A SUBSTELLAR COMMON PROPER-MOTION COMPANION TO THE PLEIAD H II 1348

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

Geissler, Kerstin; Metchev, Stanimir A.; Pham, Alfonse

2012-02-10

We announce the identification of a proper-motion companion to the star H II 1348, a K5 V member of the Pleiades open cluster. The existence of a faint point source 1.''1 away from H II 1348 was previously known from adaptive optics imaging by Bouvier et al. However, because of a high likelihood of background star contamination and in the absence of follow-up astrometry, Bouvier et al. tentatively concluded that the candidate companion was not physically associated with H II 1348. We establish the proper-motion association of the pair from adaptive optics imaging with the Palomar 5 m telescope. Adaptivemore » optics spectroscopy with the integral field spectrograph OSIRIS on the Keck 10 m telescope reveals that the companion has a spectral type of M8 {+-} 1. According to substellar evolution models, the M8 spectral type resides within the substellar mass regime at the age of the Pleiades. The primary itself is a known double-lined spectroscopic binary, which makes the resolved companion, H II 1348B, the least massive and widest component of this hierarchical triple system and the first substellar companion to a stellar primary in the Pleiades.« less

ICC Type II large-format FPA detector assemblies

NASA Astrophysics Data System (ADS)

Clynne, Thomas H.; Powers, Thomas P.

1997-08-01

ICC presents a new addition to their integrated detector assembly product line with the announcement of their type II large format staring class FPA units. A result of internally funded research and development, the ICC type II detector assembly can accommodate all existing large format staring class PtSi, InSb and MCT focal planes, up to 640 by 480. Proprietary methodologies completely eliminate all FPA stresses to allow for maximum FPA survivability. Standard optical and cryocooler interfaces allow for the use of BEI, AEG, TI SADA Hughes/Magnavox and Joule Thompson coolers. This unit has been qualified to the current SADA II thermal environmental specifications and was tailored around ICC's worldwide industry standard type IV product. Assembled in a real world flexible manufacturing environment, this unit features a wide degree of adaptability and can be easily modified to a user's specifications via standard options and add-ons that include optical interfaces, electrical interfaces and window/filter material selections.

Different subsets of natural killer T cells may vary in their roles in health and disease

PubMed Central

Kumar, Vipin; Delovitch, Terry L

2014-01-01

Natural killer T cells (NKT) can regulate innate and adaptive immune responses. Type I and type II NKT cell subsets recognize different lipid antigens presented by CD1d, an MHC class-I-like molecule. Most type I NKT cells express a semi-invariant T-cell receptor (TCR), but a major subset of type II NKT cells reactive to a self antigen sulphatide use an oligoclonal TCR. Whereas TCR-α dominates CD1d-lipid recognition by type I NKT cells, TCR-α and TCR-β contribute equally to CD1d-lipid recognition by type II NKT cells. These variable modes of NKT cell recognition of lipid–CD1d complexes activate a host of cytokine-dependent responses that can either exacerbate or protect from disease. Recent studies of chronic inflammatory and autoimmune diseases have led to a hypothesis that: (i) although type I NKT cells can promote pathogenic and regulatory responses, they are more frequently pathogenic, and (ii) type II NKT cells are predominantly inhibitory and protective from such responses and diseases. This review focuses on a further test of this hypothesis by the use of recently developed techniques, intravital imaging and mass cytometry, to analyse the molecular and cellular dynamics of type I and type II NKT cell antigen-presenting cell motility, interaction, activation and immunoregulation that promote immune responses leading to health versus disease outcomes. PMID:24428389

Design and Implementation of Multi-Input Adaptive Signal Extractions.

DTIC Science & Technology

1980-07-31

8 𔃺 - I I 2 l ~lI II~ lliiII 111111L25 I )1.4 jg16 MICROCOPY RESOLUTION TEST CHART NA110NAt ftl Ali I TANtDAN[1A I "I A U*iI L ~ I0SGALADIAEPOESN A...NUMBER 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED _EIGN AND LLEMF TATICN OF XJLTI- NPUr A j n7T 1 Ax L )DAPTIVE NLEXRACTIONS 6. ERFORMING...conventional adaptive filtering and noise cancelling coni gurIFORM l / DD I JAN 73 1473 EDITION OF I NOV 65 IS OBSOLETE UNCLASSIFIED SECURITY

Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency

PubMed Central

Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

2017-01-01

Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels. PMID:28095507

Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.

PubMed

Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

2017-01-01

Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.

Crystal Structure of Streptococcus pyogenes Cas1 and Its Interaction with Csn2 in the Type II CRISPR-Cas System.

PubMed

Ka, Donghyun; Lee, Hasup; Jung, Yi-Deun; Kim, Kyunggon; Seok, Chaok; Suh, Nayoung; Bae, Euiyoung

2016-01-05

CRISPRs and Cas proteins constitute an RNA-guided microbial immune system against invading nucleic acids. Cas1 is a universal Cas protein found in all three types of CRISPR-Cas systems, and its role is implicated in new spacer acquisition during CRISPR-mediated adaptive immunity. Here, we report the crystal structure of Streptococcus pyogenes Cas1 (SpCas1) in a type II CRISPR-Cas system and characterize its interaction with S. pyogenes Csn2 (SpCsn2). The SpCas1 structure reveals a unique conformational state distinct from type I Cas1 structures, resulting in a more extensive dimerization interface, a more globular overall structure, and a disruption of potential metal-binding sites for catalysis. We demonstrate that SpCas1 directly interacts with SpCsn2, and identify the binding interface and key residues for Cas complex formation. These results provide structural information for a type II Cas1 protein, and lay a foundation for studying multiprotein Cas complexes functioning in type II CRISPR-Cas systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design.

PubMed

Levin, Bruce; Thompson, John L P; Chakraborty, Bibhas; Levy, Gilberto; MacArthur, Robert; Haley, E Clarke

2011-08-01

TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III. (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs. In phase II, an early (24-h) outcome and adaptive sequential procedure selected one of three tenecteplase doses for phase III comparison with rt-PA. Decision rules comparing this dose to rt-PA would cause stopping for futility at phase II end, or continuation to phase III. Phase III incorporated two co-primary hypotheses, allowing for a treatment effect at either end of the trichotomized Rankin scale. Assuming no early termination, four interim analyses and one final analysis of 1908 patients provided an experiment-wise type I error rate of <0.05. Over 1,000 distribution scenarios, each involving 40,000 replications, the maximum type I error in phase III was 0.038. Inflation from the dose selection was more than offset by the one-half continuity correction in the test statistics. Inflation from repeated interim analyses was more than offset by the reduction from the clinical stopping rules for futility at the first interim analysis. Design complexity and evolving regulatory requirements lengthened the review process. (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols for futility stopping may not be followed may be allayed by submitting interim analysis results to them as these analyses occur.

Corticosteroid receptor expression in a teleost fish that displays alternative male reproductive tactics.

PubMed

Arterbery, Adam S; Deitcher, David L; Bass, Andrew H

2010-01-01

Corticosteroid signaling mechanisms mediate a wide range of adaptive physiological responses, including those essential to reproduction. Here, we investigated the presence and relative abundance of corticosteroid receptors during the breeding season in the plainfin midshipman fish (Porichthys notatus), a species that has two male reproductive morphs. Only type I "singing" males acoustically court females and aggressively defend a nest site, whereas type II "sneaker" males steal fertilizations from nesting type I males. Cloning and sequencing first identified glucocorticoid (GR) and mineralocorticoid (MR) receptors in midshipman that exhibited high sequence identity with other vertebrate GRs and MRs. Absolute-quantitative real-time PCR then revealed higher levels of GR in the central nervous system (CNS) of type II males than type I males and females, while GR levels in the sound-producing, vocal muscle and the liver were higher in type I males than type II males and females. MR expression was also greater in the CNS of type II males than type I males or females, but the differences were more modest in magnitude. Lastly, plasma levels of cortisol, the main glucocorticoid in teleosts, were 2- to 3-fold greater in type II males compared to type I males. Together, the results suggest a link between corticosteroid regulation and physiological and behavioral variation in a teleost fish that displays male alternative reproductive tactics.

Different subsets of natural killer T cells may vary in their roles in health and disease.

PubMed

Kumar, Vipin; Delovitch, Terry L

2014-07-01

Natural killer T cells (NKT) can regulate innate and adaptive immune responses. Type I and type II NKT cell subsets recognize different lipid antigens presented by CD1d, an MHC class-I-like molecule. Most type I NKT cells express a semi-invariant T-cell receptor (TCR), but a major subset of type II NKT cells reactive to a self antigen sulphatide use an oligoclonal TCR. Whereas TCR-α dominates CD1d-lipid recognition by type I NKT cells, TCR-α and TCR-β contribute equally to CD1d-lipid recognition by type II NKT cells. These variable modes of NKT cell recognition of lipid-CD1d complexes activate a host of cytokine-dependent responses that can either exacerbate or protect from disease. Recent studies of chronic inflammatory and autoimmune diseases have led to a hypothesis that: (i) although type I NKT cells can promote pathogenic and regulatory responses, they are more frequently pathogenic, and (ii) type II NKT cells are predominantly inhibitory and protective from such responses and diseases. This review focuses on a further test of this hypothesis by the use of recently developed techniques, intravital imaging and mass cytometry, to analyse the molecular and cellular dynamics of type I and type II NKT cell antigen-presenting cell motility, interaction, activation and immunoregulation that promote immune responses leading to health versus disease outcomes. © 2014 John Wiley & Sons Ltd.

Inhibition of NHEJ repair by type II-A CRISPR-Cas systems in bacteria.

PubMed

Bernheim, Aude; Calvo-Villamañán, Alicia; Basier, Clovis; Cui, Lun; Rocha, Eduardo P C; Touchon, Marie; Bikard, David

2017-12-12

Type II CRISPR-Cas systems introduce double-strand breaks into DNA of invading genetic material and use DNA fragments to acquire novel spacers during adaptation. These breaks can be the substrate of several DNA repair pathways, paving the way for interactions. We report that non-homologous end-joining (NHEJ) and type II-A CRISPR-Cas systems only co-occur once among 5563 fully sequenced prokaryotic genomes. We investigated experimentally the possible molecular interactions using the NHEJ pathway from Bacillus subtilis and the type II-A CRISPR-Cas systems from Streptococcus thermophilus and Streptococcus pyogenes. Our results suggest that the NHEJ system has no effect on CRISPR immunity. On the other hand, we provide evidence for the inhibition of NHEJ repair by the Csn2 protein. Our findings give insights on the complex interactions between CRISPR-Cas systems and repair mechanisms in bacteria, contributing to explain the scattered distribution of CRISPR-Cas systems in bacterial genome.

Ribbon Synaptic Plasticity in Gravity Sensors of Rats Flown on Neurolab

NASA Technical Reports Server (NTRS)

Ross, Muriel D.; Varelas, Joseph

2003-01-01

Previous spaceflight experiments (Space Life Sciences-1 and -2 (SLS-1 and SLS-2)) first demonstrated the extraordinary ability of gravity sensor hair cells to change the number, kind, and distribution of connections (synapses) they make to other cells while in weightlessness. The number of synapses in hair cells in one part of the inner ear (the utricle) was markedly elevated on flight day 13 (FD13) of SLS-2. Unanswered questions, however, were whether these increases in synapses occur rapidly and whether they remain stable in weightlessness. The answers have implications for long-duration human space travel. If gravity sensors can adapt quickly, crews may be able to move easily between different gravity levels, since the sensors will adapt rapidly to weightlessness on the spacecraft and then back to Earth's gravity when the mission ends. This ability to adapt is also important for recovery from balance disorders. To further our understanding of this adaptive potential (a property called neuronal synaptic plasticity), the present Neurolab research was undertaken. Our experiment examined whether: (a) increases in synapses would remain stable throughout the flight, (b) changes in the number of synapses were uniform across different portions of the gravity sensors (the utricle and saccule), and (c) synaptic changes were similar for the different types of hair cells (Type I and Type II). Utricular and saccular maculae (the gravity-sensing portions of the inner ear) were collected in flight from rats on FD2 and FD14. Samples were also collected from control rats on the ground. Tissues were prepared for ultrastructural study. Hair cells and their ribbon synapses were examined in a transmission electron microscope. Synapses were counted in all hair cells in 50 consecutive sections that crossed the striolar zone. Results indicate that utricular hair cell synapses initially increased significantly in number in both types of hair cells by FD2. Counts declined by FD14, but the mean number of synapses in utricular Type II cells remained significantly higher than in the ground control rats. For saccular samples, synaptic number in Type I and Type II cells declined on FD2, but returned to near-baseline values by FD14. These findings indicate that: (a) synaptic plasticity occurs rapidly in weightlessness, and (b) synaptic changes are not identical for the two types of hair cells or for the two maculae.

The immunoregulatory role of type I and type II NKT cells in cancer and other diseases

PubMed Central

Terabe, Masaki; Berzofsky, Jay A.

2014-01-01

NKT cells are CD1d-restricted T cells that recognize lipid antigens. They also have been shown to play critical roles in the regulation of immune responses. In the immune responses against tumors, two subsets of NKT cells, type I and type II, play opposing roles and cross-regulate each other. As members of both the innate and adaptive immune systems, which form a network of multiple components, they also interact with other immune components. Here we discuss the function of NKT cells in tumor immunity and their interaction with other regulatory cells, especially CD4+CD25+Foxp3+ regulatory T cells. PMID:24384834

Natural alcohol exposure: is ethanol the main substrate for alcohol dehydrogenases in animals?

PubMed

Hernández-Tobías, Aída; Julián-Sánchez, Adriana; Piña, Enrique; Riveros-Rosas, Héctor

2011-05-30

Alcohol dehydrogenase (ADH) activity is widely distributed in all phyla. In animals, three non-homologous NAD(P)(+)-dependent ADH protein families are reported. These arose independently throughout evolution and possess different structures and mechanisms of reaction: type I (medium-chain) ADHs are zinc-containing enzymes and comprise the most studied group in vertebrates; type II (short-chain) ADHs lack metal cofactor and have been extensively studied in Drosophila; and type III ADHs are iron-dependent/-activated enzymes that were initially identified only in microorganisms. The presence of these different ADHs in animals has been assumed to be a consequence of chronic exposure to ethanol. By far the most common natural source of ethanol is fermentation of fruit sugars by yeast, and available data support that this fruit trait evolved in concert with the characteristics of their frugivorous seed dispersers. Therefore, if the presence of ADHs in animals evolved as an adaptive response to dietary ethanol exposure, then it can be expected that the enzymogenesis of these enzymes began after the appearance of angiosperms with fleshy fruits, because substrate availability must precede enzyme selection. In this work, available evidence supporting this possibility is discussed. Phylogenetic analyses reveal that type II ADHs suffered several duplications, all of these restricted to flies (order Diptera). Induction of type II Adh by ethanol exposure, a positive correlation between ADH activity and ethanol resistance, and the fact that flies and type II Adh diversification occurred in concert with angiosperm diversification, strongly suggest that type II ADHs were recruited to allow larval flies to exploit new restricted niches with high ethanol content. In contrast, phyletic distribution of types I and III ADHs in animals showed that these appeared before angiosperms and land plants, independently of ethanol availability. Because these enzymes are not induced by ethanol exposure and possess a high affinity and/or catalytic efficiency for non-ethanol endogenous substrates, it can be concluded that the participation of types I and III ADHs in ethanol metabolism can be considered as incidental, and not adaptive. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Novel, high-intensity exercise prescription improves muscle mass, mitochondrial function, and physical capacity in individuals with Parkinson's disease

PubMed Central

Kelly, Neil A.; Ford, Matthew P.; Standaert, David G.; Watts, Ray L.; Bickel, C. Scott; Moellering, Douglas R.; Tuggle, S. Craig; Williams, Jeri Y.; Lieb, Laura; Windham, Samuel T.

2014-01-01

We conducted, in persons with Parkinson's disease (PD), a thorough assessment of neuromotor function and performance in conjunction with phenotypic analyses of skeletal muscle tissue, and further tested the adaptability of PD muscle to high-intensity exercise training. Fifteen participants with PD (Hoehn and Yahr stage 2–3) completed 16 wk of high-intensity exercise training designed to simultaneously challenge strength, power, endurance, balance, and mobility function. Skeletal muscle adaptations (P < 0.05) to exercise training in PD included myofiber hypertrophy (type I: +14%, type II: +36%), shift to less fatigable myofiber type profile, and increased mitochondrial complex activity in both subsarcolemmal and intermyofibrillar fractions (I: +45–56%, IV: +39–54%). These adaptations were accompanied by a host of functional and clinical improvements (P < 0.05): total body strength (+30–56%); leg power (+42%); single leg balance (+34%); sit-to-stand motor unit activation requirement (−30%); 6-min walk (+43 m), Parkinson's Disease Quality of Life Scale (PDQ-39, −7.8pts); Unified Parkinson's Disease Rating Scale (UPDRS) total (−5.7 pts) and motor (−2.7 pts); and fatigue severity (−17%). Additionally, PD subjects in the pretraining state were compared with a group of matched, non-PD controls (CON; did not exercise). A combined assessment of muscle tissue phenotype and neuromuscular function revealed a higher distribution and larger cross-sectional area of type I myofibers and greater type II myofiber size heterogeneity in PD vs. CON (P < 0.05). In conclusion, persons with moderately advanced PD adapt to high-intensity exercise training with favorable changes in skeletal muscle at the cellular and subcellular levels that are associated with improvements in motor function, physical capacity, and fatigue perception. PMID:24408997

Identification and functional characterization of type II toxin/antitoxin systems in Aggregatibacter actinomycetemcomitans.

PubMed

Schneider, B; Weigel, W; Sztukowska, M; Demuth, D R

2018-06-01

Type II toxin/antitoxin (TA) systems contribute to the formation of persister cells and biofilm formation for many organisms. Aggregatibacter actinomycetemcomitans thrives in the complex oral microbial community subjected to continual environmental flux. Little is known regarding the presence and function of type II TA systems in this organism or their contribution to adaptation and persistence in the biofilm. We identified 11 TA systems that are conserved across all seven serotypes of A. actinomycetemcomitans and represent the RelBE, MazEF and HipAB families of type II TA systems. The systems selectively responded to various environmental conditions that exist in the oral cavity. Two putative RelBE-like TA systems, D11S_1194-1195 and D11S_1718-1719 were induced in response to low pH and deletion of D11S_1718-1719 significantly reduced metabolic activity of stationary phase A. actinomycetemcomitans cells upon prolonged exposure to acidic conditions. The deletion mutant also exhibited reduced biofilm biomass when cultured under acidic conditions. The D11S_1194 and D11S_1718 toxin proteins inhibited in vitro translation of dihydrofolate reductase (DHFR) and degraded ribosome-associated, but not free, MS2 virus RNA. In contrast, the corresponding antitoxins (D11S_1195 and D11S_1719), or equimolar mixtures of toxin and antitoxin, had no effect on DHFR production or RNA degradation. Together, these results suggest that D11S_1194-1195 and D11S_1718-1719 are RelBE-like type II TA systems that are activated under acidic conditions and may function to cleave ribosome-associated mRNA to inhibit translation in A. actinomycetemcomitans. In vivo, these systems may facilitate A. actinomycetemcomitans adaptation and persistence in acidic local environments in the dental biofilm. © 2018 The Authors. Molecular Oral Microbiology Published by John Wiley & Sons Ltd.

Strong Converse Exponents for a Quantum Channel Discrimination Problem and Quantum-Feedback-Assisted Communication

NASA Astrophysics Data System (ADS)

Cooney, Tom; Mosonyi, Milán; Wilde, Mark M.

2016-06-01

This paper studies the difficulty of discriminating between an arbitrary quantum channel and a "replacer" channel that discards its input and replaces it with a fixed state. The results obtained here generalize those known in the theory of quantum hypothesis testing for binary state discrimination. We show that, in this particular setting, the most general adaptive discrimination strategies provide no asymptotic advantage over non-adaptive tensor-power strategies. This conclusion follows by proving a quantum Stein's lemma for this channel discrimination setting, showing that a constant bound on the Type I error leads to the Type II error decreasing to zero exponentially quickly at a rate determined by the maximum relative entropy registered between the channels. The strong converse part of the lemma states that any attempt to make the Type II error decay to zero at a rate faster than the channel relative entropy implies that the Type I error necessarily converges to one. We then refine this latter result by identifying the optimal strong converse exponent for this task. As a consequence of these results, we can establish a strong converse theorem for the quantum-feedback-assisted capacity of a channel, sharpening a result due to Bowen. Furthermore, our channel discrimination result demonstrates the asymptotic optimality of a non-adaptive tensor-power strategy in the setting of quantum illumination, as was used in prior work on the topic. The sandwiched Rényi relative entropy is a key tool in our analysis. Finally, by combining our results with recent results of Hayashi and Tomamichel, we find a novel operational interpretation of the mutual information of a quantum channel {mathcal{N}} as the optimal Type II error exponent when discriminating between a large number of independent instances of {mathcal{N}} and an arbitrary "worst-case" replacer channel chosen from the set of all replacer channels.

Adaptive clinical trial designs for European marketing authorization: a survey of scientific advice letters from the European Medicines Agency.

PubMed

Elsäßer, Amelie; Regnstrom, Jan; Vetter, Thorsten; Koenig, Franz; Hemmings, Robert James; Greco, Martina; Papaluca-Amati, Marisa; Posch, Martin

2014-10-02

Since the first methodological publications on adaptive study design approaches in the 1990s, the application of these approaches in drug development has raised increasing interest among academia, industry and regulators. The European Medicines Agency (EMA) as well as the Food and Drug Administration (FDA) have published guidance documents addressing the potentials and limitations of adaptive designs in the regulatory context. Since there is limited experience in the implementation and interpretation of adaptive clinical trials, early interaction with regulators is recommended. The EMA offers such interactions through scientific advice and protocol assistance procedures. We performed a text search of scientific advice letters issued between 1 January 2007 and 8 May 2012 that contained relevant key terms. Letters containing questions related to adaptive clinical trials in phases II or III were selected for further analysis. From the selected letters, important characteristics of the proposed design and its context in the drug development program, as well as the responses of the Committee for Human Medicinal Products (CHMP)/Scientific Advice Working Party (SAWP), were extracted and categorized. For 41 more recent procedures (1 January 2009 to 8 May 2012), additional details of the trial design and the CHMP/SAWP responses were assessed. In addition, case studies are presented as examples. Over a range of 5½ years, 59 scientific advices were identified that address adaptive study designs in phase II and phase III clinical trials. Almost all were proposed as confirmatory phase III or phase II/III studies. The most frequently proposed adaptation was sample size reassessment, followed by dropping of treatment arms and population enrichment. While 12 (20%) of the 59 proposals for an adaptive clinical trial were not accepted, the great majority of proposals were accepted (15, 25%) or conditionally accepted (32, 54%). In the more recent 41 procedures, the most frequent concerns raised by CHMP/SAWP were insufficient justifications of the adaptation strategy, type I error rate control and bias. For the majority of proposed adaptive clinical trials, an overall positive opinion was given albeit with critical comments. Type I error rate control, bias and the justification of the design are common issues raised by the CHMP/SAWP.

Evolution of natural populations in the Drosophila melanogaster sigma virus system I. Languedoc (southern France).

PubMed

Fleuriet, A; Periquet, G; Anxolabéhère, D

1990-01-01

In natural populations of Drosophila melanogaster, sigma virus is usually present in a minority of individuals. The virus is transmitted transovarially but is not contagious from fly to fly. Two viral Types (I and II) are found in populations. One of them (Type II) is better adapted to an allele for resistance to the virus, present as a polymorphism in fly populations. Previous observations have led to the hypothesis that a viral Type II originating in central France might be invading populations. The study of Languedoc populations was undertaken to examine this hypothesis. Two striking phenomena were observed. The strong increase in Type II clones frequency (from 0.53 to 0.91) confirmed that there was invasion in this region. The frequency of infected flies also increased dramatically, at levels never observed elsewhere yet, which indicates that Languedoc should present some unusual characteristics. The epidemiological consequences of such a burst, in the case of a pathogenic virus would have to be taken into consideration. Significant changes in other viral characteristics, from 1983 to 1987, in Languedoc populations have also been documented.

Afferent innervation of the utricular macula in pigeons

NASA Technical Reports Server (NTRS)

Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David

2003-01-01

Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were located in the extrastriola. The cellular organization and innervation patterns of the utricular maculae in birds appear to represent an organ in adaptive evolution, different from that observed for amphibians or mammals.

A Phase I/II adaptive design for heterogeneous groups with application to a stereotactic body radiation therapy trial.

PubMed

Wages, Nolan A; Read, Paul W; Petroni, Gina R

2015-01-01

Dose-finding studies that aim to evaluate the safety of single agents are becoming less common, and advances in clinical research have complicated the paradigm of dose finding in oncology. A class of more complex problems, such as targeted agents, combination therapies and stratification of patients by clinical or genetic characteristics, has created the need to adapt early-phase trial design to the specific type of drug being investigated and the corresponding endpoints. In this article, we describe the implementation of an adaptive design based on a continual reassessment method for heterogeneous groups, modified to coincide with the objectives of a Phase I/II trial of stereotactic body radiation therapy in patients with painful osseous metastatic disease. Operating characteristics of the Institutional Review Board approved design are demonstrated under various possible true scenarios via simulation studies. Copyright © 2015 John Wiley & Sons, Ltd.

A robust adaptive load frequency control for micro-grids.

PubMed

Khooban, Mohammad-Hassan; Niknam, Taher; Blaabjerg, Frede; Davari, Pooya; Dragicevic, Tomislav

2016-11-01

The goal of this study is to introduce a novel robust load frequency control (LFC) strategy for micro-grid(s) (MG(s)) in islanded mode operation. Admittedly, power generators in MG(s) cannot supply steady electric power output and sometimes cause unbalance between supply and demand. Battery energy storage system (BESS) is one of the effective solutions to these problems. Due to the high cost of the BESS, a new idea of Vehicle-to-Grid (V2G) is that a battery of Electric-Vehicle (EV) can be applied as a tantamount large-scale BESS in MG(s). As a result, a new robust control strategy for an islanded micro-grid (MG) is introduced that can consider electric vehicles׳ (EV(s)) effect. Moreover, in this paper, a new combination of the General Type II Fuzzy Logic Sets (GT2FLS) and the Modified Harmony Search Algorithm (MHSA) technique is applied for adaptive tuning of proportional-integral (PI) controller. Implementing General Type II Fuzzy Systems is computationally expensive. However, using a recently introduced α-plane representation, GT2FLS can be seen as a composition of several Interval Type II Fuzzy Logic Systems (IT2FLS) with a corresponding level of α for each. Real-data from an offshore wind farm in Sweden and solar radiation data in Aberdeen (United Kingdom) was used in order to examine the performance of the proposed novel controller. A comparison is made between the achieved results of Optimal Fuzzy-PI (OFPI) controller and those of Optimal Interval Type II Fuzzy-PI (IT2FPI) controller, which are of most recent advances in the area at hand. The Simulation results prove the successfulness and effectiveness of the proposed controller. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane.

PubMed

Chichger, Havovi; Cleasby, Mark E; Srai, Surjit K; Unwin, Robert J; Debnam, Edward S; Marks, Joanne

2016-06-01

What is the central question of this study? Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown. What is the main finding and its importance? In vivo models of metabolic disruption (Goto-Kakizaki type II diabetic rat and junk-food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT- and GLUT-mediated glucose uptake. A fasted model of metabolic disruption (high-fat diet) demonstrated increased GLUT2 expression only. The differential alterations of glucose transporters in response to varying metabolic stress offer insight into the therapeutic value of inhibitors. SGLT2 inhibitors are now in clinical use to reduce hyperglycaemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet-induced insulin resistance. The study used Goto-Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk-food or high-fat diets. Levels of protein kinase C-βI (PKC-βI), GLUT2, SGLT1 and SGLT2 were determined by Western blotting of purified renal BBM. GLUT- and SGLT-mediated d-[(3) H]glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. GLUT- and SGLT-mediated glucose transport was elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC-βI and SGLT1 protein. Junk-food and high-fat diet feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC-βI. However, the junk-food diet also increased SGLT1 and SGLT2 levels at the proximal tubule BBM. Glucose reabsorption across the proximal tubule BBM, via GLUT2, SGLT1 and SGLT2, is not solely dependent on glycaemic status, but is also influenced by diet-induced changes in glucose metabolism. We conclude that different metabolic disturbances result in complex adaptations in renal glucose transporter protein levels and function. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Adapting clinical guidelines in low‐resources countries: a study on the guideline on the management and prevention of type 2 diabetes mellitus in Indonesia

PubMed Central

Wangge, Grace; van der Graaf, Yolanda; van der Heijden, Geert J. M. G.

2016-01-01

Abstract Rationale, aims and objectives Most of the clinical guidelines in low‐resource countries are adaptations from preexisting international guidelines. This adaptation can be problematic when those international guidelines are not based on current evidence or original evidence‐based international guidelines are not followed. This study aims to evaluate the quality of an Indonesian type 2 diabetes mellitus guideline adapted from selected international guidelines. Methods The “Consensus on the Management and Prevention of type 2 Diabetes in Indonesia 2011” is a guideline by the Indonesian Society of Endocrinology (Perkeni). Four parent guidelines identified from its list of references were from the International Diabetes Federation (IDF), American Association of Clinical Endocrinologist (AACE), American Diabetes Association (ADA), and one jointly released by ADA and European Association for the Study of Diabetes (EASD). Two reviewers independently assessed its quality using the Appraisal of Guidelines, Research and Evaluation Collaboration (AGREE II) instrument. Six recommendations were compared: (1) screening for diabetes; (2) diagnosis; (3) control of hyperglycemia; (4) target blood glucose; (5) target blood pressure; and (6) treatment of dyslipidemia. Results Perkeni's guideline satisfied 55% of the AGREE II items, while its parent guidelines satisfied 59% to 74%. Perkeni's shows low score on “rigor of development” and “applicability” and the lowest score in the “scope and purpose” domain. Differences were found in 4 recommendations: the screening of diabetes, control of hyperglycemia, target blood glucose, and treatment of dyslipidemia. In 3 of 4, Perkeni followed the ADA's recommendation. Conclusion Derivation of recommendations from parent guidelines and their adaptation to the context of Indonesian health care lacks transparency. When guidelines are either derived from other guidelines or adapted for use in different context, evidence‐based practice principles should be followed and adhered to. PMID:27592587

Adapting clinical guidelines in low-resources countries: a study on the guideline on the management and prevention of type 2 diabetes mellitus in Indonesia.

PubMed

Widyahening, Indah S; Wangge, Grace; van der Graaf, Yolanda; van der Heijden, Geert J M G

2017-02-01

Most of the clinical guidelines in low-resource countries are adaptations from preexisting international guidelines. This adaptation can be problematic when those international guidelines are not based on current evidence or original evidence-based international guidelines are not followed. This study aims to evaluate the quality of an Indonesian type 2 diabetes mellitus guideline adapted from selected international guidelines. The "Consensus on the Management and Prevention of type 2 Diabetes in Indonesia 2011" is a guideline by the Indonesian Society of Endocrinology (Perkeni). Four parent guidelines identified from its list of references were from the International Diabetes Federation (IDF), American Association of Clinical Endocrinologist (AACE), American Diabetes Association (ADA), and one jointly released by ADA and European Association for the Study of Diabetes (EASD). Two reviewers independently assessed its quality using the Appraisal of Guidelines, Research and Evaluation Collaboration (AGREE II) instrument. Six recommendations were compared: (1) screening for diabetes; (2) diagnosis; (3) control of hyperglycemia; (4) target blood glucose; (5) target blood pressure; and (6) treatment of dyslipidemia. Perkeni's guideline satisfied 55% of the AGREE II items, while its parent guidelines satisfied 59% to 74%. Perkeni's shows low score on "rigor of development" and "applicability" and the lowest score in the "scope and purpose" domain. Differences were found in 4 recommendations: the screening of diabetes, control of hyperglycemia, target blood glucose, and treatment of dyslipidemia. In 3 of 4, Perkeni followed the ADA's recommendation. Derivation of recommendations from parent guidelines and their adaptation to the context of Indonesian health care lacks transparency. When guidelines are either derived from other guidelines or adapted for use in different context, evidence-based practice principles should be followed and adhered to. © 2016 The Authors Journal of Evaluation in Clinical Practice Published by John Wiley & Sons Ltd.

Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov

PubMed Central

Bothwell, Laura E; Avorn, Jerry; Khan, Nazleen F; Kesselheim, Aaron S

2018-01-01

Objectives This review investigates characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials. Design Review of adaptive design clinical trials in EMBASE, PubMed, Cochrane Registry of Controlled Clinical Trials, Web of Science and ClinicalTrials.gov. Phase I and seamless Phase I/II trials were excluded. Variables extracted from trials included basic study characteristics, adaptive design features, size and use of independent data monitoring committees (DMCs) and blinded interim analyses. We also examined use of the adaptive trials in new drug submissions to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) and recorded regulators’ experiences with adaptive designs. Results 142 studies met inclusion criteria. There has been a recent growth in publicly reported use of adaptive designs among researchers around the world. The most frequently appearing types of adaptations were seamless Phase II/III (57%), group sequential (21%), biomarker adaptive (20%), and adaptive dose-finding designs (16%). About one-third (32%) of trials reported an independent DMC, while 6% reported blinded interim analysis. We found that 9% of adaptive trials were used for FDA product approval consideration, and 12% were used for EMA product approval consideration. International regulators had mixed experiences with adaptive trials. Many product applications with adaptive trials had extensive correspondence between drug sponsors and regulators regarding the adaptive designs, in some cases with regulators requiring revisions or alterations to research designs. Conclusions Wider use of adaptive designs will necessitate new drug application sponsors to engage with regulatory scientists during planning and conduct of the trials. Investigators need to more consistently report protections intended to preserve confidentiality and minimise potential operational bias during interim analysis. PMID:29440155

Novel Pelagic Iron-Oxidizing Zetaproteobacteria from the Chesapeake Bay Oxic-Anoxic Transition Zone.

PubMed

Chiu, Beverly K; Kato, Shingo; McAllister, Sean M; Field, Erin K; Chan, Clara S

2017-01-01

Chemolithotrophic iron-oxidizing bacteria (FeOB) could theoretically inhabit any environment where Fe(II) and O 2 (or nitrate) coexist. Until recently, marine Fe-oxidizing Zetaproteobacteria had primarily been observed in benthic and subsurface settings, but not redox-stratified water columns. This may be due to the challenges that a pelagic lifestyle would pose for Zetaproteobacteria, given low Fe(II) concentrations in modern marine waters and the possibility that Fe oxyhydroxide biominerals could cause cells to sink. However, we recently cultivated Zetaproteobacteria from the Chesapeake Bay oxic-anoxic transition zone, suggesting that they can survive and contribute to biogeochemical cycling in a stratified estuary. Here we describe the isolation, characterization, and genomes of two new species, Mariprofundus aestuarium CP-5 and Mariprofundus ferrinatatus CP-8, which are the first Zetaproteobacteria isolates from a pelagic environment. We looked for adaptations enabling strains CP-5 and CP-8 to overcome the challenges of living in a low Fe redoxcline with frequent O 2 fluctuations due to tidal mixing. We found that the CP strains produce distinctive dreadlock-like Fe oxyhydroxide structures that are easily shed, which would help cells maintain suspension in the water column. These oxides are by-products of Fe(II) oxidation, likely catalyzed by the putative Fe(II) oxidase encoded by the cyc2 gene, present in both CP-5 and CP-8 genomes; the consistent presence of cyc2 in all microaerophilic FeOB and other FeOB genomes supports its putative role in Fe(II) oxidation. The CP strains also have two gene clusters associated with biofilm formation (Wsp system and the Widespread Colonization Island) that are absent or rare in other Zetaproteobacteria. We propose that biofilm formation enables the CP strains to attach to FeS particles and form flocs, an advantageous strategy for scavenging Fe(II) and developing low [O 2 ] microenvironments within more oxygenated waters. However, the CP strains appear to be adapted to somewhat higher concentrations of O 2 , as indicated by the presence of genes encoding aa 3 -type cytochrome c oxidases, but not the cbb 3 -type found in all other Zetaproteobacteria isolate genomes. Overall, our results reveal adaptations for life in a physically dynamic, low Fe(II) water column, suggesting that niche-specific strategies can enable Zetaproteobacteria to live in any environment with Fe(II).

Novel Pelagic Iron-Oxidizing Zetaproteobacteria from the Chesapeake Bay Oxic–Anoxic Transition Zone

PubMed Central

Chiu, Beverly K.; Kato, Shingo; McAllister, Sean M.; Field, Erin K.; Chan, Clara S.

2017-01-01

Chemolithotrophic iron-oxidizing bacteria (FeOB) could theoretically inhabit any environment where Fe(II) and O2 (or nitrate) coexist. Until recently, marine Fe-oxidizing Zetaproteobacteria had primarily been observed in benthic and subsurface settings, but not redox-stratified water columns. This may be due to the challenges that a pelagic lifestyle would pose for Zetaproteobacteria, given low Fe(II) concentrations in modern marine waters and the possibility that Fe oxyhydroxide biominerals could cause cells to sink. However, we recently cultivated Zetaproteobacteria from the Chesapeake Bay oxic–anoxic transition zone, suggesting that they can survive and contribute to biogeochemical cycling in a stratified estuary. Here we describe the isolation, characterization, and genomes of two new species, Mariprofundus aestuarium CP-5 and Mariprofundus ferrinatatus CP-8, which are the first Zetaproteobacteria isolates from a pelagic environment. We looked for adaptations enabling strains CP-5 and CP-8 to overcome the challenges of living in a low Fe redoxcline with frequent O2 fluctuations due to tidal mixing. We found that the CP strains produce distinctive dreadlock-like Fe oxyhydroxide structures that are easily shed, which would help cells maintain suspension in the water column. These oxides are by-products of Fe(II) oxidation, likely catalyzed by the putative Fe(II) oxidase encoded by the cyc2 gene, present in both CP-5 and CP-8 genomes; the consistent presence of cyc2 in all microaerophilic FeOB and other FeOB genomes supports its putative role in Fe(II) oxidation. The CP strains also have two gene clusters associated with biofilm formation (Wsp system and the Widespread Colonization Island) that are absent or rare in other Zetaproteobacteria. We propose that biofilm formation enables the CP strains to attach to FeS particles and form flocs, an advantageous strategy for scavenging Fe(II) and developing low [O2] microenvironments within more oxygenated waters. However, the CP strains appear to be adapted to somewhat higher concentrations of O2, as indicated by the presence of genes encoding aa3-type cytochrome c oxidases, but not the cbb3-type found in all other Zetaproteobacteria isolate genomes. Overall, our results reveal adaptations for life in a physically dynamic, low Fe(II) water column, suggesting that niche-specific strategies can enable Zetaproteobacteria to live in any environment with Fe(II). PMID:28769885

Changes in skeletal muscle with aging: effects of exercise training.

PubMed

Rogers, M A; Evans, W J

1993-01-01

There is an approximate 30% decline in muscle strength and a 40% reduction in muscle area between the second and seventh decades of life. Thus, the loss of muscle mass with aging appears to be the major factor in the age-related loss of muscle strength. The loss of muscle mass is partially due to a significant decline in the numbers of both Type I and Type II muscle fibers plus a decrease in the size of the muscle cells, with the Type II fibers showing a preferential atrophy. There appears to be no loss of glycolytic capacity in senescent skeletal muscle whereas muscle oxidative enzyme activity and muscle capillarization decrease by about 25%. Vigorous endurance exercise training in older people, where the stimulus is progressively increased, elicits a proliferation of muscle capillaries, an increase in oxidative enzyme activity, and a significant improvement in VO2max. Likewise, progressive resistive training in older individuals results in muscle hypertrophy and increased strength, if the training stimulus is of a sufficient intensity and duration. Since older individuals adapt to resistive and endurance exercise training in a similar fashion to young people, the decline in the muscle's metabolic and force-producing capacity can no longer be considered as an inevitable consequence of the aging process. Rather, the adaptations in aging skeletal muscle to exercise training may prevent sarcopenia, enhance the ease of carrying out the activities of daily living, and exert a beneficial effect on such age-associated diseases as Type II diabetes, coronary artery disease, hypertension, osteoporosis, and obesity.

People with Usher Syndrome, Type II: Issues and Adaptations.

ERIC Educational Resources Information Center

Miner, I. D.

1997-01-01

Describes the experiences of individuals with Usher Syndrome, discusses the lack of appropriate services and the failure of professionals to provide sufficient information on the condition, and stresses the importance of access to information and the acquisition of new skills before the visual impairment becomes severe. (Author/CR)

STL-based Analysis of TRAIL-induced Apoptosis Challenges the Notion of Type I/Type II Cell Line Classification

PubMed Central

Bertaux, François; Maler, Oded; Batt, Gregory

2013-01-01

Extrinsic apoptosis is a programmed cell death triggered by external ligands, such as the TNF-related apoptosis inducing ligand (TRAIL). Depending on the cell line, the specific molecular mechanisms leading to cell death may significantly differ. Precise characterization of these differences is crucial for understanding and exploiting extrinsic apoptosis. Cells show distinct behaviors on several aspects of apoptosis, including (i) the relative order of caspases activation, (ii) the necessity of mitochondria outer membrane permeabilization (MOMP) for effector caspase activation, and (iii) the survival of cell lines overexpressing Bcl2. These differences are attributed to the activation of one of two pathways, leading to classification of cell lines into two groups: type I and type II. In this work we challenge this type I/type II cell line classification. We encode the three aforementioned distinguishing behaviors in a formal language, called signal temporal logic (STL), and use it to extensively test the validity of a previously-proposed model of TRAIL-induced apoptosis with respect to experimental observations made on different cell lines. After having solved a few inconsistencies using STL-guided parameter search, we show that these three criteria do not define consistent cell line classifications in type I or type II, and suggest mutants that are predicted to exhibit ambivalent behaviors. In particular, this finding sheds light on the role of a feedback loop between caspases, and reconciliates two apparently-conflicting views regarding the importance of either upstream or downstream processes for cell-type determination. More generally, our work suggests that these three distinguishing behaviors should be merely considered as type I/II features rather than cell-type defining criteria. On the methodological side, this work illustrates the biological relevance of STL-diagrams, STL population data, and STL-guided parameter search implemented in the tool Breach. Such tools are well-adapted to the ever-increasing availability of heterogeneous knowledge on complex signal transduction pathways. PMID:23675292

Is automated kinetic measurement superior to end-point for advanced oxidation protein product?

PubMed

Oguz, Osman; Inal, Berrin Bercik; Emre, Turker; Ozcan, Oguzhan; Altunoglu, Esma; Oguz, Gokce; Topkaya, Cigdem; Guvenen, Guvenc

2014-01-01

Advanced oxidation protein product (AOPP) was first described as an oxidative protein marker in chronic uremic patients and measured with a semi-automatic end-point method. Subsequently, the kinetic method was introduced for AOPP assay. We aimed to compare these two methods by adapting them to a chemistry analyzer and to investigate the correlation between AOPP and fibrinogen, the key molecule responsible for human plasma AOPP reactivity, microalbumin, and HbA1c in patients with type II diabetes mellitus (DM II). The effects of EDTA and citrate-anticogulated tubes on these two methods were incorporated into the study. This study included 93 DM II patients (36 women, 57 men) with HbA1c levels > or = 7%, who were admitted to the diabetes and nephrology clinics. The samples were collected in EDTA and in citrate-anticoagulated tubes. Both methods were adapted to a chemistry analyzer and the samples were studied in parallel. In both types of samples, we found a moderate correlation between the kinetic and the endpoint methods (r = 0.611 for citrate-anticoagulated, r = 0.636 for EDTA-anticoagulated, p = 0.0001 for both). We found a moderate correlation between fibrinogen-AOPP and microalbumin-AOPP levels only in the kinetic method (r = 0.644 and 0.520 for citrate-anticoagulated; r = 0.581 and 0.490 for EDTA-anticoagulated, p = 0.0001). We conclude that adaptation of the end-point method to automation is more difficult and it has higher between-run CV% while application of the kinetic method is easier and it may be used in oxidative stress studies.

Ontogenetic and evolutionary effects of predation and competition on nine-spined stickleback (Pungitius pungitius) body size.

PubMed

Välimäki, Kaisa; Herczeg, Gábor

2012-07-01

1. Individual- and population-level variation in body size and growth often correlates with many fitness traits. Predation and food availability are expected to affect body size and growth as important agents of both natural selection and phenotypic plasticity. How differences in predation and food availability affect body size/growth during ontogeny in populations adapted to different predation and competition regimes is rarely studied. 2. Nine-spined stickleback (Pungitius pungitius) populations originating from habitats with varying levels of predation and competition are known to be locally adapted to their respective habitats in terms of body size and growth. Here, we studied how different levels of perceived predation risk and competition during ontogeny affect the reaction norms of body size and growth in (i) marine and pond populations adapted to different levels of predation and competition and (ii) different sexes. We reared nine-spined stickleback in a factorial experiment under two levels of perceived predation risk (present/absent) and competition (high/low food supply). 3. We found divergence in the reaction norms at two levels: (i) predation-adapted marine stickleback had stronger reactions to predatory cues than intraspecific competition-adapted pond stickleback, the latter being more sensitive to available food than the marine fish and (ii) females reacting more strongly to the treatments than males. 4. The repeated, habitat-dependent nature of the differences suggests that natural selection is the agent behind the observed patterns. Our results suggest that genetic adaptation to certain environmental factors also involves an increase in the range of expressible phenotypic plasticity. We found support for this phenomenon at two levels: (i) across populations driven by habitat type and (ii) within populations driven by sex. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

CRISPRTarget

PubMed Central

Biswas, Ambarish; Gagnon, Joshua N.; Brouns, Stan J.J.; Fineran, Peter C.; Brown, Chris M.

2013-01-01

The bacterial and archaeal CRISPR/Cas adaptive immune system targets specific protospacer nucleotide sequences in invading organisms. This requires base pairing between processed CRISPR RNA and the target protospacer. For type I and II CRISPR/Cas systems, protospacer adjacent motifs (PAM) are essential for target recognition, and for type III, mismatches in the flanking sequences are important in the antiviral response. In this study, we examine the properties of each class of CRISPR. We use this information to provide a tool (CRISPRTarget) that predicts the most likely targets of CRISPR RNAs (http://bioanalysis.otago.ac.nz/CRISPRTarget). This can be used to discover targets in newly sequenced genomic or metagenomic data. To test its utility, we discover features and targets of well-characterized Streptococcus thermophilus and Sulfolobus solfataricus type II and III CRISPR/Cas systems. Finally, in Pectobacterium species, we identify new CRISPR targets and propose a model of temperate phage exposure and subsequent inhibition by the type I CRISPR/Cas systems. PMID:23492433

Ultrastructural Analysis of the Cristae Ampullares in the Squirrel Monkey (Saimiri sciureus)*

PubMed Central

Lysakowski, Anna; Goldberg, Jay M.

2008-01-01

Type I hair cells outnumber type II hair cells (HCs) in squirrel monkey (Saimiri sciureus) cristae by a nearly 3:1 ratio. Associated with this type I HC preponderance, calyx fibers make up a much larger fraction of the afferent innervation than in rodents (Fernández et al., 1995). To study how this affected synaptic architecture, we used disector methods to estimate various features associated with type I and type II HCs in central (CZ) and peripheral (PZ) zones of monkey cristae. Each type I HC makes, on average, 5–10 ribbon synapses with the inner face of a calyx ending. Inner-face synapses outnumber those on calyx outer faces by a 40:1 ratio. Expressed per afferent, there are, on average, 15 inner-face ribbon synapses, 0.38 outer-face ribbons and 2.6 efferent boutons on calyx-bearing endings. Calyceal invaginations per type I HC range from 19 in CZ to 3 in PZ. For type II HCs, there are many more ribbons and afferent boutons in PZ than in CZ, whereas efferent innervation is relatively uniform throughout the neuroepithelium. Despite outer-face ribbons being more numerous in chinchilla than in squirrel monkey, afferent discharge properties are similar (Lysakowski et al., 1995), reinforcing the importance of inner-face ribbons in synaptic transmission. Comparisons across mammalian species suggest the prevalence of type I HCs is a primate characteristic, rather than an arboreal lifestyle adaptation. Unlike cristae, type II HCs predominate in monkey maculae. Differences in hair-cell counts may reflect the stimulus magnitudes handled by semicircular canals and otolith organs. PMID:18729176

Optics in Atmospheric Propagation and Adaptive Systems II. Volume 3219

DTIC Science & Technology

1998-05-21

08] N. S. Kopeika, D. Sadot, I. Dror, Ben-Gurion Univ. of the Negev (Israel) 52 Characteristics of shipborne targets in warm coastal... Negev Beer-Sheva, Israel ABSTRACT A recent paper by Belen’kii proposed an inner scale turbulence MTF theory model to explain one of the many types of

High-Resolution Imaging of Parafoveal Cones in Different Stages of Diabetic Retinopathy Using Adaptive Optics Fundus Camera.

PubMed

Soliman, Mohamed Kamel; Sadiq, Mohammad Ali; Agarwal, Aniruddha; Sarwar, Salman; Hassan, Muhammad; Hanout, Mostafa; Graf, Frank; High, Robin; Do, Diana V; Nguyen, Quan Dong; Sepah, Yasir J

2016-01-01

To assess cone density as a marker of early signs of retinopathy in patients with type II diabetes mellitus. An adaptive optics (AO) retinal camera (rtx1™; Imagine Eyes, Orsay, France) was used to acquire images of parafoveal cones from patients with type II diabetes mellitus with or without retinopathy and from healthy controls with no known systemic or ocular disease. Cone mosaic was captured at 0° and 2°eccentricities along the horizontal and vertical meridians. The density of the parafoveal cones was calculated within 100×100-μm squares located at 500-μm from the foveal center along the orthogonal meridians. Manual corrections of the automated counting were then performed by 2 masked graders. Cone density measurements were evaluated with ANOVA that consisted of one between-subjects factor, stage of retinopathy and the within-subject factors. The ANOVA model included a complex covariance structure to account for correlations between the levels of the within-subject factors. Ten healthy participants (20 eyes) and 25 patients (29 eyes) with type II diabetes mellitus were recruited in the study. The mean (± standard deviation [SD]) age of the healthy participants (Control group), patients with diabetes without retinopathy (No DR group), and patients with diabetic retinopathy (DR group) was 55 ± 8, 53 ± 8, and 52 ± 9 years, respectively. The cone density was significantly lower in the moderate nonproliferative diabetic retinopathy (NPDR) and severe NPDR/proliferative DR groups compared to the Control, No DR, and mild NPDR groups (P < 0.05). No correlation was found between cone density and the level of hemoglobin A1c (HbA1c) or the duration of diabetes. The extent of photoreceptor loss on AO imaging may correlate positively with severity of DR in patients with type II diabetes mellitus. Photoreceptor loss may be more pronounced among patients with advanced stages of DR due to higher risk of macular edema and its sequelae.

Adaptation of the Haloarcula hispanica CRISPR-Cas system to a purified virus strictly requires a priming process

PubMed Central

Li, Ming; Wang, Rui; Zhao, Dahe; Xiang, Hua

2014-01-01

The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system mediates adaptive immunity against foreign nucleic acids in prokaryotes. However, efficient adaptation of a native CRISPR to purified viruses has only been observed for the type II-A system from a Streptococcus thermophilus industry strain, and rarely reported for laboratory strains. Here, we provide a second native system showing efficient adaptation. Infected by a newly isolated virus HHPV-2, Haloarcula hispanica type I-B CRISPR system acquired spacers discriminatively from viral sequences. Unexpectedly, in addition to Cas1, Cas2 and Cas4, this process also requires Cas3 and at least partial Cascade proteins, which are involved in interference and/or CRISPR RNA maturation. Intriguingly, a preexisting spacer partially matching a viral sequence is also required, and spacer acquisition from upstream and downstream sequences of its target sequence (i.e. priming protospacer) shows different strand bias. These evidences strongly indicate that adaptation in this system strictly requires a priming process. This requirement, if validated also true for other CRISPR systems as implied by our bioinformatic analysis, may help to explain failures to observe efficient adaptation to purified viruses in many laboratory strains, and the discrimination mechanism at the adaptation level that has confused scientists for years. PMID:24265226

Fast spacecraft adaptive attitude tracking control through immersion and invariance design

NASA Astrophysics Data System (ADS)

Wen, Haowei; Yue, Xiaokui; Li, Peng; Yuan, Jianping

2017-10-01

This paper presents a novel non-certainty-equivalence adaptive control method for the attitude tracking control problem of spacecraft with inertia uncertainties. The proposed immersion and invariance (I&I) based adaptation law provides a more direct and flexible approach to circumvent the limitations of the basic I&I method without employing any filter signal. By virtue of the adaptation high-gain equivalence property derived from the proposed adaptive method, the closed-loop adaptive system with a low adaptation gain could recover the high adaptation gain performance of the filter-based I&I method, and the resulting control torque demands during the initial transient has been significantly reduced. A special feature of this method is that the convergence of the parameter estimation error has been observably improved by utilizing an adaptation gain matrix instead of a single adaptation gain value. Numerical simulations are presented to highlight the various benefits of the proposed method compared with the certainty-equivalence-based control method and filter-based I&I control schemes.

A modified varying-stage adaptive phase II/III clinical trial design.

PubMed

Dong, Gaohong; Vandemeulebroecke, Marc

2016-07-01

Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Analysis of the type II-A CRISPR-Cas system of Streptococcus agalactiae reveals distinctive features according to genetic lineages

PubMed Central

Lier, Clément; Baticle, Elodie; Horvath, Philippe; Haguenoer, Eve; Valentin, Anne-Sophie; Glaser, Philippe; Mereghetti, Laurent; Lanotte, Philippe

2015-01-01

CRISPR-Cas systems (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) are found in 90% of archaea and about 40% of bacteria. In this original system, CRISPR arrays comprise short, almost unique sequences called spacers that are interspersed with conserved palindromic repeats. These systems play a role in adaptive immunity and participate to fight non-self DNA such as integrative and conjugative elements, plasmids, and phages. In Streptococcus agalactiae, a bacterium implicated in colonization and infections in humans since the 1960s, two CRISPR-Cas systems have been described. A type II-A system, characterized by proteins Cas9, Cas1, Cas2, and Csn2, is ubiquitous, and a type I–C system, with the Cas8c signature protein, is present in about 20% of the isolates. Unlike type I–C, which appears to be non-functional, type II-A appears fully functional. Here we studied type II-A CRISPR-cas loci from 126 human isolates of S. agalactiae belonging to different clonal complexes that represent the diversity of the species and that have been implicated in colonization or infection. The CRISPR-cas locus was analyzed both at spacer and repeat levels. Major distinctive features were identified according to the phylogenetic lineages previously defined by multilocus sequence typing, especially for the sequence type (ST) 17, which is considered hypervirulent. Among other idiosyncrasies, ST-17 shows a significantly lower number of spacers in comparison with other lineages. This characteristic could reflect the peculiar virulence or colonization specificities of this lineage. PMID:26124774

Adaptations to Curriculum at the Quartermaster School Officer Candidate Course during World War II

DTIC Science & Technology

2012-06-08

ADAPTATIONS TO CURRICULUM AT THE QUARTERMASTER SCHOOL OFFICER CANDIDATE COURSE DURING WORLD WAR II A thesis presented to the Faculty...AUG 2011 – JUNE 2012 4. TITLE AND SUBTITLE Adaptations to Curriculum at the Quartermaster School Officer Candidate Course During World War II...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The United States Army faced an officer shortage while mobilizing before World War II. General

A model of stereocilia adaptation based on single molecule mechanical studies of myosin I.

PubMed Central

Batters, Christopher; Wallace, Mark I; Coluccio, Lynne M; Molloy, Justin E

2004-01-01

We have used an optical tweezers-based apparatus to perform single molecule mechanical experiments using the unconventional myosins, Myo1b and Myo1c. The single-headed nature and slow ATPase kinetics of these myosins make them ideal for detailed studies of the molecular mechanism of force generation by acto-myosin. Myo1c exhibits several features that have not been seen using fast skeletal muscle myosin II. (i) The working stroke occurs in two, distinct phases, producing an initial 3 nm and then a further 1.5 nm of movement. (ii) Two types of binding interaction were observed: short-lived ATP-independent binding events that produced no movement and longer-lived, ATP-dependent events that produced a full working stroke. The stiffness of both types of interaction was similar. (iii) In a new type of experiment, using feedback to apply controlled displacements to a single acto-myosin cross-bridge, we found abrupt changes in force during attachment of the acto-Myo1b cross-bridge, a result that is consistent with the classical 'T2' behaviour of single muscle fibres. Given that these myosins might exhibit the classical T2 behaviour, we propose a new model to explain the slow phase of sensory adaptation of the hair cells of the inner ear. PMID:15647165

Molecular organization of the 5S rDNA gene type II in elasmobranchs.

PubMed

Castro, Sergio I; Hleap, Jose S; Cárdenas, Heiber; Blouin, Christian

2016-01-01

The 5S rDNA gene is a non-coding RNA that can be found in 2 copies (type I and type II) in bony and cartilaginous fish. Previous studies have pointed out that type II gene is a paralog derived from type I. We analyzed the molecular organization of 5S rDNA type II in elasmobranchs. Although the structure of the 5S rDNA is supposed to be highly conserved, our results show that the secondary structure in this group possesses some variability and is different than the consensus secondary structure. One of these differences in Selachii is an internal loop at nucleotides 7 and 112. These mutations observed in the transcribed region suggest an independent origin of the gene among Batoids and Selachii. All promoters were highly conserved with the exception of BoxA, possibly due to its affinity to polymerase III. This latter enzyme recognizes a dT4 sequence as stop signal, however in Rajiformes this signal was doubled in length to dT8. This could be an adaptation toward a higher efficiency in the termination process. Our results suggest that there is no TATA box in elasmobranchs in the NTS region. We also provide some evidence suggesting that the complexity of the microsatellites present in the NTS region play an important role in the 5S rRNA gene since it is significantly correlated with the length of the NTS.

Molecular organization of the 5S rDNA gene type II in elasmobranchs

PubMed Central

Castro, Sergio I.; Hleap, Jose S.; Cárdenas, Heiber; Blouin, Christian

2016-01-01

ABSTRACT The 5S rDNA gene is a non-coding RNA that can be found in 2 copies (type I and type II) in bony and cartilaginous fish. Previous studies have pointed out that type II gene is a paralog derived from type I. We analyzed the molecular organization of 5S rDNA type II in elasmobranchs. Although the structure of the 5S rDNA is supposed to be highly conserved, our results show that the secondary structure in this group possesses some variability and is different than the consensus secondary structure. One of these differences in Selachii is an internal loop at nucleotides 7 and 112. These mutations observed in the transcribed region suggest an independent origin of the gene among Batoids and Selachii. All promoters were highly conserved with the exception of BoxA, possibly due to its affinity to polymerase III. This latter enzyme recognizes a dT4 sequence as stop signal, however in Rajiformes this signal was doubled in length to dT8. This could be an adaptation toward a higher efficiency in the termination process. Our results suggest that there is no TATA box in elasmobranchs in the NTS region. We also provide some evidence suggesting that the complexity of the microsatellites present in the NTS region play an important role in the 5S rRNA gene since it is significantly correlated with the length of the NTS. PMID:26488198

IPCC Working Group II: Impacts and Adaptation Part I

NASA Astrophysics Data System (ADS)

Pulwarty, R. S.

2007-12-01

The IPCC (as opposed to the UN Framework Convention) defines climate change as" any change in climate over time, whether due to natural variability or as a result of human activity". The IPCC Working Group II (Impacts, Adaptation, Vulnerability) was charged with assessing the scientific, technical, environmental, economic, and social aspects of vulnerability to climate change, and, the negative and positive consequences for ecological systems, socio-economic sectors, and human health. The Working Group II report focused on the following issues for different sectors and regions (e.g. water, agriculture, biodiversity) and communities (coastal, island, etc.): · The role of adaptation in reducing vulnerability and impacts, · Assessment of adaptation capacity, options and constraints, and · Enhancing adaptation practice and operations. This presentation will address the following questions in the context of the results of the IPCC Fourth Assessment Report WG II: · What are the barriers, knowledge gaps, and opportunities for impacts assessments? · How are decisions about adaptation being made, and what types of adaptation strategies are being undertaken? · What are good adaptation practices and how are they learned over time? Examples will be drawn from the freshwater resources, small islands and adaptation chapters to which the presenter contributed. Many lessons have been identified but few have been implemented or evaluated over time. Adaptation occurs in the context of multiple stresses. Adaptation will be important in coping with early impacts in the near-term and continue to be important as our climate changes, regardless of how that change is derived. It is important to note that unmitigated climate change could, in the long term, exceed the capacity of different natural, managed and human systems to adapt. The assessment leads to the following conclusions: · Adaptation to climate change is already taking place, but on a limited basis · Adaptation measures are seldom undertaken in response to climate change alone · Many adaptations can be implemented at low cost, but comprehensive estimates of adaptation costs and benefits are currently lacking · Adaptive capacity is uneven across and within societies Adaptive capacity to manage as climate changes can be increased by introducing adaptation measures into development planning and operations (sometimes termed 'mainstreaming'). This can be achieved by including adaptation measures in land-use planning and infrastructure design, or by including measures to reduce vulnerability in existing disaster preparedness programs (such as introducing drought warning systems based on actual management needs). The major barriers to implementing adaptive management measures are that adaptation to climate change is not as yet a high priority, and the validity of local manifestations of global climate change remains in question. Coping with the uncertainties associated with estimates of future climate change and the impacts on economic and environmental resources means management measures must be robust enough to apply to a range of potential scenarios, some as yet undefined Greenhouse gas mitigation is not enough to reduce climatic risks, nor does identifying the need for adaptations translate into actions that reduce vulnerability. By implementing mainstreaming initiatives, adaptation to climate change will become part of, or will be consistent with, other well- established programs to increase societal resilience, particularly environmental impacts assessments, adaptive management

Spacer capture and integration by a type I-F Cas1-Cas2-3 CRISPR adaptation complex.

PubMed

Fagerlund, Robert D; Wilkinson, Max E; Klykov, Oleg; Barendregt, Arjan; Pearce, F Grant; Kieper, Sebastian N; Maxwell, Howard W R; Capolupo, Angela; Heck, Albert J R; Krause, Kurt L; Bostina, Mihnea; Scheltema, Richard A; Staals, Raymond H J; Fineran, Peter C

2017-06-27

CRISPR-Cas adaptive immune systems capture DNA fragments from invading bacteriophages and plasmids and integrate them as spacers into bacterial CRISPR arrays. In type I-E and II-A CRISPR-Cas systems, this adaptation process is driven by Cas1-Cas2 complexes. Type I-F systems, however, contain a unique fusion of Cas2, with the type I effector helicase and nuclease for invader destruction, Cas3. By using biochemical, structural, and biophysical methods, we present a structural model of the 400-kDa Cas1 4 -Cas2-3 2 complex from Pectobacterium atrosepticum with bound protospacer substrate DNA. Two Cas1 dimers assemble on a Cas2 domain dimeric core, which is flanked by two Cas3 domains forming a groove where the protospacer binds to Cas1-Cas2. We developed a sensitive in vitro assay and demonstrated that Cas1-Cas2-3 catalyzed spacer integration into CRISPR arrays. The integrase domain of Cas1 was necessary, whereas integration was independent of the helicase or nuclease activities of Cas3. Integration required at least partially duplex protospacers with free 3'-OH groups, and leader-proximal integration was stimulated by integration host factor. In a coupled capture and integration assay, Cas1-Cas2-3 processed and integrated protospacers independent of Cas3 activity. These results provide insight into the structure of protospacer-bound type I Cas1-Cas2-3 adaptation complexes and their integration mechanism.

Programmable RNA Cleavage and Recognition by a Natural CRISPR-Cas9 System from Neisseria meningitidis.

PubMed

Rousseau, Beth A; Hou, Zhonggang; Gramelspacher, Max J; Zhang, Yan

2018-03-01

The microbial CRISPR systems enable adaptive defense against mobile elements and also provide formidable tools for genome engineering. The Cas9 proteins are type II CRISPR-associated, RNA-guided DNA endonucleases that identify double-stranded DNA targets by sequence complementarity and protospacer adjacent motif (PAM) recognition. Here we report that the type II-C CRISPR-Cas9 from Neisseria meningitidis (Nme) is capable of programmable, RNA-guided, site-specific cleavage and recognition of single-stranded RNA targets and that this ribonuclease activity is independent of the PAM sequence. We define the mechanistic feature and specificity constraint for RNA cleavage by NmeCas9 and also show that nuclease null dNmeCas9 binds to RNA target complementary to CRISPR RNA. Finally, we demonstrate that NmeCas9-catalyzed RNA cleavage can be blocked by three families of type II-C anti-CRISPR proteins. These results fundamentally expand the targeting capacities of CRISPR-Cas9 and highlight the potential utility of NmeCas9 as a single platform to target both RNA and DNA. Copyright © 2018 Elsevier Inc. All rights reserved.

Traveling with Cognitive Tests: Testing the Validity of a KABC-II Adaptation in India

ERIC Educational Resources Information Center

Malda, Maike; van de Vijver, Fons J. R.; Srinivasan, Krishnamachari; Transler, Catherine; Sukumar, Prathima

2010-01-01

The authors evaluated the adequacy of an extensive adaptation of the American Kaufman Assessment Battery for Children, second edition (KABC-II), for 6- to 10-year-old Kannada-speaking children of low socioeconomic status in Bangalore, South India. The adapted KABC-II was administered to 598 children. Subtests showed high reliabilities, the…

Evolution of the P-type II ATPase gene family in the fungi and presence of structural genomic changes among isolates of Glomus intraradices.

PubMed

Corradi, Nicolas; Sanders, Ian R

2006-03-10

The P-type II ATPase gene family encodes proteins with an important role in adaptation of the cell to variation in external K+, Ca2+ and Na2+ concentrations. The presence of P-type II gene subfamilies that are specific for certain kingdoms has been reported but was sometimes contradicted by discovery of previously unknown homologous sequences in newly sequenced genomes. Members of this gene family have been sampled in all of the fungal phyla except the arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), which are known to play a key-role in terrestrial ecosystems and to be genetically highly variable within populations. Here we used highly degenerate primers on AMF genomic DNA to increase the sampling of fungal P-Type II ATPases and to test previous predictions about their evolution. In parallel, homologous sequences of the P-type II ATPases have been used to determine the nature and amount of polymorphism that is present at these loci among isolates of Glomus intraradices harvested from the same field. In this study, four P-type II ATPase sub-families have been isolated from three AMF species. We show that, contrary to previous predictions, P-type IIC ATPases are present in all basal fungal taxa. Additionally, P-Type IIE ATPases should no longer be considered as exclusive to the Ascomycota and the Basidiomycota, since we also demonstrate their presence in the Zygomycota. Finally, a comparison of homologous sequences encoding P-type IID ATPases showed unexpectedly that indel mutations among coding regions, as well as specific gene duplications occur among AMF individuals within the same field. On the basis of these results we suggest that the diversification of P-Type IIC and E ATPases followed the diversification of the extant fungal phyla with independent events of gene gains and losses. Consistent with recent findings on the human genome, but at a much smaller geographic scale, we provided evidence that structural genomic changes, such as exonic indel mutations and gene duplications are less rare than previously thought and that these also occur within fungal populations.

Adaptive control method for core power control in TRIGA Mark II reactor

NASA Astrophysics Data System (ADS)

Sabri Minhat, Mohd; Selamat, Hazlina; Subha, Nurul Adilla Mohd

2018-01-01

The 1MWth Reactor TRIGA PUSPATI (RTP) Mark II type has undergone more than 35 years of operation. The existing core power control uses feedback control algorithm (FCA). It is challenging to keep the core power stable at the desired value within acceptable error bands to meet the safety demand of RTP due to the sensitivity of nuclear research reactor operation. Currently, the system is not satisfied with power tracking performance and can be improved. Therefore, a new design core power control is very important to improve the current performance in tracking and regulate reactor power by control the movement of control rods. In this paper, the adaptive controller and focus on Model Reference Adaptive Control (MRAC) and Self-Tuning Control (STC) were applied to the control of the core power. The model for core power control was based on mathematical models of the reactor core, adaptive controller model, and control rods selection programming. The mathematical models of the reactor core were based on point kinetics model, thermal hydraulic models, and reactivity models. The adaptive control model was presented using Lyapunov method to ensure stable close loop system and STC Generalised Minimum Variance (GMV) Controller was not necessary to know the exact plant transfer function in designing the core power control. The performance between proposed adaptive control and FCA will be compared via computer simulation and analysed the simulation results manifest the effectiveness and the good performance of the proposed control method for core power control.

Information Processing Techniques Program. Volume II. Communications- Adaptive Internetting

DTIC Science & Technology

1977-09-30

LABORATORY INFORMATION PROCESSING TECHNIQUES PROGRAM VOLUME II: COMMUNICATIONS-ADAPTIVE INTERNETTING I SEMIANNUAL TECHNICAL SUMMARY REPORT TO THE...MASSACHUSETTS ABSTRACT This repori describes work performed on the Communications-Adaptive Internetting program sponsored by the Information ... information processing techniques network speech terminal communicatlons-adaptive internetting 04 links digital voice communications time-varying

Mini-marathon groups: psychological "first aid" following disasters.

PubMed

Terr, L C

1992-01-01

Large group counseling sessions for soldiers following battle have been commonly used since World War II. The author conceptualizes and demonstrates how these mini-marathon sessions can be adapted to support all ages and types of civilians involved in disasters. Mini-marathons take about 3 hours and are divided into three sections: story sharing, symptom sharing, and suggestions for self-help, including sharing tales of heroism and survival. After an initial mini-marathon session, a second session may be held emphasizing creativity. The author also describes how mini-marathons can be adapted for therapists who will lead their own sessions.

An Analysis of a Finite Element Method for Convection-Diffusion Problems. Part II. A Posteriori Error Estimates and Adaptivity.

DTIC Science & Technology

1983-03-01

AN ANALYSIS OF A FINITE ELEMENT METHOD FOR CONVECTION- DIFFUSION PROBLEMS PART II: A POSTERIORI ERROR ESTIMATES AND ADAPTIVITY by W. G. Szymczak Y 6a...PERIOD COVERED AN ANALYSIS OF A FINITE ELEMENT METHOD FOR final life of the contract CONVECTION- DIFFUSION PROBLEM S. Part II: A POSTERIORI ERROR ...Element Method for Convection- Diffusion Problems. Part II: A Posteriori Error Estimates and Adaptivity W. G. Szvmczak and I. Babu~ka# Laboratory for

A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease

USDA-ARS?s Scientific Manuscript database

The Cas9 endonuclease of the Type II-a clustered regularly interspersed short palindromic repeats (CRISPR), of Streptococcus pyogenes (SpCas9) has been adapted as a widely used tool for genome editing and genome engineering. Herein, we describe a gene encoding a novel Cas9 ortholog (BpsuCas9) and th...

Rasch analysis of the Pediatric Evaluation of Disability Inventory-computer adaptive test (PEDI-CAT) item bank for children and young adults with spinal muscular atrophy.

PubMed

Pasternak, Amy; Sideridis, Georgios; Fragala-Pinkham, Maria; Glanzman, Allan M; Montes, Jacqueline; Dunaway, Sally; Salazar, Rachel; Quigley, Janet; Pandya, Shree; O'Riley, Susan; Greenwood, Jonathan; Chiriboga, Claudia; Finkel, Richard; Tennekoon, Gihan; Martens, William B; McDermott, Michael P; Fournier, Heather Szelag; Madabusi, Lavanya; Harrington, Timothy; Cruz, Rosangel E; LaMarca, Nicole M; Videon, Nancy M; Vivo, Darryl C De; Darras, Basil T

2016-12-01

In this study we evaluated the suitability of a caregiver-reported functional measure, the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), for children and young adults with spinal muscular atrophy (SMA). PEDI-CAT Mobility and Daily Activities domain item banks were administered to 58 caregivers of children and young adults with SMA. Rasch analysis was used to evaluate test properties across SMA types. Unidimensional content for each domain was confirmed. The PEDI-CAT was most informative for type III SMA, with ability levels distributed close to 0.0 logits in both domains. It was less informative for types I and II SMA, especially for mobility skills. Item and person abilities were not distributed evenly across all types. The PEDI-CAT may be used to measure functional performance in SMA, but additional items are needed to identify small changes in function and best represent the abilities of all types of SMA. Muscle Nerve 54: 1097-1107, 2016. © 2016 Wiley Periodicals, Inc.

Spinal muscle evaluation in healthy individuals and low-back-pain patients: a literature review.

PubMed

Demoulin, Christophe; Crielaard, Jean-Michel; Vanderthommen, Marc

2007-01-01

This article reviews available techniques for spinal muscle investigation, as well as data on spinal muscles in healthy individuals and in patients with low back pain. In patients with chronic low back pain, medical imaging studies show paraspinal muscle wasting with reductions in cross-sectional surface area and fiber density. In healthy individuals, the paraspinal muscles contain a high proportion of slow-twitch fibers (Type I), reflecting their role in maintaining posture. The proportion of Type I fibers is higher in females, leading to better adaptation to aerobic exertion compared to males. Abnormalities seen in paraspinal muscles from patients with chronic low back pain include marked Type II fiber atrophy, conversion of Type I to Type II fibers, and an increased number of nonspecific abnormalities. Limited data are available from magnetic resonance spectroscopy used to investigate muscle metabolism and from near infrared spectroscopy used to measure oxygen uptake by the paraspinal muscles. Surface electromyography in patients with chronic low back pain shows increased paraspinal muscle fatigability, often with abolition of the flexion-relaxation phenomenon.

Cold-water immersion after training sessions: Effects on fiber type-specific adaptations in muscle K+ transport proteins to sprint-interval training in men.

PubMed

Christiansen, Danny; Bishop, David John; Broatch, James R; Bangsbo, Jens; McKenna, Michael John; Murphy, Robyn M

2018-05-10

Effects of regular use of cold-water immersion (CWI) on fiber type-specific adaptations in muscle K + transport proteins to intense training, along with their relationship to changes in mRNA levels after the first training session, were investigated in humans. Nineteen recreationally-active men (24{plus minus}6 y, 79.5{plus minus}10.8 kg, 44.6{plus minus}5.8 mL∙kg -1 ∙min -1 ) completed six weeks of sprint-interval cycling either without (passive rest; CON) or with training sessions followed by CWI (15 min at 10{degree sign}C; COLD). Muscle biopsies were obtained before and after training to determine abundance of Na + ,K + -ATPase isoforms (α 1-3 , β 1-3 ) and FXYD1, and after recovery treatments (+0h and +3h) on the first day of training to measure mRNA content. Training increased (p<0.05) the abundance of α 1 and β 3 in both fiber types, β 1 in type-II fibers, and decreased FXYD1 in type-I fibers, whereas α 2 and α 3 abundance was not altered by training (p>0.05). CWI after each session did not influence responses to training (p>0.05). However, α 2 mRNA increased after the first session in COLD (+0h, p<0.05), but not in CON (p>0.05). In both conditions, α 1 and β 3 mRNA increased (+3h; p <0.05), β 2 mRNA decreased (+3h; p<0.05), whereas α 3 , β 1 , and FXYD1 mRNA remained unchanged (p>0.05) after the first session. In summary, Na + ,K + -ATPase isoforms are differently regulated in type I and II muscle fibers by sprint-interval training in humans, which for most isoforms do not associate with changes in mRNA levels after the first training session. CWI neither impairs nor improves protein adaptations to intense training of importance for muscle K + regulation.

Mitochondrial fatty acid biosynthesis and muscle fiber plasticity in very long-chain acyl-CoA dehydrogenase-deficient mice.

PubMed

Tucci, Sara; Mingirulli, Nadja; Wehbe, Zeinab; Dumit, Verónica I; Kirschner, Janbernd; Spiekerkoetter, Ute

2018-01-01

The white skeletal muscle of very long-chain acyl-CoA-dehydrogenase-deficient (VLCAD -/- ) mice undergoes metabolic modification to compensate for defective β-oxidation in a progressive and time-dependent manner by upregulating glucose oxidation. This metabolic regulation seems to be accompanied by morphologic adaptation of muscle fibers toward the glycolytic fiber type II with the concomitant upregulation of mitochondrial fatty acid biosynthesis (mFASII) and lipoic acid biosynthesis. Dietary supplementation of VLCAD -/- mice with different medium-chain triglycerides over 1 year revealed that odd-chain species has no effect on muscle fiber switch, whereas even-chain species inhibit progressive metabolic adaptation. Our study shows that muscle may undergo adaptive mechanisms that are modulated by dietary supplementation. We describe for the first time a concomitant change of mFASII in this muscular adaptation process. © 2017 Federation of European Biochemical Societies.

Skeletal muscle satellite cells are located at a closer proximity to capillaries in healthy young compared with older men.

PubMed

Nederveen, Joshua P; Joanisse, Sophie; Snijders, Tim; Ivankovic, Victoria; Baker, Steven K; Phillips, Stuart M; Parise, Gianni

2016-12-01

Skeletal muscle satellite cells (SC) are instrumental in maintenance of muscle fibres, the adaptive responses to exercise, and there is an age-related decline in SC. A spatial relationship exists between SC and muscle fibre capillaries. In the present study, we aimed to investigate whether chronologic age has an impact on the spatial relationship between SC and muscle fibre capillaries. Secondly, we determined whether this spatial relationship changes in response to a single session of resistance exercise. Muscle biopsies were obtained from the vastus lateralis of previously untrained young men (YM, 24 ± 3 years; n  = 23) and older men (OM, 67 ± 4 years; n  = 22) at rest. A subset of YM ( n  = 9) performed a single bout of resistance exercise, where additional muscle biopsies taken at 24 and 72 h post-exercise recovery. Skeletal muscle fibre capillarization, SC content, and activation status were assessed using immunofluorescent microscopy of muscle cross sections. Type II muscle fibre SC and capillary content was significantly lower in the YM compared with OM ( P  < 0.05). Furthermore, type II muscle fibre SC were located at a greater distance from the nearest capillary in OM compared with YM (21.6 ± 1.3 vs. 17.0 ± 0.8 µm, respectively; P  < 0.05). In response to a single bout of exercise, we observed a significant increase in SC number and activation status ( P  < 0.05). In addition, activated vs. quiescent SC were situated closer ( P  < 0.05) to capillaries. We demonstrate that there is a greater distance between capillaries and type II fibre-associated SC in OM as compared with YM. Furthermore, quiescent SC are located significantly further away from capillaries than active SC after single bout of exercise. Our data have implications for how muscle adapts to exercise and how aging may affect such adaptations.

Comparison of Genotypes and Enterotoxin Genes Between Staphylococcus aureus Isolates from Blood and Nasal Colonizers in a Korean Hospital

PubMed Central

Peck, Kyong Ran; Baek, Jin Yang; Song, Jae-Hoon

2009-01-01

In this study, we investigated the genetic background of 70 Staphylococcus aureus isolates (36 methicillin-resistant S. aureus [MRSA] and 34 methicillin-susceptible S. aureus [MSSA]) obtained from blood at a Korean tertiary-care hospital, using spa typing, multilocus sequence typing, and SCCmec typing. In addition, the prevalence of enterotoxin (sea, seb, sec, sed, see, seg, seh, sei, and sek), tst, and pvl genes among the samples was assessed via polymerase chain reaction, and the results were compared with those of 95 isolates of S. aureus obtained from nasal swabs. All MRSA isolates from blood, except one, belonged to three major clones: sequence type (ST)5-MRSA-II, ST72-MRSA-II (or IVA), and ST239-MRSA-III, among which ST5-MRSA-II was the predominant clone. The prevalence of enterotoxin genes in the S. aureus isolates obtained from blood differed significantly from those from the nasal swabs for the sea, seb, sec, and seh gene. In particular, the seb and sec genes were detected exclusively in the MRSA isolates of ST5 or spa-CC002, thereby suggesting the co-adaptation of virulence genes with the genetic background and their contribution to biological fitness. PMID:19654937

Muscle damage and adaptation after the second bout of eccentric exercise of the knee extensors.

PubMed

Hassan, E S

2014-10-01

This study examined the muscles ability to adapt to eccentric exercise by the changes in serum myoglobin (Mb), creatine kinase (CK) activity and muscle soreness. The study involved 54 healthy young men from the 23± 2yr age group. These were distributed as subjects for three types of experiments with 18 men in each. Subjects performed 300 maximal eccentric exercises. In experiment I, after performing the first bout of exercise, they were split into three subgroups to perform the second bout after a period of 4, 6, and 8 weeks (WK), respectively. In experiment II, performed the second exercise after a period of 2, 3, and 5 wk, respectively. In experiment III, they performed four exercise bouts spaced 1 wk apart. in experiment II a significant (P<0.05) decrease in muscle soreness, serum Mb and CK was found on exercise bout 2. In experiment III, serum CK, Mb and muscle soreness responses were highest following bout 1. It was concluded that performance of a single exercise bout had a prophylactic effect on muscle soreness and serum protein responses that lasts approximately 2 wk, with the greatest adaptation occurring after one bout.

Performance of new gellan gum hydrogels combined with human articular chondrocytes for cartilage regeneration when subcutaneously implanted in nude mice.

PubMed

Oliveira, J T; Santos, T C; Martins, L; Silva, M A; Marques, A P; Castro, A G; Neves, N M; Reis, R L

2009-10-01

Gellan gum is a polysaccharide that has been recently proposed by our group for cartilage tissue-engineering applications. It is commonly used in the food and pharmaceutical industry and has the ability to form stable gels without the use of harsh reagents. Gellan gum can function as a minimally invasive injectable system, gelling inside the body in situ under physiological conditions and efficiently adapting to the defect site. In this work, gellan gum hydrogels were combined with human articular chondrocytes (hACs) and were subcutaneously implanted in nude mice for 4 weeks. The implants were collected for histological (haematoxylin and eosin and Alcian blue staining), biochemical [dimethylmethylene blue (GAG) assay], molecular (real-time PCR analyses for collagen types I, II and X, aggrecan) and immunological analyses (immunolocalization of collagen types I and II). The results showed a homogeneous cell distribution and the typical round-shaped morphology of the chondrocytes within the matrix upon implantation. Proteoglycans synthesis was detected by Alcian blue staining and a statistically significant increase of proteoglycans content was measured with the GAG assay quantified from 1 to 4 weeks of implantation. Real-time PCR analyses showed a statistically significant upregulation of collagen type II and aggrecan levels in the same periods. The immunological assays suggest deposition of collagen type II along with some collagen type I. The overall data shows that gellan gum hydrogels adequately support the growth and ECM deposition of human articular chondrocytes when implanted subcutaneously in nude mice. Copyright (c) 2009 John Wiley & Sons, Ltd.

The PerR-Regulated P1B-4-Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes.

PubMed

Turner, Andrew G; Ong, Cheryl-Lynn Y; Djoko, Karrera Y; West, Nicholas P; Davies, Mark R; McEwan, Alastair G; Walker, Mark J

2017-06-01

Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a broad spectrum of human disease. GAS has a requirement for metal homeostasis within the human host and, as such, tightly modulates metal uptake and efflux during infection. Metal acquisition systems are required to combat metal sequestration by the host, while metal efflux systems are essential to protect against metal overload poisoning. Here, we investigated the function of PmtA ( P erR-regulated m etal t ransporter A ), a P 1B-4 -type ATPase efflux pump, in invasive GAS M1T1 strain 5448. We reveal that PmtA functions as a ferrous iron [Fe(II)] efflux system. In the presence of high Fe(II) concentrations, the 5448Δ pmtA deletion mutant exhibited diminished growth and accumulated 5-fold-higher levels of intracellular Fe(II) than did the wild type and the complemented mutant. The 5448Δ pmtA deletion mutant also showed enhanced susceptibility to killing by the Fe-dependent antibiotic streptonigrin as well as increased sensitivity to hydrogen peroxide and superoxide. We suggest that the PerR-mediated control of Fe(II) efflux by PmtA is important for bacterial defense against oxidative stress. PmtA represents an exemplar for an Fe(II) efflux system in a host-adapted Gram-positive bacterial pathogen. Copyright © 2017 American Society for Microbiology.

SNAKE VENOMICS OF Crotalus tigris: THE MINIMALIST TOXIN ARSENAL OF THE DEADLIEST NEARTIC RATTLESNAKE VENOM

PubMed Central

CALVETE, Juan J.; PÉREZ, Alicia; LOMONTE, Bruno; SÁNCHEZ, Elda E.; SANZ, Libia

2012-01-01

We report the proteomic and antivenomic characterization of Crotalus tigris venom. This venom exhibits the highest lethality for mice among rattlesnakes and the simplest toxin proteome reported to date. The venom proteome of C. tigris comprises 7–8 gene products from 6 toxin families: the presynaptic β-neurotoxic heterodimeric PLA2, Mojave toxin, and two serine proteinases comprise, respectively, 66% and 27% of the C. tigris toxin arsenal, whereas a VEGF-like protein, a CRISP molecule, a medium-sized disintegrin, and 1–2 PIII-SVMPs, each represents 0.1–5% of the total venom proteome. This toxin profile really explains the systemic neuro- and myotoxic effects observed in envenomated animals. In addition, we found that venom lethality of C. tigris and other North American rattlesnake type II venoms correlates with the concentration of Mojave toxin A-subunit, supporting the view that the neurotoxic venom phenotype of crotalid type II venoms may be described as a single-allele adaptation. Our data suggest that the evolutionary trend towards neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by paedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris, C. horridus, C. oreganus helleri, C. scutulatus scutulatus, and S. catenatus catenatus, indicated the feasibility of generating a pan-American anti-Crotalus type II antivenom, suggested by the identification of shared evolutionary trends among South American and North American Crotalus. PMID:22181673

Type II fuzzy systems for amyloid plaque segmentation in transgenic mouse brains for Alzheimer's disease quantification

NASA Astrophysics Data System (ADS)

Khademi, April; Hosseinzadeh, Danoush

2014-03-01

Alzheimer's disease (AD) is the most common form of dementia in the elderly characterized by extracellular deposition of amyloid plaques (AP). Using animal models, AP loads have been manually measured from histological specimens to understand disease etiology, as well as response to treatment. Due to the manual nature of these approaches, obtaining the AP load is labourious, subjective and error prone. Automated algorithms can be designed to alleviate these challenges by objectively segmenting AP. In this paper, we focus on the development of a novel algorithm for AP segmentation based on robust preprocessing and a Type II fuzzy system. Type II fuzzy systems are much more advantageous over the traditional Type I fuzzy systems, since ambiguity in the membership function may be modeled and exploited to generate excellent segmentation results. The ambiguity in the membership function is defined as an adaptively changing parameter that is tuned based on the local contrast characteristics of the image. Using transgenic mouse brains with AP ground truth, validation studies were carried out showing a high degree of overlap and low degree of oversegmentation (0.8233 and 0.0917, respectively). The results highlight that such a framework is able to handle plaques of various types (diffuse, punctate), plaques with varying Aβ concentrations as well as intensity variation caused by treatment effects or staining variability.

The Regularity of Sustained Firing Reveals Two Populations of Slowly Adapting Touch Receptors in Mouse Hairy Skin

PubMed Central

Wellnitz, Scott A.; Lesniak, Daine R.; Gerling, Gregory J.

2010-01-01

Touch is initiated by diverse somatosensory afferents that innervate the skin. The ability to manipulate and classify receptor subtypes is prerequisite for elucidating sensory mechanisms. Merkel cell–neurite complexes, which distinguish shapes and textures, are experimentally tractable mammalian touch receptors that mediate slowly adapting type I (SAI) responses. The assessment of SAI function in mutant mice has been hindered because previous studies did not distinguish SAI responses from slowly adapting type II (SAII) responses, which are thought to arise from different end organs, such as Ruffini endings. Thus we sought methods to discriminate these afferent types. We developed an epidermis-up ex vivo skin–nerve chamber to record action potentials from afferents while imaging Merkel cells in intact receptive fields. Using model-based cluster analysis, we found that two types of slowly adapting receptors were readily distinguished based on the regularity of touch-evoked firing patterns. We identified these clusters as SAI (coefficient of variation = 0.78 ± 0.09) and SAII responses (0.21 ± 0.09). The identity of SAI afferents was confirmed by recording from transgenic mice with green fluorescent protein–expressing Merkel cells. SAI receptive fields always contained fluorescent Merkel cells (n = 10), whereas SAII receptive fields lacked these cells (n = 5). Consistent with reports from other vertebrates, mouse SAI and SAII responses arise from afferents exhibiting similar conduction velocities, receptive field sizes, mechanical thresholds, and firing rates. These results demonstrate that mice, like other vertebrates, have two classes of slowly adapting light-touch receptors, identify a simple method to distinguish these populations, and extend the utility of skin–nerve recordings for genetic dissection of touch receptor mechanisms. PMID:20393068

Anatomic evidence for peripheral neural processing in mammalian graviceptors

NASA Technical Reports Server (NTRS)

Ross, M. D.

1985-01-01

Ultrastructural study of utricular and saccular maculas demonstrates that their innervation patterns are complex. There is a clustering of type I and type II hair cells based upon a sharing of afferents, a system of efferent-type beaded fibers that is of intramacular (mostly calyceal) origin, and a plexus-like arrangement of afferents and efferents at many sites in the neuroepithelium. Results suggest that information concerning linear acceleration is processed peripherally, beginning at the hair cell level, before being sent to the central nervous system. The findings may supply a structural basis for peripheral adaptation to a constant stimulus, and for lateral inhibition to improve signal relative to noise.

World War II Radar and Early Radio Astronomy

NASA Astrophysics Data System (ADS)

Smith, G.

2005-08-01

The pattern of radio astronomy which developed in Europe and Australia followed closely the development of metre wave radar in World War II. The leading pioneers, Ryle, Lovell, Hey and Pawsey, were all in radar research establishments in the UK and Australia. They returned to universities, recruited their colleagues into research groups and immediately started on some basic observations of solar radio waves, meteor echoes, and the galactic background. There was at first little contact with conventional astronomers. This paper traces the influence of the radar scientists and of several types of radar equipment developed during WW II, notably the German Wurzburg, which was adapted for radio research in several countries. The techniques of phased arrays and antenna switching were used in radar and aircraft installations. The influence of WW II radar can be traced at least up to 10 years after the War, when radio astronomy became accepted as a natural discipline within astronomy.

SARS-CoV pathogenesis is regulated by a STAT1 dependent but a type I, II and III interferon receptor independent mechanism.

PubMed

Frieman, Matthew B; Chen, Jun; Morrison, Thomas E; Whitmore, Alan; Funkhouser, William; Ward, Jerrold M; Lamirande, Elaine W; Roberts, Anjeanette; Heise, Mark; Subbarao, Kanta; Baric, Ralph S

2010-04-08

Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. The virus-host interactions that governed development of these acute end stage lung diseases and death are unknown. To address this question, we evaluated the role of innate immune signaling in protection from human (Urbani) and a recombinant mouse adapted SARS-CoV, designated rMA15. In contrast to most models of viral pathogenesis, infection of type I, type II or type III interferon knockout mice (129 background) with either Urbani or MA15 viruses resulted in clinical disease outcomes, including transient weight loss, denuding bronchiolitis and alveolar inflammation and recovery, identical to that seen in infection of wildtype mice. This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. In contrast, infection of STAT1-/- mice resulted in severe disease, high virus titer, extensive pulmonary lesions and 100% mortality by day 9 and 30 post-infection with rMA15 or Urbani viruses, respectively. Non-lethal in BALB/c mice, Urbani SARS-CoV infection in STAT1-/- mice caused disseminated infection involving the liver, spleen and other tissues after day 9. These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. In contrast to a well documented role in innate immunity, we propose that STAT1 also protects mice via its role as an antagonist of unrestrained cell proliferation.

The role of ultraviolet-adaptation of a marine diatom in photoenhanced toxicity of acridine.

PubMed

Wiegman, Saskia; Barranguet, Christiane; Spijkerman, Elly; Kraak, Michiel Harm Steven; Admiraal, Wim

2003-03-01

Cultures of the marine diatom Phaeodactylum tricornutum were grown under laboratory light with a different fraction of ultraviolet radiation (UV) to study the potential role of photoadaptation in determining the sensitivity to photoenhanced toxicity of acridine. In short-term experiments, a higher acridine concentration was needed to inhibit the photosynthetic electron flux, monitored with chlorophyll a fluorescence, in algae exposed to fluorescent light (low UV) than to mercury light (high UV), consistent with the expected role of UV. The two types of light in long-term exposures led to changes in the pigment composition and photosystem I (PS I) to photosystem II (PS II) stoichiometry to optimize the utilization of fluorescent and mercury light. Despite the adaptation of the photosynthetic apparatus to a small fraction of UV, long-term exposure to mercury light did show a constant sensitivity of the photosynthetic efficiency of P. tricornutum to the phototoxic acridine. It is concluded that the prime receptor of photoenhanced toxicity may be unrelated to the photosynthetic machinery.

Pupillary autonomic denervation with increasing duration of diabetes mellitus

PubMed Central

Cahill, M.; Eustace, P.; de Jesus, V.

2001-01-01

BACKGROUND/AIMS—The autonomic pupillary changes in type I and II diabetic patients without clinical evidence of diabetic autonomic neuropathy (DAN) were compared with age matched controls. The relation between pupillary and cardiovascular autonomic function was assessed in the diabetic patients.
METHODS—A case-control study was performed with diabetics grouped according to type and duration of diabetes. Static infrared pupillography was used to compare mean dark adapted pupil size and mean percentage changes in pupil size with pilocarpine 0.1% and cocaine 4% in the diabetic and control groups. All diabetic patients underwent cardiovascular autonomic function assessment using the Valsalva ratio, the 30:15 ratio, and testing for orthostatic hypotension.
RESULTS—In total, 72 type I and 69 type II diabetic patients were compared with 120 controls. Mean dark adapted pupil size was significantly smaller in diabetic groups than controls. Except for type I diabetics with disease for less than 5 years, all patient groups had significantly greater mean percentage constriction in pupil size in response to dilute pilocarpine than controls. There was no significant difference between the mean percentage dilatation in response to cocaine 4% in diabetics and controls. A high proportion of patients had normal cardiovascular autonomic function particularly when this was assessed with the Valsalva ratio.
CONCLUSIONS—Denervation hypersensitivity to dilute pilocarpine is a result of damage to the pupillary parasympathetic supply of diabetic patients. This occurs before the pupillary sympathetic pathway is affected, it can be detected early in the disease, and it may be a possible explanation for the small pupil size seen in diabetic patients. Pupillary autonomic dysfunction occurs before cardiovascular autonomic changes and detection of pupil denervation hypersensitivity to dilute pilocarpine is an inexpensive way to detect early DAN.

 PMID:11567969

Comparative analyses of Xanthomonas and Xylella complete genomes.

PubMed

Moreira, Leandro M; De Souza, Robson F; Digiampietri, Luciano A; Da Silva, Ana C R; Setubal, João C

2005-01-01

Computational analyses of four bacterial genomes of the Xanthomonadaceae family reveal new unique genes that may be involved in adaptation, pathogenicity, and host specificity. The Xanthomonas genus presents 3636 unique genes distributed in 1470 families, while Xylella genus presents 1026 unique genes distributed in 375 families. Among Xanthomonas-specific genes, we highlight a large number of cell wall degrading enzymes, proteases, and iron receptors, a set of energy metabolism genes, second copy of the type II secretion system, type III secretion system, flagella and chemotactic machinery, and the xanthomonadin synthesis gene cluster. Important genes unique to the Xylella genus are an additional copy of a type IV pili gene cluster and the complete machinery of colicin V synthesis and secretion. Intersections of gene sets from both genera reveal a cluster of genes homologous to Salmonella's SPI-7 island in Xanthomonas axonopodis pv citri and Xylella fastidiosa 9a5c, which might be involved in host specificity. Each genome also presents important unique genes, such as an HMS cluster, the kdgT gene, and O-antigen in Xanthomonas axonopodis pv citri; a number of avrBS genes and a distinct O-antigen in Xanthomonas campestris pv campestris, a type I restriction-modification system and a nickase gene in Xylella fastidiosa 9a5c, and a type II restriction-modification system and two genes related to peptidoglycan biosynthesis in Xylella fastidiosa temecula 1. All these differences imply a considerable number of gene gains and losses during the divergence of the four lineages, and are associated with structural genome modifications that may have a direct relation with the mode of transmission, adaptation to specific environments and pathogenicity of each organism.

Superconductor cable

DOEpatents

Smith, Jr., Darrell F.; Lake, Bill L.; Ballinger, Ronald G.

1988-01-01

A superconducting cable comprising an in-situ-formed type II superconductor, e.g. Nb.sub.3 Sn, in association with a stabilizing conductor both in heat transfer relationship with at least one passage adapted to carry liquified gaseous refrigerant. The conductor and said at least one passage are enclosed by a sheath comprising an alloy consisting essentially of about 49% nickel, about 4% chromium, about 3% niobium, about 1.4% titanium, about 1% aluminum, balance essentially iron.

Inspiratory muscle training in patients with chronic obstructive pulmonary disease: structural adaptation and physiologic outcomes.

PubMed

Ramirez-Sarmiento, Alba; Orozco-Levi, Mauricio; Guell, Rosa; Barreiro, Esther; Hernandez, Nuria; Mota, Susana; Sangenis, Merce; Broquetas, Joan M; Casan, Pere; Gea, Joaquim

2002-12-01

The present study was aimed at evaluating the effects of a specific inspiratory muscle training protocol on the structure of inspiratory muscles in patients with chronic obstructive pulmonary disease. Fourteen patients (males, FEV1, 24 +/- 7% predicted) were randomized to either inspiratory muscle or sham training groups. Supervised breathing using a threshold inspiratory device was performed 30 minutes per day, five times a week, for 5 consecutive weeks. The inspiratory training group was subjected to inspiratory loading equivalent to 40 to 50% of their maximal inspiratory pressure. Biopsies from external intercostal muscles and vastus lateralis (control muscle) were taken before and after the training period. Muscle samples were processed for morphometric analyses using monoclonal antibodies against myosin heavy chain isoforms I and II. Increases in both the strength and endurance of the inspiratory muscles were observed in the inspiratory training group. This improvement was associated with increases in the proportion of type I fibers (by approximately 38%, p < 0.05) and in the size of type II fibers (by approximately 21%, p < 0.05) in the external intercostal muscles. No changes were observed in the control muscle. The study demonstrates that inspiratory training induces a specific functional improvement of the inspiratory muscles and adaptive changes in the structure of external intercostal muscles.

Direct CRISPR spacer acquisition from RNA by a natural reverse-transcriptase-Cas1 fusion protein

PubMed Central

Sidote, David J.; Markham, Laura M.; Sanchez-Amat, Antonio; Bhaya, Devaki; Lambowitz, Alan M.; Fire, Andrew Z.

2016-01-01

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) systems mediate adaptive immunity in diverse prokaryotes. CRISPR-associated Cas1 and Cas2 proteins have been shown to enable adaptation to new threats in Type I and II CRISPR systems by the acquisition of short segments of DNA (“spacers”) from invasive elements. In several Type III CRISPR systems, Cas1 is naturally fused to a reverse transcriptase (RT). In the marine bacterium Marinomonas mediterranea (MMB-1), we show that an RT-Cas1 fusion enables the acquisition of RNA spacers in vivo in an RT-dependent manner. In vitro, the MMB-1 RT-Cas1 and Cas2 proteins catalyze ligation of RNA segments into the CRISPR array, followed by reverse transcription. These observations outline a host-mediated mechanism for reverse information flow from RNA to DNA. PMID:26917774

Methyl-CpG island-associated genome signature tags

DOEpatents

Dunn, John J

2014-05-20

Disclosed is a method for analyzing the organismic complexity of a sample through analysis of the nucleic acid in the sample. In the disclosed method, through a series of steps, including digestion with a type II restriction enzyme, ligation of capture adapters and linkers and digestion with a type IIS restriction enzyme, genome signature tags are produced. The sequences of a statistically significant number of the signature tags are determined and the sequences are used to identify and quantify the organisms in the sample. Various embodiments of the invention described herein include methods for using single point genome signature tags to analyze the related families present in a sample, methods for analyzing sequences associated with hyper- and hypo-methylated CpG islands, methods for visualizing organismic complexity change in a sampling location over time and methods for generating the genome signature tag profile of a sample of fragmented DNA.

Reduction of conventional dendritic cells during Plasmodium infection is dependent on activation induced cell death by type I and II interferons.

PubMed

Tamura, Takahiko; Kimura, Kazumi; Yui, Katsuyuki; Yoshida, Shigeto

2015-12-01

Dendritic cells (DCs) play critical roles in innate and adaptive immunity and in pathogenesis during the blood stage of malaria infection. The mechanisms underlying DC homeostasis during malaria infection are not well understood. In this study, the numbers of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) in the spleens after lethal rodent malaria infection were examined, and were found to be significantly reduced. Concomitant with up-regulation of maturation-associated molecules, activation of caspase-3 was significantly increased, suggesting induction of cell death. Studies using neutralizing antibody and gene-deficient mice showed that type I and II interferons were critically involved in activation induced cell death of cDCs during malaria infection. These results demonstrate that DCs rapidly disappeared following IFN-mediated DC activation, and that homeostasis of DCs was significantly impaired during malaria infection. Copyright © 2015 Elsevier Inc. All rights reserved.

Camouflage and misdirection: the full-on assault of ebola virus disease.

PubMed

Misasi, John; Sullivan, Nancy J

2014-10-23

Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and nonhuman primates. Ebola protein interactions with host cellular proteins disrupt type I and type II interferon responses, RNAi antiviral responses, antigen presentation, T-cell-dependent B cell responses, humoral antibodies, and cell-mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and "cytokine storm" that is characteristic of fatal ebolavirus infection. Here, we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade antiviral defenses.

Immunotherapeutic strategies targeting Natural killer T cell responses in cancer

PubMed Central

Shissler, Susannah C.; Bollino, Dominique R.; Tiper, Irina V.; Bates, Joshua; Derakhshandeh, Roshanak; Webb, Tonya J.

2017-01-01

Natural killer T (NKT) cells are a unique subset of lymphocytes that bridge the innate and adaptive immune system. NKT cells possess a classic αβ T-cell receptor (TCR) that is able to recognize self and foreign glycolipid antigens presented by the nonclassical class I major histocompatibility complex (MHC) molecule, CD1d. Type I NKT cells (referred to as invariant NKT cells) express a semi-invariant Vα14Jα18 TCR in mice and Vα24Jα18 TCR in humans. Type II NKT cells are CD1d-restricted T cells that express a more diverse set of TCR α chains. The two types of NKT cells often exert opposing effects especially in tumor immunity, where Type II cells generally suppress tumor immunity while Type I NKT cells can enhance antitumor immune responses. In this review, we focus on the role of NKT cells in cancer. We discuss their effector and suppressive functions, as well as describe preclinical and clinical studies utilizing therapeutic strategies focused on harnessing their potent anti-tumor effector functions, and conclude with a discussion on potential next steps for the utilization of NKT cell targeted therapies for the treatment of cancer. PMID:27393665

The NASA F-15 Intelligent Flight Control Systems: Generation II

NASA Technical Reports Server (NTRS)

Buschbacher, Mark; Bosworth, John

2006-01-01

The Second Generation (Gen II) control system for the F-15 Intelligent Flight Control System (IFCS) program implements direct adaptive neural networks to demonstrate robust tolerance to faults and failures. The direct adaptive tracking controller integrates learning neural networks (NNs) with a dynamic inversion control law. The term direct adaptive is used because the error between the reference model and the aircraft response is being compensated or directly adapted to minimize error without regard to knowing the cause of the error. No parameter estimation is needed for this direct adaptive control system. In the Gen II design, the feedback errors are regulated with a proportional-plus-integral (PI) compensator. This basic compensator is augmented with an online NN that changes the system gains via an error-based adaptation law to improve aircraft performance at all times, including normal flight, system failures, mispredicted behavior, or changes in behavior resulting from damage.

Classification of ring artifacts for their effective removal using type adaptive correction schemes.

PubMed

Anas, Emran Mohammad Abu; Lee, Soo Yeol; Hasan, Kamrul

2011-06-01

High resolution tomographic images acquired with a digital X-ray detector are often degraded by the so called ring artifacts. In this paper, a detail analysis including the classification, detection and correction of these ring artifacts is presented. At first, a novel idea for classifying rings into two categories, namely type I and type II rings, is proposed based on their statistical characteristics. The defective detector elements and the dusty scintillator screens result in type I ring and the mis-calibrated detector elements lead to type II ring. Unlike conventional approaches, we emphasize here on the separate detection and correction schemes for each type of rings for their effective removal. For the detection of type I ring, the histogram of the responses of the detector elements is used and a modified fast image inpainting algorithm is adopted to correct the responses of the defective pixels. On the other hand, to detect the type II ring, first a simple filtering scheme is presented based on the fast Fourier transform (FFT) to smooth the sum curve derived form the type I ring corrected projection data. The difference between the sum curve and its smoothed version is then used to detect their positions. Then, to remove the constant bias suffered by the responses of the mis-calibrated detector elements with view angle, an estimated dc shift is subtracted from them. The performance of the proposed algorithm is evaluated using real micro-CT images and is compared with three recently reported algorithms. Simulation results demonstrate superior performance of the proposed technique as compared to the techniques reported in the literature. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Testing the significance of psychic factors in the etiology of alopecia areata. II. Examination of personality by means of Eysenck's Personality Inventory (MPI) adapted by Choynowski].

PubMed

Wygledowska-Kania, M; Bogdanowski, T

1995-01-01

We evaluated the role of psychic factors in the etiopathogenesis of alopecia areata on the basis of Eysenck's Personality Inventory adapted by Choynowski. 55 patients were tested (28 women and 27 men). The control group consisted of 50 volunteers. The analysis of the results showed that the neurotic type of personality was predominant in the group of patients (43.64%). Neurotic personality found in such a high percentage of the patients with alopecia areata may be an additional element in the group of psychic factors that possibly have some influence on the development of the disease.

Use of Vineland Adaptive Behavior Scales-II in Children with Autism--An Indian Experience

ERIC Educational Resources Information Center

Manohari, S. M.; Raman, Vijaya; Ashok, M. V.

2013-01-01

The Vineland Adaptive Behavior Scales-II Edition 2005 (Vineland-II) is useful in assessing abilities in autism spectrum disorder, where an accurate assessment of intelligence using standardized tools is difficult both due to the unique social and communication difficulties that these children present with and the behavioral issues that occur as…

Light-Dependent OCT Structure Changes in Photoreceptor Degenerative rd 10 Mouse Retina

PubMed Central

Li, Yichao; Zhang, Yikui; Chen, Sonia; Vernon, Gregory; Wong, Wai T.

2018-01-01

Purpose Using optical coherence tomography (OCT) to analyze the effects of light/dark adaptation in a mouse model of inherited photoreceptor degeneration (rd10), and to study dynamics of subretinal fluid during the progress of retinal degeneration. Methods rd10 and wild-type (WT) C57BL/6J mice were reared in cyclic light or darkness and imaged with Bioptigen UHR-OCT or Spectralis HRA+OCT after adaptation to either light or darkness. Results OCT images from rd10 mice were analyzed at three progressive stages of degeneration. After light-adaptation, stage I (postnatal age [P]26–29) eyes demonstrated no apparent subretinal fluid. At stage II (P32–38), subretinal fluid was present and restricted to parapapillary area, while at stage III (P44–45) extensive subretinal fluid was present across many retinal areas. Following overnight dark-adaptation, WT eyes showed a large reduction in outer retinal thickness (4.6 ± 1.4 μm, n = 16), whereas this change was significantly smaller in stage I rd10 eyes (1.5 ± 0.5 μm, n = 14). In stage II rd10 eyes, dark-adaptation significantly reduced the extent of subretinal fluid, with the amount of reduction correlating with the amount of fluid pre-existing in the light-adapted state. However, dark-adaptation did not significantly alter the amount of subretinal fluid observed in stage III rd10 mice. In addition, dark-rearing of rd10 mice from P6 to P30 slowed retinal degeneration. Conclusions Visual experience in the form of light/dark adaptation exerts a significant effect on outer retinal structure in the context of photoreceptor degeneration. This effect may arise from light-dependent alterations in fluid transport across the RPE monolayer, and promote photoreceptor survival as induced by dark-rearing. PMID:29490345

Angular Superresolution for a Scanning Antenna with Simulated Complex Scatterer-Type Targets

DTIC Science & Technology

2002-05-01

Approved for public release; distribution unlimited. The Scan- MUSIC (MUltiple SIgnal Classification), or SMUSIC, algorithm was developed by the Millimeter...with the use of a single rotatable sensor scanning in an angular region of interest. This algorithm has been adapted and extended from the MUSIC ...simulation. Abstract ii iii Contents 1. Introduction 1 2. Extension of the MUSIC Algorithm for Scanning Antenna 2 2.1 Subvector Averaging Method

Rural self-reliance: the impact on health experiences of people living with type II diabetes in rural Queensland, Australia.

PubMed

Page-Carruth, Althea; Windsor, Carol; Clark, Michele

2014-01-01

The objective of the study was to explore whether and how rural culture influences type II diabetes management and to better understand the social processes that rural people construct in coping with diabetes and its complications. In particular, the study aimed to analyse the interface and interactions between rural people with type II diabetes and the Australian health care system, and to develop a theoretical understanding that reflects constructs that may be more broadly applicable. The study applied constructivist grounded theory methods within an interpretive interactionist framework. Data from 39 semi-structured interviews with rural and urban type II diabetes patients and a mix of rural health care providers were analysed to develop a theoretical understanding of the social processes that define diabetes management in that context. The analysis suggests that although type II diabetes imposes limitations that require adjustment and adaptation, these processes are actively negotiated by rural people within the environmental context to fit the salient social understandings of autonomy and self-reliance. Thus, people normalized self-reliant diabetes management behaviours because this was congruent with the rural culture. Factors that informed the actions of normalization were relationships between participants and health care professionals, support, and access to individual resources. The findings point to ways in which rural self-reliance is conceived as the primary strategy of diabetes management. People face the paradox of engaging with a health care system that at the same time maximizes individual responsibility for health and minimizes the social support by which individuals manage the condition. The emphasis on self-reliance gives some legitimacy to a lack of prevention and chronic care services. Success of diabetes management behaviours is, however, contingent on relative resources. Where there is good primary care, there develops a number of downstream effects including a sense of empowerment to manage difficult rural environmental circumstances. This has particular bearing on health outcomes for people with fewer resources.

Rural self-reliance: the impact on health experiences of people living with type II diabetes in rural Queensland, Australia

PubMed Central

Page-Carruth, Althea; Windsor, Carol; Clark, Michele

2014-01-01

Objective The objective of the study was to explore whether and how rural culture influences type II diabetes management and to better understand the social processes that rural people construct in coping with diabetes and its complications. In particular, the study aimed to analyse the interface and interactions between rural people with type II diabetes and the Australian health care system, and to develop a theoretical understanding that reflects constructs that may be more broadly applicable. Methods The study applied constructivist grounded theory methods within an interpretive interactionist framework. Data from 39 semi-structured interviews with rural and urban type II diabetes patients and a mix of rural health care providers were analysed to develop a theoretical understanding of the social processes that define diabetes management in that context. Results The analysis suggests that although type II diabetes imposes limitations that require adjustment and adaptation, these processes are actively negotiated by rural people within the environmental context to fit the salient social understandings of autonomy and self-reliance. Thus, people normalized self-reliant diabetes management behaviours because this was congruent with the rural culture. Factors that informed the actions of normalization were relationships between participants and health care professionals, support, and access to individual resources. Conclusions The findings point to ways in which rural self-reliance is conceived as the primary strategy of diabetes management. People face the paradox of engaging with a health care system that at the same time maximizes individual responsibility for health and minimizes the social support by which individuals manage the condition. The emphasis on self-reliance gives some legitimacy to a lack of prevention and chronic care services. Success of diabetes management behaviours is, however, contingent on relative resources. Where there is good primary care, there develops a number of downstream effects including a sense of empowerment to manage difficult rural environmental circumstances. This has particular bearing on health outcomes for people with fewer resources. PMID:24964859

Occurrence and activity of a type II CRISPR-Cas system in Lactobacillus gasseri.

PubMed

Sanozky-Dawes, Rosemary; Selle, Kurt; O'Flaherty, Sarah; Klaenhammer, Todd; Barrangou, Rodolphe

2015-09-01

Bacteria encode clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated genes (cas), which collectively form an RNA-guided adaptive immune system against invasive genetic elements. In silico surveys have revealed that lactic acid bacteria harbour a prolific and diverse set of CRISPR-Cas systems. Thus, the natural evolutionary role of CRISPR-Cas systems may be investigated in these ecologically, industrially, scientifically and medically important microbes. In this study, 17 Lactobacillus gasseri strains were investigated and 6 harboured a type II-A CRISPR-Cas system, with considerable diversity in array size and spacer content. Several of the spacers showed similarity to phage and plasmid sequences, which are typical targets of CRISPR-Cas immune systems. Aligning the protospacers facilitated inference of the protospacer adjacent motif sequence, determined to be 5'-NTAA-3' flanking the 3' end of the protospacer. The system in L. gasseri JV-V03 and NCK 1342 interfered with transforming plasmids containing sequences matching the most recently acquired CRISPR spacers in each strain. We report the distribution and function of a native type II-A CRISPR-Cas system in the commensal species L. gasseri. Collectively, these results open avenues for applications for bacteriophage protection and genome modification in L. gasseri, and contribute to the fundamental understanding of CRISPR-Cas systems in bacteria.

Reshaping the folding energy landscape of human carbonic anhydrase II by a single point genetic mutation Pro237His.

PubMed

Jiang, Yan; Su, Jing-Tan; Zhang, Jun; Wei, Xiang; Yan, Yong-Bin; Zhou, Hai-Meng

2008-01-01

Human carbonic anhydrase (HCA) II participates in a variety of important biological processes, and it has long been known that genetic mutations of HCA II are closely correlated to human disease. In this research, we investigated the effects of a genetic single point mutation P237, which is located on the surface of the molecule and does not participate in the HCA II catalysis, on HCA II activity, stability and folding. Spectroscopic studies revealed that the mutation caused more buried Trp residues to become accessible by solvent and caused the NMR signals to become less dispersed, but did not affect the secondary structure or the hydrophobic exposure of the protein. The mutant was less stable than the wild type enzyme against heat- and GdnHCl-induced inactivation, but its pH adaptation was similar to the wild type. The mutation slightly decreased the stability of the molten globular intermediate, but gradually affected the stability of the native state by a 10-fold reduction of the Gibbs free energy for the transition from the native state to the intermediate. This might have led to an accumulation of the aggregation-prone molten globular intermediate, which further trapped the proteins into the off-pathway aggregates during refolding and reduced the levels of active enzyme in vivo. The results herein suggested that the correct positioning of the long loop around P237 might be crucial to the folding of HCA II, particularly the formation of the active site.

Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high-intensity exercise training.

PubMed

Wyckelsma, Victoria L; Levinger, Itamar; McKenna, Michael J; Formosa, Luke E; Ryan, Michael T; Petersen, Aaron C; Anderson, Mitchell J; Murphy, Robyn M

2017-06-01

Ageing is associated with an upregulation of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) in human skeletal muscle with the increased abundance of Mfn2 being exclusive to type II muscle fibres. These changes occur despite a similar content of mitochondria, as measured by COXIV, NDUFA9 and complexes in their native states (Blue Native PAGE). Following 12 weeks of high-intensity training (HIT), older adults exhibit a robust increase in mitochondria content, while there is a decline in Mfn2 in type II fibres. We propose that the upregulation of Mfn2 and MiD49 with age may be a protective mechanism to protect against mitochondrial dysfunction, in particularly in type II skeletal muscle fibres, and that exercise may have a unique protective effect negating the need for an increased turnover of mitochondria. Mitochondrial dynamics proteins are critical for mitochondrial turnover and maintenance of mitochondrial health. High-intensity interval training (HIT) is a potent training modality shown to upregulate mitochondrial content in young adults but little is known about the effects of HIT on mitochondrial dynamics proteins in older adults. This study investigated the abundance of protein markers for mitochondrial dynamics and mitochondrial content in older adults compared to young adults. It also investigated the adaptability of mitochondria to 12 weeks of HIT in older adults. Both older and younger adults showed a higher abundance of mitochondrial respiratory chain subunits COXIV and NDUFA9 in type I compared with type II fibres, with no difference between the older adults and young groups. In whole muscle homogenates, older adults had higher mitofusin-2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) contents compared to the young group. Also, older adults had higher levels of Mfn2 in type II fibres compared with young adults. Following HIT in older adults, MiD49 and Mfn2 levels were not different in whole muscle and Mfn2 content decreased in type II fibres. Increases in citrate synthase activity (55%) and mitochondrial respiratory chain subunits COXIV (37%) and NDUFA9 (48%) and mitochondrial respiratory chain complexes (∼70-100%) were observed in homogenates and/or single fibres. These findings reveal (i) a similar amount of mitochondria in muscle from young and healthy older adults and (ii) a robust increase of mitochondrial content following 12 weeks of HIT exercise in older adults. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature.

PubMed

Janzen, Darren; Delaney, Kathleen A; Shapiro, Elsa G

2017-06-01

Sensitive, reliable measurement instruments are critical for the evaluation of disease progression and new treatments that affect the brain in the mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical phenotypes that affect the brain during development and result in devastating cognitive decline and ultimately death without treatment. Comparisons of outcomes are hindered by diverse protocols and approaches to assessment including applicability to international trials necessary in rare diseases. We review both cognitive and adaptive measures with the goal of providing evidence to a Delphi panel to come to a consensus about recommendations for clinical trials for various age groups. The results of the consensus panel are reported in an accompanying article. The following data were gathered (from internet resources and from test manuals) for each measure and summarized in the discussion: reliability, validity, date and adequacy of normative data, applicability of the measure's metrics, cross cultural validity including translations and adaptations, feasibility in the MPS population, familiarity to sites, sensitivity to change, and interpretability. If, resulting from this consensus, standard protocols are used for both natural history and treatment studies, patients, their families, and health care providers will benefit from the ability to compare study outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Hunting increases phosphorylation of calcium/calmodulin-dependent protein kinase type II in adult barn owls.

PubMed

Nichols, Grant S; DeBello, William M

2015-01-01

Juvenile barn owls readily adapt to prismatic spectacles, whereas adult owls living under standard aviary conditions do not. We previously demonstrated that phosphorylation of the cyclic-AMP response element-binding protein (CREB) provides a readout of the instructive signals that guide plasticity in juveniles. Here we investigated phosphorylation of calcium/calmodulin-dependent protein kinase II (pCaMKII) in both juveniles and adults. In contrast to CREB, we found no differences in pCaMKII expression between prism-wearing and control juveniles within the external nucleus of the inferior colliculus (ICX), the major site of plasticity. For prism-wearing adults that hunted live mice and are capable of adaptation, expression of pCaMKII was increased relative to prism-wearing adults that fed passively on dead mice and are not capable of adaptation. This effect did not bear the hallmarks of instructive information: it was not localized to rostral ICX and did not exhibit a patchy distribution reflecting discrete bimodal stimuli. These data are consistent with a role for CaMKII as a permissive rather than an instructive factor. In addition, the paucity of pCaMKII expression in passively fed adults suggests that the permissive default setting is "off" in adults.

How do type II topoisomerases use ATP hydrolysis to simplify DNA topology beyond equilibrium? Investigating the relaxation reaction of non-supercoiling type II topoisomerases

PubMed Central

Stuchinskaya, Tanya; Mitchenall, Lesley A.; Schoeffler, Allyn J.; Corbett, Kevin D.; Berger, James M.; Bates, Andrew D.; Maxwell, Anthony

2015-01-01

DNA topoisomerases control the topology of DNA (e.g. the level of supercoiling) in all cells. Type IIA topoisomerases are ATP-dependent enzymes that have been shown to simplify the topology of their DNA substrates to a level beyond that expected at equilibrium (i.e. more relaxed than the product of relaxation by ATP-independent enzymes, such as type I topoisomerases, or a lower than equilibrium level of catenation). The mechanism of this effect is currently unknown, although several models have been suggested. We have analysed the DNA relaxation reactions of type II topoisomerases to further explore this phenomenon. We find that all type IIA topoisomerases tested exhibit the effect to a similar degree and that it is not dependent on the C-terminal domains of the enzymes. As recently reported, the type IIB topoisomerase, topo VI (which is only distantly related to the type IIA enzymes), does not exhibit topology simplification. We find that topology simplification is not significantly dependent on circle size in the range ~2–9 kbp, and is not altered by reducing the free energy available from ATP hydrolysis by varying the ATP:ADP ratio. A direct test of one model (DNA tracking, i.e. sliding of a protein clamp along DNA to trap supercoils) suggests that this is unlikely to be the explanation for the effect. We conclude that geometric selection of DNA segments by the enzymes is likely to be a primary source of the effect but that it is possible that other factors contribute. We also speculate whether topology simplification might simply be an evolutionary relic, with no adaptive significance. PMID:19094994

How do type II topoisomerases use ATP hydrolysis to simplify DNA topology beyond equilibrium? Investigating the relaxation reaction of nonsupercoiling type II topoisomerases.

PubMed

Stuchinskaya, Tanya; Mitchenall, Lesley A; Schoeffler, Allyn J; Corbett, Kevin D; Berger, James M; Bates, Andrew D; Maxwell, Anthony

2009-02-06

DNA topoisomerases control the topology of DNA (e.g., the level of supercoiling) in all cells. Type IIA topoisomerases are ATP-dependent enzymes that have been shown to simplify the topology of their DNA substrates to a level beyond that expected at equilibrium (i.e., more relaxed than the product of relaxation by ATP-independent enzymes, such as type I topoisomerases, or a lower-than-equilibrium level of catenation). The mechanism of this effect is currently unknown, although several models have been suggested. We have analyzed the DNA relaxation reactions of type II topoisomerases to further explore this phenomenon. We find that all type IIA topoisomerases tested exhibit the effect to a similar degree and that it is not dependent on the supercoil-sensing C-terminal domains of the enzymes. As recently reported, the type IIB topoisomerase, topoisomerase VI (which is only distantly related to type IIA enzymes), does not exhibit topology simplification. We find that topology simplification is not significantly dependent on circle size in the range approximately 2-9 kbp and is not altered by reducing the free energy available from ATP hydrolysis by varying the ADP:ATP ratio. A direct test of one model (DNA tracking; i.e., sliding of a protein clamp along DNA to trap supercoils) suggests that this is unlikely to be the explanation for the effect. We conclude that geometric selection of DNA segments by the enzymes is likely to be a primary source of the effect, but that it is possible that other kinetic factors contribute. We also speculate whether topology simplification might simply be an evolutionary relic, with no adaptive significance.

Living supramolecular polymerization achieved by collaborative assembly of platinum(II) complexes and block copolymers

PubMed Central

Zhang, Kaka; Yeung, Margaret Ching-Lam; Leung, Sammual Yu-Lut; Yam, Vivian Wing-Wah

2017-01-01

An important feature of biological systems to achieve complexity and precision is the involvement of multiple components where each component plays its own role and collaborates with other components. Mimicking this, we report living supramolecular polymerization achieved by collaborative assembly of two structurally dissimilar components, that is, platinum(II) complexes and poly(ethylene glycol)-b-poly(acrylic acid) (PEG-b-PAA). The PAA blocks neutralize the charges of the platinum(II) complexes, with the noncovalent metal–metal and π–π interactions directing the longitudinal growth of the platinum(II) complexes into 1D crystalline nanostructures, and the PEG blocks inhibiting the transverse growth of the platinum(II) complexes and providing the whole system with excellent solubility. The ends of the 1D crystalline nanostructures have been found to be active during the assembly and remain active after the assembly. One-dimensional segmented nanostructures with heterojunctions have been produced by sequential growth of two types of platinum(II) complexes. The PAA blocks act as adapters at the heterojunctions for lattice matching between chemically and crystallographically different platinum(II) complexes, achieving heterojunctions with a lattice mismatch as large as 21%. PMID:29078381

Achilles tendon adaptation in cross-country runners across a competitive season.

PubMed

Stanley, L E; Lucero, A; Mauntel, T C; Kennedy, M; Walker, N; Marshall, S W; Padua, D A; Berkoff, D J

2018-01-01

Ultrasound tissue characterization (UTC) is an imaging tool used to quantify tendon structural integrity. UTC has quantified Achilles tendon (AT) acute response to load in athletes; however, AT response to cumulative load over a season is unknown. The purpose of this study was to evaluate AT response across a four-month competitive season in collegiate cross-country (XC) runners. Participants (n=21; male=9, female=12; age=19.8±1.2 years; height=171.9±8.9 cm; weight=60.2±8.5 kg) were imaged using the UTC device with a 10-MHz linear-array transducer mounted in a tracking device. The device captures images at 0.2 mm intervals along the AT. UTC algorithms quantified the stability of pixel brightness over every 17 contiguous transverse images into four echo types (I-IV). A total of 168 scans (n=21, bilateral limbs) were performed monthly across the four-month season (Aug=M1, Sep=M2, Oct=M3, Nov=M4). Echo-type percentages (%) were calculated from each scan. Generalized estimating equations (GEE) linear regression models evaluated echo-type % change (β) over the season (M1=reference). Type I increased from M1 to M4 (β=9.10, P<.01; 95%CI: 7.01, 11.21) and Type II decreased from M1 to M3 (β=-2.71, P=.018; 95%CI: -4.96, -0.47) and M1 to M4 (β=-10.19, P<.01; 95%CI: -12.22, -8.17). Type III increased from M1 to M3 (β=0.42, P=.003; 95%CI: 0.19, 0.65) and M1 to M4 (β=0.49, P=.002; 95%CI: 0.18, 0.81), Type IV increased from M1 to M4 (β=0.57, P<.01; 95%CI: 0.29, 0.84). A positive adaptation in AT structural integrity was observed over the XC season, with a ~10% shift from Type II to Type I UTC echo types, suggesting AT resilience to a competitive season of repetitive loading in highly trained runners. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria.

PubMed

Inaoka, Daniel Ken; Shiba, Tomoo; Sato, Dan; Balogun, Emmanuel Oluwadare; Sasaki, Tsuyoshi; Nagahama, Madoka; Oda, Masatsugu; Matsuoka, Shigeru; Ohmori, Junko; Honma, Teruki; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu

2015-07-07

Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria

PubMed Central

Inaoka, Daniel Ken; Shiba, Tomoo; Sato, Dan; Balogun, Emmanuel Oluwadare; Sasaki, Tsuyoshi; Nagahama, Madoka; Oda, Masatsugu; Matsuoka, Shigeru; Ohmori, Junko; Honma, Teruki; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu

2015-01-01

Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs. PMID:26198225

Characterization and Exploitation of CRISPR Loci in Bifidobacterium longum

PubMed Central

Hidalgo-Cantabrana, Claudio; Crawley, Alexandra B.; Sanchez, Borja; Barrangou, Rodolphe

2017-01-01

Diverse CRISPR-Cas systems provide adaptive immunity in many bacteria and most archaea, via a DNA-encoded, RNA-mediated, nucleic-acid targeting mechanism. Over time, CRISPR loci expand via iterative uptake of invasive DNA sequences into the CRISPR array during the adaptation process. These genetic vaccination cards thus provide insights into the exposure of strains to phages and plasmids in space and time, revealing the historical predatory exposure of a strain. These genetic loci thus constitute a unique basis for genotyping of strains, with potential of resolution at the strain-level. Here, we investigate the occurrence and diversity of CRISPR-Cas systems in the genomes of various Bifidobacterium longum strains across three sub-species. Specifically, we analyzed the genomic content of 66 genomes belonging to B. longum subsp. longum, B. longum subsp. infantis and B. longum subsp. suis, and identified 25 strains that carry 29 total CRISPR-Cas systems. We identify various Type I and Type II CRISPR-Cas systems that are widespread in this species, notably I-C, I-E, and II-C. Noteworthy, Type I-C systems showed extended CRISPR arrays, with extensive spacer diversity. We show how these hypervariable loci can be used to gain insights into strain origin, evolution and phylogeny, and can provide discriminatory sequences to distinguish even clonal isolates. By investigating CRISPR spacer sequences, we reveal their origin and implicate phages and prophages as drivers of CRISPR immunity expansion in this species, with redundant targeting of select prophages. Analysis of CRISPR spacer origin also revealed novel PAM sequences. Our results suggest that CRISPR-Cas immune systems are instrumental in mounting diversified viral resistance in B. longum, and show that these sequences are useful for typing across three subspecies. PMID:29033911

Characterization and Exploitation of CRISPR Loci in Bifidobacterium longum.

PubMed

Hidalgo-Cantabrana, Claudio; Crawley, Alexandra B; Sanchez, Borja; Barrangou, Rodolphe

2017-01-01

Diverse CRISPR-Cas systems provide adaptive immunity in many bacteria and most archaea, via a DNA-encoded, RNA-mediated, nucleic-acid targeting mechanism. Over time, CRISPR loci expand via iterative uptake of invasive DNA sequences into the CRISPR array during the adaptation process. These genetic vaccination cards thus provide insights into the exposure of strains to phages and plasmids in space and time, revealing the historical predatory exposure of a strain. These genetic loci thus constitute a unique basis for genotyping of strains, with potential of resolution at the strain-level. Here, we investigate the occurrence and diversity of CRISPR-Cas systems in the genomes of various Bifidobacterium longum strains across three sub-species. Specifically, we analyzed the genomic content of 66 genomes belonging to B. longum subsp. longum, B. longum subsp. infantis and B. longum subsp. suis , and identified 25 strains that carry 29 total CRISPR-Cas systems. We identify various Type I and Type II CRISPR-Cas systems that are widespread in this species, notably I-C, I-E, and II-C. Noteworthy, Type I-C systems showed extended CRISPR arrays, with extensive spacer diversity. We show how these hypervariable loci can be used to gain insights into strain origin, evolution and phylogeny, and can provide discriminatory sequences to distinguish even clonal isolates. By investigating CRISPR spacer sequences, we reveal their origin and implicate phages and prophages as drivers of CRISPR immunity expansion in this species, with redundant targeting of select prophages. Analysis of CRISPR spacer origin also revealed novel PAM sequences. Our results suggest that CRISPR-Cas immune systems are instrumental in mounting diversified viral resistance in B. longum , and show that these sequences are useful for typing across three subspecies.

Beta Ca2+/CaM-dependent kinase type II triggers upregulation of GluA1 to coordinate adaptation to synaptic inactivity in hippocampal neurons.

PubMed

Groth, Rachel D; Lindskog, Maria; Thiagarajan, Tara C; Li, Li; Tsien, Richard W

2011-01-11

Prolonged AMPA-receptor blockade in hippocampal neuron cultures leads to both an increased expression of GluA1 postsynaptically and an increase in vesicle pool size and turnover rate presynaptically, adaptive changes that extend beyond simple synaptic scaling. As a molecular correlate, expression of the β Ca(2+)/CaM-dependent kinase type II (βCaMKII) is increased in response to synaptic inactivity. Here we set out to clarify the role of βCaMKII in the various manifestations of adaptation. Knockdown of βCaMKII by lentiviral-mediated expression of shRNA prevented the synaptic inactivity-induced increase in GluA1, as did treatment with the CaM kinase inhibitor KN-93, but not the inactive analog KN-92. These results demonstrate that, spurred by AMPA-receptor blockade, up-regulation of βCaMKII promotes increased GluA1 expression. Indeed, transfection of βCaMKII, but not a kinase-dead mutant, increased GluA1 expression on dendrites and elevated vesicle turnover (Syt-Ab uptake), mimicking the effect of synaptic inactivity on both sides of the synapse. In cells with elevated βCaMKII, relief of synaptic-activity blockade uncovered an increase in the frequency of miniature excitatory postsynaptic currents that could be rapidly and fully suppressed by PhTx blockade of GluA1 receptors. This increased mini frequency involved a genuine presynaptic enhancement, not merely an increased abundance of synapses. This finding suggests that Ca(2+) flux through GluA1 receptors may trigger the acute release of a retrograde messenger. Taken together, our results indicate that synaptic inactivity-induced increases in βCaMKII expression set in motion a series of events that culminate in coordinated pre- and postsynaptic adaptations in synaptic transmission.

An immunohistochemical study of the endocrine pancreas in raptors.

PubMed

Palmieri, C; Shivaprasad, H L

2014-12-01

The cytoarchitecture of the endocrine pancreas of 10 raptors (golden eagles, peregrine falcons, Saker falcon, turkey vultures, red-tailed hawk and unspecified falcon) was examined by immunohistochemistry. Three islet types were identified: type A mixed islets composed mainly by glucagon (A)-secreting cells, type B mixed islets with predominantly insulin (B)-secreting cell component and type M mixed islets (type M) consisting of variable number of glucagon-, insulin- and somatostatin (D)-secreting cells. The latter were further characterized into Type I, II or III according to the cell distribution of the three cell types. A and D cells were also randomly scattered within the exocrine pancreas. The results of this study suggest that the classical concept in birds of a segregation of A and B cells in well-defined and distinct islets is not applicable in raptors, reflecting an evolutionary adaptation to different dietary habits and variation in developmental mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brief Report: Adaptive Behavior and Cognitive Skills for Toddlers on the Autism Spectrum

ERIC Educational Resources Information Center

Ray-Subramanian, Corey E.; Huai, Nan; Weismer, Susan Ellis

2011-01-01

This study examined adaptive behavior and cognitive skills for 125 toddlers on the autism spectrum using the recently updated Vineland-II and Bayley-III. Delays in adaptive skills were apparent at 2 years of age. As a group, toddlers on the autism spectrum had a profile of Vineland-II standard scores in which Motor Skills greater than Daily Living…

Software for Engineering Simulations of a Spacecraft

NASA Technical Reports Server (NTRS)

Shireman, Kirk; McSwain, Gene; McCormick, Bernell; Fardelos, Panayiotis

2005-01-01

Spacecraft Engineering Simulation II (SES II) is a C-language computer program for simulating diverse aspects of operation of a spacecraft characterized by either three or six degrees of freedom. A functional model in SES can include a trajectory flight plan; a submodel of a flight computer running navigational and flight-control software; and submodels of the environment, the dynamics of the spacecraft, and sensor inputs and outputs. SES II features a modular, object-oriented programming style. SES II supports event-based simulations, which, in turn, create an easily adaptable simulation environment in which many different types of trajectories can be simulated by use of the same software. The simulation output consists largely of flight data. SES II can be used to perform optimization and Monte Carlo dispersion simulations. It can also be used to perform simulations for multiple spacecraft. In addition to its generic simulation capabilities, SES offers special capabilities for space-shuttle simulations: for this purpose, it incorporates submodels of the space-shuttle dynamics and a C-language version of the guidance, navigation, and control components of the space-shuttle flight software.

DEB Type I Reconstitution Package Deployment Manual (RPDM).

DTIC Science & Technology

1981-05-01

Waveguide Assembly (d) 1177H02 TWT Power Amplifier (e) TCM-6RK-I Transmit and Receive Remote Kits 20 C" I--I- CL* Figure 8. Terminal 21 17 February...Twist Six Waveguide to Coax Adapters 1.2.1.1.1(d) TWT Power Amplifier. The power amplifier utilizes a periodic permanent magnetic focused travelling...possible to adjust input power while observing TWT output with a power meter and directional coupler. The capability of controlling the TWT drive

Inhibition of latent membrane protein 1 impairs the growth and tumorigenesis of latency II Epstein-Barr virus-transformed T cells.

PubMed

Ndour, Papa Alioune; Brocqueville, Guillaume; Ouk, Tan-Sothéa; Goormachtigh, Gautier; Morales, Olivier; Mougel, Alexandra; Bertout, Julie; Melnyk, Oleg; Fafeur, Véronique; Feuillard, Jean; Coll, Jean; Adriaenssens, Eric

2012-04-01

Epstein-Barr virus (EBV) is a common human herpesvirus. Infection with EBV is associated with several human malignancies in which the virus expresses a set of latent proteins, among which is latent membrane protein 1 (LMP1). LMP1 is able to transform numerous cell types and is considered the main oncogenic protein of EBV. The mechanism of action is based on mimicry of activated members of the tumor necrosis factor (TNF) receptor superfamily, through the ability of LMP1 to bind similar adapters and to activate signaling pathways. We previously generated two unique models: a monocytic cell line and a lymphocytic (NC5) cell line immortalized by EBV that expresses the type II latency program. Here we generated LMP1 dominant negative forms (DNs), based on fusion between green fluorescent protein (GFP) and transformation effector site 1 (TES1) or TES2 of LMP1. Then we generated cell lines conditionally expressing these DNs. These DNs inhibit NF-κB and Akt pathways, resulting in the impairment of survival processes and increased apoptosis in these cell lines. This proapoptotic effect is due to reduced interaction of LMP1 with specific adapters and the recruitment of these adapters to DNs, which enable the generation of an apoptotic complex involving TRADD, FADD, and caspase 8. Similar results were obtained with cell lines displaying a latency III program in which LMP1-DNs decrease cell viability. Finally, we prove that synthetic peptides display similar inhibitory effects in EBV-infected cells. DNs derived from LMP1 could be used to develop therapeutic approaches for malignant diseases associated with EBV.

Inhibition of Latent Membrane Protein 1 Impairs the Growth and Tumorigenesis of Latency II Epstein-Barr Virus-Transformed T Cells

PubMed Central

Ndour, Papa Alioune; Brocqueville, Guillaume; Ouk, Tan-Sothéa; Goormachtigh, Gautier; Morales, Olivier; Mougel, Alexandra; Bertout, Julie; Melnyk, Oleg; Fafeur, Véronique; Feuillard, Jean; Coll, Jean

2012-01-01

Epstein-Barr virus (EBV) is a common human herpesvirus. Infection with EBV is associated with several human malignancies in which the virus expresses a set of latent proteins, among which is latent membrane protein 1 (LMP1). LMP1 is able to transform numerous cell types and is considered the main oncogenic protein of EBV. The mechanism of action is based on mimicry of activated members of the tumor necrosis factor (TNF) receptor superfamily, through the ability of LMP1 to bind similar adapters and to activate signaling pathways. We previously generated two unique models: a monocytic cell line and a lymphocytic (NC5) cell line immortalized by EBV that expresses the type II latency program. Here we generated LMP1 dominant negative forms (DNs), based on fusion between green fluorescent protein (GFP) and transformation effector site 1 (TES1) or TES2 of LMP1. Then we generated cell lines conditionally expressing these DNs. These DNs inhibit NF-κB and Akt pathways, resulting in the impairment of survival processes and increased apoptosis in these cell lines. This proapoptotic effect is due to reduced interaction of LMP1 with specific adapters and the recruitment of these adapters to DNs, which enable the generation of an apoptotic complex involving TRADD, FADD, and caspase 8. Similar results were obtained with cell lines displaying a latency III program in which LMP1-DNs decrease cell viability. Finally, we prove that synthetic peptides display similar inhibitory effects in EBV-infected cells. DNs derived from LMP1 could be used to develop therapeutic approaches for malignant diseases associated with EBV. PMID:22258264

The Massive Progenitor of the Type II-linear Supernova 2009kr

NASA Astrophysics Data System (ADS)

Elias-Rosa, Nancy; Van Dyk, Schuyler D.; Li, Weidong; Miller, Adam A.; Silverman, Jeffrey M.; Ganeshalingam, Mohan; Boden, Andrew F.; Kasliwal, Mansi M.; Vinkó, József; Cuillandre, Jean-Charles; Filippenko, Alexei V.; Steele, Thea N.; Bloom, Joshua S.; Griffith, Christopher V.; Kleiser, Io K. W.; Foley, Ryan J.

2010-05-01

We present early-time photometric and spectroscopic observations of supernova (SN) 2009kr in NGC 1832. We find that its properties to date support its classification as Type II-linear (SN II-L), a relatively rare subclass of core-collapse supernovae (SNe). We have also identified a candidate for the SN progenitor star through comparison of pre-explosion, archival images taken with WFPC2 on board the Hubble Space Telescope with SN images obtained using adaptive optics plus NIRC2 on the 10 m Keck-II telescope. Although the host galaxy's substantial distance (~26 Mpc) results in large uncertainties in the relative astrometry, we find that if this candidate is indeed the progenitor, it is a highly luminous (M 0 V = -7.8 mag) yellow supergiant with initial mass ~18-24 M sun. This would be the first time that an SN II-L progenitor has been directly identified. Its mass may be a bridge between the upper initial mass limit for the more common Type II-plateau SNe and the inferred initial mass estimate for one Type II-narrow SN. Based in part on observations made with the NASA/ESA Hubble Space Telescope (HST), obtained from the Data Archive at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy (AURA), Inc., under NASA contract NAS 05-26555; the 6.5 m Magellan Clay Telescope located at Las Campanas Observatory, Chile; various telescopes at Lick Observatory; the 1.3 m PAIRITEL on Mt. Hopkins; the SMARTS Consortium 1.3 m telescope located at Cerro Tololo Inter-American Observatory (CTIO), Chile; the 3.6 m Canada-France-Hawaii Telescope (CFHT), which is operated by the National Research Council of Canada, the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France, and the University of Hawaii; and the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and NASA, with generous financial support from the W. M. Keck Foundation.

Resistance training increases skeletal muscle oxidative capacity and net intramuscular triglyceride breakdown in type I and II fibres of sedentary males.

PubMed

Shepherd, S O; Cocks, M; Tipton, K D; Witard, O C; Ranasinghe, A M; Barker, T A; Wagenmakers, A J M; Shaw, C S

2014-06-01

Recent in vitro and in vivo experimental observations suggest that improvements in insulin sensitivity following endurance training are mechanistically linked to increases in muscle oxidative capacity, intramuscular triglyceride (IMTG) utilization during endurance exercise and increases in the content of the lipid droplet-associated perilipin 2 (PLIN2) and perilipin 5 (PLIN5). This study investigated the hypothesis that similar adaptations may also underlie the resistance training (RT)-induced improvements in insulin sensitivity. Thirteen sedentary men (20 ± 1 years old; body mass index 24.8 ± 0.8 kg m(-2)) performed 6 weeks of whole-body RT (three times per week), and changes in peak O2 uptake (in millilitres per minute per kilogram) and insulin sensitivity were assessed. Muscle biopsies (n = 8) were obtained before and after 60 min steady-state cycling at ~65% peak O2 uptake. Immunofluorescence microscopy was used to assess changes in oxidative capacity (measured as cytochrome c oxidase protein content), IMTG and PLIN2 and PLIN5 protein content. Resistance training increased peak O2 uptake (by 8 ± 3%), COX protein content (by 46 ± 13 and 61 ± 13% in type I and II fibres, respectively) and the Matsuda insulin sensitivity index (by 47 ± 6%; all P < 0.05). In type I fibres, IMTG (by 52 ± 11%; P < 0.05) and PLIN2 content (by 107 ± 19%; P < 0.05) were increased and PLIN5 content tended to increase (by 54 ± 22%; P = 0.054) post-training. In type II fibres, PLIN2 content increased (by 57 ± 20%; P < 0.05) and IMTG (by 46 ± 17%; P = 0.1) and PLIN5 content (by 44 ± 24%; P = 0.054) tended to increase post-training. Breakdown of IMTG during moderate-intensity exercise was greater in both type I and type II fibres (by 43 ± 5 and 37 ± 5%, respectively; P < 0.05) post-RT. The results confirm the hypothesis that RT enhances muscle oxidative capacity and increases IMTG breakdown and the content of PLIN2 and PLIN5 in both type I and type II fibres during endurance-type exercise. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

HIF-1α and GLUT-1 Expression in Atypical Endometrial Hyperplasia, Type I and II Endometrial Carcinoma: A Potential Role in Pathogenesis

PubMed Central

Abdou, Asmaa Gaber; Wahed, Moshira Mohammed Abdel; Kassem, Hend Abdou

2016-01-01

Introduction Hypoxia-Inducible Factor 1α (HIF-1α) is one of the major adaptive responses to hypoxia, regulating the activity of glucose transporter -1 (GLUT-1), responsible for glucose uptake. Aim To evaluate the immunohistochemical expression of both HIF-1α and GLUT-1 in type I and II endometrial carcinoma and their correlation with the available clinicopathologic variables in each type. Materials and Methods A retrospective study was conducted on archival blocks diagnosed from pathology department between April 2010 and August 2014 included 9 cases of atypical hyperplasia and 67 cases of endometrial carcinoma. Evaluation of both HIF-1α and GLUT-1 expression using standard immunohistochemical techniques performed on cut sections from selected paraffin embedded blocks. Statistical Analysis Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS). Results HIF-1α was expressed in epithelial (88.9%, 52.2%, 61.2% and 50%) and stromal (33.3%, 74.6%. 71.4% and 83.3%) components of hyperplasia, total cases of EC, type I and II EC, respectively. GLUT-1 was expressed in the epithelial component of 88.9%, 98.5%, 98% and 100% of hyperplasia, total EC cases, type I and II EC, respectively. The necrosis related pattern of epithelial HIF-1α expression was in favour of type II (p=0.018) and grade III (p=0.038). HIF-1α H-score was associated with high apoptosis in both type I and total cases of EC (p=0.04). GLUT-1 H-score was negatively correlated with apoptotic count (p=0.04) and associated with high grade (p=0.003) and advanced stage in total EC (p=0.004). GLUT-1 H-score was correlated with the pattern of HIF-1α staining in all cases of EC (p= 0.04). Conclusion The role of HIF-1α in epithelial cells may differ from that of stromal cells in EC; however they augment the expression of each other supporting the crosstalk between them. The stepwise increase in H- score of GLUT-1 in the studied cases implies its potential role in carcinogenesis of EC. HIF-1α may promote GLUT-1 expression in EC especially surrounding areas of necrosis. The differences between type I and type II EC regarding HIF-1α and GLUT-1 expression may confirm the differences in their aetiopathogenesis. PMID:27437226

HIF-1α and GLUT-1 Expression in Atypical Endometrial Hyperplasia, Type I and II Endometrial Carcinoma: A Potential Role in Pathogenesis.

PubMed

Al-Sharaky, Dalia Rifaat; Abdou, Asmaa Gaber; Wahed, Moshira Mohammed Abdel; Kassem, Hend Abdou

2016-05-01

Hypoxia-Inducible Factor 1α (HIF-1α) is one of the major adaptive responses to hypoxia, regulating the activity of glucose transporter -1 (GLUT-1), responsible for glucose uptake. To evaluate the immunohistochemical expression of both HIF-1α and GLUT-1 in type I and II endometrial carcinoma and their correlation with the available clinicopathologic variables in each type. A retrospective study was conducted on archival blocks diagnosed from pathology department between April 2010 and August 2014 included 9 cases of atypical hyperplasia and 67 cases of endometrial carcinoma. Evaluation of both HIF-1α and GLUT-1 expression using standard immunohistochemical techniques performed on cut sections from selected paraffin embedded blocks. Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS). HIF-1α was expressed in epithelial (88.9%, 52.2%, 61.2% and 50%) and stromal (33.3%, 74.6%. 71.4% and 83.3%) components of hyperplasia, total cases of EC, type I and II EC, respectively. GLUT-1 was expressed in the epithelial component of 88.9%, 98.5%, 98% and 100% of hyperplasia, total EC cases, type I and II EC, respectively. The necrosis related pattern of epithelial HIF-1α expression was in favour of type II (p=0.018) and grade III (p=0.038). HIF-1α H-score was associated with high apoptosis in both type I and total cases of EC (p=0.04). GLUT-1 H-score was negatively correlated with apoptotic count (p=0.04) and associated with high grade (p=0.003) and advanced stage in total EC (p=0.004). GLUT-1 H-score was correlated with the pattern of HIF-1α staining in all cases of EC (p= 0.04). The role of HIF-1α in epithelial cells may differ from that of stromal cells in EC; however they augment the expression of each other supporting the crosstalk between them. The stepwise increase in H- score of GLUT-1 in the studied cases implies its potential role in carcinogenesis of EC. HIF-1α may promote GLUT-1 expression in EC especially surrounding areas of necrosis. The differences between type I and type II EC regarding HIF-1α and GLUT-1 expression may confirm the differences in their aetiopathogenesis.

Adaptive evolution in the Arabidopsis MADS-box gene family inferred from its complete resolved phylogeny

PubMed Central

Martínez-Castilla, León Patricio; Alvarez-Buylla, Elena R.

2003-01-01

Gene duplication is a substrate of evolution. However, the relative importance of positive selection versus relaxation of constraints in the functional divergence of gene copies is still under debate. Plant MADS-box genes encode transcriptional regulators key in various aspects of development and have undergone extensive duplications to form a large family. We recovered 104 MADS sequences from the Arabidopsis genome. Bayesian phylogenetic trees recover type II lineage as a monophyletic group and resolve a branching sequence of monophyletic groups within this lineage. The type I lineage is comprised of several divergent groups. However, contrasting gene structure and patterns of chromosomal distribution between type I and II sequences suggest that they had different evolutionary histories and support the placement of the root of the gene family between these two groups. Site-specific and site-branch analyses of positive Darwinian selection (PDS) suggest that different selection regimes could have affected the evolution of these lineages. We found evidence for PDS along the branch leading to flowering time genes that have a direct impact on plant fitness. Sites with high probabilities of having been under PDS were found in the MADS and K domains, suggesting that these played important roles in the acquisition of novel functions during MADS-box diversification. Detected sites are targets for further experimental analyses. We argue that adaptive changes in MADS-domain protein sequences have been important for their functional divergence, suggesting that changes within coding regions of transcriptional regulators have influenced phenotypic evolution of plants. PMID:14597714

NKT Cell Networks in the Regulation of Tumor Immunity

PubMed Central

Robertson, Faith C.; Berzofsky, Jay A.; Terabe, Masaki

2014-01-01

CD1d-restricted natural killer T (NKT) cells lie at the interface between the innate and adaptive immune systems and are important mediators of immune responses and tumor immunosurveillance. These NKT cells uniquely recognize lipid antigens, and their rapid yet specific reactions influence both innate and adaptive immunity. In tumor immunity, two NKT subsets (type I and type II) have contrasting roles in which they not only cross-regulate one another, but also impact innate immune cell populations, including natural killer, dendritic, and myeloid lineage cells, as well as adaptive populations, especially CD8+ and CD4+ T cells. The extent to which NKT cells promote or suppress surrounding cells affects the host’s ability to prevent neoplasia and is consequently of great interest for therapeutic development. Data have shown the potential for therapeutic use of NKT cell agonists and synergy with immune response modifiers in both pre-clinical studies and preliminary clinical studies. However, there is room to improve treatment efficacy by further elucidating the biological mechanisms underlying NKT cell networks. Here, we discuss the progress made in understanding NKT cell networks, their consequent role in the regulation of tumor immunity, and the potential to exploit that knowledge in a clinical setting. PMID:25389427

Addressing potential local adaptation in species distribution models: implications for conservation under climate change

USGS Publications Warehouse

Hällfors, Maria Helena; Liao, Jishan; Dzurisin, Jason D. K.; Grundel, Ralph; Hyvärinen, Marko; Towle, Kevin; Wu, Grace C.; Hellmann, Jessica J.

2016-01-01

Species distribution models (SDMs) have been criticized for involving assumptions that ignore or categorize many ecologically relevant factors such as dispersal ability and biotic interactions. Another potential source of model error is the assumption that species are ecologically uniform in their climatic tolerances across their range. Typically, SDMs to treat a species as a single entity, although populations of many species differ due to local adaptation or other genetic differentiation. Not taking local adaptation into account, may lead to incorrect range prediction and therefore misplaced conservation efforts. A constraint is that we often do not know the degree to which populations are locally adapted, however. Lacking experimental evidence, we still can evaluate niche differentiation within a species' range to promote better conservation decisions. We explore possible conservation implications of making type I or type II errors in this context. For each of two species, we construct three separate MaxEnt models, one considering the species as a single population and two of disjunct populations. PCA analyses and response curves indicate different climate characteristics in the current environments of the populations. Model projections into future climates indicate minimal overlap between areas predicted to be climatically suitable by the whole species versus population-based models. We present a workflow for addressing uncertainty surrounding local adaptation in SDM application and illustrate the value of conducting population-based models to compare with whole-species models. These comparisons might result in more cautious management actions when alternative range outcomes are considered.

Camouflage and Misdirection: The Full-On Assault of Ebola Virus Disease

PubMed Central

Misasi, John; Sullivan, Nancy J.

2014-01-01

Ebolaviruses cause a severe hemorrhagic fever syndrome that is rapidly fatal to humans and non-human primates. Ebola protein interactions with host cellular proteins disrupt Type I and Type II interferon responses, RNAi anti-viral responses, antigen presentation, T-cell mediated antibody responses, humoral antibodies and cell mediated immunity. This multifaceted approach to evasion and suppression of innate and adaptive immune responses in their target hosts leads to the severe immune dysregulation and “cytokine storm” that is characteristic of fatal ebolavirus infection. Here we highlight some of the processes by which Ebola interacts with its mammalian hosts to evade anti-viral defenses. PMID:25417101

Contrasting patterns of selection between MHC I and II across populations of Humboldt and Magellanic penguins.

PubMed

Sallaberry-Pincheira, Nicole; González-Acuña, Daniel; Padilla, Pamela; Dantas, Gisele P M; Luna-Jorquera, Guillermo; Frere, Esteban; Valdés-Velásquez, Armando; Vianna, Juliana A

2016-10-01

The evolutionary and adaptive potential of populations or species facing an emerging infectious disease depends on their genetic diversity in genes, such as the major histocompatibility complex (MHC). In birds, MHC class I deals predominantly with intracellular infections (e.g., viruses) and MHC class II with extracellular infections (e.g., bacteria). Therefore, patterns of MHC I and II diversity may differ between species and across populations of species depending on the relative effect of local and global environmental selective pressures, genetic drift, and gene flow. We hypothesize that high gene flow among populations of Humboldt and Magellanic penguins limits local adaptation in MHC I and MHC II, and signatures of selection differ between markers, locations, and species. We evaluated the MHC I and II diversity using 454 next-generation sequencing of 100 Humboldt and 75 Magellanic penguins from seven different breeding colonies. Higher genetic diversity was observed in MHC I than MHC II for both species, explained by more than one MHC I loci identified. Large population sizes, high gene flow, and/or similar selection pressures maintain diversity but limit local adaptation in MHC I. A pattern of isolation by distance was observed for MHC II for Humboldt penguin suggesting local adaptation, mainly on the northernmost studied locality. Furthermore, trans-species alleles were found due to a recent speciation for the genus or convergent evolution. High MHC I and MHC II gene diversity described is extremely advantageous for the long-term survival of the species.

Biomarker-Guided Non-Adaptive Trial Designs in Phase II and Phase III: A Methodological Review

PubMed Central

Antoniou, Miranta; Kolamunnage-Dona, Ruwanthi; Jorgensen, Andrea L.

2017-01-01

Biomarker-guided treatment is a rapidly developing area of medicine, where treatment choice is personalised according to one or more of an individual’s biomarker measurements. A number of biomarker-guided trial designs have been proposed in the past decade, including both adaptive and non-adaptive trial designs which test the effectiveness of a biomarker-guided approach to treatment with the aim of improving patient health. A better understanding of them is needed as challenges occur both in terms of trial design and analysis. We have undertaken a comprehensive literature review based on an in-depth search strategy with a view to providing the research community with clarity in definition, methodology and terminology of the various biomarker-guided trial designs (both adaptive and non-adaptive designs) from a total of 211 included papers. In the present paper, we focus on non-adaptive biomarker-guided trial designs for which we have identified five distinct main types mentioned in 100 papers. We have graphically displayed each non-adaptive trial design and provided an in-depth overview of their key characteristics. Substantial variability has been observed in terms of how trial designs are described and particularly in the terminology used by different authors. Our comprehensive review provides guidance for those designing biomarker-guided trials. PMID:28125057

Parental distress, parenting practices, and child adaptive outcomes following traumatic brain injury.

PubMed

Micklewright, Jackie L; King, Tricia Z; O'Toole, Kathleen; Henrich, Chris; Floyd, Frank J

2012-03-01

Moderate and severe pediatric traumatic brain injuries (TBI) are associated with significant familial distress and child adaptive sequelae. Our aim was to examine the relationship between parental psychological distress, parenting practices (authoritarian, permissive, authoritative), and child adaptive functioning 12-36 months following TBI or orthopedic injury (OI). Injury type was hypothesized to moderate the relationship between parental distress and child adaptive functioning, demonstrating a significantly stronger relationship in the TBI relative to OI group. Authoritarian parenting practices were hypothesized to mediate relationship between parental distress and child adaptive functioning across groups. Groups (TBI n = 21, OI n = 23) did not differ significantly on age at injury, time since injury, sex, race, or SES. Parents completed the Brief Symptom Inventory, Parenting Practices Questionnaire, and Vineland-II. Moderation and mediation hypotheses were tested using hierarchical multiple regression and a bootstrapping approach, respectively. Results supported moderation and revealed that higher parental psychological distress was associated with lower child adaptive functioning in the TBI group only. Mediation results indicated that higher parental distress was associated with authoritarian parenting practices and lower adaptive functioning across groups. Results suggest that parenting practices are an important area of focus for studies attempting to elucidate the relationship between parent and child functioning following TBI.

Adaptation and Latent Structure of the Swahili Version of Beck Depression Inventory-II in a Low Literacy Population in the Context of HIV.

PubMed

Abubakar, Amina; Kalu, Raphael Birya; Katana, Khamis; Kabunda, Beatrice; Hassan, Amin S; Newton, Charles R; Van de Vijver, Fons

2016-01-01

We set out to adapt the Beck Depression Inventory (BDI)-II in Kenya and examine its factorial structure. In the first phase we carried out in-depth interviews involving 29 adult members of the community to elicit their understanding of depression and identify aspects of the BDI-II that required adaptation. In the second phase, a modified version of BDI-II was administered to 221 adults randomly selected from the community to allow for the evaluation of its psychometric properties. In the third phase of the study we evaluated the discriminative validity of BDI-11 by comparing a randomly chosen community sample (n = 29) with caregivers of adolescents affected by HIV (n = 77). A considerable overlap between the BDI symptoms and those generated in the interviews was observed. Relevant idioms and symptoms such as 'thinking too much' and 'Kuchoka moyo (having a tired heart)' were identified. The administration of the BDI had to be modified to make it suitable for the low literacy levels of our participants. Fit indices for several models (one factorial, two-factor model and a three factor model) were all within acceptable range. Evidence indicated that while multidimensional models could be fitted, the strong correlations between the factors implied that a single factor model may be the best suited solution (alpha [0.89], and a significant correlation with locally identified items [r = 0.51]) confirmed the good psychometric properties of the adapted BDI-II. No evidence was found to support the hypothesis that somatization was more prevalent. Lastly, caregivers of HIV affected adolescents had significantly higher scores compared to adults randomly selected from the community F(1, 121) = 23.31, p < .001 indicating the discriminative validity of the adapted BDI = II. With an adapted administration procedure, the BDI-II provides an adequate measure of depressive symptoms which can be used alongside other measures for proper diagnosis in a low literacy population.

Crystal structure and enzymatic properties of chalcone isomerase from the Antarctic vascular plant Deschampsia antarctica Desv.

PubMed

Park, Sun-Ha; Lee, Chang Woo; Cho, Sung Mi; Lee, Hyoungseok; Park, Hyun; Lee, Jungeun; Lee, Jun Hyuck

2018-01-01

Chalcone isomerase (CHI) is an important enzyme for flavonoid biosynthesis that catalyzes the intramolecular cyclization of chalcones into (S)-flavanones. CHIs have been classified into two types based on their substrate specificity. Type I CHIs use naringenin chalcone as a substrate and are found in most of plants besides legumes, whereas type II CHIs in leguminous plants can also utilize isoliquiritigenin. In this study, we found that the CHI from the Antarctic plant Deschampsia antarctica (DaCHI1) is of type I based on sequence homology but can use type II CHI substrates. To clarify the enzymatic mechanism of DaCHI1 at the molecular level, the crystal structures of unliganded DaCHI1 and isoliquiritigenin-bound DaCHI1 were determined at 2.7 and 2.1 Å resolutions, respectively. The structures revealed that isoliquiritigenin binds to the active site of DaCHI1 and induces conformational changes. Additionally, the activity assay showed that while DaCHI1 exhibits substrate preference for naringenin chalcone, it can also utilize isoliquiritigenin although the catalytic activity was relatively low. Based on these results, we propose that DaCHI1 uses various substrates to produce antioxidant flavonoids as an adaptation to oxidative stresses associated with harsh environmental conditions.

Crystal structure and enzymatic properties of chalcone isomerase from the Antarctic vascular plant Deschampsia antarctica Desv.

PubMed Central

Lee, Hyoungseok; Park, Hyun; Lee, Jungeun

2018-01-01

Chalcone isomerase (CHI) is an important enzyme for flavonoid biosynthesis that catalyzes the intramolecular cyclization of chalcones into (S)-flavanones. CHIs have been classified into two types based on their substrate specificity. Type I CHIs use naringenin chalcone as a substrate and are found in most of plants besides legumes, whereas type II CHIs in leguminous plants can also utilize isoliquiritigenin. In this study, we found that the CHI from the Antarctic plant Deschampsia antarctica (DaCHI1) is of type I based on sequence homology but can use type II CHI substrates. To clarify the enzymatic mechanism of DaCHI1 at the molecular level, the crystal structures of unliganded DaCHI1 and isoliquiritigenin-bound DaCHI1 were determined at 2.7 and 2.1 Å resolutions, respectively. The structures revealed that isoliquiritigenin binds to the active site of DaCHI1 and induces conformational changes. Additionally, the activity assay showed that while DaCHI1 exhibits substrate preference for naringenin chalcone, it can also utilize isoliquiritigenin although the catalytic activity was relatively low. Based on these results, we propose that DaCHI1 uses various substrates to produce antioxidant flavonoids as an adaptation to oxidative stresses associated with harsh environmental conditions. PMID:29394293

The Arcuate Nucleus: A Site of Fast Negative Feedback for Corticosterone Secretion in Male Rats

PubMed Central

Kawata, Mitsuhiro; Escobar, Carolina

2017-01-01

Abstract Variations in circulating corticosterone (Cort) are driven by the paraventricular nucleus of the hypothalamus (PVN), mainly via the sympathetic autonomic nervous system (ANS) directly stimulating Cort release from the adrenal gland and via corticotropin-releasing hormone targeting the adenohypophysis to release adrenocorticotropic hormone (ACTH). Cort feeds back through glucocorticoid receptors (GRs). Here we show in male Wistar rats that PVN neurons projecting to the adrenal gland do not express GRs, leaving the question of how the ANS in the PVN gets information about circulating Cort levels to control the adrenal. Since the arcuate nucleus (ARC) shows a less restrictive blood–brain barrier, expresses GRs, and projects to the PVN, we investigated whether the ARC can detect and produce fast adjustments of circulating Cort. In low Cort conditions (morning), local microdialysis in the ARC with type I GR antagonist produced a fast and sustained increase of Cort. This was not observed with a type II antagonist. At the circadian peak levels of Cort (afternoon), a type II GR antagonist, but not a type I antagonist, increased Cort levels but not ACTH levels. Antagonist infusions in the PVN did not modify circulating Cort levels, demonstrating the specificity of the ARC to give Cort negative feedback. Furthermore, type I and II GR agonists in the ARC prevented the increase of Cort after stress, demonstrating the role of the ARC as sensor to modulate Cort release. Our findings show that the ARC may be essential to sense blood levels of Cort and adapt Cort secretion depending on such conditions as stress or time of day. PMID:28275717

The interferon-dependent orchestration of innate and adaptive immunity after transplantation.

PubMed

Robb, Renee J; Hill, Geoffrey R

2012-06-07

The therapeutic GVL effect after allogeneic stem cell transplantation is limited by the development of GVHD. The ultimate aim of current research is to separate the 2 processes in a meaningful fashion. The IFNs are a pleiotropic group of cytokines that were originally recognized because of their ability to interfere with viral replication. However, it is now established that these cytokines play an important role in orchestrating both innate and adaptive immunity. Multiple studies have investigated the effects of both types I and II IFN on GVHD and GVL in preclinical transplant models. The results indicate variable effects that are dependent on the period of activity within the developing immune response, the presence and type of pretransplant conditioning and the differential mechanisms, and IFN sensitivity of immune pathology within individual target organs during GVHD. This Perspective discusses the current literature on the IFNs and their potential modulation within clinical transplantation, focusing particularly on enhancing the therapeutic GVL effects.

A two-stage patient enrichment adaptive design in phase II oncology trials.

PubMed

Song, James X

2014-01-01

Illustrated is the use of a patient enrichment adaptive design in a randomized phase II trial which allows the evaluation of treatment benefits by the biomarker expression level and makes interim adjustment according to the pre-specified rules. The design was applied to an actual phase II metastatic hepatocellular carcinoma (HCC) trial in which progression-free survival (PFS) in two biomarker-defined populations is evaluated at both interim and final analyses. As an extension, a short-term biomarker is used to predict the long-term PFS in a Bayesian model in order to improve the precision of hazard ratio (HR) estimate at the interim analysis. The characteristics of the extended design are examined in a number of scenarios via simulations. The recommended adaptive design is shown to be useful in a phase II setting. When a short-term maker which correlates with the long-term PFS is available, the design can be applied in smaller early phase trials in which PFS requires longer follow-up. In summary, the adaptive design offers flexibility in randomized phase II patient enrichment trials and should be considered in an overall personalized healthcare (PHC) strategy. Copyright © 2013 Elsevier Inc. All rights reserved.

Mutations of Cytochrome b559 and PsbJ on and near the QC Site in Photosystem II Influence the Regulation of Short-Term Light Response and Photosynthetic Growth of the Cyanobacterium Synechocystis sp. PCC 6803.

PubMed

Huang, Jine-Yung; Chiu, Yi-Fang; Ortega, José M; Wang, Hsing-Ting; Tseng, Tien-Sheng; Ke, Shyue-Chu; Roncel, Mercedes; Chu, Hsiu-An

2016-04-19

The characteristic features of two types of short-term light adaptations of the photosynthetic apparatus of the cyanobacterium Synechocystis sp. PCC 6803, state transition and blue-green light-induced fluorescence quenching, were compared in wild-type and cytochrome b559 and PsbJ mutant cells with mutations on and near the QC site in photosystem II (PSII). All mutant cells grew photoautotrophically and assembled stable PSII. Thermoluminescence emission experiments showed a decrease in the stability of the S3QB(-)/S2QB(-) charge pairs in the A16FJ, S28Aβ, and V32Fβ mutant cells. When dark-adapted wild-type and mutant cells were illuminated by medium-intensity blue light, the increase in the PSII fluorescence yield (indicating a transition to state 1) was more prominent in mutant than wild-type cells. Strong blue-light conditions induced a quenching of fluorescence corresponding to nonphotochemical fluorescence quenching (NPQ). The extension of NPQ decreased significantly in the mutants, and the kinetics appeared to be affected. When similar measures were repeated on an orange carotenoid protein (OCP)-deficient background, little or no quenching was observed, which confirms that the decrease in fluorescence under strong blue light corresponded to the OCP-dependent NPQ. Immunoblot results showed that the attenuated effect of blue light-induced NPQ in mutant cells was not due to a lack of OCP. Photosynthetic growth and biomass production were greater for A16FJ, S28Aβ, and V32Fβ mutant cells than for wild-type cells under normal growth conditions. Our results suggest that mutations of cytochrome b559 and PsbJ on and near the QC site of PSII may modulate the short-term light response in cyanobacteria.

Cell-type-specific profiling of protein-DNA interactions without cell isolation using targeted DamID with next-generation sequencing.

PubMed

Marshall, Owen J; Southall, Tony D; Cheetham, Seth W; Brand, Andrea H

2016-09-01

This protocol is an extension to: Nat. Protoc. 2, 1467-1478 (2007); doi:10.1038/nprot.2007.148; published online 7 June 2007The ability to profile transcription and chromatin binding in a cell-type-specific manner is a powerful aid to understanding cell-fate specification and cellular function in multicellular organisms. We recently developed targeted DamID (TaDa) to enable genome-wide, cell-type-specific profiling of DNA- and chromatin-binding proteins in vivo without cell isolation. As a protocol extension, this article describes substantial modifications to an existing protocol, and it offers additional applications. TaDa builds upon DamID, a technique for detecting genome-wide DNA-binding profiles of proteins, by coupling it with the GAL4 system in Drosophila to enable both temporal and spatial resolution. TaDa ensures that Dam-fusion proteins are expressed at very low levels, thus avoiding toxicity and potential artifacts from overexpression. The modifications to the core DamID technique presented here also increase the speed of sample processing and throughput, and adapt the method to next-generation sequencing technology. TaDa is robust, reproducible and highly sensitive. Compared with other methods for cell-type-specific profiling, the technique requires no cell-sorting, cross-linking or antisera, and binding profiles can be generated from as few as 10,000 total induced cells. By profiling the genome-wide binding of RNA polymerase II (Pol II), TaDa can also identify transcribed genes in a cell-type-specific manner. Here we describe a detailed protocol for carrying out TaDa experiments and preparing the material for next-generation sequencing. Although we developed TaDa in Drosophila, it should be easily adapted to other organisms with an inducible expression system. Once transgenic animals are obtained, the entire experimental procedure-from collecting tissue samples to generating sequencing libraries-can be accomplished within 5 d.

Differential Distribution of Type II CRISPR-Cas Systems in Agricultural and Nonagricultural Campylobacter coli and Campylobacter jejuni Isolates Correlates with Lack of Shared Environments

PubMed Central

Pearson, Bruce M.; Louwen, Rogier; van Baarlen, Peter; van Vliet, Arnoud H.M.

2015-01-01

CRISPR (clustered regularly interspaced palindromic repeats)-Cas (CRISPR-associated) systems are sequence-specific adaptive defenses against phages and plasmids which are widespread in prokaryotes. Here we have studied whether phylogenetic relatedness or sharing of environmental niches affects the distribution and dissemination of Type II CRISPR-Cas systems, first in 132 bacterial genomes from 15 phylogenetic classes, ranging from Proteobacteria to Actinobacteria. There was clustering of distinct Type II CRISPR-Cas systems in phylogenetically distinct genera with varying G+C%, which share environmental niches. The distribution of CRISPR-Cas within a genus was studied using a large collection of genome sequences of the closely related Campylobacter species Campylobacter jejuni (N = 3,746) and Campylobacter coli (N = 486). The Cas gene cas9 and CRISPR-repeat are almost universally present in C. jejuni genomes (98.0% positive) but relatively rare in C. coli genomes (9.6% positive). Campylobacter jejuni and agricultural C. coli isolates share the C. jejuni CRISPR-Cas system, which is closely related to, but distinct from the C. coli CRISPR-Cas system found in C. coli isolates from nonagricultural sources. Analysis of the genomic position of CRISPR-Cas insertion suggests that the C. jejuni-type CRISPR-Cas has been transferred to agricultural C. coli. Conversely, the absence of the C. coli-type CRISPR-Cas in agricultural C. coli isolates may be due to these isolates not sharing the same environmental niche, and may be affected by farm hygiene and biosecurity practices in the agricultural sector. Finally, many CRISPR spacer alleles were linked with specific multilocus sequence types, suggesting that these can assist molecular epidemiology applications for C. jejuni and C. coli. PMID:26338188

Executive Function and Adaptive Behavior in Muenke Syndrome.

PubMed

Yarnell, Colin M P; Addissie, Yonit A; Hadley, Donald W; Guillen Sacoto, Maria J; Agochukwu, Nneamaka B; Hart, Rachel A; Wiggs, Edythe A; Platte, Petra; Paelecke, Yvonne; Collmann, Hartmut; Schweitzer, Tilmann; Kruszka, Paul; Muenke, Maximilian

2015-08-01

To investigate executive function and adaptive behavior in individuals with Muenke syndrome using validated instruments with a normative population and unaffected siblings as controls. Participants in this cross-sectional study included individuals with Muenke syndrome (P250R mutation in FGFR3) and their mutation-negative siblings. Participants completed validated assessments of executive functioning (Behavior Rating Inventory of Executive Function [BRIEF]) and adaptive behavior skills (Adaptive Behavior Assessment System, Second Edition [ABAS-II]). Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years). For the General Executive Composite scale of the BRIEF, 32.1% of the cohort had scores greater than +1.5 SD, signifying potential clinical significance. For the General Adaptive Composite of the ABAS-II, 28.2% of affected individuals scored in the 3rd-8th percentile of the normative population, and 56.4% were below the average category (<25th percentile). Multiple regression analysis did not identify craniosynostosis as a predictor of BRIEF (P = .70) or ABAS-II scores (P = .70). In the sibling pair analysis, affected siblings performed significantly poorer on the BRIEF General Executive Composite and the ABAS-II General Adaptive Composite. Individuals with Muenke syndrome are at an increased risk for developing adaptive and executive function behavioral changes compared with a normative population and unaffected siblings. Published by Elsevier Inc.

Integrated Procurement Management System, Version II

NASA Technical Reports Server (NTRS)

Collier, L. J.

1985-01-01

Integrated Procurement Management System, Version II (IPMS II) is online/ batch system for collecting developing, managing and disseminating procurementrelated data at NASA Johnson Space Center. Portions of IPMS II adaptable to other procurement situations.

Validation of Arabic and English versions of the ARSMA-II Acculturation Rating Scale.

PubMed

Jadalla, Ahlam; Lee, Jerry

2015-02-01

To translate and adapt the Acculturation Rating Scale of Mexican-Americans II (ARSMA-II) for Arab Americans. A multistage translation process followed by a pilot and a large study. The translated and adapted versions, Acculturation Rating Scale for Arabic Americans-II Arabic and English (ARSAA-IIA, ARSAA-IIE), were validated in a sample of 297 Arab Americans. Factor analyses with principal axis factoring extractions and direct oblimin rotations were used to identify the underlying structure of ARSAA-II. Factor analysis confirmed the underlying structure of ARSAA-II and produced two interpretable factors labeled as 'Attraction to American Culture' (AAmC) and 'Attraction to Arabic Culture' (AArC). The Cronbach's alphas of AAmC and AArC were .89 and .85 respectively. Findings support ARSAA-II A & E to assess acculturation among Arab Americans. The emergent factors of ARSAA-II support the theoretical structure of the original ARSMA-II tool and show high internal consistency.

Are heritability and selection related to population size in nature? Meta-analysis and conservation implications.

PubMed

Wood, Jacquelyn L A; Yates, Matthew C; Fraser, Dylan J

2016-06-01

It is widely thought that small populations should have less additive genetic variance and respond less efficiently to natural selection than large populations. Across taxa, we meta-analytically quantified the relationship between adult census population size (N) and additive genetic variance (proxy: h (2)) and found no reduction in h (2) with decreasing N; surveyed populations ranged from four to one million individuals (1735 h (2) estimates, 146 populations, 83 species). In terms of adaptation, ecological conditions may systematically differ between populations of varying N; the magnitude of selection these populations experience may therefore also differ. We thus also meta-analytically tested whether selection changes with N and found little evidence for systematic differences in the strength, direction or form of selection with N across different trait types and taxa (7344 selection estimates, 172 populations, 80 species). Collectively, our results (i) indirectly suggest that genetic drift neither overwhelms selection more in small than in large natural populations, nor weakens adaptive potential/h (2) in small populations, and (ii) imply that natural populations of varying sizes experience a variety of environmental conditions, without consistently differing habitat quality at small N. However, we caution that the data are currently insufficient to determine whether some small populations may retain adaptive potential definitively. Further study is required into (i) selection and genetic variation in completely isolated populations of known N, under-represented taxonomic groups, and nongeneralist species, (ii) adaptive potential using multidimensional approaches and (iii) the nature of selective pressures for specific traits.

Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation.

PubMed

Kieper, Sebastian N; Almendros, Cristóbal; Behler, Juliane; McKenzie, Rebecca E; Nobrega, Franklin L; Haagsma, Anna C; Vink, Jochem N A; Hess, Wolfgang R; Brouns, Stan J J

2018-03-27

CRISPR-Cas systems adapt their immunological memory against their invaders by integrating short DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci. While Cas1 and Cas2 make up the core machinery of the CRISPR integration process, various class I and II CRISPR-Cas systems encode Cas4 proteins for which the role is unknown. Here, we introduced the CRISPR adaptation genes cas1, cas2, and cas4 from the type I-D CRISPR-Cas system of Synechocystis sp. 6803 into Escherichia coli and observed that cas4 is strictly required for the selection of targets with protospacer adjacent motifs (PAMs) conferring I-D CRISPR interference in the native host Synechocystis. We propose a model in which Cas4 assists the CRISPR adaptation complex Cas1-2 by providing DNA substrates tailored for the correct PAM. Introducing functional spacers that target DNA sequences with the correct PAM is key to successful CRISPR interference, providing a better chance of surviving infection by mobile genetic elements. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Herpes simplex virus-2 in the genital mucosa: insights into the mucosal host response and vaccine development.

PubMed

Lee, Amanda J; Ashkar, Ali A

2012-02-01

Herpes simplex virus (HSV)-2 is the predominant cause of genital herpes and has been implicated in HIV infection and transmission. Thus far, vaccines developed against HSV-2 have been clinically ineffective in preventing infection. This review aims to summarize the innate and adaptive immune responses against HSV-2 and examines the current status of vaccine development. Both innate and adaptive immune responses are essential for an effective primary immune response and the generation of immunity. The innate response involves Toll-like receptors, natural killer cells, plasmacytoid dendritic cells, and type I, II, and III interferons. The adaptive response requires a balance between CD4+ and CD8+ T-cells for optimal viral clearance. T-regulatory cells may be involved, although their exact function has yet to be determined. Current vaccine development involves the use of HSV-2 peptides or attenuated/replication-defective HSV-2 to generate adaptive anti-HSV-2 immune responses, however the generation of innate responses may also be an important consideration. Although vaccine development has primarily focused on the adaptive response, arguments for innate involvement are emerging. A greater understanding of the innate and adaptive processes underlying the response to HSV-2 infection will provide the foundation for the development of an effective vaccine.

Sequences spanning the leader-repeat junction mediate CRISPR adaptation to phage in Streptococcus thermophilus

PubMed Central

Wei, Yunzhou; Chesne, Megan T.; Terns, Rebecca M.; Terns, Michael P.

2015-01-01

CRISPR-Cas systems are RNA-based immune systems that protect prokaryotes from invaders such as phages and plasmids. In adaptation, the initial phase of the immune response, short foreign DNA fragments are captured and integrated into host CRISPR loci to provide heritable defense against encountered foreign nucleic acids. Each CRISPR contains a ∼100–500 bp leader element that typically includes a transcription promoter, followed by an array of captured ∼35 bp sequences (spacers) sandwiched between copies of an identical ∼35 bp direct repeat sequence. New spacers are added immediately downstream of the leader. Here, we have analyzed adaptation to phage infection in Streptococcus thermophilus at the CRISPR1 locus to identify cis-acting elements essential for the process. We show that the leader and a single repeat of the CRISPR locus are sufficient for adaptation in this system. Moreover, we identified a leader sequence element capable of stimulating adaptation at a dormant repeat. We found that sequences within 10 bp of the site of integration, in both the leader and repeat of the CRISPR, are required for the process. Our results indicate that information at the CRISPR leader-repeat junction is critical for adaptation in this Type II-A system and likely other CRISPR-Cas systems. PMID:25589547

Population genomic analysis of strain variation in Leptospirillum group II bacteria involved in acid mine drainage formation.

PubMed

Simmons, Sheri L; Dibartolo, Genevieve; Denef, Vincent J; Goltsman, Daniela S Aliaga; Thelen, Michael P; Banfield, Jillian F

2008-07-22

Deeply sampled community genomic (metagenomic) datasets enable comprehensive analysis of heterogeneity in natural microbial populations. In this study, we used sequence data obtained from the dominant member of a low-diversity natural chemoautotrophic microbial community to determine how coexisting closely related individuals differ from each other in terms of gene sequence and gene content, and to uncover evidence of evolutionary processes that occur over short timescales. DNA sequence obtained from an acid mine drainage biofilm was reconstructed, taking into account the effects of strain variation, to generate a nearly complete genome tiling path for a Leptospirillum group II species closely related to L. ferriphilum (sampling depth approximately 20x). The population is dominated by one sequence type, yet we detected evidence for relatively abundant variants (>99.5% sequence identity to the dominant type) at multiple loci, and a few rare variants. Blocks of other Leptospirillum group II types ( approximately 94% sequence identity) have recombined into one or more variants. Variant blocks of both types are more numerous near the origin of replication. Heterogeneity in genetic potential within the population arises from localized variation in gene content, typically focused in integrated plasmid/phage-like regions. Some laterally transferred gene blocks encode physiologically important genes, including quorum-sensing genes of the LuxIR system. Overall, results suggest inter- and intrapopulation genetic exchange involving distinct parental genome types and implicate gain and loss of phage and plasmid genes in recent evolution of this Leptospirillum group II population. Population genetic analyses of single nucleotide polymorphisms indicate variation between closely related strains is not maintained by positive selection, suggesting that these regions do not represent adaptive differences between strains. Thus, the most likely explanation for the observed patterns of polymorphism is divergence of ancestral strains due to geographic isolation, followed by mixing and subsequent recombination.

Population Genomic Analysis of Strain Variation in Leptospirillum Group II Bacteria Involved in Acid Mine Drainage Formation

PubMed Central

Denef, Vincent J; Goltsman, Daniela S. Aliaga; Thelen, Michael P; Banfield, Jillian F

2008-01-01

Deeply sampled community genomic (metagenomic) datasets enable comprehensive analysis of heterogeneity in natural microbial populations. In this study, we used sequence data obtained from the dominant member of a low-diversity natural chemoautotrophic microbial community to determine how coexisting closely related individuals differ from each other in terms of gene sequence and gene content, and to uncover evidence of evolutionary processes that occur over short timescales. DNA sequence obtained from an acid mine drainage biofilm was reconstructed, taking into account the effects of strain variation, to generate a nearly complete genome tiling path for a Leptospirillum group II species closely related to L. ferriphilum (sampling depth ∼20×). The population is dominated by one sequence type, yet we detected evidence for relatively abundant variants (>99.5% sequence identity to the dominant type) at multiple loci, and a few rare variants. Blocks of other Leptospirillum group II types (∼94% sequence identity) have recombined into one or more variants. Variant blocks of both types are more numerous near the origin of replication. Heterogeneity in genetic potential within the population arises from localized variation in gene content, typically focused in integrated plasmid/phage-like regions. Some laterally transferred gene blocks encode physiologically important genes, including quorum-sensing genes of the LuxIR system. Overall, results suggest inter- and intrapopulation genetic exchange involving distinct parental genome types and implicate gain and loss of phage and plasmid genes in recent evolution of this Leptospirillum group II population. Population genetic analyses of single nucleotide polymorphisms indicate variation between closely related strains is not maintained by positive selection, suggesting that these regions do not represent adaptive differences between strains. Thus, the most likely explanation for the observed patterns of polymorphism is divergence of ancestral strains due to geographic isolation, followed by mixing and subsequent recombination. PMID:18651792

Whole-genome sequencing reveals clonal expansion of multiresistant Staphylococcus haemolyticus in European hospitals.

PubMed

Cavanagh, Jorunn Pauline; Hjerde, Erik; Holden, Matthew T G; Kahlke, Tim; Klingenberg, Claus; Flægstad, Trond; Parkhill, Julian; Bentley, Stephen D; Sollid, Johanna U Ericson

2014-11-01

Staphylococcus haemolyticus is an emerging cause of nosocomial infections, primarily affecting immunocompromised patients. A comparative genomic analysis was performed on clinical S. haemolyticus isolates to investigate their genetic relationship and explore the coding sequences with respect to antimicrobial resistance determinants and putative hospital adaptation. Whole-genome sequencing was performed on 134 isolates of S. haemolyticus from geographically diverse origins (Belgium, 2; Germany, 10; Japan, 13; Norway, 54; Spain, 2; Switzerland, 43; UK, 9; USA, 1). Each genome was individually assembled. Protein coding sequences (CDSs) were predicted and homologous genes were categorized into three types: Type I, core genes, homologues present in all strains; Type II, unique core genes, homologues shared by only a subgroup of strains; and Type III, unique genes, strain-specific CDSs. The phylogenetic relationship between the isolates was built from variable sites in the form of single nucleotide polymorphisms (SNPs) in the core genome and used to construct a maximum likelihood phylogeny. SNPs in the genome core regions divided the isolates into one major group of 126 isolates and one minor group of isolates with highly diverse genomes. The major group was further subdivided into seven clades (A-G), of which four (A-D) encompassed isolates only from Europe. Antimicrobial multiresistance was observed in 77.7% of the collection. High levels of homologous recombination were detected in genes involved in adherence, staphylococcal host adaptation and bacterial cell communication. The presence of several successful and highly resistant clones underlines the adaptive potential of this opportunistic pathogen. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Whole-genome sequencing reveals clonal expansion of multiresistant Staphylococcus haemolyticus in European hospitals

PubMed Central

Cavanagh, Jorunn Pauline; Hjerde, Erik; Holden, Matthew T. G.; Kahlke, Tim; Klingenberg, Claus; Flægstad, Trond; Parkhill, Julian; Bentley, Stephen D.; Sollid, Johanna U. Ericson

2014-01-01

Objectives Staphylococcus haemolyticus is an emerging cause of nosocomial infections, primarily affecting immunocompromised patients. A comparative genomic analysis was performed on clinical S. haemolyticus isolates to investigate their genetic relationship and explore the coding sequences with respect to antimicrobial resistance determinants and putative hospital adaptation. Methods Whole-genome sequencing was performed on 134 isolates of S. haemolyticus from geographically diverse origins (Belgium, 2; Germany, 10; Japan, 13; Norway, 54; Spain, 2; Switzerland, 43; UK, 9; USA, 1). Each genome was individually assembled. Protein coding sequences (CDSs) were predicted and homologous genes were categorized into three types: Type I, core genes, homologues present in all strains; Type II, unique core genes, homologues shared by only a subgroup of strains; and Type III, unique genes, strain-specific CDSs. The phylogenetic relationship between the isolates was built from variable sites in the form of single nucleotide polymorphisms (SNPs) in the core genome and used to construct a maximum likelihood phylogeny. Results SNPs in the genome core regions divided the isolates into one major group of 126 isolates and one minor group of isolates with highly diverse genomes. The major group was further subdivided into seven clades (A–G), of which four (A–D) encompassed isolates only from Europe. Antimicrobial multiresistance was observed in 77.7% of the collection. High levels of homologous recombination were detected in genes involved in adherence, staphylococcal host adaptation and bacterial cell communication. Conclusions The presence of several successful and highly resistant clones underlines the adaptive potential of this opportunistic pathogen. PMID:25038069

3-D components of a biological neural network visualized in computer generated imagery. I - Macular receptive field organization

NASA Technical Reports Server (NTRS)

Ross, Muriel D.; Cutler, Lynn; Meyer, Glenn; Lam, Tony; Vaziri, Parshaw

1990-01-01

Computer-assisted, 3-dimensional reconstructions of macular receptive fields and of their linkages into a neural network have revealed new information about macular functional organization. Both type I and type II hair cells are included in the receptive fields. The fields are rounded, oblong, or elongated, but gradations between categories are common. Cell polarizations are divergent. Morphologically, each calyx of oblong and elongated fields appears to be an information processing site. Intrinsic modulation of information processing is extensive and varies with the kind of field. Each reconstructed field differs in detail from every other, suggesting that an element of randomness is introduced developmentally and contributes to endorgan adaptability.

Synaptic Plasticity In Mammalian Gravity Sensors: Preliminary Results From SLS-2

NASA Technical Reports Server (NTRS)

Ross, M. D.; Hargens, Alan R. (Technical Monitor)

1996-01-01

Sensory conflict is the prevalent theoretical explanation for space adaptation syndrome. This ultrastructural study tests the hypothesis that peripheral gravity sensors (maculae) play a role. Results were obtained from the medial part of utricular maculae of adult rats exposed to microgravity for 14 days, and from controls. Means and statistical significance of synapse counts were calculated using SUPERANOVA(Trademark) and Scheffe's procedure for post-hoc comparisons. Preliminary findings are from 2 sets of 100 serial sections for each dataset. Synapses were doubled numerically in type II hair cells of utricular maculae collected on day 13 inflight compared to controls (11.4 +/- 7.1 vs. 5.3 +/- 3.8; p < 0.0001). Flight mean synaptic number declined rapidly postflight and became comparable to means of controls. Synapses also increased numerically in type I cells inflight (2.4 +/- 1.6 vs. 1.7 +/- 1.0; p < 0.0341). Postflight there were no significant differences in counts. Results concerning shifts in ribbon type and distribution are also largely replicating previous findings from flight studies. Results indicate that mammalian maculae are adaptive endorgans that retain the property of synaptic plasticity into the adult stage. Macular plasticity has clinical implications for balance disorders of peripheral origin.

Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term.

PubMed

Yates, Dustin T; Cadaret, Caitlin N; Beede, Kristin A; Riley, Hannah E; Macko, Antoni R; Anderson, Miranda J; Camacho, Leticia E; Limesand, Sean W

2016-06-01

Intrauterine growth restriction (IUGR) reduces muscle mass and insulin sensitivity in offspring. Insulin sensitivity varies among muscle fiber types, with Type I fibers being most sensitive. Differences in fiber-type ratios are associated with insulin resistance in adults, and thus we hypothesized that near-term IUGR sheep fetuses exhibit reduced size and proportions of Type I fibers. Placental insufficiency-induced IUGR fetuses were ∼54% smaller (P < 0.05) than controls and exhibited hypoxemia and hypoglycemia, which contributed to 6.9-fold greater (P < 0.05) plasma norepinephrine and ∼53% lower (P < 0.05) plasma insulin concentrations. IUGR semitendinosus muscles contained less (P < 0.05) myosin heavy chain-I protein (MyHC-I) and proportionally fewer (P < 0.05) Type I and Type I/IIa fibers than controls, but MyHC-II protein concentrations, Type II fibers, and Type IIx fibers were not different. IUGR biceps femoris muscles exhibited similar albeit less dramatic differences in fiber type proportions. Type I and IIa fibers are more responsive to adrenergic and insulin regulation than Type IIx and may be more profoundly impaired by the high catecholamines and low insulin in our IUGR fetuses, leading to their proportional reduction. In both muscles, fibers of each type were uniformly smaller (P < 0.05) in IUGR fetuses than controls, which indicates that fiber hypertrophy is not dependent on type but rather on other factors such as myoblast differentiation or protein synthesis. Together, our findings show that IUGR fetal muscles develop smaller fibers and have proportionally fewer Type I fibers, which is indicative of developmental adaptations that may help explain the link between IUGR and adulthood insulin resistance. Copyright © 2016 the American Physiological Society.

Particle swarm optimization: an alternative in marine propeller optimization?

NASA Astrophysics Data System (ADS)

Vesting, F.; Bensow, R. E.

2018-01-01

This article deals with improving and evaluating the performance of two evolutionary algorithm approaches for automated engineering design optimization. Here a marine propeller design with constraints on cavitation nuisance is the intended application. For this purpose, the particle swarm optimization (PSO) algorithm is adapted for multi-objective optimization and constraint handling for use in propeller design. Three PSO algorithms are developed and tested for the optimization of four commercial propeller designs for different ship types. The results are evaluated by interrogating the generation medians and the Pareto front development. The same propellers are also optimized utilizing the well established NSGA-II genetic algorithm to provide benchmark results. The authors' PSO algorithms deliver comparable results to NSGA-II, but converge earlier and enhance the solution in terms of constraints violation.

Adaptation and Latent Structure of the Swahili Version of Beck Depression Inventory-II in a Low Literacy Population in the Context of HIV

PubMed Central

Abubakar, Amina; Kalu, Raphael Birya; Katana, Khamis; Kabunda, Beatrice; Hassan, Amin S.; Newton, Charles R.; Van de Vijver, Fons

2016-01-01

Objective We set out to adapt the Beck Depression Inventory (BDI)-II in Kenya and examine its factorial structure. Methods In the first phase we carried out in-depth interviews involving 29 adult members of the community to elicit their understanding of depression and identify aspects of the BDI-II that required adaptation. In the second phase, a modified version of BDI-II was administered to 221 adults randomly selected from the community to allow for the evaluation of its psychometric properties. In the third phase of the study we evaluated the discriminative validity of BDI-11 by comparing a randomly chosen community sample (n = 29) with caregivers of adolescents affected by HIV (n = 77). Results A considerable overlap between the BDI symptoms and those generated in the interviews was observed. Relevant idioms and symptoms such as ‘thinking too much’ and ‘Kuchoka moyo (having a tired heart)’ were identified. The administration of the BDI had to be modified to make it suitable for the low literacy levels of our participants. Fit indices for several models (one factorial, two-factor model and a three factor model) were all within acceptable range. Evidence indicated that while multidimensional models could be fitted, the strong correlations between the factors implied that a single factor model may be the best suited solution (alpha [0.89], and a significant correlation with locally identified items [r = 0.51]) confirmed the good psychometric properties of the adapted BDI-II. No evidence was found to support the hypothesis that somatization was more prevalent. Lastly, caregivers of HIV affected adolescents had significantly higher scores compared to adults randomly selected from the community F(1, 121) = 23.31, p < .001 indicating the discriminative validity of the adapted BDI = II. Conclusions With an adapted administration procedure, the BDI-II provides an adequate measure of depressive symptoms which can be used alongside other measures for proper diagnosis in a low literacy population. PMID:27258530

CRISPR/Cas9 Platforms for Genome Editing in Plants: Developments and Applications.

PubMed

Ma, Xingliang; Zhu, Qinlong; Chen, Yuanling; Liu, Yao-Guang

2016-07-06

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein9 (Cas9) genome editing system (CRISPR/Cas9) is adapted from the prokaryotic type II adaptive immunity system. The CRISPR/Cas9 tool surpasses other programmable nucleases, such as ZFNs and TALENs, for its simplicity and high efficiency. Various plant-specific CRISPR/Cas9 vector systems have been established for adaption of this technology to many plant species. In this review, we present an overview of current advances on applications of this technology in plants, emphasizing general considerations for establishment of CRISPR/Cas9 vector platforms, strategies for multiplex editing, methods for analyzing the induced mutations, factors affecting editing efficiency and specificity, and features of the induced mutations and applications of the CRISPR/Cas9 system in plants. In addition, we provide a perspective on the challenges of CRISPR/Cas9 technology and its significance for basic plant research and crop genetic improvement. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Building the framework for climate change adaptation in the urban areas using participatory approach: the Czech Republic experience

NASA Astrophysics Data System (ADS)

Emmer, Adam; Hubatová, Marie; Lupač, Miroslav; Pondělíček, Michael; Šafařík, Miroslav; Šilhánková, Vladimíra; Vačkář, David

2016-04-01

The Czech Republic has experienced numerous extreme hydrometeorological / climatological events such as floods (significant ones in 1997, 2002, 2010, 2013), droughts (2013, 2015), heat waves (2015) and windstorms (2007) during past decades. These events are generally attributed to the ongoing climate change and caused loss of lives and significant material damages (up to several % of GDP in some years), especially in urban areas. To initiate the adaptation process of urban areas, the main objective was to prepare a framework for creating climate change adaptation strategies of individual cities reflecting physical-geographical and socioeconomical conditions of the Czech Republic. Three pilot cities (Hradec Králové, Žďár nad Sázavou, Dobru\\vska) were used to optimize entire procedure. Two sets of participatory seminars were organised in order to involve all key stakeholders (the city council, department of the environment, department of the crisis management, hydrometeorological institute, local experts, ...) into the process of creation of the adaptation strategy from its early stage. Lesson learned for the framework were related especially to its applicability on a local level, which is largely a matter of the understandability of the concept. Finally, this illustrative and widely applicable framework (so called 'road map to adaptation strategy') includes five steps: (i) analysis of existing strategies and plans on national, regional and local levels; (ii) analysing climate-change related hazards and key vulnerabilities; (iii) identification of adaptation needs, evaluation of existing adaptation capacity and formulation of future adaptation priorities; (iv) identification of limits and barriers for the adaptation (economical, environmental, ...); and (v) selection of specific types of adaptation measures reflecting identified adaptation needs and formulated adaptation priorities. Keywords: climate change adaptation (CCA); urban areas; participatory approach; road map

Adaptation of evidence-based guideline recommendations to address urinary incontinence in nursing home residents according to the ADAPTE-process.

PubMed

Hoedl, Manuela; Schoberer, Daniela; Halfens, Ruud J G; Lohrmann, Christa

2018-04-27

To adapt international guideline recommendations for the conservative management of urinary incontinence (UI), defined as any involuntary loss of urine, in Austrian nursing home residents following the ADAPTE-process. Many international guidelines for managing UI are available. Nevertheless, the international recommendations have not yet been adapted to address the Austrian nursing home context. This crucial adaptation process will enhance the acceptance and applicability of the recommendations as well as encourage adherence among Austrian nurses and nursing home residents. This study is a methodological study based on the ADAPTE-process, including a systematic search, quality appraisal of the guidelines using the Appraisal of Clinical Guidelines for REsearch & Evaluation II (AGREE II) instrument as well as an external review by means of a Delphi technique. The guidelines had to be topic-relevant, published within the last 3 years and achieve a rigor of development score of 80% using the AGREE II instrument. We searched international guideline databases to identify adequate guidelines. Two raters assessed the quality of each guideline, ascertaining that it fulfilled the inclusion criteria using the AGREE II instrument. We translated the identified recommendations into German and externally reviewed for their applicability in the Austrian context. We identified 1,612 hits in 10 databases. After applying inclusion and exclusion criteria, we assessed five international clinical guidelines for quality using the AGREE II instrument. One clinical guideline fulfilled the inclusion criteria. This clinical guideline contains 116 recommendations, of which 29 were applicable in the Austrian nursing home setting. We identified only one suitable guideline, possibly due to the stringent nature of the inclusion criteria. However, following low-quality guidelines may result in the use of recommendations that are not based on evidence and, therefore, may lead to suboptimal nursing care and outcomes. © 2018 John Wiley & Sons Ltd.

Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network.

PubMed

Keegan, Caroline; Krutzik, Stephan; Schenk, Mirjam; Scumpia, Philip O; Lu, Jing; Pang, Yan Ling Joy; Russell, Brandon S; Lim, Kok Seong; Shell, Scarlet; Prestwich, Erin; Su, Dan; Elashoff, David; Hershberg, Robert M; Bloom, Barry R; Belisle, John T; Fortune, Sarah; Dedon, Peter C; Pellegrini, Matteo; Modlin, Robert L

2018-05-01

Upon recognition of a microbial pathogen, the innate and adaptive immune systems are linked to generate a cell-mediated immune response against the foreign invader. The culture filtrate of Mycobacterium tuberculosis contains ligands, such as M. tuberculosis tRNA, that activate the innate immune response and secreted Ags recognized by T cells to drive adaptive immune responses. In this study, bioinformatics analysis of gene-expression profiles derived from human PBMCs treated with distinct microbial ligands identified a mycobacterial tRNA-induced innate immune network resulting in the robust production of IL-12p70, a cytokine required to instruct an adaptive Th1 response for host defense against intracellular bacteria. As validated by functional studies, this pathway contained a feed-forward loop, whereby the early production of IL-18, type I IFNs, and IL-12p70 primed NK cells to respond to IL-18 and produce IFN-γ, enhancing further production of IL-12p70. Mechanistically, tRNA activates TLR3 and TLR8, and this synergistic induction of IL-12p70 was recapitulated by the addition of a specific TLR8 agonist with a TLR3 ligand to PBMCs. These data indicate that M. tuberculosis tRNA activates a gene network involving the integration of multiple innate signals, including types I and II IFNs, as well as distinct cell types to induce IL-12p70. Copyright © 2018 by The American Association of Immunologists, Inc.

Automating curation using a natural language processing pipeline

PubMed Central

Alex, Beatrice; Grover, Claire; Haddow, Barry; Kabadjov, Mijail; Klein, Ewan; Matthews, Michael; Tobin, Richard; Wang, Xinglong

2008-01-01

Background: The tasks in BioCreative II were designed to approximate some of the laborious work involved in curating biomedical research papers. The approach to these tasks taken by the University of Edinburgh team was to adapt and extend the existing natural language processing (NLP) system that we have developed as part of a commercial curation assistant. Although this paper concentrates on using NLP to assist with curation, the system can be equally employed to extract types of information from the literature that is immediately relevant to biologists in general. Results: Our system was among the highest performing on the interaction subtasks, and competitive performance on the gene mention task was achieved with minimal development effort. For the gene normalization task, a string matching technique that can be quickly applied to new domains was shown to perform close to average. Conclusion: The technologies being developed were shown to be readily adapted to the BioCreative II tasks. Although high performance may be obtained on individual tasks such as gene mention recognition and normalization, and document classification, tasks in which a number of components must be combined, such as detection and normalization of interacting protein pairs, are still challenging for NLP systems. PMID:18834488

Videofluoroscopy of the oral phase of swallowing in eight to twelve years old children with dental malocclusion.

PubMed

Junqueira, Patricia; Costa, Milton Melciades

2013-11-01

The objective of this study was to describe the oral phase of swallowing in individuals with dental malocclusion and to generate data that would contribute to the rehabilitation of those patients. The study was based on the evaluation of the swallowing system through videofluoroscopy on thirty-four children of both genders, aged eight to twelve years old who present with Angle Class II and III dental malocclusions. Thirteen children of similar age and gender presenting normal dental occlusion formed the control group. The results indicated that the oral phase of swallowing is different between individuals with normal occlusion and malocclusion. Dental occlusion types Angle Class II and III did not present a swallowing pattern, independently of the amount of liquid ingested. The swallowing appeared effective in the oral phase of individuals with dental malocclusion, even though adaptations were identified. The outcome, in the absence of a single pattern and the efficiency of the adapted swallowing demonstrates, first a need for additional research investigating orofacial myofunctional treatment for patients with malocclusion and second how such analyses should focus on contributing positively to the rehabilitation of these patients.

Comparison of properties of medial entorhinal cortex layer II neurons in two anatomical dimensions with and without cholinergic activation.

PubMed

Yoshida, Motoharu; Jochems, Arthur; Hasselmo, Michael E

2013-01-01

Mechanisms underlying grid cell firing in the medial entorhinal cortex (MEC) still remain unknown. Computational modeling studies have suggested that cellular properties such as spike frequency adaptation and persistent firing might underlie the grid cell firing. Recent in vivo studies also suggest that cholinergic activation influences grid cell firing. Here we investigated the anatomical distribution of firing frequency adaptation, the medium spike after hyperpolarization potential (mAHP), subthreshold membrane potential oscillations, sag potential, input resistance and persistent firing, in MEC layer II principal cells using in vitro whole-cell patch clamp recordings in rats. Anatomical distributions of these properties were compared along both the dorso-ventral and medio-lateral axes, both with and without the cholinergic receptor agonist carbachol. We found that spike frequency adaptation is significantly stronger in ventral than in dorsal neurons both with and without carbachol. Spike frequency adaptation was significantly correlated with the duration of the mAHP, which also showed a gradient along the dorso-ventral axis. In carbachol, we found that about 50% of MEC layer II neurons show persistent firing which lasted more than 30 seconds. Persistent firing of MEC layer II neurons might contribute to grid cell firing by providing the excitatory drive. Dorso-ventral differences in spike frequency adaptation we report here are opposite from previous predictions by a computational model. We discuss an alternative mechanism as to how dorso-ventral differences in spike frequency adaptation could contribute to different scales of grid spacing.

Disruption of Sorting Nexin 5 Causes Respiratory Failure Associated with Undifferentiated Alveolar Epithelial Type I Cells in Mice

PubMed Central

Im, Sun-Kyoung; Jeong, HyoBin; Jeong, Hyun-Woo; Kim, Kyong-Tai; Hwang, Daehee; Ikegami, Machiko; Kong, Young-Yun

2013-01-01

Sorting nexin 5 (Snx5) has been posited to regulate the degradation of epidermal growth factor receptor and the retrograde trafficking of cation-independent mannose 6-phosphate receptor/insulin-like growth factor II receptor. Snx5 has also been suggested to interact with Mind bomb-1, an E3 ubiquitin ligase that regulates the activation of Notch signaling. However, the in vivo functions of Snx5 are largely unknown. Here, we report that disruption of the Snx5 gene in mice (Snx5-/- mice) resulted in partial perinatal lethality; 40% of Snx5-/- mice died shortly after birth due to cyanosis, reduced air space in the lungs, and respiratory failure. Histological analysis revealed that Snx5-/- mice exhibited thickened alveolar walls associated with undifferentiated alveolar epithelial type I cells. In contrast, alveolar epithelial type II cells were intact, exhibiting normal surfactant synthesis and secretion. Although the expression levels of surfactant proteins and saturated phosphatidylcholine in the lungs of Snx5-/- mice were comparable to those of Snx5+/+ mice, the expression levels of T1α, Aqp5, and Rage, markers for distal alveolar epithelial type I cells, were significantly decreased in Snx5 -/- mice. These results demonstrate that Snx5 is necessary for the differentiation of alveolar epithelial type I cells, which may underlie the adaptation to air breathing at birth. PMID:23526992

Examining Specific Effects of Context on Adaptive Behavior and Achievement in Rural Africa: Six Case Studies from Southern Province, Zambia

PubMed Central

Reich, Jodi; Hart, Lesley; Thuma, Philip E.

2011-01-01

Generally accepted as universal, the construct of adaptive behavior differs in its manifestations across different cultures and settings. The Vineland-II was translated into Chitonga and adapted to the setting of rural Southern Province, Zambia. This version was administered to the parents/caregivers of 114 children (grades 3-7, mean age = 12.94, sd = 2.34). The relationships between these children's adaptive behavior, academic achievement and cognitive ability indicators are compared to those usually observed in US samples. Results reflect no association between adaptive behavior and cognitive ability indicators, but a strong relationship between high adaptive behavior and reading-related measures. Six case studies of children with high and low scores on the Vineland-II are presented to illustrate the possible factors affecting these outcomes. PMID:22391811

Diverse and divergent protein post-translational modifications in two growth stages of a natural microbial community

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

Li, Zhou; Wang, Yingfeng; Yao, Qiuming

2014-01-01

Detailed characterization of posttranslational modifications (PTMs) of proteins in microbial communities remains a significant challenge. Here we directly identify and quantify a broad range of PTMs (hydroxylation, methylation, citrullination, acetylation, phosphorylation, methylthiolation, S-nitrosylation and nitration) in a natural microbial community from an acid mine drainage site. Approximately 29% of the identified proteins of the dominant Leptospirillum group II bacteria are modified, and 43% of modified proteins carry multiple PTM types. Most PTM events, except S-nitrosylations, have low fractional occupancy. Notably, PTM events are detected on Cas proteins involved in antiviral defense, an aspect of Cas biochemistry not considered previously. Further,more » Cas PTM profiles from Leptospirillum group II differ in early versus mature biofilms. PTM patterns are divergent on orthologues of two closely related, but ecologically differentiated, Leptospirillum group II bacteria. Our results highlight the prevalence and dynamics of PTMs of proteins, with potential significance for ecological adaptation and microbial evolution.« less

Kinetic mechanism of non-muscle myosin IIB: functional adaptations for tension generation and maintenance.

PubMed

Wang, Fei; Kovacs, Mihaly; Hu, Aihua; Limouze, John; Harvey, Estelle V; Sellers, James R

2003-07-25

Besides driving contraction of various types of muscle tissue, conventional (class II) myosins serve essential cellular functions and are ubiquitously expressed in eukaryotic cells. Three different isoforms in the human myosin complement have been identified as non-muscle class II myosins. Here we report the kinetic characterization of a human non-muscle myosin IIB subfragment-1 construct produced in the baculovirus expression system. Transient kinetic data show that most steps of the actomyosin ATPase cycle are slowed down compared with other class II myosins. The ADP affinity of subfragment-1 is unusually high even in the presence of actin filaments, and the rate of ADP release is close to the steady-state ATPase rate. Thus, non-muscle myosin IIB subfragment-1 spends a significantly higher proportion of its kinetic cycle strongly attached to actin than do the muscle myosins. This feature is even more pronounced at slightly elevated ADP levels, and it may be important in carrying out the cellular functions of this isoform working in small filamentous assemblies.

RNA-dependent RNA targeting by CRISPR-Cas9

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

Strutt, Steven C.; Torrez, Rachel M.; Kaya, Emine

Double-stranded DNA (dsDNA) binding and cleavage by Cas9 is a hallmark of type II CRISPR-Cas bacterial adaptive immunity. All known Cas9 enzymes are thought to recognize DNA exclusively as a natural substrate, providing protection against DNA phage and plasmids. Here, we show that Cas9 enzymes from both subtypes II-A and II-C can recognize and cleave single-stranded RNA (ssRNA) by an RNA-guided mechanism that is independent of a protospacer-adjacent motif (PAM) sequence in the target RNA. RNA-guided RNA cleavage is programmable and site-specific, and we find that this activity can be exploited to reduce infection by single-stranded RNA phage in vivo.more » We also demonstrate that Cas9 can direct PAM-independent repression of gene expression in bacteria. In conclusion, these results indicate that a subset of Cas9 enzymes have the ability to act on both DNA and RNA target sequences, and suggest the potential for use in programmable RNA targeting applications.« less

RNA-dependent RNA targeting by CRISPR-Cas9

DOE PAGES

Strutt, Steven C.; Torrez, Rachel M.; Kaya, Emine; ...

2018-01-05

Double-stranded DNA (dsDNA) binding and cleavage by Cas9 is a hallmark of type II CRISPR-Cas bacterial adaptive immunity. All known Cas9 enzymes are thought to recognize DNA exclusively as a natural substrate, providing protection against DNA phage and plasmids. Here, we show that Cas9 enzymes from both subtypes II-A and II-C can recognize and cleave single-stranded RNA (ssRNA) by an RNA-guided mechanism that is independent of a protospacer-adjacent motif (PAM) sequence in the target RNA. RNA-guided RNA cleavage is programmable and site-specific, and we find that this activity can be exploited to reduce infection by single-stranded RNA phage in vivo.more » We also demonstrate that Cas9 can direct PAM-independent repression of gene expression in bacteria. In conclusion, these results indicate that a subset of Cas9 enzymes have the ability to act on both DNA and RNA target sequences, and suggest the potential for use in programmable RNA targeting applications.« less

RNA-dependent RNA targeting by CRISPR-Cas9

PubMed Central

Strutt, Steven C; Torrez, Rachel M; Kaya, Emine; Negrete, Oscar A

2018-01-01

Double-stranded DNA (dsDNA) binding and cleavage by Cas9 is a hallmark of type II CRISPR-Cas bacterial adaptive immunity. All known Cas9 enzymes are thought to recognize DNA exclusively as a natural substrate, providing protection against DNA phage and plasmids. Here, we show that Cas9 enzymes from both subtypes II-A and II-C can recognize and cleave single-stranded RNA (ssRNA) by an RNA-guided mechanism that is independent of a protospacer-adjacent motif (PAM) sequence in the target RNA. RNA-guided RNA cleavage is programmable and site-specific, and we find that this activity can be exploited to reduce infection by single-stranded RNA phage in vivo. We also demonstrate that Cas9 can direct PAM-independent repression of gene expression in bacteria. These results indicate that a subset of Cas9 enzymes have the ability to act on both DNA and RNA target sequences, and suggest the potential for use in programmable RNA targeting applications. PMID:29303478

[Bile duct lesions in laparoscopic cholecystectomy].

PubMed

Siewert, J R; Ungeheuer, A; Feussner, H

1994-09-01

Laparoscopic cholecystectomy is both resulting in a slightly higher incidence of biliary lesions and a change of prevalence of the type of lesions. Damage to the biliary system occurs in 4 different types: The most severe case is the lesion with a structural defect of the hepatic or common bile duct with (IVa) or without (IVb) vascular injury. Tangential lesions without structural loss of the duct should be denominated as type III (IIIa with additional lesion to the vessels, type IIIb without). Type II comprehends late strictures without obvious intraoperative trauma to the duct. Type I includes immediate biliary fistulae of usually good prognosis. The increasing prevalence of structural defects of the bile ducts appears to be a peculiarity of laparoscopic cholecystectomy necessitating highly demanding operative repair. In the majority of cases, hepatico-jejunostomy or even intraparenchymatous anastomoses are required. Adaptation of well proven principles of open surgery is the best prevention of biliary lesions in laparoscopic cholecystectomy as well as the readiness to convert early to the open procedure.

Characterizing non-photochemical quenching in leaves through fluorescence lifetime snapshots

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

Sylak-Glassman, Emily J.; Zaks, Julia; Amarnath, Kapil

2015-03-12

A technique is described to measure the fluorescence decay profiles of intact leaves during adaptation to high light and subsequent relaxation to dark conditions. We illustrate how to ensure that photosystem II reaction centers are closed and compare data for wild type Arabidopsis thaliana with conventional pulse-amplitude modulated (PAM) fluorescence measurements. Unlike PAM measurements, the lifetime measurements are not sensitive to photobleaching or chloroplast shielding, and the form of the fluorescence decay provides additional information to test quantitative models of excitation dynamics in intact leaves.

Assessment of depression in medical patients: a systematic review of the utility of the Beck Depression Inventory-II.

PubMed

Wang, Yuan-Pang; Gorenstein, Clarice

2013-09-01

To perform a systematic review of the utility of the Beck Depression Inventory for detecting depression in medical settings, this article focuses on the revised version of the scale (Beck Depression Inventory-II), which was reformulated according to the DSM-IV criteria for major depression. We examined relevant investigations with the Beck Depression Inventory-II for measuring depression in medical settings to provide guidelines for practicing clinicians. Considering the inclusion and exclusion criteria seventy articles were retained. Validation studies of the Beck Depression Inventory-II, in both primary care and hospital settings, were found for clinics of cardiology, neurology, obstetrics, brain injury, nephrology, chronic pain, chronic fatigue, oncology, and infectious disease. The Beck Depression Inventory-II showed high reliability and good correlation with measures of depression and anxiety. Its threshold for detecting depression varied according to the type of patients, suggesting the need for adjusted cut-off points. The somatic and cognitive-affective dimension described the latent structure of the instrument. The Beck Depression Inventory-II can be easily adapted in most clinical conditions for detecting major depression and recommending an appropriate intervention. Although this scale represents a sound path for detecting depression in patients with medical conditions, the clinician should seek evidence for how to interpret the score before using the Beck Depression Inventory-II to make clinical decisions.

Chronic shin splints. Classification and management of medial tibial stress syndrome.

PubMed

Detmer, D E

1986-01-01

A clinical classification and treatment programme has been developed for chronic medial tibial stress syndrome. Medial tibial stress syndrome has been reported to be either tibial stress fracture or microfracture, tibial periostitis, or distal deep posterior chronic compartment syndrome. Three chronic types exist and may coexist: Type I (tibial microfracture, bone stress reaction or cortical fracture); type II (periostalgia from chronic avulsion of the periosteum at the periosteal-fascial junction); and type III (chronic compartment syndrome syndrome). Type I disease is treated nonoperatively. Operations for resistant types II and III medial tibial stress syndrome were performed in 41 patients. Bilaterality was common (type II, 50% type III, 88%). Seven had coexistent type II/III; one had type I/II. Preoperative symptoms averaged 24 months in type II, 6 months in type III, and 33 months in types II/III. Mean age was 22 years (15 to 51). Resting compartment pressures were normal in type II (mean 12 mm Hg) and elevated in type III and type II/III (mean 23 mm Hg). Type II and type II/III patients received fasciotomy plus periosteal cauterisation. Type III patients had fasciotomy only. All procedures were performed on an outpatient basis using local anaesthesia. Follow up was complete and averaged 6 months (2 to 14 months). Improved performance was as follows: type II, 93%, type III, 100%; type II/III, 86%. Complete cures were as follows: type II, 78%; type III, 75%; and type II/III, 57%. This experience suggests that with precise diagnosis and treatment involving minimal risk and cost the athlete has a reasonable chance of return to full activity.

Software-assisted stacking of gene modules using GoldenBraid 2.0 DNA-assembly framework.

PubMed

Vazquez-Vilar, Marta; Sarrion-Perdigones, Alejandro; Ziarsolo, Peio; Blanca, Jose; Granell, Antonio; Orzaez, Diego

2015-01-01

GoldenBraid (GB) is a modular DNA assembly technology for plant multigene engineering based on type IIS restriction enzymes. GB speeds up the assembly of transcriptional units from standard genetic parts and facilitates the stacking of several genes within the same T-DNA in few days. GBcloning is software-assisted with a set of online tools. The GBDomesticator tool assists in the adaptation of DNA parts to the GBstandard. The combination of GB-adapted parts to build new transcriptional units is assisted by the GB TU Assembler tool. Finally, the assembly of multigene modules is simulated by the GB Binary Assembler. All the software tools are available at www.gbcloning.org . Here, we describe in detail the assembly methodology to create a multigene construct with three transcriptional units for polyphenol metabolic engineering in plants.

Climate change in the oceans: evolutionary versus phenotypically plastic responses of marine animals and plants

PubMed Central

Reusch, Thorsten B H

2014-01-01

I summarize marine studies on plastic versus adaptive responses to global change. Due to the lack of time series, this review focuses largely on the potential for adaptive evolution in marine animals and plants. The approaches were mainly synchronic comparisons of phenotypically divergent populations, substituting spatial contrasts in temperature or CO2 environments for temporal changes, or in assessments of adaptive genetic diversity within populations for traits important under global change. The available literature is biased towards gastropods, crustaceans, cnidarians and macroalgae. Focal traits were mostly environmental tolerances, which correspond to phenotypic buffering, a plasticity type that maintains a functional phenotype despite external disturbance. Almost all studies address coastal species that are already today exposed to fluctuations in temperature, pH and oxygen levels. Recommendations for future research include (i) initiation and analyses of observational and experimental temporal studies encompassing diverse phenotypic traits (including diapausing cues, dispersal traits, reproductive timing, morphology) (ii) quantification of nongenetic trans-generational effects along with components of additive genetic variance (iii) adaptive changes in microbe–host associations under the holobiont model in response to global change (iv) evolution of plasticity patterns under increasingly fluctuating environments and extreme conditions and (v) joint consideration of demography and evolutionary adaptation in evolutionary rescue approaches. PMID:24454551

Three-Fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of Snake Venom Toxins

PubMed Central

Sunagar, Kartik; Jackson, Timothy N. W.; Undheim, Eivind A. B.; Ali, Syed. A.; Antunes, Agostinho; Fry, Bryan G.

2013-01-01

Three-finger toxins (3FTx) represent one of the most abundantly secreted and potently toxic components of colubrid (Colubridae), elapid (Elapidae) and psammophid (Psammophiinae subfamily of the Lamprophidae) snake venom arsenal. Despite their conserved structural similarity, they perform a diversity of biological functions. Although they are theorised to undergo adaptive evolution, the underlying diversification mechanisms remain elusive. Here, we report the molecular evolution of different 3FTx functional forms and show that positively selected point mutations have driven the rapid evolution and diversification of 3FTx. These diversification events not only correlate with the evolution of advanced venom delivery systems (VDS) in Caenophidia, but in particular the explosive diversification of the clade subsequent to the evolution of a high pressure, hollow-fanged VDS in elapids, highlighting the significant role of these toxins in the evolution of advanced snakes. We show that Type I, II and III α-neurotoxins have evolved with extreme rapidity under the influence of positive selection. We also show that novel Oxyuranus/Pseudonaja Type II forms lacking the apotypic loop-2 stabilising cysteine doublet characteristic of Type II forms are not phylogenetically basal in relation to other Type IIs as previously thought, but are the result of secondary loss of these apotypic cysteines on at least three separate occasions. Not all 3FTxs have evolved rapidly: κ-neurotoxins, which form non-covalently associated heterodimers, have experienced a relatively weaker influence of diversifying selection; while cytotoxic 3FTx, with their functional sites, dispersed over 40% of the molecular surface, have been extremely constrained by negative selection. We show that the a previous theory of 3FTx molecular evolution (termed ASSET) is evolutionarily implausible and cannot account for the considerable variation observed in very short segments of 3FTx. Instead, we propose a theory of Rapid Accumulation of Variations in Exposed Residues (RAVER) to illustrate the significance of point mutations, guided by focal mutagenesis and positive selection in the evolution and diversification of 3FTx. PMID:24253238

Advancing biotechnology with CRISPR/Cas9: recent applications and patent landscape.

PubMed

Ferreira, Raphael; David, Florian; Nielsen, Jens

2018-01-24

Clustered regularly interspaced short palindromic repeats (CRISPR) is poised to become one of the key scientific discoveries of the twenty-first century. Originating from prokaryotic and archaeal immune systems to counter phage invasions, CRISPR-based applications have been tailored for manipulating a broad range of living organisms. From the different elucidated types of CRISPR mechanisms, the type II system adapted from Streptococcus pyogenes has been the most exploited as a tool for genome engineering and gene regulation. In this review, we describe the different applications of CRISPR/Cas9 technology in the industrial biotechnology field. Next, we detail the current status of the patent landscape, highlighting its exploitation through different companies, and conclude with future perspectives of this technology.

A microstructural model of motion of macro-twin interfaces in Ni-Mn-Ga 10 M martensite

NASA Astrophysics Data System (ADS)

Seiner, Hanuš; Straka, Ladislav; Heczko, Oleg

2014-03-01

We present a continuum-based model of microstructures forming at the macro-twin interfaces in thermoelastic martensites and apply this model to highly mobile interfaces in 10 M modulated Ni-Mn-Ga martensite. The model is applied at three distinct spatial scales observed in the experiment: meso-scale (modulation twinning), micro-scale (compound a-b lamination), and nano-scale (nanotwining in the concept of adaptive martensite). We show that two mobile interfaces (Type I and Type II macro-twins) have different micromorphologies at all considered spatial scales, which can directly explain their different twinning stress observed in experiments. The results of the model are discussed with respect to various experimental observations at all three considered spatial scales.

Photosynthesis, chlorophyll fluorescence, light-harvesting system and photoinhibition resistance of a zeaxanthin-accumulating mutant of Arabidopsis thaliana.

PubMed

Tardy, F; Havaux, M

1996-06-01

The abscisic-acid-deficient aba-1 mutant of Arabidopsis thaliana is unable to epoxidize zeaxanthin. As a consequence, it contains large amounts of this carotenoid and lacks epoxy-xanthophylls. HPLC analysis of pigment contents in leaves, isolated thylakoids and preparations of the major light-harvesting complex of photosystem II (PSII) (LHC-II) indicated that zeaxanthin replaced neoxanthin, violaxanthin and antheraxanthin in the light-harvesting system of PSII in aba-1. Non-denaturing electrophoretic fractionation of solubilized thylakoids showed that the xanthophyll imbalance in aba-1 was associated with a pronounced decrease in trimeric LHC-II in favour of monomeric complexes, with a substantial increase in free pigments (mainly zeaxanthin and chlorophyll b), suggesting a decreased stability of LHC-II. The reduced thermostability of PSII in aba-1 was also deduced from in vivo chlorophyll fluorescence measurements. Wild-type and aba-1 leaves could not be distinguished on the basis of their photosynthetic performance: no significant difference was observed between the two types of leaves for light-limited and light-saturated photosynthetic oxygen evolution, PSII photochemistry and PSII to PSI electron flow. When dark-adapted leaves (grown in white light of 80 mumol m-2s-1) were suddenly exposed to red light of 150 mumol m-2s-1, there was a strong nonphotochemical quenching of chlorophyll fluorescence, the amplitude of which was virtually identical (at steady state) in aba-1 and wild-type leaves, despite the fact that the xanthophyll cycle pigment pool was completely in the form of zeaxanthin in aba-1 and almost exclusively in the form of violaxanthin in the wild type. A high concentration of zeaxanthin in aba-1 thylakoids did not, in itself, provide any particular protection against the photoinhibition of PSII. Taken together, the presented results indicate the following: (1) zeaxanthin can replace epoxy-xanthophylls in LHC-II without significantly affecting the photochemical efficiency of PSII; (2) zeaxanthin does not play any specific role in direct (thermal) energy dissipation in PSII; (3) the photoprotective action of the xanthophyll cycle (rapid photoconversion of violaxanthin to zeaxanthin) is not based on the mere substitution of violaxanthin by zeaxanthin in the chlorophyll antennae.

Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway.

PubMed

Aoki, Hironori; Yamamoto, Eiichiro; Yamano, Hiro-O; Sugai, Tamotsu; Kimura, Tomoaki; Tanaka, Yoshihito; Matsushita, Hiro-O; Yoshikawa, Kenjiro; Takagi, Ryo; Harada, Eiji; Nakaoka, Michiko; Yoshida, Yuko; Harada, Taku; Sudo, Gota; Eizuka, Makoto; Yorozu, Akira; Kitajima, Hiroshi; Niinuma, Takeshi; Kai, Masahiro; Nojima, Masanori; Suzuki, Hiromu; Nakase, Hiroshi

2018-03-15

Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L). BRAF/KRAS mutations and DNA methylation of CpG island methylator phenotype (CIMP) markers (MINT1, - 2, - 12, - 31, p16, and MLH1) were analyzed through pyrosequencing. Type II-O was tightly associated with sessile serrated adenoma/polyps (SSA/Ps) with BRAF mutation and CIMP-high. Most lesions with simple Type II or Type II-L were hyperplastic polyps, while mixtures of Type II or Type II-L plus more advanced pit patterns (III/IV) were characteristic of traditional serrated adenomas (TSAs). Type II-positive TSAs frequently exhibited BRAF mutation and CIMP-low, while Type II-L-positive TSAs were tightly associated with KRAS mutation and CIMP-low. Analysis of lesions containing both premalignant and cancerous components suggested Type II-L-positive TSAs may develop into KRAS-mutated/CIMP-low/microsatellite stable cancers, while Type II-O-positive SSA/Ps develop into BRAF-mutated/CIMP-high/microsatellite unstable cancers. These results suggest that Type II subtypes reflect distinct molecular subclasses in the serrated neoplasia pathway and that they could be useful hallmarks for identifying SLs at high risk of developing into CRC.

Examining the specific effects of context on adaptive behavior and achievement in a rural African community: six case studies from rural areas of Southern province, Zambia.

PubMed

Tan, Mei; Reich, Jodi; Hart, Lesley; Thuma, Philip E; Grigorenko, Elena L

2014-02-01

Generally accepted as universal, the construct of adaptive behavior differs in its manifestations across different cultures and settings. The Vineland-II (Sparrow et al. in Vineland Adaptive Behavior Scales, Second edn. AGS Publishing, Circle Pines, MN, 2005) was translated into Chitonga and adapted to the setting of rural Southern Province, Zambia. This version was administered to the parents/caregivers of 114 children (grades 3-7, mean age = 12.94, SD = 2.34). The relationships between these children's adaptive behavior, academic achievement and cognitive ability indicators are compared to those usually observed in US samples. Results reflect no association between adaptive behavior and cognitive ability indicators, but a strong relationship between high adaptive behavior and reading-related measures. Six case studies of children with high and low scores on the Vineland-II are presented to illustrate the possible factors affecting these outcomes.

Mimicry by asx- and ST-turns of the four main types of beta-turn in proteins.

PubMed

Duddy, William J; Nissink, J Willem M; Allen, Frank H; Milner-White, E James

2004-11-01

Hydrogen-bonded beta-turns in proteins occur in four categories: type I (the most common), type II, type II', and type I'. Asx-turns resemble beta-turns, in that both have an NH. . .OC hydrogen bond forming a ring of 10 atoms. Serine and threonine side chains also commonly form hydrogen-bonded turns, here called ST-turns. Asx-turns and ST-turns can be categorized into four classes, based on side chain rotamers and the conformation of the central turn residue, which are geometrically equivalent to the four types of beta-turns. We propose asx- and ST-turns be named using the type I, II, I', and II' beta-turn nomenclature. Using this, the frequency of occurrence of both asx- and ST-turns is: type II' > type I > type II > type I', whereas for beta-turns it is type I > type II > type I' > type II'. Almost all type II asx-turns occur as a recently described three residue feature named an asx-nest.

Helical Antifreeze Proteins Have Independently Evolved in Fishes on Four Occasions

PubMed Central

Graham, Laurie A.; Hobbs, Rod S.; Fletcher, Garth L.; Davies, Peter L.

2013-01-01

Alanine-rich α-helical (type I) antifreeze proteins (AFPs) are produced by a variety of fish species from three different orders to protect against freezing in icy seawater. Interspersed amongst and within these orders are fishes making AFPs that are completely different in both sequence and structure. The origin of this variety of types I, II, III and antifreeze glycoproteins (AFGPs) has been attributed to adaptation following sea-level glaciations that occurred after the divergence of most of the extant families of fish. The presence of similar types of AFPs in distantly related fishes has been ascribed to lateral gene transfer in the case of the structurally complex globular type II lectin-like AFPs and to convergent evolution for the AFGPs, which consist of a well-conserved tripeptide repeat. In this paper, we examine the genesis of the type I AFPs, which are intermediate in complexity. These predominantly α-helical peptides share many features, such as putative capping structures, Ala-richness and amphipathic character. We have added to the type I repertoire by cloning additional sequences from sculpin and have found that the similarities between the type I AFPs of the four distinct groups of fishes are not borne out at the nucleotide level. Both the non-coding sequences and the codon usage patterns are strikingly different. We propose that these AFPs arose via convergence from different progenitor helices with a weak affinity for ice and that their similarity is dictated by the propensity of specific amino acids to form helices and to align water on one side of the helix into an ice-like pattern. PMID:24324684

Active and adaptive Legionella CRISPR-Cas reveals a recurrent challenge to the pathogen.

PubMed

Rao, Chitong; Guyard, Cyril; Pelaz, Carmen; Wasserscheid, Jessica; Bondy-Denomy, Joseph; Dewar, Ken; Ensminger, Alexander W

2016-10-01

Clustered regularly interspaced short palindromic repeats with CRISPR-associated gene (CRISPR-Cas) systems are widely recognized as critical genome defense systems that protect microbes from external threats such as bacteriophage infection. Several isolates of the intracellular pathogen Legionella pneumophila possess multiple CRISPR-Cas systems (type I-C, type I-F and type II-B), yet the targets of these systems remain unknown. With the recent observation that at least one of these systems (II-B) plays a non-canonical role in supporting intracellular replication, the possibility remained that these systems are vestigial genome defense systems co-opted for other purposes. Our data indicate that this is not the case. Using an established plasmid transformation assay, we demonstrate that type I-C, I-F and II-B CRISPR-Cas provide protection against spacer targets. We observe efficient laboratory acquisition of new spacers under 'priming' conditions, in which initially incomplete target elimination leads to the generation of new spacers and ultimate loss of the invasive DNA. Critically, we identify the first known target of L. pneumophila CRISPR-Cas: a 30 kb episome of unknown function whose interbacterial transfer is guarded against by CRISPR-Cas. We provide evidence that the element can subvert CRISPR-Cas by mutating its targeted sequences - but that primed spacer acquisition may limit this mechanism of escape. Rather than generally impinging on bacterial fitness, this element drives a host specialization event - with improved fitness in Acanthamoeba but a reduced ability to replicate in other hosts and conditions. These observations add to a growing body of evidence that host range restriction can serve as an existential threat to L. pneumophila in the wild. © 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

Differential Distribution of Type II CRISPR-Cas Systems in Agricultural and Nonagricultural Campylobacter coli and Campylobacter jejuni Isolates Correlates with Lack of Shared Environments.

PubMed

Pearson, Bruce M; Louwen, Rogier; van Baarlen, Peter; van Vliet, Arnoud H M

2015-09-02

CRISPR (clustered regularly interspaced palindromic repeats)-Cas (CRISPR-associated) systems are sequence-specific adaptive defenses against phages and plasmids which are widespread in prokaryotes. Here we have studied whether phylogenetic relatedness or sharing of environmental niches affects the distribution and dissemination of Type II CRISPR-Cas systems, first in 132 bacterial genomes from 15 phylogenetic classes, ranging from Proteobacteria to Actinobacteria. There was clustering of distinct Type II CRISPR-Cas systems in phylogenetically distinct genera with varying G+C%, which share environmental niches. The distribution of CRISPR-Cas within a genus was studied using a large collection of genome sequences of the closely related Campylobacter species Campylobacter jejuni (N = 3,746) and Campylobacter coli (N = 486). The Cas gene cas9 and CRISPR-repeat are almost universally present in C. jejuni genomes (98.0% positive) but relatively rare in C. coli genomes (9.6% positive). Campylobacter jejuni and agricultural C. coli isolates share the C. jejuni CRISPR-Cas system, which is closely related to, but distinct from the C. coli CRISPR-Cas system found in C. coli isolates from nonagricultural sources. Analysis of the genomic position of CRISPR-Cas insertion suggests that the C. jejuni-type CRISPR-Cas has been transferred to agricultural C. coli. Conversely, the absence of the C. coli-type CRISPR-Cas in agricultural C. coli isolates may be due to these isolates not sharing the same environmental niche, and may be affected by farm hygiene and biosecurity practices in the agricultural sector. Finally, many CRISPR spacer alleles were linked with specific multilocus sequence types, suggesting that these can assist molecular epidemiology applications for C. jejuni and C. coli. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Adaptive Behaviour Assessment System: Indigenous Australian Adaptation Model (ABAS: IAAM)

ERIC Educational Resources Information Center

du Plessis, Santie

2015-01-01

The study objectives were to develop, trial and evaluate a cross-cultural adaptation of the Adaptive Behavior Assessment System-Second Edition Teacher Form (ABAS-II TF) ages 5-21 for use with Indigenous Australian students ages 5-14. This study introduced a multiphase mixed-method design with semi-structured and informal interviews, school…

The role of BST2/tetherin in infection with the feline retroviruses

PubMed Central

Dietrich, Isabelle; Hosie, Margaret J.; Willett, Brian J.

2014-01-01

The recently identified host restriction factor tetherin (BST-2, CD317) potently inhibits the release of nascent retrovirus particles from infected cells. Recently, we reported the identification and characterization of tetherin as a novel feline retroviral restriction factor. Based on homology to human tetherin we identified a putative tetherin gene in the genome of the domestic cat (Felis catus) which was found to be expressed in different feline cell lines both prior to and post treatment with either type I or type II interferon (IFN). The predicted structure of feline tetherin (feTHN) was that of a type II single-pass transmembrane protein encoding an N-terminal transmembrane anchor, central predicted coiled-coil bearing extracellular domain to promote dimerization, and a C-terminal GPI-anchor, consistent with conservation of structure between human and feline tetherin. FeTHN displayed potent inhibition of feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV-1) particle release in single-cycle replication assays. Notably, feTHN activity was resistant to antagonism by HIV-1 Vpu. However, stable ectopic expression of feTHN mRNA in different feline cell lines had no inhibitory effect on the growth of diverse primary or cell culture-adapted strains of FIV. Hence, whereas feline tetherin efficiently blocks viral particle release in single-cycle replication assays, it might not prevent dissemination of feline retroviruses in vivo. PMID:21715020

Type I intrinsically photosensitive retinal ganglion cells of early post-natal development correspond to the M4 subtype.

PubMed

Sexton, Timothy J; Bleckert, Adam; Turner, Maxwell H; Van Gelder, Russell N

2015-06-21

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate circadian light entrainment and the pupillary light response in adult mice. In early development these cells mediate different processes, including negative phototaxis and the timing of retinal vascular development. To determine if ipRGC physiologic properties also change with development, we measured ipRGC cell density and light responses in wild-type mouse retinas at post-natal days 8, 15 and 30. Melanopsin-positive cell density decreases by 17% between post-natal days 8 and 15 and by 25% between days 8 and 30. This decrease is due specifically to a decrease in cells co-labeled with a SMI-32, a marker for alpha-on ganglion cells (corresponding to adult morphologic type M4 ipRGCs). On multi-electrode array recordings, post-natal day 8 (P8) ipRGC light responses show more robust firing, reduced adaptation and more rapid recovery from short and extended light pulses than do the light responses of P15 and P30 ipRGCs. Three ipRGC subtypes - Types I-III - have been defined in early development based on sensitivity and latency on multielectrode array recordings. We find that Type I cells largely account for the unique physiologic properties of P8 ipRGCs. Type I cells have previously been shown to have relatively short latencies and high sensitivity. We now show that Type I cells show have rapid and robust recovery from long and short bright light exposures compared with Type II and III cells, suggesting differential light adaptation mechanisms between cell types. By P15, Type I ipRGCs are no longer detectable. Loose patch recordings of P8 M4 ipRGCs demonstrate Type I physiology. Type I ipRGCs are found only in early development. In addition to their previously described high sensitivity and rapid kinetics, these cells are uniquely resistant to adaptation and recover quickly and fully to short and prolonged light exposure. Type I ipRGCs correspond to the SMI-32 positive, M4 subtype and largely lose melanopsin expression in development. These cells constitute a unique morphologic and physiologic class of ipRGCs functioning early in postnatal development.

Discovery, evaluation and distribution of haplotypes of the wheat Ppd-D1 gene.

PubMed

Guo, Zhiai; Song, Yanxia; Zhou, Ronghua; Ren, Zhenglong; Jia, Jizeng

2010-02-01

Ppd-D1 is one of the most potent genes affecting the photoperiod response of wheat (Triticum aestivum). Only two alleles, insensitive Ppd-D1a and sensitive Ppd-D1b, were known previously, and these did not adequately explain the broad adaptation of wheat to photoperiod variation. In this study, five diagnostic molecular markers were employed to identify Ppd-D1 haplotypes in 492 wheat varieties from diverse geographic locations and 55 accessions of Aegilops tauschii, the D genome donor species of wheat. Six Ppd-D1 haplotypes, designated I-VI, were identified. Types II, V and VI were considered to be more ancient and types I, III and IV were considered to be derived from type II. The transcript abundances of the Ppd-D1 haplotypes showed continuous variation, being highest for haplotype I, lowest for haplotype III, and correlating negatively with varietal differences in heading time. These haplotypes also significantly affected other agronomic traits. The distribution frequency of Ppd-D1 haplotypes showed partial correlations with both latitudes and altitudes of wheat cultivation regions. The evolution, expression and distribution of Ppd-D1 haplotypes were consistent evidentially with each other. What was regarded as a pair of alleles in the past can now be considered a series of alleles leading to continuous variation.

Comparison of the Vineland Adaptive Behavior Scales, Second Edition, and the Bayley Scales of Infant and Toddler Development, Third Edition.

PubMed

Scattone, Dorothy; Raggio, Donald J; May, Warren

2011-10-01

The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II), and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were administered to 65 children between the ages of 12 and 42 months referred for developmental delays. Standard scores and age equivalents were compared across instruments. Analyses showed no statistical difference between Vineland-II ABC standard scores and cognitive levels obtained from the Bayley-III. However, Vineland-II Communication and Motor domain standard scores were significantly higher than corresponding scores on the Bayley-III. In addition, age equivalent scores were significantly higher on the Vineland-II for the fine motor subdomain. Implications for early intervention are discussed.

Unique Features of Fish Immune Repertoires: Particularities of Adaptive Immunity Within the Largest Group of Vertebrates

PubMed Central

Sunyer, Oriol J.

2016-01-01

Fishes (i.e., teleost fishes) are the largest group of vertebrates. Although their immune system is based on the fundamental receptors, pathways, and cell types found in all groups of vertebrates, fishes show a diversity of particular features that challenge some classical concepts of immunology. In this chapter, we discuss the particularities of fish immune repertoires from a comparative perspective. We examine how allelic exclusion can be achieved when multiple Ig loci are present, how isotypic diversity and functional specificity impact clonal complexity, how loss of the MHC class II molecules affects the cooperation between T and B cells, and how deep sequencing technologies bring new insights about somatic hypermutation in the absence of germinal centers. The unique coexistence of two distinct B-cell lineages respectively specialized in systemic and mucosal responses is also discussed. Finally, we try to show that the diverse adaptations of immune repertoires in teleosts can help in understanding how somatic adaptive mechanisms of immunity evolved in parallel in different lineages across vertebrates. PMID:26537384

Fatal autoimmunity in mice reconstituted with human hematopoietic stem cells encoding defective FOXP3

PubMed Central

Goettel, Jeremy A.; Biswas, Subhabrata; Lexmond, Willem S.; Yeste, Ada; Passerini, Laura; Patel, Bonny; Yang, Siyoung; Sun, Jiusong; Ouahed, Jodie; Shouval, Dror S.; McCann, Katelyn J.; Horwitz, Bruce H.; Mathis, Diane; Milford, Edgar L.; Notarangelo, Luigi D.; Roncarolo, Maria-Grazia; Fiebiger, Edda; Marasco, Wayne A.; Bacchetta, Rosa; Quintana, Francisco J.; Pai, Sung-Yun; Klein, Christoph; Muise, Aleixo M.

2015-01-01

Mice reconstituted with a human immune system provide a tractable in vivo model to assess human immune cell function. To date, reconstitution of murine strains with human hematopoietic stem cells (HSCs) from patients with monogenic immune disorders have not been reported. One obstacle precluding the development of immune-disease specific “humanized” mice is that optimal adaptive immune responses in current strains have required implantation of autologous human thymic tissue. To address this issue, we developed a mouse strain that lacks murine major histocompatibility complex class II (MHC II) and instead expresses human leukocyte antigen DR1 (HLA-DR1). These mice displayed improved adaptive immune responses when reconstituted with human HSCs including enhanced T-cell reconstitution, delayed-type hypersensitivity responses, and class-switch recombination. Following immune reconstitution of this novel strain with HSCs from a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, associated with aberrant FOXP3 function, mice developed a lethal inflammatory disorder with multiorgan involvement and autoantibody production mimicking the pathology seen in affected humans. This humanized mouse model permits in vivo evaluation of immune responses associated with genetically altered HSCs, including primary immunodeficiencies, and should facilitate the study of human immune pathobiology and the development of targeted therapeutics. PMID:25833964

Robust Video Stabilization Using Particle Keypoint Update and l1-Optimized Camera Path

PubMed Central

Jeon, Semi; Yoon, Inhye; Jang, Jinbeum; Yang, Seungji; Kim, Jisung; Paik, Joonki

2017-01-01

Acquisition of stabilized video is an important issue for various type of digital cameras. This paper presents an adaptive camera path estimation method using robust feature detection to remove shaky artifacts in a video. The proposed algorithm consists of three steps: (i) robust feature detection using particle keypoints between adjacent frames; (ii) camera path estimation and smoothing; and (iii) rendering to reconstruct a stabilized video. As a result, the proposed algorithm can estimate the optimal homography by redefining important feature points in the flat region using particle keypoints. In addition, stabilized frames with less holes can be generated from the optimal, adaptive camera path that minimizes a temporal total variation (TV). The proposed video stabilization method is suitable for enhancing the visual quality for various portable cameras and can be applied to robot vision, driving assistant systems, and visual surveillance systems. PMID:28208622

ISAARE: Information System for Adaptive, Assistive, and Recreational Equipment: Volume I: Existence; Volume II, Communication; Volume V, Adaptation.

ERIC Educational Resources Information Center

Melichar, Joseph F.

Described as part of the Information System for Adaptive, Assistive and Recreational Equipment are equipment items for physically handicapped pupils in the functional areas of existence, equipment and adaptation. Reviewed in the existence section are such items as assistive food containers and container stabilizers, feeder accessories, bowel and…

Management of convulsive status epilepticus in children: an adapted clinical practice guideline for pediatricians in Saudi Arabia

PubMed Central

Bashiri, Fahad A.; Hamad, Muddathir H.; Amer, Yasser S.; Abouelkheir, Manal M.; Mohamed, Sarar; Kentab, Amal Y.; Salih, Mustafa A.; Nasser, Mohammad N. Al; Al-Eyadhy, Ayman A.; Othman, Mohammed A. Al; Al-Ahmadi, Tahani; Iqbal, Shaikh M.; Somily, Ali M.; Wahabi, Hayfaa A.; Hundallah, Khalid J.; Alwadei, Ali H.; Albaradie, Raidah S.; Al-Twaijri, Waleed A.; Jan, Mohammed M.; Al-Otaibi, Faisal; Alnemri, Abdulrahman M.; Al-Ansary, Lubna A.

2017-01-01

Objective: To increase the use of evidence-based approaches in the diagnosis, investigations and treatment of Convulsive Status Epilepticus (CSE) in children in relevant care settings. Method: A Clinical Practice Guideline (CPG) adaptation group was formulated at a university hospital in Riyadh. The group utilized 2 CPG validated tools including the ADAPTE method and the AGREE II instrument. Results: The group adapted 3 main categories of recommendations from one Source CPG. The recommendations cover; (i)first-line treatment of CSE in the community; (ii)treatment of CSE in the hospital; and (iii)refractory CSE. Implementation tools were built to enhance knowledge translation of these recommendations including a clinical algorithm, audit criteria, and a computerized provider order entry. Conclusion: A clinical practice guideline for the Saudi healthcare context was formulated using a guideline adaptation process to support relevant clinicians managing CSE in children. PMID:28416791

Dancing with Black Holes

NASA Astrophysics Data System (ADS)

Aarseth, S. J.

2008-05-01

We describe efforts over the last six years to implement regularization methods suitable for studying one or more interacting black holes by direct N-body simulations. Three different methods have been adapted to large-N systems: (i) Time-Transformed Leapfrog, (ii) Wheel-Spoke, and (iii) Algorithmic Regularization. These methods have been tried out with some success on GRAPE-type computers. Special emphasis has also been devoted to including post-Newtonian terms, with application to moderately massive black holes in stellar clusters. Some examples of simulations leading to coalescence by gravitational radiation will be presented to illustrate the practical usefulness of such methods.

Regulation of voltage-gated Ca(2+) currents by Ca(2+)/calmodulin-dependent protein kinase II in resting sensory neurons.

PubMed

Kostic, Sandra; Pan, Bin; Guo, Yuan; Yu, Hongwei; Sapunar, Damir; Kwok, Wai-Meng; Hudmon, Andy; Wu, Hsiang-En; Hogan, Quinn H

2014-09-01

Calcium/calmodulin-dependent protein kinase II (CaMKII) is recognized as a key element in encoding depolarization activity of excitable cells into facilitated voltage-gated Ca(2+) channel (VGCC) function. Less is known about the participation of CaMKII in regulating VGCCs in resting cells. We examined constitutive CaMKII control of Ca(2+) currents in peripheral sensory neurons acutely isolated from dorsal root ganglia (DRGs) of adult rats. The small molecule CaMKII inhibitor KN-93 (1.0μM) reduced depolarization-induced ICa by 16-30% in excess of the effects produced by the inactive homolog KN-92. The specificity of CaMKII inhibition on VGCC function was shown by the efficacy of the selective CaMKII blocking peptide autocamtide-2-related inhibitory peptide in a membrane-permeable myristoylated form, which also reduced VGCC current in resting neurons. Loss of VGCC currents is primarily due to reduced N-type current, as application of mAIP selectively reduced N-type current by approximately 30%, and prior N-type current inhibition eliminated the effect of mAIP on VGCCs, while prior block of L-type channels did not reduce the effect of mAIP on total ICa. T-type currents were not affected by mAIP in resting DRG neurons. Transduction of sensory neurons in vivo by DRG injection of an adeno-associated virus expressing AIP also resulted in a loss of N-type currents. Together, these findings reveal a novel molecular adaptation whereby sensory neurons retain CaMKII support of VGCCs despite remaining quiescent. Published by Elsevier Inc.

Bioinformatics analyses of Shigella CRISPR structure and spacer classification.

PubMed

Wang, Pengfei; Zhang, Bing; Duan, Guangcai; Wang, Yingfang; Hong, Lijuan; Wang, Linlin; Guo, Xiangjiao; Xi, Yuanlin; Yang, Haiyan

2016-03-01

Clustered regularly interspaced short palindromic repeats (CRISPR) are inheritable genetic elements of a variety of archaea and bacteria and indicative of the bacterial ecological adaptation, conferring acquired immunity against invading foreign nucleic acids. Shigella is an important pathogen for anthroponosis. This study aimed to analyze the features of Shigella CRISPR structure and classify the spacers through bioinformatics approach. Among 107 Shigella, 434 CRISPR structure loci were identified with two to seven loci in different strains. CRISPR-Q1, CRISPR-Q4 and CRISPR-Q5 were widely distributed in Shigella strains. Comparison of the first and last repeats of CRISPR1, CRISPR2 and CRISPR3 revealed several base variants and different stem-loop structures. A total of 259 cas genes were found among these 107 Shigella strains. The cas gene deletions were discovered in 88 strains. However, there is one strain that does not contain cas gene. Intact clusters of cas genes were found in 19 strains. From comprehensive analysis of sequence signature and BLAST and CRISPRTarget score, the 708 spacers were classified into three subtypes: Type I, Type II and Type III. Of them, Type I spacer referred to those linked with one gene segment, Type II spacer linked with two or more different gene segments, and Type III spacer undefined. This study examined the diversity of CRISPR/cas system in Shigella strains, demonstrated the main features of CRISPR structure and spacer classification, which provided critical information for elucidation of the mechanisms of spacer formation and exploration of the role the spacers play in the function of the CRISPR/cas system.

AO Images of Asteroids, Inverting their Lightcurves, and SSA

DTIC Science & Technology

2008-09-01

telescopes, we have recently obtained images of Main- Belt asteroids with adaptive optics (AO) on the Keck-II 10 meter telescope, the world’s largest...telescopes, we have recently obtained images of Main- Belt asteroids with adaptive optics (AO) on the Keck-II 10 meter telescope, the world’s largest...AO Images of Asteroids , Inverting their Lightcurves, and SSA Jack Drummond a and Julian Christoub,c aStarfire Optical Range, Directed Energy

Adaptive ingredients against food spoilage in Japanese cuisine.

PubMed

Ohtsubo, Yohsuke

2009-12-01

Billing and Sherman proposed the antimicrobial hypothesis to explain the worldwide spice use pattern. The present study explored whether two antimicrobial ingredients (i.e. spices and vinegar) are used in ways consistent with the antimicrobial hypothesis. Four specific predictions were tested: meat-based recipes would call for more spices/vinegar than vegetable-based recipes; summer recipes would call for more spices/vinegar than winter recipes; recipes in hotter regions would call for more spices/vinegar; and recipes including unheated ingredients would call for more spices/vinegar. Spice/vinegar use patterns were compiled from two types of traditional Japanese cookbooks. Dataset I included recipes provided by elderly Japanese housewives. Dataset II included recipes provided by experts in traditional Japanese foods. The analyses of Dataset I revealed that the vinegar use pattern conformed to the predictions. In contrast, analyses of Dataset II generally supported the predictions in terms of spices, but not vinegar.

Role of recoverin in rod photoreceptor light adaptation.

PubMed

Morshedian, Ala; Woodruff, Michael L; Fain, Gordon L

2018-04-15

Recoverin is a small molecular-weight, calcium-binding protein in rod outer segments that can modulate the rate of rhodopsin phosphorylation. We describe two additional and perhaps more important functions during photoreceptor light adaptation. Recoverin influences the rate of change of adaptation. In wild-type rods, sensitivity and response integration time adapt with similar time constants of 150-200 ms. In Rv-/- rods lacking recoverin, sensitivity declines faster and integration time is already shorter and not significantly altered. During steady light exposure, rod circulating current slowly increases during a time course of tens of seconds, gradually extending the operating range of the rod. In Rv-/- rods, this mechanism is deleted, steady-state currents are already larger and rods saturate at brighter intensities. We propose that recoverin modulates spontaneous and light-activated phophodiesterase-6, the phototransduction effector enzyme, to increase sensitivity in dim light but improve responsiveness to change in brighter illumination. Recoverin is a small molecular-weight, calcium-binding protein in rod outer segments that binds to G-protein receptor kinase 1 and can alter the rate of rhodopsin phosphorylation. A change in phosphorylation should change the lifetime of light-activated rhodopsin and the gain of phototransduction, but deletion of recoverin has little effect on the sensitivity of rods either in the dark or in dim-to-moderate background light. We describe two additional functions perhaps of greater physiological significance. (i) When the ambient intensity increases, sensitivity and integration time decrease in wild-type (WT) rods with similar time constants of 150-200 ms. Recoverin is part of the mechanism controlling this process because, in Rv-/- rods lacking recoverin, sensitivity declines more rapidly and integration time is already shorter and not further altered. (ii) During steady light exposure, WT rod circulating current slowly increases during a time course of tens of seconds, gradually extending the operating range of the rod. In Rv-/- rods, this mechanism is also deleted, steady-state currents are already larger and rods saturate at brighter intensities. We argue that neither (i) nor (ii) can be caused by modulation of rhodopsin phosphorylation but may instead be produced by direct modulation of phophodiesterase-6 (PDE6), the phototransduction effector enzyme. We propose that recoverin in dark-adapted rods keeps the integration time long and the spontaneous PDE6 rate relatively high to improve sensitivity. In background light, the integration time is decreased to facilitate detection of change and motion and the spontaneous PDE6 rate decreases to augment the rod working range. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Current Status of Peroral Endoscopic Myotomy

PubMed Central

Cho, Young Kwan; Kim, Seong Hwan

2018-01-01

Peroral endoscopic myotomy (POEM) has been established as an optional treatment for achalasia. POEM is an endoluminal procedure that involves dissection of esophageal muscle fibers followed by submucosal tunneling. Inoue first attempted to use POEM for the treatment of achalasia in humans. Expanded indications of POEM include classic indications such as type I, type II, type III achalasia, failed prior treatments, including Botulinum toxin injection, endoscopic balloon dilation, laparoscopic Heller myotomy, and hypertensive motor disorders such as diffuse esophageal spasm, jackhammer esophagus. Contraindications include prior radiation therapy to the esophagus and prior extensive esophageal mucosal resection/ablation involving the POEM field. Most of the complications are minor and self-limited and can be managed conservatively. As POEM emerged as the main treatment for achalasia, various adaptations to tunnel endoscopic surgery have been attempted. Tunnel endoscopic surgery includes POEM, peroral endoscopic tumor resection, gastric peroral endoscopic pyloromyotomy. POEM has been widely accepted as a treatment for all types of achalasia, even for specific cases such as achalasia with failed prior treatments, and hypertensive motor disorders. PMID:29397656

Current Status of Peroral Endoscopic Myotomy.

PubMed

Cho, Young Kwan; Kim, Seong Hwan

2018-01-01

Peroral endoscopic myotomy (POEM) has been established as an optional treatment for achalasia. POEM is an endoluminal procedure that involves dissection of esophageal muscle fibers followed by submucosal tunneling. Inoue first attempted to use POEM for the treatment of achalasia in humans. Expanded indications of POEM include classic indications such as type I, type II, type III achalasia, failed prior treatments, including Botulinum toxin injection, endoscopic balloon dilation, laparoscopic Heller myotomy, and hypertensive motor disorders such as diffuse esophageal spasm, jackhammer esophagus. Contraindications include prior radiation therapy to the esophagus and prior extensive esophageal mucosal resection/ablation involving the POEM field. Most of the complications are minor and self-limited and can be managed conservatively. As POEM emerged as the main treatment for achalasia, various adaptations to tunnel endoscopic surgery have been attempted. Tunnel endoscopic surgery includes POEM, peroral endoscopic tumor resection, gastric peroral endoscopic pyloromyotomy. POEM has been widely accepted as a treatment for all types of achalasia, even for specific cases such as achalasia with failed prior treatments, and hypertensive motor disorders.

Emergence of Pathogenic Coronaviruses in Cats by Homologous Recombination between Feline and Canine Coronaviruses

PubMed Central

Terada, Yutaka; Matsui, Nobutaka; Noguchi, Keita; Kuwata, Ryusei; Shimoda, Hiroshi; Soma, Takehisa; Mochizuki, Masami; Maeda, Ken

2014-01-01

Type II feline coronavirus (FCoV) emerged via double recombination between type I FCoV and type II canine coronavirus (CCoV). In this study, two type I FCoVs, three type II FCoVs and ten type II CCoVs were genetically compared. The results showed that three Japanese type II FCoVs, M91-267, KUK-H/L and Tokyo/cat/130627, also emerged by homologous recombination between type I FCoV and type II CCoV and their parent viruses were genetically different from one another. In addition, the 3′-terminal recombination sites of M91-267, KUK-H/L and Tokyo/cat/130627 were different from one another within the genes encoding membrane and spike proteins, and the 5′-terminal recombination sites were also located at different regions of ORF1. These results indicate that at least three Japanese type II FCoVs emerged independently. Sera from a cat experimentally infected with type I FCoV was unable to neutralize type II CCoV infection, indicating that cats persistently infected with type I FCoV may be superinfected with type II CCoV. Our previous study reported that few Japanese cats have antibody against type II FCoV. All of these observations suggest that type II FCoV emerged inside the cat body and is unable to readily spread among cats, indicating that these recombination events for emergence of pathogenic coronaviruses occur frequently. PMID:25180686

On High and Low Starting Frequencies of Type II Radio Bursts

NASA Astrophysics Data System (ADS)

Sharma, J.; Mittal, N.

2017-06-01

We have studied the characteristics of type II radio burst during the period May 1996 to March 2015, for the solar cycle 23 and 24, observed by WIND/WAVES radio instrument. A total of 642 events were recorded by the instrument during the study period. We have divided the events with two starting frequency range (high > 1 MHz; low ≤ 1MHz) as type II1 (i.e., 1-16 MHz) radio burst and type II2 (i.e., 20 KHz - 1020 KHz) radio burst which constitute the DH and km type II radio burst observed by WIND spacecraft, and determined their time and frequency characteristics. The mean drift rate of type II1 and type II2 radio bursts is 29.76 × 10-4 MHz/s and 0.17 × 10-4 MHz/s respectively, which shows that type II1 with high start frequency hase larger drift rate than the type II2 with low starting frequencies. We have also reported that the start frequency and the drift rate of type II1 are in good correlation, with a linear correlation coefficient of 0.58.

Adaptations to Speed Endurance Training in Highly Trained Soccer Players.

PubMed

Nyberg, Michael; Fiorenza, Matteo; Lund, Anders; Christensen, Magnus; Rømer, Tue; Piil, Peter; Hostrup, Morten; Christensen, Peter M; Holbek, Simon; Ravnholt, Thomas; Gunnarsson, Thomas P; Bangsbo, Jens

2016-07-01

The present study examined whether a period of additional speed endurance training would improve intense intermittent exercise performance in highly trained soccer players during the season and whether the training changed aerobic metabolism and the level of oxidative enzymes in type I and type II muscle fibers. During the last 9 wk of the season, 13 semiprofessional soccer players performed additional speed endurance training sessions consisting of two to three sets of 8-10 repetitions of 30-m sprints with 10 s of passive recovery (SET). Before and after SET, subjects completed a double-step exercise protocol that included transitions from standing to moderate-intensity running (~75% HRmax), followed by transitions from moderate- to high-intensity running (~90% HRmax) in which pulmonary oxygen uptake (V˙O2) was determined. In addition, the yo-yo intermittent recovery test level 1 was performed, and a muscle biopsy was obtained at rest. The yo-yo intermittent recovery test level 1 performance was 11.6% ± 6.4% (mean ± SD) better (2803 ± 330 vs 3127 ± 383 m, P < 0.05) after SET compared with before SET. In the transition from standing to moderate-intensity running, phase II pulmonary V˙O2 kinetics was 11.4% ± 16.5% faster (P < 0.05), and the running economy at this intensity was 2.3% ± 3.0% better (P < 0.05). These improvements were apparent despite the content of muscle proteins regulating oxidative metabolism (3-hydroxyacyl CoA dehydrogenase, COX IV, and OXPHOS), and capillarization was reduced (P < 0.05). The content of 3-hydroxyacyl CoA dehydrogenase and citrate synthase in type I and type II fibers did not change. In highly trained soccer players, additional speed endurance training is associated with an improved ability to perform repeated high-intensity work. To what extent the training-induced changes in V˙O2 kinetics and mechanical efficiency in type I fibers caused the improvement in performance warrants further investigation.

Fatty acid composition modulates sensitivity of Legionella pneumophila to warnericin RK, an antimicrobial peptide.

PubMed

Verdon, Julien; Labanowski, Jérome; Sahr, Tobias; Ferreira, Thierry; Lacombe, Christian; Buchrieser, Carmen; Berjeaud, Jean-Marc; Héchard, Yann

2011-04-01

Warnericin RK is an antimicrobial peptide, produced by a Staphyloccocus warneri strain, described to be specifically active against Legionella, the pathogenic bacteria responsible for Legionnaires' disease. Warnericin RK is an amphiphilic alpha-helical peptide, which possesses a detergent-like mode of action. Two others peptides, δ-hemolysin I and II, produced by the same S. warneri strain, are highly similar to S. aureus δ-hemolysin and also display anti-Legionella activity. It has been recently reported that S. aureus δ-hemolysin activity on vesicles is likewise related to phospholipid acyl-chain structure, such as chain length and saturation. As staphylococcal δ-hemolysins were highly similar, we thus hypothesized that fatty acid composition of Legionella's membrane might influence the sensitivity of the bacteria to warnericin RK. Relationship between sensitivity to the peptide and fatty acid composition was then followed in various conditions. Cells in stationary phase, which were already described as less resistant than cells in exponential phase, displayed higher amounts of branched-chain fatty acids (BCFA) and short chain fatty acids. An adapted strain, able to grow at a concentration 33 fold higher than minimal inhibitory concentration of the wild type (i.e. 1μM), was isolated after repeated transfers of L. pneumophila in the presence of increased concentrations of warnericin RK. The amount of BCFA was significantly higher in the adapted strain than in the wild type strain. Also, a transcriptomic analysis of the wild type and adapted strains showed that two genes involved in fatty acid biosynthesis were repressed in the adapted strain. These genes encode enzymes involved in desaturation and elongation of fatty acids respectively. Their repression was in agreement with the decrease of unsaturated fatty acids and fatty acid chain length in the adapted strain. Conclusively, our results indicate that the increase of BCFA and the decrease of fatty acid chain length in membrane were correlated with the increase in resistance to warnericin RK. Therefore, fatty acid profile seems to play a critical role in the sensitivity of L. pneumophila to warnericin RK. Copyright © 2010 Elsevier B.V. All rights reserved.

Ion transport in goby intestine: cellular mechanism of urotensin II stimulation.

PubMed

Loretz, C A; Howard, M E; Siegel, A J

1985-08-01

The Na- and Cl-absorbing goby posterior intestinal epithelium is composed predominantly of mitochondria-rich, tall columnar cells. Glass intracellular microelectrode recording technique was applied to absorptive cells of this relatively leaky epithelium to measure apical cell membrane potential difference (psi mc) and apical membrane fractional resistance. As determined by ion-substitution studies, absorptive cells are characterized by a large, Ba2+-inhibitable apical K conductance, which is a major factor determining psi mc and smaller Cl and Na conductances. Inhibition of the apical Na-Cl-coupled influx directly by furosemide or indirectly by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine produced hyperpolarization of psi mc, consistent with the greater apical membrane conductance to Cl than Na. The urophysial neurosecretory peptide urotensin II, which stimulates Na-Cl-coupled absorption, markedly depolarized psi mc in posterior intestinal tissues from 5% seawater-adapted gobies. This response is consistent with a stimulatory effect of urotensin II at the apical membrane carrier rather than at the basolateral Na-K-ATPase. Urotensin II is without effect on psi mc in tissues from seawater-adapted fish and somatostatin, a natural analogue of urotensin II, is without effect on tissues from fish adapted to either salinity. This specificity parallels that determined using radiotracer fluxes.

Photosystem II Photochemistry and Phycobiliprotein of the Red Algae Kappaphycus alvarezii and Their Implications for Light Adaptation

PubMed Central

Wang, Jinfeng; Zhu, Jianyi; Yao, Chunyan; Liu, Jianguo; Qin, Song; Jiang, Peng

2013-01-01

Photosystem II photochemistry and phycobiliprotein (PBP) genes of red algae Kappaphycus alvarezii, raw material of κ-carrageenan used in food and pharmaceutical industries, were analyzed in this study. Minimum saturating irradiance (I k) of this algal species was less than 115 μmol m−2 s−1. Its actual PSII efficiency (yield II) increased when light intensity enhanced and decreased when light intensity reached 200 μmol m−2 s−1. Under dim light, yield II declined at first and then increased on the fourth day. Under high light, yield II retained a stable value. These results indicate that K. alvarezii is a low-light-adapted species but possesses regulative mechanisms in response to both excessive and deficient light. Based on the PBP gene sequences, K. alvarezii, together with other red algae, assembled faster and showed a closer relationship with LL-Prochlorococcus compared to HL-Prochlorococcus. Many amino acid loci in PBP sequences of K. alvarezii were conserved with those of LL-Prochlorococcus. However, loci conserved with HL-Prochlorococcus but divergent with LL-Prochlorococcus were also found. The diversities of PE and PC are proposed to have played some roles during the algal evolution and divergence of light adaption. PMID:24380080

Photosystem II photochemistry and phycobiliprotein of the red algae Kappaphycus alvarezii and their implications for light adaptation.

PubMed

Guan, Xiangyu; Wang, Jinfeng; Zhu, Jianyi; Yao, Chunyan; Liu, Jianguo; Qin, Song; Jiang, Peng

2013-01-01

Photosystem II photochemistry and phycobiliprotein (PBP) genes of red algae Kappaphycus alvarezii, raw material of κ -carrageenan used in food and pharmaceutical industries, were analyzed in this study. Minimum saturating irradiance (I k) of this algal species was less than 115 μmol m(-2) s(-1). Its actual PSII efficiency (yield II) increased when light intensity enhanced and decreased when light intensity reached 200 μmol m(-2) s(-1). Under dim light, yield II declined at first and then increased on the fourth day. Under high light, yield II retained a stable value. These results indicate that K. alvarezii is a low-light-adapted species but possesses regulative mechanisms in response to both excessive and deficient light. Based on the PBP gene sequences, K. alvarezii, together with other red algae, assembled faster and showed a closer relationship with LL-Prochlorococcus compared to HL-Prochlorococcus. Many amino acid loci in PBP sequences of K. alvarezii were conserved with those of LL-Prochlorococcus. However, loci conserved with HL-Prochlorococcus but divergent with LL-Prochlorococcus were also found. The diversities of PE and PC are proposed to have played some roles during the algal evolution and divergence of light adaption.

Association between adaptive behaviour and age in adults with Down syndrome without dementia: examining the range and severity of adaptive behaviour problems.

PubMed

Makary, A T; Testa, R; Tonge, B J; Einfeld, S L; Mohr, C; Gray, K M

2015-08-01

Studies on adaptive behaviour and ageing in adults with Down syndrome (DS) (without dementia) have typically analysed age-related change in terms of the total item scores on questionnaires. This research extends the literature by investigating whether the age-related changes in adaptive abilities could be differentially attributed to changes in the number or severity (intensity) of behavioural questionnaire items endorsed. The Adaptive Behaviour Assessment System-II Adult (ABAS-II Adult) was completed by parents and caregivers of 53 adults with DS aged between 16 and 56 years. Twenty adults with DS and their parents/caregivers were a part of a longitudinal study, which provided two time points of data. In addition 33 adults with DS and their parents/caregivers from a cross-sectional study were included. Random effects regression analyses were used to examine the patterns in item scores associated with ageing. Increasing age was found to be significantly associated with lower adaptive behaviour abilities for all the adaptive behaviour composite scores, expect for the practical composite. These associations were entirely related to fewer ABAS-II Adult items being selected as present for the older participants, as opposed to the scores being attributable to lower item severity. This study provides evidence for a differential pattern of age-related change for various adaptive behaviour skills in terms of range, but not severity. Possible reasons for this pattern will be discussed. Overall, these findings suggest that adults with DS may benefit from additional support in terms of their social and conceptual abilities as they age. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Adaptive and Innate Transforming Growth Factor β Signaling Impact Herpes Simplex Virus 1 Latency and Reactivation▿

PubMed Central

Allen, Sariah J.; Mott, Kevin R.; Wechsler, Steven L.; Flavell, Richard A.; Town, Terrence; Ghiasi, Homayon

2011-01-01

Innate and adaptive immunity play important protective roles by combating herpes simplex virus 1 (HSV-1) infection. Transforming growth factor β (TGF-β) is a key negative cytokine regulator of both innate and adaptive immune responses. Yet, it is unknown whether TGF-β signaling in either immune compartment impacts HSV-1 replication and latency. We undertook genetic approaches to address these issues by infecting two different dominant negative TGF-β receptor type II transgenic mouse lines. These mice have specific TGF-β signaling blockades in either T cells or innate cells. Mice were ocularly infected with HSV-1 to evaluate the effects of restricted innate or adaptive TGF-β signaling during acute and latent infections. Limiting innate cell but not T cell TGF-β signaling reduced virus replication in the eyes of infected mice. On the other hand, blocking TGF-β signaling in either innate cells or T cells resulted in decreased latency in the trigeminal ganglia of infected mice. Furthermore, inhibiting TGF-β signaling in T cells reduced cell lysis and leukocyte infiltration in corneas and trigeminal ganglia during primary HSV-1 infection of mice. These findings strongly suggest that TGF-β signaling, which generally functions to dampen immune responses, results in increased HSV-1 latency. PMID:21880769

Adaptive Core Simulation Employing Discrete Inverse Theory - Part II: Numerical Experiments

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

Abdel-Khalik, Hany S.; Turinsky, Paul J.

2005-07-15

Use of adaptive simulation is intended to improve the fidelity and robustness of important core attribute predictions such as core power distribution, thermal margins, and core reactivity. Adaptive simulation utilizes a selected set of past and current reactor measurements of reactor observables, i.e., in-core instrumentation readings, to adapt the simulation in a meaningful way. The companion paper, ''Adaptive Core Simulation Employing Discrete Inverse Theory - Part I: Theory,'' describes in detail the theoretical background of the proposed adaptive techniques. This paper, Part II, demonstrates several computational experiments conducted to assess the fidelity and robustness of the proposed techniques. The intentmore » is to check the ability of the adapted core simulator model to predict future core observables that are not included in the adaption or core observables that are recorded at core conditions that differ from those at which adaption is completed. Also, this paper demonstrates successful utilization of an efficient sensitivity analysis approach to calculate the sensitivity information required to perform the adaption for millions of input core parameters. Finally, this paper illustrates a useful application for adaptive simulation - reducing the inconsistencies between two different core simulator code systems, where the multitudes of input data to one code are adjusted to enhance the agreement between both codes for important core attributes, i.e., core reactivity and power distribution. Also demonstrated is the robustness of such an application.« less

Proportion of collagen type II in the extracellular matrix promotes the differentiation of human adipose-derived mesenchymal stem cells into nucleus pulposus cells.

PubMed

Tao, Yiqing; Zhou, Xiaopeng; Liu, Dongyu; Li, Hao; Liang, Chengzhen; Li, Fangcai; Chen, Qixin

2016-01-01

During degeneration process, the catabolism of collagen type II and anabolism of collagen type I in nucleus pulposus (NP) may influence the bioactivity of transplanted cells. Human adipose-derived mesenchymal stem cells (hADMSCs) were cultured as a micromass or in a series of gradual proportion hydrogels of a mix of collagen types I and II. Cell proliferation and cytotoxicity were detected using CCK-8 and LDH assays respectively. The expression of differentiation-related genes and proteins, including SOX9, aggrecan, collagen type I, and collagen type II, was examined using RT-qPCR and Western blotting. Novel phenotypic genes were also detected by RT-qPCR and western blotting. Alcian blue and dimethylmethylene blue assays were used to investigate sulfate proteoglycan expression, and PI3K/AKT, MAPK/ERK, and Smad signaling pathways were examined by Western blotting. The results showed collagen hydrogels have good biocompatibility, and cell proliferation increased after collagen type II treatment. Expressions of SOX9, aggrecan, and collagen type II were increased in a collagen type II dependent manner. Sulfate proteoglycan synthesis increased in proportion to collagen type II concentration. Only hADMSCs highly expressed NP cell marker KRT19 in collagen type II culture. Additionally, phosphorylated Smad3, which is associated with phosphorylated ERK, was increased after collagen type II-stimulation. The concentration and type of collagen affect hADMSC differentiation into NP cells. Collagen type II significantly ameliorates hADMSC differentiation into NP cells and promotes extracellular matrix synthesis. Therefore, anabolism of collagen type I and catabolism of type II may attenuate the differentiation and biosynthesis of transplanted stem cells. © 2016 International Union of Biochemistry and Molecular Biology.

Effect of lineage-specific metabolic traits of Lactobacillus reuteri on sourdough microbial ecology.

PubMed

Lin, Xiaoxi B; Gänzle, Michael G

2014-09-01

This study determined the effects of specific metabolic traits of Lactobacillus reuteri on its competitiveness in sourdoughs. The competitiveness of lactobacilli in sourdough generally depends on their growth rate; acid resistance additionally contributes to competitiveness in sourdoughs with long fermentation times. Glycerol metabolism via glycerol dehydratase (gupCDE) accelerates growth by the regeneration of reduced cofactors; glutamate metabolism via glutamate decarboxylase (gadB) increases acid resistance by generating a proton motive force. Glycerol and glutamate metabolisms are lineage-specific traits in L. reuteri; therefore, this study employed glycerol dehydratase-positive sourdough isolates of human-adapted L. reuteri lineage I, glutamate decarboxylase-positive strains of rodent-adapted L. reuteri lineage II, as well as mutants with deletions in gadB or gupCDE. The competitivenesses of the strains were quantified by inoculation of wheat and sorghum sourdoughs with defined strains, followed by propagation of doughs with a 10% inoculum and 12-h or 72-h fermentation cycles. Lineage I L. reuteri strains dominated sourdoughs propagated with 12-h fermentation cycles; lineage II L. reuteri strains dominated sourdoughs propagated with 72-h fermentation cycles. L. reuteri 100-23ΔgadB was outcompeted by its wild-type strain in sourdoughs fermented with 72-h fermentation cycles; L. reuteri FUA3400ΔgupCDE was outcompeted by its wild-type strain in sourdoughs fermented with both 12-h and 72-h fermentation cycles. Competition experiments with isogenic pairs of strains resulted in a constant rate of strain displacement of the less competitive mutant strain. In conclusion, lineage-specific traits of L. reuteri determine the competitiveness of this species in sourdough fermentations. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency.

PubMed

Todkar, Abhijeet; Picard, Nicolas; Loffing-Cueni, Dominique; Sorensen, Mads V; Mihailova, Marija; Nesterov, Viatcheslav; Makhanova, Natalia; Korbmacher, Christoph; Wagner, Carsten A; Loffing, Johannes

2015-02-01

Aldosterone-independent mechanisms may contribute to K(+) homeostasis. We studied aldosterone synthase knockout (AS(-/-)) mice to define renal control mechanisms of K(+) homeostasis in complete aldosterone deficiency. AS(-/-) mice were normokalemic and tolerated a physiologic dietary K(+) load (2% K(+), 2 days) without signs of illness, except some degree of polyuria. With supraphysiologic K(+) intake (5% K(+)), AS(-/-) mice decompensated and became hyperkalemic. High-K(+) diets induced upregulation of the renal outer medullary K(+) channel in AS(-/-) mice, whereas upregulation of the epithelial sodium channel (ENaC) sufficient to increase the electrochemical driving force for K(+) excretion was detected only with a 2% K(+) diet. Phosphorylation of the thiazide-sensitive NaCl cotransporter was consistently lower in AS(-/-) mice than in AS(+/+) mice and was downregulated in mice of both genotypes in response to increased K(+) intake. Inhibition of the angiotensin II type 1 receptor reduced renal creatinine clearance and apical ENaC localization, and caused severe hyperkalemia in AS(-/-) mice. In contrast with the kidney, the distal colon of AS(-/-) mice did not respond to dietary K(+) loading, as indicated by Ussing-type chamber experiments. Thus, renal adaptation to a physiologic, but not supraphysiologic, K(+) load can be achieved in aldosterone deficiency by aldosterone-independent activation of the renal outer medullary K(+) channel and ENaC, to which angiotensin II may contribute. Enhanced urinary flow and reduced activity of the thiazide-sensitive NaCl cotransporter may support renal adaptation by activation of flow-dependent K(+) secretion and increased intratubular availability of Na(+) that can be reabsorbed in exchange for K(+) secreted. Copyright © 2015 by the American Society of Nephrology.

Behavioral differences among subjects with Prader-Willi syndrome and type I or type II deletion and maternal disomy.

PubMed

Butler, Merlin G; Bittel, Douglas C; Kibiryeva, Nataliya; Talebizadeh, Zohreh; Thompson, Travis

2004-03-01

To determine whether phenotypic differences exist among individuals with Prader-Willi syndrome with either type I or type II deletions of chromosome 15 or maternal disomy 15 leading to a better understanding of cause and pathophysiology of this classical genetic syndrome. We analyzed clinical, anthropometric, and behavioral data in 12 individuals (5 men, 7 women; mean age: 25.9 +/- 8.8 years) with PWS and a type I (TI) deletion, 14 individuals (6 men, 8 women; mean age: 19.6 +/- 6.5 years) with PWS and a type II (TII) deletion, and 21 individuals (10 men, 11 women; mean age: 23.6 +/- 9.2 years) with PWS and maternal disomy 15 (UPD). The deletion type was determined by genotyping of DNA markers between proximal chromosome 15 breakpoints BP1 and BP2. TI deletions are approximately 500 kb larger than TII deletions. Several validated psychological and behavioral tests were used to assess phenotypic characteristics of individuals with PWS representing the 3 genetic subtypes. Significant differences were found between the 2 deletion groups and those with UPD in multiple psychological and behavioral tests, but no differences were observed in other clinical or anthropometric data studied. Adaptive behavior scores were generally worse in individuals with PWS and the TI deletion, and specific obsessive-compulsive behaviors were more evident in the TI individuals compared with those with UPD. Individuals with PWS with TI deletions also had poorer reading and math skills as well as visual-motor integration. Our study indicates that individuals with TI deletion generally have more behavioral and psychological problems than individuals with the TII deletion or UPD. Four recently identified genes have been identified in the chromosome region between BP1 and BP2 with 1 of the genes (NIPA-1) expressed in mouse brain tissue but not thought to be imprinted. It may be important for brain development or function. These genes are deleted in individuals with TI deletion and are implicated in compulsive behavior and lower intellectual ability in individuals with TI versus TII.

Adaptation and adaptation transfer characteristics of five different saccade types in the monkey

PubMed Central

Fuchs, Albert F.; Soetedjo, Robijanto

2015-01-01

Shifts in the direction of gaze are accomplished by different kinds of saccades, which are elicited under different circumstances. Saccade types include targeting saccades to simple jumping targets, delayed saccades to visible targets after a waiting period, memory-guided (MG) saccades to remembered target locations, scanning saccades to stationary target arrays, and express saccades after very short latencies. Studies of human cases and neurophysiological experiments in monkeys suggest that separate pathways, which converge on a common locus that provides the motor command, generate these different types of saccade. When behavioral manipulations in humans cause targeting saccades to have persistent dysmetrias as might occur naturally from growth, aging, and injury, they gradually adapt to reduce the dysmetria. Although results differ slightly between laboratories, this adaptation generalizes or transfers to all the other saccade types mentioned above. Also, when one of the other types of saccade undergoes adaptation, it often transfers to another saccade type. Similar adaptation and transfer experiments, which allow inferences to be drawn about the site(s) of adaptation for different saccade types, have yet to be done in monkeys. Here we show that simian targeting and MG saccades adapt more than express, scanning, and delayed saccades. Adaptation of targeting saccades transfers to all the other saccade types. However, the adaptation of MG saccades transfers only to delayed saccades. These data suggest that adaptation of simian targeting saccades occurs on the pathway common to all saccade types. In contrast, only the delayed saccade command passes through the adaptation site of the MG saccade. PMID:25855693

Modic changes in lumbar spine: prevalence and distribution patterns of end plate oedema and end plate sclerosis.

PubMed

Xu, Lei; Chu, Bin; Feng, Yang; Xu, Feng; Zou, Yue-Fen

2016-01-01

The purpose of this study is to evaluate the distribution of end plate oedema in different types of Modic change especially in mixed type and to analyze the presence of end plate sclerosis in various types of Modic change. 276 patients with low back pain were scanned with 1.5-T MRI. Three radiologists assessed the MR images by T1 weighted, T2 weighted and fat-saturation T2 weighted sequences and classified them according to the Modic changes. Pure oedematous end plate signal changes were classified as Modic Type I; pure fatty end plate changes were classified as Modic Type II; and pure sclerotic end plate changes as Modic Type III. A mixed feature of both Types I and II with predominant oedematous signal change is classified as Modic I-II, and a mixture of Types I and II with predominant fatty change is classified as Modic II-I. Thus, the mixed types can further be subdivided into seven subtypes: Types I-II, Types II-I, Types I-III, Types III-I, Types II-III, Types III-II and Types I-III. During the same period, 52 of 276 patients who underwent CT and MRI were retrospectively reviewed to determine end plate sclerosis. (1) End plate oedema: of the 2760 end plates (276 patients) examined, 302 end plates showed Modic changes, of which 82 end plates showed mixed Modic changes. The mixed Modic changes contain 92.7% of oedematous changes. The mixed types especially Types I-II and Types II-I made up the majority of end plate oedematous changes. (2) End plate sclerosis: 52 of 276 patients were examined by both MRI and CT. Of the 520 end plates, 93 end plates showed Modic changes, of which 34 end plates have shown sclerotic changes in CT images. 11.8% of 34 end plates have shown Modic Type I, 20.6% of 34 end plates have shown Modic Type II, 2.9% of 34 end plates have shown Modic Type III and 64.7% of 34 end plates have shown mixed Modic type. End plate oedema makes up the majority of mixed types especially Types I-II and Types II-I. The end plate sclerosis on CT images may not just mean Modic Type III but does exist in all types of Modic changes, especially in mixed Modic types, and may reflect vertebral body mineralization rather than change in the bone marrow. End plate oedema and end plate sclerosis are present in a large proportion of mixed types.

GoldenBraid: An Iterative Cloning System for Standardized Assembly of Reusable Genetic Modules

PubMed Central

Sarrion-Perdigones, Alejandro; Falconi, Erica Elvira; Zandalinas, Sara I.; Juárez, Paloma; Fernández-del-Carmen, Asun; Granell, Antonio; Orzaez, Diego

2011-01-01

Synthetic Biology requires efficient and versatile DNA assembly systems to facilitate the building of new genetic modules/pathways from basic DNA parts in a standardized way. Here we present GoldenBraid (GB), a standardized assembly system based on type IIS restriction enzymes that allows the indefinite growth of reusable gene modules made of standardized DNA pieces. The GB system consists of a set of four destination plasmids (pDGBs) designed to incorporate multipartite assemblies made of standard DNA parts and to combine them binarily to build increasingly complex multigene constructs. The relative position of type IIS restriction sites inside pDGB vectors introduces a double loop (“braid”) topology in the cloning strategy that allows the indefinite growth of composite parts through the succession of iterative assembling steps, while the overall simplicity of the system is maintained. We propose the use of GoldenBraid as an assembly standard for Plant Synthetic Biology. For this purpose we have GB-adapted a set of binary plasmids for A. tumefaciens-mediated plant transformation. Fast GB-engineering of several multigene T-DNAs, including two alternative modules made of five reusable devices each, and comprising a total of 19 basic parts are also described. PMID:21750718

GoldenBraid: an iterative cloning system for standardized assembly of reusable genetic modules.

PubMed

Sarrion-Perdigones, Alejandro; Falconi, Erica Elvira; Zandalinas, Sara I; Juárez, Paloma; Fernández-del-Carmen, Asun; Granell, Antonio; Orzaez, Diego

2011-01-01

Synthetic Biology requires efficient and versatile DNA assembly systems to facilitate the building of new genetic modules/pathways from basic DNA parts in a standardized way. Here we present GoldenBraid (GB), a standardized assembly system based on type IIS restriction enzymes that allows the indefinite growth of reusable gene modules made of standardized DNA pieces. The GB system consists of a set of four destination plasmids (pDGBs) designed to incorporate multipartite assemblies made of standard DNA parts and to combine them binarily to build increasingly complex multigene constructs. The relative position of type IIS restriction sites inside pDGB vectors introduces a double loop ("braid") topology in the cloning strategy that allows the indefinite growth of composite parts through the succession of iterative assembling steps, while the overall simplicity of the system is maintained. We propose the use of GoldenBraid as an assembly standard for Plant Synthetic Biology. For this purpose we have GB-adapted a set of binary plasmids for A. tumefaciens-mediated plant transformation. Fast GB-engineering of several multigene T-DNAs, including two alternative modules made of five reusable devices each, and comprising a total of 19 basic parts are also described.

Insights into the strategies used by related group II introns to adapt successfully for the colonisation of a bacterial genome

PubMed Central

Martínez-Rodríguez, Laura; García-Rodríguez, Fernando M; Molina-Sánchez, María Dolores; Toro, Nicolás; Martínez-Abarca, Francisco

2014-01-01

Group II introns are self-splicing RNAs and site-specific mobile retroelements found in bacterial and organellar genomes. The group II intron RmInt1 is present at high copy number in Sinorhizobium meliloti species, and has a multifunctional intron-encoded protein (IEP) with reverse transcriptase/maturase activities, but lacking the DNA-binding and endonuclease domains. We characterized two RmInt1-related group II introns RmInt2 from S. meliloti strain GR4 and Sr.md.I1 from S. medicae strain WSM419 in terms of splicing and mobility activities. We used both wild-type and engineered intron-donor constructs based on ribozyme ΔORF-coding sequence derivatives, and we determined the DNA target requirements for RmInt2, the element most distantly related to RmInt1. The excision and mobility patterns of intron-donor constructs expressing different combinations of IEP and intron RNA provided experimental evidence for the co-operation of IEPs and intron RNAs from related elements in intron splicing and, in some cases, in intron homing. We were also able to identify the DNA target regions recognized by these IEPs lacking the DNA endonuclease domain. Our results provide new insight into the versatility of related group II introns and the possible co-operation between these elements to facilitate the colonization of bacterial genomes. PMID:25482895

Insights into the strategies used by related group II introns to adapt successfully for the colonisation of a bacterial genome.

PubMed

Martínez-Rodríguez, Laura; García-Rodríguez, Fernando M; Molina-Sánchez, María Dolores; Toro, Nicolás; Martínez-Abarca, Francisco

2014-01-01

Group II introns are self-splicing RNAs and site-specific mobile retroelements found in bacterial and organellar genomes. The group II intron RmInt1 is present at high copy number in Sinorhizobium meliloti species, and has a multifunctional intron-encoded protein (IEP) with reverse transcriptase/maturase activities, but lacking the DNA-binding and endonuclease domains. We characterized two RmInt1-related group II introns RmInt2 from S. meliloti strain GR4 and Sr.md.I1 from S. medicae strain WSM419 in terms of splicing and mobility activities. We used both wild-type and engineered intron-donor constructs based on ribozyme ΔORF-coding sequence derivatives, and we determined the DNA target requirements for RmInt2, the element most distantly related to RmInt1. The excision and mobility patterns of intron-donor constructs expressing different combinations of IEP and intron RNA provided experimental evidence for the co-operation of IEPs and intron RNAs from related elements in intron splicing and, in some cases, in intron homing. We were also able to identify the DNA target regions recognized by these IEPs lacking the DNA endonuclease domain. Our results provide new insight into the versatility of related group II introns and the possible co-operation between these elements to facilitate the colonization of bacterial genomes.

Comparing the effects of positive and negative feedback in information-integration category learning.

PubMed

Freedberg, Michael; Glass, Brian; Filoteo, J Vincent; Hazeltine, Eliot; Maddox, W Todd

2017-01-01

Categorical learning is dependent on feedback. Here, we compare how positive and negative feedback affect information-integration (II) category learning. Ashby and O'Brien (2007) demonstrated that both positive and negative feedback are required to solve II category problems when feedback was not guaranteed on each trial, and reported no differences between positive-only and negative-only feedback in terms of their effectiveness. We followed up on these findings and conducted 3 experiments in which participants completed 2,400 II categorization trials across three days under 1 of 3 conditions: positive feedback only (PFB), negative feedback only (NFB), or both types of feedback (CP; control partial). An adaptive algorithm controlled the amount of feedback given to each group so that feedback was nearly equated. Using different feedback control procedures, Experiments 1 and 2 demonstrated that participants in the NFB and CP group were able to engage II learning strategies, whereas the PFB group was not. Additionally, the NFB group was able to achieve significantly higher accuracy than the PFB group by Day 3. Experiment 3 revealed that these differences remained even when we equated the information received on feedback trials. Thus, negative feedback appears significantly more effective for learning II category structures. This suggests that the human implicit learning system may be capable of learning in the absence of positive feedback.

A Review of Computer-Based Human Behavior Representations and Their Relation to Military Simulations

DTIC Science & Technology

2003-08-01

described by Emery and Trist (1960), activity theory introduced by Vygotsky in the 1930s and formalized by Leont’ev (1979) and situated cognition theory by...II-6 B. Adaptive Resonance Theory (ART) .......................................................... II-6 1. Model...II-31 G. Cognitive Complexity Theory (CCT

Genetics Home Reference: distal hereditary motor neuropathy, type II

MedlinePlus

... hereditary motor neuropathy, type II Distal hereditary motor neuropathy, type II Printable PDF Open All Close All ... the expand/collapse boxes. Description Distal hereditary motor neuropathy, type II is a progressive disorder that affects ...

Examining the Specific Effects of Context on Adaptive Behavior and Achievement in a Rural African Community: Six Case Studies from Rural Areas of Southern Province, Zambia

ERIC Educational Resources Information Center

Tan, Mei; Reich, Jodi; Hart, Lesley; Thuma, Philip E.; Grigorenko, Elena L.

2014-01-01

Generally accepted as universal, the construct of adaptive behavior differs in its manifestations across different cultures and settings. The Vineland-II (Sparrow et al. in "Vineland Adaptive Behavior Scales, Second edn." AGS Publishing, Circle Pines, MN, 2005) was translated into Chitonga and adapted to the setting of rural Southern…

Floquet Weyl semimetals in light-irradiated type-II and hybrid line-node semimetals

NASA Astrophysics Data System (ADS)

Chen, Rui; Zhou, Bin; Xu, Dong-Hui

2018-04-01

Type-II Weyl semimetals have recently attracted intensive research interest because they host Lorentz-violating Weyl fermions as quasiparticles. The discovery of type-II Weyl semimetals evokes the study of type-II line-node semimetals (LNSMs) whose linear dispersion is strongly tilted near the nodal ring. We present here a study on the circularly polarized light-induced Floquet states in type-II LNSMs, as well as those in hybrid LNSMs that have a partially overtilted linear dispersion in the vicinity of the nodal ring. We illustrate that two distinct types of Floquet Weyl semimetal (WSM) states can be induced in periodically driven type-II and hybrid LNSMs, and the type of Floquet WSMs can be tuned by the direction and intensity of the incident light. We construct phase diagrams of light-irradiated type-II and hybrid LNSMs which are quite distinct from those of light-irradiated type-I LNSMs. Moreover, we show that photoinduced Floquet type-I and type-II WSMs can be characterized by the emergence of different anomalous Hall conductivities.

Casein Kinase 1α Mediates the Degradation of Receptors for Type I and Type II Interferons Caused by Hemagglutinin of Influenza A Virus.

PubMed

Xia, Chuan; Wolf, Jennifer J; Vijayan, Madhuvanthi; Studstill, Caleb J; Ma, Wenjun; Hahm, Bumsuk

2018-04-01

Although influenza A virus (IAV) evades cellular defense systems to effectively propagate in the host, the viral immune-evasive mechanisms are incompletely understood. Our recent data showed that hemagglutinin (HA) of IAV induces degradation of type I IFN receptor 1 (IFNAR1). Here, we demonstrate that IAV HA induces degradation of type II IFN (IFN-γ) receptor 1 (IFNGR1), as well as IFNAR1, via casein kinase 1α (CK1α), resulting in the impairment of cellular responsiveness to both type I and II IFNs. IAV infection or transient HA expression induced degradation of both IFNGR1 and IFNAR1, whereas HA gene-deficient IAV failed to downregulate the receptors. IAV HA caused the phosphorylation and ubiquitination of IFNGR1, leading to the lysosome-dependent degradation of IFNGR1. Influenza viral HA strongly decreased cellular sensitivity to type II IFNs, as it suppressed the activation of STAT1 and the induction of IFN-γ-stimulated genes in response to exogenously supplied recombinant IFN-γ. Importantly, CK1α, but not p38 MAP kinase or protein kinase D2, was proven to be critical for HA-induced degradation of both IFNGR1 and IFNAR1. Pharmacologic inhibition of CK1α or small interfering RNA (siRNA)-based knockdown of CK1α repressed the degradation processes of both IFNGR1 and IFNAR1 triggered by IAV infection. Further, CK1α was shown to be pivotal for proficient replication of IAV. Collectively, the results suggest that IAV HA induces degradation of IFN receptors via CK1α, creating conditions favorable for viral propagation. Therefore, the study uncovers a new immune-evasive pathway of influenza virus. IMPORTANCE Influenza A virus (IAV) remains a grave threat to humans, causing seasonal and pandemic influenza. Upon infection, innate and adaptive immunity, such as the interferon (IFN) response, is induced to protect hosts against IAV infection. However, IAV seems to be equipped with tactics to evade the IFN-mediated antiviral responses, although the detailed mechanisms need to be elucidated. In the present study, we show that IAV HA induces the degradation of the type II IFN receptor IFNGR1 and thereby substantially attenuates cellular responses to IFN-γ. Of note, a cellular kinase, casein kinase 1α (CK1α), is crucial for IAV HA-induced degradation of both IFNGR1 and IFNAR1. Accordingly, CK1α is proven to positively regulate IAV propagation. Thus, this study unveils a novel strategy employed by IAV to evade IFN-mediated antiviral activities. These findings may provide new insights into the interplay between IAV and host immunity to impact influenza virus pathogenicity. Copyright © 2018 American Society for Microbiology.

Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides

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

Du Yuzhe; Nomura, Yoshiko; Luo Ningguang

2009-01-15

Pyrethroid insecticides are classified as type I or type II based on their distinct symptomology and effects on sodium channel gating. Structurally, type II pyrethroids possess an {alpha}-cyano group at the phenylbenzyl alcohol position, which is lacking in type I pyrethroids. Both type I and type II pyrethroids inhibit deactivation consequently prolonging the opening of sodium channels. However, type II pyrethroids inhibit the deactivation of sodium channels to a greater extent than type I pyrethroids inducing much slower decaying of tail currents upon repolarization. The molecular basis of a type II-specific action, however, is not known. Here we report themore » identification of a residue G{sup 1111} and two positively charged lysines immediately downstream of G{sup 1111} in the intracellular linker connecting domains II and III of the cockroach sodium channel that are specifically involved in the action of type II pyrethroids, but not in the action of type I pyrethroids. Deletion of G{sup 1111}, a consequence of alternative splicing, reduced the sodium channel sensitivity to type II pyrethroids, but had no effect on channel sensitivity to type I pyrethroids. Interestingly, charge neutralization or charge reversal of two positively charged lysines (Ks) downstream of G{sup 1111} had a similar effect. These results provide the molecular insight into the type II-specific interaction of pyrethroids with the sodium channel at the molecular level.« less

Intradermal infections of mice by low numbers of african trypanosomes are controlled by innate resistance but enhance susceptibility to reinfection.

PubMed

Wei, Guojian; Bull, Harold; Zhou, Xia; Tabel, Henry

2011-02-01

Antibodies are required to control blood-stage forms of African trypanosomes in humans and animals. Here, we report that intradermal infections by low numbers of African trypanosomes are controlled by innate resistance but prime the adaptive immune response to increase susceptibility to a subsequent challenge. Mice were found 100 times more resistant to intradermal infections by Trypanosoma congolense or Trypanosoma brucei than to intraperitoneal infections. B cell-deficient and RAG2(-/-) mice are as resistant as wild-type mice to intradermal infections, whereas inducible nitric oxide synthase (iNOS)(-/-) mice and wild-type mice treated with antibody to tumor necrosis factor (TNF) α are more susceptible. We conclude that primary intradermal infections with low numbers of parasites are controlled by innate defense mediated by induced nitric oxide (NO). CD1d(-/-) and major histocompatibility complex (MHC) class II(-/-) mice are more resistant than wild-type mice to primary intradermal infections. Trypanosome-specific spleen cells, as shown by cytokine production, are primed as early as 24 h after intradermal infection. Infecting mice intradermally with low numbers of parasites, or injecting them intradermally with a trypanosomal lysate, makes mice more susceptible to an intradermal challenge. We suggest that intradermal infections with low numbers of trypanosomes or injections with trypanosomal lysates prime the adaptive immune system to suppress protective immunity to an intradermal challenge.

Interplanetary type II radio bursts and their association with CMEs and flares

NASA Astrophysics Data System (ADS)

Shanmugaraju, A.; Suresh, K.; Vasanth, V.; Selvarani, G.; Umapathy, S.

2018-06-01

We study the characteristics of the CMEs and their association with the end-frequency of interplanetary (IP)-type-II bursts by analyzing a set of 138 events (IP-type-II bursts-flares-CMEs) observed during the period 1997-2012. The present analysis consider only the type II bursts having starting frequency < 14 MHz to avoid the extension of coronal type IIs. The selected events are classified into three groups depending on the end-frequency of type IIs as follows, (A) Higher, (B) Intermediate and (C) Lower end-frequency. We compare characteristics of CMEs, flares and type II burst for the three selected groups of events and report some of the important differences. The observed height of CMEs is compared with the height of IP type IIs estimated using the electron density models. By applying a density multiplier (m) to this model, the density has been constrained both in the upper corona and in the interplanetary medium, respectively as m= 1 to 10 and m = 1 to 3. This study indicates that there is a correlation between the observed CME height and estimated type II height for groups B and C events whereas this correlation is absent in group A. In all the groups (A, B & C), the different heights of CMEs and type II reveal that the type IIs are not only observed at the nose but also at the flank of the CMEs.

Diversity and evolution of phycobilisomes in marine Synechococcus spp.: a comparative genomics study.

PubMed

Six, Christophe; Thomas, Jean-Claude; Garczarek, Laurence; Ostrowski, Martin; Dufresne, Alexis; Blot, Nicolas; Scanlan, David J; Partensky, Frédéric

2007-01-01

Marine Synechococcus owe their specific vivid color (ranging from blue-green to orange) to their large extrinsic antenna complexes called phycobilisomes, comprising a central allophycocyanin core and rods of variable phycobiliprotein composition. Three major pigment types can be defined depending on the major phycobiliprotein found in the rods (phycocyanin, phycoerythrin I or phycoerythrin II). Among strains containing both phycoerythrins I and II, four subtypes can be distinguished based on the ratio of the two chromophores bound to these phycobiliproteins. Genomes of eleven marine Synechococcus strains recently became available with one to four strains per pigment type or subtype, allowing an unprecedented comparative genomics study of genes involved in phycobilisome metabolism. By carefully comparing the Synechococcus genomes, we have retrieved candidate genes potentially required for the synthesis of phycobiliproteins in each pigment type. This includes linker polypeptides, phycobilin lyases and a number of novel genes of uncharacterized function. Interestingly, strains belonging to a given pigment type have similar phycobilisome gene complements and organization, independent of the core genome phylogeny (as assessed using concatenated ribosomal proteins). While phylogenetic trees based on concatenated allophycocyanin protein sequences are congruent with the latter, those based on phycocyanin and phycoerythrin notably differ and match the Synechococcus pigment types. We conclude that the phycobilisome core has likely evolved together with the core genome, while rods must have evolved independently, possibly by lateral transfer of phycobilisome rod genes or gene clusters between Synechococcus strains, either via viruses or by natural transformation, allowing rapid adaptation to a variety of light niches.

In silico genomic insights into aspects of food safety and defense mechanisms of a potentially probiotic Lactobacillus pentosus MP-10 isolated from brines of naturally fermented Aloreña green table olives.

PubMed

Abriouel, Hikmate; Pérez Montoro, Beatriz; Casado Muñoz, María Del Carmen; Knapp, Charles W; Gálvez, Antonio; Benomar, Nabil

2017-01-01

Lactobacillus pentosus MP-10, isolated from brines of naturally fermented Aloreña green table olives, exhibited high probiotic potential. The genome sequence of L. pentosus MP-10 is currently considered the largest genome among lactobacilli, highlighting the microorganism's ecological flexibility and adaptability. Here, we analyzed the complete genome sequence for the presence of acquired antibiotic resistance and virulence determinants to understand their defense mechanisms and explore its putative safety in food. The annotated genome sequence revealed evidence of diverse mobile genetic elements, such as prophages, transposases and transposons involved in their adaptation to brine-associated niches. In-silico analysis of L. pentosus MP-10 genome sequence identified a CRISPR (clustered regularly interspaced short palindromic repeats)/cas (CRISPR-associated protein genes) as an immune system against foreign genetic elements, which consisted of six arrays (4-12 repeats) and eleven predicted cas genes [CRISPR1 and CRISPR2 consisted of 3 (Type II-C) and 8 (Type I) genes] with high similarity to L. pentosus KCA1. Bioinformatic analyses revealed L. pentosus MP-10 to be absent of acquired antibiotic resistance genes, and most resistance genes were related to efflux mechanisms; no virulence determinants were found in the genome. This suggests that L. pentosus MP-10 could be considered safe and with high-adaptation potential, which could facilitate its application as a starter culture and probiotic in food preparations.

Ly49 Receptors: Innate and Adaptive Immune Paradigms

PubMed Central

Rahim, Mir Munir A.; Tu, Megan M.; Mahmoud, Ahmad Bakur; Wight, Andrew; Abou-Samra, Elias; Lima, Patricia D. A.; Makrigiannis, Andrew P.

2014-01-01

The Ly49 receptors are type II C-type lectin-like membrane glycoproteins encoded by a family of highly polymorphic and polygenic genes within the mouse natural killer (NK) gene complex. This gene family is designated Klra, and includes genes that encode both inhibitory and activating Ly49 receptors in mice. Ly49 receptors recognize class I major histocompatibility complex-I (MHC-I) and MHC-I-like proteins on normal as well as altered cells. Their functional homologs in humans are the killer cell immunoglobulin-like receptors, which recognize HLA class I molecules as ligands. Classically, Ly49 receptors are described as being expressed on both the developing and mature NK cells. The inhibitory Ly49 receptors are involved in NK cell education, a process in which NK cells acquire function and tolerance toward cells that express “self-MHC-I.” On the other hand, the activating Ly49 receptors recognize altered cells expressing activating ligands. New evidence shows a broader Ly49 expression pattern on both innate and adaptive immune cells. Ly49 receptors have been described on multiple NK cell subsets, such as uterine NK and memory NK cells, as well as NKT cells, dendritic cells, plasmacytoid dendritic cells, macrophages, neutrophils, and cells of the adaptive immune system, such as activated T cells and regulatory CD8+ T cells. In this review, we discuss the expression pattern and proposed functions of Ly49 receptors on various immune cells and their contribution to immunity. PMID:24765094

Bacterial Superantigens Promote Acute Nasopharyngeal Infection by Streptococcus pyogenes in a Human MHC Class II-Dependent Manner

PubMed Central

Kasper, Katherine J.; Zeppa, Joseph J.; Wakabayashi, Adrienne T.; Xu, Stacey X.; Mazzuca, Delfina M.; Welch, Ian; Baroja, Miren L.; Kotb, Malak; Cairns, Ewa; Cleary, P. Patrick; Haeryfar, S. M. Mansour; McCormick, John K.

2014-01-01

Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as ‘trademark’ virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC –II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms. PMID:24875883

Reversed gender ratio of autism spectrum disorder in Smith-Magenis syndrome.

PubMed

Nag, Heidi Elisabeth; Nordgren, Ann; Anderlid, Britt-Marie; Nærland, Terje

2018-01-01

A substantial amount of research shows a higher rate of autistic type of problems in males compared to females. The 4:1 male to female ratio is one of the most consistent findings in autism spectrum disorder (ASD).Lately, the interest in studying ASD in genetic disorders has increased, and research has shown a higher prevalence of ASD in some genetic disorders than in the general population.Smith-Magenis syndrome (SMS) is a rare and complex genetic syndrome caused by an interstitial deletion of chromosome 17p11.2 or a mutation on the retinoic acid induced 1 gene. The disorder is characterised by intellectual disability, multiple congenital anomalies, obesity, neurobehavioural abnormalities and a disrupted circadian sleep-wake pattern. Parents of 28 persons with SMS between 5 and 50 years old participated in this study. A total of 12 of the persons with SMS were above the age of 18 at the time of the study. A total of 11 came from Sweden and 17 were from Norway.We collected information regarding the number of autism spectrum symptoms using the Social Communication Questionnaire (SCQ) and the Social Responsiveness Scale (SRS). Adaptive behaviour was also measured using the Vineland Adaptive Behavior Scale II. The level of intellectual disability was derived from a review of the medical chart. We found significant gender differences in ASD symptomatology using the SCQ and SRS questionnaires. We found approximately three females per male above the SCQ cutoff. The same differences were not found in the intellectual level and adaptive behaviour or for behavioural and emotional problems.Gender had an independent contribution in a regression model predicting the total SCQ score, and neither the Vineland Adaptive Behavior Scale II nor the Developmental Behaviour Checklist had an independent contribution to the SCQ scores. We found a clear reversed gender difference in ASD symptomatology in persons with SMS. This may be relevant in the search for female protective factors assumed to explain the male bias in ASD.

Solar Type II Radio Bursts and IP Type II Events

NASA Technical Reports Server (NTRS)

Cane, H. V.; Erickson, W. C.

2005-01-01

We have examined radio data from the WAVES experiment on the Wind spacecraft in conjunction with ground-based data in order to investigate the relationship between the shocks responsible for metric type II radio bursts and the shocks in front of coronal mass ejections (CMEs). The bow shocks of fast, large CMEs are strong interplanetary (IP) shocks, and the associated radio emissions often consist of single broad bands starting below approx. 4 MHz; such emissions were previously called IP type II events. In contrast, metric type II bursts are usually narrowbanded and display two harmonically related bands. In addition to displaying complete dynamic spectra for a number of events, we also analyze the 135 WAVES 1 - 14 MHz slow-drift time periods in 2001-2003. We find that most of the periods contain multiple phenomena, which we divide into three groups: metric type II extensions, IP type II events, and blobs and bands. About half of the WAVES listings include probable extensions of metric type II radio bursts, but in more than half of these events, there were also other slow-drift features. In the 3 yr study period, there were 31 IP type II events; these were associated with the very fastest CMEs. The most common form of activity in the WAVES events, blobs and bands in the frequency range between 1 and 8 MHz, fall below an envelope consistent with the early signatures of an IP type II event. However, most of this activity lasts only a few tens of minutes, whereas IP type II events last for many hours. In this study we find many examples in the radio data of two shock-like phenomena with different characteristics that occur simultaneously in the metric and decametric/hectometric bands, and no clear example of a metric type II burst that extends continuously down in frequency to become an IP type II event. The simplest interpretation is that metric type II bursts, unlike IP type II events, are not caused by shocks driven in front of CMEs.

Bayesian adaptive phase II screening design for combination trials.

PubMed

Cai, Chunyan; Yuan, Ying; Johnson, Valen E

2013-01-01

Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Simulation studies show that the proposed design substantially outperforms the conventional multiarm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while allocating substantially more patients to efficacious treatments. The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while providing higher power to identify the best treatment at the end of the trial.

Type I and II Endometrial Cancers: Have They Different Risk Factors?

PubMed Central

Setiawan, Veronica Wendy; Yang, Hannah P.; Pike, Malcolm C.; McCann, Susan E.; Yu, Herbert; Xiang, Yong-Bing; Wolk, Alicja; Wentzensen, Nicolas; Weiss, Noel S.; Webb, Penelope M.; van den Brandt, Piet A.; van de Vijver, Koen; Thompson, Pamela J.; Strom, Brian L.; Spurdle, Amanda B.; Soslow, Robert A.; Shu, Xiao-ou; Schairer, Catherine; Sacerdote, Carlotta; Rohan, Thomas E.; Robien, Kim; Risch, Harvey A.; Ricceri, Fulvio; Rebbeck, Timothy R.; Rastogi, Radhai; Prescott, Jennifer; Polidoro, Silvia; Park, Yikyung; Olson, Sara H.; Moysich, Kirsten B.; Miller, Anthony B.; McCullough, Marjorie L.; Matsuno, Rayna K.; Magliocco, Anthony M.; Lurie, Galina; Lu, Lingeng; Lissowska, Jolanta; Liang, Xiaolin; Lacey, James V.; Kolonel, Laurence N.; Henderson, Brian E.; Hankinson, Susan E.; Håkansson, Niclas; Goodman, Marc T.; Gaudet, Mia M.; Garcia-Closas, Montserrat; Friedenreich, Christine M.; Freudenheim, Jo L.; Doherty, Jennifer; De Vivo, Immaculata; Courneya, Kerry S.; Cook, Linda S.; Chen, Chu; Cerhan, James R.; Cai, Hui; Brinton, Louise A.; Bernstein, Leslie; Anderson, Kristin E.; Anton-Culver, Hoda; Schouten, Leo J.; Horn-Ross, Pamela L.

2013-01-01

Purpose Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Patients and Methods Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Results Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m2 increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (Pheterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. Conclusion The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed. PMID:23733771

Molecular biomarkers monitoring human skeletal muscle fibres and microvasculature following long-term bed rest with and without countermeasures

PubMed Central

Salanova, M; Schiffl, G; Püttmann, B; Schoser, B G; Blottner, D

2008-01-01

The cellular mechanisms of human skeletal muscle adaptation to disuse are largely unknown. The aim of this study was to determine the morphological and biochemical changes of the lower limb soleus and vastus lateralis muscles following 60 days of head-down tilt bed rest in women with and without exercise countermeasure using molecular biomarkers monitoring functional cell compartments. Muscle biopsies were taken before (pre) and after bed rest (post) from a bed rest-only and a bed rest exercise group (n = 8, each). NOS1 and NOS3/PECAM, markers of myofibre ‘activity’ and capillary density, and MuRF1 (E3 ubiquitin-ligase), a marker of proteolysis, were documented by confocal immunofluorescence and immunoblot analyses. Morphometrical parameters (myofibre cross-sectional area, type I/II distribution) were largely preserved in muscles from the exercise group with a robust trend for type II hypertrophy in vastus lateralis. In the bed rest-only group, the relative NOS1 immunostaining intensity was decreased at type I and II myofibre membranes, while the bed rest plus exercise group compensated for this loss particularly in soleus. In the microvascular network, NOS3 expression and the capillary-to-fibre ratio were both increased in the exercise group. Elevated MuRF1 immunosignals found in subgroups of atrophic myofibres probably reflected accelerated proteolysis. Immunoblots revealed overexpression of the MuRF1 protein in the soleus of the bed rest-only group (> 35% vs. pre). We conclude that exercise countermeasure during bed rest affected both NOS/NO signalling and proteolysis in female skeletal muscle. Maintenance of NO signalling mechanisms and normal protein turnover by exercise countermeasure may be crucial steps to attenuate human skeletal muscle atrophy and to maintain cell function following chronic disuse. PMID:18221329

An RNA polymerase II-driven Ebola virus minigenome system as an advanced tool for antiviral drug screening.

PubMed

Nelson, Emily V; Pacheco, Jennifer R; Hume, Adam J; Cressey, Tessa N; Deflubé, Laure R; Ruedas, John B; Connor, John H; Ebihara, Hideki; Mühlberger, Elke

2017-10-01

Ebola virus (EBOV) causes a severe disease in humans with the potential for significant international public health consequences. Currently, treatments are limited to experimental vaccines and therapeutics. Therefore, research into prophylaxis and antiviral strategies to combat EBOV infections is of utmost importance. The requirement for high containment laboratories to study EBOV infection is a limiting factor for conducting EBOV research. To overcome this issue, minigenome systems have been used as valuable tools to study EBOV replication and transcription mechanisms and to screen for antiviral compounds at biosafety level 2. The most commonly used EBOV minigenome system relies on the ectopic expression of the T7 RNA polymerase (T7), which can be limiting for certain cell types. We have established an improved EBOV minigenome system that utilizes endogenous RNA polymerase II (pol II) as a driver for the synthesis of minigenome RNA. We show here that this system is as efficient as the T7-based minigenome system, but works in a wider range of cell types, including biologically relevant cell types such as bat cells. Importantly, we were also able to adapt this system to a reliable and cost-effective 96-well format antiviral screening assay with a Z-factor of 0.74, indicative of a robust assay. Using this format, we identified JG40, an inhibitor of Hsp70, as an inhibitor of EBOV replication, highlighting the potential for this system as a tool for antiviral drug screening. In summary, this updated EBOV minigenome system provides a convenient and effective means of advancing the field of EBOV research. Copyright © 2017 Elsevier B.V. All rights reserved.

Fibroblasts Lead the Way: A Unified View of 3D Cell Motility.

PubMed

Petrie, Ryan J; Yamada, Kenneth M

2015-11-01

Primary human fibroblasts are remarkably adaptable, able to migrate in differing types of physiological 3D tissue and on rigid 2D tissue culture surfaces. The crawling behavior of these and other vertebrate cells has been studied intensively, which has helped generate the concept of the cell motility cycle as a comprehensive model of 2D cell migration. However, this model fails to explain how cells force their large nuclei through the confines of a 3D matrix environment and why primary fibroblasts can use more than one mechanism to move in 3D. Recent work shows that the intracellular localization of myosin II activity is governed by cell-matrix interactions to both force the nucleus through the extracellular matrix (ECM) and dictate the type of protrusions used to migrate in 3D. Published by Elsevier Ltd.

Bergmann's Rule, Adaptation, and Thermoregulation in Arctic Animals: Conflicting Perspectives from Physiology, Evolutionary Biology, and Physical Anthropology After World War II.

PubMed

Hagen, Joel B

2017-05-01

Bergmann's rule and Allen's rule played important roles in mid-twentieth century discussions of adaptation, variation, and geographical distribution. Although inherited from the nineteenth-century natural history tradition these rules gained significance during the consolidation of the modern synthesis as evolutionary theorists focused attention on populations as units of evolution. For systematists, the rules provided a compelling rationale for identifying geographical races or subspecies, a function that was also picked up by some physical anthropologists. More generally, the rules provided strong evidence for adaptation by natural selection. Supporters of the rules tacitly, or often explicitly, assumed that the clines described by the rules reflected adaptations for thermoregulation. This assumption was challenged by the physiologists Laurence Irving and Per Scholander based on their arctic research conducted after World War II. Their critique spurred a controversy played out in a series of articles in Evolution, in Ernst Mayr's Animal Species and Evolution, and in the writings of other prominent evolutionary biologists and physical anthropologists. Considering this episode highlights the complexity and ambiguity of important biological concepts such as adaptation, homeostasis, and self-regulation. It also demonstrates how different disciplinary orientations and styles of scientific research influenced evolutionary explanations, and the consequent difficulties of constructing a truly synthetic evolutionary biology in the decades immediately following World War II.

AMOBH: Adaptive Multiobjective Black Hole Algorithm.

PubMed

Wu, Chong; Wu, Tao; Fu, Kaiyuan; Zhu, Yuan; Li, Yongbo; He, Wangyong; Tang, Shengwen

2017-01-01

This paper proposes a new multiobjective evolutionary algorithm based on the black hole algorithm with a new individual density assessment (cell density), called "adaptive multiobjective black hole algorithm" (AMOBH). Cell density has the characteristics of low computational complexity and maintains a good balance of convergence and diversity of the Pareto front. The framework of AMOBH can be divided into three steps. Firstly, the Pareto front is mapped to a new objective space called parallel cell coordinate system. Then, to adjust the evolutionary strategies adaptively, Shannon entropy is employed to estimate the evolution status. At last, the cell density is combined with a dominance strength assessment called cell dominance to evaluate the fitness of solutions. Compared with the state-of-the-art methods SPEA-II, PESA-II, NSGA-II, and MOEA/D, experimental results show that AMOBH has a good performance in terms of convergence rate, population diversity, population convergence, subpopulation obtention of different Pareto regions, and time complexity to the latter in most cases.

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

Pavitt, Ania S.; Bylaska, Eric J.; Tratnyek, Paul G.

As described in the main text, we classified our voltammograms into four types. For phenols, most compounds were type I or type II, except four phenols that were type III (4-nitrophenol, 4-cyanophenol, DNOC, and 4-hydroxyacetphenone); and two phenols that were type IV (4-aminophenol and dopamine). Almost all of the compounds gave the same type by SCV and SWV, except for 2,4-dinitrophenol (whose current went up and down and therefore could be considered a type II or III), 4-cyanophenol (which fell into a type III for SCV, but whose current went up and down in SWV (type II or III)), andmore » 4-hydroxyacetophenone (which was a type III in SCV, but a type II in SWV). The majority of the anilines were type I except for p-toluidine (type II) and 4-methyl-3-nitroaniline and 2-methoxy-5-nitroaniline (both were type I for SWV, but for SCV fell into type III and type II respectively).« less

Oxidation potentials of phenols and anilines: correlation analysis of electrochemical and theoretical values

DOE PAGES

Pavitt, Ania S.; Bylaska, Eric J.; Tratnyek, Paul G.

2017-02-10

As described in the main text, we classified our voltammograms into four types. For phenols, most compounds were type I or type II, except four phenols that were type III (4-nitrophenol, 4-cyanophenol, DNOC, and 4-hydroxyacetphenone); and two phenols that were type IV (4-aminophenol and dopamine). Almost all of the compounds gave the same type by SCV and SWV, except for 2,4-dinitrophenol (whose current went up and down and therefore could be considered a type II or III), 4-cyanophenol (which fell into a type III for SCV, but whose current went up and down in SWV (type II or III)), andmore » 4-hydroxyacetophenone (which was a type III in SCV, but a type II in SWV). The majority of the anilines were type I except for p-toluidine (type II) and 4-methyl-3-nitroaniline and 2-methoxy-5-nitroaniline (both were type I for SWV, but for SCV fell into type III and type II respectively).« less

Experiments with Unusual Oxidation States

ERIC Educational Resources Information Center

Kauffman, G. B.

1975-01-01

Describes four synthesis experiments, adapted for the general chemistry laboratory, in which compounds in unusual oxidation are prepared. The abnormal oxidation states involved in the synthesis products are: silver (II), chromium (II), lead (IV), and bromine (I). (MLH)

Past and current perspective on new therapeutic targets for Type-II diabetes.

PubMed

Patil, Pradip D; Mahajan, Umesh B; Patil, Kalpesh R; Chaudhari, Sandip; Patil, Chandragouda R; Agrawal, Yogeeta O; Ojha, Shreesh; Goyal, Sameer N

2017-01-01

Loss of pancreatic β-cell function is a hallmark of Type-II diabetes mellitus (DM). It is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Recently, United Kingdom Prospective Diabetes Study reported that Type-II DM is a progressive disorder. Although, DM can be treated initially by monotherapy with oral agent; eventually, it may require multiple drugs. Additionally, insulin therapy is needed in many patients to achieve glycemic control. Pharmacological approaches are unsatisfactory in improving the consequences of insulin resistance. Single therapeutic approach in the treatment of Type-II DM is unsuccessful and usually a combination therapy is adopted. Increased understanding of biochemical, cellular and pathological alterations in Type-II DM has provided new insight in the management of Type-II DM. Knowledge of underlying mechanisms of Type-II DM development is essential for the exploration of novel therapeutic targets. Present review provides an insight into therapeutic targets of Type-II DM and their role in the development of insulin resistance. An overview of important signaling pathways and mechanisms in Type-II DM is provided for the better understanding of disease pathology. This review includes case studies of drugs that are withdrawn from the market. The experience gathered from previous studies and knowledge of Type-II DM pathways can guide the anti-diabetic drug development toward the discovery of clinically viable drugs that are useful in Type-II DM.

On the source conditions for herringbone structure in type II solar radio bursts

NASA Technical Reports Server (NTRS)

Cane, H. V.; White, S. M.

1989-01-01

An investigation is made of the correlation of the occurrence of the herringbone phenomenon in type II solar radio bursts with various flare properties. It is shown that herringbone is strongly correlated with the intensity of the type II burst: whereas about 21 percent of all type II bursts show herringbone, about 60 percent of the most intense bursts contain herringbone. This fact can explain most of the correlations between herringbone and other properties such as intense type III bursts, type IV emission, and high type II starting frequencies. It is also shown that when this is taken into account, there is no need to postulate two classes of type II burst in order to explain why there appears to be a difference in herringbone occurrence between the set of type II bursts associated with the leading edges of coronal mass ejections, and those not so associated. It is argued that the data are consistent with the idea that all coronal type II bursts are due to blast waves from flares.

Phase I/II adaptive design for drug combination oncology trials

PubMed Central

Wages, Nolan A.; Conaway, Mark R.

2014-01-01

Existing statistical methodology on dose finding for combination chemotherapies has focused on toxicity considerations alone in finding a maximum tolerated dose combination to recommend for further testing of efficacy in a phase II setting. Recently, there has been increasing interest in integrating phase I and phase II trials in order to facilitate drug development. In this article, we propose a new adaptive phase I/II method for dual-agent combinations that takes into account both toxicity and efficacy after each cohort inclusion. The primary objective, both within and at the conclusion of the trial, becomes finding a single dose combination with an acceptable level of toxicity that maximizes efficacious response. We assume that there exist monotone dose–toxicity and dose–efficacy relationships among doses of one agent when the dose of other agent is fixed. We perform extensive simulation studies that demonstrate the operating characteristics of our proposed approach, and we compare simulated results to existing methodology in phase I/II design for combinations of agents. PMID:24470329

Transcriptome Analysis of Invasive Plants in Response to Mineral Toxicity of Reclaimed Coal-Mine Soil in the Appalachian Region.

PubMed

Saminathan, Thangasamy; Malkaram, Sridhar A; Patel, Dharmesh; Taylor, Kaitlyn; Hass, Amir; Nimmakayala, Padma; Huber, David H; Reddy, Umesh K

2015-09-01

Efficient postmining reclamation requires successful revegetation. By using RNA sequencing, we evaluated the growth response of two invasive plants, goutweed (Aegopodium podagraria L.) and mugwort (Artemisia vulgaris), grown in two Appalachian acid-mine soils (MS-I and -II, pH ∼ 4.6). Although deficient in macronutrients, both soils contained high levels of plant-available Al, Fe and Mn. Both plant types showed toxicity tolerance, but metal accumulation differed by plant and site. With MS-I, Al accumulation was greater for mugwort than goutweed (385 ± 47 vs 2151 ± 251 μg g-1). Al concentration was similar between mine sites, but its accumulation in mugwort was greater with MS-I than MS-II, with no difference in accumulation by site for goutweed. An in situ approach revealed deregulation of multiple factors such as transporters, transcription factors, and metal chelators for metal uptake or exclusion. The two plant systems showed common gene expression patterns for different pathways. Both plant systems appeared to have few common heavy-metal pathway regulators addressing mineral toxicity/deficiency in both mine sites, which implies adaptability of invasive plants for efficient growth at mine sites with toxic waste. Functional genomics can be used to screen for plant adaptability, especially for reclamation and phytoremediation of contaminated soils and waters.

Post-eclosion odor experience modifies olfactory receptor neuron coding in Drosophila

PubMed Central

Iyengar, Atulya; Chakraborty, Tuhin Subhra; Goswami, Sarit Pati; Wu, Chun-Fang; Siddiqi, Obaid

2010-01-01

Olfactory responses of Drosophila undergo pronounced changes after eclosion. The flies develop attraction to odors to which they are exposed and aversion to other odors. Behavioral adaptation is correlated with changes in the firing pattern of olfactory receptor neurons (ORNs). In this article, we present an information-theoretic analysis of the firing pattern of ORNs. Flies reared in a synthetic odorless medium were transferred after eclosion to three different media: (i) a synthetic medium relatively devoid of odor cues, (ii) synthetic medium infused with a single odorant, and (iii) complex cornmeal medium rich in odors. Recordings were made from an identified sensillum (type II), and the Jensen–Shannon divergence (DJS) was used to assess quantitatively the differences between ensemble spike responses to different odors. Analysis shows that prolonged exposure to ethyl acetate and several related esters increases sensitivity to these esters but does not improve the ability of the fly to distinguish between them. Flies exposed to cornmeal display varied sensitivity to these odorants and at the same time develop greater capacity to distinguish between odors. Deprivation of odor experience on an odorless synthetic medium leads to a loss of both sensitivity and acuity. Rich olfactory experience thus helps to shape the ORNs response and enhances its discriminative power. The experiments presented here demonstrate an experience-dependent adaptation at the level of the receptor neuron. PMID:20448199

Post-eclosion odor experience modifies olfactory receptor neuron coding in Drosophila.

PubMed

Iyengar, Atulya; Chakraborty, Tuhin Subhra; Goswami, Sarit Pati; Wu, Chun-Fang; Siddiqi, Obaid

2010-05-25

Olfactory responses of Drosophila undergo pronounced changes after eclosion. The flies develop attraction to odors to which they are exposed and aversion to other odors. Behavioral adaptation is correlated with changes in the firing pattern of olfactory receptor neurons (ORNs). In this article, we present an information-theoretic analysis of the firing pattern of ORNs. Flies reared in a synthetic odorless medium were transferred after eclosion to three different media: (i) a synthetic medium relatively devoid of odor cues, (ii) synthetic medium infused with a single odorant, and (iii) complex cornmeal medium rich in odors. Recordings were made from an identified sensillum (type II), and the Jensen-Shannon divergence (D(JS)) was used to assess quantitatively the differences between ensemble spike responses to different odors. Analysis shows that prolonged exposure to ethyl acetate and several related esters increases sensitivity to these esters but does not improve the ability of the fly to distinguish between them. Flies exposed to cornmeal display varied sensitivity to these odorants and at the same time develop greater capacity to distinguish between odors. Deprivation of odor experience on an odorless synthetic medium leads to a loss of both sensitivity and acuity. Rich olfactory experience thus helps to shape the ORNs response and enhances its discriminative power. The experiments presented here demonstrate an experience-dependent adaptation at the level of the receptor neuron.

Unfinished Business: Evolution of the MHC and the Adaptive Immune System of Jawed Vertebrates.

PubMed

Kaufman, Jim

2018-04-26

The major histocompatibility complex (MHC) is a large genetic region with many genes, including the highly polymorphic classical class I and II genes that play crucial roles in adaptive as well as innate immune responses. The organization of the MHC varies enormously among jawed vertebrates, but class I and II genes have not been found in other animals. How did the MHC arise, and are there underlying principles that can help us to understand the evolution of the MHC? This review considers what it means to be an MHC and the potential importance of genome-wide duplication, gene linkage, and gene coevolution for the emergence and evolution of an adaptive immune system. Then it considers what the original antigen-specific receptor and MHC molecule might have looked like, how peptide binding might have evolved, and finally the importance of adaptive immunity in general.

Temporal Response of Angiogenesis and Hypertrophy to Resistance Training in Young Men.

PubMed

Holloway, Tanya M; Snijders, Tim; VAN Kranenburg, Janneau; VAN Loon, Luc J C; Verdijk, Lex B

2018-01-01

Although endurance exercise training promotes angiogenesis and improves metabolic health, the effect of resistance training on this process is less well defined. We hypothesized that capillarization would increase proportionally, and concurrently, with muscle fiber hypertrophy in response to resistance training in young men. In this double-blind, randomized control trial, 36 men (22 ± 1 yr) were randomized to placebo or protein supplementation, and participated in 12 wk of resistance training. Skeletal muscle biopsies were collected before and after 2, 4, 8, and 12 wk of training. Immunohistochemistry assessed fiber type-specific size and capillarization. Western blot and reverse transcription polymerase chain reaction assessed proteins involved in the molecular regulation of angiogenesis. Resistance training effectively increased Type I (15% ± 4%; P < 0.01) and Type II fiber cross-sectional area (28% ± 5%; P < 0.0001), an effect that tended to be further enhanced with protein supplementation in Type II fibers (P = 0.078). Capillary-to-fiber ratio significantly increased in Type I (P = 0.001) and II (P = 0.015) fibers after 12 wk of resistance exercise training and was evident after only 2 wk. Capillary-to-fiber perimeter exchange index increased in the Type I fibers only (P = 0.054) after 12 wk of training. Training resulted in a reduction in vascular endothelial growth factor mRNA. A (P = 0.008), while vascular endothelial growth factor receptor 2 (P = 0.016), hypoxia-inducible factor 1α (P = 0.016), and endothelial nitric oxide synthase (P = 0.01) increased in both groups. Hypoxia-inducible factor 1α protein content was higher in the protein group (main group effect, P = 0.02), and endothelial nitric oxide synthase content demonstrated a divergent relationship (time-group interaction, P = 0.049). This study presents novel evidence that microvascular adaptations and the molecular pathways involved are elevated after 2 wk of a 12-wk resistance training program. Increases in muscle fiber cross-sectional area are effectively matched by the changes in the microvasculature, providing further support for resistance training programs to optimize metabolic health.

[Clinical study of severe anorexia nervosa: the role of intravenous hyperalimentation therapy].

PubMed

Denda, K; Kitagawa, N; Shimanaka, S

1997-01-01

In order to understand the psychopathology of severe anorexia nervosa (AN), and determine appropriate therapeutic approaches, a clinical study was conducted on 13 patients with severe AN who were hospitalized and were treated with intravenous hyperalimentation (IVH). The patients were divided into three types based on their clinical symptoms and initiating factors: Type I (Restricting Type; "Non-dieters"), Type II (Restricting Type: "Dieters"). Type III (Binge-eating/Purging Type). The clinical features of each type were evaluated. Based on this evaluation, the basic approach and the role of IVH in the treatment of each type are described as follows. Type I: The patients experience loss of appetite and subsequently, suffer involuntary weight loss as a result of psychological or physical stresses at school and/or home. Since the patients do not intentionally restrict food intake, they cannot explain the loss of appetite. The age at onset of this type is the youngest among the three groups. The patients are introverted, passive and not good at expressing their emotions. Therefore, it is often difficult to deepen the emotional commitment further. It is possible to understand the pathology of Type I through the psychosomatic model. IVH therapy promotes benign regression for Type I patients, so that the mother-child relationship may be restored. As the therapeutic progress, the mother child relationship occasionally become ambivalent. In such a case, it is important for the treatment team to support independent activities of the patients. Type II: The patients lose weight by intentionally restricting necessary food intake for reasons such as beauty or sports. Any experience of failure in studies or sports or trouble in complex personal relations can trigger the onset of AN. Weight loss is looked as a great achievement, whereas weight gain is recognized as a serious failure of self-control. Since type II patients understand the necessity of receiving treatment, it is possible to establish a trusting relationship during therapy. Their prognosis is generally good. The psychotherapeutic approach for Type II patients is most effective in the context of a weight gain program utilizing behavior therapy. It is important for the therapist to integrate psychological approach with physiological approach using IVH, and to modify cognitive distortion and body image disturbance. Type III: The patients have regularly engaged in binge eating or purging (or both) in the progress of AN. But as they intensely fear becoming fat, they refuse to maintain a minimally normal body weight. Therefore, they exhibit recurrently inappropriate compensatory behavior in order to prevent weight gain. In the therapeutic sessions, they often become ambivalent and unstable, showing dissatisfaction and reacting strongly against their therapists. The age at onset is the oldest of the three types. The prognosis is not good in many cases. IVH therapy may be required only in life-threatening situation for Type III patients. And severe bulimic patients may require sufficient drug treatment. The patients should be trained for interpersonal relationships at the day care unit or the occupational therapy unit. And they should be encouraged to adapt to real life.

Implementing New Non-Chromate Coatings Systems (Briefing Charts)

DTIC Science & Technology

2011-02-09

Initiate Cr6+ authorization process for continued Cr6+ use using the form, Authorization to Use Hexavalent Chromium. YES NO • Approval of...Aluminum and magnesium anodizing • Hard Chrome Plating • Type II conversion coating on aluminum alloys under chromated primer • Type II conversion coating...Elimination of Hexavalent Chromium 80% 5% 14% 1% Type II Type III Type IC Type IC Fatigue Critical 50% 50% Type II Type IC FRC-SE (JAX) Fully Integrated FRC

A Guide to Computer Simulations of Three Adaptive Instructional Models for the Advanced Instructional System Phases II and III. Final Report.

ERIC Educational Resources Information Center

Hansen, Duncan N.; And Others

Computer simulations of three individualized adaptive instructional models (AIM) were undertaken to determine if these models function as prescribed in Air Force technical training programs. In addition, the project sought to develop a user's guide for effective understanding of adaptive models during field implementation. Successful simulations…

Adaptive Behavior Ratings Correlate with Symptomatology and IQ among Individuals with High-Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

Kenworthy, Lauren; Case, Laura; Harms, Madeline B.; Martin, Alex; Wallace, Gregory L.

2010-01-01

Caregiver report on the Adaptive Behavior Assessment System-II (ABAS) for 40 high-functioning individuals with Autism Spectrum Disorders (ASD) and 30 typically developing (TD) individuals matched for age, IQ, and sex ratio revealed global adaptive behavior deficits in ASD, with social skills impairments particularly prominent. Within the ASD…

Effects of Resistance Training in Youth Athletes on Muscular Fitness and Athletic Performance: A Conceptual Model for Long-Term Athlete Development

PubMed Central

Granacher, Urs; Lesinski, Melanie; Büsch, Dirk; Muehlbauer, Thomas; Prieske, Olaf; Puta, Christian; Gollhofer, Albert; Behm, David G.

2016-01-01

During the stages of long-term athlete development (LTAD), resistance training (RT) is an important means for (i) stimulating athletic development, (ii) tolerating the demands of long-term training and competition, and (iii) inducing long-term health promoting effects that are robust over time and track into adulthood. However, there is a gap in the literature with regards to optimal RT methods during LTAD and how RT is linked to biological age. Thus, the aims of this scoping review were (i) to describe and discuss the effects of RT on muscular fitness and athletic performance in youth athletes, (ii) to introduce a conceptual model on how to appropriately implement different types of RT within LTAD stages, and (iii) to identify research gaps from the existing literature by deducing implications for future research. In general, RT produced small-to-moderate effects on muscular fitness and athletic performance in youth athletes with muscular strength showing the largest improvement. Free weight, complex, and plyometric training appear to be well-suited to improve muscular fitness and athletic performance. In addition, balance training appears to be an important preparatory (facilitating) training program during all stages of LTAD but particularly during the early stages. As youth athletes become more mature, specificity, and intensity of RT methods increase. This scoping review identified research gaps that are summarized in the following and that should be addressed in future studies: (i) to elucidate the influence of gender and biological age on the adaptive potential following RT in youth athletes (especially in females), (ii) to describe RT protocols in more detail (i.e., always report stress and strain-based parameters), and (iii) to examine neuromuscular and tendomuscular adaptations following RT in youth athletes. PMID:27242538

Combining Spitzer Parallax and Keck II Adaptive Optics Imaging to Measure the Mass of a Solar-like Star Orbited by a Cold Gaseous Planet Discovered by Microlensing

NASA Astrophysics Data System (ADS)

Beaulieu, J.-P.; Batista, V.; Bennett, D. P.; Marquette, J.-B.; Blackman, J. W.; Cole, A. A.; Coutures, C.; Danielski, C.; Dominis Prester, D.; Donatowicz, J.; Fukui, A.; Koshimoto, N.; Lončarić, K.; Morales, J. C.; Sumi, T.; Suzuki, D.; Henderson, C.; Shvartzvald, Y.; Beichman, C.

2018-02-01

To obtain accurate mass measurements for cold planets discovered by microlensing, it is usually necessary to combine light curve modeling with at least two lens mass–distance relations. The physical parameters of the planetary system OGLE-2014-BLG-0124L have been constrained thanks to accurate parallax effect between ground-based and simultaneous space-based Spitzer observations. Here, we resolved the source+lens star from sub-arcsecond blends in H-band using adaptive optics (AO) observations with NIRC2 mounted on Keck II telescope. We identify additional flux, coincident with the source to within 160 mas. We estimate the potential contributions to this blended light (chance-aligned star, additional companion to the lens or to the source) and find that 85% of the NIR flux is due to the lens star at H L = 16.63 ± 0.06 and K L = 16.44 ± 0.06. We combined the parallax constraint and the AO constraint to derive the physical parameters of the system. The lensing system is composed of a mid-late type G main sequence star of M L = 0.9 ± 0.05 M ⊙ located at D L = 3.5 ± 0.2 kpc in the Galactic disk. Taking the mass ratio and projected separation from the original study leads to a planet of M p = 0.65 ± 0.044 M Jupiter at 3.48 ± 0.22 au. Excellent parallax measurements from simultaneous ground-space observations have been obtained on the microlensing event OGLE-2014-BLG-0124, but it is only when they are combined with ∼30 minutes of Keck II AO observations that the physical parameters of the host star are well measured.

Experimental viral evolution to specific host MHC genotypes reveals fitness and virulence trade-offs in alternative MHC types.

PubMed

Kubinak, Jason L; Ruff, James S; Hyzer, Cornelius Whitney; Slev, Patricia R; Potts, Wayne K

2012-02-28

The unprecedented genetic diversity found at vertebrate MHC (major histocompatibility complex) loci influences susceptibility to most infectious and autoimmune diseases. The evolutionary explanation for how these polymorphisms are maintained has been controversial. One leading explanation, antagonistic coevolution (also known as the Red Queen), postulates a never-ending molecular arms race where pathogens evolve to evade immune recognition by common MHC alleles, which in turn provides a selective advantage to hosts carrying rare MHC alleles. This cyclical process leads to negative frequency-dependent selection and promotes MHC diversity if two conditions are met: (i) pathogen adaptation must produce trade-offs that result in pathogen fitness being higher in familiar (i.e., host MHC genotype adapted to) vs. unfamiliar host MHC genotypes; and (ii) this adaptation must produce correlated patterns of virulence (i.e., disease severity). Here we test these fundamental assumptions using an experimental evolutionary approach (serial passage). We demonstrate rapid adaptation and virulence evolution of a mouse-specific retrovirus to its mammalian host across multiple MHC genotypes. Critically, this adaptive response results in trade-offs (i.e., antagonistic pleiotropy) between host MHC genotypes; both viral fitness and virulence is substantially higher in familiar versus unfamiliar MHC genotypes. These data are unique in experimentally confirming the requisite conditions of the antagonistic coevolution model of MHC evolution and providing quantification of fitness effects for pathogen and host. These data help explain the unprecedented diversity of MHC genes, including how disease-causing alleles are maintained.

Software Reviews.

ERIC Educational Resources Information Center

Science and Children, 1988

1988-01-01

Reviews five software packages for use with school age children. Includes "Science Toolkit Module 2: Earthquake Lab"; "Adaptations and Identification"; "Geoworld"; "Body Systems II Series: The Blood System: A Liquid of Life," all for Apple II, and "Science Courseware: Life Science/Biology" for…

Outcomes from ovarian cancer screening in the PLCO trial: Histologic heterogeneity impacts detection, overdiagnosis and survival.

PubMed

Temkin, Sarah M; Miller, Eric A; Samimi, Goli; Berg, Christine D; Pinsky, Paul; Minasian, Lori

2017-12-01

A mortality benefit from screening for ovarian cancer has never been demonstrated. The aim of this study was to evaluate the screening outcomes for different histologic subtypes of ovarian cancers. Women in the screening arm of the Prostate, Lung, Colorectal and Ovarian Screening Trial underwent CA-125 and transvaginal ultrasound annually for 3-5 years. We compared screening test characteristics (including overdiagnosis) and outcomes by tumour type (type II versus other) and study arm (screening versus usual care). Of 78,215 women randomised, 496 women were diagnosed with ovarian cancer. Of the tumours that were characterised (n = 413; 83%), 74% (n = 305) were type II versus 26% other (n = 108). Among screened patients, 70% of tumours were type II compared to 78% in usual care (p = 0.09). Within the screening arm, 29% of type II tumours were screen detected compared to 54% of the others (p < 0.01). The sensitivity of screening was 65% for type II tumours versus 86% for other types (p = 0.02). 15% of type II screen-detected tumours were stage I/II, compared to 81% of other tumours (p < 0.01). The overdiagnosis rate was lower for type II compared to other tumours (28.2% versus 72.2%; p < 0.01). Ovarian cancer-specific survival was worse for type II tumours compared to others (p < 0.01). Survival was similar for type II (p = 0.74) or other types (p = 0.32) regardless of study arm. Test characteristics of screening for ovarian cancer differed for type II tumours compared to other ovarian tumours. Type II tumours were less likely to be screen diagnosed, early stage at diagnosis or overdiagnosed. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Kinetic Mechanism for Cytochrome P450 Metabolism of Type II Binding Compounds: Evidence Supporting Direct Reduction

PubMed Central

Pearson, Joshua; Dahal, Upendra P.; Rock, Daniel; Peng, Chi-Chi; Schenk, James O.; Joswig-Jones, Carolyn; Jones, Jeffrey P.

2011-01-01

The metabolic stability of a drug is an important property that should be optimized during drug design and development. Nitrogen incorporation is hypothesized to increase the stability by coordination of nitrogen to the heme iron of cytochrome P450, a binding mode that is referred to as type II binding. However, we noticed that the type II binding compound 1 has less metabolic stability at subsaturating conditions than a closely related type I binding compound 3. Three kinetic models will be presented for type II binder metabolism; 1) Dead-end type II binding, 2) a rapid equilibrium between type I and II binding modes before reduction, and 3) a direct reduction of the type II coordinated heme. Data will be presented on reduction rates of iron, the off rates of substrate (using surface plasmon resonance) and the catalytic rate constants. These data argue against the dead-end, and rapid equilibrium models, leaving the direct reduction kinetic mechanism for metabolism of the type II binding compound 1. PMID:21530484

Nematocytes: Discovery and characterization of a novel anculeate hemocyte in Drosophila falleni and Drosophila phalerata.

PubMed

Bozler, Julianna; Kacsoh, Balint Z; Bosco, Giovanni

2017-01-01

Immune challenges, such as parasitism, can be so pervasive and deleterious that they constitute an existential threat to a species' survival. In response to these ecological pressures, organisms have developed a wide array of novel behavioral, cellular, and molecular adaptations. Research into these immune defenses in model systems has resulted in a revolutionary understanding of evolution and functional biology. As the field has expanded beyond the limited number of model organisms our appreciation of evolutionary innovation and unique biology has widened as well. With this in mind, we have surveyed the hemolymph of several non-model species of Drosophila. Here we identify and describe a novel hemocyte, type-II nematocytes, found in larval stages of numerous Drosophila species. Examined in detail in Drosophila falleni and Drosophila phalerata, we find that these remarkable cells are distinct from previously described hemocytes due to their anucleate state (lacking a nucleus) and unusual morphology. Type-II nematocytes are long, narrow cells with spindle-like projections extending from a cell body with high densities of mitochondria and microtubules, and exhibit the ability to synthesize proteins. These properties are unexpected for enucleated cells, and together with our additional characterization, we demonstrate that these type-II nematocytes represent a biological novelty. Surprisingly, despite the absence of a nucleus, we observe through live cell imaging that these cells remain motile with a highly dynamic cellular shape. Furthermore, these cells demonstrate the ability to form multicellular structures, which we suggest may be a component of the innate immune response to macro-parasites. In addition, live cell imaging points to a large nucleated hemocyte, type-I nematocyte, as the progenitor cell, leading to enucleation through a budding or asymmetrical division process rather than nuclear ejection: This study is the first to report such a process of enucleation. Here we describe these cells in detail for the first time and examine their evolutionary history in Drosophila.

Computerized Adaptive Testing (CAT): A User Manual

DTIC Science & Technology

1984-03-12

NPRDC TR 84-32 COMPUTERIZED ADAPTIVE TESTING ( CAT ): A USER MANUAL Susan Hardwick Lawrence Eastman Ross Cooper Rehab Group, Incorporated San...a ~EI’IOD COVIRED COMPUTERIZED ADAPTIVE TESTING ( CAT ) Final Report Aug 1981-June 1982 A USER MANUAL 1. ~l:l’t,ORMINCI ORCI. RE~ORT NUM.I:R 62-83...II nee• .. _, entl ldentll)’ ,,. llloclr _,.,) A joint-service effort is underway to develop a computerized adaptive testing ( CAT ) system and to

Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

PubMed

Sloan, M A; Alexandrov, A V; Tegeler, C H; Spencer, M P; Caplan, L R; Feldmann, E; Wechsler, L R; Newell, D W; Gomez, C R; Babikian, V L; Lefkowitz, D; Goldman, R S; Armon, C; Hsu, C Y; Goodin, D S

2004-05-11

To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

Orbital Fibroblasts From Thyroid Eye Disease Patients Differ in Proliferative and Adipogenic Responses Depending on Disease Subtype

PubMed Central

Kuriyan, Ajay E.; Woeller, Collynn F.; O'Loughlin, Charles W.; Phipps, Richard P.; Feldon, Steven E.

2013-01-01

Purpose. Thyroid eye disease (TED) patients are classified as type I (predominantly fat compartment enlargement) or type II (predominantly extraocular muscle enlargement) based on orbital imaging. Orbital fibroblasts (OFs) can be driven to proliferate or differentiate into adipocytes in vitro. We tested the hypothesis that type I OFs undergo more adipogenesis than type II OFs, whereas type II OFs proliferate more than type I OFs. We also examined the effect of cyclooxygenase (COX) inhibitors on OF adipogenesis and proliferation. Methods. Type I, type II, and non-TED OFs were treated with transforming growth factor-beta (TGFβ) to induce proliferation and with 15-deoxy-Δ−12,14-prostaglandin J2 (15d-PGJ2) to induce adipogenesis. Proliferation was measured using the [3H]thymidine assay, and adipogenesis was measured using the AdipoRed assay, Oil Red O staining, and flow cytometry. The effect of COX inhibition on adipogenesis and proliferation was also studied. Results. Type II OFs incorporated 1.7-fold more [3H]thymidine than type I OFs (P < 0.05). Type I OFs accumulated 4.8-fold more lipid than type II OFs (P < 0.05) and 12.6-fold more lipid than non-TED OFs (P < 0.05). Oil Red O staining and flow cytometry also demonstrated increased adipogenesis in type I OFs compared to type II and non-TED OFs. Cyclooxygenase inhibition significantly decreased proliferation and adipogenesis in type II OFs, but not type I OFs. Conclusions. We have demonstrated that OFs from TED patients have heterogeneous responses to proproliferative and proadipogenic stimulators in vitro in a manner that corresponds to their different clinical manifestations. Furthermore, we demonstrated a differential effect of COX inhibitors on type I and type II OF proliferation and adipogenesis. PMID:24135759

Non-mineralized fibrocartilage shows the lowest elastic modulus in the rabbit supraspinatus tendon insertion: measurement with scanning acoustic microscopy.

PubMed

Sano, Hirotaka; Saijo, Yoshifumi; Kokubun, Shoichi

2006-01-01

The acoustic properties of rabbit supraspinatus tendon insertions were measured by scanning acoustic microscopy. After cutting parallel to the supraspinatus tendon fibers, specimens were fixed with 10% neutralized formalin, embedded in paraffin, and sectioned. Both the sound speed and the attenuation constant were measured at the insertion site. The 2-dimensional distribution of the sound speed and that of the attenuation constant were displayed with color-coded scales. The acoustic properties reflected both the histologic architecture and the collagen type. In the tendon proper and the non-mineralized fibrocartilage, the sound speed and attenuation constant gradually decreased as the predominant collagen type changed from I to II. In the mineralized fibrocartilage, they increased markedly with the mineralization of the fibrocartilaginous tissue. These results indicate that the non-mineralized fibrocartilage shows the lowest elastic modulus among 4 zones at the insertion site, which could be interpreted as an adaptation to various types of biomechanical stress.

Bioinformatics analysis of organizational and expressional characterizations of the IFNs, IRFs and CRFBs in grass carp Ctenopharyngodon idella.

PubMed

Liao, Zhiwei; Wan, Quanyuan; Su, Jianguo

2016-08-01

Interferons (IFNs) play crucial roles in the immune response of defense against viral infection and bacteria invasion. In the present study, we systematically identified and characterized the IFNs, their regulatory factors (Interferon Regulatory Factors, IRFs) and receptors (Cytokine Receptor Family B, CRFBs) in grass carp (Ctenopharyngodon idella). Grass carp IFNs can be classified into type I IFN (IFN-I) and type II IFN (IFN-II) like other teleosts. IFN-I consist of two groups with two (group I) or four (group II) cysteines in the mature peptide and can be further divided into three subgroups (IFN-a, -c and -d), containing four members: IFN1, IFN2, IFN3, IFN4 in grass carp. IFN-II contain two members, IFNγ2 with the similarity to mammalian IFNγ and a cyprinid specific IFNγ1 (IFNγ-rel) molecule. mRNA expression analyses of IFNs discovered that IFN1 and IFN-II were sustainably expressed in many tissues, while other IFN members were transiently expressed in specific tissues and time points. In the immune response, IFN transcriptions are primarily regulated through multiple IRFs after grass carp reovirus (GCRV) challenge. IRF family possess thirteen members in grass carp, which can be further divided into four subfamilies (IRF-1, -3, -4 and -5 subfamily), each of them plays different roles in the innate and adaptive immunity via various signaling pathways to interact with IFNs (mainly IFN-I). IFNs have to bind receptors (CRFBs) to perform their functions. CRFBs as IFN receptors contain six members in grass carp. The structure and expression characterizations of IFNs, IRFs and CRFBs were analyzed using bioinformatics tools. These results might provide basic data for the further functional research of IFN system, and deeply understand fish immune mechanisms against virus infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optic nerve signals in a neuromorphic chip II: Testing and results.

PubMed

Zaghloul, Kareem A; Boahen, Kwabena

2004-04-01

Seeking to match the brain's computational efficiency, we draw inspiration from its neural circuits. To model the four main output (ganglion) cell types found in the retina, we morphed outer and inner retina circuits into a 96 x 60-photoreceptor, 3.5 x 3.3 mm2, 0.35 microm-CMOS chip. Our retinomorphic chip produces spike trains for 3600 ganglion cells (GCs), and consumes 62.7 mW at 45 spikes/s/GC. This chip, which is the first silicon retina to successfully model inner retina circuitry, approaches the spatial density of the retina. We present experimental measurements showing that the chip's subthreshold current-mode circuits realize luminance adaptation, bandpass spatiotemporal filtering, temporal adaptation and contrast gain control. The four different GC outputs produced by our chip encode light onset or offset in a sustained or transient fashion, producing a quadrature-like representation. The retinomorphic chip's circuit design is described in a companion paper [Zaghloul and Boahen (2004)].

Modelling daily dissolved oxygen concentration using least square support vector machine, multivariate adaptive regression splines and M5 model tree

NASA Astrophysics Data System (ADS)

Heddam, Salim; Kisi, Ozgur

2018-04-01

In the present study, three types of artificial intelligence techniques, least square support vector machine (LSSVM), multivariate adaptive regression splines (MARS) and M5 model tree (M5T) are applied for modeling daily dissolved oxygen (DO) concentration using several water quality variables as inputs. The DO concentration and water quality variables data from three stations operated by the United States Geological Survey (USGS) were used for developing the three models. The water quality data selected consisted of daily measured of water temperature (TE, °C), pH (std. unit), specific conductance (SC, μS/cm) and discharge (DI cfs), are used as inputs to the LSSVM, MARS and M5T models. The three models were applied for each station separately and compared to each other. According to the results obtained, it was found that: (i) the DO concentration could be successfully estimated using the three models and (ii) the best model among all others differs from one station to another.

SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells

PubMed Central

Mossel, Eric C.; Wang, Jieru; Jeffers, Scott; Edeen, Karen E.; Wang, Shuanglin; Cosgrove, Gregory P.; Funk, C. Joel; Manzer, Rizwan; Miura, Tanya A.; Pearson, Leonard D.; Holmes, Kathryn V.; Mason, Robert J.

2008-01-01

Severe acute respiratory syndrome (SARS) is a disease characterized by diffuse alveolar damage. We isolated alveolar type II cells and maintained them in a highly differentiated state. Type II cell cultures supported SARS-CoV replication as evidenced by RT-PCR detection of viral subgenomic RNA and an increase in virus titer. Virus titers were maximal by 24 hours and peaked at approximately 105 pfu/mL. Two cell types within the cultures were infected. One cell type was type II cells, which were positive for SP-A, SP-C, cytokeratin, a type II cell-specific monoclonal antibody, and Ep-CAM. The other cell type was composed of spindle-shaped cells that were positive for vimentin and collagen III and likely fibroblasts. Viral replication was not detected in type I-like cells or macrophages. Hence, differentiated adult human alveolar type II cells were infectible but alveolar type I-like cells and alveolar macrophages did not support productive infection. PMID:18022664

The hierarchy of stability and predictability in orthognathic surgery with rigid fixation: an update and extension.

PubMed

Proffit, William R; Turvey, Timothy A; Phillips, Ceib

2007-04-30

A hierarchy of stability exists among the types of surgical movements that are possible with orthognathic surgery. This report updates the hierarchy, focusing on comparison of the stability of procedures when rigid fixation is used. Two procedures not previously placed in the hierarchy now are included: correction of asymmetry is stable with rigid fixation and repositioning of the chin also is very stable. During the first post-surgical year, surgical movements in patients treated for Class II/long face problems tend to be more stable than those treated for Class III problems. Clinically relevant changes (more than 2 mm) occur in a surprisingly large percentage of orthognathic surgery patients from one to five years post-treatment, after surgical healing is complete. During the first post-surgical year, patients treated for Class II/long face problems are more stable than those treated for Class III problems; from one to five years post-treatment, some patients in both groups experience skeletal change, but the Class III patients then are more stable than the Class II/long face patients. Fewer patients exhibit long-term changes in the dental occlusion than skeletal changes, because the dentition usually adapts to the skeletal change.

Alveolar type II cell-fibroblast interactions, synthesis and secretion of surfactant and type I collagen.

PubMed

Griffin, M; Bhandari, R; Hamilton, G; Chan, Y C; Powell, J T

1993-06-01

During alveolar development and alveolar repair close contacts are established between fibroblasts and lung epithelial cells through gaps in the basement membrane. Using co-culture systems we have investigated whether these close contacts influence synthesis and secretion of the principal surfactant apoprotein (SP-A) by cultured rat lung alveolar type II cells and the synthesis and secretion of type I collagen by fibroblasts. The alveolar type II cells remained cuboidal and grew in colonies on fibroblast feeder layers and on Matrigel-coated cell culture inserts but were progressively more flattened on fixed fibroblast monolayers and plastic. Alveolar type II cells cultured on plastic released almost all their SP-A into the medium by 4 days. Alveolar type II cells cultured on viable fibroblasts or Matrigel-coated inserts above fibroblasts accumulated SP-A in the medium at a constant rate for the first 4 days, and probably recycle SP-A by endocytosis. The amount of mRNA for SP-A was very low after 4 days of culture of alveolar type II cells on plastic, Matrigel-coated inserts or fixed fibroblast monolayers: relatively, the amount of mRNA for SP-A was increased 4-fold after culture of alveolar type II cells on viable fibroblasts. Co-culture of alveolar type II cells with confluent human dermal fibroblasts stimulated by 2- to 3-fold the secretion of collagen type I into the culture medium, even after the fibroblasts' growth had been arrested with mitomycin C. Collagen secretion, by fibroblasts, also was stimulated 2-fold by conditioned medium from alveolar type II cells cultured on Matrigel. The amount of mRNA for type I collagen increased only modestly when fibroblasts were cultured in this conditioned medium. This stimulation of type I collagen secretion diminished as the conditioned medium was diluted out, but at high dilutions further stimulation occurred, indicating that a factor that inhibited collagen secretion also was being diluted out. The conditioned medium contained low levels of IGF-1 and the stimulation of type I collagen secretion was abolished when the conditioned medium was pre-incubated with antibodies to insulin-like growth factor 1 (IGF-1). There are important reciprocal interactions between alveolar type II cells and fibroblasts in co-culture. Direct contacts between alveolar type II cells and fibroblasts appear to have a trophic effect on cultured alveolar type II cells, increasing the levels of mRNA for SP-A. Rat lung alveolar type II cells appear to release a factor (possibly IGF-1) that stimulates type I collagen secretion by fibroblasts.

Excitonic transitions in highly efficient (GaIn)As/Ga(AsSb) type-II quantum-well structures

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

Gies, S.; Kruska, C.; Berger, C.

2015-11-02

The excitonic transitions of the type-II (GaIn)As/Ga(AsSb) gain medium of a “W”-laser structure are characterized experimentally by modulation spectroscopy and analyzed using microscopic quantum theory. On the basis of the very good agreement between the measured and calculated photoreflectivity, the type-I or type-II character of the observable excitonic transitions is identified. Whereas the energetically lowest three transitions exhibit type-II character, the subsequent energetically higher transitions possess type-I character with much stronger dipole moments. Despite the type-II character, the quantum-well structure exhibits a bright luminescence.

Brief Report: Adaptive Functioning in Children with ASD, ADHD and ASD + ADHD

ERIC Educational Resources Information Center

Ashwood, Karen L.; Tye, Charlotte; Azadi, Bahare; Cartwright, Sally; Asherson, Philip; Bolton, Patrick

2015-01-01

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often co-occur. Children with ASD and ADHD demonstrate deficits in adaptive functioning, yet pure and comorbid groups have not been directly compared. Vineland Adaptive Behaviour Scales (VABS-II) data were examined in boys with ASD (n = 17), ADHD (n = 31) and…

Relationships between Adaptive Behaviours, Personal Factors, and Participation of Young Children.

PubMed

Killeen, Hazel; Shiel, Agnes; Law, Mary; O'Donovan, Donough J; Segurado, Ricardo; Anaby, Dana

2017-12-19

To examine the extent to which personal factors (age, socioeconomic grouping, and preterm birth) and adaptive behaviour explain the participation patterns of young children. 65 Children 2-5 years old with and without a history of preterm birth and no physical or intellectual disability were selected by convenience sampling from Galway University Hospital, Ireland. Interviews with parents were conducted using the Adaptive Behaviour Assessment System, Second Edition (ABAS-II) and the Assessment of Preschool Children's Participation (APCP). Linear regression models were used to identify associations between the ABAS-II scores, personal factors, and APCP scores for intensity and diversity of participation. Adaptive behaviour explained 21% of variance in intensity of play, 18% in intensity of Skill Development, 7% in intensity of Active Physical Recreation, and 6% in intensity of Social Activities controlling for age, preterm birth, and socioeconomic grouping. Age explained between 1% and 11% of variance in intensity of participation scores. Adapted behaviour (13%), Age (17%), and socioeconomic grouping (5%) explained a significant percentage of variance in diversity of participation controlling for the other variables.  Adaptive behaviour had a unique contribution to children's intensity and diversity of participation, suggesting its importance.

Stem cells in the Drosophila digestive system.

PubMed

Zeng, Xiankun; Chauhan, Chhavi; Hou, Steven X

2013-01-01

Adult stem cells maintain tissue homeostasis by continuously replenishing damaged, aged and dead cells in any organism. Five types of region and organ-specific multipotent adult stem cells have been identified in the Drosophila digestive system: intestinal stem cells (ISCs) in the posterior midgut; hindgut intestinal stem cells (HISCs) at the midgut/hindgut junction; renal and nephric stem cells (RNSCs) in the Malpighian Tubules; type I gastric stem cells (GaSCs) at foregut/midgut junction; and type II gastric stem cells (GSSCs) at the middle of the midgut. Despite the fact that each type of stem cell is unique to a particular organ, they share common molecular markers and some regulatory signaling pathways. Due to the simpler tissue structure, ease of performing genetic analysis, and availability of abundant mutants, Drosophila serves as an elegant and powerful model system to study complex stem cell biology. The recent discoveries, particularly in the Drosophila ISC system, have greatly advanced our understanding of stem cell self-renewal, differentiation, and the role of stem cells play in tissue homeostasis/regeneration and adaptive tissue growth.

NKT cell subsets as key participants in liver physiology and pathology

PubMed Central

Bandyopadhyay, Keya; Marrero, Idania; Kumar, Vipin

2016-01-01

Natural killer T (NKT) cells are innate-like lymphocytes that generally recognize lipid antigens and are enriched in microvascular compartments of the liver. NKT cells can be activated by self- or microbial-lipid antigens and by signaling through toll-like receptors. Following activation, NKT cells rapidly secrete pro-inflammatory or anti-inflammatory cytokines and chemokines, and thereby determine the milieu for subsequent immunity or tolerance. It is becoming clear that two different subsets of NKT cells—type I and type II—have different modes of antigen recognition and have opposing roles in inflammatory liver diseases. Here we focus mainly on the roles of both NKT cell subsets in the maintenance of immune tolerance and inflammatory diseases in liver. Furthermore, how the differential activation of type I and type II NKT cells influences other innate cells and adaptive immune cells to result in important consequences for tissue integrity is discussed. It is crucial that better reagents, including CD1d tetramers, be used in clinical studies to define the roles of NKT cells in liver diseases in patients. PMID:26972772

Bayesian adaptive phase II screening design for combination trials

PubMed Central

Cai, Chunyan; Yuan, Ying; Johnson, Valen E

2013-01-01

Background Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Methods Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Results Simulation studies show that the proposed design substantially outperforms the conventional multiarm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while allocating substantially more patients to efficacious treatments. Limitations The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. Conclusions The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while providing higher power to identify the best treatment at the end of the trial. PMID:23359875

A literature review of applied adaptive design methodology within the field of oncology in randomised controlled trials and a proposed extension to the CONSORT guidelines.

PubMed

Mistry, Pankaj; Dunn, Janet A; Marshall, Andrea

2017-07-18

The application of adaptive design methodology within a clinical trial setting is becoming increasingly popular. However the application of these methods within trials is not being reported as adaptive designs hence making it more difficult to capture the emerging use of these designs. Within this review, we aim to understand how adaptive design methodology is being reported, whether these methods are explicitly stated as an 'adaptive design' or if it has to be inferred and to identify whether these methods are applied prospectively or concurrently. Three databases; Embase, Ovid and PubMed were chosen to conduct the literature search. The inclusion criteria for the review were phase II, phase III and phase II/III randomised controlled trials within the field of Oncology that published trial results in 2015. A variety of search terms related to adaptive designs were used. A total of 734 results were identified, after screening 54 were eligible. Adaptive designs were more commonly applied in phase III confirmatory trials. The majority of the papers performed an interim analysis, which included some sort of stopping criteria. Additionally only two papers explicitly stated the term 'adaptive design' and therefore for most of the papers, it had to be inferred that adaptive methods was applied. Sixty-five applications of adaptive design methods were applied, from which the most common method was an adaptation using group sequential methods. This review indicated that the reporting of adaptive design methodology within clinical trials needs improving. The proposed extension to the current CONSORT 2010 guidelines could help capture adaptive design methods. Furthermore provide an essential aid to those involved with clinical trials.

Controlling false-negative errors in microarray differential expression analysis: a PRIM approach.

PubMed

Cole, Steve W; Galic, Zoran; Zack, Jerome A

2003-09-22

Theoretical considerations suggest that current microarray screening algorithms may fail to detect many true differences in gene expression (Type II analytic errors). We assessed 'false negative' error rates in differential expression analyses by conventional linear statistical models (e.g. t-test), microarray-adapted variants (e.g. SAM, Cyber-T), and a novel strategy based on hold-out cross-validation. The latter approach employs the machine-learning algorithm Patient Rule Induction Method (PRIM) to infer minimum thresholds for reliable change in gene expression from Boolean conjunctions of fold-induction and raw fluorescence measurements. Monte Carlo analyses based on four empirical data sets show that conventional statistical models and their microarray-adapted variants overlook more than 50% of genes showing significant up-regulation. Conjoint PRIM prediction rules recover approximately twice as many differentially expressed transcripts while maintaining strong control over false-positive (Type I) errors. As a result, experimental replication rates increase and total analytic error rates decline. RT-PCR studies confirm that gene inductions detected by PRIM but overlooked by other methods represent true changes in mRNA levels. PRIM-based conjoint inference rules thus represent an improved strategy for high-sensitivity screening of DNA microarrays. Freestanding JAVA application at http://microarray.crump.ucla.edu/focus

Multicomponent Exercise Improves Hemodynamic Parameters and Mobility, but Not Maximal Walking Speed, Transfer Capacity, and Executive Function of Older Type II Diabetic Patients.

PubMed

Coelho Junior, Hélio José; Callado Sanches, Iris; Doro, Marcio; Asano, Ricardo Yukio; Feriani, Daniele Jardim; Brietzke, Cayque; Gonçalves, Ivan de Oliveira; Uchida, Marco Carlos; Capeturo, Erico Chagas; Rodrigues, Bruno

2018-01-01

The present study aimed to investigate the effects of a 6-month multicomponent exercise program (MCEP) on functional, cognitive, and hemodynamic parameters of older Type 2 diabetes mellitus (T2DM) patients. Moreover, additional analyses were performed to evaluate if T2DM patients present impaired adaptability in response to physical exercise when compared to nondiabetic volunteers. A total of 72 T2DM patients and 72 age-matched healthy volunteers (CG) were recruited and submitted to functional, cognitive, and hemodynamic evaluations before and after six months of a MCEP. The program of exercise was performed twice a week at moderate intensity. Results indicate T2DM and nondiabetic patients present an increase in mobility (i.e., usual walking speed) after the MCEP. However, improvements in maximal walking speed, transfer capacity, and executive function were only observed in the CG. On the other hand, only T2DM group reveals a marked decline in blood pressure. In conclusion, data of the current study indicate that a 6-month MCEP improves mobility and reduce blood pressure in T2DM patients. However, maximal walking speed, transfer capacity, and executive function were only improved in CG, indicating that T2DM may present impaired adaptability in response to physical stimulus.

Whole-brain MRI phenotyping in dysplasia-related frontal lobe epilepsy.

PubMed

Hong, Seok-Jun; Bernhardt, Boris C; Schrader, Dewi S; Bernasconi, Neda; Bernasconi, Andrea

2016-02-16

To perform whole-brain morphometry in patients with frontal lobe epilepsy and evaluate the utility of group-level patterns for individualized diagnosis and prognosis. We compared MRI-based cortical thickness and folding complexity between 2 frontal lobe epilepsy cohorts with histologically verified focal cortical dysplasia (FCD) (13 type I; 28 type II) and 41 closely matched controls. Pattern learning algorithms evaluated the utility of group-level findings to predict histologic FCD subtype, the side of the seizure focus, and postsurgical seizure outcome in single individuals. Relative to controls, FCD type I displayed multilobar cortical thinning that was most marked in ipsilateral frontal cortices. Conversely, type II showed thickening in temporal and postcentral cortices. Cortical folding also diverged, with increased complexity in prefrontal cortices in type I and decreases in type II. Group-level findings successfully guided automated FCD subtype classification (type I: 100%; type II: 96%), seizure focus lateralization (type I: 92%; type II: 86%), and outcome prediction (type I: 92%; type II: 82%). FCD subtypes relate to diverse whole-brain structural phenotypes. While cortical thickening in type II may indicate delayed pruning, a thin cortex in type I likely results from combined effects of seizure excitotoxicity and the primary malformation. Group-level patterns have a high translational value in guiding individualized diagnostics. © 2016 American Academy of Neurology.

Type II endoleak after endovascular abdominal aortic aneurysm repair: a conservative approach with selective intervention is safe and cost-effective.

PubMed

Steinmetz, Eric; Rubin, Brian G; Sanchez, Luis A; Choi, Eric T; Geraghty, Patrick J; Baty, Jack; Thompson, Robert W; Flye, M Wayne; Hovsepian, David M; Picus, Daniel; Sicard, Gregorio A

2004-02-01

The conservative versus therapeutic approach to type II endoleak after endovascular repair of abdominal aortic aneurysm (EVAR) has been controversial. The purpose of this study was to evaluate the safety and cost-effectiveness of the conservative approach of embolizing type II endoleak only when persistent for more than 6 months and associated with aneurysm sac growth of 5 mm or more. Data for 486 consecutive patients who underwent EVAR were analyzed for incidence and outcome of type II endoleaks. Spiral computed tomography (CT) scans were reviewed, and patient outcome was evaluated at either office visit or telephone contact. Patients with new or late-appearing type II endoleak were evaluated with spiral CT at 6-month intervals to evaluate both persistence of the endoleak and size of the aneurysm sac. Persistent (>or=6 months) type II endoleak and aneurysm sac growth of 5 mm or greater were treated with either translumbar glue or coil embolization of the lumbar source, or transarterial coil embolization of the inferior mesenteric artery. Type II endoleaks were detected in 90 (18.5%) patients. With a mean follow-up of 21.7 +/- 16 months, only 35 (7.2%) patients had type II endoleak that persisted for 6 months or longer. Aneurysm sac enlargement was noted in 5 patients, representing 1% of the total series. All 5 patients underwent successful translumbar sac embolization (n = 4) or transarterial inferior mesenteric artery embolization (n = 4) at a mean follow-up of 18.2 +/- 8.0 months, with no recurrence or aneurysm sac growth. No patient with treated or untreated type II endoleak has had rupture of the aneurysm. The mean global cost for treatment of persistent type II endoleak associated with aneurysm sac growth was US dollars 6695.50 (hospital cost plus physician reimbursement). Treatment in the 30 patients with persistent type II endoleak but no aneurysm sac growth would have represented an additional cost of US dollars 200000 or more. The presence or absence of a type II endoleak did not affect survival (78% vs 73%) at 48 months. Selective intervention to treat type II endoleak that persists for 6 months and is associated with aneurysm enlargement seems to be both safe and cost-effective. Longer follow-up will determine whether this conservative approach to management of type II endoleak is the standard of care.

NGC628 with SITELLE: I. Imaging spectroscopy of 4285 H II region candidates

NASA Astrophysics Data System (ADS)

Rousseau-Nepton, L.; Robert, C.; Martin, R. P.; Drissen, L.; Martin, T.

2018-07-01

This is the first paper of a series dedicated to nebular physics and the chemical evolution of nearby galaxies by investigating large samples of H II regions with the Canada-France-Hawaii Telescope imaging spectrograph SITELLE (Spectro-Imageur à Transformée de Fourier pour l'Étude en Long et en Large des raies d'Émission). We present a technique adapted to imaging spectroscopy to identify and extract parameters from 4285 H II region candidates found in the disc of NGC 628. Using both the spatial and spectral capabilities of SITELLE, our technique enables the extraction of the position, dust extinction, velocity, H α profile, diffuse ionized gas (DIG) background, luminosity, size, morphological type, and the emission-line fluxes for individual spaxels and the integrated spectrum for each region. We have produced a well-sampled H II region luminosity function and studied its variation with galactocentric radius and level of the DIG background. We found a slope α of -1.12 ± 0.03 with no evidence of a break at high luminosity. Based on the width of the region profile, bright regions are rather compact, while faint regions are seen over a wide range of sizes. The radius function reveals a slope of -1.81 ± 0.02. BPT diagrams of the individual spaxels and integrated line ratios confirm that most detections are H II regions. Also, maps of the line ratios show complex variations of the ionization conditions within H II regions. All this information is compiled in a new catalogue for H II regions. The objective of this data base is to provide a complete sample which will be used to study the whole parameter space covered by the physical conditions in active star-forming regions.

Full-Scale Flight Research Testbeds: Adaptive and Intelligent Control

NASA Technical Reports Server (NTRS)

Pahle, Joe W.

2008-01-01

This viewgraph presentation describes the adaptive and intelligent control methods used for aircraft survival. The contents include: 1) Motivation for Adaptive Control; 2) Integrated Resilient Aircraft Control Project; 3) Full-scale Flight Assets in Use for IRAC; 4) NASA NF-15B Tail Number 837; 5) Gen II Direct Adaptive Control Architecture; 6) Limited Authority System; and 7) 837 Flight Experiments. A simulated destabilization failure analysis along with experience and lessons learned are also presented.

Cells adapted to the proteasome inhibitor 4-hydroxy- 5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival.

PubMed

Princiotta, M F; Schubert, U; Chen, W; Bennink, J R; Myung, J; Crews, C M; Yewdell, J W

2001-01-16

The proteasome is the primary protease used by cells for degrading proteins and generating peptide ligands for class I molecules of the major histocompatibility complex. Based on the properties of cells adapted to grow in the presence of the proteasome inhibitor 4-hydroxy-5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone (NLVS), it was proposed that proteasomes can be replaced by alternative proteolytic systems, particularly a large proteolytic complex with a tripeptidyl peptidase II activity. Here we show that NLVS-adapted cells retain sensitivity to a number of highly specific proteasome inhibitors with regard to antigenic peptide generation, accumulation of polyubiquitinated proteins, degradation of p53, and cell viability. In addition, we show that in the same assays (with a single minor exception), NLVS-adapted cells are about as sensitive as nonselected cells to Ala-Ala-Phe-chloromethylketone, a specific inhibitor of tripeptidyl peptidase II activity. Based on these findings, we conclude that proteasomes still have essential proteolytic functions in adapted cells that are not replaced by Ala-Ala-Phe-chloromethylketone-sensitive proteases.

The Role of NKT Cells in Tumor Immunity

PubMed Central

Terabe, Masaki; Berzofsky, Jay A.

2009-01-01

NKT cells are a relatively newly recognized member of the immune community, with profound effects on the rest of the immune system despite their small numbers. They are true T cells with a T cell receptor (TCR), but unlike conventional T cells that detect peptide antigens presented by conventional major histocompatibility (MHC) molecules, NKT cells recognize lipid antigens presented by CD1d, a non-classical MHC molecule. As members of both the innate and adaptive immune systems, they bridge the gap between these, and respond rapidly to set the tone for subsequent immune responses. They fill a unique niche in providing the immune system a cellular arm to recognize lipid antigens. They play both effector and regulatory roles in infectious and autoimmune diseases. Furthermore, subsets of NKT cells can play distinct and sometimes opposing roles. In cancer, type I NKT cells, defined by their invariant TCR using Vα14Jα18 in mice and Vα24Jα18 in humans, are mostly protective, by producing interferon-γ to activate NK and CD8+ T cells and by activating dendritic cells to make IL-12. In contrast, type II NKT cells, characterized by more diverse TCRs recognizing lipids presented by CD1d, primarily inhibit tumor immunity. Moreover, type I and type II NKT cells counter-regulate each other, forming a new immunoregulatory axis. Because NKT cells respond rapidly, the balance along this axis can greatly influence other immune responses that follow. Therefore, learning to manipulate the balance along the NKT regulatory axis may be critical to devising successful immunotherapies for cancer. PMID:19055947

Effect of nutrient deficiencies on in vitro Th1 and Th2 cytokine response of peripheral blood mononuclear cells to Plasmodium falciparum infection

PubMed Central

2010-01-01

Background An appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology. In malaria endemic countries, this immunological balance may be influenced by micronutrient deficiencies. Methods Peripheral blood mononuclear cells from Tanzanian preschool children were stimulated in vitro with Plasmodium falciparum-parasitized red blood cells to determine T-cell responses to malaria under different conditions of nutrient deficiencies and malaria status. Results The data obtained indicate that zinc deficiency is associated with an increase in TNF response by 37%; 95% CI: 14% to 118% and IFN-γ response by 74%; 95% CI: 24% to 297%. Magnesium deficiency, on the other hand, was associated with an increase in production of IL-13 by 80%; 95% CI: 31% to 371% and a reduction in IFN-γ production. These results reflect a shift in cytokine profile to a more type I cytokine profile and cell-cell mediated responses in zinc deficiency and a type II response in magnesium deficiency. The data also reveal a non-specific decrease in cytokine production in children due to iron deficiency anaemia that is largely associated with malaria infection status. Conclusions The pathological sequels of malaria potentially depend more on the balance between type I and type II cytokine responses than on absolute suppression of these cytokines and this balance may be influenced by a combination of micronutrient deficiencies and malaria status. PMID:20546583

[PS II photochemical efficiency in flag leaf of wheat varieties and its adaptation to strong sun- light intensity on farmland of Xiangride in Qinghai Province, Northwest China].

PubMed

Shi, Sheng-Bo; Chen, Wen-Jie; Shi, Rui; Li, Miao; Zhang, Huai-Gang; Sun, Ya-Nan

2014-09-01

Taking four wheat varieties developed by Northwest Institute of Plateau Biology, Chinese Academy of Sciences, as test materials, with the measurement of content of photosynthetic pigments, leaf area, fresh and dry mass of flag leaf, the PS II photochemistry efficiency of abaxial and adaxial surface of flag leaf and its adaptation to strong solar radiation during the period of heading stage in Xiangride region were investigated with the pulse-modulated in-vivo chlorophyll fluorescence technique. The results indicated that flag leaf angle mainly grew in horizontal state in Gaoyuan 314, Gaoyuan 363 and Gaoyuan 584, and mainly in vertical state in Gaoyuan 913 because of its smaller leaf area and larger width. Photosynthetic pigments were different among the 4 varieties, and positively correlated with intrinsic PS II photochemistry efficiencies (Fv/Fm). In clear days, especially at noon, the photosynthetic photoinhibition was more serious in abaxial surface of flag leaf due to directly facing the solar radiation, but it could recover after reduction of sunlight intensity in the afternoon, which meant that no inactive damage happened in PS II reaction centers. There were significant differences of PS II actual and maximum photochemical efficiencies at the actinic light intensity (ΦPS II and Fv'/Fm') between abaxial and adaxial surface, and their relative variation trends were on the contrary. The photochemical and non-photochemical quenching coefficients (qP and NPQ) had a similar tendency in both abaxial and adaxial surfaces. Although ΦPS II and qP were lower in adaxial surface of flag leaf, the Fv'/Fm' was significantly higher, which indicated that the potential PS II capture efficiency of excited energy was higher. The results demonstrated that process of photochemical and non-photochemical quenching could effectively dissipate excited energy caused by strong solar radiation, and there were higher adaptation capacities in wheat varieties natively cultivated in Qinghai-Tibetan Plateau area.

34 CFR 300.39 - Special education.

Code of Federal Regulations, 2010 CFR

2010-07-01

... hospitals and institutions, and in other settings; and (ii) Instruction in physical education. (2) Special... their parents as a part of the regular education program. (2) Physical education means— (i) The... (ii) Includes special physical education, adapted physical education, movement education, and motor...

Characteristics of interplanetary type II radio emission and the relationship to shock and plasma properties

NASA Technical Reports Server (NTRS)

Lengyel-Frey, D.; Stone, R. G.

1989-01-01

A large sample of type II events is the basis of the present study of the properties of interplanetary type II bursts' radio-emission properties. Type II spectra seem to be composed of fundamental and harmonic components of plasma emission, where the intensity of the fundamental component increases relative to the harmonic as the burst evolves with heliocentric distance; burst average flux density increases as a power of the associated shock's average velocity. Solar wind density structures may have a significant influence on type II bandwidths.

An ecological analysis of food outlet density and prevalence of type II diabetes in South Carolina counties.

PubMed

AlHasan, Dana M; Eberth, Jan Marie

2016-01-05

Studies suggest that the built environment with high numbers of fast food restaurants and convenience stores and low numbers of super stores and grocery stores are related to obesity, type II diabetes mellitus, and other chronic diseases. Since few studies assess these relationships at the county level, we aim to examine fast food restaurant density, convenience store density, super store density, and grocery store density and prevalence of type II diabetes among counties in South Carolina. Pearson's correlation between four types of food outlet densities- fast food restaurants, convenience stores, super stores, and grocery stores- and prevalence of type II diabetes were computed. The relationship between each of these food outlet densities were mapped with prevalence of type II diabetes, and OLS regression analysis was completed adjusting for county-level rates of obesity, physical inactivity, density of recreation facilities, unemployment, households with no car and limited access to stores, education, and race. We showed a significant, negative relationship between fast food restaurant density and prevalence of type II diabetes, and a significant, positive relationship between convenience store density and prevalence of type II diabetes. In adjusted analysis, the food outlet densities (of any type) was not associated with prevalence of type II diabetes. This ecological analysis showed no associations between fast food restaurants, convenience stores, super stores, or grocery stores densities and the prevalence of type II diabetes. Consideration of environmental, social, and cultural determinants, as well as individual behaviors is needed in future research.

Morphological diversity of microstructures occurring in selected recent bivalve shells and their ecological implications

NASA Astrophysics Data System (ADS)

Brom, Krzysztof Roman; Szopa, Krzysztof

2016-12-01

Environmental adaptation of molluscs during evolution has led to form biomineral exoskeleton - shell. The main compound of their shells is calcium carbonate, which is represented by calcite and/or aragonite. The mineral part, together with the biopolymer matrix, forms many types of microstructures, which are differ in texture. Different types of internal shell microstructures are characteristic for some bivalve groups. Studied bivalve species (freshwater species - duck mussel (Anodonta anatina Linnaeus, 1758) and marine species - common cockle (Cerastoderma edule Linnaeus, 1758), lyrate Asiatic hard clam (Meretrix lyrata Sowerby II, 1851) and blue mussel (Mytilus edulis Linnaeus, 1758)) from different locations and environmental conditions, show that the internal shell microstructure with the shell morphology and thickness have critical impact to the ability to survive in changing environment and also to the probability of surviving predator attack. Moreover, more detailed studies on molluscan structures might be responsible for create mechanically resistant nanomaterials.

Detecting Protected Health Information in Heterogeneous Clinical Notes.

PubMed

Henriksson, Aron; Kvist, Maria; Dalianis, Hercules

2017-01-01

To enable secondary use of healthcare data in a privacy-preserving manner, there is a need for methods capable of automatically identifying protected health information (PHI) in clinical text. To that end, learning predictive models from labeled examples has emerged as a promising alternative to rule-based systems. However, little is known about differences with respect to PHI prevalence in different types of clinical notes and how potential domain differences may affect the performance of predictive models trained on one particular type of note and applied to another. In this study, we analyze the performance of a predictive model trained on an existing PHI corpus of Swedish clinical notes and applied to a variety of clinical notes: written (i) in different clinical specialties, (ii) under different headings, and (iii) by persons in different professions. The results indicate that domain adaption is needed for effective detection of PHI in heterogeneous clinical notes.

On the Origin of Reverse Transcriptase-Using CRISPR-Cas Systems and Their Hyperdiverse, Enigmatic Spacer Repertoires.

PubMed

Silas, Sukrit; Makarova, Kira S; Shmakov, Sergey; Páez-Espino, David; Mohr, Georg; Liu, Yi; Davison, Michelle; Roux, Simon; Krishnamurthy, Siddharth R; Fu, Becky Xu Hua; Hansen, Loren L; Wang, David; Sullivan, Matthew B; Millard, Andrew; Clokie, Martha R; Bhaya, Devaki; Lambowitz, Alan M; Kyrpides, Nikos C; Koonin, Eugene V; Fire, Andrew Z

2017-07-11

Cas1 integrase is the key enzyme of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas adaptation module that mediates acquisition of spacers derived from foreign DNA by CRISPR arrays. In diverse bacteria, the cas1 gene is fused (or adjacent) to a gene encoding a reverse transcriptase (RT) related to group II intron RTs. An RT-Cas1 fusion protein has been recently shown to enable acquisition of CRISPR spacers from RNA. Phylogenetic analysis of the CRISPR-associated RTs demonstrates monophyly of the RT-Cas1 fusion, and coevolution of the RT and Cas1 domains. Nearly all such RTs are present within type III CRISPR-Cas loci, but their phylogeny does not parallel the CRISPR-Cas type classification, indicating that RT-Cas1 is an autonomous functional module that is disseminated by horizontal gene transfer and can function with diverse type III systems. To compare the sequence pools sampled by RT-Cas1-associated and RT-lacking CRISPR-Cas systems, we obtained samples of a commercially grown cyanobacterium- Arthrospira platensis Sequencing of the CRISPR arrays uncovered a highly diverse population of spacers. Spacer diversity was particularly striking for the RT-Cas1-containing type III-B system, where no saturation was evident even with millions of sequences analyzed. In contrast, analysis of the RT-lacking type III-D system yielded a highly diverse pool but reached a point where fewer novel spacers were recovered as sequencing depth was increased. Matches could be identified for a small fraction of the non-RT-Cas1-associated spacers, and for only a single RT-Cas1-associated spacer. Thus, the principal source(s) of the spacers, particularly the hypervariable spacer repertoire of the RT-associated arrays, remains unknown. IMPORTANCE While the majority of CRISPR-Cas immune systems adapt to foreign genetic elements by capturing segments of invasive DNA, some systems carry reverse transcriptases (RTs) that enable adaptation to RNA molecules. From analysis of available bacterial sequence data, we find evidence that RT-based RNA adaptation machinery has been able to join with CRISPR-Cas immune systems in many, diverse bacterial species. To investigate whether the abilities to adapt to DNA and RNA molecules are utilized for defense against distinct classes of invaders in nature, we sequenced CRISPR arrays from samples of commercial-scale open-air cultures of Arthrospira platensis , a cyanobacterium that contains both RT-lacking and RT-containing CRISPR-Cas systems. We uncovered a diverse pool of naturally occurring immune memories, with the RT-lacking locus acquiring a number of segments matching known viral or bacterial genes, while the RT-containing locus has acquired spacers from a distinct sequence pool for which the source remains enigmatic. Copyright © 2017 Silas et al.

Acoustic Type-II Weyl Nodes from Stacking Dimerized Chains

NASA Astrophysics Data System (ADS)

Yang, Zhaoju; Zhang, Baile

2016-11-01

Lorentz-violating type-II Weyl fermions, which were missed in Weyl's prediction of nowadays classified type-I Weyl fermions in quantum field theory, have recently been proposed in condensed matter systems. The semimetals hosting type-II Weyl fermions offer a rare platform for realizing many exotic physical phenomena that are different from type-I Weyl systems. Here we construct the acoustic version of a type-II Weyl Hamiltonian by stacking one-dimensional dimerized chains of acoustic resonators. This acoustic type-II Weyl system exhibits distinct features in a finite density of states and unique transport properties of Fermi-arc-like surface states. In a certain momentum space direction, the velocity of these surface states is determined by the tilting direction of the type-II Weyl nodes rather than the chirality dictated by the Chern number. Our study also provides an approach of constructing acoustic topological phases at different dimensions with the same building blocks.

Photoinhibition of Photosystems I and II Using Chlorophyll Fluorescence Measurements

ERIC Educational Resources Information Center

Quiles, Maria Jose

2005-01-01

In this study the photoinhibition of photosystems (PS) I and II caused by exposure to high intensity light in oat ("Avena sativa," var Prevision) is measured by the emission of chlorophyll fluorescence in intact leaves adapted to darkness. The maximal quantum yield of PS II was lower in plants grown under high light intensity than in plants grown…

In silico genomic insights into aspects of food safety and defense mechanisms of a potentially probiotic Lactobacillus pentosus MP-10 isolated from brines of naturally fermented Aloreña green table olives

PubMed Central

Pérez Montoro, Beatriz; Casado Muñoz, María del Carmen; Knapp, Charles W.; Gálvez, Antonio; Benomar, Nabil

2017-01-01

Lactobacillus pentosus MP-10, isolated from brines of naturally fermented Aloreña green table olives, exhibited high probiotic potential. The genome sequence of L. pentosus MP-10 is currently considered the largest genome among lactobacilli, highlighting the microorganism’s ecological flexibility and adaptability. Here, we analyzed the complete genome sequence for the presence of acquired antibiotic resistance and virulence determinants to understand their defense mechanisms and explore its putative safety in food. The annotated genome sequence revealed evidence of diverse mobile genetic elements, such as prophages, transposases and transposons involved in their adaptation to brine-associated niches. In-silico analysis of L. pentosus MP-10 genome sequence identified a CRISPR (clustered regularly interspaced short palindromic repeats)/cas (CRISPR-associated protein genes) as an immune system against foreign genetic elements, which consisted of six arrays (4–12 repeats) and eleven predicted cas genes [CRISPR1 and CRISPR2 consisted of 3 (Type II-C) and 8 (Type I) genes] with high similarity to L. pentosus KCA1. Bioinformatic analyses revealed L. pentosus MP-10 to be absent of acquired antibiotic resistance genes, and most resistance genes were related to efflux mechanisms; no virulence determinants were found in the genome. This suggests that L. pentosus MP-10 could be considered safe and with high-adaptation potential, which could facilitate its application as a starter culture and probiotic in food preparations. PMID:28651019

Mimicry by asx- and ST-turns of the four main types of β-turn in proteins

PubMed Central

Duddy, William J.; Nissink, J. Willem M.; Allen, Frank H.; Milner-White, E. James

2004-01-01

Hydrogen-bonded β-turns in proteins occur in four categories: type I (the most common), type II, type II’, and type I’. Asx-turns resemble β-turns, in that both have an NH. . .OC hydrogen bond forming a ring of 10 atoms. Serine and threonine side chains also commonly form hydrogen-bonded turns, here called ST-turns. Asx-turns and ST-turns can be categorized into four classes, based on side chain rotamers and the conformation of the central turn residue, which are geometrically equivalent to the four types of β-turns. We propose asx- and ST-turns be named using the type I, II, I’, and II’ β-turn nomenclature. Using this, the frequency of occurrence of both asx- and ST-turns is: type II’ > type I > type II > type I’, whereas for β-turns it is type I > type II > type I’ > type II’. Almost all type II asx-turns occur as a recently described three residue feature named an asx-nest. PMID:15459339

Quaternion-based adaptive output feedback attitude control of spacecraft using Chebyshev neural networks.

PubMed

Zou, An-Min; Dev Kumar, Krishna; Hou, Zeng-Guang

2010-09-01

This paper investigates the problem of output feedback attitude control of an uncertain spacecraft. Two robust adaptive output feedback controllers based on Chebyshev neural networks (CNN) termed adaptive neural networks (NN) controller-I and adaptive NN controller-II are proposed for the attitude tracking control of spacecraft. The four-parameter representations (quaternion) are employed to describe the spacecraft attitude for global representation without singularities. The nonlinear reduced-order observer is used to estimate the derivative of the spacecraft output, and the CNN is introduced to further improve the control performance through approximating the spacecraft attitude motion. The implementation of the basis functions of the CNN used in the proposed controllers depends only on the desired signals, and the smooth robust compensator using the hyperbolic tangent function is employed to counteract the CNN approximation errors and external disturbances. The adaptive NN controller-II can efficiently avoid the over-estimation problem (i.e., the bound of the CNNs output is much larger than that of the approximated unknown function, and hence, the control input may be very large) existing in the adaptive NN controller-I. Both adaptive output feedback controllers using CNN can guarantee that all signals in the resulting closed-loop system are uniformly ultimately bounded. For performance comparisons, the standard adaptive controller using the linear parameterization of spacecraft attitude motion is also developed. Simulation studies are presented to show the advantages of the proposed CNN-based output feedback approach over the standard adaptive output feedback approach.

Biomarker-Guided Adaptive Trial Designs in Phase II and Phase III: A Methodological Review

PubMed Central

Antoniou, Miranta; Jorgensen, Andrea L; Kolamunnage-Dona, Ruwanthi

2016-01-01

Background Personalized medicine is a growing area of research which aims to tailor the treatment given to a patient according to one or more personal characteristics. These characteristics can be demographic such as age or gender, or biological such as a genetic or other biomarker. Prior to utilizing a patient’s biomarker information in clinical practice, robust testing in terms of analytical validity, clinical validity and clinical utility is necessary. A number of clinical trial designs have been proposed for testing a biomarker’s clinical utility, including Phase II and Phase III clinical trials which aim to test the effectiveness of a biomarker-guided approach to treatment; these designs can be broadly classified into adaptive and non-adaptive. While adaptive designs allow planned modifications based on accumulating information during a trial, non-adaptive designs are typically simpler but less flexible. Methods and Findings We have undertaken a comprehensive review of biomarker-guided adaptive trial designs proposed in the past decade. We have identified eight distinct biomarker-guided adaptive designs and nine variations from 107 studies. Substantial variability has been observed in terms of how trial designs are described and particularly in the terminology used by different authors. We have graphically displayed the current biomarker-guided adaptive trial designs and summarised the characteristics of each design. Conclusions Our in-depth overview provides future researchers with clarity in definition, methodology and terminology for biomarker-guided adaptive trial designs. PMID:26910238

CRISPR Typing and Antibiotic Resistance Correlates with Polyphyletic Distribution in Human Isolates of Salmonella Kentucky.

PubMed

Vosik, Dorothy; Tewari, Deepanker; Dettinger, Lisa; M'ikanatha, Nkuchia M; Shariat, Nikki W

2018-02-01

Although infrequently associated with reported salmonellosis in humans, Salmonella enterica, subsp. enterica serovar Kentucky (ser. Kentucky) is the most common nonclinical, nonhuman serovar reported in the United States. The goal of this study was to use Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-multi-virulence-locus sequence typing (MVLST) to subtype a collection of human clinical isolates of ser. Kentucky submitted to the Pennsylvania Department of Health and to determine the extent of antibiotic resistance in these strains. This analysis highlighted the polyphyletic nature of ser. Kentucky, and separated our isolates into two groups, Group I and Group II, which were equally represented in our collection. Furthermore, antimicrobial susceptibility testing on all isolates using a National Antimicrobial Resistance Monitoring System (NARMS) panel of antibiotics demonstrated that resistance profiles could be divided into two groups. Group I isolates were resistant to cephems and penicillins, whereas Group II isolates were resistant to quinolones, gentamicin, and sulfisoxazole. Collectively, 50% of isolates were resistant to three or more classes of antibiotics and 30% were resistant to five or more classes. The correlation of antibiotic resistance with the two different lineages may reflect adaptation within two distinct reservoirs of ser. Kentucky, with differential exposure to antimicrobials.

Aphids transform and detoxify the mycotoxin deoxynivalenol via a type II biotransformation mechanism yet unknown in animals.

PubMed

De Zutter, N; Audenaert, K; Arroyo-Manzanares, N; De Boevre, M; Van Poucke, C; De Saeger, S; Haesaert, G; Smagghe, G

2016-12-08

Biotransformation of mycotoxins in animals comprises phase I and phase II metabolisation reactions. For the trichothecene deoxynivalenol (DON), several phase II biotransformation reactions have been described resulting in DON-glutathiones, DON-glucuronides and DON-sulfates made by glutathione-S-transferases, uridine-diphosphoglucuronyl transferases and sulfotransferases, respectively. These metabolites can be easily excreted and are less toxic than their free compounds. Here, we demonstrate for the first time in the animal kingdom the conversion of DON to DON-3-glucoside (DON-3G) via a model system with plant pathogenic aphids. This phase II biotransformation mechanism has only been reported in plants. As the DON-3G metabolite was less toxic for aphids than DON, this conversion is considered a detoxification reaction. Remarkably, English grain aphids (Sitobion avenae) which co-occur with the DON producer Fusarium graminearum on wheat during the development of fusarium symptoms, tolerate DON much better and convert DON to DON-3G more efficiently than pea aphids (Acyrthosiphon pisum), the latter being known to feed on legumes which are no host for F. graminearum. Using a non-targeted high resolution mass spectrometric approach, we detected DON-diglucosides in aphids probably as a result of sequential glucosylation reactions. Data are discussed in the light of an eventual co-evolutionary adaptation of S. avenae to DON.

Aphids transform and detoxify the mycotoxin deoxynivalenol via a type II biotransformation mechanism yet unknown in animals

PubMed Central

De Zutter, N.; Audenaert, K.; Arroyo-Manzanares, N.; De Boevre, M.; Van Poucke, C.; De Saeger, S.; Haesaert, G.; Smagghe, G.

2016-01-01

Biotransformation of mycotoxins in animals comprises phase I and phase II metabolisation reactions. For the trichothecene deoxynivalenol (DON), several phase II biotransformation reactions have been described resulting in DON-glutathiones, DON-glucuronides and DON-sulfates made by glutathione-S-transferases, uridine-diphosphoglucuronyl transferases and sulfotransferases, respectively. These metabolites can be easily excreted and are less toxic than their free compounds. Here, we demonstrate for the first time in the animal kingdom the conversion of DON to DON-3-glucoside (DON-3G) via a model system with plant pathogenic aphids. This phase II biotransformation mechanism has only been reported in plants. As the DON-3G metabolite was less toxic for aphids than DON, this conversion is considered a detoxification reaction. Remarkably, English grain aphids (Sitobion avenae) which co-occur with the DON producer Fusarium graminearum on wheat during the development of fusarium symptoms, tolerate DON much better and convert DON to DON-3G more efficiently than pea aphids (Acyrthosiphon pisum), the latter being known to feed on legumes which are no host for F. graminearum. Using a non-targeted high resolution mass spectrometric approach, we detected DON-diglucosides in aphids probably as a result of sequential glucosylation reactions. Data are discussed in the light of an eventual co-evolutionary adaptation of S. avenae to DON. PMID:27929076

Adaptive Behaviors in High-Functioning Taiwanese Children with Autism Spectrum Disorders: An Investigation of the Mediating Roles of Symptom Severity and Cognitive Ability

ERIC Educational Resources Information Center

Chang, Chen-Lin; Lung, For-Wey; Yen, Cheng-Fang; Yang, Pinchen

2013-01-01

We investigated the relationship among cognitive level, autistic severity and adaptive function in a Taiwanese sample of 94 high-functioning children with autism spectrum disorders (ASD) (mean full scale intelligent quotients FSIQ = 84.8). Parents and teachers both completed the Adaptive Behavior Assessment System-II and the Social Responsiveness…

Prehistory and History of the El Dorado Lake Area, Kansas. Phase II.

DTIC Science & Technology

1981-01-01

environmental condi- tions to which those systems were adapted . These goals pertain to both prehistoric and historic periods with research objectives accomplished...by site reconnaissance, testing and extensive data recovery excavations, and an interdisciplinary analytical approach to understanding human adaptive ...among prehistoric settlement and subsistence systems and the environmental conditions and resources to which they were adapted . Chapter 6 is a

Localization of Usher syndrome type II to chromosome 1q.

PubMed

Kimberling, W J; Weston, M D; Möller, C; Davenport, S L; Shugart, Y Y; Priluck, I A; Martini, A; Milani, M; Smith, R J

1990-06-01

Usher syndrome is characterized by congenital hearing loss, progressive visual impairment due to retinitis pigmentosa, and variable vestibular problems. The two subtypes of Usher syndrome, types I and II, can be distinguished by the degree of hearing loss and by the presence or absence of vestibular dysfunction. Type I is characterized by a profound hearing loss and totally absent vestibular responses, while type II has a milder hearing loss and normal vestibular function. Fifty-five members of eight type II Usher syndrome families were typed for three DNA markers in the distal region of chromosome 1q: D1S65 (pEKH7.4), REN (pHRnES1.9), and D1S81 (pTHH33). Statistically significant linkage was observed for Usher syndrome type II with a maximum multipoint lod score of 6.37 at the position of the marker THH33, thus localizing the Usher type II (USH2) gene to 1q. Nine families with type I Usher syndrome failed to show linkage to the same three markers. The statistical test for heterogeneity of linkage between Usher syndrome types I and II was highly significant, thus demonstrating that they are due to mutations at different genetic loci.

75 FR 43153 - Procurement List Proposed Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

...- LRG XX-LONG 8405-00-NIB-0442--Type II Blouse, Women's, Navy Work Uniform 32 X-SHORT 8405-00-NIB-0443--Type II Blouse, Women's, Navy Work Uniform 32 SHORT 8405-00-NIB-0444--Type II Blouse, Women's, Navy Work Uniform 35 X-SHORT 8405-00-NIB-0445--Type II Blouse, Women's, Navy Work Uniform 35 SHORT 8405-00...

Critical role of the tumor suppressor tuberous sclerosis complex 1 in dendritic cell activation of CD4 T cells by promoting MHC class II expression via IRF4 and CIITA.

PubMed

Pan, Hongjie; O'Brien, Thomas F; Wright, Gabriela; Yang, Jialong; Shin, Jinwook; Wright, Kenneth L; Zhong, Xiao-Ping

2013-07-15

Dendritic cell (DC) maturation is characterized by upregulation of cell-surface MHC class II (MHC-II) and costimulatory molecules, and production of a variety of cytokines that can shape both innate and adaptive immunity. Paradoxically, transcription of the MHC-II genes, as well as its activator, CIITA, is rapidly silenced during DC maturation. The mechanisms that control CIITA/MHC-II expression and silencing have not been fully understood. We report in this article that the tumor suppressor tuberous sclerosis complex 1 (TSC1) is a critical regulator of DC function for both innate and adaptive immunity. Its deficiency in DCs results in increased mammalian target of rapamycin (mTOR) complex 1 but decreased mTORC2 signaling, altered cytokine production, impaired CIITA/MHC-II expression, and defective Ag presentation to CD4 T cells after TLR4 stimulation. We demonstrate further that IFN regulatory factor 4 can directly bind to CIITA promoters, and decreased IFN regulatory factor 4 expression is partially responsible for decreased CIITA/MHC-II expression in TSC1-deficient DCs. Moreover, we identify that CIITA/MHC-II silencing during DC maturation requires mTOR complex 1 activity. Together, our data reveal unexpected roles of TSC1/mTOR that control multifaceted functions of DCs.

Adaptive Filter Design Using Type-2 Fuzzy Cerebellar Model Articulation Controller.

PubMed

Lin, Chih-Min; Yang, Ming-Shu; Chao, Fei; Hu, Xiao-Min; Zhang, Jun

2016-10-01

This paper aims to propose an efficient network and applies it as an adaptive filter for the signal processing problems. An adaptive filter is proposed using a novel interval type-2 fuzzy cerebellar model articulation controller (T2FCMAC). The T2FCMAC realizes an interval type-2 fuzzy logic system based on the structure of the CMAC. Due to the better ability of handling uncertainties, type-2 fuzzy sets can solve some complicated problems with outstanding effectiveness than type-1 fuzzy sets. In addition, the Lyapunov function is utilized to derive the conditions of the adaptive learning rates, so that the convergence of the filtering error can be guaranteed. In order to demonstrate the performance of the proposed adaptive T2FCMAC filter, it is tested in signal processing applications, including a nonlinear channel equalization system, a time-varying channel equalization system, and an adaptive noise cancellation system. The advantages of the proposed filter over the other adaptive filters are verified through simulations.

The response to oestrogen deprivation of the cartilage collagen degradation marker, CTX-II, is unique compared with other markers of collagen turnover

PubMed Central

Bay-Jensen, Anne-Christine; Tabassi, Nadine CB; Sondergaard, Lene V; Andersen, Thomas L; Dagnaes-Hansen, Frederik; Garnero, Patrick; Kassem, Moustapha; Delaissé, Jean-Marie

2009-01-01

Introduction The urinary level of the type II collagen degradation marker CTX-II is increased in postmenopausal women and in ovariectomised rats, suggesting that oestrogen deprivation induces cartilage breakdown. Here we investigate whether this response to oestrogen is also true for other type II collagen turnover markers known to be affected in osteoarthritis, and whether it relates to its presence in specific areas of cartilage tissue. Methods The type II collagen degradation markers CTX-II and Helix-II were measured in the body fluids of premenopausal and postmenopausal women and in those of ovariectomised rats receiving oestrogen or not. Levels of PIIANP, a marker of type II collagen synthesis, were also measured in rats. Rat knee cartilage was analysed for immunoreactivity of CTX-II and PIIANP and for type II collagen expression. Results As expected, urinary levels of CTX-II are significantly increased in postmenopausal women and also in oestrogen-deprived rats, although only transiently. However, in neither case were these elevations paralleled by a significant increase of Helix-II levels and PIIANP levels did not change at any time. CTX-II immunoreactivity and collagen expression were detected in different cartilage areas. The upper zone is the area where CTX-II immunoreactivity and collagen expression best reflected the differences in urinary levels of CTX-II measured in response to oestrogen. However, correlations between urinary levels of CTX-II and tissue immunostainings in individual rats were not statistically significant. Conclusions We found only a small effect of oestrogen deprivation on cartilage. It was detected by CTX-II, but not by other type II collagen turnover markers typically affected in osteoarthritis. PMID:20527083

Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training.

PubMed

West, Daniel W D; Phillips, Stuart M

2012-07-01

The purpose of this study was to investigate associations between acute exercise-induced hormone responses and adaptations to high intensity resistance training in a large cohort (n = 56) of young men. Acute post-exercise serum growth hormone (GH), free testosterone (fT), insulin-like growth factor (IGF-1) and cortisol responses were determined following an acute intense leg resistance exercise routine at the midpoint of a 12-week resistance exercise training study. Acute hormonal responses were correlated with gains in lean body mass (LBM), muscle fibre cross-sectional area (CSA) and leg press strength. There were no significant correlations between the exercise-induced elevations (area under the curve-AUC) of GH, fT and IGF-1 and gains in LBM or leg press strength. Significant correlations were found for cortisol, usually assumed to be a hormone indicative of catabolic drive, AUC with change in LBM (r = 0.29, P < 0.05) and type II fibre CSA (r = 0.35, P < 0.01) as well as GH AUC and gain in fibre area (type I: r = 0.36, P = 0.006; type II: r = 0.28, P = 0.04, but not lean mass). No correlations with strength were observed. We report that the acute exercise-induced systemic hormonal responses of cortisol and GH are weakly correlated with resistance training-induced changes in fibre CSA and LBM (cortisol only), but not with changes in strength.

Redesigning the type II' β-turn in green fluorescent protein to type I': implications for folding kinetics and stability.

PubMed

Madan, Bharat; Sokalingam, Sriram; Raghunathan, Govindan; Lee, Sun-Gu

2014-10-01

Both Type I' and Type II' β-turns have the same sense of the β-turn twist that is compatible with the β-sheet twist. They occur predominantly in two residue β-hairpins, but the occurrence of Type I' β-turns is two times higher than Type II' β-turns. This suggests that Type I' β-turns may be more stable than Type II' β-turns, and Type I' β-turn sequence and structure can be more favorable for protein folding than Type II' β-turns. Here, we redesigned the native Type II' β-turn in GFP to Type I' β-turn, and investigated its effect on protein folding and stability. The Type I' β-turns were designed based on the statistical analysis of residues in natural Type I' β-turns. The substitution of the native "GD" sequence of i+1 and i+2 residues with Type I' preferred "(N/D)G" sequence motif increased the folding rate by 50% and slightly improved the thermodynamic stability. Despite the enhancement of in vitro refolding kinetics and stability of the redesigned mutants, they showed poor soluble expression level compared to wild type. To overcome this problem, i and i + 3 residues of the designed Type I' β-turn were further engineered. The mutation of Thr to Lys at i + 3 could restore the in vivo soluble expression of the Type I' mutant. This study indicates that Type II' β-turns in natural β-hairpins can be further optimized by converting the sequence to Type I'. © 2014 Wiley Periodicals, Inc.

Type II universal spacetimes

NASA Astrophysics Data System (ADS)

Hervik, S.; Málek, T.; Pravda, V.; Pravdová, A.

2015-12-01

We study type II universal metrics of the Lorentzian signature. These metrics simultaneously solve vacuum field equations of all theories of gravitation with the Lagrangian being a polynomial curvature invariant constructed from the metric, the Riemann tensor and its covariant derivatives of an arbitrary order. We provide examples of type II universal metrics for all composite number dimensions. On the other hand, we have no examples for prime number dimensions and we prove the non-existence of type II universal spacetimes in five dimensions. We also present type II vacuum solutions of selected classes of gravitational theories, such as Lovelock, quadratic and L({{Riemann}}) gravities.

Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro

NASA Astrophysics Data System (ADS)

Tamaddon, M.; Burrows, M.; Ferreira, S. A.; Dazzi, F.; Apperley, J. F.; Bradshaw, A.; Brand, D. D.; Czernuszka, J.; Gentleman, E.

2017-03-01

Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.

Integrated care services: lessons learned from the deployment of the NEXES project.

PubMed

Hernández, Carme; Alonso, Albert; Garcia-Aymerich, Judith; Grimsmo, Anders; Vontetsianos, Theodore; García Cuyàs, Francesc; Altes, Anna Garcia; Vogiatzis, Ioannis; Garåsen, Helge; Pellise, Laura; Wienhofen, Leendert; Cano, Isaac; Meya, Montserrat; Moharra, Montserrat; Martinez, Joan Ignasi; Escarrabill, Juan; Roca, Josep

2015-01-01

To identify barriers to deployment of four articulated Integrated Care Services supported by Information Technologies in three European sites. The four services covered the entire spectrum of severity of illness. The project targeted chronic patients with obstructive pulmonary disease, cardiac failure and/or type II diabetes mellitus. One health care sector in Spain (Barcelona) (n = 11.382); six municipalities in Norway (Trondheim) (n = 450); and one hospital in Greece (Athens) (n = 388). The four services were: (i) Home-based long-term maintenance of rehabilitation effects (n = 337); (ii) Enhanced Care for frail patients, n = 1340); (iii) Home Hospitalization and Early Discharge (n = 2404); and Support for remote diagnosis (forced spirometry testing) in primary care (Support) (n = 8139). Both randomized controlled trials and pragmatic study designs were combined. Two technological approaches were compared. The Model for Assessment of Telemedicine applications was adopted. The project demonstrated: (i) Sustainability of training effects over time in chronic patients with obstructive pulmonary disease (p < 0.01); (ii) Enhanced care and fewer hospitalizations in chronic respiratory patients (p < 0.05); (iii) Reduced in-hospital days for all types of patients (p < 0.001) in Home Hospitalization/Early Discharge; and (iv) Increased quality of testing (p < 0.01) for patients with respiratory symptoms in Support, with marked differences among sites. The four integrated care services showed high potential to enhance health outcomes with cost-containment. Change management, technological approach and legal issues were major factors modulating the success of the deployment. The project generated a business plan to foster service sustainability and health innovation. Deployment strategies require site-specific adaptations.

Role of fimV in type II secretion system-dependent protein secretion of Pseudomonas aeruginosa on solid medium.

PubMed

Michel, Gérard P F; Aguzzi, Anthony; Ball, Geneviève; Soscia, Chantal; Bleves, Sophie; Voulhoux, Romé

2011-07-01

Although classical type II secretion systems (T2SSs) are widely present in Gram-negative bacteria, atypical T2SSs can be found in some species. In Pseudomonas aeruginosa, in addition to the classical T2SS Xcp, it was reported that two genes, xphA and xqhA, located outside the xcp locus were organized in an operon (PaQa) which encodes the orphan PaQa subunit. This subunit is able to associate with other components of the classical Xcp machinery to form a functional hybrid T2SS. In the present study, using a transcriptional lacZ fusion, we found that the PaQa operon was more efficiently expressed (i) on solid LB agar than in liquid LB medium, (ii) at 25 °C than at 37 °C and (iii) at an early stage of growth. These results suggested an adaptation of the hybrid system to particular environmental conditions. Transposon mutagenesis led to the finding that vfr and fimV genes are required for optimal expression of the orphan PaQa operon in the defined growth conditions used. Using an original culturing device designed to monitor secretion on solid medium, the ring-plate system, we found that T2SS-dependent secretion of exoproteins, namely the elastase LasB, was affected in a fimV deletion mutant. Our findings led to the discovery of an interplay between FimV and the global regulator Vfr triggering the modulation of the level of Vfr and consequently the modulation of T2SS-dependent secretion on solid medium.

Type II diabetes mellitus and the incidence of epithelial ovarian cancer in the cancer prevention study-II nutrition cohort.

PubMed

Gapstur, Susan M; Patel, Alpa V; Diver, W Ryan; Hildebrand, Janet S; Gaudet, Mia M; Jacobs, Eric J; Campbell, Peter T

2012-11-01

Despite consistent associations of type II diabetes mellitus with hormonally related cancers such as breast and endometrium, the relation between type II diabetes mellitus and ovarian cancer risk is unclear. Associations of type II diabetes mellitus status, duration, and insulin use with epithelial ovarian cancer overall, and with serous and nonserous histologic subtypes were examined in the Cancer Prevention Study-II Nutrition Cohort, a prospective study of U.S. men and women predominantly aged 50 years and older. Between 1992 and 2007, 524 incident epithelial ovarian cancer cases were identified among 63,440 postmenopausal women. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were computed using extended Cox regression to update diabetes status and bilateral oophorectomy status during follow-up. Type II diabetes mellitus status (RR = 1.05; 95% CI, 0.75-1.46) and duration were not associated with epithelial ovarian cancer risk. Although not statistically significantly different (P(difference) = 0.39), the RR was higher for type II diabetes mellitus with insulin use (RR = 1.28; 95% CI, 0.74-2.24) than for type II diabetes mellitus without insulin use (RR = 0.96; 95% CI, 0.64-1.43). Diabetes seemed to be more strongly associated with nonserous (RR = 1.41; 95% CI, 0.70-2.85) than serous (RR = 0.71; 95% CI, 0.41-1.23) histologic subtypes. Type II diabetes mellitus was not associated with risk of epithelial ovarian cancer, although higher risks with nonserous subtypes and among insulin users cannot be ruled out. Larger studies are needed to clarify associations of type II diabetes mellitus with or without insulin use with risk of ovarian cancer overall and by histologic subtypes. ©2012 AACR.

Military Adaptation of Kevlar for Portable Bridge Reinforcement Cables.

DTIC Science & Technology

1980-06-18

WMOFE P T GIBSON OAAKO-78-C-O0ZM UNCLASSIFIED II *3fllIIlfIIIIIIIIflf mhhhhmhm EEIIEIIIEIIII lElllIIhlEllEI EllllEElhlllIE EIIEIIIEIIIII EEllhhEhI 11111...COMMAND FORT BELVOIR, VIRGINIA 22060 L I- ,.- C1 . UNCLASS IF IFfl SECURITY CLASSIFICATION OF THIS PAGE (When Date Entered)REDISUCON II . REPORT NUMBER... ii LIST OF ILLUSTRATIONS . . . . . . . . . . . . vi LIST OF TABLES . . . . . . . . . . . . . . xi INTRODUCTION . . . . . . . . . . . . . . . 1

AUTOMATED BIOCHEMICAL IDENTIFICATION OF BACTERIAL FISH PATHOGENS USING THE ABBOTT QUANTUM II

EPA Science Inventory

The Quantum II, originally designed by Abbott Diagnostics for automated rapid identification of members of Enterobacteriaceae, was adapted for the identification of bacterial fish pathogens. he instrument operates as a spectrophotometer at a wavelength of 492.600 nm. ample cartri...

Linking autoimmunity to the origin of the adaptive immune system.

PubMed

Bayersdorf, Robert; Fruscalzo, Arrigo; Catania, Francesco

2018-01-01

In jawed vertebrates, the adaptive immune system (AIS) cooperates with the innate immune system (IIS) to protect hosts from infections. Although targeting non-self-components, the AIS also generates self-reactive antibodies which, when inadequately counter-selected, can give rise to autoimmune diseases (ADs). ADs are on the rise in western countries. Why haven't ADs been eliminated during the evolution of a ∼500 million-year old system? And why have they become more frequent in recent decades? Self-recognition is an attribute of the phylogenetically more ancient IIS and empirical data compellingly show that some self-reactive antibodies, which are classifiable as elements of the IIS rather then the AIS, may protect from (rather than cause) ADs. Here, we propose that the IIS's self-recognition system originally fathered the AIS and, as a consequence of this relationship, its activity is dampened in hygienic environments. Rather than a mere breakdown or failure of the mechanisms of self-tolerance, ADs might thus arise from architectural constraints.

Refining a complex diagnostic construct: subtyping Dysthymia with the Shedler-Westen Assessment Procedure-II.

PubMed

Huprich, Steven K; Defife, Jared; Westen, Drew

2014-01-01

We sought to determine whether meaningful subtypes of Dysthymic patients could be identified when grouping them by similar personality profiles. A random, national sample of psychiatrists and clinical psychologists (n=1201) described a randomly selected current patient with personality pathology using the descriptors in the Shedler-Westen Assessment Procedure-II (SWAP-II), completed assessments of patients' adaptive functioning, and provided DSM-IV Axis I and II diagnoses. We applied Q-factor cluster analyses to those patients diagnosed with Dysthymic Disorder. Four clusters were identified-High Functioning, Anxious/Dysphoric, Emotionally Dysregulated, and Narcissistic. These factor scores corresponded with a priori hypotheses regarding diagnostic comorbidity and level of adaptive functioning. We compared these groups to diagnostic constructs described and empirically identified in the past literature. The results converge with past and current ideas about the ways in which chronic depression and personality are related and offer an enhanced means by which to understand a heterogeneous diagnostic category that is empirically grounded and clinically useful. © 2013 Published by Elsevier B.V.

A comparative analysis of family adaptability and cohesion ratings among traumatized urban youth.

PubMed

Bellantuono, Alessandro; Saigh, Philip A; Durham, Katherine; Dekis, Constance; Hackler, Dusty; McGuire, Leah A; Yasik, Anastasia E; Halamandaris, Phill V; Oberfield, Richard A

2018-03-01

Given the need to identify psychological risk factors among traumatized youth, this study examined the family functioning of traumatized youth with or without PTSD and a nonclinical sample. The Family Adaptability and Cohesion Evaluation Scales, second edition (FACES II; Olson, Portner, & Bell, 1982), scores of youth with posttraumatic stress disorder (PTSD; n = 29) were compared with the scores of trauma-exposed youth without PTSD (n = 48) and a nontraumatized comparison group (n = 44). Child diagnostic interviews determined that all participants were free of major comorbid disorders. The FACES II scores of the participants with PTSD were not significantly different from the scores of trauma-exposed youth without PTSD and the nontraumatized comparison group. FACES II scores were also not significantly different between the trauma-exposed youth without PTSD and the nontraumatized comparison group. PTSD and trauma-exposure without PTSD were not associated with variations in the perception of family functioning as measured by the FACES II. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

High cell surface death receptor expression determines type I versus type II signaling.

PubMed

Meng, Xue Wei; Peterson, Kevin L; Dai, Haiming; Schneider, Paula; Lee, Sun-Hee; Zhang, Jin-San; Koenig, Alexander; Bronk, Steve; Billadeau, Daniel D; Gores, Gregory J; Kaufmann, Scott H

2011-10-14

Previous studies have suggested that there are two signaling pathways leading from ligation of the Fas receptor to induction of apoptosis. Type I signaling involves Fas ligand-induced recruitment of large amounts of FADD (FAS-associated death domain protein) and procaspase 8, leading to direct activation of caspase 3, whereas type II signaling involves Bid-mediated mitochondrial perturbation to amplify a more modest death receptor-initiated signal. The biochemical basis for this dichotomy has previously been unclear. Here we show that type I cells have a longer half-life for Fas message and express higher amounts of cell surface Fas, explaining the increased recruitment of FADD and subsequent signaling. Moreover, we demonstrate that cells with type II Fas signaling (Jurkat or HCT-15) can signal through a type I pathway upon forced receptor overexpression and that shRNA-mediated Fas down-regulation converts cells with type I signaling (A498) to type II signaling. Importantly, the same cells can exhibit type I signaling for Fas and type II signaling for TRAIL (TNF-α-related apoptosis-inducing ligand), indicating that the choice of signaling pathway is related to the specific receptor, not some other cellular feature. Additional experiments revealed that up-regulation of cell surface death receptor 5 levels by treatment with 7-ethyl-10-hydroxy-camptothecin converted TRAIL signaling in HCT116 cells from type II to type I. Collectively, these results suggest that the type I/type II dichotomy reflects differences in cell surface death receptor expression.

Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

PubMed

Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

2014-01-01

Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Biomarkers of Type II Synthetic Pyrethroid Pesticides in Freshwater Fish

PubMed Central

2014-01-01

Type II synthetic pyrethroids contain an alpha-cyano group which renders them more neurotoxic than their noncyano type I counterparts. A wide array of biomarkers have been employed to delineate the toxic responses of freshwater fish to various type II synthetic pyrethroids. These include hematological, enzymatic, cytological, genetic, omic and other types of biomarkers. This review puts together the applications of different biomarkers in freshwater fish species in response to the toxicity of the major type II pyrethroid pesticides and assesses their present status, while speculating on the possible future directions. PMID:24868555

Biomarkers of type II synthetic pyrethroid pesticides in freshwater fish.

PubMed

Kaviraj, Anilava; Gupta, Abhik

2014-01-01

Type II synthetic pyrethroids contain an alpha-cyano group which renders them more neurotoxic than their noncyano type I counterparts. A wide array of biomarkers have been employed to delineate the toxic responses of freshwater fish to various type II synthetic pyrethroids. These include hematological, enzymatic, cytological, genetic, omic and other types of biomarkers. This review puts together the applications of different biomarkers in freshwater fish species in response to the toxicity of the major type II pyrethroid pesticides and assesses their present status, while speculating on the possible future directions.

Three-year clinical performance of cast gold vs ceramic partial crowns.

PubMed

Federlin, M; Wagner, J; Männer, T; Hiller, K-A; Schmalz, G

2007-12-01

Cast gold partial crowns (CGPC) and partial ceramic crowns (PCC) are both accepted for restoring posterior teeth with extended lesions today. However, as esthetics in dentistry becomes increasingly important, CGPC are being progressively replaced by PCC. The aim of the present prospective split-mouth study was the comparison of the clinical performance of PCC and CGPC after 3 years of clinical service. Twenty-eight patients (11 men and 17 women) participated in the 3-year recall with a total of 56 restorations. In each patient, one CGPC (Degulor C) and one PCC (Vita Mark II ceramic/Cerec III) had been inserted at baseline. CGPC were placed using a zinc phosphate cement (Harvard); PCC were adhesively luted (Variolink II/Excite). All restorations were clinically assessed using modified US Public Health Service (USPHS) criteria at baseline, 1 year, 2 years, and 3 years after insertion. Twenty-eight CGPC and 14 PCC were placed in molars, and 14 PCC were placed in premolars. Early data were reported previously under the same study design. After 3 years, the evaluation according to USPHS criteria revealed no statistically significant differences between both types of restorations with the exception of marginal adaptation and marginal discoloration: A statistically significant difference within the PCC group (baseline/3 years) was determined for the criterion marginal adaptation. For the 3-year recall period, overall failure was 0% for CGPC and 6.9% for PCC. At 3 years, PCC meet American Dental Association Acceptance Guidelines criteria for tooth-colored restorative materials for posterior teeth.

Application of Agree II Instrument for Appraisal of Postpartum Hemorrhage Clinical Practice Guidelines in Bosnia and Herzegovina

PubMed Central

Novo, Ahmed; Subotic-popovic, Andreja; Strbac, Savka; Kandic, Alma; Horga, Mihai

2016-01-01

Introduction: Federal Minister of Health and Minister of Health and Social Welfare of the Republika Srpska as a Governmental health authorities in Federation of Bosnia and Herzegovina (FBiH) and the Republika Srpska nominated/appointed health professionals as their representatives to a multidisciplinary Guidelines Adaptation Group (GAG). This group started with its work in September 2015. The main purpose of the guidelines development exercise is to develop guidelines with worldwide recognized methodology for clinical guidelines development and adaptation. At the end of this consultancy, GAG would have develop a clinical practice guideline on Postpartum hemorrhage (PPH) through the adaptation method, starting from published international clinical guidelines and adapting it according to the country specific requirements. Methodology: During the process of identifying the best guideline for adaptation, the GAG had to pass several steps. One of the crucial steps was to identify the questions related to clinical practice and health policy for which answers are needed to be addressed by the guideline. These questions included relevant issues regarding the topic area such as diagnosis, prognosis, intervention, service delivery, and training. After that, six guidelines have been researched by the six members of the GAG to see if they answered the identified questions. Evaluating the methodological quality of the selected clinical guidelines was a second essential step before deciding which ones could best fit the needs and interests. AGREE II instrument has been chosen as methods for evaluating clinical guideline quality and appropriateness. Four appraisers conducted the assessment of each of the selected guidelines for PPH. All appraisers passed the training for the AGREE II instrument before conducting appraisals, as recommended by the AGREE collaboration. Each of the four guidelines was rated independently with the AGREE II tool by each appraiser. Results: The highest score was obtained by the WHO recommendations for postpartum hemorrhage guidelines and each of four assessors recommended it to be adapted and further implemented. Discussion: In spite of several serous attempts and two Agencies for quality improvement in BiH the whole process of guideline adaptation is still in the beginning and therefore the establishment of a strong connection with similar institutions and organizations from our region and the rest of the world is very important. Cooperation and collaboration across institutions and countries and key stakeholders have potential to significantly improve the validity and quality of the adapted guidelines and to positively influence implementation. PMID:27482138

Sampled Data Adaptive Digital Computer Control of Surface Ship Maneuvers

DTIC Science & Technology

1976-06-01

0.53 feet. Systems fcr which fuel considerations are not a motivating 157 factor lay te designed without this part of the control law ta allow finer...COXXXQXxaQXQ«^2Q£>’^ o>- —,>->>>ozor X < a. Ps4 <i i— « aC _J o < a o-*»-» ujOO • •>- o • •oo«mo z o «j II II ** » < ii ii -^ -* -,-^a:- i—— * O.-IUJ

Factorial and Hierarchical Cluster Analysis of the Adaptive Behavior Scales (Part I & II) in a Population of Older People (50 Years +) with Severe Intellectual Impairment (Mental Handicap).

ERIC Educational Resources Information Center

Moss, S. C.; Hogg, J.

1990-01-01

Principal components analysis was employed on the Adaptive Behavior Scales with scores of 122 older (mean age 63.5) individuals with severe intellectual impairment living in England. The study found the structure of adaptive skills and interpersonal maladaptive behaviors similar to that found for younger retarded adults. Two factors, personal…

Central sympathoexcitatory actions of angiotensin II: role of type 1 angiotensin II receptors.

PubMed

DiBona, G F

1999-01-01

The role of the renin-angiotensin system in the control of sympathetic nerve activity is reviewed. Two general mechanisms are considered, one that involves the effects of circulating angiotensin II (AngII) on the central nervous system and a second that involves the central nervous system effects of AngII that originates within the central nervous system. The role of type 1 AngII receptors in discrete brain sites that mediate the sympathoexcitatory actions of AngII of either circulating or central nervous system origin is examined. AngII of circulating origin has ready access to the subfornical organ and area postrema, where it can bind to type 1 AngII receptors on neurons whose connections to the nucleus tractus solitarius and rostral ventrolateral medulla result in sympathoexcitation. In the rostral ventrolateral medulla, angiotensin peptides of central nervous system origin, likely involving angiotensin species in addition to AngII and binding to receptors other than type 1 or 2 AngII receptors, tonically support sympathetic nerve activity.

On adaptive learning rate that guarantees convergence in feedforward networks.

PubMed

Behera, Laxmidhar; Kumar, Swagat; Patnaik, Awhan

2006-09-01

This paper investigates new learning algorithms (LF I and LF II) based on Lyapunov function for the training of feedforward neural networks. It is observed that such algorithms have interesting parallel with the popular backpropagation (BP) algorithm where the fixed learning rate is replaced by an adaptive learning rate computed using convergence theorem based on Lyapunov stability theory. LF II, a modified version of LF I, has been introduced with an aim to avoid local minima. This modification also helps in improving the convergence speed in some cases. Conditions for achieving global minimum for these kind of algorithms have been studied in detail. The performances of the proposed algorithms are compared with BP algorithm and extended Kalman filtering (EKF) on three bench-mark function approximation problems: XOR, 3-bit parity, and 8-3 encoder. The comparisons are made in terms of number of learning iterations and computational time required for convergence. It is found that the proposed algorithms (LF I and II) are much faster in convergence than other two algorithms to attain same accuracy. Finally, the comparison is made on a complex two-dimensional (2-D) Gabor function and effect of adaptive learning rate for faster convergence is verified. In a nutshell, the investigations made in this paper help us better understand the learning procedure of feedforward neural networks in terms of adaptive learning rate, convergence speed, and local minima.

Clinical and radiographic outcomes of femoral head fractures: excision vs. fixation of fragment in Pipkin type I: what is the optimal choice for femoral head fracture?

PubMed

Park, Kyung-Soon; Lee, Keun-Bae; Na, Bo-Ram; Yoon, Taek-Rim

2015-07-01

In this work, we present relatively long-term results of femoral head fractures with a specific focus on Pipkin type I fractures. Fifty-nine femoral head fractures were treated according to modified Pipkin's classification as follows: type I, small fragment distal to the fovea centralis (FC); type II, large fragment distal to the FC; type III, large fragment proximal to the FC; type IV, comminuted fracture. There were 15 cases of type I, 28 of type II, 9 of type III, and 7 of type IV fractures. Conservative treatment with skeletal traction was performed in 4 type II cases, excision of the fragment in 15 type I and 10 type II cases, fixation of the fragment in 14 type II and all 9 type III cases, and total hip replacement in all 7 type IV cases. The overall clinical and radiographic outcomes were evaluated using previously published criteria, focusing on the results in Pipkin type I fractures with relatively large fragments. Based on Epstein criteria, in type II fractures, excellent or good clinical results were seen in 6 of 10 patients (60.0 %) treated by excision of the fragment and 12 of 14 patients (85.7 %) treated by internal fixation (p = 0.05). Also, excellent or good radiologic results were seen in 4 of 10 (40.0 %) patients treated by excision of the fragment and 12 of 14 (85.7 %) patients treated by internal fixation (p = 0.03). Even in Pipkin type I fractures, if the fragment is large (modified Pipkin type II), early reduction and internal fixation can produce good results.

The DeBakey classification exactly reflects late outcome and re-intervention probability in acute aortic dissection with a slightly modified type II definition.

PubMed

Tsagakis, Konstantinos; Tossios, Paschalis; Kamler, Markus; Benedik, Jaroslav; Natour, Dorgam; Eggebrecht, Holger; Piotrowski, Jarowit; Jakob, Heinz

2011-11-01

The DeBakey classification was used to discriminate the extent of acute aortic dissection (AD) and was correlated to long-term outcome and re-intervention rate. A slight modification of type II subgroup definition was applied by incorporating the aortic arch, when full resectability of the dissection process was given. Between January 2001 and March 2010, 118 patients (64% male, mean age 59 years) underwent surgery for acute AD. As many as 74 were operated on for type I and 44 for type II AD. Complete resection of all entry sites was performed, including antegrade stent grafting for proximal descending lesions. Patients were comparable with respect to demographics and preoperative hemodynamic status. They underwent isolated ascending replacement, hemiarch, or total arch replacement in 7%, 26%, and 67% in type I, versus 27%, 37%, and 36% in type II, respectively. Additional descending stent grafting was performed in 33/74 (45%) type I patients. In-hospital mortality was 14%, 16% (12/74) in type I versus 9% (4/44, type II), p=0.405. After 5 years, the estimated survival rate was 63% in type I versus 80% in type II, p=0.135. In type II, no distal aortic re-intervention was required. In type I, the freedom of distal re-interventions was 82% in patients with additional stent grafting versus 53% in patients without, p=0.022. The slightly modified DeBakey classification exactly reflects late outcome and aortic re-intervention probability. Thus, in type II patients, the aorta seems to be healed without any probability of later re-operation or re-intervention. Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Convergence and Efficiency of Adaptive Importance Sampling Techniques with Partial Biasing

NASA Astrophysics Data System (ADS)

Fort, G.; Jourdain, B.; Lelièvre, T.; Stoltz, G.

2018-04-01

We propose a new Monte Carlo method to efficiently sample a multimodal distribution (known up to a normalization constant). We consider a generalization of the discrete-time Self Healing Umbrella Sampling method, which can also be seen as a generalization of well-tempered metadynamics. The dynamics is based on an adaptive importance technique. The importance function relies on the weights (namely the relative probabilities) of disjoint sets which form a partition of the space. These weights are unknown but are learnt on the fly yielding an adaptive algorithm. In the context of computational statistical physics, the logarithm of these weights is, up to an additive constant, the free-energy, and the discrete valued function defining the partition is called the collective variable. The algorithm falls into the general class of Wang-Landau type methods, and is a generalization of the original Self Healing Umbrella Sampling method in two ways: (i) the updating strategy leads to a larger penalization strength of already visited sets in order to escape more quickly from metastable states, and (ii) the target distribution is biased using only a fraction of the free-energy, in order to increase the effective sample size and reduce the variance of importance sampling estimators. We prove the convergence of the algorithm and analyze numerically its efficiency on a toy example.

A closed-loop neurobotic system for fine touch sensing

NASA Astrophysics Data System (ADS)

Bologna, L. L.; Pinoteau, J.; Passot, J.-B.; Garrido, J. A.; Vogel, J.; Ros Vidal, E.; Arleo, A.

2013-08-01

Objective. Fine touch sensing relies on peripheral-to-central neurotransmission of somesthetic percepts, as well as on active motion policies shaping tactile exploration. This paper presents a novel neuroengineering framework for robotic applications based on the multistage processing of fine tactile information in the closed action-perception loop. Approach. The integrated system modules focus on (i) neural coding principles of spatiotemporal spiking patterns at the periphery of the somatosensory pathway, (ii) probabilistic decoding mechanisms mediating cortical-like tactile recognition and (iii) decision-making and low-level motor adaptation underlying active touch sensing. We probed the resulting neural architecture through a Braille reading task. Main results. Our results on the peripheral encoding of primary contact features are consistent with experimental data on human slow-adapting type I mechanoreceptors. They also suggest second-order processing by cuneate neurons may resolve perceptual ambiguities, contributing to a fast and highly performing online discrimination of Braille inputs by a downstream probabilistic decoder. The implemented multilevel adaptive control provides robustness to motion inaccuracy, while making the number of finger accelerations covariate with Braille character complexity. The resulting modulation of fingertip kinematics is coherent with that observed in human Braille readers. Significance. This work provides a basis for the design and implementation of modular neuromimetic systems for fine touch discrimination in robotics.

Large basolateral processes on type II hair cells comprise a novel processing unit in mammalian vestibular organs

PubMed Central

Pujol, Rémy; Pickett, Sarah B.; Nguyen, Tot Bui; Stone, Jennifer S.

2014-01-01

Sensory receptors in the vestibular system (hair cells) encode head movements and drive central motor reflexes that control gaze, body movements, and body orientation. In mammals, type I and II vestibular hair cells are defined by their shape, contacts with vestibular afferent nerves, and membrane conductance. Here, we describe unique morphological features of type II vestibular hair cells in mature rodents (mice and gerbils) and bats. These features are cytoplasmic processes that extend laterally from the hair cell’s base and project under type I hair cells. Closer analysis of adult mouse utricles demonstrated that the basolateral processes of type II hair cells range in shape, size, and branching, with the longest processes extending 3–4 hair cell widths. The hair cell basolateral processes synapse upon vestibular afferent nerves and receive inputs from vestibular efferent nerves. Further, some basolateral processes make physical contacts with the processes of other type II hair cells, forming some sort of network amongst type II hair cells. Basolateral processes are rare in perinatal mice and do not attain their mature form until 3–6 weeks of age. These observations demonstrate that basolateral processes are significant signaling regions of type II vestibular hair cells, and they suggest type II hair cells may directly communicate with each other, which has not been described in vertebrates. PMID:24825750

Large basolateral processes on type II hair cells are novel processing units in mammalian vestibular organs.

PubMed

Pujol, Rémy; Pickett, Sarah B; Nguyen, Tot Bui; Stone, Jennifer S

2014-10-01

Sensory receptors in the vestibular system (hair cells) encode head movements and drive central motor reflexes that control gaze, body movements, and body orientation. In mammals, type I and II vestibular hair cells are defined by their shape, contacts with vestibular afferent nerves, and membrane conductance. Here we describe unique morphological features of type II vestibular hair cells in mature rodents (mice and gerbils) and bats. These features are cytoplasmic processes that extend laterally from the hair cell base and project under type I hair cells. Closer analysis of adult mouse utricles demonstrated that the basolateral processes of type II hair cells vary in shape, size, and branching, with the longest processes extending three to four hair cell widths. The hair cell basolateral processes synapse upon vestibular afferent nerves and receive inputs from vestibular efferent nerves. Furthermore, some basolateral processes make physical contacts with the processes of other type II hair cells, forming some sort of network among type II hair cells. Basolateral processes are rare in perinatal mice and do not attain their mature form until 3-6 weeks of age. These observations demonstrate that basolateral processes are significant signaling regions of type II vestibular hair cells and suggest that type II hair cells may directly communicate with each other, which has not been described in vertebrates. © 2014 Wiley Periodicals, Inc.

Indirect myosin immunocytochemistry for the identification of fibre types in equine skeletal muscle

NASA Technical Reports Server (NTRS)

Sinha, A. K.; Rose, R. J.; Pozgaj, I.; Hoh, J. F.

1992-01-01

The histochemical ATPase method for muscle fibre typing was first described by Brooke and Kaiser in 1970. However, problems have been found with the subdivision of type II fibres using this technique. To determine whether indirect myosin immunocytochemistry using anti-slow (5-4D), anti-fast (1A10) and anti-fast red (5-2B) monoclonal antibodies with cross reactivity for type I, II and IIa fibres, respectively, in a number of species, could identify three fibre types in equine skeletal muscle, data on fibre type composition and fibre size obtained using the two different techniques were compared. Results indicate that different myosin heavy chains can coexist in single equine muscle fibres. Type I and type II fibres were identified by immunocytochemistry, but subdivision of type II fibres was not possible. Although the percentage of type I and type II fibres was not significantly different for the two techniques, a few fibres reacted with both the 1A10 and 5-4D antibodies.

Immersion vaccination of sockeye salmon (Oncorhynchus nerka) with two pathogenic strains of Vibrio anguillarum

USGS Publications Warehouse

Gould, R.W.; Antipa, R.; Amend, D.F.

1979-01-01

Sockeye salmon (Oncorhynchus nerka) were immersion-vaccinated in suspensions containing 5 × 107, 5 × 106, 5 × 105, or 5 × 104 bacteria/mL of bivalent or monovalent, formalin-killedVibrio anguillarum, Types I and II. The fish were split into two lots and held for 54 d. At that time one lot was challenged with living, virulent V. anguillarum, Type I, and one with living, virulent V.anguillarum, Type II. Immunization with bivalent bacterin effectively protected the fish from vibriosis, but monovalent vaccine was effective only against the homologous challenge. Immunization with the highest concentration of Type I monovalent bacterin resulted in 0% Type I and 58% Type II challenge mortality. Immunization with the highest concentration of Type II monovalent bacterin resulted in 41% Type I and 0% Type II challenge mortality. Immunization with the highest concentration of bivalent Type I/Type II bacterin resulted in 2% mortality in both challenges. Protective bacterins were effective at concentrations down to 5 × 105 bacteria/mL.Key words: immersion vaccination, bivalent vaccines, Vibrio anguillarum, vibriosis.

Immersion vaccination of sockeye salmon (Oncorhynchus kisutch) with two pathogenic strains of Vibrio anguillarum

USGS Publications Warehouse

Gould, R.W.; Antipa, R.; Amend, D.F.

1979-01-01

Sockeye salmon (Oncorhynchus nerka) were immersion-vaccinated in suspensions containing 5 × 107, 5 × 106, 5 × 105, or 5 × 104 bacteria/mL of bivalent or monovalent, formalin-killed Vibrio anguillarum, Types I and II. The fish were split into two lots and held for 54 d. At that time one lot was challenged with living, virulent V. anguillarum, Type I, and one with living, virulent V. anguillarum, Type II. Immunization with bivalent bacterin effectively protected the fish from vibriosis, but monovalent vaccine was effective only against the homologous challenge. Immunization with the highest concentration of Type I monovalent bacterin resulted in 0% Type I and 58% Type II challenge mortality. Immunization with the highest concentration of Type II monovalent bacterin resulted in 41% Type I and 0% Type II challenge mortality. Immunization with the highest concentration of bivalent Type I/Type II bacterin resulted in 2% mortality in both challenges. Protective bacterins were effective at concentrations down to 5 × 105 bacteria/mL. Key words: immersion vaccination, bivalent vaccines, Vibrio anguillarum, vibriosis.

Biochemical and genetic studies in cystinuria: observations on double heterozygotes of genotype I/II

PubMed Central

Morin, Claude L.; Thompson, Margaret W.; Jackson, Sanford H.; Sass-Kortsak, Andrew

1971-01-01

10 families with cystinuria were investigated by measuring: (a) quantitative 24 hr urinary excretion of amino acids by column chromatography; (b) endogenous renal clearances of amino acids and creatinine; (c) intestinal uptake of 34C-labeled L-cystine, L-lysine, and L-arginine using jejunal mucosal biopsies; (d) oral cystine loading tests. All four of these were studied in the probands and the first two in a large number of the family members. 49 members of 8 families were found to have a regular genetic pattern as described previously by Harris, Rosenberg, and their coworkers. Clinical or biochemical differences between the homozygotes type I (recessive cystinuria) and homozygotes type II (incompletely recessive cystinuria) have not been found. Both types excreted similarly excessive amounts of cystine, lysine, arginine, and ornithine, and had high endogenous renal clearances for these four amino acids. Some homozygotes of both types had a cystine clearance higher than the glomerular filtration rate. Jejunal mucosa from both types of homozygotes exhibited near complete inability to concentrate cystine and lysine in vitro. This was also documented in vivo with oral cystine loads. The heterozygotes type I were phenotypically normal with respect to the above four measurements. The heterozygotes type II showed moderate but definite abnormalities in their urinary excretion and their renal clearances of dibasic amino acids. Of the four amino acids concerned, cystine was the most reliable marker to differentiate between the heterozygotes type II and the homozygous normals. In this study, type III cystinuria, as described by Rosenberg, was not encountered. In two additional families, double heterozygotes of genotype I/II were found. The disease affecting these is clinically and biochemically less severe than that affecting homozygotes of either type I or type II. With respect to the four parameters used in this study, the double heterozygotes type I/II have results which are intermediate between those of the homozygotes type I and II and those of the heterozygotes type II. Images PMID:5564399

Enhanced Materials Based on Submonolayer Type-II Quantum Dots

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

Tamargo, Maria C; Kuskovsky, Igor L.; Meriles, Carlos

2017-04-15

We have investigated a nanostructured material known as sub-monolayer type-II QDs, made from wide bandgap II-VI semiconductors. Our goal is to understand and exploit their tunable optical and electrical properties by taking advantage of the type-II band alignment and quantum confinement effects. Type-II ZnTe quantum dots (QDs) in a ZnSe host are particularly interesting because of their relatively large valence band and conduction band offsets. In the current award we have developed new materials based on sub-monolayer type-II QDs that may be advantageous for photovoltaic and spintronics applications. We have also expanded the structural characterization of these materials by refiningmore » the X-ray diffraction methodologies needed to investigate them. In particular, we have 1) demonstrated ZnCdTe/ZnCdSe type-II QDs materials that have ideal properties for the development of novel high efficiency “intermediate band solar cells”, 2) we developed a comprehensive approach to describe and model the growth of these ultra-small type-II QDs, 3) analysis of the evolution of the photoluminescence (PL) emission, combined with other characterization probes allowed us to predict the size and density of the QDs as a function of the growth conditions, 4) we developed and implemented novel sophisticated X-ray diffraction techniques from which accurate size and shape of the buried type-II QDs could be extracted, 5) a correlation of the shape anisotropy with polarization dependent PL was observed, confirming the QDs detailed shape and providing insight about the effects of this shape anisotropy on the physical properties of the type-II QD systems, and 6) a detailed “time-resolved Kerr rotation” investigation has led to the demonstration of enhanced electron spin lifetimes for the samples with large densities of type-II QDs and an understanding of the interplay between the QDs and Te-isoelectroic centers, a defect that forms in the spacer layers that separate the QDs.« less

Rangeland Rummy - a board game to support adaptive management of rangeland-based livestock systems.

PubMed

Farrié, B; Jouven, M; Launay, F; Moreau, J-C; Moulin, C-H; Piquet, M; Taverne, M; Tchakérian, E; Thénard, V; Martin, G

2015-01-01

Rangeland-based livestock systems have to deal with the significant instability and uncertainty of the agricultural context (policy changes, volatility of input prices, etc.), and especially of the climatic context. Thus, they are particularly concerned by adaptive management strategies. To support the development of such strategies, we developed a board game including a computer model called "Rangeland Rummy". It is to be used by groups of farmers and agricultural consultants in the context of short workshops (about 3 h). Rangeland Rummy builds upon five types of material object: (i) a game board; (ii) a calendar stick indicating the starting date of the game board; (iii) sticks marked with the feed resources available for combinations of vegetation types and their management practices; (iv) cards to define animal groups and their feeding requirements throughout the year; (v) cards related to types of feed that can be attributed to animal groups throughout the year. Using these material objects, farmers collectively design a rangeland-based livestock system. This system is immediately evaluated using a computer model, i.e. a spreadsheet providing graphs and indicators providing information on, among other things, the extent to which quantitative and qualitative animal feeding requirements are covered across the year. Playing the game thus consists in collectively and iteratively designing and evaluating rangeland-based livestock systems, while confronting the players with new contextual challenges (e.g. interannual variability of weather, volatility of input prices) or new farmers' objectives (e.g. being self-sufficient for animal feeding). An example of application of Rangeland Rummy with 3 farmers in southern France is reported. Applications show that it tends to develop farmers' adaptive capacity by stimulating their discussions and the exchange of locally-relevant knowledge on management strategies and practices in rangeland-based livestock systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

78 FR 19565 - Call for Expert Reviewers to the U.S. Government Review of the Working Group II Contribution to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... Climate Change (IPCC), Impacts, Adaptation & Vulnerability. SUMMARY: The United States Global Change... on Climate Change (IPCC), Impacts, Adaptation & Vulnerability. The United Nations Environment... socio-economic information for understanding the scientific basis of climate change, potential impacts...

Analyzing the generality of conflict adaptation effects.

PubMed

Funes, Maria Jesús; Lupiáñez, Juan; Humphreys, Glyn

2010-02-01

Conflict adaptation effects refer to the reduction of interference when the incongruent stimulus occurs immediately after an incongruent trial, compared with when it occurs after a congruent trial. The present study analyzes the key conditions that lead to adaptation effects that are specific to the type of conflict involved versus those that are conflict general. In the first 2 experiments, we combined 2 types of conflict for which compatibility arises from clearly different sources in terms of dimensional overlap while keeping the task context constant across conflict types. We found a clear pattern of specificity on conflict adaptation across conflict types. In subsequent experiments, we tested whether this pattern could be accounted in terms of feature integration processes contributing differently to repetition versus alternation of conflict types. The results clearly indicated that feature integration was not key to generating conflict type specificity on conflict adaptation. The data are consistent with there being separate modes of control for different types of cognitive conflict.

Cells adapted to the proteasome inhibitor 4-hydroxy- 5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone require enzymatically active proteasomes for continued survival

PubMed Central

Princiotta, Michael F.; Schubert, Ulrich; Chen, Weisan; Bennink, Jack R.; Myung, Jayhyuk; Crews, Craig M.; Yewdell, Jonathan W.

2001-01-01

The proteasome is the primary protease used by cells for degrading proteins and generating peptide ligands for class I molecules of the major histocompatibility complex. Based on the properties of cells adapted to grow in the presence of the proteasome inhibitor 4-hydroxy-5-iodo-3-nitrophenylacetyl-Leu-Leu-leucinal-vinyl sulfone (NLVS), it was proposed that proteasomes can be replaced by alternative proteolytic systems, particularly a large proteolytic complex with a tripeptidyl peptidase II activity. Here we show that NLVS-adapted cells retain sensitivity to a number of highly specific proteasome inhibitors with regard to antigenic peptide generation, accumulation of polyubiquitinated proteins, degradation of p53, and cell viability. In addition, we show that in the same assays (with a single minor exception), NLVS-adapted cells are about as sensitive as nonselected cells to Ala-Ala-Phe-chloromethylketone, a specific inhibitor of tripeptidyl peptidase II activity. Based on these findings, we conclude that proteasomes still have essential proteolytic functions in adapted cells that are not replaced by Ala-Ala-Phe-chloromethylketone-sensitive proteases. PMID:11149939

High-Throughput Characterization of Cascade type I-E CRISPR Guide Efficacy Reveals Unexpected PAM Diversity and Target Sequence Preferences.

PubMed

Fu, Becky Xu Hua; Wainberg, Michael; Kundaje, Anshul; Fire, Andrew Z

2017-08-01

Interactions between Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) RNAs and CRISPR-associated (Cas) proteins form an RNA-guided adaptive immune system in prokaryotes. The adaptive immune system utilizes segments of the genetic material of invasive foreign elements in the CRISPR locus. The loci are transcribed and processed to produce small CRISPR RNAs (crRNAs), with degradation of invading genetic material directed by a combination of complementarity between RNA and DNA and in some cases recognition of adjacent motifs called PAMs (Protospacer Adjacent Motifs). Here we describe a general, high-throughput procedure to test the efficacy of thousands of targets, applying this to the Escherichia coli type I-E Cascade (CRISPR-associated complex for antiviral defense) system. These studies were followed with reciprocal experiments in which the consequence of CRISPR activity was survival in the presence of a lytic phage. From the combined analysis of the Cascade system, we found that (i) type I-E Cascade PAM recognition is more expansive than previously reported, with at least 22 distinct PAMs, with many of the noncanonical PAMs having CRISPR-interference abilities similar to the canonical PAMs; (ii) PAM positioning appears precise, with no evidence for tolerance to PAM slippage in interference; and (iii) while increased guanine-cytosine (GC) content in the spacer is associated with higher CRISPR-interference efficiency, high GC content (>62.5%) decreases CRISPR-interference efficiency. Our findings provide a comprehensive functional profile of Cascade type I-E interference requirements and a method to assay spacer efficacy that can be applied to other CRISPR-Cas systems. Copyright © 2017 by the Genetics Society of America.

Type II Modic Changes May not Always Represent Fat Degeneration: A Study Using MR Fat Suppression Sequence.

PubMed

Feng, Zhiyun; Liu, Yuanhao; Wei, Wei; Hu, Shengping; Wang, Yue

2016-08-15

A radiological study of type II Modic changes (MCs). The aim of this study was to determine the characteristics of type II MCs on fat suppression (FS) magnetic resonance (MR) images and its association with radiological disc degeneration. Type II MCs are common endplate signal changes on MR images. On the basis of limited histological samples, type II MCs are thought to be stable fat degeneration. FS technique on MR, which can quantify fat content, may be an alternative to explore the pathology of MCs. To date, however, the characteristics of type II MCs on FS sequence have not been studied. Lumbar MR images conducted in a single hospital during a defined period were reviewed to include those with type II MCs and FS images. On FS images, signal status of type II MCs was visually classified as suppressed or not-suppressed. Signal intensity of vertebral regions with and without MCs was measured quantitatively on T2-weighted (T2W) and FS images to calculate fat content index and validate the visual classification. Using image analysis program Osirix, MCs size and adjacent disc degeneration were measured quantitatively. Paired t-tests and logistic regressions were used to determine the associations studied. Sixty-four lumbar MRIs were included and 150 endplates with type II MCs were studied. Although signal of 37 (24.7%) type II MCs was suppressed on FS images, that of 113 (75.3%) was not suppressed. The discs adjacent to type II MCs had lower signal intensity (0.13 ± 0.003 vs. 0.14 ± 0.004, P < 0.001), lesser disc height (9.73 ± 1.97 vs. 11.07 ± 1.99, P < 0.001) and greater bulging area (80.0 ± 31.4 vs. 61.3 ± 27.5 for anterior bulging, 33.72 ± 21.24 vs. 27.93 ± 12.79 for posterior bulging, and 113.7 ± 39.9 vs. 89.2 ± 35.2 for total bulging, P < 0.05) than normal controls. Type II MCs that were not suppressed on FS image were associated with greater age [odds ratio (OR) = 1.11, P < 0.001], lower height (OR = 0.94, P < 0.05), and greater posterior bulging (OR = 1.05, P < 0.001) at the adjacent disc. Signal of most type II MCs was not suppressed on FS MR images, suggesting that there are ongoing complicated pathologies. Type II MCs may not merely represent fat replacement. 3.

Sugar-sweetened beverage intake and the risk of type I and type II endometrial cancer among postmenopausal women.

PubMed

Inoue-Choi, Maki; Robien, Kim; Mariani, Andrea; Cerhan, James R; Anderson, Kristin E

2013-12-01

Sugar-sweetened beverage (SSB) intake has been associated with an increased risk of obesity and type II diabetes. However, its association with endometrial cancer is unclear. We evaluated dietary intake of SSB, fruit juice, sugar-free beverages, sweets/baked goods, starch, and sugars among 23,039 postmenopausal women in the Iowa Women's Health Study. Incident estrogen-dependent type I and estrogen-independent type II endometrial cancers were identified via linkage with the Surveillance Epidemiology and End Results Registry. Risks of type I and type II endometrial cancers were separately compared by energy-adjusted dietary intake in Cox proportional hazards regression models. From 1986 to 2010, 506 type I and 89 type II incident endometrial cancers were identified. An increased risk of type I endometrial cancer was observed with increasing SSB intake after adjustment for body mass index (BMI) and other cofounders (Ptrend = 0.0005). Compared with nondrinkers of SSB, the risk was 78% higher [95% confidence intervals (CI), 1.32-2.40] among women in the highest quintile of SSB intake. The observed association was not modified by BMI, physical activity, history of diabetes, or cigarette smoking. Higher risk of type I endometrial cancer was also observed with higher intake of sugars. None of the dietary items included in the analysis was associated with type II endometrial cancer risk. Higher intake of SSB and sugars was associated with an increased risk of type I, but not type II, endometrial cancer. SSB intake may be a risk factor for type I endometrial cancer regardless of other lifestyle factors. ©2013 AACR.

A Computer-Adaptive Disability Instrument for Lower Extremity Osteoarthritis Research Demonstrated Promising Breadth, Precision and Reliability

PubMed Central

Jette, Alan M.; McDonough, Christine M.; Haley, Stephen M.; Ni, Pengsheng; Olarsch, Sippy; Latham, Nancy; Hambleton, Ronald K.; Felson, David; Kim, Young-jo; Hunter, David

2012-01-01

Objective To develop and evaluate a prototype measure (OA-DISABILITY-CAT) for osteoarthritis research using Item Response Theory (IRT) and Computer Adaptive Test (CAT) methodologies. Study Design and Setting We constructed an item bank consisting of 33 activities commonly affected by lower extremity (LE) osteoarthritis. A sample of 323 adults with LE osteoarthritis reported their degree of limitation in performing everyday activities and completed the Health Assessment Questionnaire-II (HAQ-II). We used confirmatory factor analyses to assess scale unidimensionality and IRT methods to calibrate the items and examine the fit of the data. Using CAT simulation analyses, we examined the performance of OA-DISABILITY-CATs of different lengths compared to the full item bank and the HAQ-II. Results One distinct disability domain was identified. The 10-item OA-DISABILITY-CAT demonstrated a high degree of accuracy compared with the full item bank (r=0.99). The item bank and the HAQ-II scales covered a similar estimated scoring range. In terms of reliability, 95% of OA-DISABILITY reliability estimates were over 0.83 versus 0.60 for the HAQ-II. Except at the highest scores the 10-item OA-DISABILITY-CAT demonstrated superior precision to the HAQ-II. Conclusion The prototype OA-DISABILITY-CAT demonstrated promising measurement properties compared to the HAQ-II, and is recommended for use in LE osteoarthritis research. PMID:19216052

Structural prediction of a novel chitinase from the psychrophilic Glaciozyma antarctica PI12 and an analysis of its structural properties and function

NASA Astrophysics Data System (ADS)

Ramli, Aizi Nor Mazila; Mahadi, Nor Muhammad; Shamsir, Mohd Shahir; Rabu, Amir; Joyce-Tan, Kwee Hong; Murad, Abdul Munir Abdul; Illias, Rosli Md.

2012-08-01

The structure of psychrophilic chitinase (CHI II) from Glaciozyma antarctica PI12 has yet to be studied in detail. Due to its low sequence identity (<30 %), the structural prediction of CHI II is a challenge. A 3D model of CHI II was built by first using a threading approach to search for a suitable template and to generate an optimum target-template alignment, followed by model building using MODELLER9v7. Analysis of the catalytic insertion domain structure in CHI II revealed an increase in the number of aromatic residues and longer loops compared to mesophilic and thermophilic chitinases. A molecular dynamics simulation was used to examine the stability of the CHI II structure at 273, 288 and 300 K. Structural analysis of the substrate-binding cleft revealed a few exposed aromatic residues. Substitutions of certain amino acids in the surface and loop regions of CHI II conferred an increased flexibility to the enzyme, allowing for an adaptation to cold temperatures. A substrate binding comparison of CHI II with the mesophilic chitinase from Coccidioides immitis, 1D2K, suggested that the psychrophilic adaptation and catalytic activity at low temperatures were achieved through a reduction in the number of salt bridges, fewer hydrogen bonds and an increase in the exposure of the hydrophobic side chains to the solvent.

Identification of type II and type III pyoverdine receptors from Pseudomonas aeruginosa.

PubMed

de Chial, Magaly; Ghysels, Bart; Beatson, Scott A; Geoffroy, Valérie; Meyer, Jean Marie; Pattery, Theresa; Baysse, Christine; Chablain, Patrice; Parsons, Yasmin N; Winstanley, Craig; Cordwell, Stuart J; Cornelis, Pierre

2003-04-01

Pseudomonas aeruginosa produces, under conditions of iron limitation, a high-affinity siderophore, pyoverdine (PVD), which is recognized at the level of the outer membrane by a specific TonB-dependent receptor, FpvA. So far, for P. aeruginosa, three different PVDs, differing in their peptide chain, have been described (types I-III), but only the FpvA receptor for type I is known. Two PVD-producing P. aeruginosa strains, one type II and one type III, were mutagenized by a mini-TnphoA3 transposon. In each case, one mutant unable to grow in the presence of the strong iron chelator ethylenediaminedihydroxyphenylacetic acid (EDDHA) and the cognate PVD was selected. The first mutant, which had an insertion in the pvdE gene, upstream of fpvA, was unable to take up type II PVD and showed resistance to pyocin S3, which is known to use type II FpvA as receptor. The second mutant was unable to take up type III PVD and had the transposon insertion in fpvA. Cosmid libraries of the respective type II and type III PVD wild-type strains were constructed and screened for clones restoring the capacity to grow in the presence of PVD. From the respective complementing genomic fragments, type II and type III fpvA sequences were determined. When in trans, type II and type III fpvA restored PVD production, uptake, growth in the presence of EDDHA and, in the case of type II fpvA, pyocin S3 sensitivity. Complementation of fpvA mutants obtained by allelic exchange was achieved by the presence of cognate fpvA in trans. All three receptors posses an N-terminal extension of about 70 amino acids, similar to FecA of Escherichia coli, but only FpvAI has a TAT export sequence at its N-terminal end.

Adapting to the unpredictable: reproductive biology of vertebrates in the Australian wet-dry tropics.

PubMed

Shine, Richard; Brown, Gregory P

2008-01-27

In the wet-dry tropics of northern Australia, temperatures are high and stable year-round but monsoonal rainfall is highly seasonal and variable both annually and spatially. Many features of reproduction in vertebrates of this region may be adaptations to dealing with this unpredictable variation in precipitation, notably by (i) using direct proximate (rainfall-affected) cues to synchronize the timing and extent of breeding with rainfall events, (ii) placing the eggs or offspring in conditions where they will be buffered from rainfall extremes, and (iii) evolving developmental plasticity, such that the timing and trajectory of embryonic differentiation flexibly respond to local conditions. For example, organisms as diverse as snakes (Liasis fuscus, Acrochordus arafurae), crocodiles (Crocodylus porosus), birds (Anseranas semipalmata) and wallabies (Macropus agilis) show extreme annual variation in reproductive rates, linked to stochastic variation in wet season rainfall. The seasonal timing of initiation and cessation of breeding in snakes (Tropidonophis mairii) and rats (Rattus colletti) also varies among years, depending upon precipitation. An alternative adaptive route is to buffer the effects of rainfall variability on offspring by parental care (including viviparity) or by judicious selection of nest sites in oviparous taxa without parental care. A third type of adaptive response involves flexible embryonic responses (including embryonic diapause, facultative hatching and temperature-dependent sex determination) to incubation conditions, as seen in squamates, crocodilians and turtles. Such flexibility fine-tunes developmental rates and trajectories to conditions--especially, rainfall patterns--that are not predictable at the time of oviposition.

Analytical approach to an integrate-and-fire model with spike-triggered adaptation

NASA Astrophysics Data System (ADS)

Schwalger, Tilo; Lindner, Benjamin

2015-12-01

The calculation of the steady-state probability density for multidimensional stochastic systems that do not obey detailed balance is a difficult problem. Here we present the analytical derivation of the stationary joint and various marginal probability densities for a stochastic neuron model with adaptation current. Our approach assumes weak noise but is valid for arbitrary adaptation strength and time scale. The theory predicts several effects of adaptation on the statistics of the membrane potential of a tonically firing neuron: (i) a membrane potential distribution with a convex shape, (ii) a strongly increased probability of hyperpolarized membrane potentials induced by strong and fast adaptation, and (iii) a maximized variability associated with the adaptation current at a finite adaptation time scale.

Ideas II. A Sharing of Teaching Practices by Secondary School Physical Education Practitioners.

ERIC Educational Resources Information Center

Carlson, Ronald P., Ed.

This book describes physical education activity teaching ideas for the secondary school level. The first section describes curriculum ideas in such areas as adapted physical education, quality control, elective physical education, and advanced physical education. Section II describes instructional ideas involving peer teaching, skill improvement,…

Adaptive/nonadaptive proton radiation planning and outcomes in a phase II trial for locally advanced non-small cell lung cancer.

PubMed

Koay, Eugene J; Lege, David; Mohan, Radhe; Komaki, Ritsuko; Cox, James D; Chang, Joe Y

2012-12-01

To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm(3) adaptive and 86.4 cm(3) nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V(70), 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, vs nonadaptive plans. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of type-I/type-II hybrid dye sensitizer with both pyridyl group and catechol unit as anchoring group for type-I/type-II dye-sensitized solar cell.

PubMed

Ooyama, Yousuke; Furue, Kensuke; Enoki, Toshiaki; Kanda, Masahiro; Adachi, Yohei; Ohshita, Joji

2016-11-09

A type-I/type-II hybrid dye sensitizer with a pyridyl group and a catechol unit as the anchoring group has been developed and its photovoltaic performance in dye-sensitized solar cells (DSSCs) is investigated. The sensitizer has the ability to adsorb on a TiO 2 electrode through both the coordination bond at Lewis acid sites and the bidentate binuclear bridging linkage at Brønsted acid sites on the TiO 2 surface, which makes it possible to inject an electron into the conduction band of the TiO 2 electrode by the intramolecular charge-transfer (ICT) excitation (type-I pathway) and by the photoexcitation of the dye-to-TiO 2 charge transfer (DTCT) band (type-II pathway). It was found that the type-I/type-II hybrid dye sensitizer adsorbed on TiO 2 film exhibits a broad photoabsorption band originating from ICT and DTCT characteristics. Here we reveal the photophysical and electrochemical properties of the type-I/type-II hybrid dye sensitizer bearing a pyridyl group and a catechol unit, along with its adsorption modes onto TiO 2 film, and its photovoltaic performance in type-I/type-II DSSC, based on optical (photoabsorption and fluorescence spectroscopy) and electrochemical measurements (cyclic voltammetry), density functional theory (DFT) calculation, FT-IR spectroscopy of the dyes adsorbed on TiO 2 film, photocurrent-voltage (I-V) curves, incident photon-to-current conversion efficiency (IPCE) spectra, and electrochemical impedance spectroscopy (EIS) for DSSC.

Microcomputer Network for Computerized Adaptive Testing (CAT)

DTIC Science & Technology

1984-03-01

PRDC TR 84-33 \\Q.�d-33- \\ MICROCOMPUTER NETWOJlt FOR COMPUTERIZED ADAPTIVE TESTING ( CAT ) Baldwin Quan Thomas A . Park Gary Sandahl John H...ACCEIIION NO NPRDC TR 84-33 4. TITLE (-d Sul>tlllo) MICROCOMP UTER NETWORK FOR COMPUTERIZED ADA PTIVE TESTING ( CAT ) 1. Q B. uan T. A . Park...adaptive testing ( CAT ) Bayesian sequential testing 20. ABSTitACT (Continuo on ro•••• aide II noco .. _, _., ld-tlly ,.,. t.loclt _._.) DO Computerized

Computerized Adaptive Screening Test (CAST): Development for Use in Military Recruiting Stations

DTIC Science & Technology

1984-01-01

testing ( CAT ) 20. ABSTRACT (Continuo on rover .. efdo II neco .. ., ond Identity bJ’ 11/oclr -llor) The Computerized Adaptive Screening Test (CAST...effort is in progress to develop a computerized adaptive testing ( CAT ) system and to evaluate its potential for use in the military entrance...U.S. Marine Corps) has been designated as lead service for CAT system development; and the Navy Personnel Research and Development Center, as lead

The Effects of Weaning Methods on Gut Microbiota Composition and Horse Physiology

PubMed Central

Mach, Núria; Foury, Aline; Kittelmann, Sandra; Reigner, Fabrice; Moroldo, Marco; Ballester, Maria; Esquerré, Diane; Rivière, Julie; Sallé, Guillaume; Gérard, Philippe; Moisan, Marie-Pierre; Lansade, Léa

2017-01-01

Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i) the effect of two different weaning methods on the composition of gut microbiota across time and (ii) how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P) or an abrupt (A) weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d). Different host phenotypes and gut microbiota composition were studied across 6 age strata (days −30, 0, 3, 5, 7, and 30 after weaning) by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella, and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus, on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp.) were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is likely to confer better stress response adaptation following weaning. This study identified potential microbial biomarkers that could predict the likelihood for physiological adaptations to weaning in horses, although causality remains to be addressed. PMID:28790932

The Effects of Weaning Methods on Gut Microbiota Composition and Horse Physiology.

PubMed

Mach, Núria; Foury, Aline; Kittelmann, Sandra; Reigner, Fabrice; Moroldo, Marco; Ballester, Maria; Esquerré, Diane; Rivière, Julie; Sallé, Guillaume; Gérard, Philippe; Moisan, Marie-Pierre; Lansade, Léa

2017-01-01

Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i) the effect of two different weaning methods on the composition of gut microbiota across time and (ii) how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P) or an abrupt (A) weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d). Different host phenotypes and gut microbiota composition were studied across 6 age strata (days -30, 0, 3, 5, 7, and 30 after weaning) by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella , and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus , on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp.) were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is likely to confer better stress response adaptation following weaning. This study identified potential microbial biomarkers that could predict the likelihood for physiological adaptations to weaning in horses, although causality remains to be addressed.

Differential sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy.

PubMed

de Theije, C C; Langen, R C J; Lamers, W H; Gosker, H R; Schols, A M W J; Köhler, S E

2015-01-15

Hypoxia as a consequence of acute and chronic respiratory disease has been associated with muscle atrophy. This study investigated the sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy. Male mice were exposed to 8% normobaric oxygen for up to 21 days. Oxidative soleus and glycolytic extensor digitorum longus (EDL) muscles were isolated, weighed, and assayed for expression profiles of the ubiquitin-proteasome system (UPS), the autophagy-lysosome pathway (ALP), and glucocorticoid receptor (GR) and hypoxia-inducible factor-1α (HIF1α) signaling. Fiber-type composition and the capillary network were investigated. Hypoxia-induced muscle atrophy was more prominent in the EDL than the soleus muscle. Although increased expression of HIF1α target genes showed that both muscle types sensed hypoxia, their adaptive responses differed. Atrophy consistently involved a hypoxia-specific effect (i.e., not attributable to a hypoxia-mediated reduction of food intake) in the EDL only. Hypoxia-specific activation of the UPS and ALP and increased expression of the glucocorticoid receptor (Gr) and its target genes were also mainly observed in the EDL. In the soleus, stimulation of gene expression of those pathways could be mimicked to a large extent by food restriction alone. Hypoxia increased the number of capillary contacts per fiber cross-sectional area in both muscles. In the EDL, this was due to type II fiber atrophy, whereas in the soleus the absolute number of capillary contacts increased. These responses represent two distinct modes to improve oxygen supply to muscle fibers, but may aggravate muscle atrophy in chronic obstructive pulmonary disease patients who have a predominance of type II fibers. Copyright © 2015 the American Physiological Society.

Photopolymerization of highly filled dimethacrylate-based composites using Type I or Type II photoinitiators and varying co-monomer ratios.

PubMed

Randolph, Luc D; Steinhaus, Johannes; Möginger, Bernhard; Gallez, Bernard; Stansbury, Jeffrey; Palin, William M; Leloup, Gaëtane; Leprince, Julian G

2016-02-01

The use of a Type I photoinitiator (monoacylphosphine oxide, MAPO) was described as advantageous in a model formulation, as compared to the conventional Type II photoinitiator (Camphorquinone, CQ). The aim of the present work was to study the kinetics of polymerization of various composite mixtures (20-40-60-80 mol%) of bisphenol A glycidyl dimethacrylate/triethylene glycol dimethacrylate (BisGMA/TegDMA) containing either CQ or MAPO, based on real-time measurements and on the characterization of various post-cure characteristics. Polymerization kinetics were monitored by Fourier-transform near-infrared spectroscopy (FT-NIRS) and dielectric analysis (DEA). A range of postcure properties was also investigated. FT-NIRS and DEA proved complementary to follow the fast kinetics observed with both systems. Autodecceleration occurred after ≈1 s irradiation for MAPO-composites and ≈5-10 s for CQ-composites. Conversion decreased with increasing initial viscosity for both photoinitiating systems. However despite shorter light exposure (3s for MAPO vs 20s for CQ-composites), MAPO-composites yielded higher conversions for all co-monomer mixtures, except at 20 mol% BisGMA, the less viscous material. MAPO systems were associated with increased amounts of trapped free radicals, improved flexural strength and modulus, and reduced free monomer release for all co-monomer ratios, except at 20 mol% BisGMA. This work confirms the major influence of the initiation system both on the conversion and network cross-linking of highly-filled composites, and further highlights the advantages of using MAPO photoinitiating systems in highly-filled dimethacrylate-based composites provided that sufficient BisGMA content (>40 mol%) and adapted light spectrum are used. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Visuospatial learning and memory in the Cebus apella and microglial morphology in the molecular layer of the dentate gyrus and CA1 lacunosum molecular layer.

PubMed

Santos-Filho, Carlos; de Lima, Camila M; Fôro, César A R; de Oliveira, Marcus A; Magalhães, Nara G M; Guerreiro-Diniz, Cristovam; Diniz, Daniel G; Vasconcelos, Pedro F da C; Diniz, Cristovam W P

2014-11-01

We investigated whether the morphology of microglia in the molecular layer of the dentate gyrus (DG-Mol) or in the lacunosum molecular layer of CA1 (CA1-LMol) was correlated with spatial learning and memory in the capuchin monkey (Cebus apella). Learning and memory was tested in 4 monkeys with visuo-spatial, paired associated learning (PAL) tasks from the Cambridge battery of neuropsychological tests. After testing, monkeys were sacrificed, and hippocampi were sectioned. We specifically immunolabeled microglia with an antibody against the adapter binding, ionized calcium protein. Microglia were selected from the middle and outer thirds of the DG-Mol (n=268) and the CA1-LMol (n=185) for three-dimensional reconstructions created with Neurolucida and Neuroexplorer software. Cluster and discriminant analyses, based on microglial morphometric parameters, identified two major morphological microglia phenotypes (types I and II) found in both the CA1-LMol and DG-Mol of all individuals. Compared to type II, type I microglia were significantly smaller, thinner, more tortuous and ramified, and less complex (lower fractal dimensions). PAL performance was both linearly and non-linearly correlated with type I microglial morphological features from the rostral and caudal DG-Mol, but not with microglia from the CA1-LMol. These differences in microglial morphology and correlations with PAL performance were consistent with previous proposals of hippocampal regional contributions for spatial learning and memory. Our results suggested that at least two morphological microglial phenotypes provided distinct physiological roles to learning-associated activity in the rostral and caudal DG-Mol of the monkey brain. Copyright © 2014 Elsevier B.V. All rights reserved.

The hierarchy of stability and predictability in orthognathic surgery with rigid fixation: an update and extension

PubMed Central

Proffit, William R; Turvey, Timothy A; Phillips, Ceib

2007-01-01

A hierarchy of stability exists among the types of surgical movements that are possible with orthognathic surgery. This report updates the hierarchy, focusing on comparison of the stability of procedures when rigid fixation is used. Two procedures not previously placed in the hierarchy now are included: correction of asymmetry is stable with rigid fixation and repositioning of the chin also is very stable. During the first post-surgical year, surgical movements in patients treated for Class II/long face problems tend to be more stable than those treated for Class III problems. Clinically relevant changes (more than 2 mm) occur in a surprisingly large percentage of orthognathic surgery patients from one to five years post-treatment, after surgical healing is complete. During the first post-surgical year, patients treated for Class II/long face problems are more stable than those treated for Class III problems; from one to five years post-treatment, some patients in both groups experience skeletal change, but the Class III patients then are more stable than the Class II/long face patients. Fewer patients exhibit long-term changes in the dental occlusion than skeletal changes, because the dentition usually adapts to the skeletal change. PMID:17470277

Experimental studies and simulations of hydrogen pellet ablation in the stellarator TJ-II

NASA Astrophysics Data System (ADS)

Panadero, N.; McCarthy, K. J.; Koechl, F.; Baldzuhn, J.; Velasco, J. L.; Combs, S. K.; de la Cal, E.; García, R.; Hernández Sánchez, J.; Silvagni, D.; Turkin, Y.; TJ-II Team; W7-X Team

2018-02-01

Plasma core fuelling is a key issue for the development of steady-state scenarios in large magnetically-confined fusion devices, in particular for helical-type machines. At present, cryogenic pellet injection is the most promising technique for efficient fuelling. Here, pellet ablation and fuelling efficiency experiments, using a compact pellet injector, are carried out in electron cyclotron resonance and neutral beam injection heated plasmas of the stellarator TJ-II. Ablation profiles are reconstructed from light emissions collected by silicon photodiodes and a fast-frame camera system, under the assumptions that such emissions are loosely related to the ablation rate and that pellet radial acceleration is negligible. In addition, pellet particle deposition and fuelling efficiency are determined using density profiles provided by a Thomson scattering system. Furthermore, experimental results are compared with ablation and deposition profiles provided by the HPI2 pellet code, which is adapted here for the stellarators Wendelstein 7-X (W7-X) and TJ-II. Finally, the HPI2 code is used to simulate ablation and deposition profiles for pellets of different sizes and velocities injected into relevant W7-X plasma scenarios, while estimating the plasmoid drift and the fuelling efficiency of injections made from two W7-X ports.

INFLUENCE OF TYPE II DIABETES, OBESITY, AND EXPOSURE TO 2, 3, 7, 8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) EXPOSURE ON THE EXPRESSION OF HEPATIC CYP1A2 IN A MURIN MODEL OF TYPE II DIABETES

EPA Science Inventory

Influence of type II diabetes, obesity and exposure 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on the expression of hepatic CYPIA2 in a murine model of type II diabetes. SJ Godin', VM Richardson2, JJ Diliberto2, LS Birnbaum', MJ DeVito2; 'Curriculum In Toxicology, UNC-CH...

Personality Subtypes of Suicidal Adults

PubMed Central

Westen, Drew; Bradley, Rebekah

2009-01-01

Research into personality factors related to suicidality suggests substantial variability among suicide attempters. A potentially useful approach that accounts for this complexity is personality subtyping. As part of a large sample looking at personality pathology, this study used Q-factor analysis to identify subtypes of 311 adult suicide attempters using SWAP-II personality profiles. Identified subtypes included Internalizing, Emotionally Dysregulated, Dependent, Hostile-Isolated, Psychopathic, and Anxious-Somatizing. Subtypes differed in hypothesized ways on criterion variables that address their construct validity, including adaptive functioning, Axis I and II comorbidity, and etiology-related variables (e.g., history of abuse). Furthermore, dimensional ratings of the subtypes predicted adaptive functioning above DSM-based diagnoses and symptoms. PMID:19752649

Vineland-II adaptive behavior profile of children with attention-deficit/hyperactivity disorder or specific learning disorders.

PubMed

Balboni, Giulia; Incognito, Oriana; Belacchi, Carmen; Bonichini, Sabrina; Cubelli, Roberto

2017-02-01

The evaluation of adaptive behavior is informative in children with attention-deficit/hyperactivity disorder (ADHD) or specific learning disorders (SLD). However, the few investigations available have focused only on the gross level of domains of adaptive behavior. To investigate which item subsets of the Vineland-II can discriminate children with ADHD or SLD from peers with typical development. Student's t-tests, ROC analysis, logistic regression, and linear discriminant function analysis were used to compare 24 children with ADHD, 61 elementary students with SLD, and controls matched on age, sex, school level attended, and both parents' education level. Several item subsets that address not only ADHD core symptoms, but also understanding in social context and development of interpersonal relationships, allowed discrimination of children with ADHD from controls. The combination of four item subsets (Listening and attending, Expressing complex ideas, Social communication, and Following instructions) classified children with ADHD with both sensitivity and specificity of 87.5%. Only Reading skills, Writing skills, and Time and dates discriminated children with SLD from controls. Evaluation of Vineland-II scores at the level of item content categories is a useful procedure for an efficient clinical description. Copyright © 2016 Elsevier Ltd. All rights reserved.

What Drives Farmers to Make Top-Down or Bottom-Up Adaptation to Climate Change and Fluctuations? A Comparative Study on 3 Cases of Apple Farming in Japan and South Africa

PubMed Central

Fujisawa, Mariko; Kobayashi, Kazuhiko; Johnston, Peter; New, Mark

2015-01-01

Agriculture is one of the most vulnerable sectors to climate change. Farmers have been exposed to multiple stressors including climate change, and they have managed to adapt to those risks. The adaptation actions undertaken by farmers and their decision making are, however, only poorly understood. By studying adaptation practices undertaken by apple farmers in three regions: Nagano and Kazuno in Japan and Elgin in South Africa, we categorize the adaptation actions into two types: farmer initiated bottom-up adaptation and institution led top-down adaptation. We found that the driver which differentiates the type of adaptation likely adopted was strongly related to the farmers’ characteristics, particularly their dependence on the institutions, e.g. the farmers’ cooperative, in selling their products. The farmers who rely on the farmers’ cooperative for their sales are likely to adopt the institution-led adaptation, whereas the farmers who have established their own sales channels tend to start innovative actions by bottom-up. We further argue that even though the two types have contrasting features, the combinations of the both types of adaptations could lead to more successful adaptation particularly in agriculture. This study also emphasizes that more farm-level studies for various crops and regions are warranted to provide substantial feedbacks to adaptation policy. PMID:25822534

Structural and Biochemical Analyses of Regio- and Stereo-Specificities Observed in a Type II Polyketide Ketoreductase

PubMed Central

Javidpour, Pouya; Korman, Tyler Paz; Shakya, Gaurav; Tsai, Shiou-Chuan

2011-01-01

Type II polyketides include antibiotics such as tetracycline, and chemotherapeutics such as daunorubicin. Type II polyketides are biosynthesized by the type II polyketide synthase (PKS) that consists of 5 – 10 stand-alone domains. In many type II PKSs, the type II ketoreductase (KR) specifically reduce the C9-carbonyl group. How the type II KR achieves such a high regio-specificity, and the nature of stereo-specificity, are not well understood. Sequence alignment of KRs led to a hypothesis that a well-conserved 94-XGG-96 motif may be involved in controlling the stereochemistry. The stereo-specificity of single, double and triple mutant combinations of P94L, G95D and G96D were analyzed in vitro and in vivo for the actinorhodin KR (actKR). The P94L mutation is sufficient to change the stereospecificity of actKR. Binary and ternary crystal structures of both wild type and P94L actKR were solved. Together with assay results, docking simulations, and co-crystal structures, a model for stereochemical control is presented herein that elucidates how type II polyketides are introduced into the substrate pocket such that the C9-carbonyl can be reduced with high regio- and stereo-specificities. The molecular features of actKR important for regio- and stereo-specificities can potentially be applied to biosynthesize new polyketides via protein engineering that rationally controls polyketide ketoreduction. PMID:21506596

The Adaptor Protein SAP Regulates Type II NKT Cell Development, Cytokine Production and Cytotoxicity Against Lymphoma1

PubMed Central

Weng, Xiufang; Liao, Chia-Min; Bagchi, Sreya; Cardell, Susanna L.; Stein, Paul L.; Wang, Chyung-Ru

2014-01-01

CD1d-restricted NKT cells represent a unique lineage of immunoregulatory T cells that are divided into two groups, type I and type II, based on their TCR usage. Because there are no specific tools to identify type II NKT cells, little is known about their developmental requirements and functional regulation. In our previous study, we showed that signaling lymphocytic activation molecule-associated protein (SAP) is essential for the development of type II NKT cells. Here, using a type II NKT cell TCR transgenic mouse model (24αβTg), we demonstrated that CD1d-expressing hematopoietic cells but not thymic epithelial cells meditate efficient selection of type II NKT cells. Further, we showed that SAP regulates type II NKT cell development by controlling Egr2 and PLZF expression. SAP-deficient 24αβ transgenic T cells (24αβ T cells) exhibited an immature phenotype with reduced Th2 cytokine-producing capacity and diminished cytotoxicity to CD1d-expressing lymphoma cells. The impaired IL-4 production by SAP-deficient 24αβ T cells was associated with reduced IRF4 and GATA-3 induction following TCR stimulation. Collectively, these data suggest that SAP is critical for regulating type II NKT cell responses. Aberrant responses of these T cells may contribute to the immune dysregulation observed in X-linked lymphoproliferative disease caused by mutations in SAP. PMID:25236978

The adaptor protein SAP regulates type II NKT-cell development, cytokine production, and cytotoxicity against lymphoma.

PubMed

Weng, Xiufang; Liao, Chia-Min; Bagchi, Sreya; Cardell, Susanna L; Stein, Paul L; Wang, Chyung-Ru

2014-12-01

CD1d-restricted NKT cells represent a unique lineage of immunoregulatory T cells that are divided into two groups, type I and type II, based on their TCR usage. Because there are no specific tools to identify type II NKT cells, little is known about their developmental requirements and functional regulation. In our previous study, we showed that signaling lymphocytic activation molecule associated protein (SAP) is essential for the development of type II NKT cells. Here, using a type II NKT-cell TCR transgenic mouse model, we demonstrated that CD1d-expressing hematopoietic cells, but not thymic epithelial cells, meditate efficient selection of type II NKT cells. Furthermore, we showed that SAP regulates type II NKT-cell development by controlling early growth response 2 protein and promyelocytic leukemia zinc finger expression. SAP-deficient 24αβ transgenic T cells (24αβ T cells) exhibited an immature phenotype with reduced Th2 cytokine-producing capacity and diminished cytotoxicity to CD1d-expressing lymphoma cells. The impaired IL-4 production by SAP-deficient 24αβ T cells was associated with reduced IFN regulatory factor 4 and GATA-3 induction following TCR stimulation. Collectively, these data suggest that SAP is critical for regulating type II NKT cell responses. Aberrant responses of these T cells may contribute to the immune dysregulation observed in X-linked lymphoproliferative disease caused by mutations in SAP. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Herringbone bursts associated with type II solar radio emission

NASA Technical Reports Server (NTRS)

Cairns, I. H.; Robinson, R. D.

1987-01-01

Detailed observations of the herringbone (HB) fine structure on type II solar radio bursts are presented. Data from the Culgoora radiospectrograph, radiometer and radioheliograph are analyzed. The characteristic spectral profiles, frequency drift rates and exciter velocities, fluxes, source sizes, brightness temperatures, and polarizations of individual HB bursts are determined. Correlations between individual bursts within the characteristic groups of bursts and the properties of the associated type II bursts are examined. These data are compatible with HB bursts being radiation at multiples of the plasma frequency generated by electron streams accelerated by the type II shock. HB bursts are physically distinct phenomena from type II and type III bursts, differing significantly in emission processes and/or source conditions; this conclusion indicates that many of the presently available theoretical ideas for HB bursts are incorrect.

Dynamic investigation of DNA bending and wrapping by type II topoisomerases

NASA Astrophysics Data System (ADS)

Shao, Qing; Finzi, Laura; Dunlap, David

2009-11-01

Type II topoisomerases catalyze DNA decatenation and unwinding which is crucial for cell division, and therefore type II topoisomerases are some of the main targets of anti-cancer drugs. A recent crystal structure shows that, during the catalytic cycle, a yeast type II topoimerase can bend a 10 base pair DNA segment by up to 150 degrees. Bacterial gyrase, another type II topoisomerase, can wrap DNA into a tight 180 degree turn. Bending a stiff polymer like DNA requires considerable energy and could represent the rate limiting step in the catalytic (topological) cycle. Using modified deoxyribonucleotides in PCR reactions, stiffer DNA fragments have been produced and used as substrates for topoisomerase II-mediated relaxation of plectonemes introduced in single molecules using magnetic tweezers. The wrapping ability of gyrase decreases for diamino-purine-substituted DNA in which every base pair has three hydrogen-bonds. The overall rate of relaxation of plectonemes by recombinant human topoisomerase II alpha also decreases. These results reveal the dynamic properties of DNA bending and wrapping by type II topisomerases and suggest that A:T base pair melting is a rate determining step for bending and wrapping.

Effective Temperatures for Young Stars in Binaries

NASA Astrophysics Data System (ADS)

Muzzio, Ryan; Avilez, Ian; Prato, Lisa A.; Biddle, Lauren I.; Allen, Thomas; Wright-Garba, Nuria Meilani Laure; Wittal, Matthew

2017-01-01

We have observed about 100 multi-star systems, within the star forming regions Taurus and Ophiuchus, to investigate the individual stellar and circumstellar properties of both components in young T Tauri binaries. Near-infrared spectra were collected using the Keck II telescope’s NIRSPEC spectrograph and imaging data were taken with Keck II’s NIRC2 camera, both behind adaptive optics. Some properties are straightforward to measure; however, determining effective temperature is challenging as the standard method of estimating spectral type and relating spectral type to effective temperature can be subjective and unreliable. We explicitly looked for a relationship between effective temperatures empirically determined in Mann et al. (2015) and equivalent width ratios of H-band Fe and OH lines for main sequence spectral type templates common to both our infrared observations and to the sample of Mann et al. We find a fit for a wide range of temperatures and are currently testing the validity of using this method as a way to determine effective temperature robustly. Support for this research was provided by an REU supplement to NSF award AST-1313399.

Management of Type II Odontoid Fracture for Osteoporotic Bone Structure: Preliminary Report.

PubMed

Cosar, Murat; Ozer, A Fahir; Alkan, Bahadır; Guven, Mustafa; Akman, Tarık; Aras, Adem Bozkurt; Ceylan, Davut; Tokmak, Mehmet

2015-01-01

Anterior transodontoid screw fixation technique is generally chosen for the management of type II odontoid fractures. The nonunion of type II odontoid fractures is still a major problem especially in elderly and osteoporotic patients. Eleven osteoporotic type II odontoid fracured patients were presented in this article. We have divided 11 patients in two groups as classical and Ozer's technique. We have also compared (radiologically and clinically) the classical anterior transodontoid screw fixation (group II: 6 cases) and Ozer's transodontoid screw fixation technique (group I: 5 cases) retrospectively. There was no difference regaring the clinical features of the groups. However, the radiological results showed 100% fusion for Ozer's screw fixation technique and 83% fusion for the classical screw fixation technique. In conclusion, we suggest that Ozer's technique may help to increase the fusion capacity for osteoporotic type II odontoid fractures.

Designing a Semantic Bliki System to Support Different Types of Knowledge and Adaptive Learning

ERIC Educational Resources Information Center

Huang, Shiu-Li; Yang, Chia-Wei

2009-01-01

Though blogs and wikis have been used to support knowledge management and e-learning, existing blogs and wikis cannot support different types of knowledge and adaptive learning. A case in point, types of knowledge vary greatly in category and viewpoints. Additionally, adaptive learning is crucial to improving one's learning performance. This study…

A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges.

PubMed

Chen, Y H Joshua; Gesser, Richard; Luxembourg, Alain

2015-02-01

The licensed four-valent prophylactic human papillomavirus vaccine is highly efficacious in preventing cervical, vulvar, vaginal, and anal cancers and related precancers caused by human papillomavirus types 6, 11, 16, and 18. These four types account for approximately 70% of cervical cancers. A nine-valent human papillomavirus vaccine, including the four original types (6, 11, 16, and 18) plus the next five most prevalent types in cervical cancer (31, 33, 45, 52, and 58) could provide approximately 90% overall cervical cancer coverage. To expedite the nine-valent human papillomavirus vaccine clinical development, an adaptive, seamless Phase IIB/III outcome trial with ∼ 15,000 subjects was conducted to facilitate dose formulation selection and provide pivotal evidence of safety and efficacy for regulatory registrations. We discuss the design rationale and implementation challenges of the outcome trial, focusing on the adaptive feature of the seamless Phase IIB/III design. Subjects were enrolled in two parts (Part A and Part B). Approximately 1240 women, 16-26 years of age, were enrolled in Part A for Phase IIB evaluation and equally randomized to one of three dose formulations of the nine-valent human papillomavirus vaccine or the four-valent human papillomavirus vaccine (active control). Based on an interim analysis of immunogenicity and safety, one dose formulation of the nine-valent human papillomavirus vaccine was selected for evaluation in the Phase III part of the study. Subjects enrolled in Part A who received the selected dose formulation of the nine-valent human papillomavirus vaccine or four-valent human papillomavirus vaccine continued to be followed up and contributed to the final efficacy and safety analyses. In addition, ∼ 13,400 women 16-26 years of age were enrolled in Part B, randomized to nine-valent human papillomavirus vaccine at the selected dose formulation or four-valent human papillomavirus vaccine, and followed for immunogenicity, efficacy, and safety. A seamless Phase IIB/III design was justified by the extensive pre-existing knowledge of the licensed four-valent human papillomavirus vaccine and the development objectives for the nine-valent human papillomavirus vaccine. Subjects enrolled in Part A who received either the selected nine-valent human papillomavirus formulation or four-valent human papillomavirus vaccine contributed ∼ 10% of person-years of follow-up due to its earlier start-thereby maximizing the overall efficiency of the trial. Some of the challenges encountered in the implementation of the adaptive design included practical considerations during Phase IIB formulation selection by internal and external committees, End-of-Phase II discussion with health authorities and managing changes in the assay for immunological endpoints. Application of the experience and lesson learned from this seamless adaptive design to other clinical programs may depend on case-by-case consideration. A seamless Phase IIB/III adaptive design was successfully implemented in this large outcome study. The development time of the second-generation nine-valent human papillomavirus vaccine was shortened due to improved statistical efficiency. © The Author(s) 2014.

Personality Constellations of Adolescents with Histories of Traumatic Parental Separations

PubMed Central

Malone, Johanna C.; Westen, Drew; Levendosky, Alytia A.

2014-01-01

Consistent with attachment theory and a developmental psychopathology framework, a growing body of research suggests that traumatic parental separations may lead to unique pathways of personality adaptation and maladaptation. The present study both examined personality characteristics and identified personality subtypes of adolescents with histories of traumatic separations. Randomly selected psychologists and psychiatrists provided data on 236 adolescents with histories of traumatic separations using a personality pathology instrument designed for use by clinically experienced observers, the Shedler-Westen Assessment Procedure (SWAP-II-A). Using a Q factor analysis, five distinct personality subtypes were identified: internalizing/avoidant, psychopathic, resilient, impulsive dysregulated, and immature dysregulated. Initial support for the validity of the subtypes was established based on Axis I and Axis II pathology, adaptive functioning, developmental history, and family history variables. The personality subtypes demonstrated substantial incremental validity in predicting adaptive functioning, above and beyond demographic variables and histories of other traumatic experiences. PMID:24647212

The Genetics Underlying Natural Variation in the Biotic Interactions of Arabidopsis thaliana: The Challenges of Linking Evolutionary Genetics and Community Ecology.

PubMed

Roux, F; Bergelson, J

2016-01-01

In the context of global change, predicting the responses of plant communities in an ever-changing biotic environment calls for a multipronged approach at the interface of evolutionary genetics and community ecology. However, our understanding of the genetic basis of natural variation involved in mediating biotic interactions, and associated adaptive dynamics of focal plants in their natural communities, is still in its infancy. Here, we review the genetic and molecular bases of natural variation in the response to biotic interactions (viruses, bacteria, fungi, oomycetes, herbivores, and plants) in the model plant Arabidopsis thaliana as well as the adaptive value of these bases. Among the 60 identified genes are a number that encode nucleotide-binding site leucine-rich repeat (NBS-LRR)-type proteins, consistent with early examples of plant defense genes. However, recent studies have revealed an extensive diversity in the molecular mechanisms of defense. Many types of genetic variants associate with phenotypic variation in biotic interactions, even among the genes of large effect that tend to be identified. In general, we found that (i) balancing selection rather than directional selection explains the observed patterns of genetic diversity within A. thaliana and (ii) the cost/benefit tradeoffs of adaptive alleles can be strongly dependent on both genomic and environmental contexts. Finally, because A. thaliana rarely interacts with only one biotic partner in nature, we highlight the benefit of exploring diffuse biotic interactions rather than tightly associated host-enemy pairs. This challenge would help to improve our understanding of coevolutionary quantitative genetics within the context of realistic community complexity. © 2016 Elsevier Inc. All rights reserved.

Electroporation of mRNA as Universal Technology Platform to Transfect a Variety of Primary Cells with Antigens and Functional Proteins.

PubMed

Gerer, Kerstin F; Hoyer, Stefanie; Dörrie, Jan; Schaft, Niels

2017-01-01

Electroporation (EP) of mRNA into human cells is a broadly applicable method to transiently express proteins of choice in a variety of different cell types. We have spent more than a decade to optimize and adapt this method, first for antigen-loading of dendritic cells (DCs), and subsequently for T cells, B cells, bulk PBMCs, and several cell lines. In this regard, antigens were introduced, processed, and presented in context of MHC class I and II. Next to that, functional proteins like adhesion receptors, T-cell receptors (TCRs), chimeric antigen receptors (CARs), constitutively active signal transducers, and others were successfully expressed. We have also established this protocol under full GMP compliance as part of a manufacturing license to produce mRNA-electroporated DCs for therapeutic vaccination in clinical trials. Therefore, we here want to share our universal mRNA electroporation protocol and the experience we have gathered with this method. The advantages of the transfection method presented here are: (1) easy adaptation to different cell types, (2) scalability from 10 6 to approximately 10 8 cells per shot, (3) high transfection efficiency (80-99 %), (4) homogenous protein expression, (5) GMP compliance if the EP is performed in a class A clean room, and (6) no transgene integration into the genome. The provided protocol involves: Opti-MEM® as EP medium, a square-wave pulse with 500 V, and 4 mm cuvettes. To adapt the protocol to differently sized cells, simply the pulse time is altered. Next to the basic protocol, we also provide an extensive list of hints and tricks, which in our opinion are of great value for everyone who intends to use this transfection technique.

[The lysate and recombinant antigens in ELISA-test-systems for diagnostic of herpes simplex].

PubMed

Ganova, L A; Kovtoniuk, G V; Korshun, L N; Kiseleva, E K; Tereshchenko, M I; Vudmaska, M I; Moĭsa, L N; Shevchuk, V A; Spivak, N Ia

2014-08-01

The lysate and recombinant antigens of various production included informula of ELISA-test-systems were analyzed. The ELISA-test-systems are used for detection of IgG to Herpes simplex virus type I and II. For testing the panel of serums PTH 201 (BBI Inc.) were used. The samples of this panel contain antibodies to Herpes simplex virus type I and II in mixed titers. The 69 serums of donors were used too (17 samples had IgG to Herpes simplex virus type I, 23 samples to Herpes simplex virus type II and 29 samples had no antibodies to Herpes simplex virus). The diagnostic capacity of mixture of recombinant antigens gG1 Herpes simplex virus type I and gG2 Herpes simplex virus type II (The research-and-production complex "DiaprofMed") was comparable with mixture of lysate antigen Herpes simplex virus type I and II (Membrane) EIE Antigen ("Virion Ltd."). In the test-systems for differentiation of IgG to Herpes simplex virus type I the recombinant antigen gG1 Herpes simplex virus type I proved to be comparable with commercial analogue Herpes simplex virus-1 gG1M ("Viral Therapeutics Inc."'). At the same time, capacity to detect IgG to Herpes simplex virus type II in recombinant protein gG2 Herpes simplex virus type II is significantly higher than in its analogue Herpes simplex virus-2 gG2c ("Viral Therapeutics Inc.").

THE EFFECTS OF TYPE II BINDING ON METABOLIC STABILITY AND BINDING AFFINITY IN CYTOCHROME P450 CYP3A4

PubMed Central

Peng, Chi-Chi; Pearson, Josh T.; Rock, Dan A.; Joswig-Jones, Carolyn A.; Jones, Jeffrey P.

2010-01-01

One goal in drug design is to decrease clearance due to metabolism. It has been suggested that a compound’s metabolic stability can be increased by incorporation of a sp2 nitrogen into an aromatic ring. Nitrogen incorporation is hypothesized to increase metabolic stability by coordination of nitrogen to the heme iron (termed type II binding). However, questions regarding binding affinity, metabolic stability, and how metabolism of type II binders occurs remain unanswered. Herein, we use pyridinyl quinoline-4-carboxamide analogs to answer these questions. We show that type II binding can have a profound influence on binding affinity for CYP3A4, and the difference in binding affinity can be as high as 1,200 fold. We also find that type II binding compounds can be extensively metabolized, which is not consistent with the dead-end complex kinetic model assumed for type II binders. Two alternate kinetic mechanisms are presented to explain the results. The first involves a rapid equilibrium between the type II bound substrate and a metabolically oriented binding mode. The second involves direct reduction of the nitrogen-coordinated heme followed by oxygen binding. PMID:20346909

Pasteurella multocida isolated from wild birds of North America: a serotype and DNA fingerprint study of isolates from 1978 to 1993

USGS Publications Warehouse

Wilson, M.A.; Duncan, R.M.; Nordholm, G.E.; Berlowski, B.M.

1995-01-01

Serotype and DNA fingerprint methods were used to study Pasteurella multocida isolated from 320 wild birds of North America. Isolates were collected during 1978-93. The HhaI profiles of 314 isolates matched the HhaI profile of somatic reference type 1, strain X-73; somatic type 1 antigen was expressed by 310 isolates, and the serotype of four isolates was undetected. Differentiation of the 314 isolates was observed by digestion of DNA with HpaII. None of the HpaII profiles matched the HpaII profile of X-73 (designated HhaI 001/HpaII 001). Three HpaII profiles were recognized among the somatic type 1 isolates: HpaII 002 (n = 18), HpaII 003 (n = 122), and HpaII 004 (n = 174). Profile HpaII 002 was found among isolates collected during 1979-83. Profile HpaII 003 was identified from isolates collected during 1979-89, with the exception of two isolates in 1992. The HpaII 004 profile was identified from isolates collected during 1983-93. Of the six remaining isolates, four expressed somatic type 4 and had HhaI profiles identical to the somatic type 4 reference strain P-1662 profile (designated HhaI 004); these isolates were differentiated by digestion of DNA with HpaII. One isolate was identified as serotype F:11, and another was serotype A:3,4. In the present study, 314 of 316 (99.4%) isolates from wild birds in the Central, Mississippi, and Pacific flyways during 1978-93, were P. multocida somatic type 1.

Persistence and failure of mean-field approximations adapted to a class of systems of delay-coupled excitable units

NASA Astrophysics Data System (ADS)

Franović, Igor; Todorović, Kristina; Vasović, Nebojša; Burić, Nikola

2014-02-01

We consider the approximations behind the typical mean-field model derived for a class of systems made up of type II excitable units influenced by noise and coupling delays. The formulation of the two approximations, referred to as the Gaussian and the quasi-independence approximation, as well as the fashion in which their validity is verified, are adapted to reflect the essential properties of the underlying system. It is demonstrated that the failure of the mean-field model associated with the breakdown of the quasi-independence approximation can be predicted by the noise-induced bistability in the dynamics of the mean-field system. As for the Gaussian approximation, its violation is related to the increase of noise intensity, but the actual condition for failure can be cast in qualitative, rather than quantitative terms. We also discuss how the fulfillment of the mean-field approximations affects the statistics of the first return times for the local and global variables, further exploring the link between the fulfillment of the quasi-independence approximation and certain forms of synchronization between the individual units.

The Hippo signal transduction network for exercise physiologists

PubMed Central

Hamilton, D. Lee; Tremblay, Annie M.

2016-01-01

The ubiquitous transcriptional coactivators Yap (gene symbol Yap1) and Taz (gene symbol Wwtr1) regulate gene expression mainly by coactivating the Tead transcription factors. Being at the center of the Hippo signaling network, Yap and Taz are regulated by the Hippo kinase cassette and additionally by a plethora of exercise-associated signals and signaling modules. These include mechanotransduction, the AKT-mTORC1 network, the SMAD transcription factors, hypoxia, glucose homeostasis, AMPK, adrenaline/epinephrine and angiotensin II through G protein-coupled receptors, and IL-6. Consequently, exercise should alter Hippo signaling in several organs to mediate at least some aspects of the organ-specific adaptations to exercise. Indeed, Tead1 overexpression in muscle fibers has been shown to promote a fast-to-slow fiber type switch, whereas Yap in muscle fibers and cardiomyocytes promotes skeletal muscle hypertrophy and cardiomyocyte adaptations, respectively. Finally, genome-wide association studies in humans have linked the Hippo pathway members LATS2, TEAD1, YAP1, VGLL2, VGLL3, and VGLL4 to body height, which is a key factor in sports. PMID:26940657

An Efficient and Adaptive Mutual Authentication Framework for Heterogeneous Wireless Sensor Network-Based Applications

PubMed Central

Kumar, Pardeep; Ylianttila, Mika; Gurtov, Andrei; Lee, Sang-Gon; Lee, Hoon-Jae

2014-01-01

Robust security is highly coveted in real wireless sensor network (WSN) applications since wireless sensors' sense critical data from the application environment. This article presents an efficient and adaptive mutual authentication framework that suits real heterogeneous WSN-based applications (such as smart homes, industrial environments, smart grids, and healthcare monitoring). The proposed framework offers: (i) key initialization; (ii) secure network (cluster) formation (i.e., mutual authentication and dynamic key establishment); (iii) key revocation; and (iv) new node addition into the network. The correctness of the proposed scheme is formally verified. An extensive analysis shows the proposed scheme coupled with message confidentiality, mutual authentication and dynamic session key establishment, node privacy, and message freshness. Moreover, the preliminary study also reveals the proposed framework is secure against popular types of attacks, such as impersonation attacks, man-in-the-middle attacks, replay attacks, and information-leakage attacks. As a result, we believe the proposed framework achieves efficiency at reasonable computation and communication costs and it can be a safeguard to real heterogeneous WSN applications. PMID:24521942

A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes

PubMed Central

Shu, Lingling; Hoo, Ruby L. C.; Wu, Xiaoping; Pan, Yong; Lee, Ida P. C.; Cheong, Lai Yee; Bornstein, Stefan R; Rong, Xianglu; Guo, Jiao; Xu, Aimin

2017-01-01

The adipokine adipocyte fatty acid-binding protein (A-FABP) has been implicated in obesity-related cardio-metabolic complications. Here we show that A-FABP increases thermogenesis by promoting the conversion of T4 to T3 in brown adipocytes. We find that A-FABP levels are increased in both white (WAT) and brown (BAT) adipose tissues and the bloodstream in response to thermogenic stimuli. A-FABP knockout mice have reduced thermogenesis and whole-body energy expenditure after cold stress or after feeding a high-fat diet, which can be reversed by infusion of recombinant A-FABP. Mechanistically, A-FABP induces the expression of type-II iodothyronine deiodinase in BAT via inhibition of the nuclear receptor liver X receptor α, thereby leading to the conversion of thyroid hormone from its inactive form T4 to active T3. The thermogenic responses to T4 are abrogated in A-FABP KO mice, but enhanced by A-FABP. Thus, A-FABP acts as a physiological stimulator of BAT-mediated adaptive thermogenesis. PMID:28128199

An efficient and adaptive mutual authentication framework for heterogeneous wireless sensor network-based applications.

PubMed

Kumar, Pardeep; Ylianttila, Mika; Gurtov, Andrei; Lee, Sang-Gon; Lee, Hoon-Jae

2014-02-11

Robust security is highly coveted in real wireless sensor network (WSN) applications since wireless sensors' sense critical data from the application environment. This article presents an efficient and adaptive mutual authentication framework that suits real heterogeneous WSN-based applications (such as smart homes, industrial environments, smart grids, and healthcare monitoring). The proposed framework offers: (i) key initialization; (ii) secure network (cluster) formation (i.e., mutual authentication and dynamic key establishment); (iii) key revocation; and (iv) new node addition into the network. The correctness of the proposed scheme is formally verified. An extensive analysis shows the proposed scheme coupled with message confidentiality, mutual authentication and dynamic session key establishment, node privacy, and message freshness. Moreover, the preliminary study also reveals the proposed framework is secure against popular types of attacks, such as impersonation attacks, man-in-the-middle attacks, replay attacks, and information-leakage attacks. As a result, we believe the proposed framework achieves efficiency at reasonable computation and communication costs and it can be a safeguard to real heterogeneous WSN applications.

Fishing Farmers or Farming Fishers? Fishing Typology of Inland Small-Scale Fishing Households and Fisheries Management in Singkarak Lake, West Sumatra, Indonesia

NASA Astrophysics Data System (ADS)

Yuerlita; Perret, Sylvain Roger; Shivakoti, Ganesh P.

2013-07-01

Technical and socio-economic characteristics are known to determine different types of fishers and their livelihood strategies. Faced with declining fish and water resources, small-scale fisheries engage into transformations in livelihood and fishing practices. The paper is an attempt to understand these changes and their socio-economic patterns, in the case of Singkarak Lake in West Sumatra, Indonesia. Based upon the hypothesis that riparian communities have diverse, complex yet structured and dynamic livelihood systems, the paper's main objective is to study, document and model the actual diversity in livelihood, practices and performance of inland small-scale fisheries along the Singkarak Lake, to picture how households are adapted to the situation, and propose an updated, workable model (typology) of those for policy. Principal component analysis and cluster analysis were used to develop a typology of fishing households. The results show that small-scale fishers can be classified into different types characterized by distinct livelihood strategies. Three household types are identified, namely "farming fishers" households (type I, 30 %), "fishing farmers" households (type II, 30 %), and "mainly fishers" households (type III, 40 %). There are significant differences among these groups in the number of boats owned, annual fishing income, agriculture income and farming experience. Type I consists of farming fishers, well equipped, with high fishing costs and income, yet with the lowest return on fishing assets. They are also landowners with farming income, showing the lowest return on land capital. Type II includes poor fishing farmers, landowners with higher farming income; they show the highest return on land asset. They have less fishing equipment, costs and income. Type III (mainly fishers) consists of poorer, younger fishers, with highest return on fishing assets and on fishing costs. They have little land, low farming income, and diversified livelihood sources. The nature of their livelihood strategies is discussed for each identified group. This helps to understand the complexity and diversity of small-scale fishers, particularly in the study area which is still poorly known. This paper concludes with policy implication and possible management initiatives for environmentally prudent policy aiming at improvement of fishers' livelihood.

Fishing farmers or farming fishers? Fishing typology of inland small-scale fishing households and fisheries management in singkarak lake, west sumatra, indonesia.

PubMed

Yuerlita; Perret, Sylvain Roger; Shivakoti, Ganesh P

2013-07-01

Technical and socio-economic characteristics are known to determine different types of fishers and their livelihood strategies. Faced with declining fish and water resources, small-scale fisheries engage into transformations in livelihood and fishing practices. The paper is an attempt to understand these changes and their socio-economic patterns, in the case of Singkarak Lake in West Sumatra, Indonesia. Based upon the hypothesis that riparian communities have diverse, complex yet structured and dynamic livelihood systems, the paper's main objective is to study, document and model the actual diversity in livelihood, practices and performance of inland small-scale fisheries along the Singkarak Lake, to picture how households are adapted to the situation, and propose an updated, workable model (typology) of those for policy. Principal component analysis and cluster analysis were used to develop a typology of fishing households. The results show that small-scale fishers can be classified into different types characterized by distinct livelihood strategies. Three household types are identified, namely "farming fishers" households (type I, 30 %), "fishing farmers" households (type II, 30 %), and "mainly fishers" households (type III, 40 %). There are significant differences among these groups in the number of boats owned, annual fishing income, agriculture income and farming experience. Type I consists of farming fishers, well equipped, with high fishing costs and income, yet with the lowest return on fishing assets. They are also landowners with farming income, showing the lowest return on land capital. Type II includes poor fishing farmers, landowners with higher farming income; they show the highest return on land asset. They have less fishing equipment, costs and income. Type III (mainly fishers) consists of poorer, younger fishers, with highest return on fishing assets and on fishing costs. They have little land, low farming income, and diversified livelihood sources. The nature of their livelihood strategies is discussed for each identified group. This helps to understand the complexity and diversity of small-scale fishers, particularly in the study area which is still poorly known. This paper concludes with policy implication and possible management initiatives for environmentally prudent policy aiming at improvement of fishers' livelihood.

Genetic heterogeneity of Usher syndrome type II.

PubMed Central

Pieke Dahl, S; Kimberling, W J; Gorin, M B; Weston, M D; Furman, J M; Pikus, A; Möller, C

1993-01-01

Usher syndrome is an autosomal recessive disorder characterised by retinitis pigmentosa and congenital sensorineural hearing loss. A gene for Usher syndrome type II (USH2) has been localised to chromosome 1q32-q41. DNA from a family with four of seven sibs affected with clinical characteristics of Usher syndrome type II was genotyped using markers spanning the 1q32-1q41 region. These included D1S70 and D1S81, which are believed to flank USH2. Genotypic results and subsequent linkage analysis indicated non-linkage of this family to these markers. The A test analysis for heterogeneity with this family and 32 other Usher type II families was statistically significant at p < 0.05. Further clinical evaluation of this family was done in light of the linkage results to determine if any phenotypic characteristics would allow for clinical identification of the unlinked type. No clear phenotypic differences were observed; however, this unlinked family may represent a previously unreported subtype of Usher type II characterised by a milder form of retinitis pigmentosa and mild vestibular abnormalities. Heterogeneity of Usher syndrome type II complicates efforts to isolate and clone Usher syndrome genes using linkage analysis and limits the use of DNA markers in early detection of Usher type II. Images PMID:7901420

Fermentation of Acid-pretreated Corn Stover to Ethanol Without Detoxification Using Pichia stipitis

NASA Astrophysics Data System (ADS)

Agbogbo, Frank K.; Haagensen, Frank D.; Milam, David; Wenger, Kevin S.

In this work, the effect of adaptation on P. stipitis fermentation using acidpretreated corn stover hydrolyzates without detoxification was examined. Two different types of adaptation were employed, liquid hydrolyzate and solid state agar adaptation. Fermentation of 12.5% total solids undetoxified acid-pretreated corn stover was performed in shake flasks at different rotation speeds. At low rotation speed (100 rpm), both liquid hydrolyzate and solid agar adaptation highly improved the sugar consumption rate as well as ethanol production rate compared to the wild-type strains. The fermentation rate was higher for solid agar-adapted strains compared to liquid hydrolyzate-adapted strains. At a higher rotation speed (150 rpm), there was a faster sugar consumption and ethanol production for both the liquid-adapted and the wild-type strains. However, improvements in the fermentation rate between the liquid-adapted and wild strains were less pronounced at the high rotation speed.

The Role of Adaptive Behavior in Autism Spectrum Disorders: Implications for Functional Outcome

ERIC Educational Resources Information Center

Kanne, Stephen M.; Gerber, Andrew J.; Quirmbach, Linda M.; Sparrow, Sara S.; Cicchetti, Domenic V.; Saulnier, Celine A.

2011-01-01

The relationship between adaptive functioning and autism symptomatology was examined in 1,089 verbal youths with ASD examining results on Vineland-II, IQ, and measures of ASD severity. Strong positive relationships were found between Vineland subscales and IQ. Vineland Composite was negatively associated with age. IQ accounted a significant amount…

Ecological adaptations in Douglas-fir populations. II. Western Montana

Treesearch

Gerald E. Rehfeldt

1982-01-01

Populations of Douglas-fir (Pseudotsuga menziesii var. glauca) from Montana west of the Continental Divide were compared in common environments. Differentiation was observed for six variables reflecting growth potential, phenology and cold hardiness. Adaptation of populations for numerous traits is viewed as a balance between selection of high growth potential in...

A Comparative Analysis of Family Adaptability and Cohesion Ratings among Traumatized Urban Youth

ERIC Educational Resources Information Center

Bellantuono, Alessandro; Saigh, Philip A.; Durham, Katherine; Dekis, Constance; Hackler, Dusty; McGuire, Leah A.; Yasik, Anastasia E.; Halamandaris, Phill V.; Oberfield, Richard A.

2018-01-01

Objective: Given the need to identify psychological risk factors among traumatized youth, this study examined the family functioning of traumatized youth with or without PTSD and a nonclinical sample. Method: The Family Adaptability and Cohesion Evaluation Scales, second edition (FACES II; Olson, Portner, & Bell, 1982), scores of youth with…

Adaptive variation in Pinus ponderosa from Intermountain regions. II. Middle Columbia River system

Treesearch

Gerald Rehfeldt

1986-01-01

Seedling populations were grown and compared in common environments. Statistical analyses detected genetic differences between populations for numerous traits reflecting growth potential and periodicity of shoot elongation. Multiple regression models described an adaptive landscape in which populations from low elevations have a high growth potential while those from...

34 CFR 462.11 - What must an application contain?

Code of Federal Regulations, 2013 CFR

2013-07-01

... (ii) Examinees, for adaptive tests in which items are selected in real time. (d) Maintenance..., including the number of times the test has been administered; and (5) For a computerized adaptive test, the... termination conditions; (iii) Score the test; and (iv) Control for item exposure. (e) Match of content to the...

34 CFR 462.11 - What must an application contain?

Code of Federal Regulations, 2014 CFR

2014-07-01

... (ii) Examinees, for adaptive tests in which items are selected in real time. (d) Maintenance..., including the number of times the test has been administered; and (5) For a computerized adaptive test, the... termination conditions; (iii) Score the test; and (iv) Control for item exposure. (e) Match of content to the...

34 CFR 462.11 - What must an application contain?

Code of Federal Regulations, 2012 CFR

2012-07-01

... (ii) Examinees, for adaptive tests in which items are selected in real time. (d) Maintenance..., including the number of times the test has been administered; and (5) For a computerized adaptive test, the... termination conditions; (iii) Score the test; and (iv) Control for item exposure. (e) Match of content to the...

Adaptation mechanism of interlimb coordination in human split-belt treadmill walking through learning of foot contact timing: a robotics study

PubMed Central

Fujiki, Soichiro; Aoi, Shinya; Funato, Tetsuro; Tomita, Nozomi; Senda, Kei; Tsuchiya, Kazuo

2015-01-01

Human walking behaviour adaptation strategies have previously been examined using split-belt treadmills, which have two parallel independently controlled belts. In such human split-belt treadmill walking, two types of adaptations have been identified: early and late. Early-type adaptations appear as rapid changes in interlimb and intralimb coordination activities when the belt speeds of the treadmill change between tied (same speed for both belts) and split-belt (different speeds for each belt) configurations. By contrast, late-type adaptations occur after the early-type adaptations as a gradual change and only involve interlimb coordination. Furthermore, interlimb coordination shows after-effects that are related to these adaptations. It has been suggested that these adaptations are governed primarily by the spinal cord and cerebellum, but the underlying mechanism remains unclear. Because various physiological findings suggest that foot contact timing is crucial to adaptive locomotion, this paper reports on the development of a two-layered control model for walking composed of spinal and cerebellar models, and on its use as the focus of our control model. The spinal model generates rhythmic motor commands using an oscillator network based on a central pattern generator and modulates the commands formulated in immediate response to foot contact, while the cerebellar model modifies motor commands through learning based on error information related to differences between the predicted and actual foot contact timings of each leg. We investigated adaptive behaviour and its mechanism by split-belt treadmill walking experiments using both computer simulations and an experimental bipedal robot. Our results showed that the robot exhibited rapid changes in interlimb and intralimb coordination that were similar to the early-type adaptations observed in humans. In addition, despite the lack of direct interlimb coordination control, gradual changes and after-effects in the interlimb coordination appeared in a manner that was similar to the late-type adaptations and after-effects observed in humans. The adaptation results of the robot were then evaluated in comparison with human split-belt treadmill walking, and the adaptation mechanism was clarified from a dynamic viewpoint. PMID:26289658

Adaptation mechanism of interlimb coordination in human split-belt treadmill walking through learning of foot contact timing: a robotics study.

PubMed

Fujiki, Soichiro; Aoi, Shinya; Funato, Tetsuro; Tomita, Nozomi; Senda, Kei; Tsuchiya, Kazuo

2015-09-06

Human walking behaviour adaptation strategies have previously been examined using split-belt treadmills, which have two parallel independently controlled belts. In such human split-belt treadmill walking, two types of adaptations have been identified: early and late. Early-type adaptations appear as rapid changes in interlimb and intralimb coordination activities when the belt speeds of the treadmill change between tied (same speed for both belts) and split-belt (different speeds for each belt) configurations. By contrast, late-type adaptations occur after the early-type adaptations as a gradual change and only involve interlimb coordination. Furthermore, interlimb coordination shows after-effects that are related to these adaptations. It has been suggested that these adaptations are governed primarily by the spinal cord and cerebellum, but the underlying mechanism remains unclear. Because various physiological findings suggest that foot contact timing is crucial to adaptive locomotion, this paper reports on the development of a two-layered control model for walking composed of spinal and cerebellar models, and on its use as the focus of our control model. The spinal model generates rhythmic motor commands using an oscillator network based on a central pattern generator and modulates the commands formulated in immediate response to foot contact, while the cerebellar model modifies motor commands through learning based on error information related to differences between the predicted and actual foot contact timings of each leg. We investigated adaptive behaviour and its mechanism by split-belt treadmill walking experiments using both computer simulations and an experimental bipedal robot. Our results showed that the robot exhibited rapid changes in interlimb and intralimb coordination that were similar to the early-type adaptations observed in humans. In addition, despite the lack of direct interlimb coordination control, gradual changes and after-effects in the interlimb coordination appeared in a manner that was similar to the late-type adaptations and after-effects observed in humans. The adaptation results of the robot were then evaluated in comparison with human split-belt treadmill walking, and the adaptation mechanism was clarified from a dynamic viewpoint. © 2015 The Authors.

Spectrum of Lyapunov exponents of non-smooth dynamical systems of integrate-and-fire type.

PubMed

Zhou, Douglas; Sun, Yi; Rangan, Aaditya V; Cai, David

2010-04-01

We discuss how to characterize long-time dynamics of non-smooth dynamical systems, such as integrate-and-fire (I&F) like neuronal network, using Lyapunov exponents and present a stable numerical method for the accurate evaluation of the spectrum of Lyapunov exponents for this large class of dynamics. These dynamics contain (i) jump conditions as in the firing-reset dynamics and (ii) degeneracy such as in the refractory period in which voltage-like variables of the network collapse to a single constant value. Using the networks of linear I&F neurons, exponential I&F neurons, and I&F neurons with adaptive threshold, we illustrate our method and discuss the rich dynamics of these networks.

Portable outgas detection apparatus

DOEpatents

Haney, Steven Julian; Malinowski, Michael E.

2004-05-11

A portable device for detecting surface outgas contaminants of an article includes: (i) a portable housing that has a chamber which is in communication with a port that is adapted to be sealably attached to a surface of the article; (ii) a mass spectrometer that is coupled to the chamber for analyzing gaseous materials in the chamber; and (iii) means for generating a vacuum within the chamber thereby drawing outgas contaminants from the surface of the article into the chamber for analysis by the mass spectrometer. By performing a mass spectrometric analysis of the surface of interest and comparing the data with mass spectrometric data ascertained with the device from a clean surface, the type and amount of outgas contaminants, if any, can be determined.

Adaptive Clinical Trials: Advantages and Disadvantages of Various Adaptive Design Elements.

PubMed

Korn, Edward L; Freidlin, Boris

2017-06-01

There is a wide range of adaptive elements of clinical trial design (some old and some new), with differing advantages and disadvantages. Classical interim monitoring, which adapts the design based on early evidence of superiority or futility of a treatment arm, has long been known to be extremely useful. A more recent application of interim monitoring is in the use of phase II/III designs, which can be very effective (especially in the setting of multiple experimental treatments and a reliable intermediate end point) but do have the cost of having to commit earlier to the phase III question than if separate phase II and phase III trials were performed. Outcome-adaptive randomization is an older technique that has recently regained attention; it increases trial complexity and duration without offering substantial benefits to the patients in the trial. The use of adaptive trials with biomarkers is new and has great potential for efficiently identifying patients who will be helped most by specific treatments. Master protocols in which trial arms and treatment questions are added to an ongoing trial can be especially efficient in the biomarker setting, where patients are screened for entry into different subtrials based on evolving knowledge about targeted therapies. A discussion of three recent adaptive clinical trials (BATTLE-2, I-SPY 2, and FOCUS4) highlights the issues. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

Velocity, force, power, and Ca2+ sensitivity of fast and slow monkey skeletal muscle fibers

NASA Technical Reports Server (NTRS)

Fitts, R. H.; Bodine, S. C.; Romatowski, J. G.; Widrick, J. J.

1998-01-01

In this study, we determined the contractile properties of single chemically skinned fibers prepared from the medial gastrocnemius (MG) and soleus (Sol) muscles of adult male rhesus monkeys and assessed the effects of the spaceflight living facility known as the experiment support primate facility (ESOP). Muscle biopsies were obtained 4 wk before and immediately after an 18-day ESOP sit, and fiber type was determined by immunohistochemical techniques. The MG slow type I fiber was significantly smaller than the MG type II, Sol type I, and Sol type II fibers. The ESOP sit caused a significant reduction in the diameter of type I and type I/II (hybrid) fibers of Sol and MG type II and hybrid fibers but no shift in fiber type distribution. Single-fiber peak force (mN and kN/m2) was similar between fiber types and was not significantly different from values previously reported for other species. The ESOP sit significantly reduced the force (mN) of Sol type I and MG type II fibers. This decline was entirely explained by the atrophy of these fiber types because the force per cross-sectional area (kN/m2) was not altered. Peak power of Sol and MG fast type II fiber was 5 and 8.5 times that of slow type I fiber, respectively. The ESOP sit reduced peak power by 25 and 18% in Sol type I and MG type II fibers, respectively, and, for the former fiber type, shifted the force-pCa relationship to the right, increasing the Ca2+ activation threshold and the free Ca2+ concentration, eliciting half-maximal activation. The ESOP sit had no effect on the maximal shortening velocity (Vo) of any fiber type. Vo of the hybrid fibers was only slightly higher than that of slow type I fibers. This result supports the hypothesis that in hybrid fibers the slow myosin heavy chain would be expected to have a disproportionately greater influence on Vo.

Sex-specific effect of endothelin in the blood pressure response to acute angiotensin II in growth-restricted rats

PubMed Central

Intapad, Suttira; Ojeda, Norma B.; Varney, Elliott; Royals, Thomas P.; Alexander, Barbara T.

2015-01-01

The renal endothelin system contributes to sex differences in blood pressure with males demonstrating greater endothelin type-A receptor-mediated responses relative to females. Intrauterine growth restriction programs hypertension and enhanced renal sensitivity to acute angiotensin II in male growth-restricted rats. Endothelin is reported to work synergistically with angiotensin II. Thus, this study tested the hypothesis that endothelin augments the blood pressure response to acute angiotensin II in male growth-restricted rats. Systemic and renal hemodynamics were determined in response to acute angiotensin II (100 nanogram/kilogram/minute for 30 minutes) with and without the endothelin type-A receptor antagonist, ABT 627(10 nanogram/kilogram/minute for 30 minutes), in rats pretreated with enalapril (250 milligram/Liter for one week) to normalize the endogenous renin angiotensin system. Endothelin type-A receptor blockade reduced angiotensin II-mediated increases in blood pressure in male control and male growth-restricted rats. Endothelin type-A receptor blockade also abolished hyper-responsiveness to acute angiotensin II in male growth-restricted rats. Yet, blood pressure remained significantly elevated above baseline following endothelin type-A receptor blockade suggesting that factors in addition to endothelin contribute to the basic angiotensin II-induced pressor response in male rats. We also determined sex-specific effects of endothelin on acute angiotensin II-mediated hemodynamic responses. Endothelin type-A receptor blockade did not reduce acute angiotensin II-mediated increases in blood pressure in female control or growth-restricted rats, intact or ovariectomized. Thus, these data suggest that endothelin type-A receptor blockade contributes to hypersensitivity to acute angiotensin II in male growth-restricted rats and further supports the sex-specific effect of endothelin on blood pressure. PMID:26459423

Performance-based robotic assistance during rhythmic arm exercises.

PubMed

Leconte, Patricia; Ronsse, Renaud

2016-09-13

Rhythmic and discrete upper-limb movements are two fundamental motor primitives controlled by different neural pathways, at least partially. After stroke, both primitives can be impaired. Both conventional and robot-assisted therapies mainly train discrete functional movements like reaching and grasping. However, if the movements form two distinct neural and functional primitives, both should be trained to recover the complete motor repertoire. Recent studies show that rhythmic movements tend to be less impaired than discrete ones, so combining both movement types in therapy could support the execution of movements with a higher degree of impairment by movements that are performed more stably. A new performance-based assistance method was developed to train rhythmic movements with a rehabilitation robot. The algorithm uses the assist-as-needed paradigm by independently assessing and assisting movement features of smoothness, velocity, and amplitude. The method relies on different building blocks: (i) an adaptive oscillator captures the main movement harmonic in state variables, (ii) custom metrics measure the movement performance regarding the three features, and (iii) adaptive forces assist the patient. The patient is encouraged to improve performance regarding these three features with assistance forces computed in parallel to each other. The method was tested with simulated jerky signals and a pilot experiment with two stroke patients, who were instructed to make circular movements with an end-effector robot with assistance during half of the trials. Simulation data reveal sensitivity of the metrics for assessing the features while limiting interference between them. The assistance's effectiveness with stroke patients is established since it (i) adapts to the patient's real-time performance, (ii) improves patient motor performance, and (iii) does not lead the patient to slack. The smoothness assistance was by far the most used by both patients, while it provided no active mechanical work to the patient on average. Our performance-based assistance method for training rhythmic movements is a viable candidate to complement robot-assisted upper-limb therapies for training a larger motor repertoire.

A watershed-based adaptive knowledge system for developing ecosystem stakeholder partnerships

NASA Astrophysics Data System (ADS)

Lin, Hebin; Thornton, Jeffrey A.; Shadrin, Nickolai

2015-11-01

This study proposes a Watershed-based Adaptive Knowledge System (WAKES) to consistently coordinate multiple stakeholders in developing sustainable partnerships for ecosystem management. WAKES is extended from the institutional mechanism of Payments for Improving Ecosystem Services at the Watershed-scale (PIES-W). PIES-W is designed relating to the governance of ecosystem services fl ows focused on a lake as a resource stock connecting its infl owing and outfl owing rivers within its watershed. It explicitly realizes the values of conservation services provided by private land managers and incorporates their activities into the public organizing framework for ecosystem management. It implicitly extends the "upstream-to-downstream" organizing perspective to a broader vision of viewing the ecosystems as comprised of both "watershed landscapes" and "marine landscapes". Extended from PIES-W, WAKES specifies two corresponding feedback: Framework I and II. Framework I is a relationship matrix comprised of three input-output structures of primary governance factors intersecting three subsystems of a watershed with regard to ecosystem services and human stakeholders. Framework II is the Stakeholder-and-Information structure channeling five types of information among four stakeholder groups in order to enable the feedbacks mechanism of Framework I. WAKES identifies the rationales behind three fundamental information transformations, illustrated with the Transboundary Diagnostic Analysis and the Strategic Action Program of the Bermejo River Binational Basin. These include (1) translating scientific knowledge into public information within the Function-and-Service structure corresponding to the ecological subsystem, (2) incorporating public perceptions into political will within the Service- and- Value structure corresponding to the economic subsystem, and (3) integrating scientific knowledge, public perceptions and political will into management options within the Value-and-Stakeholder structure corresponding to the social subsystem. This study seeks to share a vision of social adaptation for a global sustainable future through developing a network to adopt contributions from and forming partnerships among all ecosystem stakeholders.

Light-adaptation of photosystem II is mediated by the plastoquinone pool.

PubMed

Ahrling, Karin A; Peterson, Sindra

2003-07-01

During the first few enzymatic turnovers after dark-adaptation of photosystem II (PSII), the relaxation rate of the EPR signals from the Mn cluster and Y(D)(*) are significantly enhanced. This light-adaptation process has been suggested to involve the appearance of a new paramagnet on the PSII donor side [Peterson, S., Ahrling, K., Högblom, J., and Styring, S. (2003) Biochemistry 42, 2748-2758]. In the present study, a correlation is established between the observed relaxation enhancement and the redox state of the quinone pool. It is shown that the addition of quinol to dark-adapted PSII membrane fragments induces relaxation enhancement already after a single oxidation of the Mn, comparable to that observed after five oxidations in samples with quinones (PPBQ or DQ) added. The saturation behavior of Y(D)(*) revealed that with quinol added in the dark, a single flash was necessary for the relaxation enhancement to occur. The quinol-induced relaxation enhancement of PSII was also activated by illumination at 200 K. Whole thylakoids, with no artificial electron acceptor present but with an intact plastoquinone pool, displayed the same relaxation enhancement on the fifth flash as membrane fragments with exogenous quinones present. We conclude that (i) reduction of the quinone pool induces the relaxation enhancement of the PSII donor-side paramagnets, (ii) light is required for the quinol to effect the relaxation enhancement, and (iii) light-adaptation occurs in the intact thylakoid system, when the endogenous plastoquinone pool is gradually reduced by PSII turnover. It seems clear that a species on the PSII donor side is reduced by the quinol, to become a potent paramagnetic relaxer. On the basis of XANES reports, we suggest that this species may be the Mn ions not involved in the cyclic redox changes of the oxygen-evolving complex.

How type II CRISPR-Cas establish immunity through Cas1-Cas2-mediated spacer integration.

PubMed

Xiao, Yibei; Ng, Sherwin; Nam, Ki Hyun; Ke, Ailong

2017-10-05

CRISPR (clustered regularly interspaced short palindromic repeats) and the nearby Cas (CRISPR-associated) operon establish an RNA-based adaptive immunity system in prokaryotes. Molecular memory is created when a short foreign DNA-derived prespacer is integrated into the CRISPR array as a new spacer. Whereas the RNA-guided CRISPR interference mechanism varies widely among CRISPR-Cas systems, the spacer integration mechanism is essentially identical. The conserved Cas1 and Cas2 proteins form an integrase complex consisting of two distal Cas1 dimers bridged by a Cas2 dimer. The prespacer is bound by Cas1-Cas2 as a dual-forked DNA, and the terminal 3'-OH of each 3' overhang serves as an attacking nucleophile during integration. The prespacer is preferentially integrated into the leader-proximal region of the CRISPR array, guided by the leader sequence and a pair of inverted repeats inside the CRISPR repeat. Spacer integration in the well-studied Escherichia coli type I-E CRISPR system also relies on the bacterial integration host factor. In type II-A CRISPR, however, Cas1-Cas2 alone integrates spacers efficiently in vitro; other Cas proteins (such as Cas9 and Csn2) have accessory roles in the biogenesis phase of prespacers. Here we present four structural snapshots from the type II-A system of Enterococcus faecalis Cas1 and Cas2 during spacer integration. Enterococcus faecalis Cas1-Cas2 selectively binds to a splayed 30-base-pair prespacer bearing 4-nucleotide 3' overhangs. Three molecular events take place upon encountering a target: first, the Cas1-Cas2-prespacer complex searches for half-sites stochastically, then it preferentially interacts with the leader-side CRISPR repeat, and finally, it catalyses a nucleophilic attack that connects one strand of the leader-proximal repeat to the prespacer 3' overhang. Recognition of the spacer half-site requires DNA bending and leads to full integration. We derive a mechanistic framework to explain the stepwise spacer integration process and the leader-proximal preference.

How Type II CRISPR-Cas establish immunity through Cas1-Cas2 mediated spacer integration

PubMed Central

Xiao, Yibei; Ng, Sherwin; Nam, Ki Hyun; Ke, Ailong

2017-01-01

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the nearby cas (CRISPR-associated) operon establish an RNA-based adaptive immunity system in prokaryotes1–5. Molecular memory is created when a short foreign DNA-derived prespacer is integrated into the CRISPR array as a new spacer6–9. Whereas the RNA-guided CRISPR interference mechanism varies widely among CRISPR-Cas systems, the spacer integration mechanism is essentially identical7–9. The conserved Cas1 and Cas2 proteins form an integrase complex consisting two distal Cas1 dimers bridged by a Cas2 dimer in the middle6,10. The prespacer is bound by Cas1-Cas2 as a dual forked DNA, and the terminal 3′-OH of each 3′-overhang serves as an attacking nucleophile during integration11–14. Importantly, the prespacer is preferentially integrated into the leader-proximal region of the CRISPR array1,7,10,15, guided by the leader sequence and a pair of inverted repeats (IRs) inside the CRISPR repeat7,15–20. Spacer integration in the most well-studied Escherichia coli Type I-E CRISPR system further relies on the bacterial Integration Host Factor (IHF)21,22. In Type II-A CRISPR, however, Cas1-Cas2 alone integrates spacer efficiently in vitro18; other Cas proteins (Cas9 and Csn2) play accessory roles in prespacer biogenesis17,23. Focusing on the Enterococcus faecalis Type II-A system24, here we report four structure snapshots of Cas1-Cas2 during spacer integration. EfaCas1-Cas2 selectively binds to a splayed 30-bp prespacer bearing 4-nt 3′-overhangs. Three molecular events take place upon encountering a target: Cas1-Cas2/prespacer first searches for half-sites stochastically, then preferentially interacts with the leader-side CRISPR repeat and catalyzes a nucleophilic attack that connects one strand of the leader-proximal repeat to the prespacer 3′-overhang. Recognition of the spacer half-site requires DNA bending and leads to full integration. We derive a mechanistic framework explaining the stepwise spacer integration process and the leader-proximal preference. PMID:28869593

Differential accumulation of photosynthetic proteins regulates diurnal photochemical adjustments of PSII in common fig (Ficus carica L.) leaves.

PubMed

Mlinarić, Selma; Antunović Dunić, Jasenka; Skendrović Babojelić, Martina; Cesar, Vera; Lepeduš, Hrvoje

2017-02-01

Molecular processes involved in photosystem II adaptation of woody species to diurnal changes in light and temperature conditions are still not well understood. Regarding this, here we investigated differences between young and mature leaves of common fig (Ficus carica L.) in photosynthetic performance as well as accumulation of the main photosynthetic proteins: light harvesting complex II, D1 protein and Rubisco large subunit. Investigated leaf types revealed different adjustment mechanisms to keep effective photosynthesis. Rather stable diurnal accumulation of light harvesting complex II in mature leaves enabled efficient excitation energy utilization (negative L-band) what triggered faster D1 protein degradation at high light. However, after photoinhibition, greater accumulation of D1 during the night enabled them faster recovery. So, the most photosynthetic parameters, as the maximum quantum yield for primary photochemistry, electron transport and overall photosynthetic efficiency in mature leaves successfully restored to their initial values at 1a.m. Reduced connectivity of light harvesting complexes II to its reaction centers (positive L-band) in young leaves increased dissipation of excess light causing less pressure to D1 and its slower degradation. Decreased electron transport in young leaves, due to reduced transfer beyond primary acceptor Q A - most probably additionally induced degradation of Rubisco large subunit what consequently led to the stronger decrease of overall photosynthetic efficiency in young leaves at noon. Copyright © 2016 Elsevier GmbH. All rights reserved.

A unifying concept: pancreatic ductal anatomy both predicts and determines the major complications resulting from pancreatitis.

PubMed

Nealon, William H; Bhutani, Manoop; Riall, Taylor S; Raju, Gottumukkala; Ozkan, Orhan; Neilan, Ryan

2009-05-01

Precepts about acute pancreatitis, necrotizing pancreatitis, and pancreatic fluid collections or pseudocyst rarely include the impact of pancreatic ductal injuries on their natural course and outcomes. We previously examined and established a system to categorize ductal changes. We sought a unifying concept that may predict course and direct therapies in these complex patients. We use our system categorizing ductal changes in pseudocyst of the pancreas and severe necrotizing pancreatitis (type I, normal duct; type II, duct stricture; type III, duct occlusion or "disconnected duct"; and type IV, chronic pancreatitis). From 1985 to 2006, a policy was implemented of routine imaging (cross-sectional, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiopancreatography). Clinical outcomes were measured. Among 563 patients with pseudocyst, 142 resolved spontaneously (87% of type I, 5% of type II, and no type III, and 3% of type IV). Percutaneous drainage was successful in 83% of type I, 49% of type II, and no type III or type IV. Among 174 patients with severe acute pancreatitis percutaneous drainage was successful in 64% of type I, 38% of type II, and no type III. Operative debridement was required in 39% of type I and 83% and 85% of types II and III, respectively. Persistent fistula after debridement occurred in 27%, 54%, and 85% of types I, II, and III ducts, respectively. Late complications correlated with duct injury. Pancreatic ductal changes predict spontaneous resolution, success of nonoperative measures, and direct therapies in pseudocyst. Ductal changes also predict patients with necrotizing pancreatitis who are most likely to have immediate and delayed complications.

How Prevention Curricula are Taught under Real-World Conditions: Types of and Reasons for Teacher Curriculum Adaptations

ERIC Educational Resources Information Center

Miller-Day, Michelle; Pettigrew, Jonathan; Hecht, Michael L.; Shin, YoungJu; Graham, John; Krieger, Janice

2013-01-01

Purpose: As interventions are disseminated widely, issues of fidelity and adaptation become increasingly critical to understand. This study aims to describe the types of adaptations made by teachers delivering a school-based substance use prevention curriculum and their reasons for adapting program content. Design/methodology/approach: To…

Impulsiveness and energetics in solar flares with and without type II radio bursts - A comparison of hard X-ray characteristics for over 2500 solar flares

NASA Astrophysics Data System (ADS)

Pearson, Douglas H.; Nelson, Robert; Kojoian, Gabriel; Seal, James

1989-01-01

The hard X-ray characteristics of more than 2500 solar flares are used to study the relative size, impulsiveness, and energetics of flares with and without type II radio bursts. A quantitative definition of the hard X-ray impulsiveness is introduced, which may be applied to a large number of events unambiguously. It is found that the flares with type II bursts are generally not significantly larger, more impulsive, or more energetic than those without type II bursts. Also, no evidence is found to suggest a simple classification of the flares as either 'impulsive' or 'gradual'. Because type II bursts are present even in small flares with relatively unimpulsive energy releases, it is concluded that changes in the ambient conditions of the solar atmosphere causing an unusually low Alfven speed may be important in the generation of the shock wave that produces type II radio bursts.

Diversity of Survival Patterns among Escherichia coli O157:H7 Genotypes Subjected to Food-Related Stress Conditions.

PubMed

Elhadidy, Mohamed; Álvarez-Ordóñez, Avelino

2016-01-01

The purpose of this study was to evaluate the resistance patterns to food-related stresses of Shiga toxin producing Escherichia coli O157:H7 strains belonging to specific genotypes. A total of 33 E. coli O157:H7 strains were exposed to seven different stress conditions acting as potential selective pressures affecting the transmission of E. coli O157:H7 to humans through the food chain. These stress conditions included cold, oxidative, osmotic, acid, heat, freeze-thaw, and starvation stresses. The genotypes used for comparison included lineage-specific polymorphism, Shiga-toxin-encoding bacteriophage insertion sites, clade type, tir (A255T) polymorphism, Shiga toxin 2 subtype, and antiterminator Q gene allele. Bacterial resistance to different stressors was calculated by determining D-values (times required for inactivation of 90% of the bacterial population), which were then subjected to univariate and multivariate analyses. In addition, a relative stress resistance value, integrating resistance values to all tested stressors, was calculated for each bacterial strain and allowed for a ranking-type classification of E. coli O157:H7 strains according to their environmental robustness. Lineage I/II strains were found to be significantly more resistant to acid, cold, and starvation stress than lineage II strains. Similarly, tir (255T) and clade 8 encoding strains were significantly more resistant to acid, heat, cold, and starvation stress than tir (255A) and non-clade 8 strains. Principal component analysis, which allows grouping of strains with similar stress survival characteristics, separated strains of lineage I and I/II from strains of lineage II, which in general showed reduced survival abilities. Results obtained suggest that lineage I/II, tir (255T), and clade 8 strains, which have been previously reported to be more frequently associated with human disease cases, have greater multiple stress resistance than strains of other genotypes. The results from this study provide a better insight into how selective pressures encountered through the food chain may play a role in the epidemiology of STEC O157:H7 through controlling the transmission of highly adapted strains to humans.

Diversity of Survival Patterns among Escherichia coli O157:H7 Genotypes Subjected to Food-Related Stress Conditions

PubMed Central

Elhadidy, Mohamed; Álvarez-Ordóñez, Avelino

2016-01-01

The purpose of this study was to evaluate the resistance patterns to food-related stresses of Shiga toxin producing Escherichia coli O157:H7 strains belonging to specific genotypes. A total of 33 E. coli O157:H7 strains were exposed to seven different stress conditions acting as potential selective pressures affecting the transmission of E. coli O157:H7 to humans through the food chain. These stress conditions included cold, oxidative, osmotic, acid, heat, freeze-thaw, and starvation stresses. The genotypes used for comparison included lineage-specific polymorphism, Shiga-toxin-encoding bacteriophage insertion sites, clade type, tir (A255T) polymorphism, Shiga toxin 2 subtype, and antiterminator Q gene allele. Bacterial resistance to different stressors was calculated by determining D-values (times required for inactivation of 90% of the bacterial population), which were then subjected to univariate and multivariate analyses. In addition, a relative stress resistance value, integrating resistance values to all tested stressors, was calculated for each bacterial strain and allowed for a ranking-type classification of E. coli O157:H7 strains according to their environmental robustness. Lineage I/II strains were found to be significantly more resistant to acid, cold, and starvation stress than lineage II strains. Similarly, tir (255T) and clade 8 encoding strains were significantly more resistant to acid, heat, cold, and starvation stress than tir (255A) and non-clade 8 strains. Principal component analysis, which allows grouping of strains with similar stress survival characteristics, separated strains of lineage I and I/II from strains of lineage II, which in general showed reduced survival abilities. Results obtained suggest that lineage I/II, tir (255T), and clade 8 strains, which have been previously reported to be more frequently associated with human disease cases, have greater multiple stress resistance than strains of other genotypes. The results from this study provide a better insight into how selective pressures encountered through the food chain may play a role in the epidemiology of STEC O157:H7 through controlling the transmission of highly adapted strains to humans. PMID:27014242

Genome-wide association studies for the identification of biomarkers in metabolic diseases.

PubMed

Pattin, Kristine A; Moore, Jason H

2010-01-01

The field of genetics as it relates to metabolic disorders such as obesity and type II diabetes is complicated, and along with the medical research community, great strides are being taken to begin to understand the biological and genetic underpinnings of these diseases, with the hope of improving therapeutic, diagnostic and preventive strategies. Although research on metabolic disorders has been continuing for decades, the completion of the Human Genome Project in 2003 and the International HapMap Project in 2005 gave rise to an abundance of research tools, such as genome-wide genotyping, which allow researchers to conduct genome-wide association studies (GWAS) for detecting genetic variants that confer increased or decreased susceptibility to such complex diseases. In this review, the complex nature of metabolic disorders is discussed, specifically obesity and type II diabetes, as well as the limitations of the GWAS as applied to these disorders. While acknowledging limitations of GWAS, it is hoped to provide an insight about how GWAS can be adapted and advantageous in the clinical setting, enhancing prevention, diagnosis and treatment of these diseases. To be able to use the GWAS in a clinical setting is a complex challenge, yet it is hoped that in the future this tool will ultimately allow the development of pharmaceutical options that are capable of targeting the cause of metabolic disorders, not just the symptoms themselves.

Molecular Architecture of Plant Thylakoids under Physiological and Light Stress Conditions: A Study of Lipid–Light-Harvesting Complex II Model Membranes[C][W

PubMed Central

Janik, Ewa; Bednarska, Joanna; Zubik, Monika; Puzio, Michal; Luchowski, Rafal; Grudzinski, Wojciech; Mazur, Radoslaw; Garstka, Maciej; Maksymiec, Waldemar; Kulik, Andrzej; Dietler, Giovanni; Gruszecki, Wieslaw I.

2013-01-01

In this study, we analyzed multibilayer lipid-protein membranes composed of the photosynthetic light-harvesting complex II (LHCII; isolated from spinach [Spinacia oleracea]) and the plant lipids monogalcatosyldiacylglycerol and digalactosyldiacylglycerol. Two types of pigment-protein complexes were analyzed: those isolated from dark-adapted leaves (LHCII) and those from leaves preilluminated with high-intensity light (LHCII-HL). The LHCII-HL complexes were found to be partially phosphorylated and contained zeaxanthin. The results of the x-ray diffraction, infrared imaging microscopy, confocal laser scanning microscopy, and transmission electron microscopy revealed that lipid-LHCII membranes assemble into planar multibilayers, in contrast with the lipid-LHCII-HL membranes, which form less ordered structures. In both systems, the protein formed supramolecular structures. In the case of LHCII-HL, these structures spanned the multibilayer membranes and were perpendicular to the membrane plane, whereas in LHCII, the structures were lamellar and within the plane of the membranes. Lamellar aggregates of LHCII-HL have been shown, by fluorescence lifetime imaging microscopy, to be particularly active in excitation energy quenching. Both types of structures were stabilized by intermolecular hydrogen bonds. We conclude that the formation of trans-layer, rivet-like structures of LHCII is an important determinant underlying the spontaneous formation and stabilization of the thylakoid grana structures, since the lamellar aggregates are well suited to dissipate excess energy upon overexcitation. PMID:23898030

Molecular architecture of plant thylakoids under physiological and light stress conditions: a study of lipid-light-harvesting complex II model membranes.

PubMed

Janik, Ewa; Bednarska, Joanna; Zubik, Monika; Puzio, Michal; Luchowski, Rafal; Grudzinski, Wojciech; Mazur, Radoslaw; Garstka, Maciej; Maksymiec, Waldemar; Kulik, Andrzej; Dietler, Giovanni; Gruszecki, Wieslaw I

2013-06-01

In this study, we analyzed multibilayer lipid-protein membranes composed of the photosynthetic light-harvesting complex II (LHCII; isolated from spinach [Spinacia oleracea]) and the plant lipids monogalcatosyldiacylglycerol and digalactosyldiacylglycerol. Two types of pigment-protein complexes were analyzed: those isolated from dark-adapted leaves (LHCII) and those from leaves preilluminated with high-intensity light (LHCII-HL). The LHCII-HL complexes were found to be partially phosphorylated and contained zeaxanthin. The results of the x-ray diffraction, infrared imaging microscopy, confocal laser scanning microscopy, and transmission electron microscopy revealed that lipid-LHCII membranes assemble into planar multibilayers, in contrast with the lipid-LHCII-HL membranes, which form less ordered structures. In both systems, the protein formed supramolecular structures. In the case of LHCII-HL, these structures spanned the multibilayer membranes and were perpendicular to the membrane plane, whereas in LHCII, the structures were lamellar and within the plane of the membranes. Lamellar aggregates of LHCII-HL have been shown, by fluorescence lifetime imaging microscopy, to be particularly active in excitation energy quenching. Both types of structures were stabilized by intermolecular hydrogen bonds. We conclude that the formation of trans-layer, rivet-like structures of LHCII is an important determinant underlying the spontaneous formation and stabilization of the thylakoid grana structures, since the lamellar aggregates are well suited to dissipate excess energy upon overexcitation.

Time course of hydrogen peroxide-thioredoxin balance and its influence on the intracellular signalling in myocardial infarction.

PubMed

Schenkel, Paulo Cavalheiro; Tavares, Angela Maria Vicente; Fernandes, Rafael Oliveira; Diniz, Gabriela Placoná; Ludke, Ana Raquel Lehenbauer; Ribeiro, Maria Flavia Marques; Araujo, Alex Sander da Rosa; Barreto-Chaves, Maria Luiza; Belló-Klein, Adriane

2012-06-01

We investigated the myocardial thioredoxin-1 and hydrogen peroxide concentrations and their association with some prosurvival and pro-apoptotic proteins, during the transition from myocardial infarction (MI) to heart failure in rats. Male Wistar rats were divided into the following six groups: three sham-operated groups and three MI groups, each at at 2, 7 and 28 days postsurgery. Cardiac function was analysed by echocardiography; the concentration of H(2)O(2) and the ratio of reduced to oxidized glutathione were measured spectrophotometrically, while the myocardial immunocontent of thioredoxin-1, angiotensin II, angiotensin II type 1 and type 2 receptors, p-JNK/JNK, p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK3β/GSK3β was evaluated by Western blot. Our results show that thioredoxin-1 appears to make an important contribution to the reduced H(2)O(2) concentration. It was associated with lower JNK expression in the early period post-MI (2 days). However, thioredoxin-1 decreased, while renin-angiotensin system markers and levels of H(2)O(2) increased, over 28 days post-MI, in parallel with some signalling proteins involved in maladaptative cardiac remodelling and ventricular dysfunction. These findings provide insight into the time course profile of endogenous antioxidant adaptation to ischaemic injury, which may be useful for the design of therapeutical strategies targeting oxidative stress post-MI.

Quality of Type II Diabetes Care in Primary Health Care Centers in Kuwait: Employment of a Diabetes Quality Indicator Set (DQIS).

PubMed

Badawi, Dalia; Saleh, Shadi; Natafgi, Nabil; Mourad, Yara; Behbehani, Kazem

2015-01-01

Diabetes Mellitus is one of the major public health challenges, affecting more than 347 million adults worldwide. The impact of diabetes necessitates assessing the quality of care received by people with diabetes, especially in countries with a significant diabetes burden such as Kuwait. This paper aimed at piloting an approach for measuring Type II diabetes care performance through the use of a diabetes quality indicator set (DQIS) in primary health care. The DQIS for Kuwait was adapted from that developed by the National Diabetes Quality Improvement Alliance and the International Diabetes Federation. Five key care domains/measures were employed: (1) Blood glucose level measurement, (2) Cholesterol level measurement, (3) Blood pressure measurement, (4) Kidney function testing and (5) Smoking status check. The sample included the four major primary health care centers with the highest case load in Kuwait City, 4,241 patients in 2012 and 3,211 in 2010. Findings revealed the applicability and utility of employing performance indicators for diabetes care in Kuwait. Furthermore, findings revealed that many of the primary health care centers have achieved noteworthy improvement in diabetes care between 2010 and 2012, with the exception of smoking status check. The DQIS can help policymakers identify performance gaps and investigate key system roadblocks related to diabetes care in Kuwait.

Peatland succession induces a shift in the community composition of Sphagnum-associated active methanotrophs.

PubMed

Putkinen, Anuliina; Larmola, Tuula; Tuomivirta, Tero; Siljanen, Henri M P; Bodrossy, Levente; Tuittila, Eeva-Stiina; Fritze, Hannu

2014-06-01

Sphagnum-associated methanotrophs (SAM) are an important sink for the methane (CH4) formed in boreal peatlands. We aimed to reveal how peatland succession, which entails a directional change in several environmental variables, affects SAM and their activity. Based on the pmoA microarray results, SAM community structure changes when a peatland develops from a minerotrophic fen to an ombrotrophic bog. Methanotroph subtypes Ia, Ib, and II showed slightly contrasting patterns during succession, suggesting differences in their ecological niche adaptation. Although the direct DNA-based analysis revealed a high diversity of type Ib and II methanotrophs throughout the studied peatland chronosequence, stable isotope probing (SIP) of the pmoA gene indicated they were active mainly during the later stages of succession. In contrast, type Ia methanotrophs showed active CH4 consumption in all analyzed samples. SIP-derived (13)C-labeled 16S rRNA gene clone libraries revealed a high diversity of SAM in every succession stage including some putative Methylocella/Methyloferula methanotrophs that are not detectable with the pmoA-based approach. In addition, a high diversity of 16S rRNA gene sequences likely representing cross-labeled nonmethanotrophs was discovered, including a significant proportion of Verrucomicrobia-related sequences. These results help to predict the effects of changing environmental conditions on SAM communities and activity. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

The drama of the continuous increase in end-stage renal failure in patients with type II diabetes mellitus.

PubMed

Rychlík, I; Miltenberger-Miltenyi, G; Ritz, E

1998-01-01

Type II diabetes mellitus has become the leading cause of end-stage renal failure in many countries of Western Europe. In all European countries, even in those with a relatively low prevalence of diabetic nephropathy, the number of patients with type II diabetes mellitus admitted for renal replacement therapy has recently increased continuously. Survival and medical rehabilitation of patients with type II diabetes on renal replacement therapy is significantly worse than in non-diabetic patients. It is obvious that in order to stem the tide, intense efforts are necessary (i) to inform the medical community about the renal risk of type II diabetes and the striking effectiveness of preventive measures, (ii) to provide better care for diabetic patients, and (iii) to reduce the high prevalence of diabetes in the population by modification of the Western life style.

Novel apparatus and methods for performing remotely controlled particle-solid interaction experiments at CERN

NASA Astrophysics Data System (ADS)

Krause, H. F.; Deveney, E. F.; Jones, N. L.; Vane, C. R.; Datz, S.; Knudsen, H.; Grafström, P.; Schuch, R.

1997-04-01

Recent atomic physics studies involving ultrarelativistic Pb ions required solid target positioners, scintillators, and a sophisticated data acquisition and control system placed in a remote location at the CERN Super Proton Synchrotron near Geneva, Switzerland. The apparatus, installed in a high-radiation zone underground, had to (i) function for months, (ii) automatically respond to failures such as power outages and particle-induced computer upsets, and (iii) communicate with the outside world via a telephone line. The heart of the apparatus developed was an Apple Macintosh-based CAMAC system that answered the telephone and interpreted and executed remote control commands that (i) sensed and set targets, (ii) controlled voltages and discriminator levels for scintillators, (iii) modified data acquisition hardware logic, (iv) reported control information, and (v) automatically synchronized data acquisition to the CERN spill cycle via a modem signal and transmitted experimental data to a remote computer. No problems were experienced using intercontinental telephone connections at 1200 baud. Our successful "virtual laboratory" approach that uses off-the-shelf electronics is generally adaptable to more conventional bench-type experiments.

Crosslinked type II collagen matrices: preparation, characterization, and potential for cartilage engineering.

PubMed

Pieper, J S; van der Kraan, P M; Hafmans, T; Kamp, J; Buma, P; van Susante, J L C; van den Berg, W B; Veerkamp, J H; van Kuppevelt, T H

2002-08-01

The limited intrinsic repair capacity of articular cartilage has stimulated continuing efforts to develop tissue engineered analogues. Matrices composed of type II collagen and chondroitin sulfate (CS), the major constituents of hyaline cartilage, may create an appropriate environment for the generation of cartilage-like tissue. In this study, we prepared, characterized, and evaluated type 11 collagen matrices with and without CS. Type II collagen matrices were prepared using purified, pepsin-treated, type II collagen. Techniques applied to prepare type I collagen matrices were found unsuitable for type II collagen. Crosslinking of collagen and covalent attachment of CS was performed using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide. Porous matrices were prepared by freezing and lyophilization, and their physico-chemical characteristics (degree of crosslinking, denaturing temperature, collagenase-resistance, amount of CS incorporated) established. Matrices were evaluated for their capacity to sustain chondrocyte proliferation and differentiation in vitro. After 7 d of culture, chondrocytes were mainly located at the periphery of the matrices. In contrast to type I collagen, type II collagen supported the distribution of cells throughout the matrix. After 14 d of culture, matrices were surfaced with a cartilagenous-like layer, and occasionally clusters of chondrocytes were present inside the matrix. Chondrocytes proliferated and differentiated as indicated by biochemical analyses, ultrastructural observations, and reverse transcriptase PCR for collagen types I, II and X. No major differences were observed with respect to the presence or absence of CS in the matrices.

Greenhouse evaluation of commercial soybean cultivars adapted to the northern United States for resistance to charcoal rot

USDA-ARS?s Scientific Manuscript database

Thirty (30) and sixty-seven (67) commercially available soybean (Glycine max (L.) Merr) cultivars from Wisconsin (Maturity group (MG) I-II) and Indiana (MG II-III), respectively, were evaluated for charcoal rot (CR; Macrophomina phaseolina (Tassi) Goid) resistance using a cut-stem greenhouse assay. ...

Military Curricula for Vocational & Technical Education. Light Frame Construction II.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This training manual for a secondary-postsecondary level course in light frame construction II is one of a number of military-developed curriculum packages selected for adaptation to vocational instruction and curriculum development in a civilian setting. Purpose stated for the fifty-five hour course is for students to interpret construction…

Variation in MHC class II B genes in marbled murrelets: implications for delineating conservation units

Treesearch

C. Vásquez-Carrillo; V. Friesen; L. Hall; M.Z. Peery

2013-01-01

Conserving genetic variation is critical for maintaining the evolutionary potential and viability of a species. Genetic studies seeking to delineate conservation units, however, typically focus on characterizing neutral genetic variation and may not identify populations harboring local adaptations. Here, variation at two major histocompatibility complex (MHC) class II...

Surgical management of morbidity due to lymphatic filariasis: the usefulness of a standardized international clinical classification of hydroceles.

PubMed

Capuano, G P; Capuano, C

2012-03-01

The objective of this work is to evaluate the usefulness of a standardized clinical classification of hydroceles in lymphatic filariasis endemic countries to guide their surgical management. 64 patients with hydroceles were operated in 2009-2010, in Level II hospitals (WHO classification), during two visits to Fiji, by the same mobile surgical team. The number of hydroceles treated was 83. We developed and evaluated a much needed clinical classification of hydroceles based on four criteria: Type (uni/bilateral); Side (left/right); Stage of enlargement of the scrotum rated from I to VI; Grade of burial of the penis rated from 0 to 4. It lead to the conclusion that 1) A Stage I or II hydrocele, associated with Grade 0 or 1 penis burial could be considered a "Simple Hydrocele". The surgical treatment is simple with no anticipated early complication. WHO Level II of health care structure seems adapted. 2) A Stage III or IV hydrocele associated with Grade 2, 3 or 4 penis burial could be considered a "Complicated Hydrocele". The operation is longer, more complicated and the possibility of occurrence of complications seems greater. A level III health care facility would be more adapted under the normal functioning of the health system. We conclude that a standardized clinical classification of hydroceles based on the Stage of enlargement of the scrotum and the Grade of burial of the penis appears to be a useful tool to guide the decision about the level of care and the surgical technique required. We use the same classification for penoscrotal lymphoedema. A decision tree is presented for the management of hydroceles in lymphatic filariasis endemic countries which could usefully complement the "Algorithm for management of scrotal swelling" proposed by WHO in 2002. An international classification system of hydroceles would also allow standardization and facilitate study design and comparisons of their results.

Type II solar radio burst band-splitting: Measure of coronal magnetic field strength

NASA Astrophysics Data System (ADS)

Mahrous, Ayman; Alielden, Khaled; Vršnak, Bojan; Youssef, Mohamed

2018-07-01

Studies of the relationship between solar radio bursts and CMEs are essential for understanding of the nature of type II bursts. In this study, we examine the type II solar radio burst recorded on 16 March 2016 by the Learmonth radio spectrograph and compare its characteristics with the kinematics of the associated CMEs observed by STEREO and SOHO spacecraft. The burst showed a well-defined band-split, which was used to estimate the magnetic field strength in the solar corona. The magnetic field decreases from ≈ 4 G at R ≈ 2.6 R⊙ to 0.62 G at R ≈ 3.77 R⊙ depending on the coronal electron density model employed. We found that two CMEs occurred successively in a 4-h interval. During this interval, a type II radio burst occurred, lasting for about 10 min. Tracking of the shock that produced type II burst and comparison with the CMEs heights as observed by STEREO and SOHO spacecraft help us to deduce the driver of the shock. According to the analysis, the type II burst occurrence was associated with the interaction of the shock driven by the second CME with a streamer located south of the first CME, since that the type II band-split significantly increased during the shock-streamer interaction. Our results show that the analysis of the type II burst band-split supplemented by the coronagraphic observations of the corona is an important tool for the understanding of the coronal eruptive processes.

Transposable Elements as Stress Adaptive Capacitors Induce Genomic Instability in Fungal Pathogen Magnaporthe oryzae

PubMed Central

Chadha, Sonia; Sharma, Mradul

2014-01-01

A fundamental problem in fungal pathogenesis is to elucidate the evolutionary forces responsible for genomic rearrangements leading to races with fitter genotypes. Understanding the adaptive evolutionary mechanisms requires identification of genomic components and environmental factors reshaping the genome of fungal pathogens to adapt. Herein, Magnaporthe oryzae, a model fungal plant pathogen is used to demonstrate the impact of environmental cues on transposable elements (TE) based genome dynamics. For heat shock and copper stress exposed samples, eight TEs belonging to class I and II family were employed to obtain DNA profiles. Stress induced mutant bands showed a positive correlation with dose/duration of stress and provided evidences of TEs role in stress adaptiveness. Further, we demonstrate that genome dynamics differ for the type/family of TEs upon stress exposition and previous reports of stress induced MAGGY transposition has underestimated the role of TEs in M. oryzae. Here, we identified Pyret, MAGGY, Pot3, MINE, Mg-SINE, Grasshopper and MGLR3 as contributors of high genomic instability in M. oryzae in respective order. Sequencing of mutated bands led to the identification of LTR-retrotransposon sequences within regulatory regions of psuedogenes. DNA transposon Pot3 was identified in the coding regions of chromatin remodelling protein containing tyrosinase copper-binding and PWWP domains. LTR-retrotransposons Pyret and MAGGY are identified as key components responsible for the high genomic instability and perhaps these TEs are utilized by M. oryzae for its acclimatization to adverse environmental conditions. Our results demonstrate how common field stresses change genome dynamics of pathogen and provide perspective to explore the role of TEs in genome adaptability, signalling network and its impact on the virulence of fungal pathogens. PMID:24709911

Adapted ice cream as a nutritional supplement in cancer patients: impact on quality of life and nutritional status.

PubMed

Casas, Francese; León, Concha; Jovell, Esther; Gómez, Joana; Corvitto, Angelo; Blanco, Remei; Alfaro, Jordi; Ángel Seguí, Miguel; Saigí, Eugeni; Massanés, Toni; Sala, Carme; Librán, Anna; Arcusa, Angels

2012-01-01

The aim of this study was to assess the impact of adapted ice cream as a dietary supplement on the quality of life (QLQ) of malnourished patients with cancer. We present an exploratory prospective observational study comparing two patterns of nutrition in cancer patients admitted during the study period who presented malnutrition disorders: adapted ice cream (Group I: 39 patients) and nutritional supplements (Group II: 31 patients). Patients were selected from two different hospitals from the same Oncologic Institute. QLQ was evaluated with the Hospital Anxiety and Depression Scale (HADS) and QLQ of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30). Nutrition was determined by the PG-SGA test. HADS showed significant differences in anxiety (p = 0.023) and depression (p = 0.011) at the end of the study only in Group I. QLQ-C30 revealed statistically significant differences in baseline measures of global dimension between the two groups (Group I: 40.64-56.36 CI; Group II: 25.70-43.11 CI; p = 0.017). Differences were also present in the social dimension (Group I: 77.42-93.51 CI; Group II: 55.85-82.85 CI; p = 0.039). Statistically significant differences were observed between the two groups at the end of the study in the global scale: Group I had 49.36-63.88 CI and Group II had 33.05-51.88 CI (p = 0.016), and in the fatigue scale: Group I had 36.19-53.83 CI and Group II had mean = 65.87, 52.50-79.23 CI (p = 0.007). The administration of ice cream could cover, in part, the social aspect of food and improve QLQ in malnourished cancer patients. These results are encouraging and deserve further confirmation.

Regional analysis of whole cell currents from hair cells of the turtle posterior crista.

PubMed

Brichta, Alan M; Aubert, Anne; Eatock, Ruth Anne; Goldberg, Jay M

2002-12-01

The turtle posterior crista is made up of two hemicristae, each consisting of a central zone containing type I and type II hair cells and a surrounding peripheral zone containing only type II hair cells and extending from the planum semilunatum to the nonsensory torus. Afferents from various regions of a hemicrista differ in their discharge properties. To see if afferent diversity is related to the basolateral currents of the hair cells innervated, we selectively harvested type I and II hair cells from the central zone and type II hair cells from two parts of the peripheral zone, one near the planum and the other near the torus. Voltage-dependent currents were studied with the whole cell, ruptured-patch method and characterized in voltage-clamp mode. We found regional differences in both outwardly and inwardly rectifying voltage-sensitive currents. As in birds and mammals, type I hair cells have a distinctive outwardly rectifying current (I(K,L)), which begins activating at more hyperpolarized voltages than do the outward currents of type II hair cells. Activation of I(K,L) is slow and sigmoidal. Maximal outward conductances are large. Outward currents in type II cells vary in their activation kinetics. Cells with fast kinetics are associated with small conductances and with partial inactivation during 200-ms depolarizing voltage steps. Almost all type II cells in the peripheral zone and many in the central zone have fast kinetics. Some type II cells in the central zone have large outward currents with slow kinetics and little inactivation. Although these currents resemble I(K,L), they can be distinguished from the latter both electrophysiologically and pharmacologically. There are two varieties of inwardly rectifying currents in type II hair cells: activation of I(K1) is rapid and monoexponential, whereas that of I(h) is slow and sigmoidal. Many type II cells either have both inward currents or only have I(K1); very few cells only have I(h). Inward currents are less conspicuous in type I cells. Type II cells near the torus have smaller outwardly rectifying currents and larger inwardly rectifying currents than those near the planum, but the differences are too small to account for variations in discharge properties of bouton afferents innervating the two regions of the peripheral zone. The large outward conductances seen in central cells, by lowering impedances, may contribute to the low rotational gains of some central-zone afferents.

Integrated care services: lessons learned from the deployment of the NEXES project

PubMed Central

Hernández, Carme; Alonso, Albert; Garcia-Aymerich, Judith; Grimsmo, Anders; Vontetsianos, Theodore; García Cuyàs, Francesc; Altes, Anna Garcia; Vogiatzis, Ioannis; Garåsen, Helge; Pellise, Laura; Wienhofen, Leendert; Cano, Isaac; Meya, Montserrat; Moharra, Montserrat; Martinez, Joan Ignasi; Escarrabill, Juan; Roca, Josep

2015-01-01

Objectives To identify barriers to deployment of four articulated Integrated Care Services supported by Information Technologies in three European sites. The four services covered the entire spectrum of severity of illness. The project targeted chronic patients with obstructive pulmonary disease, cardiac failure and/or type II diabetes mellitus. Setting One health care sector in Spain (Barcelona) (n = 11.382); six municipalities in Norway (Trondheim) (n = 450); and one hospital in Greece (Athens) (n = 388). Method The four services were: (i) Home-based long-term maintenance of rehabilitation effects (n = 337); (ii) Enhanced Care for frail patients, n = 1340); (iii) Home Hospitalization and Early Discharge (n = 2404); and Support for remote diagnosis (forced spirometry testing) in primary care (Support) (n = 8139). Both randomized controlled trials and pragmatic study designs were combined. Two technological approaches were compared. The Model for Assessment of Telemedicine applications was adopted. Results The project demonstrated: (i) Sustainability of training effects over time in chronic patients with obstructive pulmonary disease (p < 0.01); (ii) Enhanced care and fewer hospitalizations in chronic respiratory patients (p < 0.05); (iii) Reduced in-hospital days for all types of patients (p < 0.001) in Home Hospitalization/Early Discharge; and (iv) Increased quality of testing (p < 0.01) for patients with respiratory symptoms in Support, with marked differences among sites. Conclusions The four integrated care services showed high potential to enhance health outcomes with cost-containment. Change management, technological approach and legal issues were major factors modulating the success of the deployment. The project generated a business plan to foster service sustainability and health innovation. Deployment strategies require site-specific adaptations. PMID:26034465

Quality assessment of recent evidence-based clinical practice guidelines for management of type 2 diabetes mellitus in adults using the AGREE II instrument.

PubMed

Anwer, Muhammad A; Al-Fahed, Ousama B; Arif, Samir I; Amer, Yasser S; Titi, Maher A; Al-Rukban, Mohammed O

2018-02-01

Type 2 diabetes mellitus (T2DM) is a worldwide and national public health problem that has a great impact on the population in Saudi Arabia. High-quality clinical practice guidelines (CPGs) are cornerstones in improving the health care provided for patients with diabetes. This study evaluated the methodological rigour, transparency, and applicability of recently published CPGs. Our group conducted a systematic search for recently published CPGs for T2DM. The searching and screening for Source CPGs were guided by tools from the ADAPTE methods with specific inclusion/exclusion criteria. Five reviewers using the second version of the Appraisal of Guidelines for Research and Evaluation (AGREE II) Instrument independently assessed the quality of the retrieved Source CPGs. Domains of Scope and purpose and Clarity of presentation received the highest scores in all CPGs. Most of the assessed CPGs (86%) were considered with high overall quality and were recommended for use. Rigour of development and applicability domains were together highest in 3 CPGs (43%). The overall high quality of DM CPGs published in the last 3 years demonstrated the continuous development and improvement in CPG methodologies and standards. Health care professionals should consider the quality of any CPG for T2DM before deciding to use it in their daily clinical practice. Three CPGs have been identified, using the AGREE criteria, as high-quality and trustworthy. Ideally, the resources provided by the AGREE trust including the AGREE II Instrument should be used by a clinician to scan through the large number of published T2DM CPGs to identify the CPGs with high methodological quality and applicability. © 2017 John Wiley & Sons, Ltd.

Blue-light reception in Phycomyces phototropism: evidence for two photosystems operating in low- and high-intensity ranges

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

Galland, P.; Lipson, E.D.

1987-01-01

Phototropism in the fungus Phycomyces is mediated by two photosystems that are optimized for the low-intensity region (below 10(-6) W X m-2) and the high-intensity region (above 10(-6) W X m-2). These photosystems can be distinguished under special experimental conditions, in which sporangiophores grown in the dark are suddenly exposed to continuous unilateral light. With this treatment, the bending occurs in two steps. Below 10(-6) W X m-2, an early-response component (15-min latency) and a late-response component (50- to 70-min latency) are observed that are mediated by photosystem I. Above 10(-6) W X m-2, the early component is augmented bymore » an intermediate component with a 40-min delay that is mediated by photosystem II. The two photosystems are distinguished further by their wavelength sensitivities and adaptation kinetics. Photosystem I is more effective at 334, 347, and 550 nm than photosystem II, but it is less effective at 383 nm. At wavelength 450 nm, the dark-adaptation kinetics associated with photosystem I are approximately half as fast as those associated with photosystem II. However, the light-adaptation kinetics of photosystem I are approximately equal to 3 times faster than the kinetics associated with photosystem II. The existence of two photosystems clarifies several behavioral features of Phycomyces and helps explain how the sporangiophore can manage the full range of 10 decades.« less

Hybrid capture-II and LCR-E7 PCR assays for HPV typing in cervical cytologic samples.

PubMed

Yamazaki, H; Sasagawa, T; Basha, W; Segawa, T; Inoue, M

2001-10-15

As part of an ongoing cohort study in the Hokuriku region of Japan, cervical cell samples from histologically confirmed normal (n = 114) or abnormal (n = 286) women were examined for the presence of HPV DNA using a second-generation hybrid capture assay (HCA-II) and LCR-E7 PCR. HCA-II detected low-risk (HPV-6, -11, -42, 43 and -44) and high-risk (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59 and -68) HPV types, while LCR-E7 PCR detected an additional 7 HPV types and some uncharacterized types. In screening of high-grade squamous intraepithelial lesions (HSILs) and invasive cervical cancer, the sensitivities of HCA-II and LCR-E7 PCR testing the high-risk HPV types were 83% and 81%, respectively, while the specificity of both assays was 93%. The sensitivity of LCR-E7 PCR increased to 87%, which was significantly higher than that in HCA-II, when testing both high-risk and other HPV types. Sixty-eight inconsistent results (17% of total tested) from HCA-II and LCR-E7 PCR were due to (i) low copy number of HPV genome (false-negative for HCA-II, 5.3% and for LCR-E7 PCR, 1.3%), (ii) infection with HPV types undetectable by HCA-II (4.8%), (iii) multiple HPV infections (5%) or (iv) unknown reasons (0.8%). LCR-E7 PCR revealed that infections with HPV-16, -18, -31, -33, -35, -51, -52, -56, -58 or -67 was a high risk for cancer since these types predominated in HSIL and invasive cervical cancer. Samples showing high relative light units (>20) with a high-risk probe in HCA-II also gave positive results in LCR-E7 PCR and were generally associated with abnormal cervical lesions. Thus, we propose that both HCA-II and LCR-E7 PCR are valuable screening tests for premalignant and malignant cervical lesions. Copyright 2001 Wiley-Liss, Inc.

Investigation on the Mechanism and Failure Mode of Laser Transmission Spot Welding Using PMMA Material for the Automotive Industry

PubMed Central

Wang, Xiao; Liu, Baoguang; Liu, Wei; Zhong, Xuejiao; Jiang, Yingjie; Liu, Huixia

2017-01-01

To satisfy the need of polymer connection in lightweight automobiles, a study on laser transmission spot welding using polymethyl methacrylate (PMMA) is conducted by using an Nd:YAG pulse laser. The influence of three variables, namely peak voltages, defocusing distances and the welding type (type I (pulse frequency and the duration is 25 Hz, 0.6 s) and type II (pulse frequency and the duration is 5 Hz, 3 s)) to the welding quality was investigated. The result showed that, in the case of the same peak voltages and defocusing distances, the number of bubbles for type I was obviously more than type II. The failure mode of type I was the base plate fracture along the solder joint, and the connection strength of type I was greater than type II. The weld pool diameter:depth ratio for type I was significantly greater than type II. It could be seen that there was a certain relationship between the weld pool diameter:depth ratio and the welding strength. By the finite element simulation, the weld pool for type I was more slender than type II, which was approximately the same as the experimental results. PMID:28772383

Investigation on the Mechanism and Failure Mode of Laser Transmission Spot Welding Using PMMA Material for the Automotive Industry.

PubMed

Wang, Xiao; Liu, Baoguang; Liu, Wei; Zhong, Xuejiao; Jiang, Yingjie; Liu, Huixia

2017-01-01

To satisfy the need of polymer connection in lightweight automobiles, a study on laser transmission spot welding using polymethyl methacrylate (PMMA) is conducted by using an Nd:YAG pulse laser. The influence of three variables, namely peak voltages, defocusing distances and the welding type (type I (pulse frequency and the duration is 25 Hz, 0.6 s) and type II (pulse frequency and the duration is 5 Hz, 3 s)) to the welding quality was investigated. The result showed that, in the case of the same peak voltages and defocusing distances, the number of bubbles for type I was obviously more than type II. The failure mode of type I was the base plate fracture along the solder joint, and the connection strength of type I was greater than type II. The weld pool diameter:depth ratio for type I was significantly greater than type II. It could be seen that there was a certain relationship between the weld pool diameter:depth ratio and the welding strength. By the finite element simulation, the weld pool for type I was more slender than type II, which was approximately the same as the experimental results.

Emendation of Propionibacterium acnes subsp. acnes (Deiko et al. 2015) and proposal of Propionibacterium acnes type II as Propionibacterium acnes subsp. defendens subsp. nov.

PubMed

McDowell, Andrew; Barnard, Emma; Liu, Jared; Li, Huiying; Patrick, Sheila

2016-12-01

Recently, it has been proposed that strains of Propionibacterium acnes from the type III genetic division should be classified as P. acnessubsp. elongatum subsp. nov., with strains from the type I and II divisions collectively classified as P. acnessubsp. acnes subsp. nov. Under such a taxonomic re-appraisal, we believe that types I and II should also have their own separate rank of subspecies. In support of this, we describe a polyphasic taxonomic study based on the analysis of publicly available multilocus and whole-genome sequence datasets, alongside a systematic review of previously published phylogenetic, genomic, phenotypic and clinical data. Strains of types I and II form highly distinct clades on the basis of multilocus sequence analysis (MLSA) and whole-genome phylogenetic reconstructions. In silico or digital DNA-DNA similarity values also fall within the 70-80 % boundary recommended for bacterial subspecies. Furthermore, we see important differences in genome content, including the presence of an active CRISPR/Cas system in type II strains, but not type I, and evidence for increasing linkage equilibrium within the separate divisions. Key biochemical differences include positive test results for β-haemolytic, neuraminidase and sorbitol fermentation activities with type I strains, but not type II. We now propose that type I strains should be classified as P. acnessubsp. acnes subsp. nov., and type II as P. acnessubsp. defendens subsp. nov. The type strain of P. acnessubsp. acnes subsp. nov. is NCTC 737T (=ATCC 6919T=JCM 6425T=DSM 1897T=CCUG 1794T), while the type strain of P. acnessubsp. defendens subsp. nov. is ATCC 11828 (=JCM 6473=CCUG 6369).

Genotyping of samples from German patients with ocular, cerebral and systemic toxoplasmosis reveals a predominance of Toxoplasma gondii type II.

PubMed

Herrmann, Daland C; Maksimov, Pavlo; Hotop, Andrea; Groß, Uwe; Däubener, Walter; Liesenfeld, Oliver; Pleyer, Uwe; Conraths, Franz J; Schares, Gereon

2014-10-01

Toxoplasmosis is an important zoonosis transmitted from animals to humans world-wide. In order to determine Toxoplasma gondii genotypes in individuals living in Germany and to compare findings with those in animals, we analysed nine independent and unlinked genetic markers (nSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) by PCR-RFLP in 83 archived T. gondii-positive DNA samples from patients with ocular toxoplasmosis (n=35), toxoplasmic encephalitis (n=32), systemic toxoplasmosis after bone-marrow transplantation (n=15) and congenital toxoplasmosis (n=1). In 46 of these 83 samples the presence of T. gondii DNA was confirmed by conventional end-point PCR. Among these, 17 T. gondii-positive samples were typed at all nine loci. The majority (15/17, 88.2%) of these samples were of T. gondii type II (i.e., including both, the Apico type II and Apico type I variants). In addition, in one sample a T. gondii type II/type III allele combination and in another sample a T. gondii genotype displaying type III alleles at all markers was observed. In the remaining 11 samples, in which T. gondii could only be partially typed, exclusively type II (n=10) or type III (n=1) alleles were observed. Results of the present study suggest that the majority of patients in Germany are infected with type II T. gondii regardless of the clinical manifestation of toxoplasmosis. This finding is in accord with the predominance of type II T. gondii in oocysts isolated from cats and in tissues of other intermediate hosts in Germany. Copyright © 2014 Elsevier GmbH. All rights reserved.

Essential core of the Hawking–Ellis types

NASA Astrophysics Data System (ADS)

Martín-Moruno, Prado; Visser, Matt

2018-06-01

The Hawking–Ellis (Segre–Plebański) classification of possible stress–energy tensors is an essential tool in analyzing the implications of the Einstein field equations in a more-or-less model-independent manner. In the current article the basic idea is to simplify the Hawking–Ellis type I, II, III, and IV classification by isolating the ‘essential core’ of the type II, type III, and type IV stress–energy tensors; this being done by subtracting (special cases of) type I to simplify the (Lorentz invariant) eigenvalue structure as much as possible without disturbing the eigenvector structure. We will denote these ‘simplified cores’ type II0, type III0, and type IV0. These ‘simplified cores’ have very nice and simple algebraic properties. Furthermore, types I and II0 have very simple classical interpretations, while type IV0 is known to arise semi-classically (in renormalized expectation values of standard stress–energy tensors). In contrast type III0 stands out in that it has neither a simple classical interpretation, nor even a simple semi-classical interpretation. We will also consider the robustness of this classification considering the stability of the different Hawking–Ellis types under perturbations. We argue that types II and III are definitively unstable, whereas types I and IV are stable.

An {alpha}1(II) Gly{sup 913} to cys substitution prevents the matrix incorporation of type II collagen which is replaced with type I and III collagens in cartilage from a patient with hypochondrogenesis

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

Mundlos, S.; Chan, D.; Bateman, J.F.

1996-05-03

A heterozygous mutation in the COL2A1 gene was identified in a patient with hypochondrogenesis. The mutation was a single nucleotide transition of G3285T that resulted in an amino acid substitution of Cys for Gly{sup 913} in the {alpha}1(II) chain of type II collagen. This amino acid change disrupted the obligatory Gly-X-Y triplet motif required for the normal formation of a stable collagen triple helix and prevented the deposition of type II collagen into the proposita`s cartilage, which contained predominantly type I and III collagens and minor amounts of type XI collagen. Biosynthetic analysis of collagens produced and secreted by themore » patient`s chondrocytes cultured in alginate beads was consistent with the in vivo matrix composition, demonstrating that the main products were type I and III collagens, along with type XI collagen. The synthesis of the cartilage-specific type XI collagen at similar levels to controls indicated that the isolated cartilage cells had re-differentiated to the chondrocyte phenotype. The chondrocytes also produced small amounts of type II collagen, but this was post-translationally overmodified and not secreted. These data further delineate the biochemical and phenotypic consequences of mutations in the COL2A1 gene and suggest that cartilage formation and bone development can take place in the absence of type II collagen. 23 refs., 5 figs.« less

Subtype-dependent postnatal development of taste receptor cells in mouse fungiform taste buds.

PubMed

Ohtubo, Yoshitaka; Iwamoto, Masafumi; Yoshii, Kiyonori

2012-06-01

Taste buds contain two types of taste receptor cells, inositol 1,4,5-triphosphate receptor type 3-immunoreactive cells (type II cells) and synaptosomal-associating protein-25-immunoreactive cells (type III cells). We investigated their postnatal development in mouse fungiform taste buds immunohistochemically and electrophysiologically. The cell density, i.e. the number of cells per taste bud divided by the maximal area of the horizontal cross-section of the taste bud, of type II cells increased by postnatal day (PD)49, where as that of type III cells was unchanged throughout the postnatal observation period and was equal to that of the adult cells at PD1. The immunoreactivity of taste bud cell subtypes was the same as that of their respective subtypes in adult mice throughout the postnatal observation period. Almost all type II cells were immunoreactive to gustducin at PD1, and then the ratio of gustducin-immunoreactive type II cells to all type II cells decreased to a saturation level, ∼60% of all type II cells, by PD15. Type II and III cells generated voltage-gated currents similar to their respective adult cells even at PD3. These results show that infant taste receptor cells are as excitable as those of adults and propagate in a subtype-dependent manner. The relationship between the ratio of each taste receptor cell subtype to all cells and taste nerve responses are discussed. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

A genetic marker of the ACKR1 gene is present in patients with Type II congenital smell loss who have type I hyposmia and hypogeusia

PubMed Central

Stateman, William A.; Knöppel, Alexandra B.; Flegel, Willy A.; Henkin, Robert I.

2015-01-01

PURPOSE Our previous study of Type II congenital smell loss patients revealed a statistically significant lower prevalence of an FY (ACKR1, formerly DARC) haplotype compared to controls. The present study correlates this genetic feature with subgroups of patients defined by specific smell and taste functions. METHODS Smell and taste function measurements were performed by use of olfactometry and gustometry to define degree of abnormality of smell and taste function. Smell loss was classified as anosmia or hyposmia (types I, II or III). Taste loss was similarly classified as ageusia or hypogeusia (types I, II or III). Based upon these results patient erythrocyte antigen expression frequencies were categorized by smell and taste loss with results compared between patients within the Type II group and published controls. RESULTS Comparison of antigen expression frequencies revealed a statistically significant decrease in incidence of an Fyb haplotype only among patients with type I hyposmia and any form of taste loss (hypogeusia). In all other patient groups erythrocyte antigens were expressed at normal frequencies. CONCLUSIONS Data suggest that Type II congenital smell loss patients who exhibit both type I hyposmia and hypogeusia are genetically distinct from all other patients with Type II congenital smell loss. This distinction is based on decreased Fyb expression which correlated with abnormalities in two sensory modalities (hyposmia type I and hypogeusia). Only patients with these two specific sensory abnormalities expressed the Fyb antigen (encoded by the ACKR1 gene on the long arm of chromosome 1) at frequencies different from controls. PMID:27968956

Restriction enzyme body doubles and PCR cloning: on the general use of type IIs restriction enzymes for cloning.

PubMed

Tóth, Eszter; Huszár, Krisztina; Bencsura, Petra; Kulcsár, Péter István; Vodicska, Barbara; Nyeste, Antal; Welker, Zsombor; Tóth, Szilvia; Welker, Ervin

2014-01-01

The procedure described here allows the cloning of PCR fragments containing a recognition site of the restriction endonuclease (Type IIP) used for cloning in the sequence of the insert. A Type IIS endonuclease--a Body Double of the Type IIP enzyme--is used to generate the same protruding palindrome. Thus, the insert can be cloned to the Type IIP site of the vector without digesting the PCR product with the same Type IIP enzyme. We achieve this by incorporating the recognition site of a Type IIS restriction enzyme that cleaves the DNA outside of its recognition site in the PCR primer in such a way that the cutting positions straddle the desired overhang sequence. Digestion of the PCR product by the Body Double generates the required overhang. Hitherto the use of Type IIS restriction enzymes in cloning reactions has only been used for special applications, the approach presented here makes Type IIS enzymes as useful as Type IIP enzymes for general cloning purposes. To assist in finding Body Double enzymes, we summarised the available Type IIS enzymes which are potentially useful for Body Double cloning and created an online program (http://group.szbk.u-szeged.hu/welkergr/body_double/index.html) for the selection of suitable Body Double enzymes and the design of the appropriate primers.

Specific Molecular Signatures for Type II Crustins in Penaeid Shrimp Uncovered by the Identification of Crustin-Like Antimicrobial Peptides in Litopenaeus vannamei

PubMed Central

Barreto, Cairé; Coelho, Jaqueline da Rosa; Yuan, Jianbo; Xiang, Jianhai; Perazzolo, Luciane Maria

2018-01-01

Crustins form a large family of antimicrobial peptides (AMPs) in crustaceans composed of four sub-groups (Types I-IV). Type II crustins (Type IIa or “Crustins” and Type IIb or “Crustin-like”) possess a typical hydrophobic N-terminal region and are by far the most representative sub-group found in penaeid shrimp. To gain insight into the molecular diversity of Type II crustins in penaeids, we identified and characterized a Type IIb crustin in Litopenaeus vannamei (Crustin-like Lv) and compared Type II crustins at both molecular and transcriptional levels. Although L. vannamei Type II crustins (Crustin Lv and Crustin-like Lv) are encoded by separate genes, they showed a similar tissue distribution (hemocytes and gills) and transcriptional response to the shrimp pathogens Vibrio harveyi and White spot syndrome virus (WSSV). As Crustin Lv, Crustin-like Lv transcripts were found to be present early in development, suggesting a maternal contribution to shrimp progeny. Altogether, our in silico and transcriptional data allowed to conclude that (1) each sub-type displays a specific amino acid signature at the C-terminal end holding both the cysteine-rich region and the whey acidic protein (WAP) domain, and that (2) shrimp Type II crustins evolved from a common ancestral gene that conserved a similar pattern of transcriptional regulation. PMID:29337853

Endogenous and maximal sarcoplasmic reticulum calcium content and calsequestrin expression in type I and type II human skeletal muscle fibres.

PubMed

Lamboley, C R; Murphy, R M; McKenna, M J; Lamb, G D

2013-12-01

The relationship between sarcoplasmic reticulum (SR) Ca(2+) content and calsequestrin (CSQ) isoforms was investigated in human skeletal muscle. A fibre-lysing assay was used to quantify the endogenous Ca(2+) content and maximal Ca(2+) capacity of the SR in skinned segments of type I and type II fibres from vastus lateralis muscles of young healthy adults. Western blotting of individual fibres showed the great majority contained either all fast or all slow isoforms of myosin heavy chain (MHC), troponins C and I, tropomyosin and SERCA, and that the strontium sensitivity of the force response was closely indicative of the troponin C isoform present. The endogenous SR Ca(2+) content was slightly lower in type I compared to type II fibres (0.76 ± 0.03 and 0.85 ± 0.02 mmol Ca(2+) per litre of fibre, respectively), with virtually all of this Ca(2+) evidently being in the SR, as it could be rapidly released with a caffeine-low [Mg(2+)] solution (only 0.08 ± 0.01 and <0.07 mmol l(-1), respectively, remaining). The maximal Ca(2+) content that could be reached with SR Ca(2+) loading was 1.45 ± 0.04 and 1.79 ± 0.03 mmol l(-1) in type I and type II fibres, respectively (P < 0.05). In non-lysed skinned fibres, where the SR remained functional, repeated cycles of caffeine-induced Ca(2+) release and subsequent Ca(2+) reloading similarly indicated that (i) maximal SR Ca(2+) content was lower in type I fibres than in type II fibres (P < 0.05), and (ii) the endogenous Ca(2+) content represented a greater percentage of maximal content in type I fibres compared to type II fibres (∼59% and 41%, respectively, P < 0.05). Type II fibres were found on average to contain ∼3-fold more CSQ1 and ∼5-fold less CSQ2 than type I fibres (P < 0.001). The findings are consistent with the SR Ca(2+) content characteristics in human type II fibres being primarily determined by the CSQ1 abundance, and in type I fibres by the combined amounts of both CSQ1 and CSQ2.

Endogenous and maximal sarcoplasmic reticulum calcium content and calsequestrin expression in type I and type II human skeletal muscle fibres

PubMed Central

Lamboley, C R; Murphy, R M; McKenna, M J; Lamb, G D

2013-01-01

The relationship between sarcoplasmic reticulum (SR) Ca2+ content and calsequestrin (CSQ) isoforms was investigated in human skeletal muscle. A fibre-lysing assay was used to quantify the endogenous Ca2+ content and maximal Ca2+ capacity of the SR in skinned segments of type I and type II fibres from vastus lateralis muscles of young healthy adults. Western blotting of individual fibres showed the great majority contained either all fast or all slow isoforms of myosin heavy chain (MHC), troponins C and I, tropomyosin and SERCA, and that the strontium sensitivity of the force response was closely indicative of the troponin C isoform present. The endogenous SR Ca2+ content was slightly lower in type I compared to type II fibres (0.76 ± 0.03 and 0.85 ± 0.02 mmol Ca2+ per litre of fibre, respectively), with virtually all of this Ca2+ evidently being in the SR, as it could be rapidly released with a caffeine-low [Mg2+] solution (only 0.08 ± 0.01 and <0.07 mmol l−1, respectively, remaining). The maximal Ca2+ content that could be reached with SR Ca2+ loading was 1.45 ± 0.04 and 1.79 ± 0.03 mmol l−1 in type I and type II fibres, respectively (P < 0.05). In non-lysed skinned fibres, where the SR remained functional, repeated cycles of caffeine-induced Ca2+ release and subsequent Ca2+ reloading similarly indicated that (i) maximal SR Ca2+ content was lower in type I fibres than in type II fibres (P < 0.05), and (ii) the endogenous Ca2+ content represented a greater percentage of maximal content in type I fibres compared to type II fibres (∼59% and 41%, respectively, P < 0.05). Type II fibres were found on average to contain ∼3–fold more CSQ1 and ∼5–fold less CSQ2 than type I fibres (P < 0.001). The findings are consistent with the SR Ca2+ content characteristics in human type II fibres being primarily determined by the CSQ1 abundance, and in type I fibres by the combined amounts of both CSQ1 and CSQ2. PMID:24127619

Prevalent genotypes of Toxoplasma gondii in pregnant women and patients from Crete and Cyprus.

PubMed

Messaritakis, Ippokratis; Detsika, Maria; Koliou, Maria; Sifakis, Stavros; Antoniou, Maria

2008-08-01

Molecular genotyping has been used to characterize Toxoplasma gondii strains into the three clonal lineages known as types I, II, and III. To characterize T. gondii strains from Greece and Cyprus, polymerase chain reaction-restriction fragment length polymorphism analysis on the GRA6 gene was performed directly on 20 clinical samples from 18 humans (11 pregnant women, six patients with lymphadenopathy, and one patient positive for human immunodeficiency virus) and two rats. Characterization of T. gondii types was performed after digestion of amplified products with Mse I. The 20 strains were characterized as type II (20%) and type III (80%). Of these strains, 19 originated from the island of Crete (4 strains type II and 15 strains type III), and 1 from the island of Cyprus (type III). Although both type II and type III strains were found, type III was the most prevalent in Crete.

Creation of a type IIS restriction endonuclease with a long recognition sequence

PubMed Central

Lippow, Shaun M.; Aha, Patti M.; Parker, Matthew H.; Blake, William J.; Baynes, Brian M.; Lipovšek, Daša

2009-01-01

Type IIS restriction endonucleases cleave DNA outside their recognition sequences, and are therefore particularly useful in the assembly of DNA from smaller fragments. A limitation of type IIS restriction endonucleases in assembly of long DNA sequences is the relative abundance of their target sites. To facilitate ligation-based assembly of extremely long pieces of DNA, we have engineered a new type IIS restriction endonuclease that combines the specificity of the homing endonuclease I-SceI with the type IIS cleavage pattern of FokI. We linked a non-cleaving mutant of I-SceI, which conveys to the chimeric enzyme its specificity for an 18-bp DNA sequence, to the catalytic domain of FokI, which cuts DNA at a defined site outside the target site. Whereas previously described chimeric endonucleases do not produce type IIS-like precise DNA overhangs suitable for ligation, our chimeric endonuclease cleaves double-stranded DNA exactly 2 and 6 nt from the target site to generate homogeneous, 5′, four-base overhangs, which can be ligated with 90% fidelity. We anticipate that these enzymes will be particularly useful in manipulation of DNA fragments larger than a thousand bases, which are very likely to contain target sites for all natural type IIS restriction endonucleases. PMID:19304757

Lorentz-violating type-II Dirac fermions in transition metal dichalcogenide PtTe2.

PubMed

Yan, Mingzhe; Huang, Huaqing; Zhang, Kenan; Wang, Eryin; Yao, Wei; Deng, Ke; Wan, Guoliang; Zhang, Hongyun; Arita, Masashi; Yang, Haitao; Sun, Zhe; Yao, Hong; Wu, Yang; Fan, Shoushan; Duan, Wenhui; Zhou, Shuyun

2017-08-15

Topological semimetals have recently attracted extensive research interests as host materials to condensed matter physics counterparts of Dirac and Weyl fermions originally proposed in high energy physics. Although Lorentz invariance is required in high energy physics, it is not necessarily obeyed in condensed matter physics, and thus Lorentz-violating type-II Weyl/Dirac fermions could be realized in topological semimetals. The recent realization of type-II Weyl fermions raises the question whether their spin-degenerate counterpart-type-II Dirac fermions-can be experimentally realized too. Here, we report the experimental evidence of type-II Dirac fermions in bulk stoichiometric PtTe 2 single crystal. Angle-resolved photoemission spectroscopy measurements and first-principles calculations reveal a pair of strongly tilted Dirac cones along the Γ-A direction, confirming PtTe 2 as a type-II Dirac semimetal. Our results provide opportunities for investigating novel quantum phenomena (e.g., anisotropic magneto-transport) and topological phase transition.Whether the spin-degenerate counterpart of Lorentz-violating Weyl fermions, the Dirac fermions, can be realized remains as an open question. Here, Yan et al. report experimental evidence of such type-II Dirac fermions in bulk PtTe 2 single crystal with a pair of strongly tilted Dirac cones.

Human T-Cell Lymphotropic Virus Type 1 Open Reading Frame II-Encoded p30II Is Required for In Vivo Replication: Evidence of In Vivo Reversion

PubMed Central

Silverman, Lee R.; Phipps, Andrew J.; Montgomery, Andrew; Ratner, Lee; Lairmore, Michael D.

2004-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma and exhibits high genetic stability in vivo. HTLV-1 contains four open reading frames (ORFs) in its pX region. ORF II encodes two proteins, p30II and p13II, both of which are incompletely characterized. p30II localizes to the nucleus or nucleolus and has distant homology to the transcription factors Oct-1, Pit-1, and POU-M1. In vitro studies have demonstrated that at low concentrations, p30II differentially regulates cellular and viral promoters through an interaction with CREB binding protein/p300. To determine the in vivo significance of p30II, we inoculated rabbits with cell lines expressing either a wild-type clone of HTLV-1 (ACH.1) or a clone containing a mutation in ORF II, which eliminated wild-type p30II expression (ACH.30.1). ACH.1-inoculated rabbits maintained higher HTLV-1-specific antibody titers than ACH.30.1-inoculated rabbits, and all ACH.1-inoculated rabbits were seropositive for HTLV-1, whereas only two of six ACH.30.1-inoculated rabbits were seropositive. Provirus could be consistently PCR amplified from peripheral blood mononuclear cell (PBMC) DNA in all ACH.1-inoculated rabbits but in only three of six ACH.30.1-inoculated rabbits. Quantitative competitive PCR indicated higher PBMC proviral loads in ACH.1-inoculated rabbits. Interestingly, sequencing of ORF II from PBMC of provirus-positive ACH.30.1-inoculated rabbits revealed a reversion to wild-type sequence with evidence of early coexistence of mutant and wild-type sequence. Our data provide evidence that HTLV-1 must maintain its key accessory genes to survive in vivo and that in vivo pressures select for maintenance of wild-type ORF II gene products during the early course of infection. PMID:15047799

The functional morphology of color changing in a spider: development of ommochrome pigment granules.

PubMed

Insausti, Teresita C; Casas, Jérôme

2008-03-01

Studies on the formation of ommochrome pigment granules are very few, despite their generalized occurrence as screening pigments in insect eyes. This is particularly true for ommochrome granules responsible for epidermal coloration. The aims of this study were to characterize the localization of major body pigments in a color changing mimetic spider, Misumena vatia (Thomisidae), and to describe the formation and location of ommochrome pigment granules responsible for the spider's color change from white to yellow. The unpigmented cuticula of this spider is transparent. Both the guanine localized in guanine cells in the opisthosoma and the uric acid localized in epidermis cells in the prosoma are responsible for the white coloration. The bright yellow color is due to the combination of ommochrome pigment granules and the white reflectance from coincident guanine and/or uric acid. The formation of ommochrome pigment granules in epidermis cells proceeds via three distinctive steps. Translucent, UV fluorescent, progranules (type I) are produced by a dense network of endoplasmic reticulum associated with numerous mitochondria and glycogen rosettes. These progranules are present in white spiders only, and regularly distributed in the cytoplasm. The merging of several progranules of type I into a transient state (progranule type II) leads to the formation of granules (type III) characterized by their lack of fluorescence, their spherical sections and their osmophilic-electron-dense contents. They are found in yellow spiders and in the red stripes on the body sides. Their color varies from yellow to red. Thus, white spiders contain only type I granules, yellow tinted spiders contain type II and III granules and bright yellow spiders contain only type III granules. We present a synthetic view of the ontogeny of ommochrome granules. We discuss the physiology of color changing and the nature of the chemical compounds in the different types of granules. Extended studies on the ultrastructural modification and physiological processes associated with color change are required before any statement about the adaptiveness of the color change can be made.

Type II solar radio bursts, interplanetary shocks, and energetic particle events

NASA Technical Reports Server (NTRS)

Cane, H. V.; Stone, R. G.

1984-01-01

Using the ISEE-3 radio astronomy experiment data 37 interplanetary (IP) type II bursts have been identified in the period September 1978 to December 1981. These events and the associated phenomena are listed. The events are preceded by intense, soft X ray events with long decay times (LDEs) and type II and/or type IV bursts at meter wavelengths. The meter wavelength type II bursts are usually intense and exhibit herringbone structure. The extension of the herringbone structure into the kilometer wavelength range results in the occurrence of a shock accelerated (SA) event. The majority of the interplanetary type II bursts are associated with energetic particle events. These results support other studies awhich indicate that energetic solar particles detected at 1 A.U. are generated by shock acceleration. From a preliminary analysis of the available data there appears to be a high correlation with white light coronal transients.

Adenocarcinoma of the lung with scattered consolidation: radiological-pathological correlation and prognosis.

PubMed

Jiang, Binghu; Takashima, Shodayu; Hakucho, Tomoaki; Hodaka, Numasaki; Yasuhiko, Tomita; Masahiko, Higashiyama

2013-10-01

To investigate the clinicopathological features and prognosis in patients with adenocarcinoma of the lung with scattered consolidation (ALSC). Between January 2006 and March 2010, 139 consecutive patients with lung adenocarcinoma of ≤3 cm, who underwent pulmonary resection for lung cancer, were investigated retrospectively. Radiologic classification was based on the findings of thin-section CT such as the presence of consolidation or ground-glass opacity (GGO). Type I (n=15) and Type II (n=14), showed a pure GGO and a mixed GGO with consolidation <50%, respectively. Type IV (n=38) and Type V (n=52) showed a mixed GGO with consolidation ≥50% and a pure consolidation, respectively. Type III (n=20) was the adenocarcinoma of the lung with scattered consolidation (ALSC). The clinicopathological features and prognosis of ALSC was investigated with comparative analysis and survival analysis. Because of the similar recurrence rate for Type I and Type II (P=1.000), Type IV and Type V (P=0.343), we merged Type I and Type II as Type I+II, Type IV and Type V as Type IV+V, respectively. In the 20 (14.4%) patients with ALSC, lymph node metastasis was not observed, and it was rare in lymphatic invasion and vascular invasion. On the basis of IASLC/ATS/ERS 2011 classification, 80% of the ALSC were preinvasive lesions. In Noguchi classification, there was no significant difference between Type I+II and ALSC (P=0.260). The prognosis of ALSC was similar to Type I+II (P=0.408), but better than Type IV+V (P=0.040). Adenocarcinoma of the lung with scattered consolidation (ALSC) on thin-section CT was a relatively favorable prognostic factor. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Combined Final Report for Colony II Project

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

Kale, Laxmikant; Jones, Terry; Moreira, Jose

2013-10-23

(This report was originally submmited by the lead PI (Terry Jones, ORNL) on October 22, 2013 to the program manager, Lucy Nowell. It is being submitted from University of Illinois in accordance with instructions). HPC Colony II seeks to provide portable performance for leadership class machines. Our strategy is based on adaptive system software that aims to make the intelligent decisions necessary to allow domain scientists to safely focus on their task at hand and allow the system software stack to adapt their application to the underlying architecture. This report describes the research undertaken towards these objectives and the resultsmore » obtained over the performance period of the project.« less

Rare association of spondylo costal dysostosis with split cord malformations type II: A case report and a brief review of literature

PubMed Central

Srinivas, Bhavanam Hanuma; Puligopu, Aneel Kumar; Sukhla, Dinesh; Ranganath, Prajnya

2014-01-01

Spondylo costal dysostosis (SCD) is a genetic skeletal disorder characterized by a variety of costo-vertebral malformations. SCD with type I split cord malformation (SCM) have been reported in the literature. We report an unusual association of SCD with type II SCM. Imaging studies revealed multiple vertebral segmentations, rib malformations, spina bifida and low lying cord with type II SCM at the D12-L3 level. She underwent detethering of the cord. To the best of our knowledge, this is the first report of the association of SCD with type II SCM. PMID:25250070

A risk-based approach to flood management decisions in a nonstationary world

NASA Astrophysics Data System (ADS)

Rosner, Ana; Vogel, Richard M.; Kirshen, Paul H.

2014-03-01

Traditional approaches to flood management in a nonstationary world begin with a null hypothesis test of "no trend" and its likelihood, with little or no attention given to the likelihood that we might ignore a trend if it really existed. Concluding a trend exists when it does not, or rejecting a trend when it exists are known as type I and type II errors, respectively. Decision-makers are poorly served by statistical and/or decision methods that do not carefully consider both over- and under-preparation errors, respectively. Similarly, little attention is given to how to integrate uncertainty in our ability to detect trends into a flood management decision context. We show how trend hypothesis test results can be combined with an adaptation's infrastructure costs and damages avoided to provide a rational decision approach in a nonstationary world. The criterion of expected regret is shown to be a useful metric that integrates the statistical, economic, and hydrological aspects of the flood management problem in a nonstationary world.

[Limits of cardiac functional adaptation in "top level" resistance athletes].

PubMed

Carù, B; Righetti, G; Bossi, M; Gerosa, C; Gazzotti, G; Maranetto, D

2001-02-01

Sports activity, particularly when performed at high level, provokes cardiovascular adjustments depending on the type of sport and on the level of the load. We evaluated 15 athletes from the Italian national team during a non-agonistic period of cross country skiing, with non-invasive tests including exercise test, color Doppler echocardiography, Holter monitoring, physical examination and standard rest electrocardiogram. Physical examination, rest electrocardiogram, exercise testing and echocardiography were all within the range of the expected values for this type of subjects. Holter monitoring recorded during the periods of agonistic activity revealed significant hypokinetic arrhythmias such as severe bradycardia, pauses, I and II degree atrioventricular blocks, and complete atrioventricular block in 2 cases; these features were not observed on Holter monitoring recorded during the non-agonistic period. The perfect health status of subjects and their racing results may bring about physiological functional adjustments, but these observations suggest the need for a follow-up to evaluate possible pathologic outcomes.

Cognitive Adaptation Theory and Breast Cancer Recurrence: Are There Limits?

ERIC Educational Resources Information Center

Tomich, Patricia L.; Helgeson, Vicki S.

2006-01-01

Relations of the components of cognitive adaptation theory (self-esteem, optimism, control) to quality of life and benefit finding were examined for 70 women (91% Caucasian) diagnosed with Stage I, II, or III breast cancer over 5 years ago. Half of these women experienced a recurrence within the 5 years; the other half remained disease free. Women…

20 CFR 220.128 - Age as a vocational factor.

Code of Federal Regulations, 2010 CFR

2010-04-01

... or her ability to— (i) Adapt to a new work situation; and (ii) Do work in competition with others. (2... new work situation. In some circumstances, the Board considers age 45 a handicap in adapting to a new work setting (see Rule 201.17 in appendix 2 of this part). (c) Person approaching advanced age. If the...

User-Adaptable Microcomputer Graphics Software for Life Science Instruction. Final Project Report.

ERIC Educational Resources Information Center

Spain, James D.

The objectives of the SUMIT project was to develop, evaluate, and disseminate 20 course modules (microcomputer programs) for instruction in general biology and ecology. To encourage broad utilization, the programs were designed for the Apple II microcomputer and written in Applesoft Basic with a user-adaptable format. Each package focused on a key…

College Adapter Program Curriculum Design. Manpower Education Monograph Series, Volume II.

ERIC Educational Resources Information Center

Higher Education Development Fund, New York, NY.

The College Adapter Program (CAP) is a program to train inner-city young men and women with high potential for post-secondary technical training. These young men and women either have dropped out of high school, or have been insufficiently prepared in high school for further educational training. The Curriculum Design monograph is a statement of…

Type I and II β-turns prediction using NMR chemical shifts.

PubMed

Wang, Ching-Cheng; Lai, Wen-Chung; Chuang, Woei-Jer

2014-07-01

A method for predicting type I and II β-turns using nuclear magnetic resonance (NMR) chemical shifts is proposed. Isolated β-turn chemical-shift data were collected from 1,798 protein chains. One-dimensional statistical analyses on chemical-shift data of three classes β-turn (type I, II, and VIII) showed different distributions at four positions, (i) to (i + 3). Considering the central two residues of type I β-turns, the mean values of Cο, Cα, H(N), and N(H) chemical shifts were generally (i + 1) > (i + 2). The mean values of Cβ and Hα chemical shifts were (i + 1) < (i + 2). The distributions of the central two residues in type II and VIII β-turns were also distinguishable by trends of chemical shift values. Two-dimensional cluster analyses on chemical-shift data show positional distributions more clearly. Based on these propensities of chemical shift classified as a function of position, rules were derived using scoring matrices for four consecutive residues to predict type I and II β-turns. The proposed method achieves an overall prediction accuracy of 83.2 and 84.2% with the Matthews correlation coefficient values of 0.317 and 0.632 for type I and II β-turns, indicating that its higher accuracy for type II turn prediction. The results show that it is feasible to use NMR chemical shifts to predict the β-turn types in proteins. The proposed method can be incorporated into other chemical-shift based protein secondary structure prediction methods.

Lifshitz Transitions, Type-II Dirac and Weyl Fermions, Event Horizon and All That

NASA Astrophysics Data System (ADS)

Volovik, G. E.; Zhang, K.

2017-12-01

The type-II Weyl and type-II Dirac points emerge in semimetals and also in relativistic systems. In particular, the type-II Weyl fermions may emerge behind the event horizon of black holes. In this case the horizon with Painlevé-Gullstrand metric serves as the surface of the Lifshitz transition. This relativistic analogy allows us to simulate the black hole horizon and Hawking radiation using the fermionic superfluid with supercritical velocity, and the Dirac and Weyl semimetals with the interface separating the type-I and type-II states. The difference between such type of the artificial event horizon and that which arises in acoustic metric is discussed. At the Lifshitz transition between type-I and type-II fermions the Dirac lines may also emerge, which are supported by the combined action of topology and symmetry. The type-II Weyl and Dirac points also emerge as the intermediate states of the topological Lifshitz transitions. Different configurations of the Fermi surfaces, involved in such Lifshitz transition, are discussed. In one case the type-II Weyl point connects the Fermi pockets and the Lifshitz transition corresponds to the transfer of the Berry flux between the Fermi pockets. In the other case the type-II Weyl point connects the outer and inner Fermi surfaces. At the Lifshitz transition the Weyl point is released from both Fermi surfaces. They loose their Berry flux, which guarantees the global stability, and without the topological support the inner surface disappears after shrinking to a point at the second Lifshitz transition. These examples reveal the complexity and universality of topological Lifshitz transitions, which originate from the ubiquitous interplay of a variety of topological characters of the momentum-space manifolds. For the interacting electrons, the Lifshitz transitions may lead to the formation of the dispersionless (flat) band with zero energy and singular density of states, which opens the route to room-temperature superconductivity. Originally, the idea of the enhancement of T_c due to flat band has been put forward by the nuclear physics community, and this also demonstrates the close connections between different areas of physics.

Laser beam projection with adaptive array of fiber collimators. II. Analysis of atmospheric compensation efficiency.

PubMed

Lachinova, Svetlana L; Vorontsov, Mikhail A

2008-08-01

We analyze the potential efficiency of laser beam projection onto a remote object in atmosphere with incoherent and coherent phase-locked conformal-beam director systems composed of an adaptive array of fiber collimators. Adaptive optics compensation of turbulence-induced phase aberrations in these systems is performed at each fiber collimator. Our analysis is based on a derived expression for the atmospheric-averaged value of the mean square residual phase error as well as direct numerical simulations. Operation of both conformal-beam projection systems is compared for various adaptive system configurations characterized by the number of fiber collimators, the adaptive compensation resolution, and atmospheric turbulence conditions.

Genetics Home Reference: otopalatodigital syndrome type 2

MedlinePlus

... Testing (1 link) Genetic Testing Registry: Oto-palato-digital syndrome, type II Other Diagnosis and Management Resources ( ... syndrome FPO OPD syndrome, type 2 oto-palato-digital syndrome, type II Taybi syndrome Related Information How ...

Positions of type II fundamental and harmonic sources in the 30-100 MHZ range

NASA Technical Reports Server (NTRS)

Sawant, H. S.; Gergely, T. E.; Kundu, M. R.

1982-01-01

An excellent example of a type III-V burst followed by a type II burst with fundamental and harmonic bands was observed on June 18, 1979 at the Clark Lake Radio Observatory. The observations are described in detail and their implications are discussed with regard to the problem of directionality with respect to the magnetic field lines of the collisionless MHD shock wave generated at the start of the flash phase. It is found that the positions of type III and type II (F) bursts at a number of frequencies are essentially the same, which implies that the shock responsible for the type II radiation follows the path of the type III exciter, that is, the shock propagates along the open field lines.

Space Density Of Optically-Selected Type II Quasars From The SDSS

NASA Astrophysics Data System (ADS)

Reyes, Reinabelle; Zakamska, N. L.; Strauss, M. A.; Green, J.; Krolik, J. H.; Shen, Y.; Richards, G. T.

2007-12-01

Type II quasars are luminous Active Galactic Nuclei (AGN) whose central regions are obscured by large amounts of gas and dust. In this poster, we present a catalog of 887 type II quasars with redshifts z<0.83 from the Sloan Digital Sky Survey (SDSS), selected based on their emission lines, and derive the 1/Vmax [OIII] 5007 luminosity function from this sample. Since some objects may not be included in the sample because they lack strong emission lines, the derived luminosity function is only a lower limit. We also derive the [OIII] 5007 luminosity function for a sample of type I (broad-line) quasars in the same redshift range. Taking [OIII] 5007 luminosity as a tracer of intrinsic luminosity in both type I and type II quasars, we obtain lower limits to the type II quasar fraction as a function of [OIII] 5007 luminosity, from L[OIII] = 108.3 to 1010 Lsun, which roughly correspond to bolometric luminosities of 1044 to 1046 erg/s.

Intake of coffee, caffeine and other methylxanthines and risk of Type I vs Type II endometrial cancer.

PubMed

Uccella, S; Mariani, A; Wang, A H; Vierkant, R A; Cliby, W A; Robien, K; Anderson, K E; Cerhan, J R

2013-10-01

Coffee and other sources of methylxanthines and risk of Type I vs Type II endometrial cancer (EC) have not been evaluated previously. Prospective cohort of 23,356 postmenopausal women with 471 Type I and 71 Type II EC cases. Type I EC was statistically significantly associated with caffeinated (relative risk (RR)=0.65 for 4+ cups per day vs ≤1 cup per month: 95% confidence interval (CI): 0.47-0.89) but not decaffeinated (RR=0.76; 95% CI: 0.50-1.15) coffee intake; there were no associations with tea, cola or chocolate, or for Type II EC. The inverse association with caffeinated coffee intake was specific to women with a body mass index 30+ kg m(-2) (RR=0.56; 95% CI: 0.36-0.89). Coffee may protect against Type I EC in obese postmenopausal women.

Effect of cholesterol depletion on exocytosis of alveolar type II cells.

PubMed

Chintagari, Narendranath Reddy; Jin, Nili; Wang, Pengcheng; Narasaraju, Telugu Akula; Chen, Jiwang; Liu, Lin

2006-06-01

Alveolar epithelial type II cells secrete lung surfactant via exocytosis. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) are implicated in this process. Lipid rafts, the cholesterol- and sphingolipid-rich microdomains, may offer a platform for protein organization on the cell membrane. We tested the hypothesis that lipid rafts organize exocytotic proteins in type II cells and are essential for the fusion of lamellar bodies, the secretory granules of type II cells, with the plasma membrane. The lipid rafts, isolated from type II cells using 1% Triton X-100 and a sucrose gradient centrifugation, contained the lipid raft markers, flotillin-1 and -2, whereas they excluded the nonraft marker, Na+-K+ ATPase. SNAP-23, syntaxin 2, and VAMP-2 were enriched in lipid rafts. When type II cells were depleted of cholesterol, the association of SNAREs with the lipid rafts was disrupted and the formation of fusion pore was inhibited. Furthermore, the cholesterol-depleted plasma membrane had less ability to fuse with lamellar bodies, a process mediated by annexin A2. The secretagogue-stimulated secretion of lung surfactant from type II cells was also reduced by methyl-beta-cyclodextrin. When the raft-associated cell surface protein, CD44, was cross-linked using anti-CD44 antibodies, the CD44 clusters were observed. Syntaxin 2, SNAP-23, and annexin A2 co-localized with the CD44 clusters, which were cholesterol dependent. Our results suggested that lipid rafts may form a functional platform for surfactant secretion in alveolar type II cells, and raft integrity was essential for the fusion between lamellar bodies with the plasma membrane.

Skeletal effects in Angle Class II/1 patients treated with the functional regulator type II : Cephalometric and tensor analysis.

PubMed

Schulz, Simone; Koos, Bernd; Duske, Kathrin; Stahl, Franka

2016-11-01

The purpose of this work was to employ both cephalometric and tensor analysis in characterizing the skeletal changes experienced by patients with Angle Class II/1 malocclusion during functional orthodontic treatment with the functional regulator type II. A total of 23 patients with Class II/1 malocclusion based on lateral cephalograms obtained before and after treatment with the functional regulator type II were analyzed. Another 23 patients with Angle Class II/1 malocclusion who had not undergone treatment were included as controls. Our cephalometric data attest to significant therapeutic effects of the functional regulator type II on the skeletal mandibular system, including significant advancement of the mandible, increases in effective mandibular length with enhancement of the chin profile, and reduction of growth-related bite deepening. No treatment-related effects were observed at the cranial-base and midface levels. In addition, tensor analysis revealed significant stimulation of mandibular growth in sagittal directions, without indications of growth effects on the maxilla. Its growth-pattern findings differed from those of cephalometric analysis by indicating that the appliance did promote horizontal development, which supports the functional orthodontic treatment effect in Angle Class II/1 cases. Tensor analysis yielded additional insights into sagittal and vertical growth changes not identifiable by strictly cephalometric means. The functional regulator type II was an effective treatment modality for Angle Class II/1 malocclusion and influenced the skeletal development of these patients in favorable ways.

Special tinted contact lens on colour-defects.

PubMed

Mutilab, H A; Sharanjeet-Kaur; Keu, L K; Choo, P F

2012-01-01

The objective of this study was to determine the visual function of colour-deficient subjects when wearing special red tint contact lenses. A total of 17 subjects with congenital colour vision deficiency (14 deutans and 3 protans), voluntarily participated in this study. The average age for the subjects was 23.00 ± 4.06 years old. Visual functions tested were visual acuity (LogMAR), contrast sensitivity (FACT Chart) and stereopsis (TNO and Howard Dolman tests). Two types of special red tint lenses were used in this study; Type I (light red) and Type II (dark red). The protans and deutans showed no significant changes in visual acuity and contrast sensitivity when wearing either type of contact lens. Stereopsis testing using the Horward-Dolman test gave no significant changes but significant differences were seen using the TNO test. Stereopsis using the TNO test was significantly poorer with the red tinted contact lenses compared to without for both protons and deutans. Testing binocularly with Ishihara plates showed that 88% (n=15) of patients passed the test with Type I and Type II contact lenses. When D15 test was done, 3 patients (17.6%) were 'normal' when using the Type I contact lenses and 2 patients (11.8%) were 'normal' when using the Type II contact lenses. However, with FM100Hue test, most patients showed deutan responses. Total error scores (TES) were found to be higher with Type I and Type II contact lenses compared to without. The Type I and II special tinted contact lens used in this study did not cause a reduction of visual acuity and contrast sensitivity for the colour defects. Stereopsis was also not reduced with the Type I and Type II contact lenses for the colour defects except when tested with the TNO test. Colour vision defects became difficult to detect using the Ishihara plates but FM100Hue test did not show any improvement with the Type I and Type II contact lenses.

Angiotensin II receptors in cortical and medullary adrenal tumors.

PubMed

Opocher, G; Rocco, S; Cimolato, M; Vianello, B; Arnaldi, G; Mantero, F

1997-03-01

Several pieces of evidences suggest that angiotensin II (Ang II) has mitogenic effects, and a link between Ang II receptors and adrenal tumors can be suggested. In various adrenal tumors, aldosterone-producing adenoma (APA), Cushing's adrenal adenomas (Cush), pheochromocytomas (Pheo), and adrenal carcinomas, we studied the density, affinity, and subtype of Ang II receptors. Ang II binding was tested in cell membrane homogenates. [125I]Ang II was used as ligand, and Losartan and CGP 42112 were used as selective Ang II type 1 and type 2 antagonists, respectively. In APA, Ang II receptor density was 178.5 +/- 82.7 fmol/mg: however, due to the high degree of variability, the receptor density was not significantly higher than that in nontumorous adrenal cortex (59.3 +/- 8.4 fmol/mg). In Cush, the receptor density (27.6 +/- 8.2 fmol/mg; P < 0.05) was significantly lower than that in controls, whereas in Pheo and cortical carcinoma, Ang II binding was very low and in several cases almost undetectable. There was no remarkable difference in the Ang II receptor affinity among all tissues tested. The ratio between type 1 and type 2 Ang II receptors showed a large prevalence of type 1 in controls, APA, and three cases of Cush; in two cases of Cush, this ratio was reversed. In conclusion, our data indicate that Ang II receptors are normally expressed in APA and can also be detected in Cush, whereas they have a very low density in Pheo and adrenal carcinoma. Therefore, Ang II receptors are not involved in the lack of response to Ang II that is characteristic of APA; additionally, a reduction of Ang II receptors can be associated with dedifferentiation or malignancy of adrenal tumors. Further investigation of the expression and functional characterization of Ang II receptors is required to better clarify their possible role in adrenal tumorigenesis.

77 FR 60124 - Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1010] Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical... certain drug master files, namely, Type II active pharmaceutical ingredient (API) drug master files (DMFs...

Determining the Existence of an Athletic Stigma on a NCAA Division II University Campus

ERIC Educational Resources Information Center

Parsons, Jennifer C. M.

2010-01-01

This project replicated a previous study by Simons, Bosworth, Fujita, and Jenson (2007) examining the existence of an athletic stigma on a university campus. For this investigation, the researcher adapted the original instrument and surveyed 252 athletes on a comprehensive Midwestern NCAA Division II university campus. The survey provided both…

Functional classification of mitochondrion-rich cells in euryhaline Mozambique tilapia (Oreochromis mossambicus) embryos, by means of triple immunofluorescence staining for Na+/K+-ATPase, Na +/K+/2Cl- cotransporter and CFTR anion channel

USGS Publications Warehouse

Hiroi, J.; McCormick, S.D.; Ohtani-Kaneko, R.; Kaneko, T.

2005-01-01

Mozambique tilapia Oreochromis mossambicus embryos were transferred from freshwater to seawater and vice versa, and short-term changes in the localization of three major ion transport proteins, Na+/K +-ATPase, Na+/K+/2Cl- cotransporter (NKCC) and cystic fibrosis transmembrane conductance regulator (CFTR) were examined within mitochondrion-rich cells (MRCs) in the embryonic yolk-sac membrane. Triple-color immunofluorescence staining allowed us to classify MRCs into four types: type I, showing only basolateral Na+/K +-ATPase staining; type II, basolateral Na+/K +-ATPase and apical NKCC; type III, basolateral Na+/K +-ATPase and basolateral NKCC; type IV, basolateral Na +/K+-ATPase, basolateral NKCC and apical CFTR. In freshwater, type-I, type-II and type-III cells were observed. Following transfer from freshwater to seawater, type-IV cells appeared at 12 h and showed a remarkable increase in number between 24 h and 48 h, whereas type-III cells disappeared. When transferred from seawater back to freshwater, type-IV cells decreased and disappeared at 48 h, type-III cells increased, and type-II cells, which were not found in seawater, appeared at 12 h and increased in number thereafter. Type-I cells existed consistently irrespective of salinity changes. These results suggest that type I is an immature MRC, type II is a freshwater-type ion absorptive cell, type III is a dormant type-IV cell and/or an ion absorptive cell (with a different mechanism from type II), and type IV is a seawater-type ion secretory cell. The intracellular localization of the three ion transport proteins in type-IV cells is completely consistent with a widely accepted model for ion secretion by MRCs. A new model for ion absorption is proposed based on type-II cells possessing apical NKCC.

Aroma compounds generation in citrate metabolism of Enterococcus faecium: Genetic characterization of type I citrate gene cluster.

PubMed

Martino, Gabriela P; Quintana, Ingrid M; Espariz, Martín; Blancato, Victor S; Magni, Christian

2016-02-02

Enterococcus is one of the most controversial genera belonging to Lactic Acid Bacteria. Research involving this microorganism reflects its dual behavior as regards its safety. Although it has also been associated to nosocomial infections, natural occurrence of Enterococcus faecium in food contributes to the final quality of cheese. This bacterium is capable of fermenting citrate, which is metabolized to pyruvate and finally derives in the production of the aroma compounds diacetyl, acetoin and 2,3 butanediol. Citrate metabolism was studied in E. faecium but no data about genes related to these pathways have been described. A bioinformatic approach allowed us to differentiate cit(-) (no citrate metabolism genes) from cit(+) strains in E. faecium. Furthermore, we could classify them according to genes encoding for the transcriptional regulator, the oxaloacetate decarboxylase and the citrate transporter. Thus we defined type I organization having CitI regulator (DeoR family), CitM cytoplasmic soluble oxaloacetate decarboxylase (Malic Enzyme family) and CitP citrate transporter (2-hydroxy-carboxylate transporter family) and type II organization with CitO regulator (GntR family), OAD membrane oxaloacetate decarboxylase complex (Na(+)-transport decarboxylase enzyme family) and CitH citrate transporter (CitMHS family). We isolated and identified 17 E. faecium strains from regional cheeses. PCR analyses allowed us to classify them as cit(-) or cit(+). Within the latter classification we could differentiate type I but no type II organization. Remarkably, we came upon E. faecium GM75 strain which carries the insertion sequence IS256, involved in adaptative and evolution processes of bacteria related to Staphylococcus and Enterococcus genera. In this work we describe the differential behavior in citrate transport, metabolism and aroma generation of three strains and we present results that link citrate metabolism and genetic organizations in E. faecium for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.

The Regulatory Roles of Toll-Like Receptor 4 in Secretions of Type 1/Type 2 Relative Cytokines by Splenocytes and Dendritic Cells Exposed to Clonorchis sinensis Excretory/Secretory Products.

PubMed

Hua, Hui; Du, Ying; Ma, Rui; Zhang, Bei-Bei; Yu, Qian; Li, Bo; Xu, Jiang-Tao; Li, Xiang-Yang; Tang, Ren-Xian; Yan, Chao; Zheng, Kui-Yang

2018-02-01

The roles of TLR4 in mediation of innate immune response and in regulation of adaptive immune responses triggered by Clonorchis sinensis remain unknown. In the present study, splenocytes derived from C3H/HeN (TLR4 wild ) and C3H/Hej mice (TLR4 mut ) that were infected with 45 metacercariae of C. sinensis were harvested, then stimulated by C. sinensis excretory/secretory products (ESP) or medium (control) for 48 h, respectively. Meanwhile, bone marrow-derived dendritic cells (BMDCs) from normal C3H/HeN and C3H/Hej mice were prepared and stimulated with medium, ESP, LPS, or ESP+LPS for 24 h, respectively. The supernatants were collected, and the concentrations of type 1 and type 2 relative cytokines were determined by ELISA. The maturation of BMDCs indicated by surface markers of CD80, CD86, and MHC II was evaluated by flow cytometry. The results showed that the levels of IFN-γ, IL-6, TNF-α, and IL-10 in the splenocytes from C. sinensis-infected TLR4 mut mice were significantly lower than those from TLR4 wild mice when they were further exposed to ESP. For BMDCs, the productions of the cytokines IL-12p70 and IL-10, but not IL-4, in the BMDCs from TLR4 mutation mice were predominantly decreased compared with those from TLR4 wild mice when the BMDCs were co-stimulated by ESP combined with LPS. Flow cytometry analysis showed that ESP could significantly decrease the high levels of CD80, CD86, and MHC II which were elevated by LPS. In conclusion, these data suggest that TLR4 may play a regulatory role in type 1 immune responses during C. sinensis infection.

Stellar parameters of Be stars observed with X-shooter

NASA Astrophysics Data System (ADS)

Shokry, A.; Rivinius, Th.; Mehner, A.; Martayan, C.; Hummel, W.; Townsend, R. H. D.; Mérand, A.; Mota, B.; Faes, D. M.; Hamdy, M. A.; Beheary, M. M.; Gadallah, K. A. K.; Abo-Elazm, M. S.

2018-01-01

Aims: The X-shooter archive of several thousand telluric standard star spectra was skimmed for Be and Be shell stars to derive the stellar fundamental parameters and statistical properties, in particular for the less investigated late-type Be stars and the extension of the Be phenomenon into early A stars. Methods: An adapted version of the BCD method is used, using the Balmer discontinuity parameters to determine effective temperature and surface gravity. This method is optimally suited for late B stars. The projected rotational velocity was obtained by profile fitting to the Mg ii lines of the targets, and the spectra were inspected visually for the presence of peculiar features such as the infrared Ca ii triplet or the presence of a double Balmer discontinuity. The Balmer line equivalent widths were measured, but they are only useful for determining the pure emission contribution in a subsample of Be stars owing to uncertainties in determining the photospheric contribution. Results: A total of 78, mostly late-type, Be stars, were identified in the X-shooter telluric standard star archive, out of which 48 had not been reported before. We confirm the general trend that late-type Be stars have more tenuous disks and are less variable than early-type Be stars. The relatively large number (48) of relatively bright (V> 8.5) additional Be stars casts some doubt on the statistics of late-type Be stars; they are more common than currently thought. The Be/B star fraction may not strongly depend on spectral subtype. Based on observations made with ESO Telescopes at the La Silla Paranal Observatory under program IDs 60.A-9022, 60.A-9024, 077.D-0085, 085.A-0962, 185.D-0056, 091.B-0900, and 093.D-0415.Table 6 is only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/609/A108