alkali-metal vapor cells is currently the most sensitive non-cryogenic magnetic-field sensor. Many applications in neuroscience and other fields require high resolution, high sensitivity magnetic microscopic measurements. In order to meet this need we combined a cm-size spin-exchange relaxation-free AM with a flux guide (FG) to produce an ultra-sensitive FG-AM magnetic microscope. The FG serves to transmit the target magnetic flux to the AM thus enhancing both the sensitivity and resolution for tiny magnetic objects. In this talk, we will describe a prototype FG-AM device and present experimental and numerical tests of its sensitivity and resolution. We also demonstrate that an optimized FG-AM achieves high resolution and high sensitivity sufficient to detect a magnetic field of a single neuron in a few seconds, which would be an important milestone in neuroscience. We anticipate that this unique device can be applied to the detection of a single neuron, the detection of magnetic nano-particles, which in turn are very important for detection of target molecules in national security and medical diagnostics, and non-destructive testing.

Predictive sufficiency and the use of stored internal state

NASA Technical Reports Server (NTRS)

Musliner, David J.; Durfee, Edmund H.; Shin, Kang G.

1994-01-01

In all embedded computing systems, some delay exists between sensing and acting. By choosing an action based on sensed data, a system is essentially predicting that there will be no significant changes in the world during this delay. However, the dynamic and uncertain nature of the real world can make these predictions incorrect, and thus, a system may execute inappropriate actions. Making systems more reactive by decreasing the gap between sensing and action leaves less time for predictions to err, but still provides no principled assurance that they will be correct. Using the concept of predictive sufficiency described in this paper, a system can prove that its predictions are valid, and that it will never execute inappropriate actions. In the context of our CIRCA system, we also show how predictive sufficiency allows a system to guarantee worst-case response times to changes in its environment. Using predictive sufficiency, CIRCA is able to build real-time reactive control plans which provide a sound basis for performance guarantees that are unavailable with other reactive systems.

Lack of relevant information for tumor staging in pathology reports of primary cutaneous melanoma.

PubMed

Busam, K J

2001-05-01

For the T classification of primary cutaneous melanoma, the current American Joint Committee on Cancer staging (AJCC) system relies on tumor thickness and level of invasion. A new T classification has been proposed based on thickness and ulceration. The slides and reports of 135 departmental pathology consultations of patients referred to a major cancer center with a diagnosis of primary cutaneous invasive malignant melanoma were examined. Whether the outside pathology reports contained information on tumor thickness, level of invasion, and ulceration was recorded. Dermatopathologists had issued 76.3% of the reports and general surgical pathologists, 24.3%. Information provided was as follows: tumor thickness, 97.8%; Clark level, 71.9%; and presence or absence of ulceration, 28.1%. Of the 97 melanomas with no comment on ulceration, 17 were indeed ulcerated. Thus, the lack of a comment on ulceration cannot be equated with the absence of ulceration. The present study documents that many pathology reports on melanomas lack sufficient information for AJCC staging. Therefore, review of outside pathology material is necessary not only to confirm or revise the tumor diagnosis but also to provide clinicians with histologic parameters required for AJCC staging.

Description of a Sensitive Seebeck Calorimeter Used for Cold Fusion Studies

NASA Astrophysics Data System (ADS)

Storms, Edmund

A sensitive and stable Seebeck calorimeter is described and used to determine the heat of formation of PdD. This determination can be used to show that such calorimeters are sufficiently accurate to measure the LENR effect and give support to the claims.

In vivo optical microscopy of peripheral nerve myelination with polarization sensitive-optical coherence tomography

PubMed Central

Henry, Francis P.; Wang, Yan; Rodriguez, Carissa L. R.; Randolph, Mark A.; Rust, Esther A. Z.; Winograd, Jonathan M.; de Boer, Johannes F.; Park, B. Hyle

2015-01-01

Abstract. Assessing nerve integrity and myelination after injury is necessary to provide insight for treatment strategies aimed at restoring neuromuscular function. Currently, this is largely done with electrical analysis, which lacks direct quantitative information. In vivo optical imaging with sufficient imaging depth and resolution could be used to assess the nerve microarchitecture. In this study, we examine the use of polarization sensitive-optical coherence tomography (PS-OCT) to quantitatively assess the sciatic nerve microenvironment through measurements of birefringence after applying a nerve crush injury in a rat model. Initial loss of function and subsequent recovery were demonstrated by calculating the sciatic function index (SFI). We found that the PS-OCT phase retardation slope, which is proportional to birefringence, increased monotonically with the SFI. Additionally, histomorphometric analysis of the myelin thickness and g-ratio shows that the PS-OCT slope is a good indicator of myelin health and recovery after injury. These results demonstrate that PS-OCT is capable of providing nondestructive and quantitative assessment of nerve health after injury and shows promise for continued use both clinically and experimentally in neuroscience. PMID:25858593

In vivo optical microscopy of peripheral nerve myelination with polarization sensitive-optical coherence tomography.

PubMed

Henry, Francis P; Wang, Yan; Rodriguez, Carissa L R; Randolph, Mark A; Rust, Esther A Z; Winograd, Jonathan M; de Boer, Johannes F; Park, B Hyle

2015-04-01

Assessing nerve integrity and myelination after injury is necessary to provide insight for treatment strategies aimed at restoring neuromuscular function. Currently, this is largely done with electrical analysis, which lacks direct quantitative information. In vivo optical imaging with sufficient imaging depth and resolution could be used to assess the nerve microarchitecture. In this study, we examine the use of polarization sensitive-optical coherence tomography (PS-OCT) to quantitatively assess the sciatic nerve microenvironment through measurements of birefringence after applying a nerve crush injury in a rat model. Initial loss of function and subsequent recovery were demonstrated by calculating the sciatic function index (SFI). We found that the PS-OCT phase retardation slope, which is proportional to birefringence, increased monotonically with the SFI. Additionally, histomorphometric analysis of the myelin thickness and g-ratio shows that the PS-OCT slope is a good indicator of myelin health and recovery after injury. These results demonstrate that PS-OCT is capable of providing nondestructive and quantitative assessment of nerve health after injury and shows promise for continued use both clinically and experimentally in neuroscience.

The influence of structural stigma and rejection sensitivity on young sexual minority men's daily tobacco and alcohol use

PubMed Central

Pachankis, John E.; Hatzenbuehler, Mark L.; Starks, Tyrel J.

2018-01-01

Stigma occurs at both individual and structural levels, but existing research tends to examine the effect of individual and structural forms of stigma in isolation, rather than considering potential synergistic effects. To address this gap, our study examined whether stigma at the individual level, namely gay-related rejection sensitivity, interacts with structural stigma to predict substance use among young sexual minority men. Sexual minority (n = 119) participants completed online measures of our constructs (e.g., rejection sensitivity). Participants currently resided across a broad array of geographic areas (i.e., 24 U.S. states), and had attended high school in 28 states, allowing us to capture sufficient variance in current and past forms of structural stigma, defined as (1) a lack of state-level policies providing equal opportunities for heterosexual and sexual minority individuals and (2) negative state-aggregated attitudes toward sexual minorities. To measure daily substance use, we utilized a daily diary approach, whereby all participants were asked to indicate whether they used tobacco or alcohol on nine consecutive days. Results indicated that structural stigma interacted with rejection sensitivity to predict tobacco and alcohol use, and that this relationship depended on the developmental timing of exposure to structural stigma. In contrast, rejection sensitivity did not mediate the relationship between structural stigma and substance use. These results suggest that psychological predispositions, such as rejection sensitivity, interact with features of the social environment, such as structural stigma, to predict important health behaviors among young sexual minority men. These results add to a growing body of research documenting the multiple levels through which stigma interacts to produce negative health outcomes among sexual minority individuals. PMID:24507912

Dorsal Hippocampal CREB Is Both Necessary and Sufficient for Spatial Memory

ERIC Educational Resources Information Center

Sekeres, Melanie J.; Neve, Rachael L.; Frankland, Paul W.; Josselyn, Sheena A.

2010-01-01

Although the transcription factor CREB has been widely implicated in memory, whether it is sufficient to produce spatial memory under conditions that do not normally support memory formation in mammals is unknown. We found that locally and acutely increasing CREB levels in the dorsal hippocampus using viral vectors is sufficient to induce robust…

Comprehensive viral enrichment enables sensitive respiratory virus genomic identification and analysis by next generation sequencing.

PubMed

O'Flaherty, Brigid M; Li, Yan; Tao, Ying; Paden, Clinton R; Queen, Krista; Zhang, Jing; Dinwiddie, Darrell L; Gross, Stephen M; Schroth, Gary P; Tong, Suxiang

2018-06-01

Next generation sequencing (NGS) technologies have revolutionized the genomics field and are becoming more commonplace for identification of human infectious diseases. However, due to the low abundance of viral nucleic acids (NAs) in relation to host, viral identification using direct NGS technologies often lacks sufficient sensitivity. Here, we describe an approach based on two complementary enrichment strategies that significantly improves the sensitivity of NGS-based virus identification. To start, we developed two sets of DNA probes to enrich virus NAs associated with respiratory diseases. The first set of probes spans the genomes, allowing for identification of known viruses and full genome sequencing, while the second set targets regions conserved among viral families or genera, providing the ability to detect both known and potentially novel members of those virus groups. Efficiency of enrichment was assessed by NGS testing reference virus and clinical samples with known infection. We show significant improvement in viral identification using enriched NGS compared to unenriched NGS. Without enrichment, we observed an average of 0.3% targeted viral reads per sample. However, after enrichment, 50%-99% of the reads per sample were the targeted viral reads for both the reference isolates and clinical specimens using both probe sets. Importantly, dramatic improvements on genome coverage were also observed following virus-specific probe enrichment. The methods described here provide improved sensitivity for virus identification by NGS, allowing for a more comprehensive analysis of disease etiology. © 2018 O'Flaherty et al.; Published by Cold Spring Harbor Laboratory Press.

On sufficient statistics of least-squares superposition of vector sets.

PubMed

Konagurthu, Arun S; Kasarapu, Parthan; Allison, Lloyd; Collier, James H; Lesk, Arthur M

2015-06-01

The problem of superposition of two corresponding vector sets by minimizing their sum-of-squares error under orthogonal transformation is a fundamental task in many areas of science, notably structural molecular biology. This problem can be solved exactly using an algorithm whose time complexity grows linearly with the number of correspondences. This efficient solution has facilitated the widespread use of the superposition task, particularly in studies involving macromolecular structures. This article formally derives a set of sufficient statistics for the least-squares superposition problem. These statistics are additive. This permits a highly efficient (constant time) computation of superpositions (and sufficient statistics) of vector sets that are composed from its constituent vector sets under addition or deletion operation, where the sufficient statistics of the constituent sets are already known (that is, the constituent vector sets have been previously superposed). This results in a drastic improvement in the run time of the methods that commonly superpose vector sets under addition or deletion operations, where previously these operations were carried out ab initio (ignoring the sufficient statistics). We experimentally demonstrate the improvement our work offers in the context of protein structural alignment programs that assemble a reliable structural alignment from well-fitting (substructural) fragment pairs. A C++ library for this task is available online under an open-source license.

The potential exploitation of research participants in high income countries who lack access to health care

PubMed Central

Rid, Annette; Emanuel, Ezekiel; Wendler, David

2016-01-01

There are millions of individuals living in North America and the European Union who lack access to healthcare services. When these individuals participate in research, they are at increased risk of being exposed to the risks and burdens of clinical trials without realizing the benefits that result from them. The mechanisms that have been proposed to ensure that research participants in low‐ and middle‐income countries are not exploited are unlikely to protect participants in high‐income countries. The present manuscript argues that one way to address concerns about exploitation in high‐income countries would be to require sponsors to provide targeted benefits such as medical treatment during the trial, or the study drug after the trial. The latter could be achieved through extension studies, expanded access programs, or named‐patient programs. Sponsors also might provide non‐medical benefits, such as education or social support. Ethical and regulatory guidance should be revised to ensure that research participants in high‐income countries who lack access to healthcare services receive sufficient benefits. PMID:26743927

Sequence-based screening for self-sufficient P450 monooxygenase from a metagenome library.

PubMed

Kim, B S; Kim, S Y; Park, J; Park, W; Hwang, K Y; Yoon, Y J; Oh, W K; Kim, B Y; Ahn, J S

2007-05-01

Cytochrome P450 monooxygenases (CYPs) are useful catalysts for oxidation reactions. Self-sufficient CYPs harbour a reductive domain covalently connected to a P450 domain and are known for their robust catalytic activity with great potential as biocatalysts. In an effort to expand genetic sources of self-sufficient CYPs, we devised a sequence-based screening system to identify them in a soil metagenome. We constructed a soil metagenome library and performed sequence-based screening for self-sufficient CYP genes. A new CYP gene, syk181, was identified from the metagenome library. Phylogenetic analysis revealed that SYK181 formed a distinct phylogenic line with 46% amino-acid-sequence identity to CYP102A1 which has been extensively studied as a fatty acid hydroxylase. The heterologously expressed SYK181 showed significant hydroxylase activity towards naphthalene and phenanthrene as well as towards fatty acids. Sequence-based screening of metagenome libraries is expected to be a useful approach for searching self-sufficient CYP genes. The translated product of syk181 shows self-sufficient hydroxylase activity towards fatty acids and aromatic compounds. SYK181 is the first self-sufficient CYP obtained directly from a metagenome library. The genetic and biochemical information on SYK181 are expected to be helpful for engineering self-sufficient CYPs with broader catalytic activities towards various substrates, which would be useful for bioconversion of natural products and biodegradation of organic chemicals.

The spectral sensitivity of the human short-wavelength sensitive cones derived from thresholds and color matches.

PubMed

Stockman, A; Sharpe, L T; Fach, C

1999-08-01

We used two methods to estimate short-wave (S) cone spectral sensitivity. Firstly, we measured S-cone thresholds centrally and peripherally in five trichromats, and in three blue-cone monochromats, who lack functioning middle-wave (M) and long-wave (L) cones. Secondly, we analyzed standard color-matching data. Both methods yielded equivalent results, on the basis of which we propose new S-cone spectral sensitivity functions. At short and middle-wavelengths, our measurements are consistent with the color matching data of Stiles and Burch (1955, Optica Acta, 2, 168-181; 1959, Optica Acta, 6, 1-26), and other psychophysically measured functions, such as pi 3 (Stiles, 1953, Coloquio sobre problemas opticos de la vision, 1, 65-103). At longer wavelengths, S-cone sensitivity has previously been over-estimated.

Do sufficient vitamin D levels at the end of summer in children and adolescents provide an assurance of vitamin D sufficiency at the end of winter? A cohort study.

PubMed

Shakeri, Habibesadat; Pournaghi, Seyed-Javad; Hashemi, Javad; Mohammad-Zadeh, Mohammad; Akaberi, Arash

2017-10-26

The changes in serum 25-hydroxyvitamin D (25(OH)D) in adolescents from summer to winter and optimal serum vitamin D levels in the summer to ensure adequate vitamin D levels at the end of winter are currently unknown. This study was conducted to address this knowledge gap. The study was conducted as a cohort study. Sixty-eight participants aged 7-18 years and who had sufficient vitamin D levels at the end of the summer in 2011 were selected using stratified random sampling. Subsequently, the participants' vitamin D levels were measured at the end of the winter in 2012. A receiver operating characteristic (ROC) curve was used to determine optimal cutoff points for vitamin D at the end of the summer to predict sufficient vitamin D levels at the end of the winter. The results indicated that 89.7% of all the participants had a decrease in vitamin D levels from summer to winter: 14.7% of them were vitamin D-deficient, 36.8% had insufficient vitamin D concentrations and only 48.5% where able to maintain sufficient vitamin D. The optimal cutoff point to provide assurance of sufficient serum vitamin D at the end of the winter was 40 ng/mL at the end of the summer. Sex, age and vitamin D levels at the end of the summer were significant predictors of non-sufficient vitamin D at the end of the winter. In this age group, a dramatic reduction in vitamin D was observed over the follow-up period. Sufficient vitamin D at the end of the summer did not guarantee vitamin D sufficiency at the end of the winter. We found 40 ng/mL as an optimal cutoff point.

Requirements for Minimum Sample Size for Sensitivity and Specificity Analysis

PubMed Central

Adnan, Tassha Hilda

2016-01-01

Sensitivity and specificity analysis is commonly used for screening and diagnostic tests. The main issue researchers face is to determine the sufficient sample sizes that are related with screening and diagnostic studies. Although the formula for sample size calculation is available but concerning majority of the researchers are not mathematicians or statisticians, hence, sample size calculation might not be easy for them. This review paper provides sample size tables with regards to sensitivity and specificity analysis. These tables were derived from formulation of sensitivity and specificity test using Power Analysis and Sample Size (PASS) software based on desired type I error, power and effect size. The approaches on how to use the tables were also discussed. PMID:27891446

Sufficient Dimension Reduction for Longitudinally Measured Predictors

PubMed Central

Pfeiffer, Ruth M.; Forzani, Liliana; Bura, Efstathia

2013-01-01

We propose a method to combine several predictors (markers) that are measured repeatedly over time into a composite marker score without assuming a model and only requiring a mild condition on the predictor distribution. Assuming that the first and second moments of the predictors can be decomposed into a time and a marker component via a Kronecker product structure, that accommodates the longitudinal nature of the predictors, we develop first moment sufficient dimension reduction techniques to replace the original markers with linear transformations that contain sufficient information for the regression of the predictors on the outcome. These linear combinations can then be combined into a score that has better predictive performance than the score built under a general model that ignores the longitudinal structure of the data. Our methods can be applied to either continuous or categorical outcome measures. In simulations we focus on binary outcomes and show that our method outperforms existing alternatives using the AUC, the area under the receiver-operator characteristics (ROC) curve, as a summary measure of the discriminatory ability of a single continuous diagnostic marker for binary disease outcomes. PMID:22161635

Lack of Early Improvement Predicts Poor Outcome Following Acute Intracerebral Hemorrhage.

PubMed

Yogendrakumar, Vignan; Smith, Eric E; Demchuk, Andrew M; Aviv, Richard I; Rodriguez-Luna, David; Molina, Carlos A; Silva Blas, Yolanda; Dzialowski, Imanuel; Kobayashi, Adam; Boulanger, Jean-Martin; Lum, Cheemun; Gubitz, Gord; Padma, Vasantha; Roy, Jayanta; Kase, Carlos S; Bhatia, Rohit; Ali, Myzoon; Lyden, Patrick; Hill, Michael D; Dowlatshahi, Dar

2018-04-01

There are limited data as to what degree of early neurologic change best relates to outcome in acute intracerebral hemorrhage. We aimed to derive and validate a threshold for early postintracerebral hemorrhage change that best predicts 90-day outcomes. Derivation: retrospective analysis of collated clinical stroke trial data (Virtual International Stroke Trials Archive). retrospective analysis of a prospective multicenter cohort study (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]). Neurocritical and ICUs. Patients with acute intracerebral hemorrhage presenting less than 6 hours. Derivation: 552 patients; validation: 275 patients. None. We generated a receiver operating characteristic curve for the association between 24-hour National Institutes of Health Stroke Scale change and clinical outcome. The primary outcome was a modified Rankin Scale score of 4-6 at 90 days; secondary outcomes were other modified Rankin Scale score ranges (modified Rankin Scale, 2-6, 3-6, 5-6, 6). We employed Youden's J Index to select optimal cut points and calculated sensitivity, specificity, and predictive values. We determined independent predictors via multivariable logistic regression. The derived definitions were validated in the PREDICT cohort. Twenty-four-hour National Institutes of Health Stroke Scale change was strongly associated with 90-day outcome with an area under the receiver operating characteristic curve of 0.75. Youden's method showed an optimum cut point at -0.5, corresponding to National Institutes of Health Stroke Scale change of greater than or equal to 0 (a lack of clinical improvement), which was seen in 46%. Early neurologic change accurately predicted poor outcome when defined as greater than or equal to 0 (sensitivity, 65%; specificity, 73%; positive predictive value, 70%; adjusted odds ratio, 5.05 [CI, 3.25-7.85]) or greater than or equal to 4 (sensitivity, 19%; specificity

Role of sufficient statistics in stochastic thermodynamics and its implication to sensory adaptation

NASA Astrophysics Data System (ADS)

Matsumoto, Takumi; Sagawa, Takahiro

2018-04-01

A sufficient statistic is a significant concept in statistics, which means a probability variable that has sufficient information required for an inference task. We investigate the roles of sufficient statistics and related quantities in stochastic thermodynamics. Specifically, we prove that for general continuous-time bipartite networks, the existence of a sufficient statistic implies that an informational quantity called the sensory capacity takes the maximum. Since the maximal sensory capacity imposes a constraint that the energetic efficiency cannot exceed one-half, our result implies that the existence of a sufficient statistic is inevitably accompanied by energetic dissipation. We also show that, in a particular parameter region of linear Langevin systems there exists the optimal noise intensity at which the sensory capacity, the information-thermodynamic efficiency, and the total entropy production are optimized at the same time. We apply our general result to a model of sensory adaptation of E. coli and find that the sensory capacity is nearly maximal with experimentally realistic parameters.

Eyes only? Perceiving eye contact is neither sufficient nor necessary for attentional capture by face direction.

PubMed

Böckler, Anne; van der Wel, Robrecht P R D; Welsh, Timothy N

2015-09-01

Direct eye contact and motion onset both constitute powerful cues that capture attention. Recent research suggests that (social) gaze and (non-social) motion onset influence information processing in parallel, even when combined as sudden onset direct gaze cues (i.e., faces suddenly establishing eye contact). The present study investigated the role of eye visibility for attention capture by these sudden onset face cues. To this end, face direction was manipulated (away or towards onlooker) while faces had closed eyes (eliminating visibility of eyes, Experiment 1), wore sunglasses (eliminating visible eyes, but allowing for the expectation of eyes to be open, Experiment 2), and were inverted with visible eyes (disrupting the integration of eyes and faces, Experiment 3). Participants classified targets appearing on one of four faces. Initially, two faces were oriented towards participants and two faces were oriented away from participants. Simultaneous to target presentation, one averted face became directed and one directed face became averted. Attention capture by face direction (i.e., facilitation for faces directed towards participants) was absent when eyes were closed, but present when faces wore sunglasses. Sudden onset direct faces can, hence, induce attentional capture, even when lacking eye cues. Inverted faces, by contrast, did not elicit attentional capture. Thus, when eyes cannot be integrated into a holistic face representation they are not sufficient to capture attention. Overall, the results suggest that visibility of eyes is neither necessary nor sufficient for the sudden direct face effect. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensitivity ranking for freshwater invertebrates towards hydrocarbon contaminants.

PubMed

Gerner, Nadine V; Cailleaud, Kevin; Bassères, Anne; Liess, Matthias; Beketov, Mikhail A

2017-11-01

Hydrocarbons have an utmost economical importance but may also cause substantial ecological impacts due to accidents or inadequate transportation and use. Currently, freshwater biomonitoring methods lack an indicator that can unequivocally reflect the impacts caused by hydrocarbons while being independent from effects of other stressors. The aim of the present study was to develop a sensitivity ranking for freshwater invertebrates towards hydrocarbon contaminants, which can be used in hydrocarbon-specific bioindicators. We employed the Relative Sensitivity method and developed the sensitivity ranking S hydrocarbons based on literature ecotoxicological data supplemented with rapid and mesocosm test results. A first validation of the sensitivity ranking based on an earlier field study has been conducted and revealed the S hydrocarbons ranking to be promising for application in sensitivity based indicators. Thus, the first results indicate that the ranking can serve as the core component of future hydrocarbon-specific and sensitivity trait based bioindicators.

Tissue-Specific Profiling Reveals Transcriptome Alterations in Arabidopsis Mutants Lacking Morphological Phenotypes[C][W

PubMed Central

Simon, Marissa; Bruex, Angela; Kainkaryam, Raghunandan M.; Zheng, Xiaohua; Huang, Ling; Woolf, Peter J.; Schiefelbein, John

2013-01-01

Traditional genetic analysis relies on mutants with observable phenotypes. Mutants lacking visible abnormalities may nevertheless exhibit molecular differences useful for defining gene function. To examine this, we analyzed tissue-specific transcript profiles from Arabidopsis thaliana transcription factor gene mutants with known roles in root epidermis development, but lacking a single-gene mutant phenotype due to genetic redundancy. We discovered substantial transcriptional changes in each mutant, preferentially affecting root epidermal genes in a manner consistent with the known double mutant effects. Furthermore, comparing transcript profiles of single and double mutants, we observed remarkable variation in the sensitivity of target genes to the loss of one or both paralogous genes, including preferential effects on specific branches of the epidermal gene network, likely reflecting the pathways of paralog subfunctionalization during evolution. In addition, we analyzed the root epidermal transcriptome of the transparent testa glabra2 mutant to clarify its role in the network. These findings provide insight into the molecular basis of genetic redundancy and duplicate gene diversification at the level of a specific gene regulatory network, and they demonstrate the usefulness of tissue-specific transcript profiling to define gene function in mutants lacking informative visible changes in phenotype. PMID:24014549

Drosophila larvae lacking the bcl-2 gene, buffy, are sensitive to nutrient stress, maintain increased basal target of rapamycin (Tor) signaling and exhibit characteristics of altered basal energy metabolism

PubMed Central

2012-01-01

Background B cell lymphoma 2 (Bcl-2) proteins are the central regulators of apoptosis. The two bcl-2 genes in Drosophila modulate the response to stress-induced cell death, but not developmental cell death. Because null mutants are viable, Drosophila provides an optimum model system to investigate alternate functions of Bcl-2 proteins. In this report, we explore the role of one bcl-2 gene in nutrient stress responses. Results We report that starvation of Drosophila larvae lacking the bcl-2 gene, buffy, decreases survival rate by more than twofold relative to wild-type larvae. The buffy null mutant reacted to starvation with the expected responses such as inhibition of target of rapamycin (Tor) signaling, autophagy initiation and mobilization of stored lipids. However, the autophagic response to starvation initiated faster in larvae lacking buffy and was inhibited by ectopic buffy. We demonstrate that unusually high basal Tor signaling, indicated by more phosphorylated S6K, was detected in the buffy mutant and that removal of a genomic copy of S6K, but not inactivation of Tor by rapamycin, reverted the precocious autophagy phenotype. Instead, Tor inactivation also required loss of a positive nutrient signal to trigger autophagy and loss of both was sufficient to activate autophagy in the buffy mutant even in the presence of enforced phosphoinositide 3-kinase (PI3K) signaling. Prior to starvation, the fed buffy mutant stored less lipid and glycogen, had high lactate levels and maintained a reduced pool of cellular ATP. These observations, together with the inability of buffy mutant larvae to adapt to nutrient restriction, indicate altered energy metabolism in the absence of buffy. Conclusions All animals in their natural habitats are faced with periods of reduced nutrient availability. This study demonstrates that buffy is required for adaptation to both starvation and nutrient restriction. Thus, Buffy is a Bcl-2 protein that plays an important non-apoptotic role to

INVESTIGATING UNCERTAINTY AND SENSITIVITY IN INTEGRATED MULTIMEDIA ENVIRONMENTAL MODELS: TOOLS FOR 3MRA

EPA Science Inventory

Sufficiently elucidating uncertainty and sensitivity structures in environmental models can be a difficult task, even for low-order, single-media constructs driven by a unique set of site-specific data. The ensuing challenge of examining ever more complex, integrated, higher-ord...

Studies on the optical and photoelectric properties of anthocyanin and chlorophyll as natural co-sensitizers in dye sensitized solar cell

NASA Astrophysics Data System (ADS)

Nan, Hui; Shen, He-Ping; Wang, Gang; Xie, Shou-Dong; Yang, Gui-Jun; Lin, Hong

2017-11-01

Anthocyanin and Chlorophyll extracted from Troll flower and Cypress leaf respectively are used as natural sensitizers in dye sensitized solar cells (DSCs), with their optical and electrochemical properties investigated. UV-Vis absorption measurement showed that the mixture of two dyes enabled an enhanced and wider absorption in the wavelength range of 300 nm-700 nm compared to each single dye. FTIR results proved that anthocyanin is chemically adsorbed onto the TiO2 film, while it is physical adsorption for chlorophyll. The energy level offsets on the TiO2/dye/electrolyte interface for each dye and the dye mixture with different ratios were calculated from the electrochemical analysis, which affect the electron injection and dye regeneration efficiencies. The optimized ratio of the two dyes in the mixture was found to be ∼2:5, inducing both sufficient charge transfer driving force and minimal energy loss. By incorporating this mixture into the solar cell as co-adsorbing sensitizer, the photovoltaic performance was prominently improved compared with the single dye sensitization system.

Overexpression of ARGOS Genes Modifies Plant Sensitivity to Ethylene, Leading to Improved Drought Tolerance in Both Arabidopsis and Maize.

PubMed

Shi, Jinrui; Habben, Jeffrey E; Archibald, Rayeann L; Drummond, Bruce J; Chamberlin, Mark A; Williams, Robert W; Lafitte, H Renee; Weers, Ben P

2015-09-01

Lack of sufficient water is a major limiting factor to crop production worldwide, and the development of drought-tolerant germplasm is needed to improve crop productivity. The phytohormone ethylene modulates plant growth and development as well as plant response to abiotic stress. Recent research has shown that modifying ethylene biosynthesis and signaling can enhance plant drought tolerance. Here, we report novel negative regulators of ethylene signal transduction in Arabidopsis (Arabidopsis thaliana) and maize (Zea mays). These regulators are encoded by the ARGOS gene family. In Arabidopsis, overexpression of maize ARGOS1 (ZmARGOS1), ZmARGOS8, Arabidopsis ARGOS homolog ORGAN SIZE RELATED1 (AtOSR1), and AtOSR2 reduced plant sensitivity to ethylene, leading to enhanced drought tolerance. RNA profiling and genetic analysis suggested that the ZmARGOS1 transgene acts between an ethylene receptor and CONSTITUTIVE TRIPLE RESPONSE1 in the ethylene signaling pathway, affecting ethylene perception or the early stages of ethylene signaling. Overexpressed ZmARGOS1 is localized to the endoplasmic reticulum and Golgi membrane, where the ethylene receptors and the ethylene signaling protein ETHYLENE-INSENSITIVE2 and REVERSION-TO-ETHYLENE SENSITIVITY1 reside. In transgenic maize plants, overexpression of ARGOS genes also reduces ethylene sensitivity. Moreover, field testing showed that UBIQUITIN1:ZmARGOS8 maize events had a greater grain yield than nontransgenic controls under both drought stress and well-watered conditions. © 2015 American Society of Plant Biologists. All Rights Reserved.

Energy self-sufficiency in Northampton, Massachusetts

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

Not Available

The study is not an engineering analysis but begins the process of exploring the potential for conservation and local renewable-resource development in a specific community, Northampton, Massachusetts, with the social, institutional, and environmental factors in that community taken into account. Section I is an extensive executive summary of the full study, and Section II is a detailed examination of the potential for increased local energy self-sufficiency in Northampton, including current and future demand estimates, the possible role of conservation and renewable resources, and a discussion of the economic and social implications of alternative energy systems. (MOW)

The sensitivity of EGRET to gamma ray polarization

NASA Astrophysics Data System (ADS)

Mattox, John R.

1990-05-01

A Monte Carlo simulation shows that EGRET (Energetic Gamma-Ray Experimental Telescope) does not even have sufficient sensitivity to detect 100 percent polarized gamma-rays. This is confirmed by analysis of calibration data. A Monte Carlo study shows that the sensitivity of EGRET to polarization peaks around 100 MeV. However, more than 10 5 gamma-ray events with 100 percent polarization would be required for a 3 sigma significance detection - more than available from calibration, and probably more than will result from a single score source during flight. A drift chamber gamma ray telescope under development (Hunter and Cuddapah 1989) will offer better sensitivity to polarization. The lateral position uncertainty will be improved by an order of magnitude. Also, if pair production occurs in the drift chamber gas (xenon at 2 bar) instead of tantalum foils, the effects of multiple Coulomb scattering will be reduced.

Intellectual Freedom and Economic Sufficiency as Educational Entitlements.

ERIC Educational Resources Information Center

Morse, Jane Fowler

2001-01-01

Using the theories of John Stuart Mill and Karl Marx, this article supports the educational entitlements of intellectual freedom and economic sufficiency. Explores these issues in reference to their implications for teaching, the teaching profession and its training. Concludes that ideas cannot be controlled by the interests of the dominant class.…

Mammary ductal growth is impaired in mice lacking leptin-dependent signal transducer and activator of transcription 3 signaling.

PubMed

Thorn, Stephanie R; Giesy, Sarah L; Myers, Martin G; Boisclair, Yves R

2010-08-01

Mice lacking leptin (ob/ob) or its full-length receptor (db/db) are obese and reproductively incompetent. Fertility, pregnancy, and lactation are restored, respectively, in ob/ob mice treated with leptin through mating, d 6.5 post coitum, and pregnancy. Therefore, leptin signaling is needed for lactation, but the timing of its action and the affected mammary process remain unknown. To address this issue, we used s/s mice lacking only leptin-dependent signal transducer and activator of transcription (STAT)3 signaling. These mice share many features with db/db mice, including obesity, but differ by retaining sufficient activity of the hypothalamic-pituitary-ovarian axis to support reproduction. The s/s mammary epithelium was normal at 3 wk of age but failed to expand through the mammary fat pad (MFP) during the subsequent pubertal period. Ductal growth failure was not corrected by estrogen therapy and did not relate to inadequate IGF-I production by the MFP or to the need for epithelial or stromal leptin-STAT3 signaling. Ductal growth failure coincided with adipocyte hypertrophy and increased MFP production of leptin, TNFalpha, and IL6. These cytokines, however, were unable to inhibit the proliferation of a collection of mouse mammary epithelial cell lines. In conclusion, the very first step of postnatal mammary development fails in s/s mice despite sufficient estrogen IGF-I and an hypothalamic-pituitary-ovarian axis capable of supporting reproduction. This failure is not caused by mammary loss of leptin-dependent STAT3 signaling or by the development of inflammation. These data imply the existence of an unknown mechanism whereby leptin-dependent STAT3 signaling and obesity alter mammary ductal development.

Estimation of resist sensitivity for extreme ultraviolet lithography using an electron beam

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

Oyama, Tomoko Gowa, E-mail: ohyama.tomoko@qst.go.jp; Oshima, Akihiro; Tagawa, Seiichi, E-mail: tagawa@sanken.osaka-u.ac.jp

2016-08-15

It is a challenge to obtain sufficient extreme ultraviolet (EUV) exposure time for fundamental research on developing a new class of high sensitivity resists for extreme ultraviolet lithography (EUVL) because there are few EUV exposure tools that are very expensive. In this paper, we introduce an easy method for predicting EUV resist sensitivity by using conventional electron beam (EB) sources. If the chemical reactions induced by two ionizing sources (EB and EUV) are the same, the required absorbed energies corresponding to each required exposure dose (sensitivity) for the EB and EUV would be almost equivalent. Based on this theory, wemore » calculated the resist sensitivities for the EUV/soft X-ray region. The estimated sensitivities were found to be comparable to the experimentally obtained sensitivities. It was concluded that EB is a very useful exposure tool that accelerates the development of new resists and sensitivity enhancement processes for 13.5 nm EUVL and 6.x nm beyond-EUVL (BEUVL).« less

Manipulations of extracellular Loop 2 in α1 GlyR ultra-sensitive ethanol receptors (USERs) enhance receptor sensitivity to isoflurane, ethanol, and lidocaine, but not propofol

PubMed Central

Naito, Anna; Muchhala, Karan H.; Trang, Janice; Asatryan, Liana; Trudell, James R.; Homanics, Gregg E.; Alkana, Ronald L.; Davies, Daryl L.

2015-01-01

We recently developed Ultra-Sensitive Ethanol Receptors (USERs) as a novel tool for investigation of single receptor subunit populations sensitized to extremely low ethanol concentrations that do not affect other receptors in the nervous system. To this end, we found that mutations within the extracellular Loop 2 region of glycine receptors (GlyRs) and γ-aminobutyric acid type A receptors (GABAARs) can significantly increase receptor sensitivity to micro-molar concentrations of ethanol resulting in up to a 100-fold increase in ethanol sensitivity relative to wild type (WT) receptors. The current study investigated: 1) Whether structural manipulations of Loop 2 in α1 GlyRs could similarly increase receptor sensitivity to other anesthetics; and 2) If mutations exclusive to the C-terminal end of Loop 2 are sufficient to impart these changes. We expressed α1 GlyR USERs in Xenopus oocytes and tested the effects of three classes of anesthetics, isoflurane (volatile), propofol (intravenous), and lidocaine (local), known to enhance glycine-induced chloride currents using two-electrode voltage clamp electrophysiology. Loop 2 mutations produced a significant 10-fold increase in isoflurane and lidocaine sensitivity, but no increase in propofol sensitivity compared to WT α1 GlyRs. Interestingly, we also found that structural manipulations in the C-terminal end of Loop 2 were sufficient and selective for α1 GlyR modulation by ethanol, isoflurane, and lidocaine. These studies are the first to report the extracellular region of α1 GlyRs as a site of lidocaine action. Overall, the findings suggest that Loop 2 of α1 GlyRs is a key region that mediates isoflurane and lidocaine modulation. Moreover, the results identify important amino acids in Loop 2 that regulate isoflurane, lidocaine, and ethanol action. Collectively, these data indicate the commonality of the sites for isoflurane, lidocaine, and ethanol action, and the structural requirements for allosteric modulation on �

Redox self-sufficient whole cell biotransformation for amination of alcohols.

PubMed

Klatte, Stephanie; Wendisch, Volker F

2014-10-15

Whole cell biotransformation is an upcoming tool to replace common chemical routes for functionalization and modification of desired molecules. In the approach presented here the production of various non-natural (di)amines was realized using the designed whole cell biocatalyst Escherichia coli W3110/pTrc99A-ald-adh-ta with plasmid-borne overexpression of genes for an l-alanine dehydrogenase, an alcohol dehydrogenase and a transaminase. Cascading alcohol oxidation with l-alanine dependent transamination and l-alanine dehydrogenase allowed for redox self-sufficient conversion of alcohols to the corresponding amines. The supplementation of the corresponding (di)alcohol precursors as well as amino group donor l-alanine and ammonium chloride were sufficient for amination and redox cofactor recycling in a resting buffer system. The addition of the transaminase cofactor pyridoxal-phosphate and the alcohol dehydrogenase cofactor NAD(+) was not necessary to obtain complete conversion. Secondary and cyclic alcohols, for example, 2-hexanol and cyclohexanol were not aminated. However, efficient redox self-sufficient amination of aliphatic and aromatic (di)alcohols in vivo was achieved with 1-hexanol, 1,10-decanediol and benzylalcohol being aminated best. Copyright © 2014 Elsevier Ltd. All rights reserved.

7 CFR 760.614 - Lack of access.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Lack of access. 760.614 Section 760.614 Agriculture... Lack of access. In addition to other provisions for eligibility provided for in this part, the Deputy Administrator may provide assistance to participants who suffered 2008 production losses that meet the lack of...

Vaccine procurement and self-sufficiency in developing countries.

PubMed

Woodle, D

2000-06-01

This paper discusses the movement toward self-sufficiency in vaccine supply in developing countries (and countries in transition to new economic and political systems) and explains special supply concerns about vaccine as a product class. It traces some history of donor support and programmes aimed at self-financing, then continues with a discussion about self-sufficiency in terms of institutional capacity building. A number of deficiencies commonly found in vaccine procurement and supply in low- and middle-income countries are characterized, and institutional strengthening with procurement technical assistance is described. The paper also provides information about a vaccine procurement manual being developed by the United States Agency for International Development (USAID) and the World Health Organization (WHO) for use in this environment. Two brief case studies are included to illustrate the spectrum of existing capabilities and different approaches to technical assistance aimed at developing or improving vaccine procurement capability. In conclusion, the paper discusses the special nature of vaccine and issues surrounding potential integration and decentralization of vaccine supply systems as part of health sector reform.

Information trimming: Sufficient statistics, mutual information, and predictability from effective channel states

NASA Astrophysics Data System (ADS)

James, Ryan G.; Mahoney, John R.; Crutchfield, James P.

2017-06-01

One of the most basic characterizations of the relationship between two random variables, X and Y , is the value of their mutual information. Unfortunately, calculating it analytically and estimating it empirically are often stymied by the extremely large dimension of the variables. One might hope to replace such a high-dimensional variable by a smaller one that preserves its relationship with the other. It is well known that either X (or Y ) can be replaced by its minimal sufficient statistic about Y (or X ) while preserving the mutual information. While intuitively reasonable, it is not obvious or straightforward that both variables can be replaced simultaneously. We demonstrate that this is in fact possible: the information X 's minimal sufficient statistic preserves about Y is exactly the information that Y 's minimal sufficient statistic preserves about X . We call this procedure information trimming. As an important corollary, we consider the case where one variable is a stochastic process' past and the other its future. In this case, the mutual information is the channel transmission rate between the channel's effective states. That is, the past-future mutual information (the excess entropy) is the amount of information about the future that can be predicted using the past. Translating our result about minimal sufficient statistics, this is equivalent to the mutual information between the forward- and reverse-time causal states of computational mechanics. We close by discussing multivariate extensions to this use of minimal sufficient statistics.

Overexpression of ARGOS Genes Modifies Plant Sensitivity to Ethylene, Leading to Improved Drought Tolerance in Both Arabidopsis and Maize[OPEN

PubMed Central

Shi, Jinrui; Habben, Jeffrey E.; Archibald, Rayeann L.; Drummond, Bruce J.; Chamberlin, Mark A.; Williams, Robert W.; Lafitte, H. Renee; Weers, Ben P.

2015-01-01

Lack of sufficient water is a major limiting factor to crop production worldwide, and the development of drought-tolerant germplasm is needed to improve crop productivity. The phytohormone ethylene modulates plant growth and development as well as plant response to abiotic stress. Recent research has shown that modifying ethylene biosynthesis and signaling can enhance plant drought tolerance. Here, we report novel negative regulators of ethylene signal transduction in Arabidopsis (Arabidopsis thaliana) and maize (Zea mays). These regulators are encoded by the ARGOS gene family. In Arabidopsis, overexpression of maize ARGOS1 (ZmARGOS1), ZmARGOS8, Arabidopsis ARGOS homolog ORGAN SIZE RELATED1 (AtOSR1), and AtOSR2 reduced plant sensitivity to ethylene, leading to enhanced drought tolerance. RNA profiling and genetic analysis suggested that the ZmARGOS1 transgene acts between an ethylene receptor and CONSTITUTIVE TRIPLE RESPONSE1 in the ethylene signaling pathway, affecting ethylene perception or the early stages of ethylene signaling. Overexpressed ZmARGOS1 is localized to the endoplasmic reticulum and Golgi membrane, where the ethylene receptors and the ethylene signaling protein ETHYLENE-INSENSITIVE2 and REVERSION-TO-ETHYLENE SENSITIVITY1 reside. In transgenic maize plants, overexpression of ARGOS genes also reduces ethylene sensitivity. Moreover, field testing showed that UBIQUITIN1:ZmARGOS8 maize events had a greater grain yield than nontransgenic controls under both drought stress and well-watered conditions. PMID:26220950

Development of an XTT tetrazolium salt-based assay for detection of specific hyperthermia sensitizers in a high-flux screening programme.

PubMed

Lechpammer, S; Asea, A; Mallick, R; Zhong, R; Sherman, M Y; Calderwood, S K

2002-01-01

It is now possible to search for new drugs using high-throughput screening of chemical libraries accumulated over the past few years. To detect potential new hyperthermia sensitizers, we are screening for chemical inhibitors of thermotolerance. For the screening of a large chemical library, a rapid and simple assay based on the XTT-tetrazolium salt with the addition of intermediate electron acceptor, phenazine methosulphate (PMS) as a promoter, was developed. It was found that the sensitivity of the XTT/PMS assay is sufficient for assessing thermal cell killing and thermotolerance, although it was highly dependent on cell number and type. When the formazan assay system was challenged with the bioflavonoid drug quercetin (up to 25mm) and validated against the clonogenic cell survival assay, significant decreases in thermotolerant cell viability were observed, directly reflecting inhibition of thermotolerance. Although short-term assays can, in some instances, underestimate overall cell killing, the dose dependency of inhibition of thermotolerance by quercetin recorded in this study by clonogenic and XTT/PMS assays was similar. Application of the XTT/PMS assay in chemical library screening was highly effective in differentiating potential thermotolerance inhibitors from both chemicals with lack of efficacy and from toxic compounds. Taken together, these results show that the XTT/PMS assay, when carried out under careful conditions, is well suited for primary high-flux screen of many thousands of compounds, thus opening up new areas for discovery of hyperthermia sensitizers.

Isolation and characterization of an Escherichia coli mutant lacking cytochrome d terminal oxidase.

PubMed Central

Green, G N; Gennis, R B

1983-01-01

A screening procedure was devised which permitted the isolation of a cytochrome d-deficient mutant by its failure to oxidize the artificial electron donor N,N,N',N'-tetramethyl-p-phenylenediamine. Cytochrome a1 and probably cytochrome b558 were also missing in the mutant. Growth and oxygen uptake rates were similar for both parent and mutant strains. However, the strain lacking cytochrome d had an increased sensitivity to cyanide, indicating that cytochrome d confers some resistance to this respiratory inhibitor. The gene responsible for these phenotypes has been named cyd and maps between tolA and sucB. PMID:6304009

Tinnitus sensitization: a neurophysiological pathway of chronic complex tinnitus.

PubMed

Zenner, Hans P

2006-01-01

A novel neuro- and psychophysiological pathway for central cognition of tinnitus, i.e. tinnitus sensitization, is presented here. As a complement to the neurophysiological pathway for the conditioned reflex according to Jastreboff, which permits therapeutic procedures to bring about an extinction of the tinnitus (e.g. by the acoustic tinnitus retraining therapy), sensitization can be treated with procedures that act at the cognitive level. Since on the one hand therapeutic extinction procedures (e.g. the therapeutic application of sound) are still to be proven effective in controlled studies, while on the other cognitive interventions such as cognitive behavioral therapies have in fact acquired evidence level IIa in prospective studies, it is indeed appropriate to discuss whether the earlier neurophysiological model of a conditioned reflex is sufficient on its own, and whether in fact it needs to be complemented with the sensitization model.

The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo.

PubMed

Neugebauer, Judith M; Kwon, Sunjong; Kim, Hyung-Seok; Donley, Nathan; Tilak, Anup; Sopory, Shailaja; Christian, Jan L

2015-05-05

Bone morphogenetic proteins 4 and 7 (BMP4 and BMP7) are morphogens that signal as either homodimers or heterodimers to regulate embryonic development and adult homeostasis. BMP4/7 heterodimers exhibit markedly higher signaling activity than either homodimer, but the mechanism underlying the enhanced activity is unknown. BMPs are synthesized as inactive precursors that dimerize and are then cleaved to generate both the bioactive ligand and prodomain fragments, which lack signaling activity. Our study reveals a previously unknown requirement for the BMP4 prodomain in promoting heterodimer activity. We show that BMP4 and BMP7 precursor proteins preferentially or exclusively form heterodimers when coexpressed in vivo. In addition, we show that the BMP4 prodomain is both necessary and sufficient for generation of stable heterodimeric ligands with enhanced activity and can enable homodimers to signal in a context in which they normally lack activity. Our results suggest that intrinsic properties of the BMP4 prodomain contribute to the relative bioactivities of homodimers versus heterodimers in vivo. These findings have clinical implications for the use of BMPs as regenerative agents for the treatment of bone injury and disease.

Implications of the lack of desiccation tolerance in recalcitrant seeds.

PubMed

Berjak, Patricia; Pammenter, Norman W

2013-11-22

A suite of interacting processes and mechanisms enables tolerance of desiccation and storage (conservation) of orthodox seeds in the dry state. While this is a long-term option under optimized conditions, dry orthodox seeds are not immortal, with life spans having been characterized as short, intermediate and long. Factors facilitating desiccation tolerance are metabolic "switch-off" and intracellular dedifferentiation. Recalcitrant seeds lack these mechanisms, contributing significantly to their desiccation sensitivity. Consequently, recalcitrant seeds, which are shed at high water contents, can be stored only in the short-term, under conditions not allowing dehydration. The periods of such hydrated storage are constrained by germination that occurs without the need for extraneous water, and the proliferation of seed-associated fungi. Cryopreservation is viewed as the only option for long-term conservation of the germplasm of recalcitrant-seeded species. This is not easily achieved, as each of the necessary procedures imposes oxidative damage. Intact recalcitrant seeds cannot be cryopreserved, the common practice being to use excised embryos or embryonic axes as explants. Dehydration is a necessary procedure prior to exposure to cryogenic temperatures, but this is associated with metabolism-linked injury mediated by uncontrolled reactive oxygen species generation and failing anti-oxidant systems. While the extent to which this occurs can be curtailed by maximizing drying rate (flash drying) it cannot be completely obviated. Explant cooling for, and rewarming after, cryostorage must necessarily be rapid, to avoid ice crystallization. The ramifications of desiccation sensitivity are discussed, as are problems involved in cryostorage, particularly those accompanying dehydration and damage consequent upon ice crystallization. While desiccation sensitivity is a "fact" of seed recalcitrance, resolutions of the difficulties involved germplasm conservation are possible as

Co-evolution of cooperation and cognition: the impact of imperfect deliberation and context-sensitive intuition

PubMed Central

Kagan, Ari; Rand, David G.

2017-01-01

How does cognitive sophistication impact cooperation? We explore this question using a model of the co-evolution of cooperation and cognition. In our model, agents confront social dilemmas and coordination games, and make decisions using intuition or deliberation. Intuition is automatic and effortless, but relatively (although not necessarily completely) insensitive to context. Deliberation, conversely, is costly but relatively (although not necessarily perfectly) sensitive to context. We find that regardless of the sensitivity of intuition and imperfection of deliberation, deliberating undermines cooperation in social dilemmas, whereas deliberating can increase cooperation in coordination games if intuition is sufficiently sensitive. Furthermore, when coordination games are sufficiently likely, selection favours a strategy whose intuitive response ignores the contextual cues available and cooperates across contexts. Thus, we see how simple cognition can arise from active selection for simplicity, rather than just be forced to be simple due to cognitive constraints. Finally, we find that when deliberation is imperfect, the favoured strategy increases cooperation in social dilemmas (as a result of reducing deliberation) as the benefit of cooperation to the recipient increases. PMID:28330915

Portfolio of Research in Welfare and Family Self-Sufficiency: FY 2014. OPRE Report 2015-15

ERIC Educational Resources Information Center

Administration for Children & Families, 2015

2015-01-01

The Division of Economic Independence within the Office of Planning, Research and Evaluation (OPRE) has primary responsibility for welfare and family self-sufficiency research. OPRE's research in the area of welfare and family self-sufficiency is designed to expand knowledge about effective programs to promote employment, self-sufficiency, and…

How, When, and Where? Assessing Renewable Energy Self-Sufficiency at the Neighborhood Level.

PubMed

Grosspietsch, David; Thömmes, Philippe; Girod, Bastien; Hoffmann, Volker H

2018-02-20

Self-sufficient decentralized systems challenge the centralized energy paradigm. Although scholars have assessed specific locations and technological aspects, it remains unclear how, when, and where energy self-sufficiency could become competitive. To address this gap, we develop a techno-economic model for energy self-sufficient neighborhoods that integrates solar photovoltaics (PV), conversion, and storage technologies. We assess the cost of 100% self-sufficiency for both electricity and heat, comparing different technical configurations for a stylized neighborhood in Switzerland and juxtaposing these findings with projections on market and technology development. We then broaden the scope and vary the neighborhood's composition (residential share) and geographic position (along different latitudes). Regarding how to design self-sufficient neighborhoods, we find two promising technical configurations. The "PV-battery-hydrogen" configuration is projected to outperform a fossil-fueled and grid-connected reference configuration when energy prices increase by 2.5% annually and cost reductions in hydrogen-related technologies by a factor of 2 are achieved. The "PV-battery" configuration would allow achieving parity with the reference configuration sooner, at 21% cost reduction. Additionally, more cost-efficient deployment is found in neighborhoods where the end-use is small commercial or mixed and in regions where seasonal fluctuations are low and thus allow for reducing storage requirements.

Ultra-sensitive magnetic microscopy with an atomic magnetometer and flux guides

NASA Astrophysics Data System (ADS)

Kim, Young Jin; Savukov, Igor

Many applications in neuroscience, biomedical research, and material science require high-sensitivity, high-resolution magnetometry. In order to meet this need we recently combined a cm-size spin-exchange relaxation-free Atomic Magnetometer (AM) with a flux guide (FG) to produce ultra-sensitive FG-AM magnetic microscopy. The FG serves to transmit the target magnetic flux to the AM thus enhancing both the sensitivity and resolution to tiny magnetic objects. In this talk, we will describe existing and next generation FG-AM devices and present experimental and numerical tests of its sensitivity and resolution. We demonstrate that an optimized FG-AM has sufficient resolution and sensitivity for the detection of a small number of neurons, which would be an important milestone in neuroscience. In addition, as a demonstration of one possible application of the FG-AM device, we conducted high-resolution magnetic imaging of micron-size magnetic particles. We will show that the device can produce clear microscopic magnetic image of 10 μm-size magnetic particles.

High levels of wheel running protect against behavioral sensitization to cocaine.

PubMed

Renteria Diaz, Laura; Siontas, Dora; Mendoza, Jose; Arvanitogiannis, Andreas

2013-01-15

Although there is no doubt that the direct action of stimulant drugs on the brain is necessary for sensitization to their behavioral stimulating effects, several experiments indicate that drug action is often not sufficient to produce sensitization. There is considerable evidence that many individual characteristics and experiential variables can modulate the behavioral and neural changes that are seen following repeated exposure to stimulant drugs. In the work presented here, we examined whether chronic wheel running would modulate behavioral sensitization to cocaine, and whether any such influence was contingent on individual differences in wheel running. We found that a 5- or 10-week experience with wheel running protects against behavioral sensitization to cocaine but only in animals with a natural tendency to run the most. Understanding the mechanism underlying the modulating effect of wheel running on behavioral sensitization may have important implications for future studies on the link between drug-induced behavioral and neural adaptations. Copyright © 2012 Elsevier B.V. All rights reserved.

Entrepreneurship by any other name: self-sufficiency versus innovation.

PubMed

Parker Harris, Sarah; Caldwell, Kate; Renko, Maija

2014-01-01

Entrepreneurship has been promoted as an innovative strategy to address the employment of people with disabilities. Research has predominantly focused on the self-sufficiency aspect without fully integrating entrepreneurship literature in the areas of theory, systems change, and demonstration projects. Subsequently there are gaps in services, policies, and research in this field that, in turn, have limited our understanding of the support needs and barriers or facilitators of entrepreneurs with disabilities. A thorough analysis of the literature in these areas led to the development of two core concepts that need to be addressed in integrating entrepreneurship into disability employment research and policy: clarity in operational definitions and better disability statistics and outcome measures. This article interrogates existing research and policy efforts in this regard to argue for a necessary shift in the field from focusing on entrepreneurship as self-sufficiency to understanding entrepreneurship as innovation.

Is there sufficient evidence for tuning fork tests in diagnosing fractures? A systematic review.

PubMed

Mugunthan, Kayalvili; Doust, Jenny; Kurz, Bodo; Glasziou, Paul

2014-08-04

To determine the diagnostic accuracy of tuning fork tests for detecting fractures. Systematic review of primary studies evaluating the diagnostic accuracy of tuning fork tests for the presence of fracture. We searched MEDLINE, CINAHL, AMED, EMBASE, Sports Discus, CAB Abstracts and Web of Science from commencement to November 2012. We manually searched the reference lists of any review papers and any identified relevant studies. Two reviewers independently reviewed the list of potentially eligible studies and rated the studies for quality using the QUADAS-2 tool. Data were extracted to form 2×2 contingency tables. The primary outcome measure was the accuracy of the test as measured by its sensitivity and specificity with 95% CIs. We included six studies (329 patients), with two types of tuning fork tests (pain induction and loss of sound transmission). The studies included patients with an age range 7-60 years. The prevalence of fracture ranged from 10% to 80%. The sensitivity of the tuning fork tests was high, ranging from 75% to 100%. The specificity of the tests was highly heterogeneous, ranging from 18% to 95%. Based on the studies in this review, tuning fork tests have some value in ruling out fractures, but are not sufficiently reliable or accurate for widespread clinical use. The small sample size of the studies and the observed heterogeneity make generalisable conclusion difficult. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo.

PubMed

Ward, Patricia J; Jones, Laura N; Mulligan, Amanda; Goolsby, William; Wilhelm, Jennifer C; English, Arthur W

2016-01-01

Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation) that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2), we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2) to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555) was greater in mice that received optical treatment. Thus, the acute (1 hour), one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-). We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons.

Identifying Determinants of PARP Inhibitor Sensitivity in Ovarian Cancer

DTIC Science & Technology

2015-10-01

such as those lacking functional BRCA1 are highly sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. Ovarian cancer patients that harbored...Principal Investigator (Last, first, middle): Johnson, Neil  Dr. Johnson’s mentor, Dr. Jeffrey Boyd, left Fox Chase for Florida International

Online Learning in Higher Education: Necessary and Sufficient Conditions

ERIC Educational Resources Information Center

Lim, Cher Ping

2005-01-01

The spectacular development of information and communication technologies through the Internet has provided opportunities for students to explore the virtual world of information. In this article, the author discusses the necessary and sufficient conditions for successful online learning in educational institutions. The necessary conditions…

When is Information Sufficient for Action Search with Unreliable Yet Informative Intelligence

DTIC Science & Technology

2016-03-30

information: http://pubsonline.informs.org When Is Information Sufficient for Action? Search with Unreliable yet Informative Intelligence Michael Atkinson... Search with Unreliable yet Informative Intelligence. Operations Research Published online in Articles in Advance 30 Mar 2016 . http://dx.doi.org/10.1287...print) � ISSN 1526-5463 (online) http://dx.doi.org/10.1287/opre.2016.1488 © 2016 INFORMS When Is Information Sufficient for Action? Search with

The sensitivity of catchment hypsometry and hypsometric properties to DEM resolution and polynomial order

NASA Astrophysics Data System (ADS)

Liffner, Joel W.; Hewa, Guna A.; Peel, Murray C.

2018-05-01

Derivation of the hypsometric curve of a catchment, and properties relating to that curve, requires both use of topographical data (commonly in the form of a Digital Elevation Model - DEM), and the estimation of a functional representation of that curve. An early investigation into catchment hypsometry concluded 3rd order polynomials sufficiently describe the hypsometric curve, without the consideration of higher order polynomials, or the sensitivity of hypsometric properties relating to the curve. Another study concluded the hypsometric integral (HI) is robust against changes in DEM resolution, a conclusion drawn from a very limited sample size. Conclusions from these earlier studies have resulted in the adoption of methods deemed to be "sufficient" in subsequent studies, in addition to assumptions that the robustness of the HI extends to other hypsometric properties. This study investigates and demonstrates the sensitivity of hypsometric properties to DEM resolution, DEM type and polynomial order through assessing differences in hypsometric properties derived from 417 catchments and sub-catchments within South Australia. The sensitivity of hypsometric properties across DEM types and polynomial orders is found to be significant, which suggests careful consideration of the methods chosen to derive catchment hypsometric information is required.

Propeptides are sufficient to regulate organelle-specific pH-dependent activation of furin and proprotein convertase 1/3.

PubMed

Dillon, Stephanie L; Williamson, Danielle M; Elferich, Johannes; Radler, David; Joshi, Rajendra; Thomas, Gary; Shinde, Ujwal

2012-10-12

The proprotein convertases (PCs) furin and proprotein convertase 1/3 (PC1) cleave substrates at dibasic residues along the eukaryotic secretory/endocytic pathway. PCs are evolutionarily related to bacterial subtilisin and are synthesized as zymogens. They contain N-terminal propeptides (PRO) that function as dedicated catalysts that facilitate folding and regulate activation of cognate proteases through multiple-ordered cleavages. Previous studies identified a histidine residue (His69) that functions as a pH sensor in the propeptide of furin (PRO(FUR)), which regulates furin activation at pH~6.5 within the trans-Golgi network. Although this residue is conserved in the PC1 propeptide (PRO(PC1)), PC1 nonetheless activates at pH~5.5 within the dense core secretory granules. Here, we analyze the mechanism by which PRO(FUR) regulates furin activation and examine why PRO(FUR) and PRO(PC1) differ in their pH-dependent activation. Sequence analyses establish that while both PRO(FUR) and PRO(PC1) are enriched in histidines when compared with cognate catalytic domains and prokaryotic orthologs, histidine content in PRO(FUR) is ~2-fold greater than that in PRO(PC1), which may augment its pH sensitivity. Spectroscopy and molecular dynamics establish that histidine protonation significantly unfolds PRO(FUR) when compared to PRO(PC1) to enhance autoproteolysis. We further demonstrate that PRO(FUR) and PRO(PC1) are sufficient to confer organelle sensing on folding and activation of their cognate proteases. Swapping propeptides between furin and PC1 transfers pH-dependent protease activation in a propeptide-dictated manner in vitro and in cells. Since prokaryotes lack organelles and eukaryotic PCs evolved from propeptide-dependent, not propeptide-independent prokaryotic subtilases, our results suggest that histidine enrichment may have enabled propeptides to evolve to exploit pH gradients to activate within specific organelles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Assessing sufficient capability: A new approach to economic evaluation.

PubMed

Mitchell, Paul Mark; Roberts, Tracy E; Barton, Pelham M; Coast, Joanna

2015-08-01

Amartya Sen's capability approach has been discussed widely in the health economics discipline. Although measures have been developed to assess capability in economic evaluation, there has been much less attention paid to the decision rules that might be applied alongside. Here, new methods, drawing on the multidimensional poverty and health economics literature, are developed for conducting economic evaluation within the capability approach and focusing on an objective of achieving "sufficient capability". This objective more closely reflects the concern with equity that pervades the capability approach and the method has the advantage of retaining the longitudinal aspect of estimating outcome that is associated with quality-adjusted life years (QALYs), whilst also drawing on notions of shortfall associated with assessments of poverty. Economic evaluation from this perspective is illustrated in an osteoarthritis patient group undergoing joint replacement, with capability wellbeing assessed using ICECAP-O. Recommendations for taking the sufficient capability approach forward are provided. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Psychometric Framework for the Evaluation of Instructional Sensitivity

ERIC Educational Resources Information Center

Naumann, Alexander; Hochweber, Jan; Klieme, Eckhard

2016-01-01

Although there is a common understanding of instructional sensitivity, it lacks a common operationalization. Various approaches have been proposed, some focusing on item responses, others on test scores. As approaches often do not produce consistent results, previous research has created the impression that approaches to instructional sensitivity…

Non-randomized response model for sensitive survey with noncompliance.

PubMed

Wu, Qin; Tang, Man-Lai

2016-12-01

Collecting representative data on sensitive issues has long been problematic and challenging in public health prevalence investigation (e.g. non-suicidal self-injury), medical research (e.g. drug habits), social issue studies (e.g. history of child abuse), and their interdisciplinary studies (e.g. premarital sexual intercourse). Alternative data collection techniques that can be adopted to study sensitive questions validly become more important and necessary. As an alternative to the famous Warner randomized response model, non-randomized response triangular model has recently been developed to encourage participants to provide truthful responses in surveys involving sensitive questions. Unfortunately, both randomized and non-randomized response models could underestimate the proportion of subjects with the sensitive characteristic as some respondents do not believe that these techniques can protect their anonymity. As a result, some authors hypothesized that lack of trust and noncompliance should be highest among those who have the most to lose and the least to use for the anonymity provided by using these techniques. Some researchers noticed the existence of noncompliance and proposed new models to measure noncompliance in order to get reliable information. However, all proposed methods were based on randomized response models which require randomizing devices, restrict the survey to only face-to-face interview and are lack of reproductivity. Taking the noncompliance into consideration, we introduce new non-randomized response techniques in which no covariate is required. Asymptotic properties of the proposed estimates for sensitive characteristic as well as noncompliance probabilities are developed. Our proposed techniques are empirically shown to yield accurate estimates for both sensitive and noncompliance probabilities. A real example about premarital sex among university students is used to demonstrate our methodologies. © The Author(s) 2014.

Ethanol-related behaviors in mice lacking the sigma-1 receptor.

PubMed

Valenza, Marta; DiLeo, Alyssa; Steardo, Luca; Cottone, Pietro; Sabino, Valentina

2016-01-15

The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulant addiction; however, fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents. The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors. We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3-20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed. Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was instead unaltered in the mutants. Our results prove that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol. Copyright © 2015 Elsevier B.V. All rights reserved.

Ethanol-related behaviors in mice lacking the sigma-1 receptor

PubMed Central

Valenza, Marta; DiLeo, Alyssa; Steardo, Luca; Cottone, Pietro; Sabino, Valentina

2015-01-01

Rationale The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulants addiction, but fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents. Objectives The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors. Methods We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3%–20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed. Results Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was unaltered in the mutants. Conclusions Our results suggest that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol. PMID:26462569

Conditional loss of progranulin in neurons is not sufficient to cause neuronal ceroid lipofuscinosis-like neuropathology in mice.

PubMed

Petkau, Terri L; Blanco, Jake; Leavitt, Blair R

2017-10-01

Progranulin deficiency due to heterozygous null mutations in the GRN gene is a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations cause neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. Progranulin is a secreted glycoprotein expressed in both neurons and microglia, but not astrocytes, in the brain. We generated conditional progranulin-knockout mice that lack progranulin in nestin-expressing cells (Nes-cKO mice), which include most neurons as well as astrocytes. We confirmed near complete knockout of progranulin in neurons in Nes-cKO mice, while microglial progranulin levels remained similar to that of wild-type animals. Overall brain progranulin levels were reduced by about 50% in Nes-cKO, and no Grn was detected in primary Nes-cKO neurons. Nes-cKO mice aged to 12months did not display any increase in lipofuscin deposition, microgliosis, or astrogliosis in the four brain regions examined, though increases were observed for most of these measures in Grn-null animals. We conclude that neuron-specific loss of progranulin is not sufficient to cause similar neuropathological changes to those seen in constitutive Grn-null animals. Our results suggest that increased lipofuscinosis and gliosis in Grn-null animals are not caused by intrinsic progranulin deficiency in neurons, and that microglia-derived progranulin may be sufficient to maintain neuronal health and homeostasis in the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Greater learnability is not sufficient to produce cultural universals.

PubMed

Rafferty, Anna N; Griffiths, Thomas L; Ettlinger, Marc

2013-10-01

Looking across human societies reveals regularities in the languages that people speak and the concepts that they use. One explanation that has been proposed for these "cultural universals" is differences in the ease with which people learn particular languages and concepts. A difference in learnability means that languages and concepts possessing a particular property are more likely to be accurately transmitted from one generation of learners to the next. Intuitively, this difference could allow languages and concepts that are more learnable to become more prevalent after multiple generations of cultural transmission. If this is the case, the prevalence of languages and concepts with particular properties can be explained simply by demonstrating empirically that they are more learnable. We evaluate this argument using mathematical analysis and behavioral experiments. Specifically, we provide two counter-examples that show how greater learnability need not result in a property becoming prevalent. First, more learnable languages and concepts can nonetheless be less likely to be produced spontaneously as a result of transmission failures. We simulated cultural transmission in the laboratory to show that this can occur for memory of distinctive items: these items are more likely to be remembered, but not generated spontaneously once they have been forgotten. Second, when there are many languages or concepts that lack the more learnable property, sheer numbers can swamp the benefit produced by greater learnability. We demonstrate this using a second series of experiments involving artificial language learning. Both of these counter-examples show that simply finding a learnability bias experimentally is not sufficient to explain why a particular property is prevalent in the languages or concepts used in human societies: explanations for cultural universals based on cultural transmission need to consider the full set of hypotheses a learner could entertain and all of

76 FR 55407 - Announcement of Funding Awards; Public and Indian Housing Family Self-Sufficiency Program Under...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-07

...; Public and Indian Housing Family Self-Sufficiency Program Under the Resident Opportunity and Self... (NOFA) for the Public and Indian Housing Family Self-Sufficiency Program Under the Resident Opportunity.... Appendix A--List of Public and Indian Housing Family Self-Sufficiency Program Under the Resident...

Towards a Sufficient Theory of Transition in Cognitive Development.

ERIC Educational Resources Information Center

Wallace, J. G.

The work reported aims at the construction of a sufficient theory of transition in cognitive development. The method of theory construction employed is computer simulation of cognitive process. The core of the model of transition presented comprises self-modification processes that, as a result of continuously monitoring an exhaustive record of…

Role of L-alanine for redox self-sufficient amination of alcohols.

PubMed

Klatte, Stephanie; Wendisch, Volker F

2015-01-23

In white biotechnology biocatalysis represents a key technology for chemical functionalization of non-natural compounds. The plasmid-born overproduction of an alcohol dehydrogenase, an L-alanine-dependent transaminase and an alanine dehydrogenase allows for redox self-sufficient amination of alcohols in whole cell biotransformation. Here, conditions to optimize the whole cell biocatalyst presented in (Bioorg Med Chem 22:5578-5585, 2014), and the role of L-alanine for efficient amine functionalization of 1,10-decanediol to 1,10-diaminodecane were analyzed. The enzymes of the cascade for amine functionalization of alcohols were characterized in vitro to find optimal conditions for an efficient process. Transaminase from Chromobacterium violaceum, TaCv, showed three-fold higher catalytic efficiency than transaminase from Vibrio fluvialis, TaVf, and improved production at 37°C. At 42°C, TaCv was more active, which matched thermostable alcohol dehydrogenase and alanine dehydrogenase and improved the 1,10-diaminodecane production rate four-fold. To study the role of L-alanine in the whole cell biotransformation, the L-alanine concentration was varied and 1,10.diaminodecane formation tested with constant 10 mM 1,10- decanediol and 100 mM NH4Cl. Only 5.6% diamine product were observed without added L-alanine. L-alanine concentrations equimolar to that of the alcohol enabled for 94% product formation but higher L-alanine concentrations allowed for 100% product formation. L-alanine was consumed by the E. coli biocatalyst, presumably due to pyruvate catabolism since up to 16 mM acetate accumulated. Biotransformation employing E. coli strain YYC202/pTrc99a-ald-adh-ta Cv, which is unable to catabolize pyruvate, resulted in conversion with a selectivity of 42 mol-%. Biotransformation with E. coli strains only lacking pyruvate oxidase PoxB showed similar reduced amination of 1,10-decanediol indicating that oxidative decarboxylation of pyruvate to acetate by PoxB is primarily

[Sufficiency with water-soluble vitamins and state of bone in pregnant women].

PubMed

Vrzhesinskaya, O A; Pereverzeva, O G; Gmoshinskaya, M V; Kodentsova, V M; Safronova, A I; Korosteleva, M M; Aleshina, I V; Fandeeva, T A

2015-01-01

Vitamin status and bone strength have been estimated in 91 pregnant women (29.3 ± 4.6 years old) from Moscow by non-invasive methods. Sufficiency with vitamins C, B2, B6 has been evaluated by morning urinary excretion of ascorbic acid, riboflavin and 4-piridoxic acid determined by visual titration and fluorimetric methods. The rate of bone resorption has been measured by the ratio of urinary calcium and creatinine, determined by complexometric titration and spectrophotometrically. The study of the bone strength has been conducted using an ultrasonic densitometer (the speed of the ultrasonic waves along the cortical layer). The lack of vitamin C was found in 20.4% .of the women surveyed, vitamin B2--in 27.4%. Vitamin B6 deficiency was detected most frequently (90%). Excretion of vitamins B2 and B6 in women in the third trimester of pregnancy was lower as compared with the women in the first and second trimester. In 53.3% of the women surveyed an increase in urinary excretion of calcium per creatinine has been observed. Excretion of group B vitamins (especially vitamin B6, 1.75 fold, p < 0.05) in women taking vitamin supplements was higher compared to non-taking vitamins that indicates the better sufficiency of the organism with these vitamins. Among women who took vitamin complexes, inadequate supply with water-soluble vitamins C, B2 and B6 was detected less frequently (the difference was significant for vitamin B2) than among women who did not intake vitamin complexes (in 11.9, 27.7 and 42.4% vs 16.1, 54.8 and 48.8 %). The rate of bone resorption (Ca/creatinine) in women taking vitamins was smaller (0.19 ± 0.09 vs 0.24 ± 0.14, p > 0.05). Ca/creatinine ratio was within normal range in 40% of women who intake vitamins, while in women not taking vitamins--only in 22.2%; this value exceeded the upper limit of norm in the rest. The strength of bone was broken in women in the second and third trimester of pregnancy, having worse supply of vitamins. The percentage of

Cross-cultural comparison of lack of regular physical activity among college students: Universal versus transversal.

PubMed

Seo, Dong-Chul; Torabi, Mohammad R; Jiang, Nan; Fernandez-Rojas, Xinia; Park, Bock-Hee

2009-01-01

This study examined cultural influence on personal and behavioral correlates of lack of regular physical activity (PA) among college students in four countries, i.e., the United States, Costa Rica, India, and South Korea. Public universities were randomly chosen among the four countries. A total of 4,685 students participated in the study during the 2006-2007 academic year with a response rate of 90.1%. The vast majority of the questions on the instrument were adopted from the Youth Risk Behavior Survey and the Behavioral Risk Factor Surveillance System questionnaires. The instrument was translated into Spanish and Korean and then back-translated into English to check accuracy of the translation. Low fruit consumption was a culture-universal predictor of lack of regular PA. Gender, perceived body weight, vegetable consumption, and cigarette smoking were culture-specific predictors, indicating PA might be a transversal value. Body mass index, binge drinking, and TV/video watching were not associated with lack of regular PA in any of the four countries. While PA is valued across different segments of many cultures, given the several culture-specific predictors, PA appears to be more transversal than universal. Therefore, culturally sensitive interventions are necessary to promote PA among young adults.

A Test of the Homogeneous versus Heterogeneous Categories of the Repression-Sensitization Dimension

ERIC Educational Resources Information Center

Millimet, C. Raymond; Cohen, Howard J.

1973-01-01

A study was designed to examine further the psychometric relationships between the Marlowe-Crown Social Desirability Scale (MC-SDS) and a Repression-Sensitization (R-S) scale in order to affirm or deny the meaningfulness of pairing these two personality measures. The relationships between these measures was considered to be of sufficiently high…

Low levels of glutathione are sufficient for survival of keratinocytes after UV irradiation and for healing of mouse skin wounds.

PubMed

Telorack, Michèle; Abplanalp, Jeannette; Werner, Sabine

2016-08-01

Reduced levels of the cellular antioxidant glutathione are associated with premature skin aging, cancer and impaired wound healing, but the in vivo functions of glutathione in the skin remain largely unknown. Therefore, we analyzed mice lacking the modifier subunit of the glutamate cysteine ligase (Gclm), the enzyme that catalyzes the rate-limiting step of glutathione biosynthesis. Glutathione levels in the skin of these mice were reduced by 70 %. However, neither skin development and homeostasis, nor UVA- or UVB-induced apoptosis in the epidermis were affected. Histomorphometric analysis of excisional wounds did not reveal wound healing abnormalities in young Gclm-deficient mice, while the area of hyperproliferative epithelium as well as keratinocyte proliferation were affected in aged mice. These findings suggest that low levels of glutathione are sufficient for wound repair in young mice, but become rate-limiting upon aging.

Predicting individual contrast sensitivity functions from acuity and letter contrast sensitivity measurements

PubMed Central

Thurman, Steven M.; Davey, Pinakin Gunvant; McCray, Kaydee Lynn; Paronian, Violeta; Seitz, Aaron R.

2016-01-01

Contrast sensitivity (CS) is widely used as a measure of visual function in both basic research and clinical evaluation. There is conflicting evidence on the extent to which measuring the full contrast sensitivity function (CSF) offers more functionally relevant information than a single measurement from an optotype CS test, such as the Pelli–Robson chart. Here we examine the relationship between functional CSF parameters and other measures of visual function, and establish a framework for predicting individual CSFs with effectively a zero-parameter model that shifts a standard-shaped template CSF horizontally and vertically according to independent measurements of high contrast acuity and letter CS, respectively. This method was evaluated for three different CSF tests: a chart test (CSV-1000), a computerized sine-wave test (M&S Sine Test), and a recently developed adaptive test (quick CSF). Subjects were 43 individuals with healthy vision or impairment too mild to be considered low vision (acuity range of −0.3 to 0.34 logMAR). While each test demands a slightly different normative template, results show that individual subject CSFs can be predicted with roughly the same precision as test–retest repeatability, confirming that individuals predominantly differ in terms of peak CS and peak spatial frequency. In fact, these parameters were sufficiently related to empirical measurements of acuity and letter CS to permit accurate estimation of the entire CSF of any individual with a deterministic model (zero free parameters). These results demonstrate that in many cases, measuring the full CSF may provide little additional information beyond letter acuity and contrast sensitivity. PMID:28006065

Is the Supply of Mathematics and Science Teachers Sufficient?

ERIC Educational Resources Information Center

Ingersoll, Richard M.; Perda, David

2010-01-01

This study seeks to empirically ground the debate over mathematics and science teacher shortages and evaluate the extent to which there is, or is not, sufficient supply of teachers in these fields. The authors' analyses of nationally representative data from multiple sources show that math and science are the fields most difficult to staff, but…

AOP: An R Package For Sufficient Causal Analysis in Pathway ...

EPA Pesticide Factsheets

Summary: How can I quickly find the key events in a pathway that I need to monitor to predict that a/an beneficial/adverse event/outcome will occur? This is a key question when using signaling pathways for drug/chemical screening in pharma-cology, toxicology and risk assessment. By identifying these sufficient causal key events, we have fewer events to monitor for a pathway, thereby decreasing assay costs and time, while maximizing the value of the information. I have developed the “aop” package which uses backdoor analysis of causal net-works to identify these minimal sets of key events that are suf-ficient for making causal predictions. Availability and Implementation: The source and binary are available online through the Bioconductor project (http://www.bioconductor.org/) as an R package titled “aop”. The R/Bioconductor package runs within the R statistical envi-ronment. The package has functions that can take pathways (as directed graphs) formatted as a Cytoscape JSON file as input, or pathways can be represented as directed graphs us-ing the R/Bioconductor “graph” package. The “aop” package has functions that can perform backdoor analysis to identify the minimal set of key events for making causal predictions.Contact: burgoon.lyle@epa.gov This paper describes an R/Bioconductor package that was developed to facilitate the identification of key events within an AOP that are the minimal set of sufficient key events that need to be tested/monit

Intracellular singlet oxygen photosensitizers: on the road to solving the problems of sensitizer degradation, bleaching and relocalization.

PubMed

da Silva, Elsa F F; Pimenta, Frederico M; Pedersen, Brian W; Blaikie, Frances H; Bosio, Gabriela N; Breitenbach, Thomas; Westberg, Michael; Bregnhøj, Mikkel; Etzerodt, Michael; Arnaut, Luis G; Ogilby, Peter R

2016-02-01

Selected singlet oxygen photosensitizers have been examined from the perspective of obtaining a molecule that is sufficiently stable under conditions currently employed to study singlet oxygen behavior in single mammalian cells. Reasonable predictions about intracellular sensitizer stability can be made based on solution phase experiments that approximate the intracellular environment (e.g., solutions containing proteins). Nevertheless, attempts to construct a stable sensitizer based solely on the expected reactivity of a given functional group with singlet oxygen are generally not sufficient for experiments in cells; it is difficult to construct a suitable chromophore that is impervious to all of the secondary and/or competing degradative processes that are present in the intracellular environment. On the other hand, prospects are reasonably positive when one considers the use of a sensitizer encapsulated in a specific protein; the local environment of the chromophore is controlled, degradation as a consequence of bimolecular reactions can be mitigated, and genetic engineering can be used to localize the encapsulated sensitizer in a given cellular domain. Also, the option of directly exciting oxygen in sensitizer-free experiments provides a useful complementary tool. These latter systems bode well with respect to obtaining more accurate control of the "dose" of singlet oxygen used to perturb a cell; a parameter that currently limits mechanistic studies of singlet-oxygen-mediated cell signaling.

When Sufficiently Processed, Semantically Related Distractor Pictures Hamper Picture Naming.

PubMed

Matushanskaya, Asya; Mädebach, Andreas; Müller, Matthias M; Jescheniak, Jörg D

2016-11-01

Prominent speech production models view lexical access as a competitive process. According to these models, a semantically related distractor picture should interfere with target picture naming more strongly than an unrelated one. However, several studies failed to obtain such an effect. Here, we demonstrate that semantic interference is obtained, when the distractor picture is sufficiently processed. Participants named one of two pictures presented in close temporal succession, with color cueing the target. Experiment 1 induced the prediction that the target appears first. When this prediction was violated (distractor first), semantic interference was observed. Experiment 2 ruled out that the time available for distractor processing was the driving force. These results show that semantically related distractor pictures interfere with the naming response when they are sufficiently processed. The data thus provide further support for models viewing lexical access as a competitive process.

Necessary and sufficient conditions for R₀ to be a sum of contributions of fertility loops.

PubMed

Rueffler, Claus; Metz, Johan A J

2013-03-01

Recently, de-Camino-Beck and Lewis (Bull Math Biol 69:1341-1354, 2007) have presented a method that under certain restricted conditions allows computing the basic reproduction ratio R₀ in a simple manner from life cycle graphs, without, however, giving an explicit indication of these conditions. In this paper, we give various sets of sufficient and generically necessary conditions. To this end, we develop a fully algebraic counterpart of their graph-reduction method which we actually found more useful in concrete applications. Both methods, if they work, give a simple algebraic formula that can be interpreted as the sum of contributions of all fertility loops. This formula can be used in e.g. pest control and conservation biology, where it can complement sensitivity and elasticity analyses. The simplest of the necessary and sufficient conditions is that, for irreducible projection matrices, all paths from birth to reproduction have to pass through a common state. This state may be visible in the state representation for the chosen sampling time, but the passing may also occur in between sampling times, like a seed stage in the case of sampling just before flowering. Note that there may be more than one birth state, like when plants in their first year can already have different sizes at the sampling time. Also the common state may occur only later in life. However, in all cases R₀ allows a simple interpretation as the expected number of new individuals that in the next generation enter the common state deriving from a single individual in this state. We end with pointing to some alternative algebraically simple quantities with properties similar to those of R₀ that may sometimes be used to good effect in cases where no simple formula for R₀ exists.

Ebola virus proteins NP, VP35, and VP24 are essential and sufficient to mediate nucleocapsid transport.

PubMed

Takamatsu, Yuki; Kolesnikova, Larissa; Becker, Stephan

2018-01-30

The intracytoplasmic movement of nucleocapsids is a crucial step in the life cycle of enveloped viruses. Determination of the viral components necessary for viral nucleocapsid transport competency is complicated by the dynamic and complex nature of nucleocapsid assembly and the lack of appropriate model systems. Here, we established a live-cell imaging system based on the ectopic expression of fluorescent Ebola virus (EBOV) fusion proteins, allowing the visualization and analysis of the movement of EBOV nucleocapsid-like structures with different protein compositions. Only three of the five EBOV nucleocapsid proteins-nucleoprotein, VP35, and VP24-were necessary and sufficient to form transport-competent nucleocapsid-like structures. The transport of these structures was found to be dependent on actin polymerization and to have dynamics that were undistinguishable from those of nucleocapsids in EBOV-infected cells. The intracytoplasmic movement of nucleocapsid-like structures was completely independent of the viral matrix protein VP40 and the viral surface glycoprotein GP. However, VP40 greatly enhanced the efficiency of nucleocapsid recruitment into filopodia, the sites of EBOV budding.

Maintaining gender sensitivity in the family practice: facilitators and barriers.

PubMed

Celik, Halime; Lagro-Janssen, Toine; Klinge, Ineke; van der Weijden, Trudy; Widdershoven, Guy

2009-12-01

This study aims to identify the facilitators and barriers perceived by General Practitioners (GPs) to maintain a gender perspective in family practice. Nine semi-structured interviews were conducted among nine pairs of GPs. The data were analysed by means of deductive content analysis using theory-based methods to generate facilitators and barriers to gender sensitivity. Gender sensitivity in family practice can be influenced by several factors which ultimately determine the extent to which a gender sensitive approach is satisfactorily practiced by GPs in the doctor-patient relationship. Gender awareness, repetition and reminders, motivation triggers and professional guidelines were found to facilitate gender sensitivity. On the other hand, lacking skills and routines, scepticism, heavy workload and the timing of implementation were found to be barriers to gender sensitivity. While the potential effect of each factor affecting gender sensitivity in family practice has been elucidated, the effects of the interplay between these factors still need to be determined.

Sensitivity and comparison evaluation of Saturn 5 liquid penetrants

NASA Technical Reports Server (NTRS)

Jones, G. H.

1973-01-01

Results of a sensitivity and comparison evaluation performed on six liquid penetrants that were used on the Saturn 5 vehicle and other space hardware to detect surface discontinuities are described. The relationship between penetrant materials and crack definition capabilities, the optimum penetrant materials evaluation method, and the optimum measurement methods for crack dimensions were investigated. A unique method of precise developer thickness control was envolved, utilizing clear radiographic film and a densitometer. The method of evaluation included five aluminum alloy, 2219-T87, specimens that were heated and then quenched in cold water to produce cracks. The six penetrants were then applied, one at a time, and the crack indications were counted and recorded for each penetrant for comparison purposes. Measurements were made by determining the visual crack indications per linear inch and then sectioning the specimens for a metallographic count of the cracks present. This method provided a numerical approach for assigning a sensitivity index number to the penetrants. Of the six penetrants evaluated, two were not satisfactory (one was not sufficiently sensitive and the other was to sensitive, giving false indications). The other four were satisfactory with approximately the same sensitivity in the range of 78 to 80.5 percent of total cracks detected.

Is self-sufficiency financially viable and ethically justifiable?--a commercial viewpoint.

PubMed

Christie, R B

1994-12-01

Manufacturers of blood products have to maintain the highest possible standards for plasma screening and good manufacturing practices to ensure maximum purity and viral safety. The private sector companies have much experience in implementing and complying with national and international regulations. These requirements involve considerable cost in the areas of (1) plasma collection facilities, (2) research and clinical research, (3) manufacture, and (4) quality control. Total self-sufficiency would mean the loss of many existing resources. An alternative would be a collaboration between the public and private sectors to meet the needs of all patients who require plasma derived products. The current definition of self-sufficiency suggests that it is not financially viable.

Anxiety Sensitivity as a Prospective Predictor of Alcohol Use Disorders

ERIC Educational Resources Information Center

Schmidt, Norman B.; Buckner, Julia D.; Keough, Meghan E.

2007-01-01

Emerging evidence suggests that elevated anxiety sensitivity (AS) is associated with substance use disorders. However, prospective evidence regarding this association is currently lacking. The primary aim of the present study was to determine whether AS is involved in the pathogenesis of substance-related psychopathology. A large, nonclinical…

Climate Sensitivity in the Anthropocene

NASA Technical Reports Server (NTRS)

Previdi, M.; Liepert, B. G.; Peteet, Dorothy M.; Hansen, J.; Beerling, D. J.; Broccoli, A. J.; Frolking, S.; Galloway, J. N.; Heimann, M.; LeQuere, C.;

Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments

NASA Astrophysics Data System (ADS)

Loo, Lit-Hsin; Bougen-Zhukov, Nicola Michelle; Tan, Wei-Ling Cecilia

2017-03-01

Signaling pathways can generate different cellular responses to the same cytotoxic agents. Current quantitative models for predicting these differential responses are usually based on large numbers of intracellular gene products or signals at different levels of signaling cascades. Here, we report a study to predict cellular sensitivity to tumor necrosis factor alpha (TNFα) using high-throughput cellular imaging and machine-learning methods. We measured and compared 1170 protein phosphorylation events in a panel of human lung cancer cell lines based on different signals, subcellular regions, and time points within one hour of TNFα treatment. We found that two spatiotemporal-specific changes in an intermediate signaling protein, p90 ribosomal S6 kinase (RSK), are sufficient to predict the TNFα sensitivity of these cell lines. Our models could also predict the combined effects of TNFα and other kinase inhibitors, many of which are not known to target RSK directly. Therefore, early spatiotemporal-specific changes in intermediate signals are sufficient to represent the complex cellular responses to these perturbations. Our study provides a general framework for the development of rapid, signaling-based cytotoxicity screens that may be used to predict cellular sensitivity to a cytotoxic agent, or identify co-treatments that may sensitize or desensitize cells to the agent.

Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments

PubMed Central

Loo, Lit-Hsin; Bougen-Zhukov, Nicola Michelle; Tan, Wei-Ling Cecilia

2017-01-01

Signaling pathways can generate different cellular responses to the same cytotoxic agents. Current quantitative models for predicting these differential responses are usually based on large numbers of intracellular gene products or signals at different levels of signaling cascades. Here, we report a study to predict cellular sensitivity to tumor necrosis factor alpha (TNFα) using high-throughput cellular imaging and machine-learning methods. We measured and compared 1170 protein phosphorylation events in a panel of human lung cancer cell lines based on different signals, subcellular regions, and time points within one hour of TNFα treatment. We found that two spatiotemporal-specific changes in an intermediate signaling protein, p90 ribosomal S6 kinase (RSK), are sufficient to predict the TNFα sensitivity of these cell lines. Our models could also predict the combined effects of TNFα and other kinase inhibitors, many of which are not known to target RSK directly. Therefore, early spatiotemporal-specific changes in intermediate signals are sufficient to represent the complex cellular responses to these perturbations. Our study provides a general framework for the development of rapid, signaling-based cytotoxicity screens that may be used to predict cellular sensitivity to a cytotoxic agent, or identify co-treatments that may sensitize or desensitize cells to the agent. PMID:28272488

High-sensitivity detection of TNT

PubMed Central

Pushkarsky, Michael B.; Dunayevskiy, Ilya G.; Prasanna, Manu; Tsekoun, Alexei G.; Go, Rowel; Patel, C. Kumar N.

2006-01-01

We report high-sensitivity detection of 2,4,6-trinitrotoluene (TNT) by using laser photoacoustic spectroscopy where the laser radiation is obtained from a continuous-wave room temperature high-power quantum cascade laser in an external grating cavity geometry. The external grating cavity quantum cascade laser is continuously tunable over ≈400 nm around 7.3 μm and produces a maximum continuous-wave power of ≈200 mW. The IR spectroscopic signature of TNT is sufficiently different from that of nitroglycerine so that unambiguous detection of TNT without false positives from traces of nitroglycerine is possible. We also report the results of spectroscopy of acetylene in the 7.3-μm region to demonstrate continuous tunability of the IR source. PMID:17164325

Stability and delay sensitivity of neutral fractional-delay systems.

PubMed

Xu, Qi; Shi, Min; Wang, Zaihua

2016-08-01

This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

Where in the Oregon Trail Is Carmen Sandiego? A Commentary on Software and Its Sensitivity to Diversity.

ERIC Educational Resources Information Center

Guzman, Delrita Cruz

2002-01-01

Addresses cultural biases, language biases, cultural sensitivity, and the authenticity of educational software for children, critiquing several popular educational programs and revealing the pitfalls of software design and the problem among software engineers (lack of training and lack of cultural knowledge). Proposes tips to help parents and…

Piezoresistive pressure sensor with high sensitivity for medical application using peninsula-island structure

NASA Astrophysics Data System (ADS)

Xu, Tingzhong; Wang, Hongyan; Xia, Yong; Zhao, Zhiming; Huang, Mimi; Wang, Jiuhong; Zhao, Libo; Zhao, Yulong; Jiang, Zhuangde

2017-12-01

A novel micro-electromechanical systems piezoresistive pressure sensor with a diagonally positioned peninsula-island structure has high sensitivity for ultralow- pressure measurement. The pressure sensor was designed with a working range of 0-500 Pa and had a high sensitivity of 0.06 mV·V-1·Pa-1. The trade-off between high sensitivity and linearity was alleviated. Moreover, the influence of the installation angle on the sensing chip output was analyzed, and an application experiment of the sensor was conducted using the built pipettor test platform. Findings indicated that the proposed pressure sensor had sufficient resolution ability and accuracy to detect the pressure variation in the pipettor chamber. Therefore, the proposed pressure sensor has strong potential for medical equipment application.

Application of the remote-sensing communication model to a time-sensitive wildfire remote-sensing system

Treesearch

Christopher D. Lippitt; Douglas A. Stow; Philip J. Riggan

2016-01-01

Remote sensing for hazard response requires a priori identification of sensor, transmission, processing, and distribution methods to permit the extraction of relevant information in timescales sufficient to allow managers to make a given time-sensitive decision. This study applies and demonstrates the utility of the Remote Sensing Communication...

75 FR 16493 - Announcement of Funding Awards for the Public and Indian Housing Family Self-Sufficiency Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-01

... Awards for the Public and Indian Housing Family Self-Sufficiency Program Under the Resident Opportunity... (NOFA) for the Public and Indian Housing Family Self-Sufficiency Program under the Resident Opportunity... Public and Indian Housing Family Self-Sufficiency Program under the Resident Opportunity and Self...

77 FR 14540 - Announcement of Funding Awards for the Public and Indian Housing Family Self-Sufficiency Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-12

... Awards for the Public and Indian Housing Family Self-Sufficiency Program Under the Resident Opportunity... Funding Availability (NOFA) for the Public and Indian Housing Family Self-Sufficiency Program under the... amounts of the 238 awards made under the Public and Indian Housing Family Self-Sufficiency Program under...

Development of Temperature Sensitive Paints for the Detection of Small Temperature Differences

NASA Technical Reports Server (NTRS)

Oglesby, Donald M.; Upchurch, Billy T.; Sealey, Bradley S.; Leighty, Bradley D.; Burkett, Cecil G., Jr.; Jalali, Amir

1997-01-01

Temperature sensitive paints (TSP s) have recently been used to detect small temperature differences on aerodynamic model surfaces. These types of applications impose stringent performance requirements on a paint system. The TSP s must operate over a broad temperature range, must be physically robust (cannot chip or peel), must be polishable to at least the smoothness of the model surface, and must have sufficient sensitivity to detect small temperature differences. TSP coatings based on the use of metal complexes in polymer binders were developed at NASA Langley Research Center which meet most of the requirements for detection of small temperature differences under severe environmental conditions.

Lack of Set Theory Relevant Prerequisite Knowledge

ERIC Educational Resources Information Center

Dogan-Dunlap, Hamide

2006-01-01

Many students struggle with college mathematics topics due to a lack of mastery of prerequisite knowledge. Set theory language is one such prerequisite for linear algebra courses. Many students' mistakes on linear algebra questions reveal a lack of mastery of set theory knowledge. This paper reports the findings of a qualitative analysis of a…

Lack of association between deletion polymorphism of BIM gene and in vitro drug sensitivity in B-cell precursor acute lymphoblastic leukemia.

PubMed

Huang, Meixian; Miyake, Kunio; Kagami, Keiko; Abe, Masako; Shinohara, Tamao; Watanabe, Atsushi; Somazu, Shinpei; Oshiro, Hiroko; Goi, Kumiko; Goto, Hiroaki; Minegishi, Masayoshi; Iwamoto, Shotaro; Kiyokawa, Nobutaka; Sugita, Kanji; Inukai, Takeshi

2017-09-01

A deletion polymorphism in the BIM gene was identified as an intrinsic mechanism for resistance to tyrosine kinase inhibitor in chronic myeloid leukemia patients in East Asia. BIM is also involved in the responses to glucocorticoid and chemotherapy in acute lymphoblastic leukemia (ALL), suggesting a possible association between deletion polymorphism of BIM and the chemosensitivity of ALL. Thus, we analyzed 72 B-cell precursor (BCP)-ALL cell lines established from Japanese patients. Indeed, higher BIM gene expression was associated with good in vitro sensitivities to glucocorticoid and chemotherapeutic agents used in induction therapy. We also analyzed the methylation status of the BIM gene promoter by next generation sequencing of genome bisulfite PCR products, since genetic polymorphism could be insignificant when epigenetically inactivated. Hypermethylation of the BIM gene promoter was associated with lower BIM gene expression and poorer sensitivity to vincristine. Of note, however, the prevalence of a deletion polymorphism was not associated with the BIM gene expression level or drug sensitivities in BCP-ALL cell lines, in which the BIM gene was unmethylated. These observations suggest that an association of a deletion polymorphism of BIM and the response to induction therapy in BCP-ALL may be clinically minimal. Copyright © 2017. Published by Elsevier Ltd.

Asymmetric Zinc Phthalocyanines as Dye-Sensitized Solar Cells

NASA Astrophysics Data System (ADS)

Tunc, Gulenay; Yavuz, Yunus; Gurek, Aysegul; Canimkurbey, Betul; Kosemen, Arif; San, Sait Eren; Ahsen, Vefa

Dye-sensitized solar cells (DSSCs) have received increasing attention due to their high incident to photon efficiency, easy fabrication and low production cost . Tremendous research efforts have been devoted to the development of new and efficient sensitizers suitable for practical use. In TiO2-based DSSCs, efficiencies of up to 11.4% under simulated sunlight have been obtained with rutheniumepolypyridyl complexes. However, the main drawback of ruthenium complexes is the lack of absorption in the red region of the visible light and the high cost. For this reason, dyes with large and stable p-conjugated systems such as porphyrins and phthalocyanines are important classes of potential sensitizers for highly efficient DSSCs. Phthalocyanines (Pcs) have been widely used as sensitizers because of their improved light-harvesting properties in the far red- and near-IR spectral regions and their extraordinary robustness [1]. In this work, a series of asymmetric Zn(II) Pcs bearing a carboxylic acid group and six hexylthia groups either at the peripheral or non-peripheral positions have been designed and synthesized to investigate the influence of the COOH group and the positions of hexylthia groups on the dye-sensitized solar cell (DSSC) performance.

Sensitivity of Spacebased Microwave Radiometer Observations to Ocean Surface Evaporation

NASA Technical Reports Server (NTRS)

Liu, Timothy W.; Li, Li

2000-01-01

Ocean surface evaporation and the latent heat it carries are the major components of the hydrologic and thermal forcing on the global oceans. However, there is practically no direct in situ measurements. Evaporation estimated from bulk parameterization methods depends on the quality and distribution of volunteer-ship reports which are far less than satisfactory. The only way to monitor evaporation with sufficient temporal and spatial resolutions to study global environment changes is by spaceborne sensors. The estimation of seasonal-to-interannual variation of ocean evaporation, using spacebased measurements of wind speed, sea surface temperature (SST), and integrated water vapor, through bulk parameterization method,s was achieved with reasonable success over most of the global ocean, in the past decade. Because all the three geophysical parameters can be retrieved from the radiance at the frequencies measured by the Scanning Multichannel Microwave Radiometer (SMMR) on Nimbus-7, the feasibility of retrieving evaporation directly from the measured radiance was suggested and demonstrated using coincident brightness temperatures observed by SMMR and latent heat flux computed from ship data, in the monthly time scale. However, the operational microwave radiometers that followed SMMR, the Special Sensor Microwave/Imager (SSM/I), lack the low frequency channels which are sensitive to SST. This low frequency channels are again included in the microwave imager (TMI) of the recently launched Tropical Rain Measuring Mission (TRMM). The radiance at the frequencies observed by both TMI and SSM/I were simulated through an atmospheric radiative transfer model using ocean surface parameters and atmospheric temperature and humidity profiles produced by the reanalysis of the European Center for Medium Range Weather Forecast (ECMWF). From the same ECMWF data set, coincident evaporation is computed using a surface layer turbulent transfer model. The sensitivity of the radiance to

Staple Food Self-Sufficiency of Farmers Household Level in The Great Solo

NASA Astrophysics Data System (ADS)

Darsono

2017-04-01

Analysis of food security level of household is a novelty of measurement standards which usually includes regional and national levels. With household approach is expected to provide the basis of sharp food policy formulation. The purpose of this study are to identify the condition of self-sufficiency in staple foods, and to find the main factors affecting the dynamics of self-sufficiency in staple foods on farm household level in Great Solo. Using primary data from 50 farmers in the sample and secondary data in Great Solo (Surakarta city, Boyolali, Sukoharjo, Karanganyar, Wonogiri, Sragen and Klaten). Compiled panel data were analyzed with linear probability regression models to produce a good model. The results showed that farm households in Great Solo has a surplus of staple food (rice) with an average consumption rate of 96.8 kg/capita/year. This number is lower than the national rate of 136.7 kg/capita/year. The main factors affecting the level of food self-sufficiency in the farmer household level are: rice production, rice consumption, land tenure, and number of family members. Key recommendations from this study are; improvement scale of the land cultivation for rice farming and non-rice diversification consumption.

STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS

PubMed Central

Landsteiner, K.; Chase, M. W.

1939-01-01

Experiments are described on the latency period in sensitization to poison ivy and on the time necessary for the agent to remain in contact with the skin. The chief matter of investigation concerned the manner in which the whole skin becomes sensitive following treatment at a particular site, and especially whether this is effected by way of the epidermis. Two methods were used to interrupt the continuity of the skin, one by cutting through both skin and the underlying thin muscular layer, the other by removing a strip of skin so as to spare the skin muscle. These procedures led to different results when poison ivy extract was applied to the areas thus isolated. In the first case, sensitization was mostly prevented, whereas with the second method generalized hypersensitiveness occurred almost uniformly. An explanation is to be found in the severance of the lymph vessels lying on the surface of the muscular layer, pointing to the necessity of a free lymph passage. On the other hand the experiments prove that general sensitization is not dependent upon maintaining the integrity of the skin around a treated area. An inhibition of sensitization by incisions extending through the panniculus carnosus was seen to some extent in anaphylactic sensitization with protein antigens, namely when sufficiently small amounts were employed. PMID:19870876

Global sensitivity analysis of multiscale properties of porous materials

NASA Astrophysics Data System (ADS)

Um, Kimoon; Zhang, Xuan; Katsoulakis, Markos; Plechac, Petr; Tartakovsky, Daniel M.

2018-02-01

Ubiquitous uncertainty about pore geometry inevitably undermines the veracity of pore- and multi-scale simulations of transport phenomena in porous media. It raises two fundamental issues: sensitivity of effective material properties to pore-scale parameters and statistical parameterization of Darcy-scale models that accounts for pore-scale uncertainty. Homogenization-based maps of pore-scale parameters onto their Darcy-scale counterparts facilitate both sensitivity analysis (SA) and uncertainty quantification. We treat uncertain geometric characteristics of a hierarchical porous medium as random variables to conduct global SA and to derive probabilistic descriptors of effective diffusion coefficients and effective sorption rate. Our analysis is formulated in terms of solute transport diffusing through a fluid-filled pore space, while sorbing to the solid matrix. Yet it is sufficiently general to be applied to other multiscale porous media phenomena that are amenable to homogenization.

Analysis of the sensitivity of in vitro bioassays for androgenic, progestagenic, glucocorticoid, thyroid and estrogenic activity: Suitability for drinking and environmental waters.

PubMed

Leusch, Frederic D L; Neale, Peta A; Hebert, Armelle; Scheurer, Marco; Schriks, Merijn C M

2017-02-01

The presence of endocrine disrupting chemicals in the aquatic environment poses a risk for ecosystem health. Consequently there is a need for sensitive tools, such as in vitro bioassays, to monitor endocrine activity in environmental waters. The aim of the current study was to assess whether current in vitro bioassays are suitable to detect endocrine activity in a range of water types. The reviewed assays included androgenic (n=11), progestagenic (n=6), glucocorticoid (n=5), thyroid (n=5) and estrogenic (n=8) activity in both agonist and antagonist mode. Existing in vitro bioassay data were re-evaluated to determine assay sensitivity, with the calculated method detection limit compared with measured hormonal activity in treated wastewater, surface water and drinking water to quantify whether the studied assays were sufficiently sensitive for environmental samples. With typical sample enrichment, current in vitro bioassays are sufficiently sensitive to detect androgenic activity in treated wastewater and surface water, with anti-androgenic activity able to be detected in most environmental waters. Similarly, with sufficient enrichment, the studied mammalian assays are able to detect estrogenic activity even in drinking water samples. Fewer studies have focused on progestagenic and glucocorticoid activity, but some of the reviewed bioassays are suitable for detecting activity in treated wastewater and surface water. Even less is known about (anti)thyroid activity, but the available data suggests that the more sensitive reviewed bioassays are still unlikely to detect this type of activity in environmental waters. The findings of this review can help provide guidance on in vitro bioassay selection and required sample enrichment for optimised detection of endocrine activity in environmental waters. Copyright © 2016 Elsevier Ltd. All rights reserved.

A flexible tactile sensitive sheet using a hetero-core fiber optic sensor

NASA Astrophysics Data System (ADS)

Fujino, S.; Yamazaki, H.; Hosoki, A.; Watanabe, K.

2014-05-01

In this report, we have designed a tactile sensitive sheet based on a hetero-core fiber-optic sensor, which realize an areal sensing by using single sensor potion in one optical fiber line. Recently, flexible and wide-area tactile sensing technology is expected to applied to acquired biological information in living space and robot achieve long-term care services such as welfare and nursing-care and humanoid technology. A hetero-core fiber-optic sensor has several advantages such as thin and flexible transmission line, immunity to EMI. Additionally this sensor is sensitive to moderate bending actions with optical loss changes and is independent of temperature fluctuation. Thus, the hetero-core fiber-optic sensor can be suitable for areal tactile sensing. We measure pressure characteristic of the proposed sensitive sheet by changing the pressure position and pinching characteristic on the surface. The proposed tactile sensitive sheet shows monotonic responses on the whole sensitive sheet surface although different sensitivity by the position is observed at the sensitive sheet surface. Moreover, the tactile sensitive sheet could sufficiently detect the pinching motion. In addition, in order to realize the discrimination between pressure and pinch, we fabricated a doubled-over sensor using a set of tactile sensitive sheets, which has different kinds of silicon robbers as a sensitive sheet surface. In conclusion, the flexible material could be given to the tactile sensation which is attached under proposed sensitive sheet.

Forebrain-specific CRF overproduction during development is sufficient to induce enduring anxiety and startle abnormalities in adult mice.

PubMed

Toth, Mate; Gresack, Jodi E; Bangasser, Debra A; Plona, Zach; Valentino, Rita J; Flandreau, Elizabeth I; Mansuy, Isabelle M; Merlo-Pich, Emilio; Geyer, Mark A; Risbrough, Victoria B

2014-05-01

Corticotropin releasing factor (CRF) regulates physiological and behavioral responses to stress. Trauma in early life or adulthood is associated with increased CRF in the cerebrospinal fluid and heightened anxiety. Genetic variance in CRF receptors is linked to altered risk for stress disorders. Thus, both heritable differences and environmentally induced changes in CRF neurotransmission across the lifespan may modulate anxiety traits. To test the hypothesis that CRF hypersignaling is sufficient to modify anxiety-related phenotypes (avoidance, startle, and conditioned fear), we induced transient forebrain-specific overexpression of CRF (CRFOE) in mice (1) during development to model early-life stress, (2) in adulthood to model adult-onset stress, or (3) across the entire postnatal lifespan to model heritable increases in CRF signaling. The consequences of these manipulations on CRF peptide levels and behavioral responses were examined in adulthood. We found that transient CRFOE during development decreased startle habituation and prepulse inhibition, and increased avoidance (particularly in females) recapitulating the behavioral effects of lifetime CRFOE despite lower CRF peptide levels at testing. In contrast, CRFOE limited to adulthood reduced contextual fear learning in females and increased startle reactivity in males but did not change avoidance or startle plasticity. These findings suggest that forebrain CRFOE limited to development is sufficient to induce enduring alterations in startle plasticity and anxiety, while forebrain CRFOE during adulthood results in a different phenotype profile. These findings suggest that startle circuits are particularly sensitive to forebrain CRFOE, and that the impact of CRFOE may be dependent on the time of exposure.

Neuro-genetic system for optimization of GMI samples sensitivity.

PubMed

Pitta Botelho, A C O; Vellasco, M M B R; Hall Barbosa, C R; Costa Silva, E

2016-03-01

Magnetic sensors are largely used in several engineering areas. Among them, magnetic sensors based on the Giant Magnetoimpedance (GMI) effect are a new family of magnetic sensing devices that have a huge potential for applications involving measurements of ultra-weak magnetic fields. The sensitivity of magnetometers is directly associated with the sensitivity of their sensing elements. The GMI effect is characterized by a large variation of the impedance (magnitude and phase) of a ferromagnetic sample, when subjected to a magnetic field. Recent studies have shown that phase-based GMI magnetometers have the potential to increase the sensitivity by about 100 times. The sensitivity of GMI samples depends on several parameters, such as sample length, external magnetic field, DC level and frequency of the excitation current. However, this dependency is yet to be sufficiently well-modeled in quantitative terms. So, the search for the set of parameters that optimizes the samples sensitivity is usually empirical and very time consuming. This paper deals with this problem by proposing a new neuro-genetic system aimed at maximizing the impedance phase sensitivity of GMI samples. A Multi-Layer Perceptron (MLP) Neural Network is used to model the impedance phase and a Genetic Algorithm uses the information provided by the neural network to determine which set of parameters maximizes the impedance phase sensitivity. The results obtained with a data set composed of four different GMI sample lengths demonstrate that the neuro-genetic system is able to correctly and automatically determine the set of conditioning parameters responsible for maximizing their phase sensitivities. Copyright © 2015 Elsevier Ltd. All rights reserved.

A PDE Sensitivity Equation Method for Optimal Aerodynamic Design

NASA Technical Reports Server (NTRS)

Borggaard, Jeff; Burns, John

1996-01-01

The use of gradient based optimization algorithms in inverse design is well established as a practical approach to aerodynamic design. A typical procedure uses a simulation scheme to evaluate the objective function (from the approximate states) and its gradient, then passes this information to an optimization algorithm. Once the simulation scheme (CFD flow solver) has been selected and used to provide approximate function evaluations, there are several possible approaches to the problem of computing gradients. One popular method is to differentiate the simulation scheme and compute design sensitivities that are then used to obtain gradients. Although this black-box approach has many advantages in shape optimization problems, one must compute mesh sensitivities in order to compute the design sensitivity. In this paper, we present an alternative approach using the PDE sensitivity equation to develop algorithms for computing gradients. This approach has the advantage that mesh sensitivities need not be computed. Moreover, when it is possible to use the CFD scheme for both the forward problem and the sensitivity equation, then there are computational advantages. An apparent disadvantage of this approach is that it does not always produce consistent derivatives. However, for a proper combination of discretization schemes, one can show asymptotic consistency under mesh refinement, which is often sufficient to guarantee convergence of the optimal design algorithm. In particular, we show that when asymptotically consistent schemes are combined with a trust-region optimization algorithm, the resulting optimal design method converges. We denote this approach as the sensitivity equation method. The sensitivity equation method is presented, convergence results are given and the approach is illustrated on two optimal design problems involving shocks.

Leadership, the Logic of Sufficiency and the Sustainability of Education

ERIC Educational Resources Information Center

Bottery, Mike

2012-01-01

The notion of sufficiency has not yet entered mainstream educational thinking, and it still has to make its mark upon educational leadership. However, a number of related concepts--particularly those of sustainability and complexity theory--are beginning to be noticed. This article examines these two concepts and uses them to critique the…

Helping Low-Income Mothers with Criminal Records Achieve Self-Sufficiency.

ERIC Educational Resources Information Center

Brown, Rebecca

2000-01-01

This issue of WIN (Welfare Information Network) Issue Notes focuses on helping low-income mothers with criminal records achieve self-sufficiency. Section 1 offers background. Section 2 answers these policy questions: why states might want to focus on serving low-income mothers with criminal records; how states can encourage employers to hire…

Scrambled eggs: A highly sensitive molecular diagnostic workflow for Fasciola species specific detection from faecal samples.

PubMed

Calvani, Nichola Eliza Davies; Windsor, Peter Andrew; Bush, Russell David; Šlapeta, Jan

2017-09-01

Fasciolosis, due to Fasciola hepatica and Fasciola gigantica, is a re-emerging zoonotic parasitic disease of worldwide importance. Human and animal infections are commonly diagnosed by the traditional sedimentation and faecal egg-counting technique. However, this technique is time-consuming and prone to sensitivity errors when a large number of samples must be processed or if the operator lacks sufficient experience. Additionally, diagnosis can only be made once the 12-week pre-patent period has passed. Recently, a commercially available coprological antigen ELISA has enabled detection of F. hepatica prior to the completion of the pre-patent period, providing earlier diagnosis and increased throughput, although species differentiation is not possible in areas of parasite sympatry. Real-time PCR offers the combined benefits of highly sensitive species differentiation for medium to large sample sizes. However, no molecular diagnostic workflow currently exists for the identification of Fasciola spp. in faecal samples. A new molecular diagnostic workflow for the highly-sensitive detection and quantification of Fasciola spp. in faecal samples was developed. The technique involves sedimenting and pelleting the samples prior to DNA isolation in order to concentrate the eggs, followed by disruption by bead-beating in a benchtop homogeniser to ensure access to DNA. Although both the new molecular workflow and the traditional sedimentation technique were sensitive and specific, the new molecular workflow enabled faster sample throughput in medium to large epidemiological studies, and provided the additional benefit of speciation. Further, good correlation (R2 = 0.74-0.76) was observed between the real-time PCR values and the faecal egg count (FEC) using the new molecular workflow for all herds and sampling periods. Finally, no effect of storage in 70% ethanol was detected on sedimentation and DNA isolation outcomes; enabling transport of samples from endemic to non

Scrambled eggs: A highly sensitive molecular diagnostic workflow for Fasciola species specific detection from faecal samples

PubMed Central

Calvani, Nichola Eliza Davies; Windsor, Peter Andrew; Bush, Russell David

2017-01-01

Background Fasciolosis, due to Fasciola hepatica and Fasciola gigantica, is a re-emerging zoonotic parasitic disease of worldwide importance. Human and animal infections are commonly diagnosed by the traditional sedimentation and faecal egg-counting technique. However, this technique is time-consuming and prone to sensitivity errors when a large number of samples must be processed or if the operator lacks sufficient experience. Additionally, diagnosis can only be made once the 12-week pre-patent period has passed. Recently, a commercially available coprological antigen ELISA has enabled detection of F. hepatica prior to the completion of the pre-patent period, providing earlier diagnosis and increased throughput, although species differentiation is not possible in areas of parasite sympatry. Real-time PCR offers the combined benefits of highly sensitive species differentiation for medium to large sample sizes. However, no molecular diagnostic workflow currently exists for the identification of Fasciola spp. in faecal samples. Methodology/Principal findings A new molecular diagnostic workflow for the highly-sensitive detection and quantification of Fasciola spp. in faecal samples was developed. The technique involves sedimenting and pelleting the samples prior to DNA isolation in order to concentrate the eggs, followed by disruption by bead-beating in a benchtop homogeniser to ensure access to DNA. Although both the new molecular workflow and the traditional sedimentation technique were sensitive and specific, the new molecular workflow enabled faster sample throughput in medium to large epidemiological studies, and provided the additional benefit of speciation. Further, good correlation (R2 = 0.74–0.76) was observed between the real-time PCR values and the faecal egg count (FEC) using the new molecular workflow for all herds and sampling periods. Finally, no effect of storage in 70% ethanol was detected on sedimentation and DNA isolation outcomes; enabling

Resource Utilization and Site Selection for a Self-Sufficient Martian Outpost

NASA Technical Reports Server (NTRS)

Barker, Donald; Chamitoff, Gregory; James, George

1998-01-01

As a planet with striking similarities to Earth, Mars is an important focus for scientific research aimed at understanding the processes of planetary evolution and the formation of our solar system. Fortunately, Mars is also a planet with abundant natural resources, including assessible materials that can be used to support human life and to sustain a self-sufficient martian outpost. Resources required include water, breathable air, food, shelter, energy, and fuel. Through a mission design based on in situ resource development, we can establish a permanent outpost on Mars beginning with the first manned mission. This paper examines the potential for supporting the first manned mission with the objective of achieving self-sufficiency through well-understood resource development and a program of rigorous scientific research aimed at extending that capability. We examine the potential for initially extracting critical resources from the martian environment, and discuss the scientific investigations required to identify additional resources in the atmosphere, on the surface, and within the subsurface. We also discuss our current state of knowledge of Mars, technical considerations of resource utilization, and using unmanned missions' data for selecting an optimal site. The primary goal of achieving self-sufficiency on Mars would accelerate the development of human colonization beyond Earth, while providing a robust and permanent martian base from which humans can explore and conduct long-term research on planetary evolution, the solar system, and life itself.

Tensor sufficient dimension reduction

PubMed Central

Zhong, Wenxuan; Xing, Xin; Suslick, Kenneth

2015-01-01

Tensor is a multiway array. With the rapid development of science and technology in the past decades, large amount of tensor observations are routinely collected, processed, and stored in many scientific researches and commercial activities nowadays. The colorimetric sensor array (CSA) data is such an example. Driven by the need to address data analysis challenges that arise in CSA data, we propose a tensor dimension reduction model, a model assuming the nonlinear dependence between a response and a projection of all the tensor predictors. The tensor dimension reduction models are estimated in a sequential iterative fashion. The proposed method is applied to a CSA data collected for 150 pathogenic bacteria coming from 10 bacterial species and 14 bacteria from one control species. Empirical performance demonstrates that our proposed method can greatly improve the sensitivity and specificity of the CSA technique. PMID:26594304

A misfolded protein conformation is not a sufficient condition for in vivo glucosylation by the UDP-Glc:glycoprotein glucosyltransferase.

PubMed

Fernández, F; D'Alessio, C; Fanchiotti, S; Parodi, A J

1998-10-15

A key element in the quality control of glycoprotein folding is the UDP-Glc:glycoprotein glucosyltransferase (GT), which in cell-free assays exclusively glucosylates misfolded glycoproteins. In order to test if such a protein conformation is a sufficient condition for in vivo glucosylation of all N-linked oligosaccharides by GT, a Schizosaccharomyces pombe double mutant (gls2/alg6) was constructed. With this mutant, Man9GlcNAc2 is transferred to proteins and no removal of glucose units added by GT occurs as it lacks glucosidase II. The same proportion of glucosylated (Glc1Man9GlcNAc2) and unglucosylated (Man9GlcNAc2 and Man8GlcNAc2) endoplasmic reticulum (ER)-specific compounds was produced when cells were pre-incubated for 10, 20 or 30 min and further incubated with [14C]glucose for 10 min at 28 degrees C with or without 5 mM dithiothreitol (DTT), thus indicating not only that DTT did not affect protein glucosylation but also that no increased glucosylation of glycoproteins occurred in the presence of the drug. Monitoring Golgi-specific modifications of oligosaccharides after pulse-chase experiments performed in the presence or absence of 5 mM DTT showed that exit of the bulk of glycoproteins synthesized from the ER and thence their proper folding had been prevented by the drug. Cells pulse-chase labeled at 37 degrees C in the absence of DTT also yielded glucosylated and unglucosylated protein-linked oligosaccharides without Golgi-specific modifications. It was concluded that a misfolded protein conformation is not a sufficient condition for in vivo glucosylation of all N-linked oligosaccharides by GT.

Assessing sufficiency of thermal riverscapes for resilient salmon and steelhead populations

EPA Science Inventory

Resilient salmon populations require river networks that provide water temperature regimes sufficient to support a diversity of salmonid life histories across space and time. Efforts to protect, enhance and restore watershed thermal regimes for salmon may target specific location...

Human NKCC2 cation–Cl– co-transporter complements lack of Vhc1 transporter in yeast vacuolar membranes.

PubMed

Petrezselyova, Silvia; Dominguez, Angel; Herynkova, Pavla; Macias, Juan F; Sychrova, Hana

2013-10-01

Cation–chloride co-transporters serve to transport Cl– and alkali metal cations. Whereas a large family of these exists in higher eukaryotes, yeasts only possess one cation–chloride co-transporter, Vhc1, localized to the vacuolar membrane. In this study, the human cation–chloride co-transporter NKCC2 complemented the phenotype of VHC1 deletion in Saccharomyces cerevisiae and its activity controlled the growth of salt-sensitive yeast cells in the presence of high KCl, NaCl and LiCl. A S. cerevisiae mutant lacking plasma-membrane alkali–metal cation exporters Nha1 and Ena1-5 and the vacuolar cation–chloride co-transporter Vhc1 is highly sensitive to increased concentrations of alkali–metal cations, and it proved to be a suitable model for characterizing the substrate specificity and transport activity of human wild-type and mutated cation–chloride co-transporters. Copyright © 2013 John Wiley & Sons, Ltd.

Gravitropism: interaction of sensitivity modulation and effector redistribution

NASA Technical Reports Server (NTRS)

Evans, M. L.

1991-01-01

Our increasing capabilities for quantitative hormone analysis and automated high resolution growth studies have allowed a reassessment of the classical Cholodny-Went hypothesis of gravitropism. According to this hypothesis, gravity induces redistribution of auxin toward the lower side of the organ and this causes the growth asymmetry that leads to reorientation. Arguments against the Cholodny-Went hypothesis that were based primarily on concerns over the timing and magnitude of the development of hormone asymmetry are countered by recent evidence that such asymmetry develops early and is sufficiently large to account for curvature. Thus, it appears that the Cholodny-Went hypothesis is fundamentally valid. However, recent comparative studies of the kinetics of curvature and the timing of the development of hormone asymmetry indicate that this hypothesis alone cannot account for the intricacies of the gravitropic response. It appears that time-dependent gravity-induced changes in hormone sensitivity as well as changes in sensitivity of the gravity receptor play important roles in the response.

42 CFR 110.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Sufficient documentation for eligibility and benefits determinations. 110.72 Section 110.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Secretarial Determinations...

42 CFR 110.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Sufficient documentation for eligibility and benefits determinations. 110.72 Section 110.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Secretarial Determinations...

42 CFR 110.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Sufficient documentation for eligibility and benefits determinations. 110.72 Section 110.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Secretarial Determinations...

42 CFR 110.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Sufficient documentation for eligibility and benefits determinations. 110.72 Section 110.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Secretarial Determinations...

Differences in psychosocial responses to pain between sufficiently and insufficiently active adults with arthritis.

PubMed

Cary, Miranda A; Brittain, Danielle R; Gyurcsik, Nancy C

2017-07-01

Adults with arthritis struggle to meet the physical activity recommendation for disease self-management. Identifying psychosocial factors that differentiate adults who meet (sufficiently active) or do not meet (insufficiently active) the recommendation is needed. This study sought to examine differences in psychosocial responses to arthritis pain among adults who were sufficiently or insufficiently active. This prospective study included adults with medically diagnosed arthritis (N = 136, M age  = 49.75 ± 13.88 years) who completed two online surveys: (1) baseline: pain and psychosocial responses to pain and (2) two weeks later: physical activity. Psychosocial responses examined in this study were psychological flexibility in response to pain, pain anxiety and maladaptive responses to pain anxiety. A between-groups MANCOVA comparing sufficiently active (n = 87) to insufficiently active (n = 49) participants on psychosocial responses, after controlling for pain intensity, was significant (p = .005). Follow-up ANOVA's revealed that sufficiently active participants reported significantly higher psychological flexibility and used maladaptive responses less often compared to insufficiently active participants (p's < .05). These findings provide preliminary insight into the psychosocial profile of adults at risk for nonadherence due to their responses to arthritis pain.

Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics

PubMed Central

Shi, Tujin; Su, Dian; Liu, Tao; Tang, Keqi; Camp, David G.; Qian, Wei-Jun; Smith, Richard D.

2012-01-01

Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the low ng/mL to pg/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides including posttranslational modifications (PTMs), as well as advances in MS instrumentation which have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed. PMID:22577010

Development of an ultra-sensitive Simoa assay to enable GDF11 detection: a comparison across bioanalytical platforms.

PubMed

Myzithras, Maria; Li, Hua; Bigwarfe, Tammy; Waltz, Erica; Gupta, Priyanka; Low, Sarah; Hayes, David B; MacDonnell, Scott; Ahlberg, Jennifer; Franti, Michael; Roberts, Simon

2016-03-01

Four bioanalytical platforms were evaluated to optimize sensitivity and enable detection of recombinant human GDF11 in biological matrices; ELISA, Meso Scale Discovery, Gyrolab xP Workstation and Simoa HD-1. Results & methodology: After completion of custom assay development, the single-molecule ELISA (Simoa) achieved the greatest sensitivity with a lower limit of quantitation of 0.1 ng/ml, an improvement of 100-fold over the next sensitive platform (MSD). This improvement was essential to enable detection of GDF11 in biological samples, and without the technology the sensitivity achieved on the other platforms would not have been sufficient. Other factors such as ease of use, cost, assay time and automation capability can also be considered when developing custom immunoassays, based on the requirements of the bioanalyst.

Role of superoxide–nitric oxide interactions in the accelerated age-related loss of muscle mass in mice lacking Cu,Zn superoxide dismutase

PubMed Central

Sakellariou, Giorgos K; Pye, Deborah; Vasilaki, Aphrodite; Zibrik, Lea; Palomero, Jesus; Kabayo, Tabitha; McArdle, Francis; Van Remmen, Holly; Richardson, Arlan; Tidball, James G; McArdle, Anne; Jackson, Malcolm J

2011-01-01

Summary Mice lacking Cu,Zn superoxide dismutase (SOD1) show accelerated, age-related loss of muscle mass. Lack of SOD1 may lead to increased superoxide, reduced nitric oxide (NO), and increased peroxynitrite, each of which could initiate muscle fiber loss. Single muscle fibers from flexor digitorum brevis of wild-type (WT) and Sod1−/− mice were loaded with NO-sensitive (4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate, DAF-FM) and superoxide-sensitive (dihydroethidium, DHE) probes. Gastrocnemius muscles were analyzed for SOD enzymes, nitric oxide synthases (NOS), and 3-nitrotyrosine (3-NT) content. A lack of SOD1 did not increase superoxide availability at rest because no increase in ethidium or 2-hydroxyethidium (2-HE) formation from DHE was seen in fibers from Sod1−/− mice compared with those from WT mice. Fibers from Sod1−/− mice had decreased NO availability (decreased DAF-FM fluorescence), increased 3-NT in muscle proteins indicating increased peroxynitrite formation and increased content of peroxiredoxin V (a peroxynitrite reductase), compared with WT mice. Muscle fibers from Sod1−/− mice showed substantially reduced generation of superoxide in response to contractions compared with fibers from WT mice. Inhibition of NOS did not affect DHE oxidation in fibers from WT or Sod1−/− mice at rest or during contractions, but transgenic mice overexpressing nNOS showed increased DAF-FM fluorescence and reduced DHE oxidation in resting muscle fibers. It is concluded that formation of peroxynitrite in muscle fibers is a major effect of lack of SOD1 in Sod1−/− mice and may contribute to fiber loss in this model, and that NO regulates superoxide availability and peroxynitrite formation in muscle. PMID:21443684

A checklist to facilitate cultural awareness and sensitivity

PubMed Central

Seibert, P; Stridh-Igo, P; Zimmerman, C

2002-01-01

United States of America demographic profiles illustrate a nation rich in cultural and racial diversity. Approximately 29% of the population are minorities and demographic projections indicate an increase to 50% by the year 2050. This creates a highly mobile and constantly changing environment, revealing the need for new levels of cultural awareness and sensitivity. These issues are particularly critical in the medical community where medical professionals must understand the impact cultural differences and barriers can have on evaluation, treatment, and rehabilitation. During times of stress, such as when injury strikes, problems associated with lack of cultural sensitivity are intensified. Cultural diversity is of particular concern when standard measures for diagnosis and prognosis are derived from established norms for responding, because culture defines norms. This paper details a ten point checklist designed to facilitate cultural awareness and sensitivity in medical settings to ensure maximum successful recovery and outcomes for all patients. PMID:12042396

Mapping the architecture of the HIV-lTat circuit: A decision-making circuit that lacks bistability and exploits stochastic noise

PubMed Central

Razooky, Brandon S.; Weinberger, Leor S.

2014-01-01

Upon infection of a CD4+ T cell, HIV-l appears to ‘choose’ between two alternate fates: active replication or a long-lived dormant statetermed proviral latency. A transcriptional positive-feedback loop generated by the HIV-l Tat protein appears sufficient to mediate this decision. Here, we describea coupled wet-lab and computational approach that uses mathematical modeling and live-cell time-lapse microscopy to map the architecture of the HIV-l Tat transcriptional regulatorycircuit and generate predictive models of HIV-l latency. This approach provided the first characterization of a ‘decision-making’ circuit that lacks bistability andinstead exploits stochastic fluctuations in cellular molecules (i.e. noise) to generate a decision between an on or off transcriptional state. PMID:21167940

Rotation sensitivity analysis of a two-dimensional array of coupled resonators

NASA Astrophysics Data System (ADS)

Zamani Aghaie, Kiarash; Vigneron, Pierre-Baptiste; Digonnet, Michel J. F.

2015-03-01

In this paper, we study the rotation sensitivity of a gyroscope made of a two-dimensional array of coupled resonators consisting of N columns of one-dimensional coupled resonant optical waveguides (CROWs) connected by two bus waveguides, each CROW consisting of M identical ring resonators. We show that the maximum rotation sensitivity of this structure is a strong function of the parity of the number of rows M. For an odd number of rows, and when the number of columns is small, the maximum sensitivity is high, and it is slightly lower than the maximum sensitivity of a single-ring resonator with two input/output waveguides (the case M = N = 1), which is a resonant waveguide optical gyroscope (RWOG). For an even M and small N, the maximum sensitivity is much lower than that of the RWOG. Increasing the number columns N increases the sensitivity of an even-row 2D CROW sublinearly, as N0.39, up to 30 columns. In comparison, the maximum sensitivity of an RWOG of equal area increases faster, as √N. The sensitivity of the 2D CROW therefore always lags behind that of the RWOG. For a 2×2 CROW, if the spacing between the columns L is increased sufficiently the maximum sensitivity increases linearly with L due to the presence of a composite Mach- Zehnder interferometer in the structure. However, for equal footprints this sensitivity is also not larger than that of a single-ring resonator. Regardless of the number of rows and columns and the spacing, for the same footprint and propagation loss, a 2D CROW gyroscope is not more sensitive than an RWOG.

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

Sobol' sensitivity analysis for stressor impacts on honeybee ...

EPA Pesticide Factsheets

We employ Monte Carlo simulation and nonlinear sensitivity analysis techniques to describe the dynamics of a bee exposure model, VarroaPop. Daily simulations are performed of hive population trajectories, taking into account queen strength, foraging success, mite impacts, weather, colony resources, population structure, and other important variables. This allows us to test the effects of defined pesticide exposure scenarios versus controlled simulations that lack pesticide exposure. The daily resolution of the model also allows us to conditionally identify sensitivity metrics. We use the variancebased global decomposition sensitivity analysis method, Sobol’, to assess firstand secondorder parameter sensitivities within VarroaPop, allowing us to determine how variance in the output is attributed to each of the input variables across different exposure scenarios. Simulations with VarroaPop indicate queen strength, forager life span and pesticide toxicity parameters are consistent, critical inputs for colony dynamics. Further analysis also reveals that the relative importance of these parameters fluctuates throughout the simulation period according to the status of other inputs. Our preliminary results show that model variability is conditional and can be attributed to different parameters depending on different timescales. By using sensitivity analysis to assess model output and variability, calibrations of simulation models can be better informed to yield more

Insulin Sensitivity as a Key Mediator of Growth Hormone Actions on Longevity

PubMed Central

Panici, Jacob A.; Bonkowski, Michael S.; Hughes, Larry F.; Bartke, Andrzej

2009-01-01

Reduced insulin sensitivity and glucose intolerance have been long suspected of having important involvement in aging. Here we report that in studies of calorie restriction (CR) effects in mutant (Prop1df and growth hormone receptor knockout [GHRKO]) and normal mice, insulin sensitivity was strongly associated with longevity. Of particular interest was enhancement of the already increased insulin sensitivity in CR df/df mice in which longevity was also further extended and the lack of changes in insulin sensitivity in calorically restricted GHRKO mice in which there was no further increase in average life span. We suggest that enhanced insulin sensitivity, in conjunction with reduced insulin levels, may represent an important (although almost certainly not exclusive) mechanism of increased longevity in hypopituitary, growth hormone (GH)-resistant, and calorie-restricted animals. We also report that the effects of GH treatment on insulin sensitivity may be limited to the period of GH administration. PMID:19304940

Cyclin D2 is sufficient to drive β cell self-renewal and regeneration.

PubMed

Tschen, Shuen-Ing; Zeng, Chun; Field, Loren; Dhawan, Sangeeta; Bhushan, Anil; Georgia, Senta

2017-01-01

Diabetes results from an inadequate mass of functional β cells, due to either β cell loss caused by autoimmune destruction (type I diabetes) or β cell failure in response to insulin resistance (type II diabetes). Elucidating the mechanisms that regulate β cell mass may be key to developing new techniques that foster β cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal β cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive β cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in β cells, we show that cyclin D2 overexpression increases β cell self-renewal post-weaning and results in increased β cell mass. β cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. β cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive β cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in β cells of cyclin D2 -/- mice. Transgenic overexpression of cyclin D2 in cyclin D2 - / - β cells was sufficient to restore β cell mass, maintain normoglycaemia, and improve regenerative capacity when compared with cyclin D2 -/- littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate β cell self-renewal and that manipulation of its expression could be used to enhance β cell regeneration.

Photosynthetic Electron Transport Chain of Chlamydomonas reinhardi VI. Electron Transport in Mutant Strains Lacking Either Cytochrome 553 or Plastocyanin 1

PubMed Central

Gorman, Donald S.; Levine, R. P.

1966-01-01

A mutant strain of Chlamydomonas reinhardi, ac-206, lacks cytochrome 553, at least in an active and detectable form. Chloroplast fragments of this mutant strain are inactive in the photoreduction of NADP when the source of electrons is water, but they are active when the electron source is 2,6-dichlorophenolindophenol and ascorbate. The addition of either cytochrome 553 or plastocyanin, obtained from the wild-type strain, has no effect upon the photosynthetic activities of the mutant strain. Cells of the mutant strain lack both the soluble and insoluble forms of cytochrome 553, but they possess the mitochondrial type cytochrome c. Thus, the loss of cytochrome 553 appears to be specific. Another mutant strain, ac-208, lacks plastocyanin, or possesses it in an inactive and undetectable form. Chloroplast fragments of ac-208 are inactive in the photoreduction of NADP with either water or 2,6-dichlorophenolindophenol and ascorbate as electron donors. However, these reactions are restored upon the addition of plastocyanin. The addition of cytochrome 553 has no effect. The measurement of light-induced absorbance changes with ac-208 reveal that, in the absence of plastocyanin, light fails to sensitize the oxidation of cytochrome 553, but it will sensitize its reduction. However, the addition of plastocyanin restores the light-induced cytochrome oxidation. A third mutant strain, ac-208 (sup.) carries a suppressor mutation that partially restores the wild phenotype. This mutant strain appears to possess a plastocyanin that is less stable than that of the wild-type strain. The observations with the mutant strains are discussed in terms of the sequence of electron transport System II → cytochrome 553 → plastocyanin → System I. PMID:16656453

Impact of Market Behavior, Fleet Composition, and Ancillary Services on Revenue Sufficiency

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

Frew, Bethany

This presentation provides an overview of new and ongoing NREL research that aims to improve our understanding of reliability and revenue sufficiency challenges through modeling tools within a markets framework.

CaFe2O4 as a self-sufficient solar energy converter

NASA Astrophysics Data System (ADS)

Tablero, C.

2017-10-01

An ideal solar energy to electricity or fuel converter should work without the use of any external bias potential. An analysis of self-sufficiency when CaFe2O4 is used to absorb the sunlight is carried out based on the CaFe2O4 absorption coefficient. We started to obtain this coefficient theoretically within the experimental bandgap range in order to fix the interval of possible values of photocurrents, maximum absorption efficiencies, and photovoltages and thus that of self-sufficiency considering only the radiative processes. Also for single-gap CaFe2O4, we evaluate an alternative for increasing the photocurrent and maximum absorption efficiency based on inserting an intermediate band using high doping or alloying.

Characterizing performance of ultra-sensitive accelerometers

NASA Technical Reports Server (NTRS)

Sebesta, Henry

1990-01-01

An overview is given of methodology and test results pertaining to the characterization of ultra sensitive accelerometers. Two issues are of primary concern. The terminology ultra sensitive accelerometer is used to imply instruments whose noise floors and resolution are at the state of the art. Hence, the typical approach of verifying an instrument's performance by measuring it with a yet higher quality instrument (or standard) is not practical. Secondly, it is difficult to find or create an environment with sufficiently low background acceleration. The typical laboratory acceleration levels will be at several orders of magnitude above the noise floor of the most sensitive accelerometers. Furthermore, this background must be treated as unknown since the best instrument available is the one to be tested. A test methodology was developed in which two or more like instruments are subjected to the same but unknown background acceleration. Appropriately selected spectral analysis techniques were used to separate the sensors' output spectra into coherent components and incoherent components. The coherent part corresponds to the background acceleration being measured by the sensors being tested. The incoherent part is attributed to sensor noise and data acquisition and processing noise. The method works well for estimating noise floors that are 40 to 50 dB below the motion applied to the test accelerometers. The accelerometers being tested are intended for use as feedback sensors in a system to actively stabilize an inertial guidance component test platform.

Featured Article: Dexamethasone and rosiglitazone are sufficient and necessary for producing functional adipocytes from mesenchymal stem cells

PubMed Central

Ezquer, Fernando; Espinosa, Maximiliano; Arango-Rodriguez, Martha; Puebla, Carlos; Sobrevia, Luis; Conget, Paulette

2015-01-01

The final product of adipogenesis is a functional adipocyte. This mature cell acquires the necessary machinery for lipid metabolism, loses its proliferation potential, increases its insulin sensitivity, and secretes adipokines. Multipotent mesechymal stromal cells have been recognized as a source of adipocytes both in vivo and in vitro. The in vitro adipogenic differentiation of human MSC (hMSC) has been induced up to now by using a complex stimulus which includes dexamethasone, 3-isobutyl-1-methylxanthine, indomethacin, and insulin (a classical cocktail) and evaluated according to morphological changes. The present work was aimed at demonstrating that the simultaneous activation of dexamethasone’s canonical signaling pathways, through the glucocorticoid receptor and CCAAT-enhancer-binding proteins (C/EBPs) and rosiglitazone through peroxisome proliferator-activated receptor gamma (PPAR-gamma) is sufficient yet necessary for inducing hMSC adipogenic differentiation. It was also ascertained that hMSC exposed just to dexamethasone and rosiglitazone (D&R) differentiated into cells which accumulated neutral lipid droplets, expressed C/EBP-alpha, PPAR-gamma, aP2, lipoprotein lipase, acyl-CoA synthetase, phosphoenolpyruvate carboxykinase, adiponectin, and leptin genes but did not proliferate. Glucose uptake was dose dependent on insulin stimulus and high levels of adipokines were secreted (i.e. displaying not only the morphology but also expressing mature adipocytes’ specific genes and functional characteristics). This work has demonstrated that (i) the activating C/EBPs and PPAR-gamma signaling pathways were sufficient to induce adipogenic differentiation from hMSC, (ii) D&R producing functional adipocytes from hMSC, (iii) D&R induce adipogenic differentiation from mammalian MSC (including those which are refractory to classical adipogenic differentiation stimuli). D&R would thus seem to be a useful tool for MSC characterization, studying adipogenesis pathways and

Contextual sensitivity in scientific reproducibility

PubMed Central

Van Bavel, Jay J.; Mende-Siedlecki, Peter; Brady, William J.; Reinero, Diego A.

2016-01-01

In recent years, scientists have paid increasing attention to reproducibility. For example, the Reproducibility Project, a large-scale replication attempt of 100 studies published in top psychology journals found that only 39% could be unambiguously reproduced. There is a growing consensus among scientists that the lack of reproducibility in psychology and other fields stems from various methodological factors, including low statistical power, researcher’s degrees of freedom, and an emphasis on publishing surprising positive results. However, there is a contentious debate about the extent to which failures to reproduce certain results might also reflect contextual differences (often termed “hidden moderators”) between the original research and the replication attempt. Although psychologists have found extensive evidence that contextual factors alter behavior, some have argued that context is unlikely to influence the results of direct replications precisely because these studies use the same methods as those used in the original research. To help resolve this debate, we recoded the 100 original studies from the Reproducibility Project on the extent to which the research topic of each study was contextually sensitive. Results suggested that the contextual sensitivity of the research topic was associated with replication success, even after statistically adjusting for several methodological characteristics (e.g., statistical power, effect size). The association between contextual sensitivity and replication success did not differ across psychological subdisciplines. These results suggest that researchers, replicators, and consumers should be mindful of contextual factors that might influence a psychological process. We offer several guidelines for dealing with contextual sensitivity in reproducibility. PMID:27217556

Contextual sensitivity in scientific reproducibility.

PubMed

Van Bavel, Jay J; Mende-Siedlecki, Peter; Brady, William J; Reinero, Diego A

2016-06-07

In recent years, scientists have paid increasing attention to reproducibility. For example, the Reproducibility Project, a large-scale replication attempt of 100 studies published in top psychology journals found that only 39% could be unambiguously reproduced. There is a growing consensus among scientists that the lack of reproducibility in psychology and other fields stems from various methodological factors, including low statistical power, researcher's degrees of freedom, and an emphasis on publishing surprising positive results. However, there is a contentious debate about the extent to which failures to reproduce certain results might also reflect contextual differences (often termed "hidden moderators") between the original research and the replication attempt. Although psychologists have found extensive evidence that contextual factors alter behavior, some have argued that context is unlikely to influence the results of direct replications precisely because these studies use the same methods as those used in the original research. To help resolve this debate, we recoded the 100 original studies from the Reproducibility Project on the extent to which the research topic of each study was contextually sensitive. Results suggested that the contextual sensitivity of the research topic was associated with replication success, even after statistically adjusting for several methodological characteristics (e.g., statistical power, effect size). The association between contextual sensitivity and replication success did not differ across psychological subdisciplines. These results suggest that researchers, replicators, and consumers should be mindful of contextual factors that might influence a psychological process. We offer several guidelines for dealing with contextual sensitivity in reproducibility.

Thermophysical property sensitivity effects in steel solidification

NASA Technical Reports Server (NTRS)

Overfelt, Tony

1993-01-01

The simulation of advanced solidification processes via digital computer techniques has gained widespread acceptance during the last decade or so. Models today can predict transient temperature fields, fluid flow fields, important microstructural parameters, and potential defects in castings. However, the lack of accurate thermophysical property data on important industrial alloys threatens to limit the ability of manufacturers to fully capitalize on the technology's benefits. A study of the sensitivity of one such numerical model of a steel plate casting to imposed variations in the data utilized for the thermal conductivity, specific heat, density, and heat of fusion is described. The sensitivity of the data's variability is characterized by its effects on the net solidification time of various points along the centerline of the plate casting. Recommendations for property measurements are given and the implications of data uncertainty for modelers are discussed.

29 CFR 18.602 - Lack of personal knowledge.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Lack of personal knowledge. 18.602 Section 18.602 Labor... OFFICE OF ADMINISTRATIVE LAW JUDGES Rules of Evidence Witnesses § 18.602 Lack of personal knowledge. A... witness has personal knowledge of the matter. Evidence to prove personal knowledge may, but need not...

Programs To Create Economic Self-Sufficiency for Women in Public Housing.

ERIC Educational Resources Information Center

Smith, Cynthia; DeTardo-Bora, Kimberly; Durbin, Latrisha

The Wheeling Housing Authority in Wheeling, West Virginia, conducted two residential programs to help women living in public housing develop economic self-sufficiency. The Learning Independence from Employment (LIFE) program was an intensive 3-week program designed to accomplish the following objectives: improve participants' communication skills…

Global effect of the lack of inorganic polyphosphate in the extremophilic archaeon Sulfolobus solfataricus: A proteomic approach.

PubMed

Soto, Daniela F; Recalde, Alejandra; Orell, Alvaro; Albers, Sonja-Verena; Paradela, Alberto; Navarro, Claudio A; Jerez, Carlos A

2018-03-01

Inorganic polyphosphates (polyP) are present in all living cells and several important functions have been described for them. They are involved in the response to stress conditions, such as nutrient depletion, oxidative stress and toxic metals amongst others. A recombinant strain of Sulfolobus solfataricus unable to accumulate polyP was designed by the overexpression of its endogenous ppx gene. The overall impact of the lack of polyP on this S. solfataricus polyP (-) strain was analyzed by using quantitative proteomics (isotope-coded protein label, ICPL). Stress-related proteins, such as peroxiredoxins and heat shock proteins, proteins involved in metabolism and several others were produced at higher levels in the ppx expression strain. The polyP deficient strain showed an increased copper sensitivity and an earlier transcriptional up-regulation of copA gene coding for the P-type copper-exporting ATPase. This implies a complementary function of both copper resistance systems. These results strongly suggests that the lack of polyP makes this hyperthermophilic archaeon more sensitive to toxic conditions, such as an exposure to metals or other harmful stimuli, emphasizing the importance of this inorganic phosphate polymers in the adaptations to live in the environmental conditions in which thermoacidophilic archaea thrive. Inorganic polyphosphate (polyP) are ubiquitous molecules with many functions in living organisms. Few studies related to these polymers have been made in archaea. The construction of a polyP deficient recombinant strain of Sulfolobus solfataricus allowed the study of the global changes in the proteome of this thermoacidophilic archaeon in the absence of polyP compared with the wild type strain. The results obtained using quantitative proteomics suggest an important participation of polyP in the oxidative stress response of the cells and as having a possible metabolic role in the cell, as previously described in bacteria. The polyP deficient strain

Quantum Markov chains, sufficiency of quantum channels, and Rényi information measures

NASA Astrophysics Data System (ADS)

Datta, Nilanjana; Wilde, Mark M.

2015-12-01

A short quantum Markov chain is a tripartite state {ρ }{ABC} such that system A can be recovered perfectly by acting on system C of the reduced state {ρ }{BC}. Such states have conditional mutual information I(A;B| C) equal to zero and are the only states with this property. A quantum channel {N} is sufficient for two states ρ and σ if there exists a recovery channel using which one can perfectly recover ρ from {N}(ρ ) and σ from {N}(σ ). The relative entropy difference D(ρ \\parallel σ )-D({N}(ρ )\\parallel {N}(σ )) is equal to zero if and only if {N} is sufficient for ρ and σ. In this paper, we show that these properties extend to Rényi generalizations of these information measures which were proposed in (Berta et al 2015 J. Math. Phys. 56 022205; Seshadreesan et al 2015 J. Phys. A: Math. Theor. 48 395303), thus providing an alternate characterization of short quantum Markov chains and sufficient quantum channels. These results give further support to these quantities as being legitimate Rényi generalizations of the conditional mutual information and the relative entropy difference. Along the way, we solve some open questions of Ruskai and Zhang, regarding the trace of particular matrices that arise in the study of monotonicity of relative entropy under quantum operations and strong subadditivity of the von Neumann entropy.

Sufficiency of Mesolimbic Dopamine Neuron Stimulation for the Progression to Addiction.

PubMed

Pascoli, Vincent; Terrier, Jean; Hiver, Agnès; Lüscher, Christian

2015-12-02

The factors causing the transition from recreational drug consumption to addiction remain largely unknown. It has not been tested whether dopamine (DA) is sufficient to trigger this process. Here we use optogenetic self-stimulation of DA neurons of the ventral tegmental area (VTA) to selectively mimic the defining commonality of addictive drugs. All mice readily acquired self-stimulation. After weeks of abstinence, cue-induced relapse was observed in parallel with a potentiation of excitatory afferents onto D1 receptor-expressing neurons of the nucleus accumbens (NAc). When the mice had to endure a mild electric foot shock to obtain a stimulation, some stopped while others persevered. The resistance to punishment was associated with enhanced neural activity in the orbitofrontal cortex (OFC) while chemogenetic inhibition of the OFC reduced compulsivity. Together, these results show that stimulating VTA DA neurons induces behavioral and cellular hallmarks of addiction, indicating sufficiency for the induction and progression of the disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Soil organic matter mineralization of permafrost peat lands and sensitivity to temperature and lack of oxygen

NASA Astrophysics Data System (ADS)

Lamprecht, Richard E.; Diáková, Kateřina; Voigt, Carolina; Šantrůčková, Hana; Martikainen, Pertti; Biasi, Christina

2017-04-01

Globally, a significant pool of soil organic carbon (SOC) (Tarnocai et al. 2009) is stored in arctic peatlands where extensive permafrost prevents the decomposition of old soil organic matter (SOM). Vulnerability of ancient organic depositions in changing environment becomes a considerable issue in future climate models. Palsa mires, a typical cryogenic peatland type in subarctic tundra, are not only an important SOC pool but also have been reported as a source of nitrous oxide (N2O) (Marushchak et al. 2011). Microbial SOM mineralization and its sensitivity to changing environmental conditions are crucial to understand future C losses and greenhouse gas (GHG) fluxes in this abundant landform of subarctic region. The purpose of this experiment was to determine potential SOM mineralization in different layers of deep soil cores from an Arctic peatland. First, we aimed to define a response of C losses and GHG exchange rates to temperature and aerobic/anaerobic conditions in different peat layers down to the permafrost and beyond. Secondly, we sought for relations among SOM mineralization, nutrient availability and parameters of indigenous microbial community. Finally, we attempted to link the potential SOM mineralization of the different peat layers with surface GHG fluxes from a proceeding study conducted with the same, intact soil cores. Five deep peat soil cores were separated into five layers (0 20, 20 40, 40 60 cm, permafrost interface and permafrost layer). Homogenized peat was incubated in a factorial set-up of three temperatures (4, 10, and 16 °C) under aerobic and anaerobic conditions. At the beginning and the end of the total 5.5-months incubation period, we determined C and N availability, microbial biomass and potential activities of extracellular enzymes. Heterotrophic respiration (CO2), methane (CH4) and nitrous oxide (N2O) emissions were monitored weekly at the initial phase and biweekly later during the incubation. First results show that C-loss from

Post-Disaster Food and Nutrition from Urban Agriculture: A Self-Sufficiency Analysis of Nerima Ward, Tokyo.

PubMed

Sioen, Giles Bruno; Sekiyama, Makiko; Terada, Toru; Yokohari, Makoto

2017-07-10

Background : Post-earthquake studies from around the world have reported that survivors relying on emergency food for prolonged periods of time experienced several dietary related health problems. The present study aimed to quantify the potential nutrient production of urban agricultural vegetables and the resulting nutritional self-sufficiency throughout the year for mitigating post-disaster situations. Methods : We estimated the vegetable production of urban agriculture throughout the year. Two methods were developed to capture the production from professional and hobby farms: Method I utilized secondary governmental data on agricultural production from professional farms, and Method II was based on a supplementary spatial analysis to estimate the production from hobby farms. Next, the weight of produced vegetables [t] was converted into nutrients [kg]. Furthermore, the self-sufficiency by nutrient and time of year was estimated by incorporating the reference consumption of vegetables [kg], recommended dietary allowance of nutrients per capita [mg], and population statistics. The research was conducted in Nerima, the second most populous ward of Tokyo's 23 special wards. Self-sufficiency rates were calculated with the registered residents. Results : The estimated total vegetable production of 5660 tons was equivalent to a weight-based self-sufficiency rate of 6.18%. The average nutritional self-sufficiencies of Methods I and II were 2.48% and 0.38%, respectively, resulting in an aggregated average of 2.86%. Fluctuations throughout the year were observed according to the harvest seasons of the available crops. Vitamin K (6.15%) had the highest self-sufficiency of selected nutrients, while calcium had the lowest (0.96%). Conclusions : This study suggests that depending on the time of year, urban agriculture has the potential to contribute nutrients to diets during post-disaster situations as disaster preparedness food. Emergency responses should be targeted

Post-Disaster Food and Nutrition from Urban Agriculture: A Self-Sufficiency Analysis of Nerima Ward, Tokyo

PubMed Central

Sekiyama, Makiko; Terada, Toru; Yokohari, Makoto

2017-01-01

Background: Post-earthquake studies from around the world have reported that survivors relying on emergency food for prolonged periods of time experienced several dietary related health problems. The present study aimed to quantify the potential nutrient production of urban agricultural vegetables and the resulting nutritional self-sufficiency throughout the year for mitigating post-disaster situations. Methods: We estimated the vegetable production of urban agriculture throughout the year. Two methods were developed to capture the production from professional and hobby farms: Method I utilized secondary governmental data on agricultural production from professional farms, and Method II was based on a supplementary spatial analysis to estimate the production from hobby farms. Next, the weight of produced vegetables [t] was converted into nutrients [kg]. Furthermore, the self-sufficiency by nutrient and time of year was estimated by incorporating the reference consumption of vegetables [kg], recommended dietary allowance of nutrients per capita [mg], and population statistics. The research was conducted in Nerima, the second most populous ward of Tokyo’s 23 special wards. Self-sufficiency rates were calculated with the registered residents. Results: The estimated total vegetable production of 5660 tons was equivalent to a weight-based self-sufficiency rate of 6.18%. The average nutritional self-sufficiencies of Methods I and II were 2.48% and 0.38%, respectively, resulting in an aggregated average of 2.86%. Fluctuations throughout the year were observed according to the harvest seasons of the available crops. Vitamin K (6.15%) had the highest self-sufficiency of selected nutrients, while calcium had the lowest (0.96%). Conclusions: This study suggests that depending on the time of year, urban agriculture has the potential to contribute nutrients to diets during post-disaster situations as disaster preparedness food. Emergency responses should be targeted according

Cyclin D2 is sufficient to drive β cell self-renewal and regeneration

PubMed Central

2017-01-01

ABSTRACT Diabetes results from an inadequate mass of functional β cells, due to either β cell loss caused by autoimmune destruction (type I diabetes) or β cell failure in response to insulin resistance (type II diabetes). Elucidating the mechanisms that regulate β cell mass may be key to developing new techniques that foster β cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal β cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive β cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in β cells, we show that cyclin D2 overexpression increases β cell self-renewal post-weaning and results in increased β cell mass. β cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. β cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive β cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in β cells of cyclin D2−/− mice. Transgenic overexpression of cyclin D2 in cyclin D2−/− β cells was sufficient to restore β cell mass, maintain normoglycaemia, and improve regenerative capacity when compared with cyclin D2−/− littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate β cell self-renewal and that manipulation of its expression could be used to enhance β cell regeneration. PMID:28763258

MSEBAG: a dynamic classifier ensemble generation based on `minimum-sufficient ensemble' and bagging

NASA Astrophysics Data System (ADS)

Chen, Lei; Kamel, Mohamed S.

2016-01-01

In this paper, we propose a dynamic classifier system, MSEBAG, which is characterised by searching for the 'minimum-sufficient ensemble' and bagging at the ensemble level. It adopts an 'over-generation and selection' strategy and aims to achieve a good bias-variance trade-off. In the training phase, MSEBAG first searches for the 'minimum-sufficient ensemble', which maximises the in-sample fitness with the minimal number of base classifiers. Then, starting from the 'minimum-sufficient ensemble', a backward stepwise algorithm is employed to generate a collection of ensembles. The objective is to create a collection of ensembles with a descending fitness on the data, as well as a descending complexity in the structure. MSEBAG dynamically selects the ensembles from the collection for the decision aggregation. The extended adaptive aggregation (EAA) approach, a bagging-style algorithm performed at the ensemble level, is employed for this task. EAA searches for the competent ensembles using a score function, which takes into consideration both the in-sample fitness and the confidence of the statistical inference, and averages the decisions of the selected ensembles to label the test pattern. The experimental results show that the proposed MSEBAG outperforms the benchmarks on average.

Anaplerotic input is sufficient to induce time-dependent potentiation of insulin release in rat pancreatic islets.

PubMed

Gunawardana, Subhadra C; Liu, Yi-Jia; Macdonald, Michael J; Straub, Susanne G; Sharp, Geoffrey W G

2004-11-01

Nutrients that induce biphasic insulin release, such as glucose and leucine, provide acetyl-CoA and anaplerotic input in the beta-cell. The first phase of release requires increased ATP production leading to increased intracellular Ca(2+) concentration ([Ca(2+)](i)). The second phase requires increased [Ca(2+)](i) and anaplerosis. There is strong evidence to indicate that the second phase is due to augmentation of Ca(2+)-stimulated release via the K(ATP) channel-independent pathway. To test whether the phenomenon of time-dependent potentiation (TDP) has similar properties to the ATP-sensitive K(+) channel-independent pathway, we monitored the ability of different agents that provide acetyl-CoA and anaplerotic input or both of these inputs to induce TDP. The results show that anaplerotic input is sufficient to induce TDP. Interestingly, among the agents tested, the nonsecretagogue glutamine, the nonhydrolyzable analog of leucine aminobicyclo[2.2.1]heptane-2-carboxylic acid, and succinic acid methyl ester all induced TDP, and all significantly increased alpha-ketoglutarate levels in the islets. In conclusion, anaplerosis that enhances the supply and utilization of alpha-ketoglutarate in the tricarboxylic acid cycle appears to play an essential role in the generation of TDP.

Call It a Monster for Lack of Anything Else

PubMed Central

Roe, David; Hasson-Ohayon, Ilanit; Kravetz, Shlomo; Yanos, Phil T.; Lysaker, Paul H.

2011-01-01

Individuals diagnosed with schizophrenia often appear to be unaware of having an illness or actively reject their diagnostic label. It is unclear, however, how this lack of awareness relates to important outcomes. Broadening the definition of awareness to include “narrative insight” may clarify this issue. The objective of this study was to identify profiles of narrative insight and test how these relate to standardized measure of insight. Sixty-five individuals with schizophrenia spectrum disorders participated in an assessment that included the Scale of Unawareness of Mental Disorder (SUMD) and an in-depth semi-structured interview. Qualitative analysis revealed 5 central themes related to insight on the basis of which each interview was then rated. Cluster analysis of these ratings resulted in 4 profiles of narrative insight: (1) accepts illness/rejects label, (2) rejects illness/searches for a name (3) passive insight of illness and label, and (4) integrative insight. The SUMD differentiated between individuals assigned to profile 2 who showed low insight to their illness and those assigned to the other profiles of narrative insight, but could not differentiae between them. Results support the claim that illness narratives are multifaceted and that traditional measures of insight may not be sensitive to different ways in which people understand their illness. PMID:19077852

Lack of relation between drug-seeking behavior in an addiction model and the expression of behavioral sensitization in response to ethanol challenge in mice.

PubMed

Ribeiro, A F; Pigatto, G; Goeldner, F O; Lopes, J F; de Lacerda, R B

2008-01-01

Drug-induced sensitization has been associated with enhanced self-administration and may contribute to addiction. The possible association between sensitization and voluntary ethanol consumption using an addiction model was investigated. Mice (n = 60) were individually housed with ad libitum access to food and had free choice between ethanol (5% and 10%) and water in a four-phase paradigm: free choice (12 weeks), withdrawal (2 weeks), re-exposure (2 weeks), and quinine-adulteration (2 weeks). Control mice (n = 10) had access to water. Mice were characterized as addicted (n = 10, ethanol preference without reducing intake with adulterated ethanol), heavy (n = 22, ethanol preference but reduced intake with adulterated ethanol), and light (n = 21, water preference). Oral ethanol then was withdrawn, and 24 h later mice received a 2 g/kg ethanol (i.p.) challenge dose or saline, and ambulation was evaluated 10 min later. Half of the classified mice received daily 2 g/kg ethanol injections for 14 days, and ambulation was assessed 10 min after the last dose. Acute ethanol increased ambulation in all groups compared to the control group, and chronic ethanol induced sensitization, showing no difference among ethanol-treated mice. The data suggest that independent neural mechanisms are responsible for the development of addiction and sensitization.

Cellular requirements for cutaneous sensitivity elicitation.

PubMed

Aoki, I

1985-01-01

The role of glass-adherent cells in cutaneous sensitivity (CS) elicitation has been analyzed in this study. CS responses have been revealed to be mediated by at least two distinct subsets of genetically restricted T cells: I-restricted 'DTH-like' T cells and K/D-restricted 'CTL-like' T cells. Both T-cell responses require I-A-positive glass-adherent cell populations, which lack T-cell markers, to manifest their activities. The role of the adherent cells is different in the 'DTH-like' responses and the 'CTL-like' responses. The disparities between the present results and previous contentions are discussed in this paper.

RNA from Trained Aplysia Can Induce an Epigenetic Engram for Long-Term Sensitization in Untrained Aplysia.

PubMed

Bédécarrats, Alexis; Chen, Shanping; Pearce, Kaycey; Cai, Diancai; Glanzman, David L

2018-01-01

The precise nature of the engram, the physical substrate of memory, remains uncertain. Here, it is reported that RNA extracted from the central nervous system of Aplysia given long-term sensitization (LTS) training induced sensitization when injected into untrained animals; furthermore, the RNA-induced sensitization, like training-induced sensitization, required DNA methylation. In cellular experiments, treatment with RNA extracted from trained animals was found to increase excitability in sensory neurons, but not in motor neurons, dissociated from naïve animals. Thus, the behavioral, and a subset of the cellular, modifications characteristic of a form of nonassociative long-term memory (LTM) in Aplysia can be transferred by RNA. These results indicate that RNA is sufficient to generate an engram for LTS in Aplysia and are consistent with the hypothesis that RNA-induced epigenetic changes underlie memory storage in Aplysia .

RNA from Trained Aplysia Can Induce an Epigenetic Engram for Long-Term Sensitization in Untrained Aplysia

PubMed Central

Chen, Shanping; Pearce, Kaycey; Cai, Diancai

2018-01-01

The precise nature of the engram, the physical substrate of memory, remains uncertain. Here, it is reported that RNA extracted from the central nervous system of Aplysia given long-term sensitization (LTS) training induced sensitization when injected into untrained animals; furthermore, the RNA-induced sensitization, like training-induced sensitization, required DNA methylation. In cellular experiments, treatment with RNA extracted from trained animals was found to increase excitability in sensory neurons, but not in motor neurons, dissociated from naïve animals. Thus, the behavioral, and a subset of the cellular, modifications characteristic of a form of nonassociative long-term memory (LTM) in Aplysia can be transferred by RNA. These results indicate that RNA is sufficient to generate an engram for LTS in Aplysia and are consistent with the hypothesis that RNA-induced epigenetic changes underlie memory storage in Aplysia. PMID:29789810

Demonstration of a Sensitive Method to Measure Nuclear-Spin-Dependent Parity Violation

NASA Astrophysics Data System (ADS)

Altuntaş, Emine; Ammon, Jeffrey; Cahn, Sidney B.; DeMille, David

2018-04-01

Nuclear-spin-dependent parity violation (NSD-PV) effects in atoms and molecules arise from Z0 boson exchange between electrons and the nucleus, and from the magnetic interaction between electrons and the parity-violating nuclear anapole moment. We demonstrate measurements of NSD-PV that use an enhancement of the effect in diatomic molecules, here using the test system 138Ba 19. Our sensitivity surpasses that of any previous atomic parity violation measurement. We show that systematic errors can be suppressed to at least the level of the present statistical sensitivity. We measure the matrix element W of the NSD-PV interaction with total uncertainty δ W /(2 π )<0.7 Hz , for each of two configurations where W must have different signs. This sensitivity would be sufficient to measure NSD-PV effects of the size anticipated across a wide range of nuclei including 137Ba in 137BaF, where |W |/(2 π )≈5 Hz is expected.

Gravitropism: Interaction of Sensitivity Modulation and Effector Redistribution 1

PubMed Central

Evans, Michael L.

1991-01-01

Our increasing capabilities for quantitative hormone analysis and automated high resolution growth studies have allowed a reassessment of the classical Cholodny-Went hypothesis of gravitropism. According to this hypothesis, gravity induces redistribution of auxin toward the lower side of the organ and this causes the growth asymmetry that leads to reorientation. Arguments against the Cholodny-Went hypothesis that were based primarily on concerns over the timing and magnitude of the development of hormone asymmetry are countered by recent evidence that such asymmetry develops early and is sufficiently large to account for curvature. Thus, it appears that the Cholodny-Went hypothesis is fundamentally valid. However, recent comparative studies of the kinetics of curvature and the timing of the development of hormone asymmetry indicate that this hypothesis alone cannot account for the intricacies of the gravitropic response. It appears that time-dependent gravity-induced changes in hormone sensitivity as well as changes in sensitivity of the gravity receptor play important roles in the response. PMID:11537485

VHL deletion impairs mammary alveologenesis but is not sufficient for mammary tumorigenesis.

PubMed

Seagroves, Tiffany N; Peacock, Danielle L; Liao, Debbie; Schwab, Luciana P; Krueger, Robin; Handorf, Charles R; Haase, Volker H; Johnson, Randall S

2010-05-01

Overexpression of hypoxia inducible factor-1 (HIF-1)alpha, which is common in most solid tumors, correlates with poor prognosis and high metastatic risk in breast cancer patients. Because HIF-1alpha protein stability is tightly controlled by the tumor suppressor von Hippel-Lindau (VHL), deletion of VHL results in constitutive HIF-1alpha expression. To determine whether VHL plays a role in normal mammary gland development, and if HIF-1alpha overexpression is sufficient to initiate breast cancer, Vhl was conditionally deleted in the mammary epithelium using the Cre/loxP system. During first pregnancy, loss of Vhl resulted in decreased mammary epithelial cell proliferation and impaired alveolar differentiation; despite these phenotypes, lactation was sufficient to support pup growth. In contrast, in multiparous dams, Vhl(-/-) mammary glands exhibited a progressive loss of alveolar epithelium, culminating in lactation failure. Deletion of Vhl in the epithelium also impacted the mammary stroma, as there was increased microvessel density accompanied by hemorrhage and increased immune cell infiltration. However, deletion of Vhl was not sufficient to induce mammary tumorigenesis in dams bred continuously for up to 24 months of age. Moreover, co-deletion of Hif1a could not rescue the Vhl(-/-)-dependent phenotype as dams were unable to successfully lactate during the first lactation. These results suggest that additional VHL-regulated genes besides HIF1A function to maintain the proliferative and regenerative potential of the breast epithelium.

Molecular engineering of cyanine dyes to design a panchromatic response in Co-sensitized dye-sensitized solar cells

DOE PAGES

Pepe, Giulio; Cole, Jacqueline M.; Waddell, Paul G.; ...

2016-04-05

Cyanines are optically tunable dyes with high molar extinction coefficients, suitable for applications in co-sensitized dye-sensitized solar cells (DSCs); yet, barely thus applied. This might be due to the lack of a rational molecular design strategy that efficiently exploits cyanine properties. This study computationally re-designs these dyes, to broaden their optical absorption spectrum and create dye···TiO 2 binding and co-sensitization functionality. This is achieved via a stepwise molecular engineering approach. Firstly, the structural and optical properties of four parent dyes are experimentally and computationally investigated: 3,3’-diethyloxacarbocyanine iodide, 3,3’-diethylthiacarbocyanine iodide, 3,3’-diethylthiadicarbocyanine iodide and 3,3’-diethylthiatricarbocyanine iodide. Secondly, the molecules are theoretically modifiedmore » and their energetics are analyzed and compared to the parent dyes. A dye···TiO 2 anchoring group (carboxylic or cyanoacrylic acid), absent from the parent dyes, is chemically substituted at different molecular positions to investigate changes in optical absorption. We find that cyanoacrylic acid substitution at the para-quinoidal position affects the absorption wavelength of all parent dyes, with an optimal bathochromic shift of ca. 40 nm. The theoretical lengthening of the polymethine chain is also shown to effect dye absorption. Two molecularly engineered dyes are proposed as promising co-sensitizers. Finally, corresponding dye···TiO 2 adsorption energy calculations corroborate their applicability, demonstrating the potential of cyanine dyes in DSC research.« less

Rapid insulin sensitivity test (RIST).

PubMed

Lautt, W W; Wang, X; Sadri, P; Legare, D J; Macedo, M P

1998-12-01

A rapid insulin sensitivity test (RIST) was recently introduced to assess insulin action in vivo (H. Xie, L. Zhu, Y.L. Zhang, D.J. Legare, and W.W. Lautt. J. Pharmacol. Toxicol. Methods, 35: 77-82. 1996). This technical report describes the current recommended standard operating procedure for the use of the RIST in rats based upon additional experience with approximately 100 tests. We describe the manufacture and use of an arterial-venous shunt that allows rapid multiple arterial samples and intravenous administration of drugs. The RIST procedure involves determination of a stable arterial glucose baseline to define the ideal euglycemic level to be maintained following a 5-min infusion of insulin, with the RIST index being the amount of glucose required to be infused to maintain euglycemia over the test period. Insulin administration by a 5-min infusion is preferable to a 30-s bolus administration. No significant difference was determined between the use of Toronto pork-beef or human insulin. Four consecutive RISTs were carried out in the same animal over 4-5 h with no tendency for change with time. The RIST index is sufficiently sensitive and reproducible to permit establishment of insulin dose-response curves and interference of insulin action by elimination of hepatic parasympathetic nerves, using atropine. This technical report provides the current recommended standard operating procedure for the RIST.

Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles.

PubMed

Lei, Lei; Spradling, Allan C

2013-05-21

Whether or not mammalian females generate new oocytes during adulthood from germ-line stem cells to sustain the ovarian follicle pool has recently generated controversy. We used a sensitive lineage-labeling system to determine whether stem cells are needed in female adult mice to compensate for follicular losses and to directly identify active germ-line stem cells. Primordial follicles generated during fetal life are highly stable, with a half-life during adulthood of 10 mo, and thus are sufficient to sustain adult oogenesis without a source of renewal. Moreover, in normal mice or following germ-cell depletion with Busulfan, only stable, single oocytes are lineage-labeled, rather than cell clusters indicative of new oocyte formation. Even one germ-line stem cell division per 2 wk would have been detected by our method, based on the kinetics of fetal follicle formation. Thus, adult female mice neither require nor contain active germ-line stem cells or produce new oocytes in vivo.

Ablation of proliferating neural stem cells during early life is sufficient to reduce adult hippocampal neurogenesis.

PubMed

Youssef, Mary; Krish, Varsha S; Kirshenbaum, Greer S; Atsak, Piray; Lass, Tamara J; Lieberman, Sophie R; Leonardo, E David; Dranovsky, Alex

2018-05-09

Environmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al., 2014), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Bringing gender sensitivity into healthcare practice: a systematic review.

PubMed

Celik, Halime; Lagro-Janssen, Toine A L M; Widdershoven, Guy G A M; Abma, Tineke A

2011-08-01

Despite the body of literature on gender dimensions and disparities between the sexes in health, practical improvements will not be realized effectively as long as we lack an overview of the ways how to implement these ideas. This systematic review provides a content analysis of literature on the implementation of gender sensitivity in health care. Literature was identified from CINAHL, PsycINFO, Medline, EBSCO and Cochrane (1998-2008) and the reference lists of relevant articles. The quality and relevance of 752 articles were assessed and finally 11 original studies were included. Our results demonstrate that the implementation of gender sensitivity includes tailoring opportunities and barriers related to the professional, organizational and the policy level. As gender disparities are embedded in healthcare, a multiple track approach to implement gender sensitivity is needed to change gendered healthcare systems. Conventional approaches, taking into account one barrier and/or opportunity, fail to prevent gender inequality in health care. For gender-sensitive health care we need to change systems and structures, but also to enhance understanding, raise awareness and develop skills among health professionals. To bring gender sensitivity into healthcare practice, interventions should address a range of factors. Copyright © 2010. Published by Elsevier Ireland Ltd.

Development of a high sensitivity pinhole type gamma camera using semiconductors for low dose rate fields

NASA Astrophysics Data System (ADS)

Ueno, Yuichiro; Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi; Fujishima, Yasutake; Yoshida, Akira; Umegaki, Kikuo

2018-06-01

We developed a pinhole type gamma camera, using a compact detector module of a pixelated CdTe semiconductor, which has suitable sensitivity and quantitative accuracy for low dose rate fields. In order to improve the sensitivity of the pinhole type semiconductor gamma camera, we adopted three methods: a signal processing method to set the discriminating level lower, a high sensitivity pinhole collimator and a smoothing image filter that improves the efficiency of the source identification. We tested basic performances of the developed gamma camera and carefully examined effects of the three methods. From the sensitivity test, we found that the effective sensitivity was about 21 times higher than that of the gamma camera for high dose rate fields which we had previously developed. We confirmed that the gamma camera had sufficient sensitivity and high quantitative accuracy; for example, a weak hot spot (0.9 μSv/h) around a tree root could be detected within 45 min in a low dose rate field test, and errors of measured dose rates with point sources were less than 7% in a dose rate accuracy test.

Economic evaluations of alcohol prevention interventions: Is the evidence sufficient? A review of methodological challenges.

PubMed

Hill, Sarah R; Vale, Luke; Hunter, David; Henderson, Emily; Oluboyede, Yemi

2017-12-01

Public health interventions have unique characteristics compared to health technologies, which present additional challenges for economic evaluation (EE). High quality EEs that are able to address the particular methodological challenges are important for public health decision-makers. In England, they are even more pertinent given the transition of public health responsibilities in 2013 from the National Health Service to local government authorities where new agents are shaping policy decisions. Addressing alcohol misuse is a globally prioritised public health issue. This article provides a systematic review of EE and priority-setting studies for interventions to prevent and reduce alcohol misuse published internationally over the past decade (2006-2016). This review appraises the EE and priority-setting evidence to establish whether it is sufficient to meet the informational needs of public health decision-makers. 619 studies were identified via database searches. 7 additional studies were identified via hand searching journals, grey literature and reference lists. 27 met inclusion criteria. Methods identified included cost-utility analysis (18), cost-effectiveness analysis (6), cost-benefit analysis (CBA) (1), cost-consequence analysis (CCA) (1) and return-on-investment (1). The review identified a lack of consideration of methodological challenges associated with evaluating public health interventions and limited use of methods such as CBA and CCA which have been recommended as potentially useful for EE in public health. No studies using other specific priority-setting tools were identified. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics

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

Shi, Tujin; Su, Dian; Liu, Tao

2012-04-01

Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the pg/mL to low ng/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in the cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides or their posttranslational modifications (PTMs), as well as advances in MS instrumentation, whichmore » have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed.« less

Three-dimensional Fréchet sensitivity kernels for electromagnetic wave propagation

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

Strickland, C. E.; Johnson, T. C.; Odom, R. I.

2015-08-28

Electromagnetic imaging methods are useful tools for monitoring subsurface changes in pore-fluid content and the associated changes in electrical permittivity and conductivity. The most common method for georadar tomography uses a high frequency ray-theoretic approximation that is valid when material variations are sufficiently small relative to the wavelength of the propagating wave. Georadar methods, however, often utilize electromagnetic waves that propagate within heterogeneous media at frequencies where ray theory may not be applicable. In this paper we describe the 3-D Fréchet sensitivity kernels for EM wave propagation. Various data functional types are formulated that consider all three components of themore » electric wavefield and incorporate near-, intermediate-, and far-field contributions. We show that EM waves exhibit substantial variations for different relative source-receiver component orientations. The 3-D sensitivities also illustrate out-of-plane effects that are not captured in 2-D sensitivity kernels and can influence results obtained using 2-D inversion methods to image structures that are in reality 3-D.« less

Pre-study feasibility and identifying sensitivity analyses for protocol pre-specification in comparative effectiveness research.

PubMed

Girman, Cynthia J; Faries, Douglas; Ryan, Patrick; Rotelli, Matt; Belger, Mark; Binkowitz, Bruce; O'Neill, Robert

2014-05-01

The use of healthcare databases for comparative effectiveness research (CER) is increasing exponentially despite its challenges. Researchers must understand their data source and whether outcomes, exposures and confounding factors are captured sufficiently to address the research question. They must also assess whether bias and confounding can be adequately minimized. Many study design characteristics may impact on the results; however, minimal if any sensitivity analyses are typically conducted, and those performed are post hoc. We propose pre-study steps for CER feasibility assessment and to identify sensitivity analyses that might be most important to pre-specify to help ensure that CER produces valid interpretable results.

Reported chemical sensitivities in a health survey of United Kingdon military personnel

PubMed Central

Reid, S; Hotopf, M; Hull, L; Ismail, K; Unwin, C; Wessely, S

2002-01-01

Method: Cross sectional postal survey of three cohorts of United Kingdom military personnel comprising Gulf veterans (n=3531), those who had served in Bosnia (n=2050), and those serving during the Gulf war but not deployed there (Era cohort, n=2614). Results: Sensitivity to at least one everyday chemical was reported by a considerable proportion of all three cohorts, and particularly by veterans of the Gulf war (Era: 14%; Bosnia: 13%; Gulf: 28%). Conclusion: Reported chemical sensitivities were common in all three military cohorts. Our understanding of chemical sensitivities remains limited and objective evidence for a causal link between low level exposures to chemicals and reported symptoms is lacking. Given their frequency in the population, further work in this area is necessary. PMID:11886951

Correlation, necessity, and sufficiency: Common errors in the scientific reasoning of undergraduate students for interpreting experiments.

PubMed

Coleman, Aaron B; Lam, Diane P; Soowal, Lara N

2015-01-01

Gaining an understanding of how science works is central to an undergraduate education in biology and biochemistry. The reasoning required to design or interpret experiments that ask specific questions does not come naturally, and is an essential part of the science process skills that must be learned for an understanding of how scientists conduct research. Gaps in these reasoning skills make it difficult for students to become proficient in reading primary scientific literature. In this study, we assessed the ability of students in an upper-division biochemistry laboratory class to use the concepts of correlation, necessity, and sufficiency in interpreting experiments presented in a format and context that is similar to what they would encounter when reading a journal article. The students were assessed before and after completion of a laboratory module where necessary vs. sufficient reasoning was used to design and interpret experiments. The assessment identified two types of errors that were commonly committed by students when interpreting experimental data. When presented with an experiment that only establishes a correlation between a potential intermediate and a known effect, students frequently interpreted the intermediate as being sufficient (causative) for the effect. Also, when presented with an experiment that tests only necessity for an intermediate, they frequently made unsupported conclusions about sufficiency, and vice versa. Completion of the laboratory module and instruction in necessary vs. sufficient reasoning showed some promise for addressing these common errors. © 2015 The International Union of Biochemistry and Molecular Biology.

Characterisation of 2,4-Dinitroanisole: An Ingredient for Use in Low Sensitivity Melt Cast Formulations

DTIC Science & Technology

2006-08-01

PETN/TNT 50/50 PMMA Polymethyl methacrylate RDX Cyclotrimethylenetrinitramine RS-RDX Reduced Sensitivity RDX SEM Scanning electron... toxicological data was available on DNAN. It had been proposed that due to the increased solubility of DNAN over TNT in aqueous solution at biologically...While the toxicological study [18], concluded that the vapour pressure of DNAN was not sufficient to cause concerns over inhalation of DNAN during

Local sensitivities of the gulf stream separation

DOE PAGES

Schoonover, Joseph; Dewar, William K.; Wienders, Nicolas; ...

2016-12-05

Robust and accurate Gulf Stream separation remains an unsolved problem in general circulation modeling whose resolution will positively impact the ocean and climate modeling communities. Oceanographic literature does not face a shortage of plausible hypotheses that attempt to explain the dynamics of the Gulf Stream separation, yet a single theory that the community agrees on is missing. We investigate the impact of the Deep Western Boundary Current, coastline curvature, and continental shelf steepening on the Gulf Stream separation within regional configurations of the MIT General Circulation Model. Artificial modifications to the regional bathymetry are introduced to investigate the sensitivity ofmore » the separation to each of these factors. Metrics for subsurface separation detection confirm the direct link between flow separation and the surface expression of the Gulf Stream in the Mid-Atlantic Bight. Conversely, the Gulf Stream separation exhibits minimal sensitivity to the presence of the DWBC and coastline curvature. The implications of these results to the development of a “separation recipe” for ocean modeling are discussed. Furthermore, we conclude adequate topographic resolution is a necessary, but not sufficient, condition for proper Gulf Stream separation.« less

The Extracellular Matrix Protein TGFBI Induces Microtubule Stabilization and Sensitizes Ovarian Cancers to Paclitaxel

PubMed Central

Ahmed, Ahmed Ashour; Mills, Anthony D.; Ibrahim, Ashraf E.K.; Temple, Jillian; Blenkiron, Cherie; Vias, Maria; Massie, Charlie E.; Iyer, N. Gopalakrishna; McGeoch, Adam; Crawford, Robin; Nicke, Barbara; Downward, Julian; Swanton, Charles; Bell, Stephen D.; Earl, Helena M.; Laskey, Ronald A.; Caldas, Carlos; Brenton, James D.

2007-01-01

Summary The extracellular matrix (ECM) can induce chemotherapy resistance via AKT-mediated inhibition of apoptosis. Here, we show that loss of the ECM protein TGFBI (transforming growth factor beta induced) is sufficient to induce specific resistance to paclitaxel and mitotic spindle abnormalities in ovarian cancer cells. Paclitaxel-resistant cells treated with recombinant TGFBI protein show integrin-dependent restoration of paclitaxel sensitivity via FAK- and Rho-dependent stabilization of microtubules. Immunohistochemical staining for TGFBI in paclitaxel-treated ovarian cancers from a prospective clinical trial showed that morphological changes of paclitaxel-induced cytotoxicity were restricted to areas of strong expression of TGFBI. These data show that ECM can mediate taxane sensitivity by modulating microtubule stability. PMID:18068629

The extracellular matrix protein TGFBI induces microtubule stabilization and sensitizes ovarian cancers to paclitaxel.

PubMed

Ahmed, Ahmed Ashour; Mills, Anthony D; Ibrahim, Ashraf E K; Temple, Jillian; Blenkiron, Cherie; Vias, Maria; Massie, Charlie E; Iyer, N Gopalakrishna; McGeoch, Adam; Crawford, Robin; Nicke, Barbara; Downward, Julian; Swanton, Charles; Bell, Stephen D; Earl, Helena M; Laskey, Ronald A; Caldas, Carlos; Brenton, James D

2007-12-01

The extracellular matrix (ECM) can induce chemotherapy resistance via AKT-mediated inhibition of apoptosis. Here, we show that loss of the ECM protein TGFBI (transforming growth factor beta induced) is sufficient to induce specific resistance to paclitaxel and mitotic spindle abnormalities in ovarian cancer cells. Paclitaxel-resistant cells treated with recombinant TGFBI protein show integrin-dependent restoration of paclitaxel sensitivity via FAK- and Rho-dependent stabilization of microtubules. Immunohistochemical staining for TGFBI in paclitaxel-treated ovarian cancers from a prospective clinical trial showed that morphological changes of paclitaxel-induced cytotoxicity were restricted to areas of strong expression of TGFBI. These data show that ECM can mediate taxane sensitivity by modulating microtubule stability.

Lack of Gender and Age Differences in Pain Measurements Following Exercise in People with Chronic Whiplash-Associated Disorders.

PubMed

Ickmans, Kelly; Malfliet, Anneleen; De Kooning, Margot; Goudman, Lisa; Hubloue, Ives; Schmitz, Tom; Goubert, Dorien; Aguilar-Ferrandiz, Maria Encarnacion

2017-09-01

Individuals with chronic whiplash associated disorders (WAD) present persistent pain in the absence of structural pathology. In these people, altered central pain processing and central sensitization are observed. The role of personal factors, such as gender and age, on pain processing mechanisms in chronic WAD, however, is still unclear. This study investigated possible gender- and age-related differences in self-reported and experimental pain measurements in people with chronic WAD. Besides the exercise-induced response on pain measurements between gender and age subgroups was recorded. Case-control study. University Hospital, Brussels. Self-reported pain and experimental pain measurements (pressure pain thresholds [PPT], occlusion cuff pressure, temporal summation, and conditioned pain modulation) were performed in 52 individuals (26 chronic WAD patients and 26 healthy controls), before and after a submaximal cycle exercise. Lower PPTs and occlusion cuff pressures were shown in chronic WAD in comparison with healthy controls. No gender and age differences regarding PPTs, occlusion cuff pressures and conditioned pain modulation were found in chronic WAD. Within the chronic WAD group, men showed higher self-reported pain compared to women and younger adults showed enhanced generalized pain facilitation compared to older adults. In addition, chronic WAD patients are able to inhibit exercise-induced hyperalgesia, but no gender and age differences in pain response following exercise were found. This study was sufficiently powered to detect differences between the chronic WAD and control group. However, a sufficient power was not reached when patients were divided in age and gender groups. Furthermore, only mechanical stimuli were included in the experimental pain measurements. Besides, psychosocial factors were not taken into account. Some alterations of altered pain processing are present in chronic WAD patients, however not in response to exercise. No gender and

Inositol 1,4,5-trisphosphate receptor type II (InsP3R-II) is reduced in obese mice, but metabolic homeostasis is preserved in mice lacking InsP3R-II

PubMed Central

Feriod, Colleen N.; Nguyen, Lily; Jurczak, Michael J.; Kruglov, Emma A.; Nathanson, Michael H.; Shulman, Gerald I.; Bennett, Anton M.

2014-01-01

Inositol 1,4,5-trisphosphate receptor type II (InsP3R-II) is the most prevalent isoform of the InsP3R in hepatocytes and is concentrated under the canalicular membrane, where it plays an important role in bile secretion. We hypothesized that altered calcium (Ca2+) signaling may be involved in metabolic dysfunction, as InsP3R-mediated Ca2+ signals have been implicated in the regulation of hepatic glucose homeostasis. Here, we find that InsP3R-II, but not InsP3R-I, is reduced in the livers of obese mice. In our investigation of the functional consequences of InsP3R-II deficiency, we found that organic anion secretion at the canalicular membrane and Ca2+ signals were impaired. However, mice lacking InsP3R-II showed no deficits in energy balance, glucose production, glucose tolerance, or susceptibility to hepatic steatosis. Thus, our results suggest that reduced InsP3R-II expression is not sufficient to account for any disruptions in metabolic homeostasis that are observed in mouse models of obesity. We conclude that metabolic homeostasis is maintained independently of InsP3R-II. Loss of InsP3R-II does impair secretion of bile components; therefore, we suggest that conditions of obesity would lead to a decrease in this Ca2+-sensitive process. PMID:25315698

Anxiety sensitivity levels: a predictor of treatment compliance or avoidance.

PubMed

Weiner, Arthur A

2013-01-01

The goal of this article is to stress the importance of understanding the presence of varying levels of pretreatment anxiety sensitivity to certain anticipated dental events and the role it plays as a predictor of anxious behavior and patient responses when individuals are confronted with fear-causing events, such as dental treatment. The varying intensity of anxiety sensitivity levels (ASL) in individuals serves to lessen or heighten the anxious and fearful response to potentially anxiety-provoking stimuli, such as pain. This level of anxiety sensitivity can often be traced back to the degree of knowledge or lack of information possessed by the patient regarding anticipated treatment and the practitioner's degree of acumen and completeness in history gathering. It has been suggested clinically that the level of anxiety sensitivity is directly related to the ability to predict whether or not treatment compliance will be achieved in an individual. Knowing the factors-either physiological or psychological-that are in play and that produce negative and aversive responses within a patient before and during treatment is key to solving these barriers to dental care.

[Sensitivity and antibiotic resistance in infections of the musculoskeletal system].

PubMed

Mata-Hernández, Argenis; Rivera-Villa, Adrián Huematzin; Miguel-Pérez, Adrián; Pérez-Atanasio, José Manuel; Torres-González, Rubén

2016-01-01

Infections of the musculoskeletal system are a devastating complication for patients, due to it's long rehabilitation process and even sometimes the removal of the implant, the chronicity of infection, is often due to lack of coverage in empirical antibiotics. A retrospective, observational, descriptive cohort study was performed. All cultures form musculoskeletal system infected patients reported of sensitivity and resistance of germs isolated were analyzed. A total of 143 positive results were included. Reported more frequent germ Staphylococcus aureus accounted for 75 positive cases, followed by Escherichia coli with 31 positive results. Antibiotics with better sensitivity according to the type of microorganisms were trimethoprim-sulfamethoxazole and vancomycin, levofloxacin and linezolid, gentamicin, erythromycin and amikacin. Regarding antibiotic resistance, those reported with the highest percentage were penicillin G, amoxicillin with clavulanic acid and ampicillin. We recommend using empirical treatments in musculoskeletal system infections, trimethoprim-sulfamethoxazole are the best choice because they have the same sensitivity compare with vancomycin and a resistance rate of 7.6%. Betalactamics have a high percentage of resistance and low sensitivity so we must consider alternatives.

Earless toads sense low frequencies but miss the high notes.

PubMed

Womack, Molly C; Christensen-Dalsgaard, Jakob; Coloma, Luis A; Chaparro, Juan C; Hoke, Kim L

2017-10-11

Sensory losses or reductions are frequently attributed to relaxed selection. However, anuran species have lost tympanic middle ears many times, despite anurans' use of acoustic communication and the benefit of middle ears for hearing airborne sound. Here we determine whether pre-existing alternative sensory pathways enable anurans lacking tympanic middle ears (termed earless anurans) to hear airborne sound as well as eared species or to better sense vibrations in the environment. We used auditory brainstem recordings to compare hearing and vibrational sensitivity among 10 species (six eared, four earless) within the Neotropical true toad family (Bufonidae). We found that species lacking middle ears are less sensitive to high-frequency sounds, however, low-frequency hearing and vibrational sensitivity are equivalent between eared and earless species. Furthermore, extratympanic hearing sensitivity varies among earless species, highlighting potential species differences in extratympanic hearing mechanisms. We argue that ancestral bufonids may have sufficient extratympanic hearing and vibrational sensitivity such that earless lineages tolerated the loss of high frequency hearing sensitivity by adopting species-specific behavioural strategies to detect conspecifics, predators and prey. © 2017 The Author(s).

Further Results on Sufficient LMI Conditions for H∞ Static Output Feedback Control of Discrete-Time Systems

NASA Astrophysics Data System (ADS)

Feng, Zhi-Yong; Xu, Li; Matsushita, Shin-Ya; Wu, Min

Further results on sufficient LMI conditions for H∞ static output feedback (SOF) control of discrete-time systems are presented in this paper, which provide some new insights into this issue. First, by introducing a slack variable with block-triangular structure and choosing the coordinate transformation matrix properly, the conservativeness of one kind of existing sufficient LMI condition is further reduced. Then, by introducing a slack variable with linear matrix equality constraint, another kind of sufficient LMI condition is proposed. Furthermore, the relation of these two kinds of LMI conditions are revealed for the first time through analyzing the effect of different choices of coordinate transformation matrices. Finally, a numerical example is provided to demonstrate the effectiveness and merits of the proposed methods.

Sensitization and Interoception as Key Neurological Concepts in Osteopathy and Other Manual Medicines.

PubMed

D'Alessandro, Giandomenico; Cerritelli, Francesco; Cortelli, Pietro

2016-01-01

Historically, approaches used in manual medicine to explain patient reported symptoms have been focused on the so-called exteroceptive paradigm. Arguably, this mindset lacks an appropriate "reading system" able to interpret musculoskeletal disorders from a different perspective, where the properties of the nervous system are embraced into a more holistic and functional-related context. Interestingly, if the underpinning mechanisms of a given treatment scenario/effect are taking into account, the majority of research outcomes focuses on a proprioceptive/exteroceptive explanation, leaving ting aside the additional or even central role of interoception. Currently, to date, the application of theoretical knowledge acquired on the relatively recent neuroscientific concepts and evidence concerning of interoception, sensitization, touch, autonomic functions, inflammation, and pain into a clinical/research manual medicine scenario is lacking, even if theoretically, the impact on the possible etiological mechanisms and treatment effects seems to be important. Here, we propose the conceptual foundations for a new way of interpreting and reading patients' clinical reported outcomes scenario based on interoception and sensitization. We argue that this will provide a foundation to create the ground for future research focusing on the hypotheses that manual therapies, specifically osteopathy, can intercede with sensitization states, at all levels, using interoceptive pathways.

Sensitization and Interoception as Key Neurological Concepts in Osteopathy and Other Manual Medicines

PubMed Central

D'Alessandro, Giandomenico; Cerritelli, Francesco; Cortelli, Pietro

2016-01-01

Historically, approaches used in manual medicine to explain patient reported symptoms have been focused on the so-called exteroceptive paradigm. Arguably, this mindset lacks an appropriate “reading system” able to interpret musculoskeletal disorders from a different perspective, where the properties of the nervous system are embraced into a more holistic and functional-related context. Interestingly, if the underpinning mechanisms of a given treatment scenario/effect are taking into account, the majority of research outcomes focuses on a proprioceptive/exteroceptive explanation, leaving ting aside the additional or even central role of interoception. Currently, to date, the application of theoretical knowledge acquired on the relatively recent neuroscientific concepts and evidence concerning of interoception, sensitization, touch, autonomic functions, inflammation, and pain into a clinical/research manual medicine scenario is lacking, even if theoretically, the impact on the possible etiological mechanisms and treatment effects seems to be important. Here, we propose the conceptual foundations for a new way of interpreting and reading patients' clinical reported outcomes scenario based on interoception and sensitization. We argue that this will provide a foundation to create the ground for future research focusing on the hypotheses that manual therapies, specifically osteopathy, can intercede with sensitization states, at all levels, using interoceptive pathways. PMID:27013961

Food Self-Sufficiency across scales: How local can we go?

NASA Astrophysics Data System (ADS)

Pradhan, Prajal; Lüdeke, Matthias K. B.; Reusser, Dominik E.; Kropp, Jürgen P.

2013-04-01

"Think global, act local" is a phrase often used in sustainability debates. Here, we explore the potential of regions to go for local supply in context of sustainable food consumption considering both the present state and the plausible future scenarios. We analyze data on the gridded crop calories production, the gridded livestock calories production, the gridded feed calories use and the gridded food calories consumption in 5' resolution. We derived these gridded data from various sources: Global Agro-ecological Zone (GAEZ v3.0), Gridded Livestock of the World (GLW), FAOSTAT, and Global Rural-Urban Mapping Project (GRUMP). For scenarios analysis, we considered changes in population, dietary patterns and possibility of obtaining the maximum potential yield. We investigate the food self-sufficiency multiple spatial scales. We start from the 5' resolution (i.e. around 10 km x 10 km in the equator) and look at 8 levels of aggregation ranging from the plausible lowest administrative level to the continental level. Results for the different spatial scales show that about 1.9 billion people live in the area of 5' resolution where enough calories can be produced to sustain their food consumption and the feed used. On the country level, about 4.4 billion population can be sustained without international food trade. For about 1 billion population from Asia and Africa, there is a need for cross-continental food trade. However, if we were able to achieve the maximum potential crop yield, about 2.6 billion population can be sustained within their living area of 5' resolution. Furthermore, Africa and Asia could be food self-sufficient by achieving their maximum potential crop yield and only round 630 million populations would be dependent on the international food trade. However, the food self-sufficiency status might differ under consideration of the future change in population, dietary patterns and climatic conditions. We provide an initial approach for investigating the

Necessary and sufficient criterion for extremal quantum correlations in the simplest Bell scenario

NASA Astrophysics Data System (ADS)

Ishizaka, Satoshi

2018-05-01

In the study of quantum nonlocality, one obstacle is that the analytical criterion for identifying the boundaries between quantum and postquantum correlations has not yet been given, even in the simplest Bell scenario. We propose a plausible, analytical, necessary and sufficient condition ensuring that a nonlocal quantum correlation in the simplest scenario is an extremal boundary point. Our extremality condition amounts to certifying an information-theoretical quantity; the probability of guessing a measurement outcome of a distant party optimized using any quantum instrument. We show that this quantity can be upper and lower bounded from any correlation in a device-independent way, and we use numerical calculations to confirm that coincidence of the upper and lower bounds appears to be necessary and sufficient for the extremality.

High spatial validity is not sufficient to elicit voluntary shifts of attention.

PubMed

Pauszek, Joseph R; Gibson, Bradley S

2016-10-01

Previous research suggests that the use of valid symbolic cues is sufficient to elicit voluntary shifts of attention. The present study interpreted this previous research within a broader theoretical context which contends that observers will voluntarily use symbolic cues to orient their attention in space when the temporal costs of using the cues are perceived to be less than the temporal costs of searching without the aid of the cues. In this view, previous research has not addressed the sufficiency of valid symbolic cues, because the temporal cost of using the cues is usually incurred before the target display appears. To address this concern, 70%-valid spatial word cues were presented simultaneously with a search display. In addition, other research suggests that opposing cue-dependent and cue-independent spatial biases may operate in these studies and alter standard measures of orienting. After identifying and controlling these opposing spatial biases, the results of two experiments showed that the word cues did not elicit voluntary shifts of attention when the search task was relatively easy but did when the search task was relatively difficult. Moreover, the findings also showed that voluntary use of the word cues changed over the course of the experiment when the task was difficult, presumably because the temporal cost of searching without the cue lessened as the task got easier with practice. Altogether, the present findings suggested that the factors underlying voluntary control are multifaceted and contextual, and that spatial validity alone is not sufficient to elicit voluntary shifts of attention.

Hepatic glucocorticoid receptor antagonism is sufficient to reduce elevated hepatic glucose output and improve glucose control in animal models of type 2 diabetes.

PubMed

Jacobson, Peer B; von Geldern, Thomas W; Ohman, Lars; Osterland, Marie; Wang, Jiahong; Zinker, Bradley; Wilcox, Denise; Nguyen, Phong T; Mika, Amanda; Fung, Steven; Fey, Thomas; Goos-Nilsson, Annika; Grynfarb, Marlena; Barkhem, Tomas; Marsh, Kennan; Beno, David W A; Nga-Nguyen, Bach; Kym, Philip R; Link, James T; Tu, Noah; Edgerton, Dale S; Cherrington, Alan; Efendic, Suad; Lane, Benjamin C; Opgenorth, Terry J

2005-07-01

Glucocorticoids amplify endogenous glucose production in type 2 diabetes by increasing hepatic glucose output. Systemic glucocorticoid blockade lowers glucose levels in type 2 diabetes, but with several adverse consequences. It has been proposed, but never demonstrated, that a liver-selective glucocorticoid receptor antagonist (LSGRA) would be sufficient to reduce hepatic glucose output (HGO) and restore glucose control to type 2 diabetic patients with minimal systemic side effects. A-348441 [(3b,5b,7a,12a)-7,12-dihydroxy-3-{2-[{4-[(11b,17b)-17-hydroxy-3-oxo-17-prop-1-ynylestra-4,9-dien-11-yl] phenyl}(methyl)amino]ethoxy}cholan-24-oic acid] represents the first LSGRA with significant antidiabetic activity. A-348441 antagonizes glucocorticoid-up-regulated hepatic genes, normalizes postprandial glucose in diabetic mice, and demonstrates synergistic effects on blood glucose in these animals when coadministered with an insulin sensitizer. In insulin-resistant Zucker fa/fa rats and fasted conscious normal dogs, A-348441 reduces HGO with no acute effect on peripheral glucose uptake. A-348441 has no effect on the hypothalamic pituitary adrenal axis or on other measured glucocorticoid-induced extrahepatic responses. Overall, A-348441 demonstrates that an LSGRA is sufficient to reduce elevated HGO and normalize blood glucose and may provide a new therapeutic approach for the treatment of type 2 diabetes.

Comparison of Two Global Sensitivity Analysis Methods for Hydrologic Modeling over the Columbia River Basin

NASA Astrophysics Data System (ADS)

Hameed, M.; Demirel, M. C.; Moradkhani, H.

2015-12-01

Global Sensitivity Analysis (GSA) approach helps identify the effectiveness of model parameters or inputs and thus provides essential information about the model performance. In this study, the effects of the Sacramento Soil Moisture Accounting (SAC-SMA) model parameters, forcing data, and initial conditions are analysed by using two GSA methods: Sobol' and Fourier Amplitude Sensitivity Test (FAST). The simulations are carried out over five sub-basins within the Columbia River Basin (CRB) for three different periods: one-year, four-year, and seven-year. Four factors are considered and evaluated by using the two sensitivity analysis methods: the simulation length, parameter range, model initial conditions, and the reliability of the global sensitivity analysis methods. The reliability of the sensitivity analysis results is compared based on 1) the agreement between the two sensitivity analysis methods (Sobol' and FAST) in terms of highlighting the same parameters or input as the most influential parameters or input and 2) how the methods are cohered in ranking these sensitive parameters under the same conditions (sub-basins and simulation length). The results show the coherence between the Sobol' and FAST sensitivity analysis methods. Additionally, it is found that FAST method is sufficient to evaluate the main effects of the model parameters and inputs. Another conclusion of this study is that the smaller parameter or initial condition ranges, the more consistency and coherence between the sensitivity analysis methods results.

Evaluating Emergent Constraints for Equilibrium Climate Sensitivity

DOE PAGES

Caldwell, Peter M.; Zelinka, Mark D.; Klein, Stephen A.

2018-04-23

Emergent constraints are quantities that are observable from current measurements and have skill predicting future climate. Here, this study explores 19 previously proposed emergent constraints related to equilibrium climate sensitivity (ECS; the global-average equilibrium surface temperature response to CO 2 doubling). Several constraints are shown to be closely related, emphasizing the importance for careful understanding of proposed constraints. A new method is presented for decomposing correlation between an emergent constraint and ECS into terms related to physical processes and geographical regions. Using this decomposition, one can determine whether the processes and regions explaining correlation with ECS correspond to the physicalmore » explanation offered for the constraint. Shortwave cloud feedback is generally found to be the dominant contributor to correlations with ECS because it is the largest source of intermodel spread in ECS. In all cases, correlation results from interaction between a variety of terms, reflecting the complex nature of ECS and the fact that feedback terms and forcing are themselves correlated with each other. For 4 of the 19 constraints, the originally proposed explanation for correlation is borne out by our analysis. These four constraints all predict relatively high climate sensitivity. The credibility of six other constraints is called into question owing to correlation with ECS coming mainly from unexpected sources and/or lack of robustness to changes in ensembles. Another six constraints lack a testable explanation and hence cannot be confirmed. Lastly, the fact that this study casts doubt upon more constraints than it confirms highlights the need for caution when identifying emergent constraints from small ensembles.« less

Evaluating Emergent Constraints for Equilibrium Climate Sensitivity

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

Caldwell, Peter M.; Zelinka, Mark D.; Klein, Stephen A.

Emergent constraints are quantities that are observable from current measurements and have skill predicting future climate. Here, this study explores 19 previously proposed emergent constraints related to equilibrium climate sensitivity (ECS; the global-average equilibrium surface temperature response to CO 2 doubling). Several constraints are shown to be closely related, emphasizing the importance for careful understanding of proposed constraints. A new method is presented for decomposing correlation between an emergent constraint and ECS into terms related to physical processes and geographical regions. Using this decomposition, one can determine whether the processes and regions explaining correlation with ECS correspond to the physicalmore » explanation offered for the constraint. Shortwave cloud feedback is generally found to be the dominant contributor to correlations with ECS because it is the largest source of intermodel spread in ECS. In all cases, correlation results from interaction between a variety of terms, reflecting the complex nature of ECS and the fact that feedback terms and forcing are themselves correlated with each other. For 4 of the 19 constraints, the originally proposed explanation for correlation is borne out by our analysis. These four constraints all predict relatively high climate sensitivity. The credibility of six other constraints is called into question owing to correlation with ECS coming mainly from unexpected sources and/or lack of robustness to changes in ensembles. Another six constraints lack a testable explanation and hence cannot be confirmed. Lastly, the fact that this study casts doubt upon more constraints than it confirms highlights the need for caution when identifying emergent constraints from small ensembles.« less

Sufficient and necessary condition of separability for generalized Werner states

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

Deng Dongling; Chen Jingling

2009-02-15

In a celebrated paper [Optics Communications 179, 447, 2000], A.O. Pittenger and M.H. Rubin presented for the first time a sufficient and necessary condition of separability for the generalized Werner states. Inspired by their ideas, we generalized their method to a more general case. We obtain a sufficient and necessary condition for the separability of a specific class of N d-dimensional system (qudits) states, namely special generalized Werner state (SGWS): W{sup [d{sup N}]}(v)=(1-v)(I{sup (N)})/(d{sup N}) +v|{psi}{sub d}{sup N}><{psi}{sub d}{sup N}|, where |{psi}{sub d}{sup N}>={sigma}{sub i=0}{sup d-1}{alpha}{sub i}|i...i> is an entangled pure state of N qudits system and {alpha}{sub i} satisfiesmore » two restrictions: (i) {sigma}{sub i=0}{sup d-1}{alpha}{sub i}{alpha}{sub i}*=1; (ii) Matrix 1/d (I{sup (1)}+T{sigma}{sub i{ne}}{sub j}{alpha}{sub i}|i>

Motion-based prediction is sufficient to solve the aperture problem

PubMed Central

Perrinet, Laurent U; Masson, Guillaume S

2012-01-01

In low-level sensory systems, it is still unclear how the noisy information collected locally by neurons may give rise to a coherent global percept. This is well demonstrated for the detection of motion in the aperture problem: as luminance of an elongated line is symmetrical along its axis, tangential velocity is ambiguous when measured locally. Here, we develop the hypothesis that motion-based predictive coding is sufficient to infer global motion. Our implementation is based on a context-dependent diffusion of a probabilistic representation of motion. We observe in simulations a progressive solution to the aperture problem similar to physiology and behavior. We demonstrate that this solution is the result of two underlying mechanisms. First, we demonstrate the formation of a tracking behavior favoring temporally coherent features independently of their texture. Second, we observe that incoherent features are explained away while coherent information diffuses progressively to the global scale. Most previous models included ad-hoc mechanisms such as end-stopped cells or a selection layer to track specific luminance-based features as necessary conditions to solve the aperture problem. Here, we have proved that motion-based predictive coding, as it is implemented in this functional model, is sufficient to solve the aperture problem. This solution may give insights in the role of prediction underlying a large class of sensory computations. PMID:22734489

Broad Detection of Alterations Predicted to Confer Lack of Benefit From EGFR Antibodies or Sensitivity to Targeted Therapy in Advanced Colorectal Cancer.

PubMed

Rankin, Andrew; Klempner, Samuel J; Erlich, Rachel; Sun, James X; Grothey, Axel; Fakih, Marwan; George, Thomas J; Lee, Jeeyun; Ross, Jeffrey S; Stephens, Philip J; Miller, Vincent A; Ali, Siraj M; Schrock, Alexa B

2016-09-28

A KRAS mutation represented the first genomic biomarker to predict lack of benefit from anti-epidermal growth factor receptor (EGFR) antibody therapy in advanced colorectal cancer (CRC). Expanded RAS testing has further refined the treatment approach, but understanding of genomic alterations underlying primary and acquired resistance is limited and further study is needed. We prospectively analyzed 4,422 clinical samples from patients with advanced CRC, using hybrid-capture based comprehensive genomic profiling (CGP) at the request of the individual treating physicians. Comparison with prior molecular testing results, when available, was performed to assess concordance. We identified a RAS/RAF pathway mutation or amplification in 62% of cases, including samples harboring KRAS mutations outside of the codon 12/13 hotspot region in 6.4% of cases. Among cases with KRAS non-codon 12/13 alterations for which prior test results were available, 79 of 90 (88%) were not identified by focused testing. Of 1,644 RAS/RAF wild-type cases analyzed by CGP, 31% harbored a genomic alteration (GA) associated with resistance to anti-EGFR therapy in advanced CRC including mutations in PIK3CA, PTEN, EGFR, and ERBB2. We also identified other targetable GA, including novel kinase fusions, receptor tyrosine kinase amplification, activating point mutations, as well as microsatellite instability. Extended genomic profiling reliably detects alterations associated with lack of benefit to anti-EGFR therapy in advanced CRC, while simultaneously identifying alterations potentially important in guiding treatment. The use of CGP during the course of clinical care allows for the refined selection of appropriate targeted therapies and clinical trials, increasing the chance of clinical benefit and avoiding therapeutic futility. Comprehensive genomic profiling (CGP) detects diverse genomic alterations associated with lack of benefit to anti-epidermal growth factor receptor therapy in advanced

Sleep budgets in a globalizing world: biocultural interactions influence sleep sufficiency among Egyptian families

PubMed Central

Worthman, Carol M.; Brown, Ryan A.

2013-01-01

Declines in self-reported sleep quotas with globalizing lifestyle changes have focused attention on their possible role in rising global health problems such as obesity or depression. Cultural factors that act across the life course and support sleep sufficiency have received scant attention, nor have the potential interactions of cultural and biological factors in age-related changes in sleep behavior been systematically investigated. This study examines the effects of cultural norms for napping and sleeping arrangements along with sleep schedules, age, and gender on sleep budgets among Egyptian households. Data were collected in 2000 from 16 households with 78 members aged 3–56 years at two sites in Egypt (Cairo and an agrarian village). Each participant provided one week of continuous activity records and details of each sleep event. Records showed that nighttime sleep onsets were late and highly variable. Napping was common and, along with wake time flexibility, played a key role in maintaining sleep sufficiency throughout the life course into later middle age. Cosleeping was prevalent and exhibited contrasting associations with reduced duration and sufficiency of both nocturnal and total sleep, and with earlier, more regular, and less disrupted sleep. Daily sleep quotas met published guidelines and showed age-related changes similar to existing reports, but differed in how they were achieved. Cultural norms organizing sleep practices by age and gender appear to tap their intrinsic biological properties as well. Moreover, flexibility in how sleep was achieved contributed to sleep sufficiency. The findings suggest how biocultural dynamics can play key roles in sleep patterns that sustain favorable sleep quotas from infancy onwards in populations pursuing globalizing contemporary lifestyles. PMID:22651897

75 FR 39035 - Housing Choice Voucher (HCV) Family Self-Sufficiency (FSS) Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-07

...) Family Self-Sufficiency (FSS) Program AGENCY: Office of the Chief Information Officer, HUD. ACTION... Department is soliciting public comments on the subject proposal. The FSS program, which was established in... coordinate the use of public housing assistance and assistance under the Section 8 rental certificate and...

Leptin action in the ventromedial hypothalamic nucleus is sufficient, but not necessary, to normalize diabetic hyperglycemia.

PubMed

Meek, Thomas H; Matsen, Miles E; Dorfman, Mauricio D; Guyenet, Stephan J; Damian, Vincent; Nguyen, Hong T; Taborsky, Gerald J; Morton, Gregory J

2013-09-01

In rodent models of type 1 diabetes, leptin administration into brain ventricles normalizes blood glucose at doses that have no effect when given peripherally. The ventromedial nucleus of the hypothalamus (VMN) is a potential target for leptin's antidiabetic effects because leptin-sensitive neurons in this brain area are implicated in glucose homeostasis. To test this hypothesis, we injected leptin directly into the bilateral VMN of rats with streptozotocin-induced uncontrolled diabetes mellitus. This intervention completely normalized both hyperglycemia and the elevated rates of hepatic glucose production and plasma glucagon levels but had no effect on tissue glucose uptake in the skeletal muscle or brown adipose tissue as measured using tracer dilution techniques during a basal clamp. To determine whether VMN leptin signaling is required for leptin-mediated normalization of diabetic hyperglycemia, we studied mice in which the leptin receptor gene was deleted in VMN steroidogenic factor 1 neurons using cre-loxP technology. Our findings indicate leptin action within these neurons is not required for the correction of diabetic hyperglycemia by central leptin infusion. We conclude that leptin signaling in the VMN is sufficient to mediate leptin's antidiabetic action but may not be necessary for this effect. Leptin action within a distributed neuronal network may mediate its effects on glucose homeostasis.

[Effect of vitamin beverages on vitamin sufficiency of the workers of Pskov Hydroelectric Power-Plant].

PubMed

Spiricheva, T V; Vrezhesinskaia, O A; Beketova, N A; Pereverzeva, O G; Kosheleva, O V; Kharitonchik, L A; Kodentsova, V M; Iudina, A V; Spirichev, V B

2010-01-01

The research of influence of vitamin complexes in the form of a drink or kissel on vitamin sufficiency of working persons has been carried out. Long inclusion (6,5 months) in a diet of vitamin drinks containing about 80% from recommended daily consumption of vitamins, was accompanied by trustworthy improvement of vitamins C and B6 sufficiency and prevention of seasonal deterioration of beta-carotene status. As initially surveyed have been well provided with vitamins A and E, their blood serum level increase had not occurred.

Necessary and sufficient conditions for discrete wavelet frames in CN

NASA Astrophysics Data System (ADS)

Deepshikha; Vashisht, Lalit K.

2017-07-01

We present necessary and sufficient conditions with explicit frame bounds for a discrete wavelet system of the form {DaTk ϕ } a ∈ U(N) , k ∈IN to be a frame for the unitary space CN. It is shown that the canonical dual of a discrete wavelet frame for CN has the same structure. This is not true (well known) for canonical dual of a wavelet frame for L2(R) . Several numerical examples are given to illustrate the results.

Spatial contrast sensitivity at twilight: luminance, monocularity, and oxygenation.

PubMed

Connolly, Desmond M

2010-05-01

Visual performance in dim light is compromised by lack of oxygen (hypoxia). The possible influence of altered oxygenation on foveal contrast sensitivity under mesopic (twilight) viewing conditions is relevant to aircrew flying at night, including when using night vision devices, but is poorly documented. Foveal contrast sensitivity was measured binocularly and monocularly in 12 subjects at 7 spatial frequencies, ranging from 0.5 to approximately 16 cycles per degree, using sinusoidal Gabor patch gratings. Hypoxic performance breathing 14.1% oxygen, equivalent to altitude exposure at 3048 m (10,000 ft), was compared with breathing air at sea level (normoxia) at low photopic (28 cd x m(-2)), borderline upper mesopic (approximately 2.1 cd x m(-2)) and midmesopic (approximately 0.26 cd x m(-2)) luminance. Mesopic performance was also assessed breathing 100% oxygen (hyperoxia). Typical 'inverted U' log/log plots of the contrast sensitivity function were obtained, with elevated thresholds (reduced sensitivity) at lower luminance. Binocular viewing enhanced sensitivity by a factor approximating square root of 2 for most conditions, supporting neural summation of the contrast signal, but had greater influence at the lowest light level and highest spatial frequencies (8.26 and 16.51 cpd). Respiratory challenges had no effect. Contrast sensitivity is poorer when viewing monocularly and especially at midmesopic luminance, with relevance to night flying. The foveal contrast sensitivity function is unaffected by respiratory disturbance when twilight conditions favor cone vision, despite known effects on retinal illumination (pupil size). The resilience of the contrast sensitivity function belies the vulnerability of foveal low contrast acuity to mild hypoxia at mesopic luminance.

10 CFR 503.21 - Lack of alternate fuel supply.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Lack of alternate fuel supply. 503.21 Section 503.21 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS NEW FACILITIES Temporary Exemptions for New Facilities § 503.21 Lack of alternate fuel supply. (a) Eligibility. Section 211(a)(1) of the Act provides for...

PKMζ is necessary and sufficient for synaptic clustering of PSD-95.

PubMed

Shao, Charles Y; Sondhi, Rachna; van de Nes, Paula S; Sacktor, Todd Charlton

2012-07-01

The persistent activity of protein kinase Mzeta (PKMζ), a brain-specific, constitutively active protein kinase C isoform, maintains synaptic long-term potentiation (LTP). Structural remodeling of the postsynaptic density is believed to contribute to the expression of LTP. We therefore examined the role of PKMζ in reconfiguring PSD-95, the major postsynaptic scaffolding protein at excitatory synapses. In primary cultures of hippocampal neurons, PKMζ activity was critical for increasing the size of PSD-95 clusters during chemical LTP (cLTP). Increasing PKMζ activity by overexpressing the kinase in hippocampal neurons was sufficient to increase PSD-95 cluster size, spine size, and postsynaptic AMPAR subunit GluA2. Overexpression of an inactive mutant of PKMζ did not increase PSD-95 clustering, and applications of the ζ-pseudosubstrate inhibitor ZIP reversed the PKMζ-mediated increases in PSD-95 clustering, indicating that the activity of PKMζ is necessary to induce and maintain the increased size of PSD-95 clusters. Thus the persistent activity of PKMζ is both necessary and sufficient for maintaining increases of PSD-95 clusters, providing a unified mechanism for long-term functional and structural modifications of synapses. Copyright © 2011 Wiley Periodicals, Inc.

Eph A10-modified pH-sensitive liposomes loaded with novel triphenylphosphine-docetaxel conjugate possess hierarchical targetability and sufficient antitumor effect both in vitro and in vivo.

PubMed

Zhang, Jiulong; Yang, Chunrong; Pan, Shuang; Shi, Menghao; Li, Jie; Hu, Haiyang; Qiao, Mingxi; Chen, Dawei; Zhao, Xiuli

2018-11-01

Mitochondrial-targeting therapy was considered to be a promising approach for the efficient treatment of cancer while positive charge induced nonspecific cytotoxicity severely limits its application. To overcome this drawback, a novel mitochondria targeted conjugate triphenylphosphine-docetaxel (TD) has been synthesized successfully and incorporated it into liposomes (EPSLP/TD), which possessed excellent pH-sensitive characteristic, EphA 10 mediated active targetability as well as mitochondria-targeting capability. EPSLP/TD was characterized to have a small particle size, high-encapsulation efficiency and excellent pH-sensitive characteristic. Compared with DTX-loaded liposomes (EPSLP/DTX), EPSLP/TD possessed higher cytotoxicity against MCF-7 cell line. Mitochondrial-targeting assay demonstrated mitochondria-targeting moiety triphenylphosphine (TPP) could efficiently deliver DTX to mitochondria. Western immunoblotting assay indicated that EPSLP/TD could efficiently deliver antitumor drug to mitochondria and induce cell apoptosis via mitochondria-mediated apoptosis pathway. In vivo antitumor study demonstrated EPSLP/TD owed excellent in vivo antitumor activity. Histological assay demonstrated EPSLP/TD showed strongly apoptosis inducing effect, anti-proliferation effect and anti-angiogenesis effect. This work investigated the potential of hierarchical targeting pH-sensitive liposomes is a suitable carrier to activate mitochondria-mediated apoptosis pathway for cancer therapy.

Extraversion and taste sensitivity.

PubMed

Zverev, Yuriy; Mipando, Mwapatsa

2008-03-01

The rationale for investigating the gustatory reactivity as influenced by personality dimensions was suggested by some prior findings of an association between extraversion and acuity in other sensory systems. Detection thresholds for sweet, salty, and bitter qualities of taste were measured in 60 young healthy male and female volunteers using a two-alternative forced-choice technique. Personality of the responders was assessed using the Eysenck Personality Inventory. Multivariate analysis of variance failed to demonstrate a statistically significant interaction between an extraversion-introversion score, neuroticism score, smoking, gender and age. The only reliable negative association was found between the body mass index (BMI) and taste sensitivity (Roy's largest root = 0.05, F(7436.5) = 8.34, P = 0.003). Possible reasons for lack of differences between introverts and extraverts in the values of taste detection thresholds were discussed.

Geometric derivations of minimal sets of sufficient multiview constraints

USGS Publications Warehouse

Thomas, Orrin H.; Oshel, Edward R.

2012-01-01

Geometric interpretations of four of the most common determinant formulations of multiview constraints are given, showing that they all enforce the same geometry and that all of the forms commonly in use in the machine vision community are a subset of a more general form. Generalising the work of Yi Ma yields a new general 2 x 2 determinant trilinear and 3 x 3 determinant quadlinear. Geometric descriptions of degenerate multiview constraints are given, showing that it is necessary, but insufficient, that the determinant equals zero. Understanding the degeneracies leads naturally into proofs for minimum sufficient sets of bilinear, trilinear and quadlinear constraints for arbitrary numbers of conjugate observations.

Challenges and strategies for conducting sensitive research with an Arab American population.

PubMed

Timraz, Shahrazad M; Alhasanat, Dalia I; Albdour, Maha M; Lewin, Linda; Giurgescu, Carmen; Kavanaugh, Karen

2017-02-01

Recruiting minority groups such as Arab Americans (Ar-Am) for research studies has been challenging. To date no studies were found that explicitly addressed challenges to recruit Ar-Am for sensitive research. The purpose of this article is to present the challenges across three pilot studies that involved Ar-Am samples and the strategies that were implemented to overcome these challenges. The challenges faced with conducting studies with Ar-Am included difficulty for participants to express emotions, influence of male/female authority to consent for the study, lack of trust to disclose sensitive information, language barrier, and slow recruitment. Having bilingual female recruiters of Arabic descent, engaging the women's family members in the consent process, and addressing the sensitive topics in culturally appropriate language were effective strategies to overcome these challenges. These strategies might be helpful for other researchers who recruit Ar-Am for sensitive research. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrating ethics in design through the value-sensitive design approach.

PubMed

Cummings, Mary L

2006-10-01

The Accreditation Board of Engineering and Technology (ABET) has declared that to achieve accredited status, 'engineering programs must demonstrate that their graduates have an understanding of professional and ethical responsibility.' Many engineering professors struggle to integrate this required ethics instruction in technical classes and projects because of the lack of a formalized ethics-in-design approach. However, one methodology developed in human-computer interaction research, the Value-Sensitive Design approach, can serve as an engineering education tool which bridges the gap between design and ethics for many engineering disciplines. The three major components of Value-Sensitive Design, conceptual, technical, and empirical, exemplified through a case study which focuses on the development of a command and control supervisory interface for a military cruise missile.

Lack of Methylated Hopanoids Renders the Cyanobacterium Nostoc punctiforme Sensitive to Osmotic and pH Stress

PubMed Central

Garby, Tamsyn J.; Matys, Emily D.; Ongley, Sarah E.; Salih, Anya; Larkum, Anthony W. D.; Walter, Malcolm R.

2017-01-01

ABSTRACT To investigate the function of 2-methylhopanoids in modern cyanobacteria, the hpnP gene coding for the radical S-adenosyl methionine (SAM) methylase protein that acts on the C-2 position of hopanoids was deleted from the filamentous cyanobacterium Nostoc punctiforme ATCC 29133S. The resulting ΔhpnP mutant lacked all 2-methylhopanoids but was found to produce much higher levels of two bacteriohopanepentol isomers than the wild type. Growth rates of the ΔhpnP mutant cultures were not significantly different from those of the wild type under standard growth conditions. Akinete formation was also not impeded by the absence of 2-methylhopanoids. The relative abundances of the different hopanoid structures in akinete-dominated cultures of the wild-type and ΔhpnP mutant strains were similar to those of vegetative cell-dominated cultures. However, the ΔhpnP mutant was found to have decreased growth rates under both pH and osmotic stress, confirming a role for 2-methylhopanoids in stress tolerance. Evidence of elevated photosystem II yield and NAD(P)H-dependent oxidoreductase activity in the ΔhpnP mutant under stress conditions, compared to the wild type, suggested that the absence of 2-methylhopanoids increases cellular metabolic rates under stress conditions. IMPORTANCE As the first group of organisms to develop oxygenic photosynthesis, Cyanobacteria are central to the evolutionary history of life on Earth and the subsequent oxygenation of the atmosphere. To investigate the origin of cyanobacteria and the emergence of oxygenic photosynthesis, geobiologists use biomarkers, the remnants of lipids produced by different organisms that are found in geologic sediments. 2-Methylhopanes have been considered indicative of cyanobacteria in some environmental settings, with the parent lipids 2-methylhopanoids being present in many contemporary cyanobacteria. We have created a Nostoc punctiforme ΔhpnP mutant strain that does not produce 2-methylhopanoids to assess the

Lack of Methylated Hopanoids Renders the Cyanobacterium Nostoc punctiforme Sensitive to Osmotic and pH Stress.

PubMed

Garby, Tamsyn J; Matys, Emily D; Ongley, Sarah E; Salih, Anya; Larkum, Anthony W D; Walter, Malcolm R; Summons, Roger E; Neilan, Brett A

2017-07-01

To investigate the function of 2-methylhopanoids in modern cyanobacteria, the hpnP gene coding for the radical S -adenosyl methionine (SAM) methylase protein that acts on the C-2 position of hopanoids was deleted from the filamentous cyanobacterium Nostoc punctiforme ATCC 29133S. The resulting Δ hpnP mutant lacked all 2-methylhopanoids but was found to produce much higher levels of two bacteriohopanepentol isomers than the wild type. Growth rates of the Δ hpnP mutant cultures were not significantly different from those of the wild type under standard growth conditions. Akinete formation was also not impeded by the absence of 2-methylhopanoids. The relative abundances of the different hopanoid structures in akinete-dominated cultures of the wild-type and Δ hpnP mutant strains were similar to those of vegetative cell-dominated cultures. However, the Δ hpnP mutant was found to have decreased growth rates under both pH and osmotic stress, confirming a role for 2-methylhopanoids in stress tolerance. Evidence of elevated photosystem II yield and NAD(P)H-dependent oxidoreductase activity in the Δ hpnP mutant under stress conditions, compared to the wild type, suggested that the absence of 2-methylhopanoids increases cellular metabolic rates under stress conditions. IMPORTANCE As the first group of organisms to develop oxygenic photosynthesis, Cyanobacteria are central to the evolutionary history of life on Earth and the subsequent oxygenation of the atmosphere. To investigate the origin of cyanobacteria and the emergence of oxygenic photosynthesis, geobiologists use biomarkers, the remnants of lipids produced by different organisms that are found in geologic sediments. 2-Methylhopanes have been considered indicative of cyanobacteria in some environmental settings, with the parent lipids 2-methylhopanoids being present in many contemporary cyanobacteria. We have created a Nostoc punctiforme Δ hpnP mutant strain that does not produce 2-methylhopanoids to assess the

Investigation of Professional Self Sufficiency Levels of Physical Education and Sports Teachers

ERIC Educational Resources Information Center

Saracaoglu, Asuman Seda; Ozsaker, Murat; Varol, Rana

2012-01-01

The present research aimed at detecting professional self sufficiency levels of physical education and sports teachers who worked in Izmir Province and at investigating them in terms of some variables. For data collection, Teacher's Sense of Efficacy Scale-developed by Moran and Woolfolk-Hoy (2001) and Turkish validity and reliability studies…

The Evolution of the Chinese Armaments Industry from 1860 to Present: The Search for Self-Sufficiency

DTIC Science & Technology

1986-06-06

1 ••!•!• JVl *WF ^J in #^ The Evolution of the Chinese Armaments Industry from 1860 ^-* to Present: The Search for Self -sufficiency CD...Evolution if the Chinese Armaments Industry from 1860 to Present: The Search for Self -sufficiency 12 PERSONAL AUTHOR(S) Major Donald A. Green 13...the abil- for self - ernments from t the end of 20 DISTRIBUTION/AVAILABILITY OF ABSTRACT (3 UNCLASSIFIED/UNLIMITED • SAME AS RPT. O DTK USERS

Fragrances Categorized According to Relative Human Skin Sensitization Potency

PubMed Central

Api, Anne Marie; Parakhia, Rahul; O'Brien, Devin; Basketter, David A.

2017-01-01

Background The development of non-animal alternatives for skin sensitization potency prediction is dependent upon the availability of a sufficient dataset whose human potency is well characterized. Previously, establishment of basic categorization criteria for 6 defined potency categories, allowed 131 substances to be allocated into them entirely on the basis of human information. Objectives To supplement the original dataset with an extended range of fragrance substances. Methods A more fully described version of the original criteria was used to assess 89 fragrance chemicals, allowing their allocation into one of the 6 potency categories. Results None of the fragrance substances were assigned to the most potent group, category 1, whereas 11 were category 2, 22 were category 3, 37 were category 4, and 19 were category 5. Although none were identified as non-sensitizing, note that substances in category 5 also do not pass the threshold for regulatory classification. Conclusions The combined datasets of >200 substances placed into potency categories solely on the basis of human data provides an essential resource for the elaboration and evaluation of predictive non-animal methods. PMID:28691948

A sensitive, handheld vapor sensor based on microcantilevers

NASA Astrophysics Data System (ADS)

Pinnaduwage, L. A.; Hedden, D. L.; Gehl, A.; Boiadjiev, V. I.; Hawk, J. E.; Farahi, R. H.; Thundat, T.; Houser, E. J.; Stepnowski, S.; McGill, R. A.; Deel, L.; Lareau, R. T.

2004-11-01

We report the development of a handheld sensor based on piezoresistive microcantilevers that does not depend on optical detection, yet has high detection sensitivity. The sensor is able to detect vapors from the plastic explosives pentaerythritol tetranitrate and hexahydro-1,3,5-triazine at levels below 10 parts per trillion within few seconds of exposure under ambient conditions. A differential measurement technique has yielded a rugged sensor that is unaffected by vibration and is able to function as a "sniffer." The microelectromechanical system sensor design allows for the incorporation of hundreds of microcantilevers with suitable coatings in order to achieve sufficient selectivity in the future, and thus could provide an inexpensive, unique platform for the detection of chemical, biological, and explosive materials.

IL-4/IL-13 Heteroreceptor Influences Th17 Cell Conversion and Sensitivity to Regulatory T Cell Suppression To Restrain Experimental Allergic Encephalomyelitis.

PubMed

Barik, Subhasis; Ellis, Jason S; Cascio, Jason A; Miller, Mindy M; Ukah, Tobechukwu K; Cattin-Roy, Alexis N; Zaghouani, Habib

2017-10-01

IL-4 and IL-13 have been defined as anti-inflammatory cytokines that can counter myelin-reactive T cells and modulate experimental allergic encephalomyelitis. However, it is not known whether endogenous IL-4 and IL-13 contribute to the maintenance of peripheral tolerance and whether their function is coordinated with T regulatory cells (Tregs). In this study, we used mice in which the common cytokine receptor for IL-4 and IL-13, namely the IL-4Rα/IL-13Rα1 (13R) heteroreceptor (HR), is compromised and determined whether the lack of signaling by endogenous IL-4 and IL-13 through the HR influences the function of effector Th1 and Th17 cells in a Treg-dependent fashion. The findings indicate that mice-deficient for the HR (13R -/- ) are more susceptible to experimental allergic encephalomyelitis than mice sufficient for the HR (13R +/+ ) and develop early onset and more severe disease. Moreover, Th17 cells from 13R -/- mice had reduced ability to convert to Th1 cells and displayed reduced sensitivity to suppression by Tregs relative to Th17 effectors from 13R +/+ mice. These observations suggest that IL-4 and IL-13 likely operate through the HR and influence Th17 cells to convert to Th1 cells and to acquire increased sensitivity to suppression, leading to control of immune-mediated CNS inflammation. These previously unrecognized findings shed light on the intricacies underlying the contribution of cytokines to peripheral tolerance and control of autoimmunity. Copyright © 2017 by The American Association of Immunologists, Inc.

Nature exposure sufficiency and insufficiency: The benefits of environmental preservation.

PubMed

Reddon, John R; Durante, Salvatore B

2018-01-01

Increasing industrialization, urbanization, and a failure of many world leaders to appreciate the consequences of climate change are deleteriously impacting quality of life as well as diminishing the prospects for long term survival. Economic competitiveness and corporate profitability often pre-empt environmental concerns. The calving of an iceberg in Antarctica and the hurricane activity in the Caribbean during 2017 are unfortunate illustrations of the continuing escalation of environmental issues. We provide historical and current evidence for the importance of Nature Exposure (NE) and introduce the continuum Nature Exposure Sufficiency (NES) and Insufficiency (NEI). Insufficiency includes impoverished environments (e.g., slums and prisons) where nature exposure is very limited. Nature Exposure Sufficiency (NES) is an optimal amount of exposure to nature where many benefits such as reinvigoration can be obtained by everyone. NES also has several benefits for individuals with various health conditions such as arthritis, dementia, or depression. The benefits of NE are not just derivable from parks, forests, and other natural settings. Interiors of buildings and homes can be enhanced with plants and even pictures or objects from nature. Additionally, there is abundant evidence indicating that virtual and artificial environments depicting nature can provide substantial NE and therefore contribute to general wellbeing. Besides the difficulty in achieving cooperation amongst nations, corporations, and other collectives in developing and implementing long range plans to deal with climate change, there is also sometimes an aversion at the individual level whereby people are unwilling to experience nature due to insects and other discomforts. Such individuals are often averse to supplanting the comforts of home, even temporarily, with inadequate facilities that are seemingly less pleasant than their typical dwellings. We propose using the term Nature Exposure Aversion

76 FR 39115 - Notice of Proposed Information Collection: Transformation Initiative Family Self-Sufficiency...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-05

... Information Collection: Transformation Initiative Family Self-Sufficiency Demonstration Small Grants AGENCY... information: Title of Proposal: Notice of Funding Availability for the Transformation Initiative Family Self..., think tanks, consortia, Institutions of higher education accredited by a national or regional...

α4α6β2* nicotinic acetylcholine receptor activation on ventral tegmental area dopamine neurons is sufficient to stimulate a depolarizing conductance and enhance surface AMPA receptor function.

PubMed

Engle, Staci E; Shih, Pei-Yu; McIntosh, J Michael; Drenan, Ryan M

2013-09-01

Tobacco addiction is a serious threat to public health in the United States and abroad, and development of new therapeutic approaches is a major priority. Nicotine activates and/or desensitizes nicotinic acetylcholine receptors (nAChRs) throughout the brain. nAChRs in ventral tegmental area (VTA) dopamine (DA) neurons are crucial for the rewarding and reinforcing properties of nicotine in rodents, suggesting that they may be key mediators of nicotine's action in humans. However, it is unknown which nAChR subtypes are sufficient to activate these neurons. To test the hypothesis that nAChRs containing α6 subunits are sufficient to activate VTA DA neurons, we studied mice expressing hypersensitive, gain-of-function α6 nAChRs (α6L9'S mice). In voltage-clamp recordings in brain slices from adult mice, 100 nM nicotine was sufficient to elicit inward currents in VTA DA neurons via α6β2* nAChRs. In addition, we found that low concentrations of nicotine could act selectively through α6β2* nAChRs to enhance the function of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) receptors on the surface of these cells. In contrast, α6β2* activation did not enhance N-methyl-D-aspartic acid receptor function. Finally, AMPA receptor (AMPAR) function was not similarly enhanced in brain slices from α6L9'S mice lacking α4 nAChR subunits, suggesting that α4α6β2* nAChRs are important for enhancing AMPAR function in VTA DA neurons. Together, these data suggest that activation of α4α6β2* nAChRs in VTA DA neurons is sufficient to support the initiation of cellular changes that play a role in addiction to nicotine. α4α6β2* nAChRs may be a promising target for future smoking cessation pharmacotherapy.

Navigating behavioral energy sufficiency. Results from a survey in Swiss cities on potential behavior change.

PubMed

Seidl, Roman; Moser, Corinne; Blumer, Yann

2017-01-01

Many countries have some kind of energy-system transformation either planned or ongoing for various reasons, such as to curb carbon emissions or to compensate for the phasing out of nuclear energy. One important component of these transformations is the overall reduction in energy demand. It is generally acknowledged that the domestic sector represents a large share of total energy consumption in many countries. Increased energy efficiency is one factor that reduces energy demand, but behavioral approaches (known as "sufficiency") and their respective interventions also play important roles. In this paper, we address citizens' heterogeneity regarding both their current behaviors and their willingness to realize their sufficiency potentials-that is, to reduce their energy consumption through behavioral change. We collaborated with three Swiss cities for this study. A survey conducted in the three cities yielded thematic sets of energy-consumption behavior that various groups of participants rated differently. Using this data, we identified four groups of participants with different patterns of both current behaviors and sufficiency potentials. The paper discusses intervention types and addresses citizens' heterogeneity and behaviors from a city-based perspective.

Social Work's Response to Poverty: From Benefits Dependence to Economic Self-Sufficiency

ERIC Educational Resources Information Center

Gates, Lauren B.; Koza, Jennifer; Akabas, Sheila H.

2017-01-01

Welfare reform in the 1990s represented a fundamental policy shift in the United States' response to poverty from supporting benefits dependency to promoting economic self-sufficiency. Social work's capacity to integrate this policy shift into practice is central to meeting its mission to alleviate poverty. This study looked at the preparation of…

COMPARATIVE SENSITIVITY OF DIFFERENT LIFE-STAGES OF MEDAKA (ORYZIAS LATIPES) AND BROOK TROUT (SALVELINUS FONTINALIS) TO 2,3,7,8-TCDD

EPA Science Inventory

The early life stages of fish are known to be more sensitive than the adults to the toxicological effects of 2,3,7,8-tetrachlorodibenzo(p)dioxide (TCDD). TCDD concentrations in surface waters are sufficiently low that direct exposure of the developing embryo is unlikely to be o...

Shot noise-limited Cramér-Rao bound and algorithmic sensitivity for wavelength shifting interferometry

NASA Astrophysics Data System (ADS)

Chen, Shichao; Zhu, Yizheng

2017-02-01

Sensitivity is a critical index to measure the temporal fluctuation of the retrieved optical pathlength in quantitative phase imaging system. However, an accurate and comprehensive analysis for sensitivity evaluation is still lacking in current literature. In particular, previous theoretical studies for fundamental sensitivity based on Gaussian noise models are not applicable to modern cameras and detectors, which are dominated by shot noise. In this paper, we derive two shot noiselimited theoretical sensitivities, Cramér-Rao bound and algorithmic sensitivity for wavelength shifting interferometry, which is a major category of on-axis interferometry techniques in quantitative phase imaging. Based on the derivations, we show that the shot noise-limited model permits accurate estimation of theoretical sensitivities directly from measured data. These results can provide important insights into fundamental constraints in system performance and can be used to guide system design and optimization. The same concepts can be generalized to other quantitative phase imaging techniques as well.

Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway

PubMed Central

Follansbee, Taylor L.; Gjelsvik, Kayla J.; Brann, Courtney L.; McParland, Aidan L.

2017-01-01

Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a

Psychosocial Factors and Central Sensitivity Syndromes

PubMed Central

Adams, Leah M.; Turk, Dennis C.

2016-01-01

Central sensitivity syndromes (CSSs) represent a heterogeneous group of disorders (e.g., fibromyalgia [FM], irritable bowel syndrome [IBS], chronic headache, temporomandibular disorders [TMDs], pelvic pain syndromes) that share common symptoms, with persistent pain being the most prominent feature. Although the etiology and pathophysiology of CSSs are currently incompletely understood, central sensitization has emerged as one of the significant mechanisms. Given that there are currently no known cures for CSSs, people living with these disorders must learn to cope with and manage their symptoms throughout their lives. Medical interventions alone have not proven to be sufficient for helping people with CSSs manage their symptoms. A biopsychosocial perspective that considers the ways that biological, psychological, and social factors work independently and jointly to affect a person's experience is the most effective conceptualization and guide for effective treatment. In this article, we discuss several psychological and social features that may influence the experience of a person with CSS and their symptom management, regardless of their specific diagnosis. We highlight the longitudinal aspect of adjustment to illness, the distinction between psychosocial factors as causes of symptoms versus modifiers and perpetuators of symptoms, dispel the notion that all patients with the same diagnosis are a homogeneous group (the “patient-uniformity myth”), and acknowledge the importance of environmental and situational context on symptom management for individuals with any CSS. PMID:26088211

Determination of the thermal and epithermal neutron sensitivities of an LBO chamber.

PubMed

Endo, Satoru; Sato, Hitoshi; Shimazaki, Takuto; Nakajima, Erika; Kotani, Kei; Suda, Mitsuru; Hamano, Tsuyoshi; Kajimoto, Tsuyoshi; Tanaka, Kenichi; Hoshi, Masaharu

2017-08-01

An LBO (Li 2 B 4 O 7 ) walled ionization chamber was designed to monitor the epithermal neutron fluence in boron neutron capture therapy clinical irradiation. The thermal and epithermal neutron sensitivities of the device were evaluated using accelerator neutrons from the 9 Be(d, n) reaction at a deuteron energy of 4 MeV (4 MeV d-Be neutrons). The response of the chamber in terms of the electric charge induced in the LBO chamber was compared with the thermal and epithermal neutron fluences measured using the gold-foil activation method. The thermal and epithermal neutron sensitivities obtained were expressed in units of pC cm 2 , i.e., from the chamber response divided by neutron fluence (cm -2 ). The measured LBO chamber sensitivities were 2.23 × 10 -7  ± 0.34 × 10 -7 (pC cm 2 ) for thermal neutrons and 2.00 × 10 -5  ± 0.12 × 10 -5 (pC cm 2 ) for epithermal neutrons. This shows that the LBO chamber is sufficiently sensitive to epithermal neutrons to be useful for epithermal neutron monitoring in BNCT irradiation.

Sufficient condition for a finite-time singularity in a high-symmetry Euler flow: Analysis and statistics

NASA Astrophysics Data System (ADS)

Ng, C. S.; Bhattacharjee, A.

1996-08-01

A sufficient condition is obtained for the development of a finite-time singularity in a highly symmetric Euler flow, first proposed by Kida [J. Phys. Soc. Jpn. 54, 2132 (1995)] and recently simulated by Boratav and Pelz [Phys. Fluids 6, 2757 (1994)]. It is shown that if the second-order spatial derivative of the pressure (pxx) is positive following a Lagrangian element (on the x axis), then a finite-time singularity must occur. Under some assumptions, this Lagrangian sufficient condition can be reduced to an Eulerian sufficient condition which requires that the fourth-order spatial derivative of the pressure (pxxxx) at the origin be positive for all times leading up to the singularity. Analytical as well as direct numerical evaluation over a large ensemble of initial conditions demonstrate that for fixed total energy, pxxxx is predominantly positive with the average value growing with the numbers of modes.

Differential Sensitivity to the Gender of a Person by English and Chinese Speakers

ERIC Educational Resources Information Center

Chen, Jenn-Yeu; Su, Jui-Ju

2011-01-01

Can a linguistic device of a language orient its speakers to a particular aspect of the world and result in increased sensitivity to that aspect? The question was examined with respect to the biological gender marker in English and the lack of it in Chinese. In Experiment 1, English and Chinese participants listened to stories and answered gender…

Attended but unseen: visual attention is not sufficient for visual awareness.

PubMed

Kentridge, R W; Nijboer, T C W; Heywood, C A

2008-02-12

Does any one psychological process give rise to visual awareness? One candidate is selective attention-when we attend to something it seems we always see it. But if attention can selectively enhance our response to an unseen stimulus then attention cannot be a sufficient precondition for awareness. Kentridge, Heywood & Weiskrantz [Kentridge, R. W., Heywood, C. A., & Weiskrantz, L. (1999). Attention without awareness in blindsight. Proceedings of the Royal Society of London, Series B, 266, 1805-1811; Kentridge, R. W., Heywood, C. A., & Weiskrantz, L. (2004). Spatial attention speeds discrimination without awareness in blindsight. Neuropsychologia, 42, 831-835.] demonstrated just such a dissociation in the blindsight subject GY. Here, we test whether the dissociation generalizes to the normal population. We presented observers with pairs of coloured discs, each masked by the subsequent presentation of a coloured annulus. The discs acted as primes, speeding discrimination of the colour of the annulus when they matched in colour and slowing it when they differed. We show that the location of attention modulated the size of this priming effect. However, the primes were rendered invisible by metacontrast-masking and remained unseen despite being attended. Visual attention could therefore facilitate processing of an invisible target and cannot, therefore, be a sufficient precondition for visual awareness.

Nociceptor Sensitization Depends on Age and Pain Chronicity123

PubMed Central

Dodge, Amanda K.

2016-01-01

Abstract Peripheral inflammation causes mechanical pain behavior and increased action potential firing. However, most studies examine inflammatory pain at acute, rather than chronic time points, despite the greater burden of chronic pain on patient populations, especially aged individuals. Furthermore, there is disagreement in the field about whether primary afferents contribute to chronic pain. Therefore, we sought to evaluate the contribution of nociceptor activity to the generation of pain behaviors during the acute and chronic phases of inflammation in both young and aged mice. We found that both young (2 months old) and aged (>18 months old) mice exhibited prominent pain behaviors during both acute (2 day) and chronic (8 week) inflammation. However, young mice exhibited greater behavioral sensitization to mechanical stimuli than their aged counterparts. Teased fiber recordings in young animals revealed a twofold mechanical sensitization in C fibers during acute inflammation, but an unexpected twofold reduction in firing during chronic inflammation. Responsiveness to capsaicin and mechanical responsiveness of A-mechanonociceptor (AM) fibers were also reduced chronically. Importantly, this lack of sensitization in afferent firing during chronic inflammation occurred even as these inflamed mice exhibited continued behavioral sensitization. Interestingly, C fibers from inflamed aged animals showed no change in mechanical firing compared with controls during either the acute or chronic inflammatory phases, despite strong behavioral sensitization to mechanical stimuli at these time points. These results reveal the following two important findings: (1) nociceptor sensitization to mechanical stimulation depends on age and the chronicity of injury; and (2) maintenance of chronic inflammatory pain does not rely on enhanced peripheral drive. PMID:26866058

Acceleration and sensitivity analysis of lattice kinetic Monte Carlo simulations using parallel processing and rate constant rescaling

NASA Astrophysics Data System (ADS)

Núñez, M.; Robie, T.; Vlachos, D. G.

2017-10-01

Kinetic Monte Carlo (KMC) simulation provides insights into catalytic reactions unobtainable with either experiments or mean-field microkinetic models. Sensitivity analysis of KMC models assesses the robustness of the predictions to parametric perturbations and identifies rate determining steps in a chemical reaction network. Stiffness in the chemical reaction network, a ubiquitous feature, demands lengthy run times for KMC models and renders efficient sensitivity analysis based on the likelihood ratio method unusable. We address the challenge of efficiently conducting KMC simulations and performing accurate sensitivity analysis in systems with unknown time scales by employing two acceleration techniques: rate constant rescaling and parallel processing. We develop statistical criteria that ensure sufficient sampling of non-equilibrium steady state conditions. Our approach provides the twofold benefit of accelerating the simulation itself and enabling likelihood ratio sensitivity analysis, which provides further speedup relative to finite difference sensitivity analysis. As a result, the likelihood ratio method can be applied to real chemistry. We apply our methodology to the water-gas shift reaction on Pt(111).

Combining two serological assays optimises sensitivity and specificity for the identification of Streptococcus equi subsp. equi exposure.

PubMed

Robinson, Carl; Steward, Karen F; Potts, Nicola; Barker, Colin; Hammond, Toni-ann; Pierce, Karen; Gunnarsson, Eggert; Svansson, Vilhjálmur; Slater, Josh; Newton, J Richard; Waller, Andrew S

2013-08-01

The detection of anti-Streptococcus equi antibodies in the blood serum of horses can assist with the identification of apparently healthy persistently infected carriers and the prevention of strangles outbreaks. The aim of the current study was to use genome sequencing data to develop an indirect enzyme linked immunosorbent assay (iELISA) that targets two S. equi-specific protein fragments. The sensitivity and specificity of the antigen A and antigen C iELISAs were compared to an SeM-based iELISA marketed by IDvet - diagnostic Vétérinaire (IDvet). Individually, each assay compromised specificity in order to achieve sufficient sensitivity (SeM iELISA had a sensitivity of 89.9%, but a specificity of only 77.0%) or sensitivity to achieve high specificity. However, combining the results of the antigen A and antigen C iELISAs permitted optimisation of both sensitivity (93.3%) and specificity (99.3%), providing a robust assay for the identification of horses exposed to S. equi. Copyright © 2013 Elsevier Ltd. All rights reserved.

Air-borne and tissue-borne sensitivities of bioacoustic sensors used on the skin surface.

PubMed

Zañartu, Matías; Ho, Julio C; Kraman, Steve S; Pasterkamp, Hans; Huber, Jessica E; Wodicka, George R

2009-02-01

Measurements of body sounds on the skin surface have been widely used in the medical field and continue to be a topic of current research, ranging from the diagnosis of respiratory and cardiovascular diseases to the monitoring of voice dosimetry. These measurements are typically made using light-weight accelerometers and/or air-coupled microphones attached to the skin. Although normally neglected, air-borne sounds generated by the subject or other sources of background noise can easily corrupt such recordings, which is particularly critical in the recording of voiced sounds on the skin surface. In this study, the sensitivity of commonly used bioacoustic sensors to air-borne sounds was evaluated and compared with their sensitivity to tissue-borne body sounds. To delineate the sensitivity to each pathway, the sensors were first tested in vitro and then on human subjects. The results indicated that, in general, the air-borne sensitivity is sufficiently high to significantly corrupt body sound signals. In addition, the air-borne and tissue-borne sensitivities can be used to discriminate between these components. Although the study is focused on the evaluation of voiced sounds on the skin surface, an extension of the proposed methods to other bioacoustic applications is discussed.

Quantitative patch and repeated open application testing in hydroxyisohexyl 3-cyclohexene carboxaldehyde sensitive-patients.

PubMed

Schnuch, Axel; Uter, Wolfgang; Dickel, Heinrich; Szliska, Christiane; Schliemann, Sibylle; Eben, Ricarda; Ruëff, Franziska; Gimenez-Arnau, Ana; Löffler, Harald; Aberer, Werner; Frambach, Yvonne; Worm, Margitta; Niebuhr, Margarete; Hillen, Uwe; Martin, Vera; Jappe, Uta; Frosch, Peter J; Mahler, Vera

2009-09-01

To identify the concentration of the fragrance compound hydroxyisohexyl 3-cyclohexene carboxaldehyde (INCI) (HICC) that is sufficiently low not to cause an allergic reaction in patients with proven sensitization. Repeated open application testing (ROAT) in 64 subjects with 2 preparations (perfume and cream) in different concentration (0.005-2.5%). Confirmatory patch testing with four preparations in two different concentrations (2.5% and 5%). The concentrations of HICC being tolerated by 90% of those sensitized to HICC are estimated as <88.2 ppm (cream) and <270 ppm (perfume) equivalent to 1.2 microg/cm(2) (perfume) and 4.9 microg/cm(2) (cream). Patch test preparations differed with regard to sensitivity (88.5-98.1%) and specificity (37.5-87.5%) against the ROAT result as external criterion. ROAT concentrations and the reaction strength in patch testing were inversely correlated (Kendall's tau-b: 0.69), both indicating the existence of different degrees of susceptibility. To protect 90% (50%) of people sensitized, the use concentration should be in the range of 0.009-0.027% (0.18-0.34%), depending on the product type. Taking into account these results, excessive concentrations should be avoided, as this would continue to sensitize people. Close monitoring is indispensable to prove the efficacy of any recommendations aiming to prevent induction.

[Lack of neonatologists: vocational crisis or mistaken policies?].

PubMed

Justich, Pablo R

2012-10-01

In Argentina, the difficulty in covering neonatologist's positions represent an increasing problem. The absence of a coordinated and organized health system on one hand, and the lack of adaptation of the neonatologist's role to the current situation of the maternal and child care on the other, prevent the correct assistential coverage. The inadequate work conditions, the professional risks, the wide amount of time devoted to formation and studying, and the lack of knowledge of the professionals necessities and difficulties have a negative impact when it comes to incorporate new specialists. A global approach of the problem is essential to reach enduring answers.

Temporal patterns of inputs to cerebellum necessary and sufficient for trace eyelid conditioning.

PubMed

Kalmbach, Brian E; Ohyama, Tatsuya; Mauk, Michael D

2010-08-01

Trace eyelid conditioning is a form of associative learning that requires several forebrain structures and cerebellum. Previous work suggests that at least two conditioned stimulus (CS)-driven signals are available to the cerebellum via mossy fiber inputs during trace conditioning: one driven by and terminating with the tone and a second driven by medial prefrontal cortex (mPFC) that persists through the stimulus-free trace interval to overlap in time with the unconditioned stimulus (US). We used electric stimulation of mossy fibers to determine whether this pattern of dual inputs is necessary and sufficient for cerebellar learning to express normal trace eyelid responses. We find that presenting the cerebellum with one input that mimics persistent activity observed in mPFC and the lateral pontine nuclei during trace eyelid conditioning and another that mimics tone-elicited mossy fiber activity is sufficient to produce responses whose properties quantitatively match trace eyelid responses using a tone. Probe trials with each input delivered separately provide evidence that the cerebellum learns to respond to the mPFC-like input (that overlaps with the US) and learns to suppress responding to the tone-like input (that does not). This contributes to precisely timed responses and the well-documented influence of tone offset on the timing of trace responses. Computer simulations suggest that the underlying cerebellar mechanisms involve activation of different subsets of granule cells during the tone and during the stimulus-free trace interval. These results indicate that tone-driven and mPFC-like inputs are necessary and sufficient for the cerebellum to learn well-timed trace conditioned responses.

Effector Gene Suites in Some Soil Isolates of Fusarium oxysporum Are Not Sufficient Predictors of Vascular Wilt in Tomato.

PubMed

Jelinski, Nicolas A; Broz, Karen; Jonkers, Wilfried; Ma, Li-Jun; Kistler, H Corby

2017-07-01

Seventy-four Fusarium oxysporum soil isolates were assayed for known effector genes present in an F. oxysporum f. sp. lycopersici race 3 tomato wilt strain (FOL MN-25) obtained from the same fields in Manatee County, Florida. Based on the presence or absence of these genes, four haplotypes were defined, two of which represented 96% of the surveyed isolates. These two most common effector haplotypes contained either all or none of the assayed race 3 effector genes. We hypothesized that soil isolates with all surveyed effector genes, similar to FOL MN-25, would be pathogenic toward tomato, whereas isolates lacking all effectors would be nonpathogenic. However, inoculation experiments revealed that presence of the effector genes alone was not sufficient to ensure pathogenicity on tomato. Interestingly, a nonpathogenic isolate containing the full suite of unmutated effector genes (FOS 4-4) appears to have undergone a chromosomal rearrangement yet remains vegetatively compatible with FOL MN-25. These observations confirm the highly dynamic nature of the F. oxysporum genome and support the conclusion that pathogenesis among free-living populations of F. oxysporum is a complex process. Therefore, the presence of effector genes alone may not be an accurate predictor of pathogenicity among soil isolates of F. oxysporum.

Binaural sensitivity in children who use bilateral cochlear implants.

PubMed

Ehlers, Erica; Goupell, Matthew J; Zheng, Yi; Godar, Shelly P; Litovsky, Ruth Y

2017-06-01

Children who are deaf and receive bilateral cochlear implants (BiCIs) perform better on spatial hearing tasks using bilateral rather than unilateral inputs; however, they underperform relative to normal-hearing (NH) peers. This gap in performance is multi-factorial, including the inability of speech processors to reliably deliver binaural cues. Although much is known regarding binaural sensitivity of adults with BiCIs, less is known about how the development of binaural sensitivity in children with BiCIs compared to NH children. Sixteen children (ages 9-17 years) were tested using synchronized research processors. Interaural time differences and interaural level differences (ITDs and ILDs, respectively) were presented to pairs of pitch-matched electrodes. Stimuli were 300-ms, 100-pulses-per-second, constant-amplitude pulse trains. In the first and second experiments, discrimination of interaural cues (either ITDs or ILDs) was measured using a two-interval left/right task. In the third experiment, subjects reported the perceived intracranial position of ITDs and ILDs in a lateralization task. All children demonstrated sensitivity to ILDs, possibly due to monaural level cues. Children who were born deaf had weak or absent sensitivity to ITDs; in contrast, ITD sensitivity was noted in children with previous exposure to acoustic hearing. Therefore, factors such as auditory deprivation, in particular, lack of early exposure to consistent timing differences between the ears, may delay the maturation of binaural circuits and cause insensitivity to binaural differences.

Report: EPA Travel Program Lacks Necessary Controls

EPA Pesticide Factsheets

Report #10-P-0078, March 9, 2010. The EPA travel program, which comprises EPA policies and GovTrip, lacks necessary control procedures to assure all travel authorizations were necessary and in the best interest of the government.

Improving the sensitivity and specificity of a bioanalytical assay for the measurement of certolizumab pegol.

PubMed

Smeraglia, John; Silva, John-Paul; Jones, Kieran

2017-08-01

In order to evaluate placental transfer of certolizumab pegol (CZP), a more sensitive and selective bioanalytical assay was required to accurately measure low CZP concentrations in infant and umbilical cord blood. Results & methodology: A new electrochemiluminescence immunoassay was developed to measure CZP levels in human plasma. Validation experiments demonstrated improved selectivity (no matrix interference observed) and a detection range of 0.032-5.0 μg/ml. Accuracy and precision met acceptance criteria (mean total error ≤20.8%). Dilution linearity and sample stability were acceptable and sufficient to support the method. The electrochemiluminescence immunoassay was validated for measuring low CZP concentrations in human plasma. The method demonstrated a more than tenfold increase in sensitivity compared with previous assays, and improved selectivity for intact CZP.

The Development of University Students' Self-Sufficiency Based on Interactive Technologies by Their Immersion in the Professional Activity

ERIC Educational Resources Information Center

Ljubimova, Elena Mikhaelovna; Galimullina, Elvira Zufarovna; Ibatullin, Rinat Rivkatovich

2015-01-01

The article discusses the problems of using web technologies in the development of self-sufficiency of University students. We hypothesize that real professional situations in which he/she is obliged to work independently on the basis of web technologies contribute to the development of students' self-sufficiency. It is shown that the activity…

On the possibility (or lack thereof) of agreement between experiment and computation of flows over wings at moderate Reynolds number.

PubMed

Tank, J; Smith, L; Spedding, G R

2017-02-06

The flight of many birds and bats, and their robotic counterparts, occurs over a range of chord-based Reynolds numbers from 1 × 10 4 to 1.5 × 10 5 . It is precisely over this range where the aerodynamics of simple, rigid, fixed wings becomes extraordinarily sensitive to small changes in geometry and the environment, with two sets of consequences. The first is that practical lifting devices at this scale will likely not be simple, rigid, fixed wings. The second is that it becomes non-trivial to make baseline comparisons for experiment and computation, when either one can be wrong. Here we examine one ostensibly simple case of the NACA 0012 aerofoil and make careful comparison between the technical literature, and new experiments and computations. The agreement (or lack thereof) will establish one or more baseline results and some sensitivities around them. The idea is that the diagnostic procedures will help to guide comparisons and predictions in subsequent more complex cases.

On the possibility (or lack thereof) of agreement between experiment and computation of flows over wings at moderate Reynolds number

PubMed Central

Tank, J.; Smith, L.

2017-01-01

The flight of many birds and bats, and their robotic counterparts, occurs over a range of chord-based Reynolds numbers from 1 × 104 to 1.5 × 105. It is precisely over this range where the aerodynamics of simple, rigid, fixed wings becomes extraordinarily sensitive to small changes in geometry and the environment, with two sets of consequences. The first is that practical lifting devices at this scale will likely not be simple, rigid, fixed wings. The second is that it becomes non-trivial to make baseline comparisons for experiment and computation, when either one can be wrong. Here we examine one ostensibly simple case of the NACA 0012 aerofoil and make careful comparison between the technical literature, and new experiments and computations. The agreement (or lack thereof) will establish one or more baseline results and some sensitivities around them. The idea is that the diagnostic procedures will help to guide comparisons and predictions in subsequent more complex cases. PMID:28163869

49 CFR 40.263 - What happens when an employee is unable to provide a sufficient amount of saliva for an alcohol...

Code of Federal Regulations, 2010 CFR

2010-10-01

... sufficient amount of saliva for an alcohol screening test? (a) As the STT, you must take the following steps if an employee is unable to provide sufficient saliva to complete a test on a saliva screening device (e.g., the employee does not provide sufficient saliva to activate the device). (1) You must conduct...

Hierarchical Nanogold Labels to Improve the Sensitivity of Lateral Flow Immunoassay

NASA Astrophysics Data System (ADS)

Serebrennikova, Kseniya; Samsonova, Jeanne; Osipov, Alexander

2018-06-01

Lateral flow immunoassay (LFIA) is a widely used express method and offers advantages such as a short analysis time, simplicity of testing and result evaluation. However, an LFIA based on gold nanospheres lacks the desired sensitivity, thereby limiting its wide applications. In this study, spherical nanogold labels along with new types of nanogold labels such as gold nanopopcorns and nanostars were prepared, characterized, and applied for LFIA of model protein antigen procalcitonin. It was found that the label with a structure close to spherical provided more uniform distribution of specific antibodies on its surface, indicative of its suitability for this type of analysis. LFIA using gold nanopopcorns as a label allowed procalcitonin detection over a linear range of 0.5-10 ng mL-1 with the limit of detection of 0.1 ng mL-1, which was fivefold higher than the sensitivity of the assay with gold nanospheres. Another approach to improve the sensitivity of the assay included the silver enhancement method, which was used to compare the amplification of LFIA for procalcitonin detection. The sensitivity of procalcitonin determination by this method was 10 times better the sensitivity of the conventional LFIA with gold nanosphere as a label. The proposed approach of LFIA based on gold nanopopcorns improved the detection sensitivity without additional steps and prevented the increased consumption of specific reagents (antibodies).

Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis.

PubMed

Marí, Montserrat; Caballero, Francisco; Colell, Anna; Morales, Albert; Caballeria, Juan; Fernandez, Anna; Enrich, Carlos; Fernandez-Checa, José C; García-Ruiz, Carmen

2006-09-01

The etiology of progression from steatosis to steatohepatitis (SH) remains unknown. Using nutritional and genetic models of hepatic steatosis, we show that free cholesterol (FC) loading, but not free fatty acids or triglycerides, sensitizes to TNF- and Fas-induced SH. FC distribution in endoplasmic reticulum (ER) and plasma membrane did not cause ER stress or alter TNF signaling. Rather, mitochondrial FC loading accounted for the hepatocellular sensitivity to TNF due to mitochondrial glutathione (mGSH) depletion. Selective mGSH depletion in primary hepatocytes recapitulated the susceptibility to TNF and Fas seen in FC-loaded hepatocytes; its repletion rescued FC-loaded livers from TNF-mediated SH. Moreover, hepatocytes from mice lacking NPC1, a late endosomal cholesterol trafficking protein, or from obese ob/ob mice, exhibited mitochondrial FC accumulation, mGSH depletion, and susceptibility to TNF. Thus, we propose a critical role for mitochondrial FC loading in precipitating SH, by sensitizing hepatocytes to TNF and Fas through mGSH depletion.

The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo.

PubMed

Groseth, Allison; Marzi, Andrea; Hoenen, Thomas; Herwig, Astrid; Gardner, Don; Becker, Stephan; Ebihara, Hideki; Feldmann, Heinz

2012-01-01

Among the Ebola viruses most species cause severe hemorrhagic fever in humans; however, Reston ebolavirus (REBOV) has not been associated with human disease despite numerous documented infections. While the molecular basis for this difference remains unclear, in vitro evidence has suggested a role for the glycoprotein (GP) as a major filovirus pathogenicity factor, but direct evidence for such a role in the context of virus infection has been notably lacking. In order to assess the role of GP in EBOV virulence, we have developed a novel reverse genetics system for REBOV, which we report here. Together with a previously published full-length clone for Zaire ebolavirus (ZEBOV), this provides a unique possibility to directly investigate the role of an entire filovirus protein in pathogenesis. To this end we have generated recombinant ZEBOV (rZEBOV) and REBOV (rREBOV), as well as chimeric viruses in which the glycoproteins from these two virus species have been exchanged (rZEBOV-RGP and rREBOV-ZGP). All of these viruses could be rescued and the chimeras replicated with kinetics similar to their parent virus in tissue culture, indicating that the exchange of GP in these chimeric viruses is well tolerated. However, in a mouse model of infection rZEBOV-RGP demonstrated markedly decreased lethality and prolonged time to death when compared to rZEBOV, confirming that GP does indeed contribute to the full expression of virulence by ZEBOV. In contrast, rREBOV-ZGP did not show any signs of virulence, and was in fact slightly attenuated compared to rREBOV, demonstrating that GP alone is not sufficient to confer a lethal phenotype or exacerbate disease in this model. Thus, while these findings provide direct evidence that GP contributes to filovirus virulence in vivo, they also clearly indicate that other factors are needed for the acquisition of full virulence.

The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for Virulence In Vivo

PubMed Central

Groseth, Allison; Marzi, Andrea; Hoenen, Thomas; Herwig, Astrid; Gardner, Don; Becker, Stephan; Ebihara, Hideki; Feldmann, Heinz

2012-01-01

Among the Ebola viruses most species cause severe hemorrhagic fever in humans; however, Reston ebolavirus (REBOV) has not been associated with human disease despite numerous documented infections. While the molecular basis for this difference remains unclear, in vitro evidence has suggested a role for the glycoprotein (GP) as a major filovirus pathogenicity factor, but direct evidence for such a role in the context of virus infection has been notably lacking. In order to assess the role of GP in EBOV virulence, we have developed a novel reverse genetics system for REBOV, which we report here. Together with a previously published full-length clone for Zaire ebolavirus (ZEBOV), this provides a unique possibility to directly investigate the role of an entire filovirus protein in pathogenesis. To this end we have generated recombinant ZEBOV (rZEBOV) and REBOV (rREBOV), as well as chimeric viruses in which the glycoproteins from these two virus species have been exchanged (rZEBOV-RGP and rREBOV-ZGP). All of these viruses could be rescued and the chimeras replicated with kinetics similar to their parent virus in tissue culture, indicating that the exchange of GP in these chimeric viruses is well tolerated. However, in a mouse model of infection rZEBOV-RGP demonstrated markedly decreased lethality and prolonged time to death when compared to rZEBOV, confirming that GP does indeed contribute to the full expression of virulence by ZEBOV. In contrast, rREBOV-ZGP did not show any signs of virulence, and was in fact slightly attenuated compared to rREBOV, demonstrating that GP alone is not sufficient to confer a lethal phenotype or exacerbate disease in this model. Thus, while these findings provide direct evidence that GP contributes to filovirus virulence in vivo, they also clearly indicate that other factors are needed for the acquisition of full virulence. PMID:22876185

Conceptualising the lack of health insurance coverage.

PubMed

Davis, J B

2000-01-01

This paper examines the lack of health insurance coverage in the US as a public policy issue. It first compares the problem of health insurance coverage to the problem of unemployment to show that in terms of the numbers of individuals affected lack of health insurance is a problem comparable in importance to the problem of unemployment. Secondly, the paper discusses the methodology involved in measuring health insurance coverage, and argues that the current method of estimation of the uninsured underestimates the extent that individuals go without health insurance. Third, the paper briefly introduces Amartya Sen's functioning and capabilities framework to suggest a way of representing the extent to which individuals are uninsured. Fourth, the paper sketches a means of operationalizing the Sen representation of the uninsured in terms of the disability-adjusted life year (DALY) measure.

Celiac Disease and Nonceliac Gluten Sensitivity: A Review.

PubMed

Leonard, Maureen M; Sapone, Anna; Catassi, Carlo; Fasano, Alessio

2017-08-15

The prevalence of gluten-related disorders is rising, and increasing numbers of individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. This review aims to present current evidence regarding screening, diagnosis, and treatment for celiac disease and nonceliac gluten sensitivity. Celiac disease is a gluten-induced immune-mediated enteropathy characterized by a specific genetic genotype (HLA-DQ2 and HLA-DQ8 genes) and autoantibodies (antitissue transglutaminase and antiendomysial). Although the inflammatory process specifically targets the intestinal mucosa, patients may present with gastrointestinal signs or symptoms, extraintestinal signs or symptoms, or both, suggesting that celiac disease is a systemic disease. Nonceliac gluten sensitivity is diagnosed in individuals who do not have celiac disease or wheat allergy but who have intestinal symptoms, extraintestinal symptoms, or both, related to ingestion of gluten-containing grains, with symptomatic improvement on their withdrawal. The clinical variability and the lack of validated biomarkers for nonceliac gluten sensitivity make establishing the prevalence, reaching a diagnosis, and further study of this condition difficult. Nevertheless, it is possible to differentiate specific gluten-related disorders from other conditions, based on currently available investigations and algorithms. Clinicians cannot distinguish between celiac disease and nonceliac gluten sensitivity by symptoms, as they are similar in both. Therefore, screening for celiac disease must occur before a gluten-free diet is implemented, since once a patient initiates a gluten-free diet, testing for celiac disease is no longer accurate. Celiac disease and nonceliac gluten sensitivity are common. Although both conditions are treated with a gluten-free diet, distinguishing between celiac disease and nonceliac gluten sensitivity is important for long-term therapy. Patients with celiac disease should be followed up

Infection and Transmission of Rift Valley Fever Viruses Lacking the NSs and/or NSm Genes in Mosquitoes: Potential Role for NSm in Mosquito Infection

PubMed Central

Crabtree, Mary B.; Kent Crockett, Rebekah J.; Bird, Brian H.; Nichol, Stuart T.; Erickson, Bobbie Rae; Biggerstaff, Brad J.; Horiuchi, Kalanthe; Miller, Barry R.

2012-01-01

Background Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors. Methodology and Principal Findings Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus. Conclusions/Significance In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes. PMID:22563517

Infection and transmission of Rift Valley fever viruses lacking the NSs and/or NSm genes in mosquitoes: potential role for NSm in mosquito infection.

PubMed

Crabtree, Mary B; Kent Crockett, Rebekah J; Bird, Brian H; Nichol, Stuart T; Erickson, Bobbie Rae; Biggerstaff, Brad J; Horiuchi, Kalanthe; Miller, Barry R

2012-01-01

Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors. Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus. In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes.

Modelling the effect of GRP78 on anti-oestrogen sensitivity and resistance in breast cancer

PubMed Central

Parmar, Jignesh H.; Cook, Katherine L.; Shajahan-Haq, Ayesha N.; Clarke, Pamela A. G.; Tavassoly, Iman; Clarke, Robert; Tyson, John J.; Baumann, William T.

2013-01-01

Understanding the origins of resistance to anti-oestrogen drugs is of critical importance to many breast cancer patients. Recent experiments show that knockdown of GRP78, a key gene in the unfolded protein response (UPR), can re-sensitize resistant cells to anti-oestrogens, and overexpression of GRP78 in sensitive cells can cause them to become resistant. These results appear to arise from the operation and interaction of three cellular systems: the UPR, autophagy and apoptosis. To determine whether our current mechanistic understanding of these systems is sufficient to explain the experimental results, we built a mathematical model of the three systems and their interactions. We show that the model is capable of reproducing previously published experimental results and some new data gathered specifically for this paper. The model provides us with a tool to better understand the interactions that bring about anti-oestrogen resistance and the effects of GRP78 on both sensitive and resistant breast cancer cells. PMID:24511377

Mating motives are neither necessary nor sufficient to create the beauty premium.

PubMed

Hafenbrädl, Sebastian; Dana, Jason

2017-01-01

Mating motives lead decision makers to favor attractive people, but this favoritism is not sufficient to create a beauty premium in competitive settings. Further, economic approaches to discrimination, when correctly characterized, could neatly accommodate the experimental and field evidence of a beauty premium. Connecting labor economics and evolutionary psychology is laudable, but mating motives do not explain the beauty premium.

The guinea-pig skin sensitization test revisited: an evaluation formula to predict possible sensitization levels for eight chemicals used in household products.

PubMed

Momma, J; Kitajima, S; Inoue, T

1998-02-20

In predicting human skin sensitization due to possible risky chemicals, it is not sufficient to evaluate solely the minimum induction dose (MID) or the standard challenge dose (SCD) in the Guinea Pig Maximization Test (GPMT). Nakamura et al. (1994) (Nakamura, A., Momma, J., Sekiguchi, H., Noda, T., Yamano, T., Kaniwa, M., Kojima, S., Tsuda, M., Kurokawa, Y., 1994. A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximization test. Contact Dermatitis 31, 72-85) previously measured the residual dose of chemicals in the products implicated in human allergic accidents, and stated that '... the level of chemical in the products (direct exposure-dose = DED) was similar to or higher than value of sensitization potency.' However, several of the chemicals listed in their article, show an even lower value of sensitization potency than the DED, although a potential correlation between results of the GPMT and the DED was seemed to be evident; a key question about the essential rule of those parameters therefore remains open. Using the data of Nakamura et al. (1994), we analyzed the functional rules of the three independent parameters, the MID, the SCD, and the DED on which the GPMT is based. Calculations of the degree of allergic reactions elicited in humans provided a range of discrimination constants (D) using the formula; D = DED/(MID*SCD). Possible human allergic accidents may be predicted when the dose of a candidate chemical in a chemical product (equal to DED) exceeds the value; D*(MID*SCD), following the correct evaluation of the MID as well as the SCD.

Prevalence and determinants of sufficient fruit and vegetable consumption among primary school children in Nakhon Pathom, Thailand

PubMed Central

Piaseu, Noppawan

2017-01-01

BACKGROUND/OBJECTIVES Low consumption of fruit and vegetable is frequently viewed as an important contributor to obesity risk. With increasing childhood obesity and relatively low fruit and vegetable consumption among Thai children, there is a need to identify the determinants of the intake to promote fruit and vegetable consumption effectively. SUBJECTS/METHODS This cross-sectional study was conducted at two conveniently selected primary schools in Nakhon Pathom. A total of 609 students (grade 4-6) completed questionnaires on personal and environmental factors. Adequate fruit and vegetable intakes were defined as a minimum of three servings of fruit or vegetable daily, and adequate total intake as at least 6 serves of fruit and vegetable daily. Data were analyzed using descriptive statistics, the chi-square test, and multiple logistic regression. RESULTS The proportion of children with a sufficient fruit and/or vegetable intakes was low. Covariates of child's personal and environmental factors showed significant associations with sufficient intakes of fruit and/or vegetable (P < 0.05). Logistic regression analyses showed that the following factors were positively related to sufficient intake of vegetable; lower grade, a positive attitude toward vegetable, and fruit availability at home; and that greater maternal education, a positive child's attitude toward vegetable, and fruit availability at home were significantly associated with sufficient consumption of fruits and total fruit and vegetable intake. CONCLUSIONS The present study showed that personal factors like attitude toward vegetables and socio-environmental factors, such as, greater availability of fruits were significantly associated with sufficient fruit and vegetable consumption. The importance of environmental and personal factors to successful nutrition highlights the importance of involving parents and schools. PMID:28386386

Prevalence and determinants of sufficient fruit and vegetable consumption among primary school children in Nakhon Pathom, Thailand.

PubMed

Hong, Seo Ah; Piaseu, Noppawan

2017-04-01

Low consumption of fruit and vegetable is frequently viewed as an important contributor to obesity risk. With increasing childhood obesity and relatively low fruit and vegetable consumption among Thai children, there is a need to identify the determinants of the intake to promote fruit and vegetable consumption effectively. This cross-sectional study was conducted at two conveniently selected primary schools in Nakhon Pathom. A total of 609 students (grade 4-6) completed questionnaires on personal and environmental factors. Adequate fruit and vegetable intakes were defined as a minimum of three servings of fruit or vegetable daily, and adequate total intake as at least 6 serves of fruit and vegetable daily. Data were analyzed using descriptive statistics, the chi-square test, and multiple logistic regression. The proportion of children with a sufficient fruit and/or vegetable intakes was low. Covariates of child's personal and environmental factors showed significant associations with sufficient intakes of fruit and/or vegetable ( P < 0.05). Logistic regression analyses showed that the following factors were positively related to sufficient intake of vegetable; lower grade, a positive attitude toward vegetable, and fruit availability at home; and that greater maternal education, a positive child's attitude toward vegetable, and fruit availability at home were significantly associated with sufficient consumption of fruits and total fruit and vegetable intake. The present study showed that personal factors like attitude toward vegetables and socio-environmental factors, such as, greater availability of fruits were significantly associated with sufficient fruit and vegetable consumption. The importance of environmental and personal factors to successful nutrition highlights the importance of involving parents and schools.

Protruding Domain of Capsid Protein Is Necessary and Sufficient To Determine Murine Norovirus Replication and Pathogenesis In Vivo

PubMed Central

Strong, David W.; Thackray, Larissa B.; Smith, Tom J.

2012-01-01

Human noroviruses (HuNoVs) are the major cause of epidemic, nonbacterial gastroenteritis worldwide. Due to the lack of a tractable model system and the inability to grow HuNoVs in cell culture, factors required for the norovirus (NoV) life cycle and pathogenesis in the host remain largely unknown. The discovery of murine norovirus (MNV) and the development of reverse-genetics systems for this virus provide an opportunity to study these aspects of NoV infection in vitro and in vivo. Previous studies identified a single amino acid at residue 296 in the protruding (P) domain of the capsid protein that is responsible for determining the virulence of the MNV clone MNV1.CW1 in 12956/SvEv background STAT1-deficient (STAT1−/−) mice. In this report, we identified and characterized another determinant of lethality in the P domain that is necessary and sufficient to determine the replication and pathogenesis of the MNV clones MNV1.CW3 and CR6.STL1 in C57BL/6 background STAT1−/− mice. Furthermore, we describe how the role of residue 296 in MNV virulence differs between STAT1−/− mouse strains. We also describe potential interactions between subdomains of the P domain, as well as between other virus elements, which facilitate recovery of MNV using a reverse-genetics system. PMID:22258242

13C-MFA delineates the photomixotrophic metabolism of Synechocystis sp. PCC 6803 under light- and carbon-sufficient conditions.

PubMed

You, Le; Berla, Bert; He, Lian; Pakrasi, Himadri B; Tang, Yinjie J

2014-05-01

The central carbon metabolism of cyanobacteria is under debate. For over 50 years, the lack of α-ketoglutarate dehydrogenase has led to the belief that cyanobacteria have an incomplete TCA cycle. Recent in vitro enzymatic experiments suggest that this cycle may in fact be closed. The current study employed (13) C isotopomers to delineate pathways in the cyanobacterium Synechocystis sp. PCC 6803. By tracing the incorporation of supplemented glutamate into the downstream metabolites in the TCA cycle, we observed a direct in vivo transformation of α-ketoglutarate to succinate. Additionally, isotopic tracing of glyoxylate did not show a functional glyoxylate shunt and glyoxylate was used for glycine synthesis. The photomixotrophic carbon metabolism was then profiled with (13) C-MFA under light and carbon-sufficient conditions. We observed that: (i) the in vivo flux through the TCA cycle reactions (α-ketoglutarate → succinate) was minimal (<2%); (ii) the flux ratio of CO2 fixation was six times higher than that of glucose utilization; (iii) the relative flux through the oxidative pentose phosphate pathway was low (<2%); (iv) high flux through malic enzyme served as a main route for pyruvate synthesis. Our results improve the understanding of the versatile metabolism in cyanobacteria and shed light on their application for photo-biorefineries. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The necessary and sufficient conditions of therapeutic personality change: Reactions to Rogers' 1957 article.

PubMed

Samstag, Lisa Wallner

2007-09-01

Carl Rogers' article (see record 2007-14639-002) on the necessary and sufficient conditions for personality change has had a significant impact on the field of psychotherapy and psychotherapy research. He emphasized the client as arbiter of his or her own subjective experience and tested his hypothesized therapist-offered conditions of change using recorded sessions. This aided in demystifying the therapeutic process and led to a radical shift in the listening stance of the therapist. I briefly outline my views regarding the influence of the ideas presented in this work, describe the intellectual and cultural context of the times, and discuss a number of ways in which the therapist-offered conditions for psychological transformation are neither necessary nor sufficient. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Why sensitive bacteria are resistant to hospital infection control

PubMed Central

van Kleef, Esther; Luangasanatip, Nantasit; Bonten, Marc J; Cooper, Ben S

2017-01-01

-based transmission. Observed lack of effectiveness of control measures for sensitive strains does not provide evidence that infection control interventions have been ineffective in reducing resistant strains. PMID:29260003

Why sensitive bacteria are resistant to hospital infection control.

PubMed

van Kleef, Esther; Luangasanatip, Nantasit; Bonten, Marc J; Cooper, Ben S

2017-01-01

Large reductions in the incidence of antibiotic-resistant strains of Staphylococcus aureus and Clostridium difficile have been observed in response to multifaceted hospital-based interventions. Reductions in antibiotic-sensitive strains have been smaller or non-existent. It has been argued that since infection control measures, such as hand hygiene, should affect resistant and sensitive strains equally, observed changes must have largely resulted from other factors, including changes in antibiotic use. We used a mathematical model to test the validity of this reasoning. We developed a mechanistic model of resistant and sensitive strains in a hospital and its catchment area. We assumed the resistant strain had a competitive advantage in the hospital and the sensitive strain an advantage in the community. We simulated a hospital hand hygiene intervention that directly affected resistant and sensitive strains equally. The annual incidence rate ratio (IRR) associated with the intervention was calculated for hospital- and community-acquired infections of both strains. For the resistant strain, there were large reductions in hospital-acquired infections (0.1 ≤ IRR ≤ 0.6) and smaller reductions in community-acquired infections (0.2 ≤ IRR ≤ 0.9). These reductions increased in line with increasing importance of nosocomial transmission of the strain. For the sensitive strain, reductions in hospital acquisitions were much smaller (0.6 ≤ IRR ≤ 0.9), while community acquisitions could increase or decrease (0.9 ≤ IRR ≤ 1.2). The greater the importance of the community environment for the transmission of the sensitive strain, the smaller the reductions. Counter-intuitively, infection control interventions, including hand hygiene, can have strikingly discordant effects on resistant and sensitive strains even though they target them equally. This follows from differences in their adaptation to hospital- and community-based transmission. Observed lack of

Peroral Estradiol Is Sufficient to Induce Carcinogen-Induced Mammary Tumorigenesis in Ovariectomized Rats without Progesterone

PubMed Central

Stires, Hillary; Saboya, Mariana; Globerman, Samantha P.; Cohick, Wendie S.

2016-01-01

A role for estrogens in breast cancer is widely accepted, however, recent evidence highlights that timing and exposure levels are important in determining whether they elicit harmful versus beneficial effects. The rat chemical carcinogen model has been widely used to study the effects of estrogens but conclusions on the levels that lead to tumor development and an absolute requirement for progesterone (P4) are lacking. A newer method of hormone administration mixes hormones with nut butter for peroral consumption allowing for a less stressful method of long-term administration with lower spikes in serum estradiol (E2) levels. The present study was designed to determine if estrogens alone at a physiological dose can drive carcinogen-induced tumors in ovariectomized (OVX) rats or if P4 is also required using this method of hormone administration. Short-term studies were conducted to determine the dose of estrogen (E) that would lead to increased uterine weight following OVX. Subsequently, rats were OVX on postnatal day (PND) 40 then treated daily with E (600 μg/kg/day), P4 (15 mg/kg/day), or the combination. On PND 50, all rats were injected with nitrosomethylurea to induce mammary tumors. Uterine weights, body weights, and serum E2 levels were measured to demonstrate the efficacy of the method for increasing E2 levels during long-term treatment. After 26 weeks, tumor incidence was similar in Sham, E, and E + P4 animals indicating that E was sufficient to induce tumorigenesis when hormone levels were normalized by this method. This study demonstrates peroral administration can be used in long-term studies to elucidate relationships between different types and levels of steroid hormones. PMID:27611094

Nonlinear mathematical modeling and sensitivity analysis of hydraulic drive unit

NASA Astrophysics Data System (ADS)

Kong, Xiangdong; Yu, Bin; Quan, Lingxiao; Ba, Kaixian; Wu, Liujie

2015-09-01

The previous sensitivity analysis researches are not accurate enough and also have the limited reference value, because those mathematical models are relatively simple and the change of the load and the initial displacement changes of the piston are ignored, even experiment verification is not conducted. Therefore, in view of deficiencies above, a nonlinear mathematical model is established in this paper, including dynamic characteristics of servo valve, nonlinear characteristics of pressure-flow, initial displacement of servo cylinder piston and friction nonlinearity. The transfer function block diagram is built for the hydraulic drive unit closed loop position control, as well as the state equations. Through deriving the time-varying coefficient items matrix and time-varying free items matrix of sensitivity equations respectively, the expression of sensitivity equations based on the nonlinear mathematical model are obtained. According to structure parameters of hydraulic drive unit, working parameters, fluid transmission characteristics and measured friction-velocity curves, the simulation analysis of hydraulic drive unit is completed on the MATLAB/Simulink simulation platform with the displacement step 2 mm, 5 mm and 10 mm, respectively. The simulation results indicate that the developed nonlinear mathematical model is sufficient by comparing the characteristic curves of experimental step response and simulation step response under different constant load. Then, the sensitivity function time-history curves of seventeen parameters are obtained, basing on each state vector time-history curve of step response characteristic. The maximum value of displacement variation percentage and the sum of displacement variation absolute values in the sampling time are both taken as sensitivity indexes. The sensitivity indexes values above are calculated and shown visually in histograms under different working conditions, and change rules are analyzed. Then the sensitivity

Behavioural and physiological mechanisms of polarized light sensitivity in birds.

PubMed

Muheim, Rachel

2011-03-12

Polarized light (PL) sensitivity is relatively well studied in a large number of invertebrates and some fish species, but in most other vertebrate classes, including birds, the behavioural and physiological mechanism of PL sensitivity remains one of the big mysteries in sensory biology. Many organisms use the skylight polarization pattern as part of a sun compass for orientation, navigation and in spatial orientation tasks. In birds, the available evidence for an involvement of the skylight polarization pattern in sun-compass orientation is very weak. Instead, cue-conflict and cue-calibration experiments have shown that the skylight polarization pattern near the horizon at sunrise and sunset provides birds with a seasonally and latitudinally independent compass calibration reference. Despite convincing evidence that birds use PL cues for orientation, direct experimental evidence for PL sensitivity is still lacking. Avian double cones have been proposed as putative PL receptors, but detailed anatomical and physiological evidence will be needed to conclusively describe the avian PL receptor. Intriguing parallels between the functional and physiological properties of PL reception and light-dependent magnetoreception could point to a common receptor system.

Basolateral junctions are sufficient to suppress epithelial invasion during Drosophila oogenesis.

PubMed

Szafranski, Przemyslaw; Goode, Scott

2007-02-01

Epithelial junctions play crucial roles during metazoan evolution and development by facilitating tissue formation, maintenance, and function. Little is known about the role of distinct types of junctions in controlling epithelial transformations leading to invasion of neighboring tissues. Discovering the key junction complexes that control these processes and how they function may also provide mechanistic insight into carcinoma cell invasion. Here, using the Drosophila ovary as a model, we show that four proteins of the basolateral junction (BLJ), Fasciclin-2, Neuroglian, Discs-large, and Lethal-giant-larvae, but not proteins of other epithelial junctions, directly suppress epithelial tumorigenesis and invasion. Remarkably, the expression pattern of Fasciclin-2 predicts which cells will invade. We compared the apicobasal polarity of BLJ tumor cells to border cells (BCs), an epithelium-derived cluster that normally migrates during mid-oogenesis. Both tumor cells and BCs differentiate a lateralized membrane pattern that is necessary but not sufficient for invasion. Independent of lateralization, derepression of motility pathways is also necessary, as indicated by a strong linear correlation between faster BC migration and an increased incidence of tumor invasion. However, without membrane lateralization, derepression of motility pathways is also not sufficient for invasion. Our results demonstrate that spatiotemporal patterns of basolateral junction activity directly suppress epithelial invasion by organizing the cooperative activity of distinct polarity and motility pathways.

Necessary and sufficient liveness condition of GS3PR Petri nets

NASA Astrophysics Data System (ADS)

Liu, GaiYun; Barkaoui, Kamel

2015-05-01

Structural analysis is one of the most important and efficient methods to investigate the behaviour of Petri nets. Liveness is a significant behavioural property of Petri nets. Siphons, as structural objects of a Petri net, are closely related to its liveness. Many deadlock control policies for flexible manufacturing systems (FMS) modelled by Petri nets are implemented via siphon control. Most of the existing methods design liveness-enforcing supervisors by adding control places for siphons based on their controllability conditions. To compute a liveness-enforcing supervisor with as much as permissive behaviour, it is both theoretically and practically significant to find an exact controllability condition for siphons. However, the existing conditions, max, max‧, and max″-controllability of siphons are all overly restrictive and generally sufficient only. This paper develops a new condition called max*-controllability of the siphons in generalised systems of simple sequential processes with resources (GS3PR), which are a net subclass that can model many real-world automated manufacturing systems. We show that a GS3PR is live if all its strict minimal siphons (SMS) are max*-controlled. Compared with the existing conditions, i.e., max-, max‧-, and max″-controllability of siphons, max*-controllability of the SMS is not only sufficient but also necessary. An example is used to illustrate the proposed method.

Experimental studies on the nature of sensitive skin.

PubMed

Kligman, A M; Sadiq, Iqbal; Zhen, Yaxian; Crosby, Marilyn

2006-11-01

In the USA, Europe and Japan 40 to 50% of women report that they have sensitive skin, defined as abnormal sub-clinical sensory responses to drugs, cosmetics and toiletries in the absence of visible signs of irritation. Itching, burning, stinging and tightness are the commonest complaints, which mainly afflict women. Manufacturers of skin care products have made available a large variety of products which are designed for persons with sensitive skin. Such products are not required by regulatory agencies to submit evidence of safety and efficacy, allowing marketers to make claims that are often exaggerated, irrational and even preposterous. The consumer with self-assessed sensitive skin has no way of judging which products are likely to be most beneficial and least harmful. The marketplace is awash with products for which there is no evidence that the rosy claims have been substantiated by appropriate testing procedures. There is no internationally accepted consensus regarding the criteria which define sensitive skin. Many papers have been published in the last 15 years, mainly originating from industry, which express widely differing views regarding what constitutes sensitive skin. For some, any adverse reaction to a product topically applied to sensitive skin, including breakouts, redness, scaling etc., a panoply of adverse reactions which is virtually meaningless. Others include environmental factors as causative, including cold, dry wind, heat and high humidity, solar radiation, etc., which add to the manifest complexities of the subject. This is the first paper in a series which provides a comprehensive review of the subject, emphasizing the all too many controversies and confusions arising from the lack of a consensus regarding the identification, classification, epidemiology, prevalence and pathogenesis of sensitive skin. Sensitive skin is a biologic reality and not a psychological, fashionable fantasy on the part of impressionable women. There is an urgent

Increased ABA sensitivity results in higher seed dormancy in soft white spring wheat cultivar ‘Zak’

USDA-ARS?s Scientific Manuscript database

As a strategy to increase the seed dormancy of soft white wheat, mutants with increased sensitivity to the plant hormone abscisic acid (ABA) were identified in mutagenized grain of soft white spring wheat ‘Zak”. Lack of seed dormancy is correlated with increased susceptibility to preharvest sprouti...

49 CFR 40.193 - What happens when an employee does not provide a sufficient amount of urine for a drug test?

Code of Federal Regulations, 2013 CFR

2013-10-01

... sufficient amount of urine for a drug test? 40.193 Section 40.193 Transportation Office of the Secretary of... § 40.193 What happens when an employee does not provide a sufficient amount of urine for a drug test... sufficient amount of urine to permit a drug test (i.e., 45 mL of urine). (b) As the collector, you must do...

49 CFR 40.193 - What happens when an employee does not provide a sufficient amount of urine for a drug test?

Code of Federal Regulations, 2011 CFR

2011-10-01

... sufficient amount of urine for a drug test? 40.193 Section 40.193 Transportation Office of the Secretary of... § 40.193 What happens when an employee does not provide a sufficient amount of urine for a drug test... sufficient amount of urine to permit a drug test (i.e., 45 mL of urine). (b) As the collector, you must do...

49 CFR 40.193 - What happens when an employee does not provide a sufficient amount of urine for a drug test?

Code of Federal Regulations, 2014 CFR

2014-10-01

... sufficient amount of urine for a drug test? 40.193 Section 40.193 Transportation Office of the Secretary of... § 40.193 What happens when an employee does not provide a sufficient amount of urine for a drug test... sufficient amount of urine to permit a drug test (i.e., 45 mL of urine). (b) As the collector, you must do...

49 CFR 40.193 - What happens when an employee does not provide a sufficient amount of urine for a drug test?

Code of Federal Regulations, 2012 CFR

2012-10-01

... sufficient amount of urine for a drug test? 40.193 Section 40.193 Transportation Office of the Secretary of... § 40.193 What happens when an employee does not provide a sufficient amount of urine for a drug test... sufficient amount of urine to permit a drug test (i.e., 45 mL of urine). (b) As the collector, you must do...

Physiological and transcriptional responses of Catalpa bungei to drought stress under sufficient- and deficient-nitrogen conditions.

PubMed

Shi, Huili; Ma, Wenjun; Song, Junyu; Lu, Mei; Rahman, Siddiq Ur; Bui, Thi Tuyet Xuan; Vu, Dinh Duy; Zheng, Huifang; Wang, Junhui; Zhang, Yi

2017-11-01

Many semi-arid ecosystems are simultaneously limited by soil water and nitrogen (N). We conducted a greenhouse experiment to address how N availability impacts drought-resistant traits of Catalpa bungei C. A. Mey at the physiological and molecular level. A factorial design was used, consisting of sufficient-N and deficient-N combined with moderate drought and well-watered conditions. Seedling biomass and major root parameters were significantly suppressed by drought under the deficient-N condition, whereas N application mitigated the inhibiting effects of drought on root growth, particularly that of fine roots with a diameter <0.2 mm. Intrinsic water-use efficiency was promoted by N addition under both water conditions, whereas stable carbon isotope compositions (δ13C) was promoted by N addition only under the well-watered condition. Nitrogen application positively impacted drought adaptive responses including osmotic adjustment and homeostasis of reactive oxygen species, the content of free proline, soluble sugar and superoxide dismutase activity: all were increased upon drought under sufficient-N conditions but not under deficient-N conditions. The extent of abscisic acid (ABA) inducement upon drought was elevated by N application. Furthermore, an N-dependent crosstalk between ABA, jasmonic acid and indole acetic acid at the biosynthesis level contributed to better drought acclimation. Moreover, the transcriptional level of most genes responsible for the ABA signal transduction pathway, and genes encoding the antioxidant enzymes and plasma membrane intrinsic proteins, are elevated upon drought only under sufficient-N addition. These observations confirmed at the molecular level that major adaptive responses to drought are dependent on sufficient N nutrition. Although N uptake was decreased under drought, N-use efficiency and transcription of most genes encoding N metabolism enzymes were elevated, demonstrating that active N metabolism positively contributed

Design of fuel cell powered data centers for sufficient reliability and availability

NASA Astrophysics Data System (ADS)

Ritchie, Alexa J.; Brouwer, Jacob

2018-04-01

It is challenging to design a sufficiently reliable fuel cell electrical system for use in data centers, which require 99.9999% uptime. Such a system could lower emissions and increase data center efficiency, but the reliability and availability of such a system must be analyzed and understood. Currently, extensive backup equipment is used to ensure electricity availability. The proposed design alternative uses multiple fuel cell systems each supporting a small number of servers to eliminate backup power equipment provided the fuel cell design has sufficient reliability and availability. Potential system designs are explored for the entire data center and for individual fuel cells. Reliability block diagram analysis of the fuel cell systems was accomplished to understand the reliability of the systems without repair or redundant technologies. From this analysis, it was apparent that redundant components would be necessary. A program was written in MATLAB to show that the desired system reliability could be achieved by a combination of parallel components, regardless of the number of additional components needed. Having shown that the desired reliability was achievable through some combination of components, a dynamic programming analysis was undertaken to assess the ideal allocation of parallel components.

Understanding Self-Sufficiency of Welfare Leavers in Illinois: Elaborating Models with Psychosocial Factors.

ERIC Educational Resources Information Center

Julnes, George; Fan, Xitao; Hayashi, Kentaro

2001-01-01

Used survey (for 1,001 adults) and administrative data (for 137,330 first-exit cases) in structural equation modeling to examine psychological and social factors as determinants of welfare dependency and self-sufficiency. Findings show well-being to be a predictor of low recidivism and high employment. (SLD)

Pathway to Self-Sufficiency: Social and Economic Development Strategies of Native American Communities.

ERIC Educational Resources Information Center

Office of Human Development Services (DHHS), Washington, DC.

In fiscal year (FY) 1984 the Administration for Native Americans awarded 227 grants for social and economic development strategies (SEDS) which would help Native American communities move toward self-sufficiency. More than half the grants were primarily for economic development; approximately one-third were for improving tribal governments, and…

From Poverty to Self-Sufficiency: The Role of Postsecondary Education in Welfare Reform.

ERIC Educational Resources Information Center

Center for Women Policy Studies, Washington, DC.

This report provides policymakers with information necessary to demonstrate that postsecondary education is an effective route from poverty to true self-sufficiency and prosperity for low-income women. It discusses the impact of the 1996 Temporary Assistance for Needy Families (TANF) statute and the TANF reauthorization bill, the Personal…

Projected sensitivity of the SuperCDMS SNOLAB experiment

DOE PAGES

Agnese, R.; Anderson, A. J.; Aramaki, T.; ...

2017-04-07

SuperCDMS SNOLAB will be a next-generation experiment aimed at directly detecting low-mass particles (with masses ≤10 GeV/c 2) that may constitute dark matter by using cryogenic detectors of two types (HV and iZIP) and two target materials (germanium and silicon). The experiment is being designed with an initial sensitivity to nuclear recoil cross sections ~1×10 –43 cm 2 for a dark matter particle mass of 1 GeV/c 2, and with capacity to continue exploration to both smaller masses and better sensitivities. The phonon sensitivity of the HV detectors will be sufficient to detect nuclear recoils from sub-GeV dark matter. Amore » detailed calibration of the detector response to low-energy recoils will be needed to optimize running conditions of the HV detectors and to interpret their data for dark matter searches. Low-activity shielding, and the depth of SNOLAB, will reduce most backgrounds, but cosmogenically produced 3H and naturally occurring 32Si will be present in the detectors at some level. Even if these backgrounds are 10 times higher than expected, the science reach of the HV detectors would be over 3 orders of magnitude beyond current results for a dark matter mass of 1 GeV/c 2. The iZIP detectors are relatively insensitive to variations in detector response and backgrounds, and will provide better sensitivity for dark matter particles with masses ≳5 GeV/c 2. The mix of detector types (HV and iZIP), and targets (germanium and silicon), planned for the experiment, as well as flexibility in how the detectors are operated, will allow us to maximize the low-mass reach, and understand the backgrounds that the experiment will encounter. In conclusion, upgrades to the experiment, perhaps with a variety of ultra-low-background cryogenic detectors, will extend dark matter sensitivity down to the “neutrino floor,” where coherent scatters of solar neutrinos become a limiting background.« less

Bioactivation of cinnamic alcohol forms several strong skin sensitizers.

PubMed

Niklasson, Ida B; Ponting, David J; Luthman, Kristina; Karlberg, Ann-Therese

2014-04-21

Cinnamic alcohol is a frequent contact allergen, causing allergic contact dermatitis (ACD) in a substantial number of individuals sensitized from contacts with fragrances. Hence, cinnamic alcohol is one of the constituents in fragrance mix I (FM I) used for screening contact allergy in dermatitis patients. Cinnamic alcohol lacks structural alerts for protein reactivity and must therefore be activated by either air oxidation or bioactivation to be able to act as a sensitizer. In the present study, we explored the bioactivation of cinnamic alcohol using human liver microsomes (HLM), and the potential pathways for these reactions were modeled by in silico (DFT) techniques. Subsequently, the reactivity of cinnamic alcohol and its metabolites toward a model hexapeptide were investigated. In addition to cinnamic aldehyde and cinnamic acid, two highly sensitizing epoxides previously unobserved in studies of bioactivation were detected in the incubations with HLMs. Formation of epoxy cinnamic aldehyde was shown (both by the liver microsomal experiments, in which no depletion of epoxy cinnamic alcohol was observed after initial formation, and by the very high activation energy found for the oxidation thereof by calculations) to proceed via cinnamic aldehyde and not epoxy cinnamic alcohol.

Reduction of renal mass is lethal in mice lacking vimentin. Role of endothelin-nitric oxide imbalance.

PubMed Central

Terzi, F; Henrion, D; Colucci-Guyon, E; Federici, P; Babinet, C; Levy, B I; Briand, P; Friedlander, G

1997-01-01

Modulation of vascular tone by chemical and mechanical stimuli is a crucial adaptive phenomenon which involves cytoskeleton elements. Disruption, by homologous recombination, of the gene encoding vimentin, a class III intermediate filament protein mainly expressed in vascular cells, was reported to result in apparently normal phenotype under physiological conditions. In this study, we evaluated whether the lack of vimentin affects vascular adaptation to pathological situations, such as reduction of renal mass, a pathological condition which usually results in immediate and sustained vasodilation of the renal vascular bed. Ablation of 3/4 of renal mass was constantly lethal within 72 h in mice lacking vimentin (Vim-/-), whereas no lethality was observed in wild-type littermates. Death in Vim-/- mice resulted from end-stage renal failure. Kidneys from Vim-/- mice synthesized more endothelin, but less nitric oxide (NO), than kidneys from normal animals. In vitro, renal resistance arteries from Vim-/- mice were selectively more sensitive to endothelin, less responsive to NO-dependent vasodilators, and exhibited an impaired flow (shear stress)- induced vasodilation, which is NO dependent, as compared with those from normal littermates. Finally, in vivo administration of bosentan, an endothelin receptor antagonist, totally prevented lethality in Vim-/- mice. These results suggest that vimentin plays a key role in the modulation of vascular tone, possibly via the tuning of endothelin-nitric oxide balance. PMID:9294120

On the role of budget sufficiency, cost efficiency, and uncertainty in species management

USGS Publications Warehouse

van der Burg, Max Post; Bly, Bartholomew B.; Vercauteren, Tammy; Grand, James B.; Tyre, Andrew J.

2014-01-01

Many conservation planning frameworks rely on the assumption that one should prioritize locations for management actions based on the highest predicted conservation value (i.e., abundance, occupancy). This strategy may underperform relative to the expected outcome if one is working with a limited budget or the predicted responses are uncertain. Yet, cost and tolerance to uncertainty rarely become part of species management plans. We used field data and predictive models to simulate a decision problem involving western burrowing owls (Athene cunicularia hypugaea) using prairie dog colonies (Cynomys ludovicianus) in western Nebraska. We considered 2 species management strategies: one maximized abundance and the other maximized abundance in a cost-efficient way. We then used heuristic decision algorithms to compare the 2 strategies in terms of how well they met a hypothetical conservation objective. Finally, we performed an info-gap decision analysis to determine how these strategies performed under different budget constraints and uncertainty about owl response. Our results suggested that when budgets were sufficient to manage all sites, the maximizing strategy was optimal and suggested investing more in expensive actions. This pattern persisted for restricted budgets up to approximately 50% of the sufficient budget. Below this budget, the cost-efficient strategy was optimal and suggested investing in cheaper actions. When uncertainty in the expected responses was introduced, the strategy that maximized abundance remained robust under a sufficient budget. Reducing the budget induced a slight trade-off between expected performance and robustness, which suggested that the most robust strategy depended both on one's budget and tolerance to uncertainty. Our results suggest that wildlife managers should explicitly account for budget limitations and be realistic about their expected levels of performance.

Expert Consensus Statement on achieving self-sufficiency in safe blood and blood products, based on voluntary non-remunerated blood donation (VNRBD).

PubMed

2012-11-01

All countries face challenges in making sufficient supplies of blood and blood products available and sustainable, while also ensuring the quality and safety of these products in the face of known and emerging threats to public health. Since 1975, the World Health Assembly (WHA) has highlighted the global need for blood safety and availability. WHA resolutions 63·12, 58·13 and 28·72, The Melbourne Declaration on 100% Voluntary Non-Remunerated Donation of Blood and Blood Components and WHO Global Blood Safety Network recommendations have reaffirmed the achievement of 'Self-sufficiency in blood and blood products based on voluntary non-remunerated blood donation (VNRBD)' as the important national policy direction for ensuring a safe, secure and sufficient supply of blood and blood products, including labile blood components and plasma-derived medicinal products. Despite some successes, self-sufficiency is not yet a reality in many countries. A consultation of experts, convened by the World Health Organization (WHO) in September 2011 in Geneva, Switzerland, addressed the urgent need to establish strategies and mechanisms for achieving self-sufficiency. Information on the current situation, and country perspectives and experiences were shared. Factors influencing the global implementation of self-sufficiency, including safety, ethics, security and sustainability of supply, trade and its potential impact on public health, availability and access for patients, were analysed to define strategies and mechanisms and provide practical guidance on achieving self-sufficiency. Experts developed a consensus statement outlining the rationale and definition of self-sufficiency in safe blood and blood products based on VNRBD and made recommendations to national health authorities and WHO. © 2012 World Health Organization. Vox Sanguinis © 2012 International Society of Blood Transfusion.

Comparison of 72-hour fecal fat quantification and the 13C-mixed triglyceride breath test in assessing pancreatic exocrine sufficiency in children with chronic pancreatitis.

PubMed

Wejnarska, Karolina; Kołodziejczyk, Elwira; Ryżko, Józef; Oracz, Grzegorz

Chronic pancreatitis (CP) in children is still a rare, although increasingly recognized entity. Over the duration of the disease several complications can be observed, two of which are major ones: endo- and exocrine insufficiency. In the medical care of children with CP it is crucial to diagnose the decreased endo- and exocrine function of the pancreas, in order to preserve patients from malnutrition and the failure to thrive. The aim of the study was to compare the usefulness of two indirect methods of assessing the pancreas exocrine function in children with CP. Ninety one patients with CP were enrolled in the study (41 boys, 50 girls, aged 2-17.8 years). Only Patients who had had both the 72-hour fecal fat quantification and the 13C-mixed triglyceride breath test (13C -MTBT) performed were selected. We compared the results of both tests for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) in detecting exocrine pancreatic insufficiency. Out of 91 patients, 12 were diagnosed with exocrine pancreatic insufficiency (EPI). The sensitivity of the fecal fat quantification was 50%, the specificity for the test was 100%. PPV and NPV were 100% and 93%, respectively. 13C-MTBT had the sensitivity of 42% and the specificity of 99%. PPV and NPV for the breath test were of 83% and 92%, respectively. No statistically significant discrepancy between the values obtained was found. Although the 72-hour fecal fat quantification remains the gold standard in detecting EPI, both of the methods that had been investigated were shown to be comparable regarding sensitivity, specificity, PPV and NPV in assessing pancreas exocrine sufficiency in children with CP. Due to the easier execution of the breath test, both for the patient and for medical personnel, its importance may increase.

Henrietta Lacks, HeLa cells, and cell culture contamination.

PubMed

Lucey, Brendan P; Nelson-Rees, Walter A; Hutchins, Grover M

2009-09-01

Henrietta Lacks died in 1951 of an aggressive adenocarcinoma of the cervix. A tissue biopsy obtained for diagnostic evaluation yielded additional tissue for Dr George O. Gey's tissue culture laboratory at Johns Hopkins (Baltimore, Maryland). The cancer cells, now called HeLa cells, grew rapidly in cell culture and became the first human cell line. HeLa cells were used by researchers around the world. However, 20 years after Henrietta Lacks' death, mounting evidence suggested that HeLa cells contaminated and overgrew other cell lines. Cultures, supposedly of tissues such as breast cancer or mouse, proved to be HeLa cells. We describe the history behind the development of HeLa cells, including the first published description of Ms Lacks' autopsy, and the cell culture contamination that resulted. The debate over cell culture contamination began in the 1970s and was not harmonious. Ultimately, the problem was not resolved and it continues today. Finally, we discuss the philosophical implications of the immortal HeLa cell line.

Randomized Controlled Trials Evaluating Effect of Television Advertising on Food Intake in Children: Why Such a Sensitive Topic is Lacking Top-Level Evidence?

PubMed

Gregori, Dario; Ballali, Simonetta; Vecchio, Maria Gabriella; Sciré, Antonella Silvia; Foltran, Francesca; Berchialla, Paola

2014-01-01

The aim of this study was to perform a systematic review of evidence coming from randomized controlled trials (RCT) aimed at assessing the effect of television advertising on food intake in children from 4 to 12 years old. Randomized controlled trials were searched in PubMed database and included if they assessed the effect of direct exposure to television food advertising over the actual energy intake of children. Seven studies out of 2166 fulfilled the inclusion criteria. The association between television advertising and energy intake is based on a very limited set of randomized researches lacking a solid ground of first-level evidence.

Educational achievement and economic self-sufficiency in adults after childhood bacterial meningitis.

PubMed

Roed, Casper; Omland, Lars Haukali; Skinhoj, Peter; Rothman, Kenneth J; Sorensen, Henrik Toft; Obel, Niels

2013-04-24

To our knowledge, no previous study has examined functioning in adult life among persons who had bacterial meningitis in childhood. To study educational achievement and economic self-sufficiency in adults diagnosed as having bacterial meningitis in childhood. Nationwide population-based cohort study using national registries of Danish-born children diagnosed as having meningococcal, pneumococcal, or Haemophilus influenzae meningitis in the period 1977-2007 (n=2784 patients). Comparison cohorts from the same population individually matched on age and sex were identified, as were siblings of all study participants. End of study period was 2010. Cumulative incidences of completed vocational education, high school education, higher education, time to first full year of economic self-sufficiency, and receipt of disability pension and differences in these outcomes at age 35 years among meningitis patients, comparison cohorts, and siblings. By age 35 years, among persons who had a history of childhood meningococcal (n=1338), pneumococcal (n=455), and H. influenzae (n=991) meningitis, an estimated 11.0% (41.5% vs 52.5%; 95% CI, 7.3%-14.7%), 10.2% (42.6% vs 52.8%; 95% CI, 3.8%-16.6%), and 5.5% (47.7% vs 53.2%; 95% CI, 1.9%-9.1%) fewer persons, respectively, had completed high school and 7.9% (29.3% vs 37.2%; 95% CI, 1.6%-14.2%), 8.9% (28.1% vs 37.0%; 95% CI, 0.6%-17.2%), and 6.5% (33.5% vs 40.0%; 95% CI, 1.4%-11.6%) fewer had attained a higher education compared with individuals from the comparison cohort. Siblings of meningococcal meningitis patients also had lower educational achievements, while educational achievements of siblings of pneumococcal and H. influenzae meningitis patients did not differ substantially from those in the general population. At end of follow-up, 3.8% (90.3% vs 94.1%; 95% CI, 1.1%-6.5%), 10.6% (84.0% vs 94.6%; 95% CI, 5.1%-16.1%), and 4.3% (90.6% vs 94.9%; 95% CI, 2.0%-6.6%) fewer meningococcal, pneumococcal, and H. influenzae meningitis patients

Behavioral Control and Reward Sensitivity in Adolescents' Risk Taking Behavior: A Longitudinal TRAILS Study.

PubMed

Peeters, Margot; Oldehinkel, Tineke; Vollebergh, Wilma

2017-01-01

Neurodevelopmental theories of risk behavior hypothesize that low behavioral control in combination with high reward sensitivity explains adolescents' risk behavior. However, empirical studies examining this hypothesis while including actual risk taking behavior in adolescence are lacking. In this study we tested whether the imbalance between behavioral control and reward sensitivity underlies risk taking behavior in adolescence, using a nationally representative longitudinal sample of 715 adolescents, of which 66% revealed an increased risk for mental health problems. To assess behavioral control at age 11 we used both self-report (effortful control) as well as behavioral measures of cognitive control (i.e., working memory and response inhibition). Reward sensitivity was assessed with the Bangor Gambling Task. The main finding of this study was that effortful control at age 11 was the best predictor of risk taking behavior (alcohol and cannabis use) at age 16, particularly among adolescents who were more reward sensitive. Risk taking behavior in adolescents might be explained by relatively weak behavioral control functioning combined with high sensitivity for reward.

41 CFR 102-5.95 - Is the comfort and/or convenience of an employee considered sufficient justification to authorize...

Code of Federal Regulations, 2010 CFR

2010-07-01

... convenience of an employee considered sufficient justification to authorize home-to-work transportation? 102-5...-to-Work Transportation § 102-5.95 Is the comfort and/or convenience of an employee considered sufficient justification to authorize home-to-work transportation? No, the comfort and/or convenience of an...

The Insensitive Ruins It All: Compositional and Compilational Influences of Social Sensitivity on Collective Intelligence in Groups.

PubMed

Meslec, Nicoleta; Aggarwal, Ishani; Curseu, Petru L

2016-01-01

A group's collective intelligence reflects its capacity to perform well across a variety of cognitive tasks and it transcends the individual intelligence of its members. Previous research shows that group members' social sensitivity is a potential antecedent of collective intelligence, yet it is still unclear whether individual or group-level indices are responsible for the positive association between social sensitivity and collective intelligence. In a comprehensive manner, we test the extent to which both compositional (lowest and highest individual score) and compilational aspects (emergent group level) of social sensitivity are associated with collective intelligence. This study has implications for research that explores groups as information processors, and for group design as it indicates how a group should be composed with respect to social sensitivity if the group is to reach high levels of collective intelligence. Our empirical results indicate that collectively intelligent groups are those in which the least socially sensitive group member has a rather high score on social sensitivity. Differently stated, (socially sensitive) group members cannot compensate for the lack of social sensitivity of the other group members.

Maximizing Health or Sufficient Capability in Economic Evaluation? A Methodological Experiment of Treatment for Drug Addiction.

PubMed

Goranitis, Ilias; Coast, Joanna; Day, Ed; Copello, Alex; Freemantle, Nick; Frew, Emma

2017-07-01

Conventional practice within the United Kingdom and beyond is to conduct economic evaluations with "health" as evaluative space and "health maximization" as the decision-making rule. However, there is increasing recognition that this evaluative framework may not always be appropriate, and this is particularly the case within public health and social care contexts. This article presents a methodological case study designed to explore the impact of changing the evaluative space within an economic evaluation from health to capability well-being and the decision-making rule from health maximization to the maximization of sufficient capability. Capability well-being is an evaluative space grounded on Amartya Sen's capability approach and assesses well-being based on individuals' ability to do and be the things they value in life. Sufficient capability is an egalitarian approach to decision making that aims to ensure everyone in society achieves a normatively sufficient level of capability well-being. The case study is treatment for drug addiction, and the cost-effectiveness of 2 psychological interventions relative to usual care is assessed using data from a pilot trial. Analyses are undertaken from a health care and a government perspective. For the purpose of the study, quality-adjusted life years (measured using the EQ-5D-5L) and years of full capability equivalent and years of sufficient capability equivalent (both measured using the ICECAP-A [ICEpop CAPability measure for Adults]) are estimated. The study concludes that different evaluative spaces and decision-making rules have the potential to offer opposing treatment recommendations. The implications for policy makers are discussed.

Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway.

PubMed

Follansbee, Taylor L; Gjelsvik, Kayla J; Brann, Courtney L; McParland, Aidan L; Longhurst, Colin A; Galko, Michael J; Ganter, Geoffrey K

2017-08-30

Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a

Micro-resonator-based electric field sensors with long durations of sensitivity

NASA Astrophysics Data System (ADS)

Ali, Amir R.

2017-05-01

In this paper, we present a new fabrication method for the whispering gallery mode (WGM) micro-sphere based electric field sensor that which allows for longer time periods of sensitivity. Recently, a WGM-based photonic electric field sensor was proposed using a coupled dielectric microsphere-beam. The external electric field imposes an electrtrostriction force on the dielectric beam, deflecting it. The beam, in turn compresses the sphere causing a shift in its WGM. As part of the fabrication process, the PDMS micro-beams and the spheres are curied at high-temperature (100oC) and subsequently poled by exposing to strong external electric field ( 8 MV/m) for two hours. The poling process allows for the deposition of surface charges thereby increasing the electrostriction effect. This methodology is called curing-then-poling (CTP). Although the sensors do become sufficiently sensitive to electric field, they start de-poling after a short period (within 10 minutes) after poling, hence losing sensitivity. In an attempt to mitigate this problem and to lock the polarization for a longer period, we use an alternate methodology whereby the beam is poled and cured simultaneously (curing-while-poling or CWP). The new fabrication method allows for the retention of polarization (and hence, sensitivity to electric field) longer ( 1500 minutes). An analysis is carried out along with preliminary experiments. Results show that electric fields as small as 100 V/m can be detected with a 300 μm diameter sphere sensor a day after poling.

Human melanomas and ovarian cancers overexpressing mechanical barrier molecule genes lack immune signatures and have increased patient mortality risk

PubMed Central

Salerno, Elise P.; Bedognetti, Davide; Mauldin, Ileana S.; Deacon, Donna H.; Shea, Sofia M.; Obeid, Joseph M.; Coukos, George; Gajewski, Thomas F.; Marincola, Francesco M.; Slingluff, Craig L.

2016-01-01

ABSTRACT We have identified eight genes whose expression in human melanoma metastases and ovarian cancers is associated with a lack of Th1 immune signatures. They encode molecules with mechanical barrier function in the skin and other normal tissues and include filaggrin (FLG), tumor-associated calcium signal transducer 2 (TACSTD2), and six desmosomal proteins (DST, DSC3, DSP, PPL, PKP3, and JUP). This association has been validated in an independent series of 114 melanoma metastases. In these, DST expression alone is sufficient to identify melanomas without immune signatures, while FLG and the other six putative barrier molecules are overexpressed in a different subset of melanomas lacking immune signatures. Similar associations have been identified in a set of 186 ovarian cancers. RNA-seq data from 471 melanomas and 307 ovarian cancers in the TCGA database further support these findings and also reveal that overexpression of barrier molecules is strongly associated with early patient mortality for melanoma (p = 0.0002) and for ovarian cancer (p < 0.01). Interestingly, this association persists for FLG for melanoma (p = 0.012) and ovarian cancer (p = 0.006), whereas DST overexpression is negatively associated with CD8+ gene expression, but not with patient survival. Thus, overexpression of FLG or DST identifies two distinct patient populations with low immune cell infiltration in these cancers, but with different prognostic implications for each. These data raise the possibility that molecules with mechanical barrier function in skin and other tissues may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction. PMID:28123876

Reliability of the Colorado Family Support Assessment: A Self-Sufficiency Matrix for Families

ERIC Educational Resources Information Center

Richmond, Melissa K.; Pampel, Fred C.; Zarcula, Flavia; Howey, Virginia; McChesney, Brenda

2017-01-01

Purpose: Family support programs commonly use self-sufficiency matrices (SSMs) to measure family outcomes, however, validation research on SSMs is sparse. This study examined the reliability of the Colorado Family Support Assessment 2.0 (CFSA 2.0) to measure family self-reliance across 14 domains (e.g., employment). Methods: Ten written case…

The criterion of subscale sufficiency and its application to the relationship between static capillary pressure, saturation and interfacial areas.

PubMed

Kurzeja, Patrick

2016-05-01

Modern imaging techniques, increased simulation capabilities and extended theoretical frameworks, naturally drive the development of multiscale modelling by the question: which new information should be considered? Given the need for concise constitutive relationships and efficient data evaluation; however, one important question is often neglected: which information is sufficient? For this reason, this work introduces the formalized criterion of subscale sufficiency. This criterion states whether a chosen constitutive relationship transfers all necessary information from micro to macroscale within a multiscale framework. It further provides a scheme to improve constitutive relationships. Direct application to static capillary pressure demonstrates usefulness and conditions for subscale sufficiency of saturation and interfacial areas.

The criterion of subscale sufficiency and its application to the relationship between static capillary pressure, saturation and interfacial areas

PubMed Central

2016-01-01

Modern imaging techniques, increased simulation capabilities and extended theoretical frameworks, naturally drive the development of multiscale modelling by the question: which new information should be considered? Given the need for concise constitutive relationships and efficient data evaluation; however, one important question is often neglected: which information is sufficient? For this reason, this work introduces the formalized criterion of subscale sufficiency. This criterion states whether a chosen constitutive relationship transfers all necessary information from micro to macroscale within a multiscale framework. It further provides a scheme to improve constitutive relationships. Direct application to static capillary pressure demonstrates usefulness and conditions for subscale sufficiency of saturation and interfacial areas. PMID:27279769

Paraneoplastic autoantibody panels: sensitivity and specificity, a retrospective cohort.

PubMed

Albadareen, Rawan; Gronseth, Gary; Goeden, Marcie; Sharrock, Matthew; Lechtenberg, Colleen; Wang, Yunxia

2017-06-01

Experts in the autoimmune paraneoplastic field recommend autoantibody testing as "panels" to improve the poor sensitivity of individual autoantibodies in detecting paraneoplastic neurological syndromes (PNS). The sensitivity of those panels was not reported to date in a fashion devoid of incorporation bias. We aimed to assess the collective sensitivity and specificity of one of the commonly used panels in detecting PNS. A single-centered retrospective cohort of all patients tested for paraneoplastic evaluation panel (PAVAL; test ID: 83380) over one year for the suspicion of PNS. Case adjudication was based on newly proposed diagnostic criteria in line with previously published literature, but modified to exclude serological status to avoid incorporation bias. Measures of diagnostic accuracy were subsequently calculated. Cases that failed to show association with malignancy within the follow-up time studied, reflecting a possibly pure autoimmune process was considered paraneoplastic-like syndromes. Out of 321 patients tested, 51 patients tested positive. Thirty-two patients met diagnostic criteria for paraneoplastic/paraneoplastic-like syndromes. The calculated collective sensitivity was 34% (95% CI: 17-53), specificity was 86% (95% CI: 81-90), Youden's index 0.2 and a positive clinical utility index 0.07 suggesting poor utility for case-detection. This is the first reported diagnostic accuracy measures of paraneoplastic panels without incorporation bias. Despite recommended panel testing to improve detection of PNS, sensitivity remains low with poor utility for case-detection. The high-calculated specificity suggests a possible role in confirming the condition in difficult cases suspicious for PNS, when enough supportive evidence is lacking on ancillary testing.

New insights into the column CH2O/NO2 ratio as an indicator of near-surface ozone sensitivity

NASA Astrophysics Data System (ADS)

Schroeder, Jason R.; Crawford, James H.; Fried, Alan; Walega, James; Weinheimer, Andrew; Wisthaler, Armin; Müller, Markus; Mikoviny, Tomas; Chen, Gao; Shook, Michael; Blake, Donald R.; Tonnesen, Gail S.

2017-08-01

Satellite-based measurements of the column CH2O/NO2 ratio have previously been used to estimate near-surface ozone (O3) sensitivity (i.e., NOx or VOC limited), and the forthcoming launch of air quality-focused geostationary satellites provides a catalyst for reevaluating the ability of satellite-measured CH2O/NO2 to be used in this manner. In this study, we use a 0-D photochemical box model to evaluate O3 sensitivity and find that the relative rate of radical termination from radical-radical interactions to radical-NOx interactions (referred to as LROx/LNOx) provides a good indicator of maximum O3 production along NOx ridgelines. Using airborne measurements from NASA's Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relative to Air Quality (DISCOVER-AQ) deployments in Colorado, Maryland, and Houston, we show that in situ measurements of CH2O/NO2 can be used to indicate O3 sensitivity, but there is an important "transition/ambiguous" range whereby CH2O/NO2 fails to categorize O3 sensitivity, and the range and span of this transition/ambiguous range varies regionally. Then, we apply these findings to aircraft-derived column density measurements from DISCOVER-AQ and find that inhomogeneities in vertical mixing in the lower troposphere further degrades the ability of column CH2O/NO2 to indicate near-surface O3 sensitivity (i.e., the transition/ambiguous range is much larger than indicated by in situ data alone), and we hypothesize that the global transition/ambiguous range is sufficiently large to make the column CH2O/NO2 ratio unuseful for classifying near-surface O3 sensitivity. Lastly, we present a case study from DISCOVER-AQ-Houston that suggests that O3 sensitivity on exceedance days may be substantially different than on nonexceedance days (which may be observable from space) and explore the diurnal evolution of O3 sensitivity, O3 production, and the column CH2O/NO2 ratio. The results of these studies suggest that

Mouse neutrophils lacking lamin B receptor expression exhibit aberrant development and lack critical functional responses

PubMed Central

Gaines, Peter; Tien, Chiung W.; Olins, Ada L.; Olins, Donald E.; Shultz, Leonard D.; Carney, Lisa; Berliner, Nancy

2008-01-01

Objective The capacity of neutrophils to eradicate bacterial infections is dependent on normal development and the activation of functional responses, which include chemotaxis and the generation of oxygen radicals during the respiratory burst. A unique feature of the neutrophil is its highly lobulated nucleus, which is thought to facilitate chemotaxis but may also play a role in other critical neutrophil functions. Nuclear lobulation is dependent on the expression of the inner nuclear envelope protein, the lamin B receptor (LBR), mutations of which cause hypolobulated neutrophil nuclei in human Pelger-Huët anomaly (PHA) and the "ichthyosis" (ic) phenotype in mice. In this study we have investigated roles for LBR in mediating neutrophil development and the activation of multiple neutrophil functions, including chemotaxis and the respiratory burst. Materials and Methods A progenitor EML cell line was generated from an ic/ic mouse, and derived cells that lacked LBR expression were induced to mature neutrophils and then examined for abnormal morphology and functional responses. Results Neutrophils derived from EML-ic/ic cells exhibited nuclear hypolobulation identical to that observed in ichthyosis mice. The ic/ic neutrophils also displayed abnormal chemotaxis, supporting the notion that nuclear segmentation augments neutrophil extravasation. Furthermore, promyelocytic forms of ic/ic cells displayed decreased proliferative responses and produced a deficient respiratory burst upon terminal maturation. Conclusions Our studies of promyelocytes that lack LBR expression have identified roles for LBR in regulating not only the morphologic maturation of the neutrophil nucleus but also proliferative and functional responses that are critical to innate immunity. PMID:18550262

Lack of Association Between Dust Mite Sensitivity and Atopic Dermatitis.

PubMed

Silverberg, Jonathan Ian; Hanifin, Jon M; Law, Sandra; White, Kevin; Storrs, Frances J

2016-01-01

Dust mites (DMs) play a role in type I respiratory allergy. Studies relating to DM irritant versus immune reactions are somewhat conflicting in atopic dermatitis (AD). The aim of this study was to assess the diagnostic use of patch testing to DM in patients with AD and other dermatitides. We performed a prospective study of 323 adults recruited in a patch testing clinic. Patch testing antigens were DM extract (0.01%, 0.1%, 1%, 10%, and 20% in petrolatum; Chemotechnique) and/or 200 index of reactivity in petrolatum (Stallergenes). Patches were placed and read at 48 hours with delayed readings after 72 to 168 hours. There was no association of DM positivity with AD, asthma, hay fever, or demographic factors. There was no association of DM positivity with the clinical diagnosis or phenotype. The number of positive (+, ++, and +++) and doubtful reactions to Chemotechnique DM extract increased with higher concentrations. Positive reactions to DM had a morphological appearance characterized by numerous discrete erythematous papules and, rarely, papulovesicles. Positive reactions to Stallergenes DM 200 IR were infrequent and all weak reactions, similar to DM 0.01%. Patch testing to DM does not seem to have clinical use for determining the etiology of dermatitis.

Bi-anchoring organic sensitizers of type D-(π-A)2 comprising thiophene-2-acetonitrile as π-spacer and malonic acid as electron acceptor for dye sensitized solar cell applications

NASA Astrophysics Data System (ADS)

Reddy, Gachumale Saritha; Ramkumar, Sekar; Asiri, Abdullah M.; Anandan, Sambandam

2015-06-01

Two new bi-anchoring organic sensitizers of type D-(π-A)2 comprising the identical π-spacer (thiophene-2-acetonitrile) and electron acceptor (malonic acid) but different aryl amine as electron donors (diphenylamine and carbazole) were synthesized, characterized and fabricated metal free dye-sensitized solar cell devices. The intra molecular charge transfer property and electrochemical property of these dyes were investigated by molecular absorption, emission, cyclic voltammetric experiments and in addition, quantum chemical calculation studies were performed to provide sufficient driving force for the electron injection into the conduction band of TiO2 which leads to efficient charge collection. Among the fabricated devices, carbazole based device exhibits high current conversion efficiency (η = 4.7%) with a short circuit current density (JSC) 15.3 mA/cm2, an open circuit photo voltage (VOC) of 0.59 V and a fill factor of 0.44 under AM 1.5 illumination (85 mW/cm2) compared to diphenylamine based device.

Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal α-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PubMed Central

Morgan, Rhodri M. L.; Hernández-Ramírez, Laura C.; Trivellin, Giampaolo; Zhou, Lihong; Roe, S. Mark; Korbonits, Márta; Prodromou, Chrisostomos

2012-01-01

Mutations of the aryl hydrocarbon receptor interacting protein (AIP) have been associated with familial isolated pituitary adenomas predisposing to young-onset acromegaly and gigantism. The precise tumorigenic mechanism is not well understood as AIP interacts with a large number of independent proteins as well as three chaperone systems, HSP90, HSP70 and TOMM20. We have determined the structure of the TPR domain of AIP at high resolution, which has allowed a detailed analysis of how disease-associated mutations impact on the structural integrity of the TPR domain. A subset of C-terminal α-7 helix (Cα-7h) mutations, R304* (nonsense mutation), R304Q, Q307* and R325Q, a known site for AhR and PDE4A5 client-protein interaction, occur beyond those that interact with the conserved MEEVD and EDDVE sequences of HSP90 and TOMM20. These C-terminal AIP mutations appear to only disrupt client-protein binding to the Cα-7h, while chaperone binding remains unaffected, suggesting that failure of client-protein interaction with the Cα-7h is sufficient to predispose to pituitary adenoma. We have also identified a molecular switch in the AIP TPR-domain that allows recognition of both the conserved HSP90 motif, MEEVD, and the equivalent sequence (EDDVE) of TOMM20. PMID:23300914

Sensitivity and Specificity of CT and Its signs for Diagnosis of Strangulation in Patients with Acute Small Bowel Obstruction.

PubMed

Jha, Ashwini Kumar; Tang, Wen Hao; Bai, Zhi Bin; Xiao, Jia Quan

2014-01-01

To perform a meta-analysis to review the sensitivity and specificity of computed tomography and different known computed yomography signs for the diagnosis of strangulation in patients with acute small bowel obstruction. A comprehensive Pubmed search was performed for all reports that evaluated the use of CT and discussed different CT criteria for the diagnosis of acute SBO. Articles published in English language from January 1978 to June 2008 were included. Review articles, case reports, pictorial essays and articles without original data were excluded. The bivariate random effect model was used to obtain pooled sensitivity and pooled specificity. Summary receiver operating curve was calculated using Meta-Disc. Software Openbugs 3.0.3 was used to summarize the data. A total of 12 studies fulfilled the inclusion criteria. The pooled sensitivity and specificity of CT in the diagnosis of strangulation was 0.720 (95% CI 0.674 to 0.763) and 0.866 (95% CI 0.837 to 0.892) respectively. Among different CT signs, mesenteric edema had highest Pooled sensitivity of 0. 741 and lack of bowel wall enhancement had highest pooled specificity of 0.991. This review demonstrates that CT is highly sensitive as well as specific in the preoperative diagnosis of strangulation SBO which are in accordance with the published studies. Our analysis also shows that "presence of mesenteric fluid" is most sensitive, and "lack of bowel wall enhancement" is most specific CT sign of strangulation, and also justifies need of large scale prospective studies to validate the results obtained as well as to determine a clinical protocol.

Analysis of DNA methylation in Arabidopsis thaliana based on methylation-sensitive AFLP markers.

PubMed

Cervera, M T; Ruiz-García, L; Martínez-Zapater, J M

2002-12-01

AFLP analysis using restriction enzyme isoschizomers that differ in their sensitivity to methylation of their recognition sites has been used to analyse the methylation state of anonymous CCGG sequences in Arabidopsis thaliana. The technique was modified to improve the quality of fingerprints and to visualise larger numbers of scorable fragments. Sequencing of amplified fragments indicated that detection was generally associated with non-methylation of the cytosine to which the isoschizomer is sensitive. Comparison of EcoRI/ HpaII and EcoRI/ MspI patterns in different ecotypes revealed that 35-43% of CCGG sites were differentially digested by the isoschizomers. Interestingly, the pattern of digestion among different plants belonging to the same ecotype is highly conserved, with the rate of intra-ecotype methylation-sensitive polymorphisms being less than 1%. However, pairwise comparisons of methylation patterns between samples belonging to different ecotypes revealed differences in up to 34% of the methylation-sensitive polymorphisms. The lack of correlation between inter-ecotype similarity matrices based on methylation-insensitive or methylation-sensitive polymorphisms suggests that whatever the mechanisms regulating methylation may be, they are not related to nucleotide sequence variation.

Unlocking Sensitivity for Visibility-based Estimators of the 21 cm Reionization Power Spectrum

NASA Astrophysics Data System (ADS)

Zhang, Yunfan Gerry; Liu, Adrian; Parsons, Aaron R.

2018-01-01

Radio interferometers designed to measure the cosmological 21 cm power spectrum require high sensitivity. Several modern low-frequency interferometers feature drift-scan antennas placed on a regular grid to maximize the number of instantaneously coherent (redundant) measurements. However, even for such maximum-redundancy arrays, significant sensitivity comes through partial coherence between baselines. Current visibility-based power-spectrum pipelines, though shown to ease control of systematics, lack the ability to make use of this partial redundancy. We introduce a method to leverage partial redundancy in such power-spectrum pipelines for drift-scan arrays. Our method cross-multiplies baseline pairs at a time lag and quantifies the sensitivity contributions of each pair of baselines. Using the configurations and beams of the 128-element Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER-128) and staged deployments of the Hydrogen Epoch of Reionization Array, we illustrate how our method applies to different arrays and predict the sensitivity improvements associated with pairing partially coherent baselines. As the number of antennas increases, we find partial redundancy to be of increasing importance in unlocking the full sensitivity of upcoming arrays.

ATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib.

PubMed

Wang, Chen; Jette, Nicholas; Moussienko, Daniel; Bebb, D Gwyn; Lees-Miller, Susan P

2017-04-01

The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Next-generation sequencing of patient tumors has revealed that ATM is altered in many human cancers including colorectal, lung, prostate, and breast. Here, we show that the colorectal cancer cell line SK-CO-1 lacks detectable ATM protein expression and is sensitive to the PARP inhibitor olaparib. Similarly, HCT116 colorectal cancer cells with shRNA depletion of ATM are sensitive to olaparib, and depletion of p53 enhances this sensitivity. Moreover, HCT116 cells are sensitive to olaparib in combination with the ATM inhibitor KU55933, and sensitivity is enhanced by deletion of p53. Together our studies suggest that PARP inhibitors may have potential for treating colorectal cancer with ATM dysfunction and/or colorectal cancer with mutation of p53 when combined with an ATM kinase inhibitor. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Virtual water and water self-sufficiency in agricultural and livestock products in Brazil.

PubMed

da Silva, Vicente de Paulo R; de Oliveira, Sonaly D; Braga, Célia C; Brito, José Ivaldo B; de Sousa, Francisco de Assis S; de Holanda, Romildo M; Campos, João Hugo B C; de Souza, Enio P; Braga, Armando César R; Rodrigues Almeida, Rafaela S; de Araújo, Lincoln E

2016-12-15

Virtual water trade is often considered a solution for restricted water availability in many regions of the world. Brazil is the world leader in the production and export of various agricultural and livestock products. The country is either a strong net importer or a strong net exporter of these products. The objective of this study is to determine the volume of virtual water contained in agricultural and livestock products imported/exported by Brazil from 1997 to 2012, and to define the water self-sufficiency index of agricultural and livestock products in Brazil. The indexes of water scarcity (WSI), water dependency (WDI) and water self-sufficiency (WSSI) were calculated for each Brazilian state. These indexes and the virtual water balance were calculated following the methodology developed by Chapagain and Hoekstra (2008) and Hoekstra and Hung (2005). The total water exports and imports embedded in agricultural and livestock products were 5.28 × 10 10 and 1.22 × 10 10  Gm 3  yr -1 , respectively, which results in positive virtual water balance of 4.05 × 10 10  Gm 3  yr -1 . Brazil is either a strong net importer or a strong net exporter of agricultural and livestock products among the Mercosur countries. Brazil has a positive virtual water balance of 1.85 × 10 10  Gm 3  yr -1 . The indexes used in this study reveal that Brazil is self-sufficient in food production, except for a few products such as wheat and rice. Horticultural products (tomato, onion, potato, cassava and garlic) make up a unique product group with negative virtual water balance in Brazil. Copyright © 2016 Elsevier Ltd. All rights reserved.

Combining Monte Carlo methods with coherent wave optics for the simulation of phase-sensitive X-ray imaging

PubMed Central

Peter, Silvia; Modregger, Peter; Fix, Michael K.; Volken, Werner; Frei, Daniel; Manser, Peter; Stampanoni, Marco

2014-01-01

Phase-sensitive X-ray imaging shows a high sensitivity towards electron density variations, making it well suited for imaging of soft tissue matter. However, there are still open questions about the details of the image formation process. Here, a framework for numerical simulations of phase-sensitive X-ray imaging is presented, which takes both particle- and wave-like properties of X-rays into consideration. A split approach is presented where we combine a Monte Carlo method (MC) based sample part with a wave optics simulation based propagation part, leading to a framework that takes both particle- and wave-like properties into account. The framework can be adapted to different phase-sensitive imaging methods and has been validated through comparisons with experiments for grating interferometry and propagation-based imaging. The validation of the framework shows that the combination of wave optics and MC has been successfully implemented and yields good agreement between measurements and simulations. This demonstrates that the physical processes relevant for developing a deeper understanding of scattering in the context of phase-sensitive imaging are modelled in a sufficiently accurate manner. The framework can be used for the simulation of phase-sensitive X-ray imaging, for instance for the simulation of grating interferometry or propagation-based imaging. PMID:24763652

Co-ordination of early and late ripening events in apples is regulated through differential sensitivities to ethylene

PubMed Central

Johnston, Jason W.; Gunaseelan, Kularajathaven; Pidakala, Paul; Wang, Mindy; Schaffer, Robert J.

2009-01-01

In this study, it is shown that anti-sense suppression of Malus domestica 1-AMINO-CYCLOPROPANE-CARBOXYLASE OXIDASE (MdACO1) resulted in fruit with an ethylene production sufficiently low to be able to assess ripening in the absence of ethylene. Exposure of these fruit to different concentrations of exogenous ethylene showed that flesh softening, volatile biosynthesis, and starch degradation, had differing ethylene sensitivity and dependency. Early ripening events such as the conversion of starch to sugars showed a low dependency for ethylene, but a high sensitivity to low concentrations of ethylene (0.01 μl l−1). By contrast, later ripening events such as flesh softening and ester volatile production showed a high dependency for ethylene but were less sensitive to low concentrations (needing 0.1 μl l−1 for a response). A sustained exposure to ethylene was required to maintain ripening, indicating that the role of ethylene may go beyond that of ripening initiation. These results suggest a conceptual model for the control of individual ripening characters in apple, based on both ethylene dependency and sensitivity. PMID:19429839

Linear stable unity-feedback system - Necessary and sufficient conditions for stability under nonlinear plant perturbations

NASA Technical Reports Server (NTRS)

Desoer, C. A.; Kabuli, M. G.

1989-01-01

The authors consider a linear (not necessarily time-invariant) stable unity-feedback system, where the plant and the compensator have normalized right-coprime factorizations. They study two cases of nonlinear plant perturbations (additive and feedback), with four subcases resulting from: (1) allowing exogenous input to Delta P or not; 2) allowing the observation of the output of Delta P or not. The plant perturbation Delta P is not required to be stable. Using the factorization approach, the authors obtain necessary and sufficient conditions for all cases in terms of two pairs of nonlinear pseudostate maps. Simple physical considerations explain the form of these necessary and sufficient conditions. Finally, the authors obtain the characterization of all perturbations Delta P for which the perturbed system remains stable.

Aging of Non-Visual Spectral Sensitivity to Light in Humans: Compensatory Mechanisms?

PubMed Central

Najjar, Raymond P.; Chiquet, Christophe; Teikari, Petteri; Cornut, Pierre-Loïc; Claustrat, Bruno; Denis, Philippe; Gronfier, Claude

2014-01-01

The deterioration of sleep in the older population is a prevalent feature that contributes to a decrease in quality of life. Inappropriate entrainment of the circadian clock by light is considered to contribute to the alteration of sleep structure and circadian rhythms in the elderly. The present study investigates the effects of aging on non-visual spectral sensitivity to light and tests the hypothesis that circadian disturbances are related to a decreased light transmittance. In a within-subject design, eight aged and five young subjects were exposed at night to 60 minute monochromatic light stimulations at 9 different wavelengths (420–620 nm). Individual sensitivity spectra were derived from measures of melatonin suppression. Lens density was assessed using a validated psychophysical technique. Although lens transmittance was decreased for short wavelength light in the older participants, melatonin suppression was not reduced. Peak of non-visual sensitivity was, however, shifted to longer wavelengths in the aged participants (494 nm) compared to young (484 nm). Our results indicate that increased lens filtering does not necessarily lead to a decreased non-visual sensitivity to light. The lack of age-related decrease in non-visual sensitivity to light may involve as yet undefined adaptive mechanisms. PMID:24465738

Fast and sensitive taxonomic classification for metagenomics with Kaiju

PubMed Central

Menzel, Peter; Ng, Kim Lee; Krogh, Anders

2016-01-01

Metagenomics emerged as an important field of research not only in microbial ecology but also for human health and disease, and metagenomic studies are performed on increasingly larger scales. While recent taxonomic classification programs achieve high speed by comparing genomic k-mers, they often lack sensitivity for overcoming evolutionary divergence, so that large fractions of the metagenomic reads remain unclassified. Here we present the novel metagenome classifier Kaiju, which finds maximum (in-)exact matches on the protein-level using the Burrows–Wheeler transform. We show in a genome exclusion benchmark that Kaiju classifies reads with higher sensitivity and similar precision compared with current k-mer-based classifiers, especially in genera that are underrepresented in reference databases. We also demonstrate that Kaiju classifies up to 10 times more reads in real metagenomes. Kaiju can process millions of reads per minute and can run on a standard PC. Source code and web server are available at http://kaiju.binf.ku.dk. PMID:27071849

Fast and sensitive taxonomic classification for metagenomics with Kaiju.

PubMed

Menzel, Peter; Ng, Kim Lee; Krogh, Anders

2016-04-13

Metagenomics emerged as an important field of research not only in microbial ecology but also for human health and disease, and metagenomic studies are performed on increasingly larger scales. While recent taxonomic classification programs achieve high speed by comparing genomic k-mers, they often lack sensitivity for overcoming evolutionary divergence, so that large fractions of the metagenomic reads remain unclassified. Here we present the novel metagenome classifier Kaiju, which finds maximum (in-)exact matches on the protein-level using the Burrows-Wheeler transform. We show in a genome exclusion benchmark that Kaiju classifies reads with higher sensitivity and similar precision compared with current k-mer-based classifiers, especially in genera that are underrepresented in reference databases. We also demonstrate that Kaiju classifies up to 10 times more reads in real metagenomes. Kaiju can process millions of reads per minute and can run on a standard PC. Source code and web server are available at http://kaiju.binf.ku.dk.

Quantified Objectives for Assessing the Contribution of Low Clouds to Climate Sensitivity and Variability

NASA Astrophysics Data System (ADS)

Del Genio, A. D.; Platnick, S. E.; Bennartz, R.; Klein, S. A.; Marchand, R.; Oreopoulos, L.; Pincus, R.; Wood, R.

2016-12-01

Low clouds are central to leading-order questions in climate and subseasonal weather predictability, and are key to the NRC panel report's goals "to understand the signals of the Earth system under a changing climate" and "for improved models and model projections." To achieve both goals requires a mix of continuity observations to document the components of the changing climate and improvements in retrievals of low cloud and boundary layer dynamical/thermodynamic properties to ensure process-oriented observations that constrain the parameterized physics of the models. We discuss four climate/weather objectives that depend sensitively on understanding the behavior of low clouds: 1. Reduce uncertainty in GCM-inferred climate sensitivity by 50% by constraining subtropical low cloud feedbacks. 2. Eliminate the GCM Southern Ocean shortwave flux bias and its effect on cloud feedback and the position of the midlatitude storm track. 3. Eliminate the double Intertropical Convergence Zone bias in GCMs and its potential effects on tropical precipitation over land and the simulation and prediction of El Niño. 4. Increase the subseasonal predictability of tropical warm pool precipitation from 20 to 30 days. We envision advances in three categories of observations that would be highly beneficial for reaching these goals: 1. More accurate observations will facilitate more thorough evaluation of clouds in GCMs. 2. Better observations of the links between cloud properties and the environmental state will be used as the foundation for parameterization improvements. 3. Sufficiently long and higher quality records of cloud properties and environmental state will constrain low cloud feedback purely observationally. To accomplish this, the greatest need is to replace A-Train instruments, which are nearing end-of-life, with enhanced versions. The requirements are sufficient horizontal and vertical resolution to capture boundary layer cloud and thermodynamic spatial structure; more

The sensitivity and specificity of thermometry and plethysmography in the assessment of hand-arm vibration syndrome.

PubMed

Thompson, Aaron; House, Ron; Manno, Michael

2008-05-01

Finger plethysmography and thermometry are objective measures used to assess the vascular aspect of hand-arm vibration syndrome (HAVS). Research to date shows poor correlation between these tests and Stockholm Workshop Scale (SWS) vascular stage. Clinicians, researchers and compensation boards require objective means to diagnose and quantify HAVS. To define the specificity and sensitivity of thermometry and plethysmography using the SWS as the reference criterion. A secondary goal was to consider cut points for the tests optimizing sensitivity and specificity. A cross-sectional analysis was conducted on HAVS patients seen at an occupational medicine specialty clinic. Plethysmography and thermometry were analyzed using SWS vascular stage as the outcome variable. Logistic regression controlled for age, smoking and time since last vibration exposure and use of vasoactive medications. The sensitivity and specificity of the combined tests were calculated using varying cut points. A total of 139 patients consented to participate in the study. Plethysmography stage 1 or greater showed the highest sensitivity (sensitivity 94% and specificity 15%). Specificity was optimized combining plethysmography stage 3 and thermometry stage 3 (specificity 98% and sensitivity 23%). Maximal diagnostic accuracy was achieved by plethysmography alone setting the criteria for a positive test as being stage 1 or greater (70%). Neither plethysmography nor thermometry either alone or in combination demonstrated sufficient sensitivity and specificity to serve as an objective correlate for SWS vascular stage. All combinations of plethysmography and thermometry showed a lower specificity than sensitivity indicating that the SWS may be less sensitive in detecting vascular pathology than the objective tests.

Drinking sucrose or saccharin enhances sensitivity of rats to quinpirole-induced yawning

PubMed Central

Serafine, Katherine M; Bentley, Todd A; Kilborn, Dylan J; Koek, Wouter; France, Charles P

2015-01-01

Diet can impact sensitivity of rats to some of the behavioral effects of drugs acting on dopamine systems. The current study tested whether continuous access to sucrose is necessary to increase yawning induced by the dopamine receptor agonist quinpirole, or if intermittent access is sufficient. These studies also tested whether sensitivity to quinpirole-induced yawning increases in rats drinking the non-caloric sweetener saccharin. Dose-response curves (0.0032–0.32 mg/kg) for quinpirole-induced yawning were determined once weekly in rats with free access to standard chow and either continuous access to water, 10% sucrose solution, or 0.1% saccharin solution, or intermittent access to sucrose or saccharin (i.e., 2 days per week with access to water on other days). Cumulative doses of quinpirole increased then decreased yawning, resulting in an inverted U-shaped dose-response curve. Continuous or intermittent access to sucrose enhanced sensitivity to quinpirole-induced yawning. Continuous, but not intermittent, access to saccharin also enhanced sensitivity to quinpirole-induced yawning. In all groups, pretreatment with the selective D3 receptor antagonist PG 01037 shifted the ascending limb of the quinpirole dose-response curve to the right, while pretreatment with the selective D2 receptor antagonist L-741626 shifted the descending limb to the right. These results suggest that even intermittent consumption of diets containing highly palatable substances (e.g. sucrose) alters sensitivity to drugs acting on dopamine systems in a manner that could be important in vulnerability to abuse drugs. PMID:26189020

Crossmodal semantic priming by naturalistic sounds and spoken words enhances visual sensitivity.

PubMed

Chen, Yi-Chuan; Spence, Charles

2011-10-01

We propose a multisensory framework based on Glaser and Glaser's (1989) general reading-naming interference model to account for the semantic priming effect by naturalistic sounds and spoken words on visual picture sensitivity. Four experiments were designed to investigate two key issues: First, can auditory stimuli enhance visual sensitivity when the sound leads the picture as well as when they are presented simultaneously? And, second, do naturalistic sounds (e.g., a dog's "woofing") and spoken words (e.g., /dɔg/) elicit similar semantic priming effects? Here, we estimated participants' sensitivity and response criterion using signal detection theory in a picture detection task. The results demonstrate that naturalistic sounds enhanced visual sensitivity when the onset of the sounds led that of the picture by 346 ms (but not when the sounds led the pictures by 173 ms, nor when they were presented simultaneously, Experiments 1-3A). At the same SOA, however, spoken words did not induce semantic priming effects on visual detection sensitivity (Experiments 3B and 4A). When using a dual picture detection/identification task, both kinds of auditory stimulus induced a similar semantic priming effect (Experiment 4B). Therefore, we suggest that there needs to be sufficient processing time for the auditory stimulus to access its associated meaning to modulate visual perception. Besides, the interactions between pictures and the two types of sounds depend not only on their processing route to access semantic representations, but also on the response to be made to fulfill the requirements of the task.

A Phenomenological Study on Lack of Motivation

ERIC Educational Resources Information Center

Educational Research and Reviews, 2013

2013-01-01

The aim of this research is to point out the underlying reasons about the lack of motivation at academic activities concerning Attribution Theory. Attribution Theory trys to understand how the people answer "why" question and how they do casual explanations. This research is a qualitative based research. It used the phenomenological…

ADC Mothers Reach Self-Sufficiency through Comprehensive Support and Family Development Services Program.

ERIC Educational Resources Information Center

Randolph, Gayle C., II; McCarthy, Karen V.

Families whose primary or sole means of financial support is derived from the welfare system are attempting to meet immediate survival needs in the same manner as families outside of the system. Project Self-Sufficiency is a program which dedicates time to building trusting relationships based on mutual respect and the belief that, with support,…

Retrocausal Effects as a Consequence of Quantum Mechanics Refined to Accommodate the Principle of Sufficient Reason

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

Stapp, Henry P.

2011-05-10

The principle of sufficient reason asserts that anything that happens does so for a reason: no definite state of affairs can come into being unless there is a sufficient reason why that particular thing should happen. This principle is usually attributed to Leibniz, although the first recorded Western philosopher to use it was Anaximander of Miletus. The demand that nature be rational, in the sense that it be compatible with the principle of sufficient reason, conflicts with a basic feature of contemporary orthodox physical theory, namely the notion that nature's response to the probing action of an observer is determinedmore » by pure chance, and hence on the basis of absolutely no reason at all. This appeal to pure chance can be deemed to have no rational fundamental place in reason-based Western science. It is argued here, on the basis of the other basic principles of quantum physics, that in a world that conforms to the principle of sufficient reason, the usual quantum statistical rules will naturally emerge at the pragmatic level, in cases where the reason behind nature's choice of response is unknown, but that the usual statistics can become biased in an empirically manifest way when the reason for the choice is empirically identifiable. It is shown here that if the statistical laws of quantum mechanics were to be biased in this way then the basically forward-in-time unfolding of empirical reality described by orthodox quantum mechanics would generate the appearances of backward-time-effects of the kind that have been reported in the scientific literature.« less

Loss of histochemical identity in mast cells lacking carboxypeptidase A.

PubMed

Feyerabend, Thorsten B; Hausser, Heinz; Tietz, Annette; Blum, Carmen; Hellman, Lars; Straus, Anita H; Takahashi, Hélio K; Morgan, Ellen S; Dvorak, Ann M; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2005-07-01

Mast cell carboxypeptidase A (Mc-cpa) is a highly conserved secretory granule protease. The onset of expression in mast cell progenitors and lineage specificity suggest an important role for Mc-cpa in mast cells. To address the function of Mc-cpa, we generated Mc-cpa-null mice. Mc-cpa-/- mast cells lacked carboxypeptidase activity, revealing that Mc-cpa is a nonredundant enzyme. While Mc-cpa-/- peritoneal mast cells were ultrastructurally normal and synthesized normal amounts of heparin, they displayed striking histochemical and biochemical hallmarks of immature mast cells. Wild-type peritoneal mast cells had a mature phenotype characterized by differential histochemical staining with proteoglycan-reactive dyes (cells do not stain with alcian blue but stain with safranin and with berberine) and a high side scatter to forward scatter ratio by flow cytometry and were detergent resistant. In contrast, Mc-cpa-/- peritoneal mast cells, like immature bone marrow-derived cultured mast cells, stained with alcian blue normally or weakly and either did not stain with safranin and berberine or stained weakly, had a low side scatter to forward scatter ratio, and were detergent sensitive. This phenotype was partially ameliorated with age. Thus, histochemistry and flow cytometry, commonly used to measure mast cell maturation, deviated from morphology in Mc-cpa-/- mice. The Mc-cpa-/- mast cell phenotype was not associated with defects in degranulation in vitro or passive cutaneous anaphylaxis in vivo. Collectively, Mc-cpa plays a crucial role for the generation of phenotypically mature mast cells.

Voltage-sensitive rhodol with enhanced two-photon brightness.

PubMed

Kulkarni, Rishikesh U; Kramer, Daniel J; Pourmandi, Narges; Karbasi, Kaveh; Bateup, Helen S; Miller, Evan W

2017-03-14

We have designed, synthesized, and applied a rhodol-based chromophore to a molecular wire-based platform for voltage sensing to achieve fast, sensitive, and bright voltage sensing using two-photon (2P) illumination. Rhodol VoltageFluor-5 (RVF5) is a voltage-sensitive dye with improved 2P cross-section for use in thick tissue or brain samples. RVF5 features a dichlororhodol core with pyrrolidyl substitution at the nitrogen center. In mammalian cells under one-photon (1P) illumination, RVF5 demonstrates high voltage sensitivity (28% ΔF/F per 100 mV) and improved photostability relative to first-generation voltage sensors. This photostability enables multisite optical recordings from neurons lacking tuberous sclerosis complex 1, Tsc1, in a mouse model of genetic epilepsy. Using RVF5, we show that Tsc1 KO neurons exhibit increased activity relative to wild-type neurons and additionally show that the proportion of active neurons in the network increases with the loss of Tsc1. The high photostability and voltage sensitivity of RVF5 is recapitulated under 2P illumination. Finally, the ability to chemically tune the 2P absorption profile through the use of rhodol scaffolds affords the unique opportunity to image neuronal voltage changes in acutely prepared mouse brain slices using 2P illumination. Stimulation of the mouse hippocampus evoked spiking activity that was readily discerned with bath-applied RVF5, demonstrating the utility of RVF5 and molecular wire-based voltage sensors with 2P-optimized fluorophores for imaging voltage in intact brain tissue.

Voltage-sensitive rhodol with enhanced two-photon brightness

PubMed Central

Kulkarni, Rishikesh U.; Kramer, Daniel J.; Pourmandi, Narges; Karbasi, Kaveh; Bateup, Helen S.

2017-01-01

We have designed, synthesized, and applied a rhodol-based chromophore to a molecular wire-based platform for voltage sensing to achieve fast, sensitive, and bright voltage sensing using two-photon (2P) illumination. Rhodol VoltageFluor-5 (RVF5) is a voltage-sensitive dye with improved 2P cross-section for use in thick tissue or brain samples. RVF5 features a dichlororhodol core with pyrrolidyl substitution at the nitrogen center. In mammalian cells under one-photon (1P) illumination, RVF5 demonstrates high voltage sensitivity (28% ΔF/F per 100 mV) and improved photostability relative to first-generation voltage sensors. This photostability enables multisite optical recordings from neurons lacking tuberous sclerosis complex 1, Tsc1, in a mouse model of genetic epilepsy. Using RVF5, we show that Tsc1 KO neurons exhibit increased activity relative to wild-type neurons and additionally show that the proportion of active neurons in the network increases with the loss of Tsc1. The high photostability and voltage sensitivity of RVF5 is recapitulated under 2P illumination. Finally, the ability to chemically tune the 2P absorption profile through the use of rhodol scaffolds affords the unique opportunity to image neuronal voltage changes in acutely prepared mouse brain slices using 2P illumination. Stimulation of the mouse hippocampus evoked spiking activity that was readily discerned with bath-applied RVF5, demonstrating the utility of RVF5 and molecular wire-based voltage sensors with 2P-optimized fluorophores for imaging voltage in intact brain tissue. PMID:28242676

Analyzing the impact of price subsidy on rice self-sufficiency level in Malaysia: A preliminary finding

NASA Astrophysics Data System (ADS)

Rahim, Farah Hanim Abdul; Abidin, Norhaslinda Zainal; Hawari, Nurul Nazihah

2017-11-01

The Malaysian government had targeted for the rice industry in the country to achieve 100% rice self-sufficiency where Malaysia's rice self-sufficiency level (SSL) is currently at 65% to 75%. Thus, the government had implemented few policies to increase the rice production in Malaysia in order to meet the growing demand of rice. In this paper, the effect of price support on the rice production system in Malaysia is investigated. This study utilizes the system dynamics approach of the rice production system in Malaysia where the complexity of the factor is interrelated and changed dynamically through time. Scenario analysis was conducted using system dynamics model by making changes on the price subsidy to see its effect on the rice production and rice SSL. The system dynamics model provides a framework for understanding the effect of price subsidy on the rice self-sufficiency level. The scenario analysis of the model shows that a 50% increase in the price subsidy leads to a substantial increase in demand as the rice price drops. Accordingly, the local production increases by 15%. However, the SSL slightly decreases as the local production is insufficient to meet the large demand.

Endocytosis and recycling of AMPA receptors lacking GluR2/3.

PubMed

Biou, Virginie; Bhattacharyya, Samarjit; Malenka, Robert C

2008-01-22

Excitatory synapses in the mammalian brain contain two types of ligand-gated ion channels: AMPA receptors (AMPARs) and NMDA receptors (NMDARs). AMPARs are responsible for generating excitatory synaptic responses, whereas NMDAR activation triggers long-lasting changes in these responses by modulating the trafficking of AMPARs toward and away from synapses. AMPARs are tetramers composed of four subunits (GluR1-GluR4), which current models suggest govern distinct AMPAR trafficking behavior during synaptic plasticity. Here, we address the roles of GluR2 and GluR3 in controlling the recycling- and activity-dependent endocytosis of AMPARs by using cultured hippocampal neurons prepared from knockout (KO) mice lacking these subunits. We find that synapses and dendritic spines form normally in cells lacking GluR2/3 and that upon NMDAR activation, GluR2/3-lacking AMPARs are endocytosed in a manner indistinguishable from GluR2-containing AMPARs in wild-type (WT) neurons. AMPARs lacking GluR2/3 also recycle to the plasma membrane identically to WT AMPARs. However, because of their permeability to calcium, GluR2-lacking but not WT AMPARs exhibited robust internalization throughout the dendritic tree in response to AMPA application. Dendritic endocytosis of AMPARs also was observed in GABAergic neurons, which express a high proportion of GluR2-lacking AMPARs. These results demonstrate that GluR2 and GluR3 are not required for activity-dependent endocytosis of AMPARs and suggest that the most important property of GluR2 in the context of AMPAR trafficking may be its influence on calcium permeability.

Sensitivity of system stability to model structure

USGS Publications Warehouse

Hosack, G.R.; Li, H.W.; Rossignol, P.A.

2009-01-01

A community is stable, and resilient, if the levels of all community variables can return to the original steady state following a perturbation. The stability properties of a community depend on its structure, which is the network of direct effects (interactions) among the variables within the community. These direct effects form feedback cycles (loops) that determine community stability. Although feedback cycles have an intuitive interpretation, identifying how they form the feedback properties of a particular community can be intractable. Furthermore, determining the role that any specific direct effect plays in the stability of a system is even more daunting. Such information, however, would identify important direct effects for targeted experimental and management manipulation even in complex communities for which quantitative information is lacking. We therefore provide a method that determines the sensitivity of community stability to model structure, and identifies the relative role of particular direct effects, indirect effects, and feedback cycles in determining stability. Structural sensitivities summarize the degree to which each direct effect contributes to stabilizing feedback or destabilizing feedback or both. Structural sensitivities prove useful in identifying ecologically important feedback cycles within the community structure and for detecting direct effects that have strong, or weak, influences on community stability. The approach may guide the development of management intervention and research design. We demonstrate its value with two theoretical models and two empirical examples of different levels of complexity. ?? 2009 Elsevier B.V. All rights reserved.

Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial

PubMed Central

2012-01-01

Background Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) is a randomized controlled trial that follows a novel multi-arm, multi-stage (MAMS) design. We describe methodological and practical issues arising with (1) stopping recruitment to research arms following a pre-planned intermediate analysis and (2) adding a new research arm during the trial. Methods STAMPEDE recruits men who have locally advanced or metastatic prostate cancer who are starting standard long-term hormone therapy. Originally there were five research and one control arms, each undergoing a pilot stage (focus: safety, feasibility), three intermediate ‘activity’ stages (focus: failure-free survival), and a final ‘efficacy’ stage (focus: overall survival). Lack-of-sufficient-activity guidelines support the pairwise interim comparisons of each research arm against the control arm; these pre-defined activity cut-off becomes increasingly stringent over the stages. Accrual of further patients continues to the control arm and to those research arms showing activity and an acceptable safety profile. The design facilitates adding new research arms should sufficiently interesting agents emerge. These new arms are compared only to contemporaneously recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is subject to adequate recruitment rates to support the overall trial aims. Results (1) Stopping Existing Therapy: After the second intermediate activity analysis, recruitment was discontinued to two research arms for lack-of-sufficient activity. Detailed preparations meant that changes were implemented swiftly at 100 international centers and recruitment continued seamlessly into Activity Stage III with 3 remaining research arms and the control arm. Further regulatory and ethical approvals were not required because this was already included in the initial trial design. (2

Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial.

PubMed

Sydes, Matthew R; Parmar, Mahesh K B; Mason, Malcolm D; Clarke, Noel W; Amos, Claire; Anderson, John; de Bono, Johann; Dearnaley, David P; Dwyer, John; Green, Charlene; Jovic, Gordana; Ritchie, Alastair W S; Russell, J Martin; Sanders, Karen; Thalmann, George; James, Nicholas D

2012-09-15

Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) is a randomized controlled trial that follows a novel multi-arm, multi-stage (MAMS) design. We describe methodological and practical issues arising with (1) stopping recruitment to research arms following a pre-planned intermediate analysis and (2) adding a new research arm during the trial. STAMPEDE recruits men who have locally advanced or metastatic prostate cancer who are starting standard long-term hormone therapy. Originally there were five research and one control arms, each undergoing a pilot stage (focus: safety, feasibility), three intermediate 'activity' stages (focus: failure-free survival), and a final 'efficacy' stage (focus: overall survival). Lack-of-sufficient-activity guidelines support the pairwise interim comparisons of each research arm against the control arm; these pre-defined activity cut-off becomes increasingly stringent over the stages. Accrual of further patients continues to the control arm and to those research arms showing activity and an acceptable safety profile. The design facilitates adding new research arms should sufficiently interesting agents emerge. These new arms are compared only to contemporaneously recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is subject to adequate recruitment rates to support the overall trial aims. (1) Stopping Existing Therapy: After the second intermediate activity analysis, recruitment was discontinued to two research arms for lack-of-sufficient activity. Detailed preparations meant that changes were implemented swiftly at 100 international centers and recruitment continued seamlessly into Activity Stage III with 3 remaining research arms and the control arm. Further regulatory and ethical approvals were not required because this was already included in the initial trial design.(2) Adding New Therapy: An application to

Faculty Sufficiency and AACSB Accreditation Compliance within a Global University: A Mathematical Modeling Approach

ERIC Educational Resources Information Center

Boronico, Jess; Murdy, Jim; Kong, Xinlu

2014-01-01

This manuscript proposes a mathematical model to address faculty sufficiency requirements towards assuring overall high quality management education at a global university. Constraining elements include full-time faculty coverage by discipline, location, and program, across multiple campus locations subject to stated service quality standards of…

The yeast rapid tRNA decay pathway competes with elongation factor 1A for substrate tRNAs and acts on tRNAs lacking one or more of several modifications.

PubMed

Dewe, Joshua M; Whipple, Joseph M; Chernyakov, Irina; Jaramillo, Laura N; Phizicky, Eric M

2012-10-01

The structural and functional integrity of tRNA is crucial for translation. In the yeast Saccharomyces cerevisiae, certain aberrant pre-tRNA species are subject to nuclear surveillance, leading to 3' exonucleolytic degradation, and certain mature tRNA species are subject to rapid tRNA decay (RTD) if they are appropriately hypomodified or bear specific destabilizing mutations, leading to 5'-3' exonucleolytic degradation by Rat1 and Xrn1. Thus, trm8-Δ trm4-Δ strains are temperature sensitive due to lack of m(7)G(46) and m(5)C and the consequent RTD of tRNA(Val(AAC)), and tan1-Δ trm44-Δ strains are temperature sensitive due to lack of ac(4)C(12) and Um(44) and the consequent RTD of tRNA(Ser(CGA)) and tRNA(Ser(UGA)). It is unknown how the RTD pathway interacts with translation and other cellular processes, and how generally this pathway acts on hypomodified tRNAs. We provide evidence here that elongation factor 1A (EF-1A) competes with the RTD pathway for substrate tRNAs, since its overexpression suppresses the tRNA degradation and the growth defect of strains subject to RTD, whereas reduced levels of EF-1A have the opposite effect. We also provide evidence that RTD acts on a variety of tRNAs lacking one or more different modifications, since trm1-Δ trm4-Δ mutants are subject to RTD of tRNA(Ser(CGA)) and tRNA(Ser(UGA)) due to lack of m(2,2)G(26) and m(5)C, and since trm8-Δ, tan1-Δ, and trm1-Δ single mutants are each subject to RTD. These results demonstrate that RTD interacts with the translation machinery and acts widely on hypomodified tRNAs.

Early nutritional support and physiotherapy improved long-term self-sufficiency in acutely ill older patients.

PubMed

Hegerová, Petra; Dědková, Zuzana; Sobotka, Luboš

2015-01-01

An acute disease is regularly associated with inflammation, decreased food intake, and low physical activity; the consequence is loss of muscle mass. However, the restoration of muscle tissue is problematic, especially in older patients. Loss of muscle mass leads to further decrease of physical activity which leads, together with recurring disease, to the progressive muscle mass loss accompanied by loss of self-sufficiency. Early nutrition support and physical activity could reverse this situation. Therefore, the aim of this study was to determine whether an active approach based on early nutritional therapy and exercise would influence the development of sarcopenia and impaired self-sufficiency during acute illness. Two hundred patients >78 y were admitted to a hospital internal medicine department and participated in a prospective, randomized controlled study. The patients were randomized to a control group receiving standard treatment (n = 100) or to an intervention group (n = 100). The intervention consisted of nutritional supplements (600 kcal, 20 g/d protein) added to a standard diet and a simultaneous intensive rehabilitation program. The tolerance of supplements and their influence on spontaneous food intake, self-sufficiency, muscle strength, and body composition were evaluated during the study period. The patients were then regularly monitored for 1 y post-discharge. The provision of nutritional supplements together with early rehabilitation led to increased total energy and protein intake while the intake of standard hospital food was not reduced. The loss of lean body mass and a decrease in self-sufficiency were apparent at discharge from the hospital and 3 mo thereafter in the control group. Nutritional supplementation and the rehabilitation program in the study group prevented these alterations. A positive effect of nutritional intervention and exercise during the hospital stay was apparent at 6 mo post-discharge. The early nutritional intervention

The Collagen Gel Droplet-embedded Culture Drug Sensitivity Test in Relapsed Hepatoblastoma.

PubMed

Goto, Hiroaki; Kitagawa, Norihiko; Sekiguchi, Hironobu; Miyagi, Yohei; Keino, Dai; Sugiyama, Masanaka; Sarashina, Takeo; Miyagawa, Naoyuki; Yokosuka, Tomoko; Hamanoue, Satoshi; Iwasaki, Fuminori; Shiomi, Masae; Goto, Shoko; Tanaka, Yukichi

2017-07-01

There are few treatment options for patients with unresectable or refractory hepatoblastoma which has failed to respond to the standard treatment. The rarity of the disease and lack of experimental materials have hampered the development of new treatments. In this study, the collagen gel droplet-embedded culture drug sensitivity test was used to evaluate the effectiveness of the multikinase inhibitors sorafenib and sunitinib, and other drugs, in relapsed hepatoblastoma tumor tissues. Tumor samples from 6 patients with relapsed hepatoblastoma were tested for drug sensitivity by the collagen gel droplet-embedded culture drug sensitivity test; evaluable results were obtained from 5 of them. All samples were judged to be sensitive to sorafenib with a 50% growth inhibitory concentration (IC50) of 0.5 to 3.1 μg/mL. Sunitinib did not achieve IC50 in 2 of 3 samples within the tested concentration range based on clinically observed serum concentrations. In the drug combination assay using a hepatoblastoma cell line, sorafenib showed synergistic effects with SN-38, an active metabolite of irinotecan. Our results provide the basic science background warranting future clinical trials of a combination of sorafenib and irinotecan for relapsed or refractory hepatoblastoma.

Generation of Recombinant Oropouche Viruses Lacking the Nonstructural Protein NSm or NSs.

PubMed

Tilston-Lunel, Natasha L; Acrani, Gustavo Olszanski; Randall, Richard E; Elliott, Richard M

2015-12-23

Oropouche virus (OROV) is a midge-borne human pathogen with a geographic distribution in South America. OROV was first isolated in 1955, and since then, it has been known to cause recurring outbreaks of a dengue-like illness in the Amazonian regions of Brazil. OROV, however, remains one of the most poorly understood emerging viral zoonoses. Here we describe the successful recovery of infectious OROV entirely from cDNA copies of its genome and generation of OROV mutant viruses lacking either the NSm or the NSs coding region. Characterization of the recombinant viruses carried out in vitro demonstrated that the NSs protein of OROV is an interferon (IFN) antagonist as in other NSs-encoding bunyaviruses. Additionally, we demonstrate the importance of the nine C-terminal amino acids of OROV NSs in IFN antagonistic activity. OROV was also found to be sensitive to IFN-α when cells were pretreated; however, the virus was still capable of replicating at doses as high as 10,000 U/ml of IFN-α, in contrast to the family prototype BUNV. We found that OROV lacking the NSm protein displayed characteristics similar to those of the wild-type virus, suggesting that the NSm protein is dispensable for virus replication in the mammalian and mosquito cell lines that were tested. Oropouche virus (OROV) is a public health threat in Central and South America, where it causes periodic outbreaks of dengue-like illness. In Brazil, OROV is the second most frequent cause of arboviral febrile illness after dengue virus, and with the current rates of urban expansion, more cases of this emerging viral zoonosis could occur. To better understand the molecular biology of OROV, we have successfully rescued the virus along with mutants. We have established that the C terminus of the NSs protein is important in interferon antagonism and that the NSm protein is dispensable for virus replication in cell culture. The tools described in this paper are important in terms of understanding this important yet

Generation of Recombinant Oropouche Viruses Lacking the Nonstructural Protein NSm or NSs

PubMed Central

Randall, Richard E.; Elliott, Richard M.

2015-01-01

ABSTRACT Oropouche virus (OROV) is a midge-borne human pathogen with a geographic distribution in South America. OROV was first isolated in 1955, and since then, it has been known to cause recurring outbreaks of a dengue-like illness in the Amazonian regions of Brazil. OROV, however, remains one of the most poorly understood emerging viral zoonoses. Here we describe the successful recovery of infectious OROV entirely from cDNA copies of its genome and generation of OROV mutant viruses lacking either the NSm or the NSs coding region. Characterization of the recombinant viruses carried out in vitro demonstrated that the NSs protein of OROV is an interferon (IFN) antagonist as in other NSs-encoding bunyaviruses. Additionally, we demonstrate the importance of the nine C-terminal amino acids of OROV NSs in IFN antagonistic activity. OROV was also found to be sensitive to IFN-α when cells were pretreated; however, the virus was still capable of replicating at doses as high as 10,000 U/ml of IFN-α, in contrast to the family prototype BUNV. We found that OROV lacking the NSm protein displayed characteristics similar to those of the wild-type virus, suggesting that the NSm protein is dispensable for virus replication in the mammalian and mosquito cell lines that were tested. IMPORTANCE Oropouche virus (OROV) is a public health threat in Central and South America, where it causes periodic outbreaks of dengue-like illness. In Brazil, OROV is the second most frequent cause of arboviral febrile illness after dengue virus, and with the current rates of urban expansion, more cases of this emerging viral zoonosis could occur. To better understand the molecular biology of OROV, we have successfully rescued the virus along with mutants. We have established that the C terminus of the NSs protein is important in interferon antagonism and that the NSm protein is dispensable for virus replication in cell culture. The tools described in this paper are important in terms of

Lack of response to unaligned chromosomes in mammalian female gametes

PubMed Central

Sebestova, Jaroslava; Danylevska, Anna; Novakova, Lucia; Kubelka, Michal; Anger, Martin

2012-01-01

Chromosome segregation errors are highly frequent in mammalian female meiosis, and their incidence gradually increases with maternal age. The fate of aneuploid eggs is obviously dependent on the stringency of mechanisms for detecting unattached or repairing incorrectly attached kinetochores. In case of their failure, the newly formed embryo will inherit the impaired set of chromosomes, which will have severe consequences for its further development. Whether spindle assembly checkpoint (SAC) in oocytes is capable of arresting cell cycle progression in response to unaligned kinetochores was discussed for a long time. It is known that abolishing SAC increases frequency of chromosome segregation errors and causes precocious entry into anaphase; SAC, therefore, seems to be essential for normal chromosome segregation in meiosis I. However, it was also reported that for anaphase-promoting complex (APC) activation, which is a prerequisite for entering anaphase; alignment of only a critical mass of kinetochores on equatorial plane is sufficient. This indicates that the function of SAC and of cooperating chromosome attachment correction mechanisms in oocytes is different from somatic cells. To analyze this phenomenon, we used live cell confocal microscopy to monitor chromosome movements, spindle formation, APC activation and polar body extrusion (PBE) simultaneously in individual oocytes at various time points during first meiotic division. Our results, using oocytes from aged animals and interspecific crosses, demonstrate that multiple unaligned kinetochores and severe congression defects are tolerated at the metaphase to anaphase transition, although such cells retain sensitivity to nocodazole. This indicates that checkpoint mechanisms, operating in oocytes at this point, are essential for accurate timing of APC activation in meiosis I, but they are insufficient in detection or correction of unaligned chromosomes, preparing thus conditions for propagation of the aneuploidy

49 CFR 40.275 - What is the effect of procedural problems that are not sufficient to cancel an alcohol test?

Code of Federal Regulations, 2010 CFR

2010-10-01

... not sufficient to cancel an alcohol test? 40.275 Section 40.275 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Alcohol Testing § 40.275 What is the effect of procedural problems that are not sufficient to...

49 CFR 40.275 - What is the effect of procedural problems that are not sufficient to cancel an alcohol test?

Code of Federal Regulations, 2014 CFR

2014-10-01

... not sufficient to cancel an alcohol test? 40.275 Section 40.275 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Alcohol Testing § 40.275 What is the effect of procedural problems that are not sufficient to...

49 CFR 40.275 - What is the effect of procedural problems that are not sufficient to cancel an alcohol test?

Code of Federal Regulations, 2011 CFR

2011-10-01

... not sufficient to cancel an alcohol test? 40.275 Section 40.275 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Alcohol Testing § 40.275 What is the effect of procedural problems that are not sufficient to...

49 CFR 40.275 - What is the effect of procedural problems that are not sufficient to cancel an alcohol test?

Code of Federal Regulations, 2012 CFR

2012-10-01

... not sufficient to cancel an alcohol test? 40.275 Section 40.275 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Alcohol Testing § 40.275 What is the effect of procedural problems that are not sufficient to...

49 CFR 40.275 - What is the effect of procedural problems that are not sufficient to cancel an alcohol test?

Code of Federal Regulations, 2013 CFR

2013-10-01

... not sufficient to cancel an alcohol test? 40.275 Section 40.275 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Alcohol Testing § 40.275 What is the effect of procedural problems that are not sufficient to...

Behavioural and physiological mechanisms of polarized light sensitivity in birds

PubMed Central

Muheim, Rachel

2011-01-01

Polarized light (PL) sensitivity is relatively well studied in a large number of invertebrates and some fish species, but in most other vertebrate classes, including birds, the behavioural and physiological mechanism of PL sensitivity remains one of the big mysteries in sensory biology. Many organisms use the skylight polarization pattern as part of a sun compass for orientation, navigation and in spatial orientation tasks. In birds, the available evidence for an involvement of the skylight polarization pattern in sun-compass orientation is very weak. Instead, cue-conflict and cue-calibration experiments have shown that the skylight polarization pattern near the horizon at sunrise and sunset provides birds with a seasonally and latitudinally independent compass calibration reference. Despite convincing evidence that birds use PL cues for orientation, direct experimental evidence for PL sensitivity is still lacking. Avian double cones have been proposed as putative PL receptors, but detailed anatomical and physiological evidence will be needed to conclusively describe the avian PL receptor. Intriguing parallels between the functional and physiological properties of PL reception and light-dependent magnetoreception could point to a common receptor system. PMID:21282180

RasGRP1 confers the phorbol ester-sensitive phenotype to EL4 lymphoma cells.

PubMed

Han, Shujie; Knoepp, Stewart M; Hallman, Mark A; Meier, Kathryn E

2007-01-01

The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to the tumor promoter phorbol 12-myristate 13-acetate (PMA). In sensitive EL4 cells, PMA causes robust Erk mitogen-activated protein kinase activation that results in growth arrest. In resistant cells, PMA induces minimal Erk activation, without growth arrest. PMA stimulates IL-2 production in sensitive, but not resistant, cells. The role of RasGRP1, a PMA-activated guanine nucleotide exchange factor for Ras, in EL4 phenotype was examined. Endogenous RasGRP1 protein is expressed at much higher levels in sensitive than in resistant cells. PMA-induced Ras activation is observed in sensitive cells but not in resistant cells lacking Ras-GRP1. PMA induces down-regulation of RasGRP1 protein in sensitive cells but increases RasGRP1 in resistant cells. Transfection of RasGRP1 into resistant cells enhances PMA-induced Erk activation. In the reverse experiment, introduction of small interfering RNA (siRNA) for RasGRP1 suppresses PMA-induced Ras and Erk activations in sensitive cells. Sensitive cells incubated with siRNA for RasGRP1 exhibit the PMA-resistant phenotype, in that they are able to proliferate in the presence of PMA and do not secrete IL-2 when stimulated with PMA. These studies indicate that the PMA-sensitive phenotype, as previously defined for the EL4 cell line, is conferred by endogenous expression of RasGRP1 protein.

Object memory effects on figure assignment: conscious object recognition is not necessary or sufficient.

PubMed

Peterson, M A; de Gelder, B; Rapcsak, S Z; Gerhardstein, P C; Bachoud-Lévi, A

2000-01-01

In three experiments we investigated whether conscious object recognition is necessary or sufficient for effects of object memories on figure assignment. In experiment 1, we examined a brain-damaged participant, AD, whose conscious object recognition is severely impaired. AD's responses about figure assignment do reveal effects from memories of object structure, indicating that conscious object recognition is not necessary for these effects, and identifying the figure-ground test employed here as a new implicit test of access to memories of object structure. In experiments 2 and 3, we tested a second brain-damaged participant, WG, for whom conscious object recognition was relatively spared. Nevertheless, effects from memories of object structure on figure assignment were not evident in WG's responses about figure assignment in experiment 2, indicating that conscious object recognition is not sufficient for effects of object memories on figure assignment. WG's performance sheds light on AD's performance, and has implications for the theoretical understanding of object memory effects on figure assignment.

Keratosis reduces sensitivity of anal cytology in detecting anal intraepithelial neoplasia.

PubMed

ElNaggar, Adam C; Santoso, Joseph T; Xie, Huiwen Bill

2012-02-01

To identify factors that may contribute to poor sensitivity of anal cytology in contrast to the sensitivity of anoscopy in heterosexual women. We analyzed 324 patients with biopsy confirmed diagnosis of genital intraepithelial neoplasia (either vulva, vaginal, or cervical) from 2006 to 2011 who underwent both anal cytology and anoscopy. Cytology, anoscopy, and biopsy results were recorded. Biopsy specimens underwent independent analysis for quality of specimen. Also, biopsy specimens were analyzed for characteristics that may contribute to correlation, or lack thereof, between anal cytology and anoscopic directed biopsy. 133 (41%) patients had abnormal anoscopy and underwent directed biopsy. 120 patients with normal anal cytology had anoscopy directed biopsies, resulting in 58 cases of AIN (sensitivity 9.4%; 0.039-0.199). This cohort was noted to have extensive keratosis covering the entire dysplastic anal lesion. 18 patients yielded abnormal anal cytology. Of these patients, 13 had anoscopic directed biopsies revealing 6 with AIN and absent keratosis (specificity 88.6%; 0.78-0.95). The κ statistic for anal cytology and anoscopy was -0.0213 (95% CI=-0.128-0.086). Keratosis reduces the sensitivity of anal cytology. Furthermore, anal cytology poorly correlates with anoscopy in the detection of AIN (κ statistic=-0.0213). Copyright © 2011 Elsevier Inc. All rights reserved.

Modified short-term guinea pig sensitization tests for detecting contact allergens as an alternative to the conventional test.

PubMed

Yanagi, M; Hoya, M; Mori, M; Katsumura, Y

2001-03-01

The conventional adjuvant and patch test (APT) method of guinea pig sensitization testing was modified in 2 ways, s-APT and s-APT(2), in order to shorten the test period. These short-term test methods consist of 72-h closed application of test material with intradermal injection of emulsified Freund's complete adjuvant (E-FCA) for 1st induction, 48-h closed application of test material with (s-APT) or without (s-APT(2)) intradermal injection of E-FCA on the 7th day for 2nd induction, and open application on the 14th day for challenge. They were compared with conventional APT by using 8 allergenic chemicals (formaldehyde, nickel sulfate, cobalt sulfate, ethyl-p-aminobenzoate (benzocaine), isoeugenol, 2-mercaptobenzothiazole, 2,4-dinitrochlorobenzene (DNCB) and 1-phenylazo-2-naphthol (Sudan I)). The short-term methods gave similar results to those of conventional APT in terms of mean response, sensitization rate and sensitization potency (challenge concentration that induces a mean response equal to 1.0). Thus, our short-term methods, which are capable of evaluating skin sensitization within 17 days, are sufficiently sensitive to detect potentially hazardous contact allergens.

Measuring What Latent Fingerprint Examiners Consider Sufficient Information for Individualization Determinations

PubMed Central

Ulery, Bradford T.; Hicklin, R. Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

2014-01-01

Latent print examiners use their expertise to determine whether the information present in a comparison of two fingerprints (or palmprints) is sufficient to conclude that the prints were from the same source (individualization). When fingerprint evidence is presented in court, it is the examiner's determination—not an objective metric—that is presented. This study was designed to ascertain the factors that explain examiners' determinations of sufficiency for individualization. Volunteer latent print examiners (n = 170) were each assigned 22 pairs of latent and exemplar prints for examination, and annotated features, correspondence of features, and clarity. The 320 image pairs were selected specifically to control clarity and quantity of features. The predominant factor differentiating annotations associated with individualization and inconclusive determinations is the count of corresponding minutiae; other factors such as clarity provided minimal additional discriminative value. Examiners' counts of corresponding minutiae were strongly associated with their own determinations; however, due to substantial variation of both annotations and determinations among examiners, one examiner's annotation and determination on a given comparison is a relatively weak predictor of whether another examiner would individualize. The extensive variability in annotations also means that we must treat any individual examiner's minutia counts as interpretations of the (unknowable) information content of the prints: saying “the prints had N corresponding minutiae marked” is not the same as “the prints had N corresponding minutiae.” More consistency in annotations, which could be achieved through standardization and training, should lead to process improvements and provide greater transparency in casework. PMID:25372036

Impact of Albedo Contrast Between Cirrus and Boundary-Layer Clouds on Climate Sensitivity

NASA Technical Reports Server (NTRS)

Chou, Ming-Dah; Lindzen, R. S.; Hou, A. Y.; Lau, William K. M. (Technical Monitor)

2001-01-01

In assessing the iris effect suggested by Lindzen et al. (2001), Fu et al. (2001) found that the response of high-level clouds to the sea surface temperature had an effect of reducing the climate sensitivity to external radiative forcing, but the effect was not as strong as LCH found. This weaker reduction in climate sensitivity was due to the smaller contrasts in albedos and effective emitting temperatures between cirrus clouds and the neighboring regions. FBH specified the albedos and the outgoing longwave radiation (OLR) in the LCH 3.5-box radiative-convective model by requiring that the model radiation budgets at the top of the atmosphere be consistent with that inferred from the Earth Radiation Budget Experiment (ERBE). In point of fact, the constraint by radiation budgets alone is not sufficient for deriving the correct contrast in radiation properties between cirrus clouds and the neighboring regions, and the approach of FBH to specifying those properties is, we feel inappropriate for assessing the iris effect.

The Esg Gene Is Involved in Nicotine Sensitivity in Drosophila melanogaster

PubMed Central

Reyes-Taboada, José Luis; Covarrubias, Alejandra A; Narvaez-Padilla, Verónica; Reynaud, Enrique

2015-01-01

In humans, there is a strong correlation between sensitivity to substances of abuse and addiction risk. This differential tolerance to drugs has a strong genetic component. The identification of human genetic factors that alter drug tolerance has been a difficult task. For this reason and taking advantage of the fact that Drosophila responds similarly to humans to many drugs, and that genetically it has a high degree of homology (sharing at least 70% of genes known to be involved in human genetic diseases), we looked for genes in Drosophila that altered their nicotine sensitivity. We developed an instantaneous nicotine vaporization technique that exposed flies in a reproducible way. The amount of nicotine sufficient to “knock out” half of control flies for 30 minutes was determined and this parameter was defined as Half Recovery Time (HRT). Two fly lines, L4 and L70, whose HRT was significantly longer than control´s were identified. The L4 insertion is a loss of function allele of the transcriptional factor escargot (esg), whereas L70 insertion causes miss-expression of the microRNA cluster miR-310-311-312-313 (miR-310c). In this work, we demonstrate that esg loss of function induces nicotine sensitivity possibly by altering development of sensory organs and neurons in the medial section of the thoracoabdominal ganglion. The ectopic expression of the miR-310c also induces nicotine sensitivity by lowering Esg levels thus disrupting sensory organs and possibly to the modulation of other miR-310c targets. PMID:26222315

The Esg Gene Is Involved in Nicotine Sensitivity in Drosophila melanogaster.

PubMed

Sanchez-Díaz, Iván; Rosales-Bravo, Fernando; Reyes-Taboada, José Luis; Covarrubias, Alejandra A; Narvaez-Padilla, Verónica; Reynaud, Enrique

2015-01-01

In humans, there is a strong correlation between sensitivity to substances of abuse and addiction risk. This differential tolerance to drugs has a strong genetic component. The identification of human genetic factors that alter drug tolerance has been a difficult task. For this reason and taking advantage of the fact that Drosophila responds similarly to humans to many drugs, and that genetically it has a high degree of homology (sharing at least 70% of genes known to be involved in human genetic diseases), we looked for genes in Drosophila that altered their nicotine sensitivity. We developed an instantaneous nicotine vaporization technique that exposed flies in a reproducible way. The amount of nicotine sufficient to "knock out" half of control flies for 30 minutes was determined and this parameter was defined as Half Recovery Time (HRT). Two fly lines, L4 and L70, whose HRT was significantly longer than control´s were identified. The L4 insertion is a loss of function allele of the transcriptional factor escargot (esg), whereas L70 insertion causes miss-expression of the microRNA cluster miR-310-311-312-313 (miR-310c). In this work, we demonstrate that esg loss of function induces nicotine sensitivity possibly by altering development of sensory organs and neurons in the medial section of the thoracoabdominal ganglion. The ectopic expression of the miR-310c also induces nicotine sensitivity by lowering Esg levels thus disrupting sensory organs and possibly to the modulation of other miR-310c targets.

Do short international layovers allow sufficient opportunity for pilots to recover?

PubMed

Lamond, Nicole; Petrilli, Renée M; Dawson, Drew; Roach, Gregory D

2006-01-01

For Australian pilots, short layovers (<40 h) are a feature of many international patterns. However, anecdotal reports suggest that flight crew members find patterns with short slips more fatiguing than those with a longer international layover, as they restrict the opportunity to obtain sufficient sleep. The current study aimed to determine whether pilots operating international patterns with short layovers have sufficient opportunity to recover prior to the inbound flight. Nineteen international pilots (ten captains, nine first officers) operating a direct return pattern from Australia to Los Angeles (LAX) with a short (n = 9) 9+/-0.8 h (mean+/-S.D) or long (n = 10) 62.2+/-0.9 h LAX layover wore an activity monitor and kept a sleep/duty diary during the pattern. Immediately before and after each flight, pilots completed a 5 min PalmPilot-based psychomotor vigilance task (Palm-PVT). Flights were of comparable duration outbound (3.5+/-0.6 h) and inbound (14.3+/-0.6 h) and timing. The amount of sleep obtained in-flight did not significantly vary as a function of layover length. However, pilots obtained significantly more sleep during the inbound (3.7+/-0.8 h) than the outbound flight (2.2+/-0.8 h). Pilots with the shorter layover obtained significantly less sleep in total during layover (14.0+/-2.7 h vs. 19.6+/-2.5), due to significantly fewer sleep periods (3.0+/-0.7 vs. 4.0+/-0.9). However, neither mean sleep duration nor the sleep obtained in the 24 h prior to the inbound flight significantly differed as a function of layover length. Response speed significantly varied across the pattern, and a significant interaction was also observed. For pilots with a short layover, response speed was significantly slower at the end of both the outbound and inbound flight, and prior to the inbound flight (i.e., at the end of layover), relative to response speed at the start of the pattern (pre-trip). Similarly, response speed for the longer layover was slower at the end of the

Is there sufficient evidence regarding signage-based stair use interventions? A sequential meta-analysis

PubMed Central

Bauman, Adrian; Milton, Karen; Kariuki, Maina; Fedel, Karla; Lewicka, Mary

2017-01-01

Objective The proliferation of studies using motivational signs to promote stair use continues unabated, with their oft-cited potential for increasing population-level physical activity participation. This study examined all stair use promotional signage studies since 1980, calculating pre-estimates and post-estimates of stair use. The aim of this project was to conduct a sequential meta-analysis to pool intervention effects, in order to determine when the evidence base was sufficient for population-wide dissemination. Design Using comparable data from 50 stair-promoting studies (57 unique estimates) we pooled data to assess the effect sizes of such interventions. Results At baseline, median stair usage across interventions was 8.1%, with an absolute median increase of 2.2% in stair use following signage-based interventions. The overall pooled OR indicated that participants were 52% more likely to use stairs after exposure to promotional signs (adjusted OR 1.52, 95% CI 1.37 to 1.70). Incremental (sequential) meta-analyses using z-score methods identified that sufficient evidence for stair use interventions has existed since 2006, with recent studies providing no further evidence on the effect sizes of such interventions. Conclusions This analysis has important policy and practice implications. Researchers continue to publish stair use interventions without connection to policymakers' needs, and few stair use interventions are implemented at a population level. Researchers should move away from repeating short-term, small-scale, stair sign interventions, to investigating their scalability, adoption and fidelity. Only such research translation efforts will provide sufficient evidence of external validity to inform their scaling up to influence population physical activity. PMID:29183924

Implications of the lack of global dimming and brightening in global climate models

NASA Astrophysics Data System (ADS)

Storelvmo, T.

2017-12-01

The global temperature trend of the last half-century is widely believed to be the result of two opposing effects; aerosol cooling and greenhouse gas (GHG) warming. While the radiative effect of increasing GHG concentrations is well-constrained, that due to anthropogenic aerosols is not, in part because observational constraints on the latter are lacking. However, long-term surface measurements of downward solar radiation (DSRS), an often-used proxy for aerosol radiative forcing, are available worldwide from the Global Energy Balance Archive (GEBA). We compare DSRS changes from 1,300 GEBA stations to those from the Coupled Model Intercomparison Project, phase 5 (CMIP5) simulations, sampled only when/where observations are available. The observed DSRS shows a strong early (1964-1990) downward trend, followed by a weaker regional trend reversal. Regional emission data for aerosols and aerosol precursors suggest that the culprit for both features was changes to the atmospheric aerosol loading. In contrast, the models show weak or negligible DSRS trends, suggesting a too weak aerosol forcing. We present sensitivity studies with a single model (CESM1.2) that aim to simultaneously reproduce the observed trends in DSRS and surface temperature.

Retrocausal Effects As A Consequence of Orthodox Quantum Mechanics Refined To Accommodate The Principle Of Sufficient Reason

NASA Astrophysics Data System (ADS)

Stapp, Henry P.

2011-11-01

The principle of sufficient reason asserts that anything that happens does so for a reason: no definite state of affairs can come into being unless there is a sufficient reason why that particular thing should happen. This principle is usually attributed to Leibniz, although the first recorded Western philosopher to use it was Anaximander of Miletus. The demand that nature be rational, in the sense that it be compatible with the principle of sufficient reason, conflicts with a basic feature of contemporary orthodox physical theory, namely the notion that nature's response to the probing action of an observer is determined by pure chance, and hence on the basis of absolutely no reason at all. This appeal to pure chance can be deemed to have no rational fundamental place in reason-based Western science. It is argued here, on the basis of the other basic principles of quantum physics, that in a world that conforms to the principle of sufficient reason, the usual quantum statistical rules will naturally emerge at the pragmatic level, in cases where the reason behind nature's choice of response is unknown, but that the usual statistics can become biased in an empirically manifest way when the reason for the choice is empirically identifiable. It is shown here that if the statistical laws of quantum mechanics were to be biased in this way then the basically forward-in-time unfolding of empirical reality described by orthodox quantum mechanics would generate the appearances of backward-time-effects of the kind that have been reported in the scientific literature.

Low-resistivity photon-transparent window attached to photo-sensitive silicon detector

DOEpatents

Holland, Stephen Edward

2000-02-15

The invention comprises a combination of a low resistivity, or electrically conducting, silicon layer that is transparent to long or short wavelength photons and is attached to the backside of a photon-sensitive layer of silicon, such as a silicon wafer or chip. The window is applied to photon sensitive silicon devices such as photodiodes, charge-coupled devices, active pixel sensors, low-energy x-ray sensors and other radiation detectors. The silicon window is applied to the back side of a photosensitive silicon wafer or chip so that photons can illuminate the device from the backside without interference from the circuit printed on the frontside. A voltage sufficient to fully deplete the high-resistivity photosensitive silicon volume of charge carriers is applied between the low-resistivity back window and the front, patterned, side of the device. This allows photon-induced charge created at the backside to reach the front side of the device and to be processed by any circuitry attached to the front side. Using the inventive combination, the photon sensitive silicon layer does not need to be thinned beyond standard fabrication methods in order to achieve full charge-depletion in the silicon volume. In one embodiment, the inventive backside window is applied to high resistivity silicon to allow backside illumination while maintaining charge isolation in CCD pixels.

The dynamic simulation model of soybean in Central Java to support food self sufficiency: A supply chain perspective

NASA Astrophysics Data System (ADS)

Oktyajati, Nancy; Hisjam, Muh.; Sutopo, Wahyudi

2018-02-01

Consider food become one of the basic human needs in order to survive so food sufficiency become very important. Food sufficiency of soybean commodity in Central Java still depends on imported soybean. Insufficiency of soybean because of there is much gap between local soybean productions and its demand. In the year 2016 the shortage of supply soybean commodity as much 68.79%. Soybean is an important and strategic commodity after rice and corn. The increasing consumption of soybean is related to increasing population, increasing incomes, changing of healthy life style. The aims of this study are to determine the soybean dynamic model based on supply chain perspective, define the proper price of local soybean to trigger increasing of local production, and to define the alternative solution to support food self sufficiency. This study will capture the real condition into dynamics model, then simulate a series of scenario into a computer program to obtain the best results. This study will be conducted the following first scenario with government intervention policy and second without government intervention policy. The best solution of the alternative can be used as government consideration for governmental policy. The results of the propose scenarios showed that self sufficiency on soybean can be achieved after the next 20 years by increasing planting area 4% and land productivity 1% per year.

A combined system of microbial fuel cell and intermittently aerated biological filter for energy self-sufficient wastewater treatment.

PubMed

Dong, Yue; Feng, Yujie; Qu, Youpeng; Du, Yue; Zhou, Xiangtong; Liu, Jia

2015-12-15

Energy self-sufficiency is a highly desirable goal of sustainable wastewater treatment. Herein, a combined system of a microbial fuel cell and an intermittently aerated biological filter (MFC-IABF) was designed and operated in an energy self-sufficient manner. The system was fed with synthetic wastewater (COD = 1000 mg L(-1)) in continuous mode for more than 3 months at room temperature (~25 °C). Voltage output was increased to 5 ± 0.4 V using a capacitor-based circuit. The MFC produced electricity to power the pumping and aeration systems in IABF, concomitantly removing COD. The IABF operating under an intermittent aeration mode (aeration rate 1000 ± 80 mL h(-1)) removed the residual nutrients and improved the water quality at HRT = 7.2 h. This two-stage combined system obtained 93.9% SCOD removal and 91.7% TCOD removal (effluent SCOD = 61 mg L(-1), TCOD = 82.8 mg L(-1)). Energy analysis indicated that the MFC unit produced sufficient energy (0.27 kWh m(-3)) to support the pumping system (0.014 kWh m(-3)) and aeration system (0.22 kWh m(-3)). These results demonstrated that the combined MFC-IABF system could be operated in an energy self-sufficient manner, resulting to high-quality effluent.

A combined system of microbial fuel cell and intermittently aerated biological filter for energy self-sufficient wastewater treatment

PubMed Central

Dong, Yue; Feng, Yujie; Qu, Youpeng; Du, Yue; Zhou, Xiangtong; Liu, Jia

2015-01-01

Energy self-sufficiency is a highly desirable goal of sustainable wastewater treatment. Herein, a combined system of a microbial fuel cell and an intermittently aerated biological filter (MFC-IABF) was designed and operated in an energy self-sufficient manner. The system was fed with synthetic wastewater (COD = 1000 mg L−1) in continuous mode for more than 3 months at room temperature (~25 °C). Voltage output was increased to 5 ± 0.4 V using a capacitor-based circuit. The MFC produced electricity to power the pumping and aeration systems in IABF, concomitantly removing COD. The IABF operating under an intermittent aeration mode (aeration rate 1000 ± 80 mL h−1) removed the residual nutrients and improved the water quality at HRT = 7.2 h. This two-stage combined system obtained 93.9% SCOD removal and 91.7% TCOD removal (effluent SCOD = 61 mg L−1, TCOD = 82.8 mg L−1). Energy analysis indicated that the MFC unit produced sufficient energy (0.27 kWh m−3) to support the pumping system (0.014 kWh m−3) and aeration system (0.22 kWh m−3). These results demonstrated that the combined MFC-IABF system could be operated in an energy self-sufficient manner, resulting to high-quality effluent. PMID:26666392

Georg Rasch and Benjamin Wright's Struggle with the Unidimensional Polytomous Model with Sufficient Statistics

ERIC Educational Resources Information Center

Andrich, David

2016-01-01

This article reproduces correspondence between Georg Rasch of The University of Copenhagen and Benjamin Wright of The University of Chicago in the period from January 1966 to July 1967. This correspondence reveals their struggle to operationalize a unidimensional measurement model with sufficient statistics for responses in a set of ordered…

NIH–Lacks Family Partnership Gives Henrietta Lacks’ Descendants a Seat at the Table | Poster

Cancer.gov

The NIH Bethesda campus recently welcomed several special guests for a presentation titled Given a Voice: Update on the NIH–Lacks Family Partnership. Henrietta Lacks’ grandchildren Jeri Lacks-Whye (who is also the Lacks family spokesperson) and David Lacks, Jr. came to speak with NIH Director Francis S. Collins, Ph.D., M.D. about the importance of protecting patients and their

Constitutive and nitrogen catabolite repression-sensitive production of Gat1 isoforms.

PubMed

Rai, Rajendra; Tate, Jennifer J; Georis, Isabelle; Dubois, Evelyne; Cooper, Terrance G

2014-01-31

Nitrogen catabolite repression (NCR)-sensitive transcription is activated by Gln3 and Gat1. In nitrogen excess, Gln3 and Gat1 are cytoplasmic, and transcription is minimal. In poor nitrogen, Gln3 and Gat1 become nuclear and activate transcription. A long standing paradox has surrounded Gat1 production. Gat1 was first reported as an NCR-regulated activity mediating NCR-sensitive transcription in gln3 deletion strains. Upon cloning, GAT1 transcription was, as predicted, NCR-sensitive and Gln3- and Gat1-activated. In contrast, Western blots of Gat1-Myc(13) exhibited two constitutively produced species. Investigating this paradox, we demonstrate that wild type Gat1 isoforms (IsoA and IsoB) are initiated at Gat1 methionines 40, 95, and/or 102, but not at methionine 1. Their low level production is the same in rich and poor nitrogen conditions. When the Myc(13) tag is placed after Gat1 Ser-233, four N-terminal Gat1 isoforms (IsoC-F) are also initiated at methionines 40, 95, and/or 102. However, their production is highly NCR-sensitive, being greater in proline than glutamine medium. Surprisingly, all Gat1 isoforms produced in sufficient quantities to be confidently analyzed (IsoA, IsoC, and IsoD) require Gln3 and UASGATA promoter elements, both requirements typical of NCR-sensitive transcription. These data demonstrate that regulated Gat1 production is more complex than previously recognized, with wild type versus truncated Gat1 proteins failing to be regulated in parallel. This is the first reported instance of Gln3 UASGATA-dependent protein production failing to derepress in nitrogen poor conditions. A Gat1-lacZ ORF swap experiment indicated sequence(s) responsible for the nonparallel production are downstream of Gat1 leucine 61.

Expression of solute carrier 7A4 (SLC7A4) in the plasma membrane is not sufficient to mediate amino acid transport activity.

PubMed

Wolf, Sabine; Janzen, Annette; Vékony, Nicole; Martiné, Ursula; Strand, Dennis; Closs, Ellen I

2002-06-15

Member 4 of human solute carrier family 7 (SLC7A4) exhibits significant sequence homology with the SLC7 subfamily of human cationic amino acid transporters (hCATs) [Sperandeo, Borsani, Incerti, Zollo, Rossi, Zuffardi, Castaldo, Taglialatela, Andria and Sebastio (1998) Genomics 49, 230-236]. It is therefore often referred to as hCAT-4 even though no convincing transport activity has been shown for this protein. We expressed SLC7A4 in Xenopus laevis oocytes, but could not detect any transport activity for cationic, neutral or anionic amino acids or for the polyamine putrescine. In addition, human glioblastoma cells stably overexpressing a fusion protein between SLC7A4 and the enhanced green fluorescent protein (EGFP) did not exhibit an increased transport activity for l-arginine. The lack of transport activity was not due to a lack of SLC7A4 protein expression in the plasma membrane, as in both cell types SLC7A4-EGFP exhibited a similar subcellular localization and level of protein expression as functional hCAT-EGFP proteins. The expression of SLC7A4 can be induced in NT2 teratocarcinoma cells by treatment with retinoic acid. However, also for this endogenously expressed SLC7A4, we could not detect any transport activity for l-arginine. Our data demonstrate that the expression of SLC7A4 in the plasma membrane is not sufficient to induce an amino acid transport activity in X. laevis oocytes or human cells. Therefore, SLC7A4 is either not an amino acid transporter or it needs additional (protein) factor(s) to be functional.

Expression of solute carrier 7A4 (SLC7A4) in the plasma membrane is not sufficient to mediate amino acid transport activity.

PubMed Central

Wolf, Sabine; Janzen, Annette; Vékony, Nicole; Martiné, Ursula; Strand, Dennis; Closs, Ellen I

2002-01-01

Member 4 of human solute carrier family 7 (SLC7A4) exhibits significant sequence homology with the SLC7 subfamily of human cationic amino acid transporters (hCATs) [Sperandeo, Borsani, Incerti, Zollo, Rossi, Zuffardi, Castaldo, Taglialatela, Andria and Sebastio (1998) Genomics 49, 230-236]. It is therefore often referred to as hCAT-4 even though no convincing transport activity has been shown for this protein. We expressed SLC7A4 in Xenopus laevis oocytes, but could not detect any transport activity for cationic, neutral or anionic amino acids or for the polyamine putrescine. In addition, human glioblastoma cells stably overexpressing a fusion protein between SLC7A4 and the enhanced green fluorescent protein (EGFP) did not exhibit an increased transport activity for l-arginine. The lack of transport activity was not due to a lack of SLC7A4 protein expression in the plasma membrane, as in both cell types SLC7A4-EGFP exhibited a similar subcellular localization and level of protein expression as functional hCAT-EGFP proteins. The expression of SLC7A4 can be induced in NT2 teratocarcinoma cells by treatment with retinoic acid. However, also for this endogenously expressed SLC7A4, we could not detect any transport activity for l-arginine. Our data demonstrate that the expression of SLC7A4 in the plasma membrane is not sufficient to induce an amino acid transport activity in X. laevis oocytes or human cells. Therefore, SLC7A4 is either not an amino acid transporter or it needs additional (protein) factor(s) to be functional. PMID:12049641

Quality and Cultural Sensitivity of Linguistically Appropriate Cardiovascular Disease Information for Chinese Immigrants: A Review of Online Resources From Heart Foundations.

PubMed

Li, Jialin; Lowres, Nicole; Jin, Kai; Zhang, Ling; Neubeck, Lis; Gallagher, Robyn

Chinese immigrants are at an increased risk for cardiovascular diseases (CVDs) compared with Chinese nationals partly because of lifestyle changes and knowledge deficits. Translated patient resources are available on the Internet and are often provided by health professionals; however, the quality and cultural sensitivity of these resources have not been reported. The aim of this study was to assess the availability, quality, and cultural sensitivity of Chinese-language information available from national "Heart Foundations" (cardiac research bodies, nongovernmental organisations) of the 5 most popular destinations of Chinese immigration. This study is a descriptive research in which national "Heart Foundation" websites were systematically searched for Chinese-language CVD patient education resources. Quality (content, identification, structure) was assessed using the Ensuring Quality Information for Patients instrument. Cultural sensitivity was evaluated using the Cultural Sensitivity Assessment Tool. From 107 identified resources, 33 were CVD specific: coronary heart disease (n = 20), arrhythmias (n = 7), and heart failure (n = 6). Quality of resources was adequate (mean Ensuring Quality Information for Patients score, 69%), but scores varied significantly (min, 60%; max, 85%). Although all resources were classified as culturally sensitive (Cultural Sensitivity Assessment Tool score ≥ 2.5), 2 resources scored low (≤2.5) for visual impact, and across all resources, written and visual domains were assessed as least culturally sensitive. Most resources lacked culturally specific references. Chinese-language CVD resources were inconsistent in the supply of key information. Quality and level of cultural sensitivity were adequate, but most resources lacked culturally specific references. Comprehensive, high-quality CVD resources powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation tailored for Chinese immigrants are urgently needed for

Fetal circulatory responses to oxygen lack.

PubMed

Jensen, A; Berger, R

1991-10-01

The knowledge on fetal and neonatal circulatory physiology accumulated by basic scientists and clinicians over the years has contributed considerably to the recent decline of perinatal morbidity and mortality. This review will summarize the peculiarities of the fetal circulation, the distribution of organ blood flow during normoxemia, and that during oxygen lack caused by various experimental perturbations. Furthermore, the relation between oxygen delivery and tissue metabolism during oxygen lack as well as evidence to support a new concept will be presented along with the principal cardiovascular mechanisms involved. Finally, blood flow and oxygen delivery to the principal fetal organs will be examined and discussed in relation to organ function. The fetal circulatory response to hypoxemia and asphyxia is a centralization of blood flow in favour of the brain, heart, and adrenals and at the expense of almost all peripheral organs, particularly of the lungs, carcass, skin and scalp. This response is qualitatively similar but quantitatively different under various experimental conditions. However, at the nadir of severe acute asphyxia the circulatory centralization cannot be maintained. Then there is circulatory decentralization, and the fetus will experience severe brain damage if not expire unless immediate resuscitation occurs. Future work in this field will have to concentrate on the important questions, what factors determine this collapse of circulatory compensating mechanisms in the fetus, how does it relate to neuronal damage, and how can the fetal brain be pharmacologically protected against the adverse effects of asphyxia.

Analysing the lack of Demand Organisation

NASA Astrophysics Data System (ADS)

Boxer, Philip; Cohen, Bernard

1998-07-01

We seek to develop means of intervention in Enterprises that will enable them to react in an effective, sustainable and timely fashion to changes in the ways that markets and demand are organized; that is, to act strategically. We take an enterprise to be some entity that seeks to provide its clients with services that they value while maintaining its ability to do so in the face of changes in the demands of its clients and in the resources at its disposal. The services that clients value form around what the organization of their demands lack. The concept of strategy therefore rests on critically evaluating the ontology and semantics of the Enterprise in relation to these holes in demand organization. We access ontology and semantics by constructing and manipulating hypothetical, first-order, mathematical models of the Enterprise's services and of its value-adding processes. Because an enterprise is an anticipatory system, its semantic domain must include representations of the enterprise's model of itself and of the market and demand organizations within which it competes. First-order (set) theory provides adequate expressive power here, but alternative, higher order, mathematical frameworks, such as Dubois' hyperincursion, provide inadequate power, particularly in relation to the analysis of the properties of emergence. Knowing exactly why and where this mathematical lack manifests in the analysis process enables effective collaboration between systems analysts and psychoanalysts, and suggest directions for mathematical research.

Reduced food access due to a lack of money, inability to lift and lack of access to a car for food shopping: a multilevel study in Melbourne, Victoria.

PubMed

Burns, Cate; Bentley, Rebecca; Thornton, Lukar; Kavanagh, Anne

2011-06-01

To describe associations between demographic and individual and area-level socio-economic variables and restricted household food access due to lack of money, inability to lift groceries and lack of access to a car to do food shopping. Multilevel study of three measures of restricted food access, i.e. running out of money to buy food, inability to lift groceries and lack of access to a car for food shopping. Multilevel logistic regression was conducted to examine the risk of each of these outcomes according to demographic and socio-economic variables. Random selection of households from fifty small areas in Melbourne, Australia, in 2003. The main food shoppers in each household (n 2564). A lack of money was significantly more likely among the young and in households with single adults. Difficulty lifting was more likely among the elderly and those born overseas. The youngest and highest age groups both reported reduced car access, as did those born overseas and single-adult households. All three factors were most likely among those with a lower individual or household socio-economic position. Increased levels of area disadvantage were independently associated with difficulty lifting and reduced car access. In Melbourne, households with lower individual socio-economic position and area disadvantage have restricted access to food because of a lack of money and/or having physical limitations due difficulty lifting or lack of access to a car for food shopping. Further research is required to explore the relationship between physical restrictions and food access.

Near-infrared sensitization in dye-sensitized solar cells.

PubMed

Park, Jinhyung; Viscardi, Guido; Barolo, Claudia; Barbero, Nadia

2013-01-01

Dye-sensitized solar cells (DSCs) are a low cost and colorful promising alternative to standard silicon photovoltaic cells. Though many of the highest efficiencies have been associated with sensitizers absorbing only in the visible portion of the solar radiation, there is a growing interest for NIR sensitization. This paper reviews the efforts made so far to find sensitizers able to absorb efficiently in the far-red NIR region of solar light. Panchromatic sensitizers as well as dyes absorbing mainly in the 650-920 nm region have been considered.

Guess LOD approach: sufficient conditions for robustness.

PubMed

Williamson, J A; Amos, C I

1995-01-01

Analysis of genetic linkage between a disease and a marker locus requires specifying a genetic model describing both the inheritance pattern and the gene frequencies of the marker and trait loci. Misspecification of the genetic model is likely for etiologically complex diseases. In previous work we have shown through analytic studies that misspecifying the genetic model for disease inheritance does not lead to excess false-positive evidence for genetic linkage provided the genetic marker alleles of all pedigree members are known, or can be inferred without bias from the data. Here, under various selection or ascertainment schemes we extend these previous results to situations in which the genetic model for the marker locus may be incorrect. We provide sufficient conditions for the asymptotic unbiased estimation of the recombination fraction under the null hypothesis of no linkage, and also conditions for the limiting distribution of the likelihood ratio test for no linkage to be chi-squared. Through simulation studies we document some situations under which asymptotic bias can result when the genetic model is misspecified. Among those situations under which an excess of false-positive evidence for genetic linkage can be generated, the most common is failure to provide accurate estimates of the marker allele frequencies. We show that in most cases false-positive evidence for genetic linkage is unlikely to result solely from the misspecification of the genetic model for disease or trait inheritance.

Lack of HXK2 induces localization of active Ras in mitochondria and triggers apoptosis in the yeast Saccharomyces cerevisiae.

PubMed

Amigoni, Loredana; Martegani, Enzo; Colombo, Sonia

2013-01-01

We recently showed that activated Ras proteins are localized to the plasma membrane and in the nucleus in wild-type cells growing exponentially on glucose, while in the hxk2Δ strain they accumulated mainly in mitochondria. An aberrant accumulation of activated Ras in these organelles was previously reported and correlated to mitochondrial dysfunction, accumulation of ROS, and cell death. Here we show that addition of acetic acid to wild-type cells results in a rapid recruitment of Ras-GTP from the nucleus and the plasma membrane to the mitochondria, providing a further proof that Ras proteins might be involved in programmed cell death. Moreover, we show that Hxk2 protects against apoptosis in S. cerevisiae. In particular, cells lacking HXK2 and showing a constitutive accumulation of activated Ras at the mitochondria are more sensitive to acetic-acid-induced programmed cell death compared to the wild type strain. Indeed, deletion of HXK2 causes an increase of apoptotic cells with several morphological and biochemical changes that are typical of apoptosis, including DNA fragmentation, externalization of phosphatidylserine, and ROS production. Finally, our results suggest that apoptosis induced by lack of Hxk2 may not require the activation of Yca1, the metacaspase homologue identified in yeast.

Loss of Histochemical Identity in Mast Cells Lacking Carboxypeptidase A

PubMed Central

Feyerabend, Thorsten B.; Hausser, Heinz; Tietz, Annette; Blum, Carmen; Hellman, Lars; Straus, Anita H.; Takahashi, Hélio K.; Morgan, Ellen S.; Dvorak, Ann M.; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2005-01-01

Mast cell carboxypeptidase A (Mc-cpa) is a highly conserved secretory granule protease. The onset of expression in mast cell progenitors and lineage specificity suggest an important role for Mc-cpa in mast cells. To address the function of Mc-cpa, we generated Mc-cpa-null mice. Mc-cpa−/− mast cells lacked carboxypeptidase activity, revealing that Mc-cpa is a nonredundant enzyme. While Mc-cpa−/− peritoneal mast cells were ultrastructurally normal and synthesized normal amounts of heparin, they displayed striking histochemical and biochemical hallmarks of immature mast cells. Wild-type peritoneal mast cells had a mature phenotype characterized by differential histochemical staining with proteoglycan-reactive dyes (cells do not stain with alcian blue but stain with safranin and with berberine) and a high side scatter to forward scatter ratio by flow cytometry and were detergent resistant. In contrast, Mc-cpa−/− peritoneal mast cells, like immature bone marrow-derived cultured mast cells, stained with alcian blue normally or weakly and either did not stain with safranin and berberine or stained weakly, had a low side scatter to forward scatter ratio, and were detergent sensitive. This phenotype was partially ameliorated with age. Thus, histochemistry and flow cytometry, commonly used to measure mast cell maturation, deviated from morphology in Mc-cpa−/− mice. The Mc-cpa−/− mast cell phenotype was not associated with defects in degranulation in vitro or passive cutaneous anaphylaxis in vivo. Collectively, Mc-cpa plays a crucial role for the generation of phenotypically mature mast cells. PMID:15988029

Lack of evidence for central sensitization in idiopathic, non-traumatic neck pain: a systematic review.

PubMed

Malfliet, Annaleen; Kregel, Jeroen; Cagnie, Barbara; Kuipers, Mandy; Dolphens, Mieke; Roussel, Nathalie; Meeus, Mira; Danneels, Lieven; Bramer, Wichor M; Nijs, Jo

2015-01-01

Chronic neck pain is a common problem with a poorly understood pathophysiology. Often no underlying structural pathology can be found and radiological imaging findings are more related to age than to a patient's symptoms. Besides its common occurrence, chronic idiopathic neck pain is also very disabling with almost 50% of all neck pain patients showing moderate disability at long-term follow-up. Central sensitization (CS) is defined as "an amplification of neural signaling within the central nervous system that elicits pain hypersensitivity," "increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input," or "an augmentation of responsiveness of central neurons to input from unimodal and polymodal receptors." There is increasing evidence for involvement of CS in many chronic pain conditions. Within the area of chronic idiopathic neck pain, there is consistent evidence for the presence and clinical importance of CS in patients with traumatic neck pain, or whiplash-associated disorders. However, the majority of chronic idiopathic neck pain patients are unrelated to a traumatic injury, and hence are termed chronic idiopathic non-traumatic neck pain. When comparing whiplash with idiopathic non-traumatic neck pain, indications for different underlying mechanisms are found. The goal of this article was to review the existing scientific literature on the role of CS in patients with chronic idiopathic non-traumatic neck pain. Systematic review. All selected studies were case control studies. A systematic search of existing, relevant literature was performed via the electronic databases Medline, Embase, Web of Science, Cinahl, PubMed, and Google Scholar. All titles and abstracts were checked to identify relevant articles. An article was considered eligible if it met following inclusion criteria: (1) participants had to be human adults (> 18 years) diagnosed with idiopathic non-traumatic chronic (present for at

Power and sensitivity of alternative fit indices in tests of measurement invariance.

PubMed

Meade, Adam W; Johnson, Emily C; Braddy, Phillip W

2008-05-01

Confirmatory factor analytic tests of measurement invariance (MI) based on the chi-square statistic are known to be highly sensitive to sample size. For this reason, G. W. Cheung and R. B. Rensvold (2002) recommended using alternative fit indices (AFIs) in MI investigations. In this article, the authors investigated the performance of AFIs with simulated data known to not be invariant. The results indicate that AFIs are much less sensitive to sample size and are more sensitive to a lack of invariance than chi-square-based tests of MI. The authors suggest reporting differences in comparative fit index (CFI) and R. P. McDonald's (1989) noncentrality index (NCI) to evaluate whether MI exists. Although a general value of change in CFI (.002) seemed to perform well in the analyses, condition specific change in McDonald's NCI values exhibited better performance than a single change in McDonald's NCI value. Tables of these values are provided as are recommendations for best practices in MI testing. PsycINFO Database Record (c) 2008 APA, all rights reserved.

Lack of modulation of gastric emptying by dietary nitrate in healthy volunteers.

PubMed

Terai, Shiho; Iijima, Katsunori; Asanuma, Kiyotaka; Ara, Nobuyuki; Uno, Kaname; Abe, Yasuhiko; Koike, Tomoyuki; Imatani, Akira; Ohara, Shuichi; Shimosegawa, Tooru

2009-05-01

Nitric oxide produced endogenously in vagal neurons modulates gastrointestinal motor activity as an important non-adrenergic and non-cholinergic neurotransmitter. Other than through endogenous biosynthesis, a high concentration of nitric oxide also occurs by chemical reactions within the stomach in the presence of gastric acid through the entero-salivary re-circulation of dietary nitrate. Although dietary nitrate can be a potential source of nitric oxide in the human stomach, there has been no report on the effect of dietary nitrate on gastric motor function. The aim of this study is to investigate the effect of dietary nitrate on gastric emptying, one of the major parameters for the gastric motor function. Fifteen healthy volunteers underwent a placebo-controlled (310 mg sodium nitrate or placebo), double-blind, crossover trial. Since a sufficient amount of gastric acid is essential for dietary nitrate-derived nitric oxide generation in the stomach, the same protocol was repeated after 1-week treatment with a proton pump inhibitor, rabeprazole. Gastric emptying was evaluated by (13)C-octanoate breath test. The sodium nitrate ingestion did not affect gastric emptying either prior to or during rabeprazole treatment, although rabeprazole treatment itself significantly delayed gastric emptying, being independent of the dietary nitrate load. Confirmation of the delayed gastric emptying with rabeprazole indicates the sensitivity of the breath test employed in the present study. In conclusion, despite the potential nitrogen source of exogenous nitric oxide, the ingestion of 310 mg sodium nitrate, which is equivalent to the average daily intake of Japanese adults, does not affect gastric emptying in healthy volunteers.

An Examination of the Role of L-Glutamate and Inosine 5'-Monophosphate in Hedonic Taste-Guided Behavior by Mice Lacking the T1R1 + T1R3 Receptor.

PubMed

Blonde, Ginger D; Spector, Alan C

2017-06-01

The heterodimeric T1R1 + T1R3 receptor is considered critical for normal signaling of L-glutamate and 5'-ribonucleotides in the oral cavity. However, some taste-guided responsiveness remains in mice lacking one subunit of the receptor, suggesting that other receptors are sufficient to support some behaviors. Here, mice lacking both receptor subunits (KO) and wild-type (WT, both n = 13) mice were tested in a battery of behavioral tests. Mice were trained and tested in gustometers with a concentration series of Maltrin-580, a maltodextrin, in a brief-access test (10-s trials) as a positive control. Similar tests followed with monosodium glutamate (MSG) with and without the ribonucleotide inosine 5'-monophosphate (IMP), but always in the presence of the epithelial sodium channel blocker amiloride (A). Brief-access tests were repeated following short-term (30-min) and long-term (48-h) exposures to MSG + A + IMP and were also conducted with sodium gluconate replacing MSG. Finally, progressive ratio tests were conducted with Maltrin-580 or MSG + A + IMP, to assess appetitive behavior while minimizing satiation. Overall, MSG generated little concentration-dependent responding in either food-restricted WT or KO mice, even in combination with IMP. However, KO mice licked less to the amino acid stimuli, a measure of consummatory behavior in the brief-access tests. In contrast, both groups initiated a similar number of trials and had a similar breakpoint in the progressive ratio task, both measures of appetitive (approach) behavior. Collectively, these results suggest that while the T1R1 + T1R3 receptor is necessary for consummatory responding to MSG (+IMP), other receptors are sufficient to maintain appetitive responding to this "umami" stimulus complex in food-restricted mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Facile Fabrication of Multi-hierarchical Porous Polyaniline Composite as Pressure Sensor and Gas Sensor with Adjustable Sensitivity

NASA Astrophysics Data System (ADS)

He, Xiao-Xiao; Li, Jin-Tao; Jia, Xian-Sheng; Tong, Lu; Wang, Xiao-Xiong; Zhang, Jun; Zheng, Jie; Ning, Xin; Long, Yun-Ze

2017-08-01

A multi-hierarchical porous polyaniline (PANI) composite which could be used in good performance pressure sensor and adjustable sensitivity gas sensor has been fabricated by a facile in situ polymerization. Commercial grade sponge was utilized as a template scaffold to deposit PANI via in situ polymerization. With abundant interconnected pores throughout the whole structure, the sponge provided sufficient surface for the growth of PANI nanobranches. The flexible porous structure helped the composite to show high performance in pressure detection with fast response and favorable recoverability and gas detection with adjustable sensitivity. The sensing mechanism of the PANI/sponge-based flexible sensor has also been discussed. The results indicate that this work provides a feasible approach to fabricate efficient sensors with advantages of low cost, facile preparation, and easy signal collection.

Facile Fabrication of Multi-hierarchical Porous Polyaniline Composite as Pressure Sensor and Gas Sensor with Adjustable Sensitivity.

PubMed

He, Xiao-Xiao; Li, Jin-Tao; Jia, Xian-Sheng; Tong, Lu; Wang, Xiao-Xiong; Zhang, Jun; Zheng, Jie; Ning, Xin; Long, Yun-Ze

2017-12-01

A multi-hierarchical porous polyaniline (PANI) composite which could be used in good performance pressure sensor and adjustable sensitivity gas sensor has been fabricated by a facile in situ polymerization. Commercial grade sponge was utilized as a template scaffold to deposit PANI via in situ polymerization. With abundant interconnected pores throughout the whole structure, the sponge provided sufficient surface for the growth of PANI nanobranches. The flexible porous structure helped the composite to show high performance in pressure detection with fast response and favorable recoverability and gas detection with adjustable sensitivity. The sensing mechanism of the PANI/sponge-based flexible sensor has also been discussed. The results indicate that this work provides a feasible approach to fabricate efficient sensors with advantages of low cost, facile preparation, and easy signal collection.

The Fatty Acid Composition of Phosphatidylglycerol and Sulfoquinovosyldiacylglycerol of Higher Plants in Relation to Chilling Sensitivity

PubMed Central

Kenrick, Janette R.; Bishop, David G.

1986-01-01

The fatty acid composition of phosphatidylglycerol and sulfoquinovosyldiacylglycerol has been measured in the leaves of 27 species of higher plants from six families whose members differed in their degrees of chilling sensitivity. The content of high melting point fatty acids (represented by the sum of hexadecanoic, trans-3-hexadecenoic and octadecanoic acids) in phosphatidylglycerols varied little between members of the same plant family and was not obviously related to the relative chilling sensitivity of members of that family. The saturated fatty acid content (hexadecanoic + octadecanoic acids) of sulfoquinovosyldiacylglycerols also appeared to be characteristic of a plant family, although some exceptions were found. In one case, (Carica papaya) the content of saturated fatty acids in sulfoquinovosyldiacylglycerol was sufficiently high to suggest that this lipid could undergo phase separations above 0°C. It is concluded that the content of high melting point fatty acids in leaf phosphatidylglycerol is not a direct indication of the chilling sensitivity of a plant, but rather may be a reflection of the genetic origin of that plant. PMID:16664962

Is there sufficient evidence regarding signage-based stair use interventions? A sequential meta-analysis.

PubMed

Bauman, Adrian; Milton, Karen; Kariuki, Maina; Fedel, Karla; Lewicka, Mary

2017-11-28

The proliferation of studies using motivational signs to promote stair use continues unabated, with their oft-cited potential for increasing population-level physical activity participation. This study examined all stair use promotional signage studies since 1980, calculating pre-estimates and post-estimates of stair use. The aim of this project was to conduct a sequential meta-analysis to pool intervention effects, in order to determine when the evidence base was sufficient for population-wide dissemination. Using comparable data from 50 stair-promoting studies (57 unique estimates) we pooled data to assess the effect sizes of such interventions. At baseline, median stair usage across interventions was 8.1%, with an absolute median increase of 2.2% in stair use following signage-based interventions. The overall pooled OR indicated that participants were 52% more likely to use stairs after exposure to promotional signs (adjusted OR 1.52, 95% CI 1.37 to 1.70). Incremental (sequential) meta-analyses using z-score methods identified that sufficient evidence for stair use interventions has existed since 2006, with recent studies providing no further evidence on the effect sizes of such interventions. This analysis has important policy and practice implications. Researchers continue to publish stair use interventions without connection to policymakers' needs, and few stair use interventions are implemented at a population level. Researchers should move away from repeating short-term, small-scale, stair sign interventions, to investigating their scalability, adoption and fidelity. Only such research translation efforts will provide sufficient evidence of external validity to inform their scaling up to influence population physical activity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effect of changes to question order on the prevalence of 'sufficient' physical activity in an Australian population survey.

PubMed

Hanley, Christine; Duncan, Mitch J; Mummery, W Kerry

2013-03-01

Population surveys are frequently used to assess prevalence, correlates and health benefits of physical activity. However, nonsampling errors, such as question order effects, in surveys may lead to imprecision in self reported physical activity. This study examined the impact of modified question order in a commonly used physical activity questionnaire on the prevalence of sufficient physical activity. Data were obtained from a telephone survey of adults living in Queensland, Australia. A total of 1243 adults participated in the computer-assisted telephone interview (CATI) survey conducted in July 2008 which included the Active Australia Questionnaire (AAQ) presented in traditional or modified order. Binary logistic regression analyses was used to examine relationships between question order and physical activity outcomes. Significant relationships were found between question order and sufficient activity, recreational walking, moderate activity, vigorous activity, and total activity. Respondents who received the AAQ in modified order were more likely to be categorized as sufficiently active (OR = 1.28, 95% CI 1.01-1.60). This study highlights the importance of question order on estimates of self reported physical activity. This study has shown that changes in question order can lead to an increase in the proportion of participants classified as sufficiently active.

Do Work Incentives Have Unintended Consequences? Measuring "Entry Effects" in the Self-Sufficiency Project.

ERIC Educational Resources Information Center

Berlin, Gordon; Bancroft, Wendy; Card, David; Lin, Winston; Robins, Philip K.

The Self-Sufficiency Project (SSP) is a Canadian social demonstration and research project designed to test an employment alternative to welfare. The SSP makes work pay by offering generous earnings supplements to long-term, single-parent welfare recipients who find full-time jobs and leave Canada's Income Assistance (IA) welfare system. The SSP's…

The Autonomous House: A Bio-Hydrogen Based Energy Self-Sufficient Approach

PubMed Central

Chen, Shang-Yuan; Chu, Chen-Yeon; Cheng, Ming-jen; Lin, Chiu-Yue

2009-01-01

In the wake of the greenhouse effect and global energy crisis, finding sources of clean, alternative energy and developing everyday life applications have become urgent tasks. This study proposes the development of an “autonomous house” emphasizing the use of modern green energy technology to reduce environmental load, achieve energy autonomy and use energy intelligently in order to create a sustainable, comfortable living environment. The houses’ two attributes are: (1) a self-sufficient energy cycle and (2) autonomous energy control to maintain environmental comfort. The autonomous house thus combines energy-conserving, carbon emission-reducing passive design with active elements needed to maintain a comfortable environment. PMID:19440531

The autonomous house: a bio-hydrogen based energy self-sufficient approach.

PubMed

Chen, Shang-Yuan; Chu, Chen-Yeon; Cheng, Ming-Jen; Lin, Chiu-Yue

2009-04-01

In the wake of the greenhouse effect and global energy crisis, finding sources of clean, alternative energy and developing everyday life applications have become urgent tasks. This study proposes the development of an "autonomous house" emphasizing the use of modern green energy technology to reduce environmental load, achieve energy autonomy and use energy intelligently in order to create a sustainable, comfortable living environment. The houses' two attributes are: (1) a self-sufficient energy cycle and (2) autonomous energy control to maintain environmental comfort. The autonomous house thus combines energy-conserving, carbon emission-reducing passive design with active elements needed to maintain a comfortable environment.

Life stage sensitivity of the marine mussel Mytilus edulis to ammonia.

PubMed

Kennedy, Alan J; Lindsay, James H; Biedenbach, James M; Harmon, Ashley R

2017-01-01

Ammonia is an important contaminant to consider in all toxicity tests. It is especially important to consider the impacts of ammonia in test methods that use sensitive water column organisms exposed to sediments or sediment extracts, such as porewater and elutriate toxicity tests. Embryo-larval development toxicity tests, such as the 48-h method using Mytilus mussel species, are particularly sensitive to ammonia. To better understand the effect thresholds across different life stages of these mussels, 6 short-term (48-h) development toxicity tests and 3 21-d toxicity tests with different-sized juvenile mussels were conducted. Two of the juvenile mussel tests involved 21-d continuous chronic exposure to ammonia, whereas the third involved an acute 2-d ammonia exposure, followed by a 19-d recovery period. The embryo-larval development test method (50% effect concentration [EC50] = 0.14-0.18 mg/L un-ionized ammonia) was 2.5 times more sensitive than the juvenile mussel 21-d survival endpoint (50% lethal concentration = 0.39 mg/L un-ionized ammonia) and 2 times more sensitive than the most sensitive sublethal juvenile mussel endpoint (EC50 = 0.26 mg/L un-ionized ammonia). Further, it was found that the juveniles recovered from a 48-h exposure to un-ionized ammonia of up to 1.1 mg/L. The data generated suggest that the embryo development endpoint was sufficiently sensitive to un-ionized ammonia to protect the chronically exposed (21 d) juvenile mussels. Environ Toxicol Chem 2017;36:89-95. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Sunlight exposure increases vitamin D sufficiency in growing pigs fed a diet formulated to exceed requirements.

PubMed

Alexander, B M; Ingold, B C; Young, J L; Fensterseifer, S R; Wechsler, P J; Austin, K J; Larson-Meyer, D E

2017-04-01

exposure. Expression of CYP27B1 was decreased (P = 0.04) in the kidney but tended to be increased (P = 0.06) in the liver after sun exposure. These results suggest limited sun exposure can efficiently increase serum concentration of vitamin D in growing pigs with varying levels of vitamin sufficiency. The lack of major changes in vitamin synthesizing enzymes suggests the 14-d exposure period did not saturate the capacity of slaughter-weight pigs to synthesize vitamin D. Copyright © 2016 Elsevier Inc. All rights reserved.

Necessary and sufficient conditions on n-qudit state for perfect teleportation of an arbitrary single qudit state

NASA Astrophysics Data System (ADS)

Shang-Guan, Li-Ying; Sun, Hong-Xiang; Wen, Qiao-Yan; Zhu, Fu-Chen

2009-12-01

Firstly, we investigate the necessary and sufficient conditions that an entangled channel of n-qubits should satisfy to carry out perfect teleportation of an arbitrary single qubit state and dense coding. It is shown that the sender can transmit two classical bits of information by sending one qubit. Further, the case of high-dimension quantum state is also considered. Utilizing n-qudit state as quantum channel, it is proposed that the necessary and sufficient conditions are {(d+2)(d-1)}/{2} in all to teleport an arbitrary single qudit state. The sender can transmit 2log2d classical bits of information to the receiver conditioned on the constraints.

Improving sensitivity to magnetic fields and electric dipole moments by using measurements of individual magnetic sublevels

NASA Astrophysics Data System (ADS)

Tang, Cheng; Zhang, Teng; Weiss, David S.

2018-03-01

We explore ways to use the ability to measure the populations of individual magnetic sublevels to improve the sensitivity of magnetic field measurements and measurements of atomic electric dipole moments (EDMs). When atoms are initialized in the m =0 magnetic sublevel, the shot-noise-limited uncertainty of these measurements is 1 /√{2 F (F +1 ) } smaller than that of a Larmor precession measurement. When the populations in the even (or odd) magnetic sublevels are combined, we show that these measurements are independent of the tensor Stark shift and the second order Zeeman shift. We discuss the complicating effect of a transverse magnetic field and show that when the ratio of the tensor Stark shift to the transverse magnetic field is sufficiently large, an EDM measurement with atoms initialized in the superposition of the stretched states can reach the optimal sensitivity.

[The concept of nutritional self-sufficiency and the demographic equilibrium of Rwanda].

PubMed

Habimana Nyirasafari, G

1987-12-01

Achieving food self-sufficiency is the basic strategy of Rwanda's 4th 5-year plan covering 1987-91. The population growth rate has increased from 3% in 1970 to 3.7% in 1983, with the population doubling between 1964 and 1985. Food production grew by about 4%/year between 1966-83, creating a slight increase in per capita food availability, but the 2171 calories available per capita is dangerously close to the theoretical minimum requirement of 2100 per day. The theoretical protein requirement is almost covered, but there is a serious shortage of oils. The increase in production since 1966 has been due almost exclusively to the extension of cultivated land. But the land supply is limited, and future production increases will need to be based on increased yields per unit cultivated. The National Office of Population has developed a simulation model that analyzes the parallel evolution of population and production so as to identify demographic and development policies that will assure food self-sufficiency and an improvement in living conditions. The population subsystem subjects the population divided by age and sex to the effects of fertility, migration, and mortality. Births are the result of 36 different fertility rates applied to the population of women aged 14-49 years. The agricultural subsystem is tied to the population subsystem by comparison of the volume of population to that of production, by estimation of the proportion of the population living exclusively by subsistence agriculture, by calculation of the potential emigration resulting from overpopulation of the countryside, and by estimation of the links between nutritional level, mortality, and duration of breastfeeding. 5 annexes contain subsystems showing effects of demographic growth on education, employment, and health. The model has various limitations including those of the reliability of its data, but it is sufficiently precise for its main function of clarifying the choices facing policymakers. 6

pH-sensitive Eudragit nanoparticles for mucosal drug delivery.

PubMed

Yoo, Jin-Wook; Giri, Namita; Lee, Chi H

2011-01-17

Drug delivery via vaginal epithelium has suffered from lack of stability due to acidic and enzymatic environments. The biocompatible pH-sensitive nanoparticles composed of Eudragit S-100 (ES) were developed to protect loaded compounds from being degraded under the rigorous vaginal conditions and achieve their therapeutically effective concentrations in the mucosal epithelium. ES nanoparticles containing a model compound (sodium fluorescein (FNa) or nile red (NR)) were prepared by the modified quasi-emulsion solvent diffusion method. Loading efficiencies were found to be 26% and 71% for a hydrophilic and a hydrophobic compound, respectively. Both hydrophilic and hydrophobic model drugs remained stable in nanoparticles at acidic pH, whereas they are quickly released from nanoparticles upon exposure at physiological pH. The confocal study revealed that ES nanoparticles were taken up by vaginal cells, followed by pH-responsive drug release, with no cytotoxic activities. The pH-sensitive nanoparticles would be a promising carrier for the vaginal-specific delivery of various therapeutic drugs including microbicides and peptides/proteins. Published by Elsevier B.V.

Primal-dual methods of shape sensitivity analysis for curvilinear cracks with nonpenetration

NASA Astrophysics Data System (ADS)

Kovtunenko, V. A.

2006-10-01

Based on a level-set description of a crack moving with a given velocity, the problem of shape perturb-ation of the crack is considered. Nonpenetration conditions are imposed between opposite crack surfaces which result in a constrained minimization problem describing equilibrium of a solid with the crack. We suggest a minimax formulation of the state problem thus allowing curvilinear (nonplanar) cracks for the consideration. Utilizing primal-dual methods of shape sensitivity analysis we obtain the general formula for a shape derivative of the potential energy, which describes an energy-release rate for the curvilinear cracks. The conditions sufficient to rewrite it in the form of a path-independent integral (J-integral) are derived.

Necessary but Not Sufficient: The North Dakota School Counselor Designate Credential

ERIC Educational Resources Information Center

DeLorme, Carolyn Schwenke

2010-01-01

More than two dozen North Dakota K-12 schools begin each academic year with a school counselor designate because of state mandates for services in each building and a lack of qualified applicants to provide these services. School counselor designates are individuals who hold a North Dakota professional educator's license, have completed a minimum…

The relationship between maternal attachment, perceived social support and breast-feeding sufficiency.

PubMed

Cinar, Nursan; Köse, Dilek; Altinkaynak, Sevin

2015-04-01

To determine the relationship between maternal attachment, perceived social support and breast-feeding sufficiency. Descriptive correlational design. A state hospital and two family health centers in Sakarya, Turkey, between June to December 2011. The sample was 122 voluntary mothers who had healthy babies of 1 - 2 months old. The data were collected by a Personal Information Form, Maternal Attachment Inventory (MAI), Multidimensional Scale of Perceived Social Support (MSPSS) and Breast-feeding Self-Efficacy Scale-Short Form (BSES-SF). The data collected were analysed by percentage distribution, mean square, independent sample t-test, Mann-Whitney U, Kruskall-Wallis and Pearson correlation. The mean age of the mothers was 25.01 ± 2.2 years, and 48.4% of them were primary school graduates. BSESSF was 61.02 ± 8.44 (16 - 70), MAI was 99.07 ± 7.19 (56 - 100) and MSPSS was 66.40 ± 13.58 (37 - 84). There was a positive, medium level, significant relationship between the total scores of BSES-SF and MAI (r=0.370, p < 0.001). There was a positive, medium level, significant relationship between the total score of BSES-SF and the score from family subdimension of MSPSS (r=0.255, p < 0.01).There was a positive, medium level, significant relationship between the total score of MAI and the total score of family subdimension of MSPSS (r=0.339, p < 0.001). Successful maternal attachment and familial support positively affected the breast-feeding sufficiency of the mother.

Mechanical stress regulates insulin sensitivity through integrin-dependent control of insulin receptor localization.

PubMed

Kim, Jung; Bilder, David; Neufeld, Thomas P

2018-01-15

Insulin resistance, the failure to activate insulin signaling in the presence of ligand, leads to metabolic diseases, including type 2 diabetes. Physical activity and mechanical stress have been shown to protect against insulin resistance, but the molecular mechanisms remain unclear. Here, we address this relationship in the Drosophila larval fat body, an insulin-sensitive organ analogous to vertebrate adipose tissue and livers. We found that insulin signaling in Drosophila fat body cells is abolished in the absence of physical activity and mechanical stress even when excess insulin is present. Physical movement is required for insulin sensitivity in both intact larvae and fat bodies cultured ex vivo. Interestingly, the insulin receptor and other downstream components are recruited to the plasma membrane in response to mechanical stress, and this membrane localization is rapidly lost upon disruption of larval or tissue movement. Sensing of mechanical stimuli is mediated in part by integrins, whose activation is necessary and sufficient for mechanical stress-dependent insulin signaling. Insulin resistance develops naturally during the transition from the active larval stage to the immotile pupal stage, suggesting that regulation of insulin sensitivity by mechanical stress may help coordinate developmental programming with metabolism. © 2018 Kim et al.; Published by Cold Spring Harbor Laboratory Press.

Sensitivity of equatorial Pacific and Indian Ocean watermasses to the position of the Indonesian Throughflow

NASA Astrophysics Data System (ADS)

Rodgers, Keith B.; Latif, Mojib; Legutke, Stephanie

2000-09-01

The sensitivity of the thermal structure of the equatorial Pacific and Indian Ocean pycnoclines to a model's representation of the Indonesian Straits connecting the two basins is investigated. Two integrations are performed using the global HOPE ocean model. The initial conditions and surface forcing for both cases are identical; the only difference between the runs is that one has an opening for the Indonesian Straits which spans the equator on the Pacific side, and the other has an opening which lies fully north of the equator. The resulting sensitivity throughout much of the upper ocean is greater than 0.5°C for both the equatorial Indian and Pacific. A realistic simulation of net Indonesian Throughflow (ITF) transport (measured in Sverdrups) is not sufficient for an adequate simulation of equatorial watermasses. The ITF must also contain a realistic admixture of northern and southern Pacific source water.

Lack of the Sodium-Driven Chloride Bicarbonate Exchanger NCBE Impairs Visual Function in the Mouse Retina

PubMed Central

Hilgen, Gerrit; Huebner, Antje K.; Tanimoto, Naoyuki; Sothilingam, Vithiyanjali; Seide, Christina; Garrido, Marina Garcia; Schmidt, Karl-Friedrich; Seeliger, Mathias W.; Löwel, Siegrid; Weiler, Reto

2012-01-01

Regulation of ion and pH homeostasis is essential for normal neuronal function. The sodium-driven chloride bicarbonate exchanger NCBE (Slc4a10), a member of the SLC4 family of bicarbonate transporters, uses the transmembrane gradient of sodium to drive cellular net uptake of bicarbonate and to extrude chloride, thereby modulating both intracellular pH (pHi) and chloride concentration ([Cl−]i) in neurons. Here we show that NCBE is strongly expressed in the retina. As GABAA receptors conduct both chloride and bicarbonate, we hypothesized that NCBE may be relevant for GABAergic transmission in the retina. Importantly, we found a differential expression of NCBE in bipolar cells: whereas NCBE was expressed on ON and OFF bipolar cell axon terminals, it only localized to dendrites of OFF bipolar cells. On these compartments, NCBE colocalized with the main neuronal chloride extruder KCC2, which renders GABA hyperpolarizing. NCBE was also expressed in starburst amacrine cells, but was absent from neurons known to depolarize in response to GABA, like horizontal cells. Mice lacking NCBE showed decreased visual acuity and contrast sensitivity in behavioral experiments and smaller b-wave amplitudes and longer latencies in electroretinograms. Ganglion cells from NCBE-deficient mice also showed altered temporal response properties. In summary, our data suggest that NCBE may serve to maintain intracellular chloride and bicarbonate concentration in retinal neurons. Consequently, lack of NCBE in the retina may result in changes in pHi regulation and chloride-dependent inhibition, leading to altered signal transmission and impaired visual function. PMID:23056253

Bumetanide-sensitive ion fluxes in vascular smooth muscle cells: lack of functional Na+, K+, 2 Cl- cotransport.

PubMed

Orlov, S N; Tremblay, J; Hamet, P

1996-09-01

To examine the involvement of Na+,K+,2Cl- cotransport in monovalent ion fluxes in vascular smooth muscle cells (VSMC), we compared the effect of bumetanide on 86Rb, 36Cl and 22Na uptake by quiescent cultures of VSMC from rat aorta. Under basal conditions, the values of bumetanide-sensitive (BS) inward and outward 86Rb fluxes were not different. Bumetanide decreased basal 86Rb uptake by 70-75% with a Ki of approximately 0.2-0.3 microM. At concentrations ranging up to 1 microM, bumetanide did not affect 36Cl influx and reduced it by 20-30% in the range from 3 to 100 microM. In contrast to 86Rb and 36Cl influx, bumetanide did not inhibit 22Na uptake by VSMC. BS 86Rb uptake was completely abolished in Na(+)- or Cl(-)-free media. In contrast to 86Rb, basal BS 36Cl influx was not affected by Nao+ and Ko+. Hyperosmotic and isosmotic shrinkage of VSMC increased 86Rb and 36Cl influx to the same extent. Shrinkage-induced increments of 86Rb and 36Cl uptake were completely abolished by bumetanide with a Ki or approximately 0.3 microM. Shrinkage did not induce BS 86Rb and 36Cl influx in (Na+ or Cl-)- and (Na+ or K+)-depleted media, respectively. In the presence of an inhibitor of Na+/H+ exchange (EIPA), neither hyperosmotic nor isosmotic shrinkage activated 22Na influx. Bumetanide (1 microM) did not modify basal VSMC volume and intracellular content of sodium, potassium and chloride but abolished the regulatory volume increase in isosmotically-shrunken VSMC. These data demonstrate the absence of the functional Na+,K+,2Cl- cotransporter in VSMC and suggest that in these cells basal and shrinkage-induced BS K+ influx is mediated by (Nao+ + Clo-)-dependent K+/K+ exchange and Nao(+)-dependent K+,Cl- cotransport, respectively.

Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors.

PubMed

Hill, Alexis S; Sahay, Amar; Hen, René

2015-09-01

Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects.

B1- non-uniformity correction of phased-array coils without measuring coil sensitivity.

PubMed

Damen, Frederick C; Cai, Kejia

2018-04-18

Parallel imaging can be used to increase SNR and shorten acquisition times, albeit, at the cost of image non-uniformity. B 1 - non-uniformity correction techniques are confounded by signal that varies not only due to coil induced B 1 - sensitivity variation, but also the object's own intrinsic signal. Herein, we propose a method that makes minimal assumptions and uses only the coil images themselves to produce a single combined B 1 - non-uniformity-corrected complex image with the highest available SNR. A novel background noise classifier is used to select voxels of sufficient quality to avoid the need for regularization. Unique properties of the magnitude and phase were used to reduce the B 1 - sensitivity to two joint additive models for estimation of the B 1 - inhomogeneity. The complementary corruption of the imaged object across the coil images is used to abate individual coil correction imperfections. Results are presented from two anatomical cases: (a) an abdominal image that is challenging in both extreme B 1 - sensitivity and intrinsic tissue signal variation, and (b) a brain image with moderate B 1 - sensitivity and intrinsic tissue signal variation. A new relative Signal-to-Noise Ratio (rSNR) quality metric is proposed to evaluate the performance of the proposed method and the RF receiving coil array. The proposed method has been shown to be robust to imaged objects with widely inhomogeneous intrinsic signal, and resilient to poorly performing coil elements. Copyright © 2018. Published by Elsevier Inc.

Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels.

PubMed

Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred; Flucher, Bernhard E

2016-06-01

Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3-S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3-S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3-S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3-S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3-S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms

Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels

PubMed Central

Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred

2016-01-01

Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3–S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3–S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3–S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3–S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3–S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular

Is the current level of training in the use of equipment for prehospital radio communication sufficient? A cross-sectional study among prehospital physicians in Denmark

PubMed Central

2017-01-01

Background Physicians working in prehospital care are expected to handle radio communication both within their own sector as well as with other divisions of the National Emergency Services. To date, no study has been conducted on the level of training received by physicians in the use of the equipment provided or on the level of competency acquired by physicians. Methods In order to investigate the self-assessed skill level acquired in the use of the TETRA (TErrestrial Trunked RAdio) authority radio for communication in a prehospital setting, a cross-sectional study was conducted by questionnaire circulated to all 454 physicians working in the Danish Emergency Medical Services. Results A lack of training was found among physicians working in prehospital care in Denmark in relation to the proper use of essential communication equipment. Prior to starting their first shift in a prehospital setting 38% of physicians reported having received no training in the use of the equipment, while 80% of physicians reported having received one1 hour of training or less. Among the majority of physicians their current level of training was sufficient for their everyday needs for prehospital communication but for 28% of physicians their current level of training was insufficient as they were unable to handle communication at this level. Conclusion As the first study in its field, this study investigated the training received in the use of essential communication equipment among physicians working in prehospital care in Denmark. The study found that competency does not appear to have been prioritised as highly as other technical skills needed to function in these settings. For the majority of physicians their current level of training was sufficient for everyday use but for a substantial minority further training is required, especially if the redundancy of the prehospital system is to be preserved. PMID:28667210

Lack of Association between Hepatitis C Virus core Gene Variation 70/91aa and Insulin Resistance.

PubMed

Scalioni, Letícia de Paula; da Silva, Allan Peres; Miguel, Juliana Custódio; Espírito Santo, Márcia Paschoal do; Marques, Vanessa Alves; Brandão-Mello, Carlos Eduardo; Villela-Nogueira, Cristiane Alves; Lewis-Ximenez, Lia Laura; Lampe, Elisabeth; Villar, Livia Melo

2017-07-21

The role of hepatitis C virus (HCV) in insulin resistance (IR) is not fully understood. The aim of this study was to determine the impact of amino acid (aa) substitutions in the core region of HCV according to IR and to identify clinical and laboratory associations. Ninety-two treatment-naive HCV patients were recruited to determine laboratory data and blood cell count. IR was determined using Homeostasis Model Assessment (HOMA) index where IR was defined as HOMA ≥2. HCV RNA load and genotype were determined by Abbott Real time HCV. HCV core region was determined by direct nucleotide sequencing. Bivariate analysis was conducted using HOMA IR ≥2 as a dependent factor. IR prevalence was 43.5% ( n = 40), vitamin D sufficiency was found in 76.1% ( n = 70) and 72.8% ( n = 67) had advanced liver fibrosis. In the bivariate analyses, elevated values of γGT ( p = 0.024) and fibrosis staging ( p = 0.004) were associated with IR, but IR was not related to core mutations. The presence of glutamine in position 70 was associated with low vitamin D concentration ( p = 0.005). In the multivariate analysis, no variable was independently associated with HOMA-IR. In conclusion, lack of association between IR and HCV core mutations in positions 70 and 91 suggests that genetic variability of this region has little impact on IR.

Designing robots for care: care centered value-sensitive design.

PubMed

van Wynsberghe, Aimee

2013-06-01

The prospective robots in healthcare intended to be included within the conclave of the nurse-patient relationship--what I refer to as care robots--require rigorous ethical reflection to ensure their design and introduction do not impede the promotion of values and the dignity of patients at such a vulnerable and sensitive time in their lives. The ethical evaluation of care robots requires insight into the values at stake in the healthcare tradition. What's more, given the stage of their development and lack of standards provided by the International Organization for Standardization to guide their development, ethics ought to be included into the design process of such robots. The manner in which this may be accomplished, as presented here, uses the blueprint of the Value-sensitive design approach as a means for creating a framework tailored to care contexts. Using care values as the foundational values to be integrated into a technology and using the elements in care, from the care ethics perspective, as the normative criteria, the resulting approach may be referred to as care centered value-sensitive design. The framework proposed here allows for the ethical evaluation of care robots both retrospectively and prospectively. By evaluating care robots in this way, we may ultimately ask what kind of care we, as a society, want to provide in the future.

Long-term sensitivity of soil carbon turnover to warming.

PubMed

Knorr, W; Prentice, I C; House, J I; Holland, E A

2005-01-20

The sensitivity of soil carbon to warming is a major uncertainty in projections of carbon dioxide concentration and climate. Experimental studies overwhelmingly indicate increased soil organic carbon (SOC) decomposition at higher temperatures, resulting in increased carbon dioxide emissions from soils. However, recent findings have been cited as evidence against increased soil carbon emissions in a warmer world. In soil warming experiments, the initially increased carbon dioxide efflux returns to pre-warming rates within one to three years, and apparent carbon pool turnover times are insensitive to temperature. It has already been suggested that the apparent lack of temperature dependence could be an artefact due to neglecting the extreme heterogeneity of soil carbon, but no explicit model has yet been presented that can reconcile all the above findings. Here we present a simple three-pool model that partitions SOC into components with different intrinsic turnover rates. Using this model, we show that the results of all the soil-warming experiments are compatible with long-term temperature sensitivity of SOC turnover: they can be explained by rapid depletion of labile SOC combined with the negligible response of non-labile SOC on experimental timescales. Furthermore, we present evidence that non-labile SOC is more sensitive to temperature than labile SOC, implying that the long-term positive feedback of soil decomposition in a warming world may be even stronger than predicted by global models.

Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.

PubMed

He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

2014-02-01

Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.

The Child's Conception of Food: The Development of Food Rejections with Special Reference to Disgust and Contamination Sensitivity.

ERIC Educational Resources Information Center

Fallon, April E.; And Others

1984-01-01

Reports the results of structured interviews with mothers of 29 children three and one-half to 12 years of age, documenting the development of four categories of food rejection based on distaste, danger, disgust, and inappropriateness. Suggests that lack of contamination sensitivity in younger children is due to their belief that chemical…

The Relationship of Social Support and Economic Self-Sufficiency to Substance Abuse Outcomes in a Long-Term Recovery Program for Women.

ERIC Educational Resources Information Center

Gregoire, Thomas K.; Snively, Carol

2001-01-01

Explores outcomes for 59 women who attended long term substance abuse treatment in a women's facility that emphasized employment and economic self sufficiency. Results revealed that reductions in substance abuse were associated with an increase in economic self sufficiency. Additionally, women living in drug free social environments had high rates…

Ultra-sensitive inertial sensors via neutral-atom interferometry

NASA Technical Reports Server (NTRS)

Clauser, John F.

1989-01-01

Upon looking at the various colossal interferometers, etc., discussed at this conference to test gravitational theory, one cannot avoid feeling that easier approaches exist. The use of low velocity, neutral atom matter waves in place of electromagnetic waves in sensitive inertial interferometer configurations is proposed. For applications, spacecraft experiments to sense a drag-free condition, to measure the Lense-Thirring precession, to measure the gravitomagnetic effect and/or the earth's geopotential (depending on altitude), and to detect long period gravitational waves are considered. Also, a terrestrial precision test of the equivalence principle on spin polarized atoms, capable of detecting effects of the 5th force is considered. While the ideas described herein are preliminary, the orders of magnitude are sufficiently tantalizing to warrant further study. Although existing proposed designs may be adequate for some of these experiments, the use of matter-wave interferometry offers reduced complexity and cost, and an absence of cryogenics.

Predator confusion is sufficient to evolve swarming behaviour

PubMed Central

Olson, Randal S.; Hintze, Arend; Dyer, Fred C.; Knoester, David B.; Adami, Christoph

2013-01-01

Swarming behaviours in animals have been extensively studied owing to their implications for the evolution of cooperation, social cognition and predator–prey dynamics. An important goal of these studies is discerning which evolutionary pressures favour the formation of swarms. One hypothesis is that swarms arise because the presence of multiple moving prey in swarms causes confusion for attacking predators, but it remains unclear how important this selective force is. Using an evolutionary model of a predator–prey system, we show that predator confusion provides a sufficient selection pressure to evolve swarming behaviour in prey. Furthermore, we demonstrate that the evolutionary effect of predator confusion on prey could in turn exert pressure on the structure of the predator's visual field, favouring the frontally oriented, high-resolution visual systems commonly observed in predators that feed on swarming animals. Finally, we provide evidence that when prey evolve swarming in response to predator confusion, there is a change in the shape of the functional response curve describing the predator's consumption rate as prey density increases. Thus, we show that a relatively simple perceptual constraint—predator confusion—could have pervasive evolutionary effects on prey behaviour, predator sensory mechanisms and the ecological interactions between predators and prey. PMID:23740485

Predator confusion is sufficient to evolve swarming behaviour.

PubMed

Olson, Randal S; Hintze, Arend; Dyer, Fred C; Knoester, David B; Adami, Christoph

2013-08-06

Swarming behaviours in animals have been extensively studied owing to their implications for the evolution of cooperation, social cognition and predator-prey dynamics. An important goal of these studies is discerning which evolutionary pressures favour the formation of swarms. One hypothesis is that swarms arise because the presence of multiple moving prey in swarms causes confusion for attacking predators, but it remains unclear how important this selective force is. Using an evolutionary model of a predator-prey system, we show that predator confusion provides a sufficient selection pressure to evolve swarming behaviour in prey. Furthermore, we demonstrate that the evolutionary effect of predator confusion on prey could in turn exert pressure on the structure of the predator's visual field, favouring the frontally oriented, high-resolution visual systems commonly observed in predators that feed on swarming animals. Finally, we provide evidence that when prey evolve swarming in response to predator confusion, there is a change in the shape of the functional response curve describing the predator's consumption rate as prey density increases. Thus, we show that a relatively simple perceptual constraint--predator confusion--could have pervasive evolutionary effects on prey behaviour, predator sensory mechanisms and the ecological interactions between predators and prey.