Extraction and characterization of ternary complexes between natural organic matter, cations, and oxyanions from a natural soil.

PubMed

Peel, Hannah R; Martin, David P; Bednar, Anthony J

2017-06-01

Natural organic matter (NOM) can have a significant influence on the mobility and fate of inorganic oxyanions, such as arsenic and selenium, in the environment. There is evidence to suggest that interactions between NOM and these oxyanions are facilitated by bridging cations (primarily Fe 3+ ) through the formation of ternary complexes. Building on previous work characterizing ternary complexes formed in the laboratory using purified NOM, this study describes the extraction and characterization of intact ternary complexes directly from a soil matrix. The complexes are stable to the basic extraction conditions (pH 12) and do not appear to change when the pH of the extract is adjusted back to neutral. The results suggest that ternary complexes between NOM, cations, and inorganic oxyanions exist in natural soils and could play a role in the speciation of inorganic oxyanions in environmental matrices. Published by Elsevier Ltd.

Complexation of lanthanides and actinides by acetohydroxamic acid

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

Taylor, R.J.; Sinkov, S.I.; Choppin, G.R.

2008-07-01

Acetohydroxamic acid (AHA) has been proposed as a suitable reagent for the complexant-based, as opposed to reductive, stripping of plutonium and neptunium ions from the tributylphosphate solvent phase in advanced PUREX or UREX processes designed for future nuclear-fuel reprocessing. Stripping is achieved by the formation of strong hydrophilic complexes with the tetravalent actinides in nitric acid solutions. To underpin such applications, knowledge of the complexation constants of AHA with all relevant actinide (5f) and lanthanide (4f) ions is therefore important. This paper reports the determination of stability constants of AHA with the heavier lanthanide ions (Dy-Yb) and also U(IV) andmore » Th(IV) ions. Comparisons with our previously published AHA stability-constant data for 4f and 5f ions are made. (authors)« less

Reconnaissance bedrock geology of the southeastern part of the Kenai quadrangle, Alaska: A section in Geologic studies in Alaska by the U.S. Geological Survey, 1998

USGS Publications Warehouse

Bradley, Dwight C.; Wilson, Frederic H.

2000-01-01

We present a new reconnaissance geologic map of the southeastern part of the Kenai quadrangle that improves on previously published maps. Melange of the McHugh Complex is now known to form a continuous strike belt that can be traced from the Seldovia to the Valdez quadrangle; a problematic 75-km-long gap in the McHugh Complex in the Kenai and Seldovia quadrangles does not exist. An Eocene near-trench pluton underlies a range of nunataks in Harding Icefield.

Improved Syntheses and Expanded Analyses of the Enantiomerically Enriched Chiral Cobalt Complexes Co(en)[subscript 3]I[subscript 3] and Co(diNOsar)Br[subscript 3

ERIC Educational Resources Information Center

McClellan, Michael J.; Cass, Marion E.

2015-01-01

This communication is a collection of additions and modifications to two previously published classic inorganic synthesis laboratory experiments. The experimental protocol for the synthesis and isolation of enantiomerically enriched ?- (or ?-)Co(en)[subscript 3]I[subscript 3] has been modified to increase reproducibility, yield, and enantiomeric…

Organic carbon accumulation in modern sediments of the Angola basin influenced by the Congo deep-sea fan

NASA Astrophysics Data System (ADS)

Baudin, François; Martinez, Philippe; Dennielou, Bernard; Charlier, Karine; Marsset, Tania; Droz, Laurence; Rabouille, Christophe

2017-08-01

Geochemical data (total organic carbon-TOC content, δ13Corg, C:N, Rock-Eval analyses) were obtained on 150 core tops from the Angola basin, with a special focus on the Congo deep-sea fan. Combined with the previously published data, the resulting dataset (322 stations) shows a good spatial and bathymetric representativeness. TOC content and δ13Corg maps of the Angola basin were generated using this enhanced dataset. The main difference in our map with previously published ones is the high terrestrial organic matter content observed downslope along the active turbidite channel of the Congo deep-sea fan till the distal lobe complex near 5000 m of water-depth. Interpretation of downslope trends in TOC content and organic matter composition indicates that lateral particle transport by turbidity currents is the primary mechanism controlling supply and burial of organic matter in the bathypelagic depths.

Extensive video-game experience alters cortical networks for complex visuomotor transformations.

PubMed

Granek, Joshua A; Gorbet, Diana J; Sergio, Lauren E

2010-10-01

Using event-related functional magnetic resonance imaging (fMRI), we examined the effect of video-game experience on the neural control of increasingly complex visuomotor tasks. Previously, skilled individuals have demonstrated the use of a more efficient movement control brain network, including the prefrontal, premotor, primary sensorimotor and parietal cortices. Our results extend and generalize this finding by documenting additional prefrontal cortex activity in experienced video gamers planning for complex eye-hand coordination tasks that are distinct from actual video-game play. These changes in activation between non-gamers and extensive gamers are putatively related to the increased online control and spatial attention required for complex visually guided reaching. These data suggest that the basic cortical network for processing complex visually guided reaching is altered by extensive video-game play. Crown Copyright © 2009. Published by Elsevier Srl. All rights reserved.

Rare earth element evidence for the petrogenesis of the banded series of the Stillwater Complex, Montana, and its anorthosites

USGS Publications Warehouse

Loferski, P.J.; Arculus, R.J.; Czamanske, G.K.

1994-01-01

A rare earth element (REE) study was made by isotope-dilution mass spectrometry of plagioclase separates from a variety of cumulates stratigraphically spanning the Banded series of the Stillwater Complex, Montana. Evaluation of parent liquid REE patterns, calculated on the basis of published plagioclase-liquid partition coefficients, shows that the range of REE ratios is too large to be attributable to fractionation of a single magma type. At least two different parental melts were present throughout the Banded series. This finding supports hypotheses of previous workers that the Stillwater Complex formed from two different parent magma types, designated the anorthosite- or A-type liquid and the ultramafic- or U-type liquid. -from Authors

Interaction between the C-terminal domains of measles virus nucleoprotein and phosphoprotein: a tight complex implying one binding site.

PubMed

Blocquel, David; Habchi, Johnny; Costanzo, Stéphanie; Doizy, Anthony; Oglesbee, Michael; Longhi, Sonia

2012-10-01

The intrinsically disordered C-terminal domain (N(TAIL) ) of the measles virus (MeV) nucleoprotein undergoes α-helical folding upon binding to the C-terminal X domain (XD) of the phosphoprotein. The N(TAIL) region involved in binding coupled to folding has been mapped to a conserved region (Box2) encompassing residues 489-506. In the previous studies published in this journal, we obtained experimental evidence supporting a K(D) for the N(TAIL) -XD binding reaction in the nM range and also showed that an additional N(TAIL) region (Box3, aa 517-525) plays a role in binding to XD. In striking contrast with these data, studies published in this journal by Kingston and coworkers pointed out a much less stable complex (K(D) in the μM range) and supported lack of involvement of Box3 in complex formation. The objective of this study was to critically re-evaluate the role of Box3 in N(TAIL) -XD binding. Since our previous studies relied on N(TAIL) -truncated forms possessing an irrelevant Flag sequence appended at their C-terminus, we, herein, generated an N(TAIL) devoid of Box3 and any additional C-terminal residues, as well as a form encompassing only residues 482-525. We then used isothermal titration calorimetry to characterize the binding reactions between XD and these N(TAIL) forms. Results effectively argue for the presence of a single XD-binding site located within Box2, in agreement with the results by Kingston et al., while providing clear experimental support for a high-affinity complex. Altogether, the present data provide mechanistic insights into the replicative machinery of MeV and clarify a hitherto highly debated point. Copyright © 2012 The Protein Society.

Interaction between the C-terminal domains of measles virus nucleoprotein and phosphoprotein: A tight complex implying one binding site

PubMed Central

Blocquel, David; Habchi, Johnny; Costanzo, Stéphanie; Doizy, Anthony; Oglesbee, Michael; Longhi, Sonia

2012-01-01

The intrinsically disordered C-terminal domain (NTAIL) of the measles virus (MeV) nucleoprotein undergoes α-helical folding upon binding to the C-terminal X domain (XD) of the phosphoprotein. The NTAIL region involved in binding coupled to folding has been mapped to a conserved region (Box2) encompassing residues 489–506. In the previous studies published in this journal, we obtained experimental evidence supporting a KD for the NTAIL–XD binding reaction in the nM range and also showed that an additional NTAIL region (Box3, aa 517–525) plays a role in binding to XD. In striking contrast with these data, studies published in this journal by Kingston and coworkers pointed out a much less stable complex (KD in the μM range) and supported lack of involvement of Box3 in complex formation. The objective of this study was to critically re-evaluate the role of Box3 in NTAIL–XD binding. Since our previous studies relied on NTAIL-truncated forms possessing an irrelevant Flag sequence appended at their C-terminus, we, herein, generated an NTAIL devoid of Box3 and any additional C-terminal residues, as well as a form encompassing only residues 482–525. We then used isothermal titration calorimetry to characterize the binding reactions between XD and these NTAIL forms. Results effectively argue for the presence of a single XD-binding site located within Box2, in agreement with the results by Kingston et al., while providing clear experimental support for a high-affinity complex. Altogether, the present data provide mechanistic insights into the replicative machinery of MeV and clarify a hitherto highly debated point. PMID:22887965

Objective Lightning Probability Forecasting for Kennedy Space Center and Cape Canaveral Air Force Station, Phase IV

NASA Technical Reports Server (NTRS)

Bauman, William H., III; Crawford, Winifred C.

2012-01-01

As with the previous year, the past year of this award has been productive and a number of important results and refereed publications either submitted or published. Some of our research results are discussed here and a list the papers submitted or published in the past year is provided. Besides our original model of an outer heliosheath source for the IBEX "ribbon" we have continued to explore alternative possibilities and further our understanding of this very complex region, especially in light of the possibility raised by the IBEX results that suggest the possibility of a 1-shock model.

NEW MEMBERS OF THE SCORPIUS-CENTAURUS COMPLEX AND AGES OF ITS SUB-REGIONS

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

Song, Inseok; Zuckerman, B.; Bessell, M. S.

2012-07-15

We have spectroscopically identified {approx}100 G-, K-, and M-type members of the Scorpius-Centaurus complex. To deduce the age of these young stars we compare their Li {lambda}6708 absorption line strengths against those of stars in the TW Hydrae association and {beta} Pictoris moving group. These line strengths indicate that Sco-Cen stars are younger than {beta} Pic stars whose ages of {approx}12 Myr have previously been derived from a kinematic traceback analysis. Our derived age, {approx}10 Myr, for stars in the Lower Centaurus Crux and Upper Centaurus Lupus subgroups of ScoCen is younger than previously published ages based on the movingmore » cluster method and upper main-sequence fitting. The discrepant ages are likely due to an incorrect (or lack of) cross-calibration between model-dependent and model-independent age-dating methods.« less

Neuronal antibodies in patients with suspected or confirmed sporadic Creutzfeldt-Jakob disease.

PubMed

Rossi, Meghan; Mead, Simon; Collinge, John; Rudge, Peter; Vincent, Angela

2015-06-01

There have been reports of patients with antibodies to neuronal antigens misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Conversely, low levels of antibodies to neuronal proteins have been reported in patients with sCJD. However, the frequency of misdiagnoses, or of antibodies in patients with subsequently confirmed sCJD, is not clear. We reviewed 256 consecutive cases of sCJD seen in the National Prion Clinic, of whom 150 had sera previously referred for selected antibody tests. Eighty-two available samples were retested for antibodies to N-methyl-d-aspartate receptor (NMDAR), the glycine receptor (GlyR), voltage-gated potassium channel (VGKC)-complex and the associated proteins, leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2). Four of the initial 150 sera referred were positive; two had antibodies to NMDAR, and two to the VGKC-complex, one of which was also positive for GlyR antibodies. Of the 82 sCJD sera retested, one had VGKC-complex antibodies confirming the previous result, two had CASPR2 and GlyR antibodies and one had CASPR2 and NMDAR antibodies; all antibodies were at low levels. Over the same period three patients with autoimmune encephalitis and high VGKC-complex antibodies were initially referred as sCJD. This study indicates that <5% patients with sCJD develop serum antibodies to these neuronal antigens and, when positive, only at low titres. By contrast, three patients referred with possible prion disease had a clinical picture in keeping with autoimmune encephalitis and very high VGKC-complex/LGI1 antibodies. Low titres of neuronal antibodies occur only rarely in suspected patients with sCJD and when present should be interpreted with caution. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Structure of the Apo Form of Bacillus stearothermophilus Phosphofructokinase

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

Mosser, Rockann; Reddy, Manchi C.M.; Bruning, John B.

2012-02-08

The crystal structure of the unliganded form of Bacillus stearothermophilus phosphofructokinase (BsPFK) was determined using molecular replacement to 2.8 {angstrom} resolution (Protein Data Bank entry 3U39). The apo BsPFK structure serves as the basis for the interpretation of any structural changes seen in the binary or ternary complexes. When the apo BsPFK structure is compared with the previously published liganded structures of BsPFK, the structural impact that the binding of the ligands produces is revealed. This comparison shows that the apo form of BsPFK resembles the substrate-bound form of BsPFK, a finding that differs from previous predictions.

New method for estimation of fluence complexity in IMRT fields and correlation with gamma analysis

NASA Astrophysics Data System (ADS)

Hanušová, T.; Vondráček, V.; Badraoui-Čuprová, K.; Horáková, I.; Koniarová, I.

2015-01-01

A new method for estimation of fluence complexity in Intensity Modulated Radiation Therapy (IMRT) fields is proposed. Unlike other previously published works, it is based on portal images calculated by the Portal Dose Calculation algorithm in Eclipse (version 8.6, Varian Medical Systems) in the plane of the EPID aS500 detector (Varian Medical Systems). Fluence complexity is given by the number and the amplitudes of dose gradients in these matrices. Our method is validated using a set of clinical plans where fluence has been smoothed manually so that each plan has a different level of complexity. Fluence complexity calculated with our tool is in accordance with the different levels of smoothing as well as results of gamma analysis, when calculated and measured dose matrices are compared. Thus, it is possible to estimate plan complexity before carrying out the measurement. If appropriate thresholds are determined which would distinguish between acceptably and overly modulated plans, this might save time in the re-planning and re-measuring process.

Building an open-source simulation platform of acoustic radiation force-based breast elastography

NASA Astrophysics Data System (ADS)

Wang, Yu; Peng, Bo; Jiang, Jingfeng

2017-03-01

Ultrasound-based elastography including strain elastography, acoustic radiation force impulse (ARFI) imaging, point shear wave elastography and supersonic shear imaging (SSI) have been used to differentiate breast tumors among other clinical applications. The objective of this study is to extend a previously published virtual simulation platform built for ultrasound quasi-static breast elastography toward acoustic radiation force-based breast elastography. Consequently, the extended virtual breast elastography simulation platform can be used to validate image pixels with known underlying soft tissue properties (i.e. ‘ground truth’) in complex, heterogeneous media, enhancing confidence in elastographic image interpretations. The proposed virtual breast elastography system inherited four key components from the previously published virtual simulation platform: an ultrasound simulator (Field II), a mesh generator (Tetgen), a finite element solver (FEBio) and a visualization and data processing package (VTK). Using a simple message passing mechanism, functionalities have now been extended to acoustic radiation force-based elastography simulations. Examples involving three different numerical breast models with increasing complexity—one uniform model, one simple inclusion model and one virtual complex breast model derived from magnetic resonance imaging data, were used to demonstrate capabilities of this extended virtual platform. Overall, simulation results were compared with the published results. In the uniform model, the estimated shear wave speed (SWS) values were within 4% compared to the predetermined SWS values. In the simple inclusion and the complex breast models, SWS values of all hard inclusions in soft backgrounds were slightly underestimated, similar to what has been reported. The elastic contrast values and visual observation show that ARFI images have higher spatial resolution, while SSI images can provide higher inclusion-to-background contrast. In summary, our initial results were consistent with our expectations and what have been reported in the literature. The proposed (open-source) simulation platform can serve as a single gateway to perform many elastographic simulations in a transparent manner, thereby promoting collaborative developments.

Nursing theory and concept development: a theoretical model of clinical nurses' intentions to stay in their current positions.

PubMed

Cowden, Tracy L; Cummings, Greta G

2012-07-01

We describe a theoretical model of staff nurses' intentions to stay in their current positions. The global nursing shortage and high nursing turnover rate demand evidence-based retention strategies. Inconsistent study outcomes indicate a need for testable theoretical models of intent to stay that build on previously published models, are reflective of current empirical research and identify causal relationships between model concepts. Two systematic reviews of electronic databases of English language published articles between 1985-2011. This complex, testable model expands on previous models and includes nurses' affective and cognitive responses to work and their effects on nurses' intent to stay. The concepts of desire to stay, job satisfaction, joy at work, and moral distress are included in the model to capture the emotional response of nurses to their work environments. The influence of leadership is integrated within the model. A causal understanding of clinical nurses' intent to stay and the effects of leadership on the development of that intention will facilitate the development of effective retention strategies internationally. Testing theoretical models is necessary to confirm previous research outcomes and to identify plausible sequences of the development of behavioral intentions. Increased understanding of the causal influences on nurses' intent to stay should lead to strategies that may result in higher retention rates and numbers of nurses willing to work in the health sector. © 2012 Blackwell Publishing Ltd.

Framework for Smart Electronic Health Record- Linked Predictive Models to Optimize Care for Complex Digestive Diseases

DTIC Science & Technology

2015-03-01

data against previous published outcomes in AP and Chronic Pancreatitis (CP). This served as useful validation of our data set before entering the...These patients can develop multiple complications from their disease. In addition, the treatments for CD (both medical and surgical ) can impose...years of diagnosis. The treatment for CD can sometimes involve very expensive medications with potentially serious side effects, as well as surgical

Structure of T7 RNA polymerase complexed to the transcriptional inhibitor T7 lysozyme.

PubMed Central

Jeruzalmi, D; Steitz, T A

1998-01-01

The T7 RNA polymerase-T7 lysozyme complex regulates phage gene expression during infection of Escherichia coli. The 2.8 A crystal structure of the complex reveals that lysozyme binds at a site remote from the polymerase active site, suggesting an indirect mechanism of inhibition. Comparison of the T7 RNA polymerase structure with that of the homologous pol I family of DNA polymerases reveals identities in the catalytic site but also differences specific to RNA polymerase function. The structure of T7 RNA polymerase presented here differs significantly from a previously published structure. Sequence similarities between phage RNA polymerases and those from mitochondria and chloroplasts, when interpreted in the context of our revised model of T7 RNA polymerase, suggest a conserved fold. PMID:9670025

U.S. Geological Survey applied research studies of the Cheyenne River System, South Dakota; description and collation of data, water years 1987-88

USGS Publications Warehouse

Goddard, K. E.

1990-01-01

The Cheyenne River System in western South Dakota has been impacted by the discharge of about 100 million metric tons of gold-mill tailings to Whitewood Creek near Lead, South Dakota. In April 1985, the U.S. Geological Survey initiated an extensive series of research studies to investigate the magnitude of the impact and to define important processes acting on the contaminated sediments present in the system. The report presents all data collected during the 1987 and 1988 water years for these research studies. Some of the data included have been published previously. Data collected in the 1985 and 1986 water years have been published in a companion report (U.S. Geological Survey Open-File Report 88-484). Hydrologic, geochemical, and biologic data are available for sites on Whitewood Creek, and the Belle Fourche and Cheyenne Rivers. Data complexity varies from routine discharge and water-quality to very complex energy-dispersive x-ray analysis. Methods for sample collection, handling and preservation, and laboratory analysis are also presented. No interpretations or complex statistical summaries are included. (See also W89-08390) (USGS)

Goal neglect and knowledge chunking in the construction of novel behaviour.

PubMed

Bhandari, Apoorva; Duncan, John

2014-01-01

Task complexity is critical in cognitive efficiency and fluid intelligence. To examine functional limits in task complexity, we examine the phenomenon of goal neglect, where participants with low fluid intelligence fail to follow task rules that they otherwise understand. Though neglect is known to increase with task complexity, here we show that - in contrast to previous accounts - the critical factor is not the total complexity of all task rules. Instead, when the space of task requirements can be divided into separate sub-parts, neglect is controlled by the complexity of each component part. The data also show that neglect develops and stabilizes over the first few performance trials, i.e. as instructions are first used to generate behaviour. In all complex behaviour, a critical process is combination of task events with retrieved task requirements to create focused attentional episodes dealing with each decision in turn. In large part, we suggest, fluid intelligence may reflect this process of converting complex requirements into effective attentional episodes. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

IL-6 Receptor Isoforms and Ovarian Cancer

DTIC Science & Technology

2013-01-01

previously de- cribed.27 Groups of mice (n 6) were dministered acetyl salicylic acid (ASA; 00 mg/kg; Sigma, St Louis, MO), phos- hate-buffered saline...indicates P .05. SA, acetyl salicylic acid ; IL6R, interleukin-6 receptor. ath. IL-6 receptor in ovarian tumors. Am J Obstet Gynecol 2010. ause they are...tumor cell proper to increase this effect . Published studies examining IL6-/- and IL6R-/- mice demonstrated a complexity of IL6 signaling for wound

MMA-EoS: A Computational Framework for Mineralogical Thermodynamics

NASA Astrophysics Data System (ADS)

Chust, T. C.; Steinle-Neumann, G.; Dolejš, D.; Schuberth, B. S. A.; Bunge, H.-P.

2017-12-01

We present a newly developed software framework, MMA-EoS, that evaluates phase equilibria and thermodynamic properties of multicomponent systems by Gibbs energy minimization, with application to mantle petrology. The code is versatile in terms of the equation-of-state and mixing properties and allows for the computation of properties of single phases, solution phases, and multiphase aggregates. Currently, the open program distribution contains equation-of-state formulations widely used, that is, Caloric-Murnaghan, Caloric-Modified-Tait, and Birch-Murnaghan-Mie-Grüneisen-Debye models, with published databases included. Through its modular design and easily scripted database, MMA-EoS can readily be extended with new formulations of equations-of-state and changes or extensions to thermodynamic data sets. We demonstrate the application of the program by reproducing and comparing physical properties of mantle phases and assemblages with previously published work and experimental data, successively increasing complexity, up to computing phase equilibria of six-component compositions. Chemically complex systems allow us to trace the budget of minor chemical components in order to explore whether they lead to the formation of new phases or extend stability fields of existing ones. Self-consistently computed thermophysical properties for a homogeneous mantle and a mechanical mixture of slab lithologies show no discernible differences that require a heterogeneous mantle structure as has been suggested previously. Such examples illustrate how thermodynamics of mantle mineralogy can advance the study of Earth's interior.

Novel species including Mycobacterium fukienense sp. is found from tuberculosis patients in Fujian Province, China, using phylogenetic analysis of Mycobacterium chelonae/abscessus complex.

PubMed

Zhang, Yuan Yuan; Li, Yan Bing; Huang, Ming Xiang; Zhao, Xiu Qin; Zhang, Li Shui; Liu, Wen En; Wan, Kang Lin

2013-11-01

To identify the novel species 'Mycobacterium fukienense' sp. nov of Mycobacterium chelonae/abscessus complex from tuberculosis patients in Fujian Province, China. Five of 27 clinical Mycobacterium isolates (Cls) were previously identified as M. chelonae/abscessus complex by sequencing the hsp65, rpoB, 16S-23S rRNA internal transcribed spacer region (its), recA and sodA house-keeping genes commonly used to describe the molecular characteristics of Mycobacterium. Clinical Mycobacterium isolates were classified according to the gene sequence using a clustering analysis program. Sequence similarity within clusters and diversity between clusters were analyzed. The 5 isolates were identified with distinct sequences exhibiting 99.8% homology in the hsp65 gene. However, a complete lack of homology was observed among the sequences of the rpoB, 16S-23S rRNA internal transcribed spacer region (its), sodA, and recA genes as compared with the M. abscessus. Furthermore, no match for rpoB, sodA, and recA genes was identified among the published sequences. The novel species, Mycobacterium fukienense, is identified from tuberculosis patients in Fujian Province, China, which does not belong to any existing subspecies of M. chelonea/abscessus complex. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

The benefits of being a video gamer in laparoscopic surgery.

PubMed

Sammut, Matthew; Sammut, Mark; Andrejevic, Predrag

2017-09-01

Video games are mainly considered to be of entertainment value in our society. Laparoscopic surgery and video games are activities similarly requiring eye-hand and visual-spatial skills. Previous studies have not conclusively shown a positive correlation between video game experience and improved ability to accomplish visual-spatial tasks in laparoscopic surgery. This study was an attempt to investigate this relationship. The aim of the study was to investigate whether previous video gaming experience affects the baseline performance on a laparoscopic simulator trainer. Newly qualified medical officers with minimal experience in laparoscopic surgery were invited to participate in the study and assigned to the following groups: gamers (n = 20) and non-gamers (n = 20). Analysis included participants' demographic data and baseline video gaming experience. Laparoscopic skills were assessed using a laparoscopic simulator trainer. There were no significant demographic differences between the two groups. Each participant performed three laparoscopic tasks and mean scores between the two groups were compared. The gamer group had statistically significant better results in maintaining the laparoscopic camera horizon ± 15° (p value = 0.009), in the complex ball manipulation accuracy rates (p value = 0.024) and completed the complex laparoscopic simulator task in a significantly shorter time period (p value = 0.001). Although prior video gaming experience correlated with better results, there were no significant differences for camera accuracy rates (p value = 0.074) and in a two-handed laparoscopic exercise task accuracy rates (p value = 0.092). The results show that previous video-gaming experience improved the baseline performance in laparoscopic simulator skills. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Direct U-Pb dating of Cretaceous and Paleocene dinosaur bones, San Juan Basin, New Mexico: COMMENT

USGS Publications Warehouse

Koenig, Alan E.; Lucas, Spencer G.; Neymark, Leonid A.; Heckert, Andrew B.; Sullivan, Robert M.; Jasinski, Steven E.; Fowler, Denver W.

2012-01-01

Based on U-Pb dating of two dinosaur bones from the San Juan Basin of New Mexico (United States), Fassett et al. (2011) claim to provide the first successful direct dating of fossil bones and to establish the presence of Paleocene dinosaurs. Fassett et al. ignore previously published work that directly questions their stratigraphic interpretations (Lucas et al., 2009), and fail to provide sufficient descriptions of instrumental, geochronological, and statistical treatments of the data to allow evaluation of the potentially complex diagenetic and recrystallization history of bone. These shortcomings lead us to question the validity of the U-Pb dates published by Fassett et al. and their conclusions regarding the existence of Paleocene dinosaurs.

Dynamic analysis of a system of hinge-connected rigid bodies with nonrigid appendages. [equations of motion

NASA Technical Reports Server (NTRS)

Likins, P. W.

1974-01-01

Equations of motion are derived for use in simulating a spacecraft or other complex electromechanical system amenable to idealization as a set of hinge-connected rigid bodies of tree topology, with rigid axisymmetric rotors and nonrigid appendages attached to each rigid body in the set. In conjunction with a previously published report on finite-element appendage vibration equations, this report provides a complete minimum-dimension formulation suitable for generic programming for digital computer numerical integration.

GCKP84-general chemical kinetics code for gas-phase flow and batch processes including heat transfer effects

NASA Technical Reports Server (NTRS)

Bittker, D. A.; Scullin, V. J.

1984-01-01

A general chemical kinetics code is described for complex, homogeneous ideal gas reactions in any chemical system. The main features of the GCKP84 code are flexibility, convenience, and speed of computation for many different reaction conditions. The code, which replaces the GCKP code published previously, solves numerically the differential equations for complex reaction in a batch system or one dimensional inviscid flow. It also solves numerically the nonlinear algebraic equations describing the well stirred reactor. A new state of the art numerical integration method is used for greatly increased speed in handling systems of stiff differential equations. The theory and the computer program, including details of input preparation and a guide to using the code are given.

Case report: Long-standing complex regional pain syndrome relieved by a cephalosporin antibiotic.

PubMed

Ware, Mark A; Bennett, Gary J

2014-07-01

We describe a young woman who had had treatment-refractory complex regional pain syndrome (CRPS) for 6 years before receiving antibiotic treatment with cefadroxil (a cephalosporin derivative) for a minor infection. Cefadroxil reduced the patient's pain and motor dysfunction (dystonia and impaired voluntary movement) within days; the pain and motor disorder returned when cefadroxil was discontinued; and both again abated when cefadroxil was re-instituted. The patient has now had symptom relief for more than 3 years on continuing cefadroxil therapy. We discuss this case in the context of previous reports of antibiotic treatment relieving neuropathic pain in experimental animals. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Respiratory complex I: 'steam engine' of the cell?

PubMed

Efremov, Rouslan G; Sazanov, Leonid A

2011-08-01

Complex I is the first enzyme of the respiratory chain and plays a central role in cellular energy production. It has been implicated in many human neurodegenerative diseases, as well as in ageing. One of the biggest membrane protein complexes, it is an L-shaped assembly consisting of hydrophilic and membrane domains. Previously, we have determined structures of the hydrophilic domain in several redox states. Last year was marked by fascinating breakthroughs in the understanding of the complete structure. We described the architecture of the membrane domain and of the entire bacterial complex I. X-ray analysis of the larger mitochondrial enzyme has also been published. The core subunits of the bacterial and mitochondrial enzymes have remarkably similar structures. The proposed mechanism of coupling between electron transfer and proton translocation involves long-range conformational changes, coordinated in part by a long α-helix, akin to the coupling rod of a steam engine. Copyright © 2011 Elsevier Ltd. All rights reserved.

Predictive Surface Complexation Modeling

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

Sverjensky, Dimitri A.

Surface complexation plays an important role in the equilibria and kinetics of processes controlling the compositions of soilwaters and groundwaters, the fate of contaminants in groundwaters, and the subsurface storage of CO 2 and nuclear waste. Over the last several decades, many dozens of individual experimental studies have addressed aspects of surface complexation that have contributed to an increased understanding of its role in natural systems. However, there has been no previous attempt to develop a model of surface complexation that can be used to link all the experimental studies in order to place them on a predictive basis. Overall,more » my research has successfully integrated the results of the work of many experimentalists published over several decades. For the first time in studies of the geochemistry of the mineral-water interface, a practical predictive capability for modeling has become available. The predictive correlations developed in my research now enable extrapolations of experimental studies to provide estimates of surface chemistry for systems not yet studied experimentally and for natural and anthropogenically perturbed systems.« less

Trans-acting RNAs as molecular probes for monitoring time-dependent structural change of an RNA complex adapting two structures.

PubMed

Maeda, Yuri; Furuta, Hiroyuki; Ikawa, Yoshiya

2011-03-01

As dynamic structural changes are pivotal for the functions of some classes of RNA molecule, it is important to develop methods to monitor structural changes in RNA in a time-dependent manner without chemical modification. Based on previous reports that trans-acting RNAs can be used as probes for analysis and control of 3D structures of target RNAs, we applied this method to monitor time-dependent structural changes in RNA. We designed and performed a proof-of-principle study using a simple model RNA complex that adopts two different structures as a target. The time-dependent structural changes in the target RNA were successfully monitored using two trans-acting RNAs, which stably form a ternary complex with the bimolecular target RNA and act as a catalyst to join two RNA fragments of the target complex, respectively. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Performance of children with developmental dyslexia on high and low topological entropy artificial grammar learning task.

PubMed

Katan, Pesia; Kahta, Shani; Sasson, Ayelet; Schiff, Rachel

2017-07-01

Graph complexity as measured by topological entropy has been previously shown to affect performance on artificial grammar learning tasks among typically developing children. The aim of this study was to examine the effect of graph complexity on implicit sequential learning among children with developmental dyslexia. Our goal was to determine whether children's performance depends on the complexity level of the grammar system learned. We conducted two artificial grammar learning experiments that compared performance of children with developmental dyslexia with that of age- and reading level-matched controls. Experiment 1 was a high topological entropy artificial grammar learning task that aimed to establish implicit learning phenomena in children with developmental dyslexia using previously published experimental conditions. Experiment 2 is a lower topological entropy variant of that task. Results indicated that given a high topological entropy grammar system, children with developmental dyslexia who were similar to the reading age-matched control group had substantial difficulty in performing the task as compared to typically developing children, who exhibited intact implicit learning of the grammar. On the other hand, when tested on a lower topological entropy grammar system, all groups performed above chance level, indicating that children with developmental dyslexia were able to identify rules from a given grammar system. The results reinforced the significance of graph complexity when experimenting with artificial grammar learning tasks, particularly with dyslexic participants.

High energy PIXE: A tool to characterize multi-layer thick samples

NASA Astrophysics Data System (ADS)

Subercaze, A.; Koumeir, C.; Métivier, V.; Servagent, N.; Guertin, A.; Haddad, F.

2018-02-01

High energy PIXE is a useful and non-destructive tool to characterize multi-layer thick samples such as cultural heritage objects. In a previous work, we demonstrated the possibility to perform quantitative analysis of simple multi-layer samples using high energy PIXE, without any assumption on their composition. In this work an in-depth study of the parameters involved in the method previously published is proposed. Its extension to more complex samples with a repeated layer is also presented. Experiments have been performed at the ARRONAX cyclotron using 68 MeV protons. The thicknesses and sequences of a multi-layer sample including two different layers of the same element have been determined. Performances and limits of this method are presented and discussed.

Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr-1.

PubMed

Zandarashvili, Levani; White, Mark A; Esadze, Alexandre; Iwahara, Junji

2015-07-08

The inducible transcription factor Egr-1 binds specifically to 9-bp target sequences containing two CpG sites that can potentially be methylated at four cytosine bases. Although it appears that complete CpG methylation would make an unfavorable steric clash in the previous crystal structures of the complexes with unmethylated or partially methylated DNA, our affinity data suggest that DNA recognition by Egr-1 is insensitive to CpG methylation. We have determined, at a 1.4-Å resolution, the crystal structure of the Egr-1 zinc-finger complex with completely methylated target DNA. Structural comparison of the three different methylation states reveals why Egr-1 can recognize the target sequences regardless of CpG methylation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Information Management for Unmanned Systems: Combining DL-Reasoning with Publish/Subscribe

NASA Astrophysics Data System (ADS)

Moser, Herwig; Reichelt, Toni; Oswald, Norbert; Förster, Stefan

Sharing capabilities and information between collaborating entities by using modem information- and communication-technology is a core principle in complex distributed civil or military mission scenarios. Previous work proved the suitability of Service-oriented Architectures for modelling and sharing the participating entities' capabilities. Albeit providing a satisfactory model for capabilities sharing, pure service-orientation curtails expressiveness for information exchange as opposed to dedicated data-centric communication principles. In this paper we introduce an Information Management System which combines OWL-Ontologies and automated reasoning with Publish/Subscribe-Systems, providing for a shared but decoupled data model. While confirming existing related research results, we emphasise the novel application and lack of practical experience of using Semantic Web technologies in areas other than originally intended. That is, aiding decision support and software design in the context of a mission scenario for an unmanned system. Experiments within a complex simulation environment show the immediate benefits of a semantic information-management and -dissemination platform: Clear separation of concerns in code and data model, increased service re-usability and extensibility as well as regulation of data flow and respective system behaviour through declarative rules.

How to Manage Rejected Scientific Papers? UNAIS as Final Solution.

PubMed

Diana, Alessandro

2012-01-01

Before publication, biomedical papers might undergo a very complex process, from journal selection, authors' motivations for submissions, modifications, and final publication or refusal. UNAIS (Unpublished Articles In Science) is an online repository in which authors can publish previously rejected scientific articles or articles that have never been submitted for publication. At UNAIS, authors can also publish the reasons behind the refusals to publication. UNAIS is more than an e-journal: it is a scientific drop box in which scientists can find indicative and negative results, as well as ideas that can inspire others. UNAIS's goal is also to help students and scientists who want to learn how to write scientific articles. UNAIS' aim is to exchange and promote knowledge. Have a look on www.unais.net.

Cortico-striatal language pathways dynamically adjust for syntactic complexity: A computational study.

PubMed

Szalisznyó, Krisztina; Silverstein, David; Teichmann, Marc; Duffau, Hugues; Smits, Anja

2017-01-01

A growing body of literature supports a key role of fronto-striatal circuits in language perception. It is now known that the striatum plays a role in engaging attentional resources and linguistic rule computation while also serving phonological short-term memory capabilities. The ventral semantic and the dorsal phonological stream dichotomy assumed for spoken language processing also seems to play a role in cortico-striatal perception. Based on recent studies that correlate deep Broca-striatal pathways with complex syntax performance, we used a previously developed computational model of frontal-striatal syntax circuits and hypothesized that different parallel language pathways may contribute to canonical and non-canonical sentence comprehension separately. We modified and further analyzed a thematic role assignment task and corresponding reservoir computing model of language circuits, as previously developed by Dominey and coworkers. We examined the models performance under various parameter regimes, by influencing how fast the presented language input decays and altering the temporal dynamics of activated word representations. This enabled us to quantify canonical and non-canonical sentence comprehension abilities. The modeling results suggest that separate cortico-cortical and cortico-striatal circuits may be recruited differently for processing syntactically more difficult and less complicated sentences. Alternatively, a single circuit would need to dynamically and adaptively adjust to syntactic complexity. Copyright © 2016. Published by Elsevier Inc.

Hidden diversity within the lizard genus Liolaemus: Genetic vs morphological divergence in the L. rothi complex (Squamata:Liolaeminae).

PubMed

Olave, Melisa; Avila, Luciano J; Sites, Jack W; Morando, Mariana

2017-02-01

Currently, Liolaemus is the second most species-rich reptile genus in the world (257 species), and predictions of its real diversity suggest that it may be the most diverse genus. Originally, Liolaemus species were described as widely distributed and morphologically variable taxa, but extensive sampling in previously unexplored geographic areas, coupled with molecular and more extensive morphological studies, have discovered an unexpectedly high number of previously undetected species. Here, we study the level of molecular vs. morphological divergence within the L. rothi complex, combining a total of 14 loci (2 mitochondrial and 12 nuclear loci) for 97 individuals, as well as morphological data (nine morphometric and 15 color pattern variables), that represent all six described species of the L. rothi complex, plus two candidate species. We use the multi-coalescent species delimitation program iBPP and resolve strong differences in molecular divergence; and each species is inferred as an independent lineage supported by high posterior probabilities. However, morphological differences are not that clear, and our modeling of morphological characters suggests differential selection pressures implying some level of morphological stasis. We discuss the role of natural selection on phenotypic traits, which may be an important factor in "hiding" the real diversity of the genus. Copyright © 2016. Published by Elsevier Inc.

Pellagra-like condition is xeroderma pigmentosum/Cockayne syndrome complex and niacin confers clinical benefit.

PubMed

Hijazi, H; Salih, M A; Hamad, M H A; Hassan, H H; Salih, S B M; Mohamed, K A; Mukhtar, M M; Karrar, Z A; Ansari, S; Ibrahim, N; Alkuraya, F S

2015-01-01

An extremely rare pellagra-like condition has been described, which was partially responsive to niacin and associated with a multisystem involvement. The condition was proposed to represent a novel autosomal recessive entity but the underlying mutation remained unknown for almost three decades. The objective of this study was to identify the causal mutation in the pellagra-like condition and investigate the mechanism by which niacin confers clinical benefit. Autozygosity mapping and exome sequencing were used to identify the causal mutation, and comet assay on patient fibroblasts before and after niacin treatment to assess its effect on DNA damage. We identified a single disease locus that harbors a novel mutation in ERCC5, thus confirming that the condition is in fact xeroderma pigmentosum/Cockayne syndrome (XP/CS) complex. Importantly, we also show that the previously described dermatological response to niacin is consistent with a dramatic protective effect against ultraviolet-induced DNA damage in patient fibroblasts conferred by niacin treatment. Our findings show the power of exome sequencing in reassigning previously described novel clinical entities, and suggest a mechanism for the dermatological response to niacin in patients with XP/CS complex. This raises interesting possibilities about the potential therapeutic use of niacin in XP. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity.

PubMed

Di Pisa, Flavio; Landi, Giacomo; Dello Iacono, Lucia; Pozzi, Cecilia; Borsari, Chiara; Ferrari, Stefania; Santucci, Matteo; Santarem, Nuno; Cordeiro-da-Silva, Anabela; Moraes, Carolina B; Alcantara, Laura M; Fontana, Vanessa; Freitas-Junior, Lucio H; Gul, Sheraz; Kuzikov, Maria; Behrens, Birte; Pöhner, Ina; Wade, Rebecca C; Costi, Maria Paola; Mangani, Stefano

2017-03-08

Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues ( 1 - 3 ) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes ( Trypanosoma brucei PTR1- Tb PTR1 and Leishmania major-Lm PTR1) and parasites ( Trypanosoma brucei and Leishmania infantum ). A crystal structure of Tb PTR1 in complex with compound 1 and the first crystal structures of Lm PTR1-flavanone complexes (compounds 1 and 3 ) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants.

Swedish and American studies show that initiatives to decrease maternal obesity could play a key role in reducing preterm birth.

PubMed

Gould, Jeffrey B; Mayo, Jonathan; Shaw, Gary M; Stevenson, David K

2014-06-01

Maternal obesity is a major source of preventable perinatal morbidity, but studies of the relationship between obesity and preterm birth have been inconsistent. This review looks at two major studies covering just under 3.5 million births, from California, USA, and Sweden. Inconsistent findings in previous studies appear to stem from the complex relationship between obesity and preterm birth. Initiatives to decrease maternal obesity represent an important strategy in reducing preterm birth. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Anterior spinal and bulbar artery supply to the posterior inferior cerebellar artery revealed by a ruptured aneurysm: case report.

PubMed

Gabrieli, Joseph; Sourour, Nader-Antoine; Chauvet, Dorian; Di Maria, Federico; Chiras, Jacques; Clarençon, Frédéric

2017-02-01

The posterior inferior cerebellar artery (PICA) is a vessel located between the intra- and extracranial circulation. The artery is characterized by a complex embryological development and numerous anatomical variants. The authors present a case of the PICA supplied by both a hypertrophic anterior spinal artery and a hypoplastic bulbar artery. This unusual arrangement somehow completes the list of previously published variants, and the spontaneous rupture of a related aneurysm confirmed the fragility of this network. The authors discuss anatomical and treatment considerations.

Water-refined solution structure of the human Grb7-SH2 domain in complex with the erbB2 receptor peptide pY1139.

PubMed

Pias, Sally C; Johnson, Dennis L; Smith, David E; Lyons, Barbara A

2012-08-01

We report a refinement in implicit water of the previously published solution structure of the Grb7-SH2 domain bound to the erbB2 receptor peptide pY1139. Structure quality measures indicate substantial improvement, with residues in the most favored regions of the Ramachandran plot increasing by 14 % and with WHAT IF statistics (Vriend, G. J. Mol. Graph., 1990, 8(1), 52-56) falling closer to expected values for well-refined structures.

Iterative Minimum Variance Beamformer with Low Complexity for Medical Ultrasound Imaging.

PubMed

Deylami, Ali Mohades; Asl, Babak Mohammadzadeh

2018-06-04

Minimum variance beamformer (MVB) improves the resolution and contrast of medical ultrasound images compared with delay and sum (DAS) beamformer. The weight vector of this beamformer should be calculated for each imaging point independently, with a cost of increasing computational complexity. The large number of necessary calculations limits this beamformer to application in real-time systems. A beamformer is proposed based on the MVB with lower computational complexity while preserving its advantages. This beamformer avoids matrix inversion, which is the most complex part of the MVB, by solving the optimization problem iteratively. The received signals from two imaging points close together do not vary much in medical ultrasound imaging. Therefore, using the previously optimized weight vector for one point as initial weight vector for the new neighboring point can improve the convergence speed and decrease the computational complexity. The proposed method was applied on several data sets, and it has been shown that the method can regenerate the results obtained by the MVB while the order of complexity is decreased from O(L 3 ) to O(L 2 ). Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Applications in Data-Intensive Computing

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

Shah, Anuj R.; Adkins, Joshua N.; Baxter, Douglas J.

2010-04-01

This book chapter, to be published in Advances in Computers, Volume 78, in 2010 describes applications of data intensive computing (DIC). This is an invited chapter resulting from a previous publication on DIC. This work summarizes efforts coming out of the PNNL's Data Intensive Computing Initiative. Advances in technology have empowered individuals with the ability to generate digital content with mouse clicks and voice commands. Digital pictures, emails, text messages, home videos, audio, and webpages are common examples of digital content that are generated on a regular basis. Data intensive computing facilitates human understanding of complex problems. Data-intensive applications providemore » timely and meaningful analytical results in response to exponentially growing data complexity and associated analysis requirements through the development of new classes of software, algorithms, and hardware.« less

Stent Repair for Complex Coarctation of Aorta.

PubMed

Suárez de Lezo, José; Romero, Miguel; Pan, Manuel; Suárez de Lezo, Javier; Segura, José; Ojeda, Soledad; Pavlovic, Djordje; Mazuelos, Francisco; López Aguilera, José; Espejo Perez, Simona

2015-08-24

This study sought to determine whether several anatomic or evolving characteristics of the coarctation may create challenging conditions for treatment. Stent repair of coarctation of aorta is an alternative to surgical correction. We analyzed our 21-year experience in the percutaneous treatment of complex coarctation of aorta. Adverse conditions for treatment were as follow: 1) complete interruption of the aortic arch (n = 11); 2) associated aneurysm (n = 18); 3) complex stenosis (n = 30); and 4) the need for re-expansion and/or restenting (n = 21). Twenty patients (33%) belonged to more than 1 group. Ten interruptions were type A and 1 was type B. The mean length of the interrupted aorta was 9 ± 11 mm. The associated aneurysms were native in 8 patients and after previous intervention in 10 patients. Aneurysm shapes were fusiform in 8 patients and saccular in 10. The following characteristics defined complex stenosis as long diffuse stenosis, very tortuous coarctation, or stenosis involving a main branch or an unusual location. Patients previously stented at an early age, required re-expansion and/or restenting after reaching 16 ± 5 years of age. Two patients had died by 1-month follow-up. The remaining 58 patients did well and were followed-up for a mean period of 10 ± 6 years. Late adverse events occurred in 3 patients (5%). All remaining patients are symptom-free, with normal baseline blood pressure. Imaging techniques revealed good patency at follow-up without associated aneurysm or restenosis. The actuarial survival free probability of all complex patients at 15 years was 92%. Stent repair of complex coarctation of aorta is feasible and safe. Initial results are maintained at later follow-up. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Kinetic analysis of hyperpolarized data with minimum a priori knowledge: Hybrid maximum entropy and nonlinear least squares method (MEM/NLS).

PubMed

Mariotti, Erika; Veronese, Mattia; Dunn, Joel T; Southworth, Richard; Eykyn, Thomas R

2015-06-01

To assess the feasibility of using a hybrid Maximum-Entropy/Nonlinear Least Squares (MEM/NLS) method for analyzing the kinetics of hyperpolarized dynamic data with minimum a priori knowledge. A continuous distribution of rates obtained through the Laplace inversion of the data is used as a constraint on the NLS fitting to derive a discrete spectrum of rates. Performance of the MEM/NLS algorithm was assessed through Monte Carlo simulations and validated by fitting the longitudinal relaxation time curves of hyperpolarized [1-(13) C] pyruvate acquired at 9.4 Tesla and at three different flip angles. The method was further used to assess the kinetics of hyperpolarized pyruvate-lactate exchange acquired in vitro in whole blood and to re-analyze the previously published in vitro reaction of hyperpolarized (15) N choline with choline kinase. The MEM/NLS method was found to be adequate for the kinetic characterization of hyperpolarized in vitro time-series. Additional insights were obtained from experimental data in blood as well as from previously published (15) N choline experimental data. The proposed method informs on the compartmental model that best approximate the biological system observed using hyperpolarized (13) C MR especially when the metabolic pathway assessed is complex or a new hyperpolarized probe is used. © 2014 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc.

Transforming growth factor β suppresses peroxisome proliferator-activated receptor γ expression via both SMAD binding and novel TGF-β inhibitory elements.

PubMed

Lakshmi, Sowmya P; Reddy, Aravind T; Reddy, Raju C

2017-04-24

Transforming growth factor β (TGF-β) contributes to wound healing and, when dysregulated, to pathological fibrosis. TGF-β and the anti-fibrotic nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) repress each other's expression, and such PPARγ down-regulation is prominent in fibrosis and mediated, via previously unknown SMAD-signaling mechanisms. Here, we show that TGF-β induces the association of SMAD3 with both SMAD4, needed for translocation of the complex into the nucleus, and the essential context-sensitive co-repressors E2F4 and p107. The complex mediates TGF-β-induced repression by binding to regulatory elements in the target promoter. In the PPARG promoter, we found that the SMAD3-SMAD4 complex binds both to a previously unknown consensus TGF-β inhibitory element (TIE) and also to canonical SMAD-binding elements (SBEs). Furthermore, the TIE and SBEs independently mediated the partial repression of PPARG transcription, the first demonstration of a TIE and SBEs functioning within the same promoter. Also, TGF-β-treated fibroblasts contained SMAD complexes that activated a SMAD target gene in addition to those repressing PPARG transcription, the first finding of such dual activity within the same cell. These findings describe in detail novel mechanisms by which TGF-β represses PPARG transcription, thereby facilitating its own pro-fibrotic activity. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

The 2015 Nucleic Acids Research Database Issue and molecular biology database collection.

PubMed

Galperin, Michael Y; Rigden, Daniel J; Fernández-Suárez, Xosé M

2015-01-01

The 2015 Nucleic Acids Research Database Issue contains 172 papers that include descriptions of 56 new molecular biology databases, and updates on 115 databases whose descriptions have been previously published in NAR or other journals. Following the classification that has been introduced last year in order to simplify navigation of the entire issue, these articles are divided into eight subject categories. This year's highlights include RNAcentral, an international community portal to various databases on noncoding RNA; ValidatorDB, a validation database for protein structures and their ligands; SASBDB, a primary repository for small-angle scattering data of various macromolecular complexes; MoonProt, a database of 'moonlighting' proteins, and two new databases of protein-protein and other macromolecular complexes, ComPPI and the Complex Portal. This issue also includes an unusually high number of cancer-related databases and other databases dedicated to genomic basics of disease and potential drugs and drug targets. The size of NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/a/, remained approximately the same, following the addition of 74 new resources and removal of 77 obsolete web sites. The entire Database Issue is freely available online on the Nucleic Acids Research web site (http://nar.oxfordjournals.org/). Published by Oxford University Press on behalf of Nucleic Acids Research 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Discovery and validation of information theory-based transcription factor and cofactor binding site motifs.

PubMed

Lu, Ruipeng; Mucaki, Eliseos J; Rogan, Peter K

2017-03-17

Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs. We obtained contiguous and bipartite information theory-based position weight matrices (iPWMs) for 93 sequence-specific TFs, discovered 23 cofactor motifs for 127 TFs and revealed six high-confidence novel motifs. The reliability and accuracy of these iPWMs were determined via four independent validation methods, including the detection of experimentally proven binding sites, explanation of effects of characterized SNPs, comparison with previously published motifs and statistical analyses. We also predict previously unreported TF coregulatory interactions (e.g. TF complexes). These iPWMs constitute a powerful tool for predicting the effects of sequence variants in known binding sites, performing mutation analysis on regulatory SNPs and predicting previously unrecognized binding sites and target genes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Attributes of advanced practice registered nurse care coordination for children with medical complexity.

PubMed

Cady, Rhonda G; Kelly, Anne M; Finkelstein, Stanley M; Looman, Wendy S; Garwick, Ann W

2014-01-01

Care coordination is an essential component of the pediatric health care home. This study investigated the attributes of relationship-based advanced practice registered nurse care coordination for children with medical complexity enrolled in a tertiary hospital-based health care home. Retrospective review of 2,628 care coordination episodes conducted by telehealth over a consecutive 3-year time period for 27 children indicated that parents initiated the majority of episodes and the most frequent reason was acute and chronic condition management. During this period, care coordination episodes tripled, with a significant increase (p < .001) between years 1 and 2. The increased episodes could explain previously reported reductions in hospitalizations for this group of children. Descriptive analysis of a program-specific survey showed that parents valued having a single place to call and assistance in managing their child's complex needs. The advanced practice registered nurse care coordination model has potential for changing the health management processes for children with medical complexity. Copyright © 2014 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

δ-dependency for privacy-preserving XML data publishing.

PubMed

Landberg, Anders H; Nguyen, Kinh; Pardede, Eric; Rahayu, J Wenny

2014-08-01

An ever increasing amount of medical data such as electronic health records, is being collected, stored, shared and managed in large online health information systems and electronic medical record systems (EMR) (Williams et al., 2001; Virtanen, 2009; Huang and Liou, 2007) [1-3]. From such rich collections, data is often published in the form of census and statistical data sets for the purpose of knowledge sharing and enabling medical research. This brings with it an increasing need for protecting individual people privacy, and it becomes an issue of great importance especially when information about patients is exposed to the public. While the concept of data privacy has been comprehensively studied for relational data, models and algorithms addressing the distinct differences and complex structure of XML data are yet to be explored. Currently, the common compromise method is to convert private XML data into relational data for publication. This ad hoc approach results in significant loss of useful semantic information previously carried in the private XML data. Health data often has very complex structure, which is best expressed in XML. In fact, XML is the standard format for exchanging (e.g. HL7 version 3(1)) and publishing health information. Lack of means to deal directly with data in XML format is inevitably a serious drawback. In this paper we propose a novel privacy protection model for XML, and an algorithm for implementing this model. We provide general rules, both for transforming a private XML schema into a published XML schema, and for mapping private XML data to the new privacy-protected published XML data. In addition, we propose a new privacy property, δ-dependency, which can be applied to both relational and XML data, and that takes into consideration the hierarchical nature of sensitive data (as opposed to "quasi-identifiers"). Lastly, we provide an implementation of our model, algorithm and privacy property, and perform an experimental analysis, to demonstrate the proposed privacy scheme in practical application. Copyright © 2014. Published by Elsevier Inc.

A review of the basics of mitochondrial bioenergetics, metabolism, and related signaling pathways in cancer cells: Therapeutic targeting of tumor mitochondria with lipophilic cationic compounds.

PubMed

Kalyanaraman, Balaraman; Cheng, Gang; Hardy, Micael; Ouari, Olivier; Lopez, Marcos; Joseph, Joy; Zielonka, Jacek; Dwinell, Michael B

2018-04-01

The present review is a sequel to the previous review on cancer metabolism published in this journal. This review focuses on the selective antiproliferative and cytotoxic effects of mitochondria-targeted therapeutics (MTTs) in cancer cells. Emerging research reveals a key role of mitochondrial respiration on tumor proliferation. Previously, a mitochondria-targeted nitroxide was shown to selectively inhibit colon cancer cell proliferation at submicromolar levels. This review is centered on the therapeutic use of MTTs and their bioenergetic profiling in cancer cells. Triphenylphosphonium cation conjugated to a parent molecule (e.g., vitamin-E or chromanol, ubiquinone, and metformin) via a linker alkyl chain is considered an MTT. MTTs selectively and potently inhibit proliferation of cancer cells and, in some cases, induce cytotoxicity. MTTs inhibit mitochondrial complex I activity and induce mitochondrial stress in cancer cells through generation of reactive oxygen species. MTTs in combination with glycolytic inhibitors synergistically inhibit tumor cell proliferation. This review discusses how signaling molecules traditionally linked to tumor cell proliferation affect tumor metabolism and bioenergetics (glycolysis, TCA cycle, and glutaminolysis). Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The stratigraphy of the Steep Rock Group, N.W. Ontario, with evidence of a major unconformity

NASA Technical Reports Server (NTRS)

Wilks, M. E.; Nisbet, E. G.

1986-01-01

The Steep Rock Group is exposed 6 km north of Atikokan, 200 km west of Thunder Bay. It is situated on the southern margin of the Wabigoon Belt of the Archaean Superior Province, N. W. Ontario. Reinvestigation of the geology of the Group has shown that the Group lies unconformably on the Tonalite Complex to the east. This unconformity has been previously suspected, from regional and ine mapping but no conclusive outcrop evidence for its existence has as yet been published. The strike of the group, comprised of Basal Conglomerate, Carbonate Member, Ore Zone and Ashrock is generally north-northwest dipping steeply to the southwest. Of the 7 contacts between the Steep Rock Group and the Tonalite Complex, 3 expose the unconformity (The Headland, S. Roberts Pit, Trueman Point), and 4 are faulted. These three outcrops demonstrate unequivocally that the Steep Rock group was laid down unconformably on the underlying Tonalite Complex, which is circa 3 Ga old.

Middle Ordovician subduction of continental crust in the Scandinavian Caledonides: an example from Tjeliken, Seve Nappe Complex, Sweden

NASA Astrophysics Data System (ADS)

Fassmer, Kathrin; Klonowska, Iwona; Walczak, Katarzyna; Andersson, Barbro; Froitzheim, Nikolaus; Majka, Jarosław; Fonseca, Raúl O. C.; Münker, Carsten; Janák, Marian; Whitehouse, Martin

2017-12-01

The Seve Nappe Complex of the Scandinavian Caledonides is thought to be derived from the distal passive margin of Baltica which collided with Laurentia in the Scandian Phase of the Caledonian Orogeny at 430-400 Ma. Parts of the Seve Nappe Complex were affected by pre-Scandian high- and ultrahigh-pressure metamorphism, in a tectonic framework that is still unclear, partly due to uncertainties about the exact timing. Previous age determinations yielded between 505 and 446 Ma, with a general trend of older ages in the North (Norrbotten) than in the South (Jämtland). New age determinations were performed on eclogite and garnet-phengite gneiss at Tjeliken in northern Jämtland. Thermodynamic modelling yielded peak metamorphic conditions of 25-27 kbar/680-760 °C for the garnet-phengite gneiss, similar to published peak metamorphic conditions of the eclogite (25-26 kbar/650-700 °C). Metamorphic rims of zircons from the garnet-phengite gneiss were dated using secondary ion mass spectrometry and yielded a concordia age of 458.9 ± 2.5 Ma. Lu-Hf garnet-whole rock dating yielded 458 ± 1.0 Ma for the eclogite. Garnet in the eclogite shows prograde major-element zoning and concentration of Lu in the cores, indicating that this age is related to garnet growth during pressure increase, i.e. subduction. The identical ages from both rock types, coinciding with published Sm-Nd ages from the eclogite, confirm subduction of the Seve Nappe Complex in Northern Jämtland during the Middle Ordovician in a fast subduction-exhumation cycle.

PrePhyloPro: phylogenetic profile-based prediction of whole proteome linkages

PubMed Central

Niu, Yulong; Liu, Chengcheng; Moghimyfiroozabad, Shayan; Yang, Yi

2017-01-01

Direct and indirect functional links between proteins as well as their interactions as part of larger protein complexes or common signaling pathways may be predicted by analyzing the correlation of their evolutionary patterns. Based on phylogenetic profiling, here we present a highly scalable and time-efficient computational framework for predicting linkages within the whole human proteome. We have validated this method through analysis of 3,697 human pathways and molecular complexes and a comparison of our results with the prediction outcomes of previously published co-occurrency model-based and normalization methods. Here we also introduce PrePhyloPro, a web-based software that uses our method for accurately predicting proteome-wide linkages. We present data on interactions of human mitochondrial proteins, verifying the performance of this software. PrePhyloPro is freely available at http://prephylopro.org/phyloprofile/. PMID:28875072

Detection of the HA-33 protein in botulinum neurotoxin type G complex by mass spectrometry.

PubMed

Kalb, Suzanne R; Baudys, Jakub; Barr, John R

2015-10-23

The disease botulism is caused by intoxication with botulinum neurotoxins (BoNTs), extremely toxic proteins which cause paralysis. This neurotoxin is produced by some members of the Clostridium botulinum and closely related species, and is produced as a protein complex consisting of the neurotoxin and neurotoxin-associated proteins (NAPs). There are seven known serotypes of BoNT, A-G, and the composition of the NAPs can differ between these serotypes. It was previously published that the BoNT/G complex consisted of BoNT/G, nontoxic-nonhemagglutinin (NTNH), Hemagglutinin 70 (HA-70), and HA-17, but that HA-33, a component of the protein complex of other serotypes of BoNT, was not found. Components of the BoNT/G complex were first separated by SDS-PAGE, and bands corresponding to components of the complex were digested and analyzed by LC-MS/MS. Gel bands were identified with sequence coverages of 91% for BoNT/G, 91% for NTNH, 89% for HA-70, and 88% for HA-17. Notably, one gel band was also clearly identified as HA-33 with 93% sequence coverage. The BoNT/G complex consists of BoNT/G, NTNH, HA-70, HA-17, and HA-33. These proteins form the progenitor form of BoNT/G, similar to all other HA positive progenitor toxin complexes.

Express implant in Urrets-Zavalia syndrome after descemet's stripping automated endothelial keratoplasty.

PubMed

Muñoz-Morales, A; del Trigo-Zamora, J R; Sánchez-Vicente, J L; Lozano-Bernal, O; Luchena-López, R

2015-10-01

The first case is described on a patient with Urrets-Zavalía syndrome after Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) in whom an ExPRESS implant was used. The ExPRESS implant is a useful tool for complex cases of post-surgical glaucoma where patients need to avoid post-operative inflammation and risks (corneal transplant patients). It is also very useful in cases with a high risk of fibrosis due to previous interventions. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

A revised Self- and Family Management Framework.

PubMed

Grey, Margaret; Schulman-Green, Dena; Knafl, Kathleen; Reynolds, Nancy R

2015-01-01

Research on self- and family management of chronic conditions has advanced over the past 6 years, but the use of simple frameworks has hampered the understanding of the complexities involved. We sought to update our previously published model with new empirical, synthetic, and theoretical work. We used synthesis of previous studies to update the framework. We propose a revised framework that clarifies facilitators and barriers, processes, proximal outcomes, and distal outcomes of self- and family management and their relationships. We offer the revised framework as a model that can be used in studies aimed at advancing self- and family management science. The use of the framework to guide studies would allow for the design of studies that can address more clearly how self-management interventions work and under what conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Crystal structure of the human 4-1BB/4-1BBL complex.

PubMed

Gilbreth, Ryan N; Oganesyan, Vaheh Y; Amdouni, Hamza; Novarra, Shabazz; Grinberg, Luba; Barnes, Arnita; Baca, Manuel

2018-05-02

4-1BBL is a member of the TNF superfamily and is the ligand for the TNFRsuperfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells and agonists of this receptor have garnered strong attention as potentialimmunotherapy agents. Broadly speaking, the structural features of TNF superfamilymembers, their receptors and ligand/receptor complexes are similar. However, apublished crystal structure of human 4-1BBL suggests that it may be unique in thisregard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4 Å resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Routine Discovery of Complex Genetic Models using Genetic Algorithms

PubMed Central

Moore, Jason H.; Hahn, Lance W.; Ritchie, Marylyn D.; Thornton, Tricia A.; White, Bill C.

2010-01-01

Simulation studies are useful in various disciplines for a number of reasons including the development and evaluation of new computational and statistical methods. This is particularly true in human genetics and genetic epidemiology where new analytical methods are needed for the detection and characterization of disease susceptibility genes whose effects are complex, nonlinear, and partially or solely dependent on the effects of other genes (i.e. epistasis or gene-gene interaction). Despite this need, the development of complex genetic models that can be used to simulate data is not always intuitive. In fact, only a few such models have been published. We have previously developed a genetic algorithm approach to discovering complex genetic models in which two single nucleotide polymorphisms (SNPs) influence disease risk solely through nonlinear interactions. In this paper, we extend this approach for the discovery of high-order epistasis models involving three to five SNPs. We demonstrate that the genetic algorithm is capable of routinely discovering interesting high-order epistasis models in which each SNP influences risk of disease only through interactions with the other SNPs in the model. This study opens the door for routine simulation of complex gene-gene interactions among SNPs for the development and evaluation of new statistical and computational approaches for identifying common, complex multifactorial disease susceptibility genes. PMID:20948983

Outcomes of complex robot-assisted extravesical ureteral reimplantation in the pediatric population.

PubMed

Arlen, Angela M; Broderick, Kristin M; Travers, Curtis; Smith, Edwin A; Elmore, James M; Kirsch, Andrew J

2016-06-01

While open ureteral reimplantation remains the gold standard for surgical treatment of vesicoureteral reflux (VUR), minimally invasive approaches offer potential benefits. This study evaluated the outcomes of children undergoing complex robot-assisted laparoscopic ureteral reimplantation (RALUR) for failed previous anti-reflux surgery, complex anatomy, or ureterovesical junction obstruction (UVJO), and compared them with patients undergoing open extravesical repair. Children undergoing complex RALUR or open extravesical ureteral reimplantation (OUR) were identified. Reimplantation was classified as complex if ureters: 1) had previous anti-reflux surgery, 2) required tapering and/or dismembering, or 3) had associated duplication or diverticulum. Seventeen children underwent complex RALUR during a 24-month period, compared with 41 OUR. The mean follow-up was 16.6 ± 6.5 months. The RALUR children were significantly older (9.3 ± 3.7 years) than the OUR patients (3.1 ± 2.7 years; P < 0.001). All RALUR patients were discharged on postoperative day one, while 24.4% of children in the open group required longer hospitalization (mean 1.3 ± 0.7 days; P = 0.03). Adjusting for age, there was no significant difference in inpatient analgesic usage between the two cohorts. Three OUR patients (7.3%) developed postoperative febrile urinary tract infection compared with a single child (5.9%) undergoing RALUR (P = 1.00). There was no significant difference in complication rate between the two groups (12.2% OUR versus 11.8% RALUR; P = 1.00). A postoperative cystogram was performed in the majority of RALUR patients, with no persistent VUR detected, and one child (6.7%) was diagnosed with contralateral reflux. Reported VUR resolution rates following robot-assisted ureteral reimplantation are varied. In the present series, children undergoing RALUR following failed previous anti-reflux surgery, with complex anatomy, or UVJO experienced a shorter length of stay but had similar analgesic requirements to those undergoing open repair. Radiographic, clinical success rates and complication risk were comparable. This study had several limitations, aside from lack of randomization. Analgesic use was limited to an inpatient setting, and pain scores were not assessed. Not all children underwent a postoperative VCUG, so the true radiographic success rate is unknown. A larger patient cohort with longer follow-up is necessary to determine predictors of radiographic and clinical failure. Older children with a previous history of anti-reflux surgery were more likely to undergo RALUR. These children had success and complication rates comparable to younger patients following complex open extravesical reimplantation, which underscores the expanding role of robot-assisted lower urinary tract reconstructive surgery in the pediatric population. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Endophthalmitis of probable endogenous origin caused by Scedosporium boydii: A case report.

PubMed

Vanzzini-Zago, Virginia; Corredor-Casas, Sonia; Rodríguez-Reyes, Abelardo; Hernández-Hernández, Francisca; Manzano-Gayosso, Patricia; Martínez, Rubén López; Orozco, Alan Ricardo Alba

2016-01-01

Mycotic ocular infections caused by the Scedosporium apiospermum species complex are challenging to treat because of the delayed diagnoses and poor responses to antifungal drugs and surgical treatment. A case of a 69-year-old male patient with a history of diabetes mellitus type 2 and prior surgery on the right femur is described. In the 10 days prior to the ophthalmic consultation he started with ocular pain, adding to a previous and progressive loss of visual acuity in his right eye. The diagnosis of endophthalmitis of probable endogenous origin was established. Despite medical treatment, the patient's condition worsened and, due to the imminent risks, an enucleation was performed. Smears of the enucleation tissue revealed fungal cells, and the cultures yielded a fungus belonging to the S. apiospermum species complex, which was identified as Scedosporium boydii by morphological characteristics and sequencing of a PCR amplicon. A diagnosis of endophthalmitis of probable endogenous origin in the right eye was based on a previous right femur surgery. Potential risk to the patient led to enucleation. Copyright © 2016 Asociación Española de Micología. Published by Elsevier Espana. All rights reserved.

The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes.

PubMed

Burroughs, Amelia; Wise, Andrew K; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y; Lang, Eric J; Apps, Richard; Cerminara, Nadia L

2017-01-01

Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes. Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets. The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear. We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number. This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition, complex spikes with a greater number of spikelets were associated with a subsequent reduction in simple spike firing rate. We therefore suggest that one important function of spikelets is the modulation of Purkinje cell simple spike firing frequency, which has implications for controlling cerebellar cortical output and motor learning. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

A defined, glucose-limited mineral medium for the cultivation of Listeria spp.

PubMed

Schneebeli, Rudolf; Egli, Thomas

2013-04-01

Members of the genus Listeria are fastidious bacteria with respect to their nutritional requirements, and several minimal media described in the literature fail to support growth of all Listeria spp. Furthermore, strict limitation by a single nutrient, e.g., the carbon source, has not been demonstrated for any of the published minimal media. This is an important prerequisite for defined studies of growth and physiology, including "omics." Based on a theoretical analysis of previously published mineral media for Listeria, an improved, well-balanced growth medium was designed. It supports the growth, not only of all tested Listeria monocytogenes strains, but of all other Listeria species, with the exception of L. ivanovii. The growth performance of L. monocytogenes strain Scott A was tested in the newly designed medium; glucose served as the only carbon and energy source for growth, whereas neither the supplied amino acids nor the buffering and complexing components (MOPS [morpholinepropanesulfonic acid] and EDTA) supported growth. Omission of amino acids, trace elements, or vitamins, alone or in combination, resulted in considerably reduced biomass yields. Furthermore, we monitored the specific growth rates of various Listeria strains cultivated in the designed mineral medium and compared them to growth in complex medium (brain heart infusion broth [BHI]). The novel mineral medium was optimized for the commonly used strain L. monocytogenes Scott A to achieve optimum cell yields and maximum specific growth rates. This mineral medium is the first published synthetic medium for Listeria that has been shown to be strictly carbon (glucose) limited.

Harvesting of novel polyhydroxyalkanaote (PHA) synthase encoding genes from a soil metagenome library using phenotypic screening.

PubMed

Schallmey, Marcus; Ly, Anh; Wang, Chunxia; Meglei, Gabriela; Voget, Sonja; Streit, Wolfgang R; Driscoll, Brian T; Charles, Trevor C

2011-08-01

We previously reported the construction of metagenomic libraries in the IncP cosmid vector pRK7813, enabling heterologous expression of these broad-host-range libraries in multiple bacterial hosts. Expressing these libraries in Sinorhizobium meliloti, we have successfully complemented associated phenotypes of polyhydroxyalkanoate synthesis mutants. DNA sequence analysis of three clones indicates that the complementing genes are homologous to, but substantially different from, known polyhydroxyalkanaote synthase-encoding genes. Thus we have demonstrated the ability to isolate diverse genes for polyhydroxyalkanaote synthesis by functional complementation of defined mutants. Such genes might be of use in the engineering of more efficient systems for the industrial production of bioplastics. The use of functional complementation will also provide a vehicle to probe the genetics of polyhydroxyalkanaote metabolism and its relation to carbon availability in complex microbial assemblages. 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

An Analysis of The Parameters Used In Speech ABR Assessment Protocols.

PubMed

Sanfins, Milaine D; Hatzopoulos, Stavros; Donadon, Caroline; Diniz, Thais A; Borges, Leticia R; Skarzynski, Piotr H; Colella-Santos, Maria Francisca

2018-04-01

The aim of this study was to assess the parameters of choice, such as duration, intensity, rate, polarity, number of sweeps, window length, stimulated ear, fundamental frequency, first formant, and second formant, from previously published speech ABR studies. To identify candidate articles, five databases were assessed using the following keyword descriptors: speech ABR, ABR-speech, speech auditory brainstem response, auditory evoked potential to speech, speech-evoked brainstem response, and complex sounds. The search identified 1288 articles published between 2005 and 2015. After filtering the total number of papers according to the inclusion and exclusion criteria, 21 studies were selected. Analyzing the protocol details used in 21 studies suggested that there is no consensus to date on a speech-ABR protocol and that the parameters of analysis used are quite variable between studies. This inhibits the wider generalization and extrapolation of data across languages and studies.

Is there an effective approach to deterring students from plagiarizing?

PubMed

Bilic-Zulle, Lidija; Azman, Josip; Frkovic, Vedran; Petrovecki, Mladen

2008-03-01

The purpose of this study was to evaluate the effectiveness of plagiarism detection software and penalty for plagiarizing in detecting and deterring plagiarism among medical students. The study was a continuation of previously published research in which second-year medical students from 2001/2002 and 2002/2003 school years were required to write an essay based on one of the four scientific articles offered by the instructor. Students from 2004/2005 (N = 92) included in present study were given the same task. Topics of two of the four articles were considered less complex, and two were more complex. One less and one more complex articles were available only as hardcopies, whereas the other two were available in electronic format. The students from 2001/2002 (N = 111) were only told to write an original essay, whereas the students from 2002/2003 (N = 87) were additionally warned against plagiarism, explained what plagiarism was, and how to avoid it. The students from 2004/2005 were warned that their essays would be examined by plagiarism detection software and that those who had plagiarized would be penalized. Students from 2004/2005 plagiarized significantly less of their essays than students from the previous two groups (2% vs. 17% vs. 21%, respectively, P < 0.001). Over time, students more frequently choose articles with more complex subjects (P < 0.001) and articles in electronic format (P < 0.001) as a source for their essays, but it did not influence the rate of plagiarism. Use of plagiarism detection software in evaluation of essays and consequent penalties had effectively deterred students from plagiarizing.

Characterization of a novel domain ‘GATE’ in the ABC protein DrrA and its role in drug efflux by the DrrAB complex

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

Zhang, Han; Rahman, Sadia; Li, Wen

2015-03-27

A novel domain, GATE (Glycine-loop And Transducer Element), is identified in the ABC protein DrrA. This domain shows sequence and structural conservation among close homologs of DrrA as well as distantly-related ABC proteins. Among the highly conserved residues in this domain are three glycines, G215, G221 and G231, of which G215 was found to be critical for stable expression of the DrrAB complex. Other conserved residues, including E201, G221, K227 and G231, were found to be critical for the catalytic and transport functions of the DrrAB transporter. Structural analysis of both the previously published crystal structure of the DrrA homologmore » MalK and the modeled structure of DrrA showed that G215 makes close contacts with residues in and around the Walker A motif, suggesting that these interactions may be critical for maintaining the integrity of the ATP binding pocket as well as the complex. It is also shown that G215A or K227R mutation diminishes some of the atomic interactions essential for ATP catalysis and overall transport function. Therefore, based on both the biochemical and structural analyses, it is proposed that the GATE domain, located outside of the previously identified ATP binding and hydrolysis motifs, is an additional element involved in ATP catalysis. - Highlights: • A novel domain ‘GATE’ is identified in the ABC protein DrrA. • GATE shows high sequence and structural conservation among diverse ABC proteins. • GATE is located outside of the previously studied ATP binding and hydrolysis motifs. • Conserved GATE residues are critical for stability of DrrAB and for ATP catalysis.« less

(Pre-) calibration of a Reduced Complexity Model of the Antarctic Contribution to Sea-level Changes

NASA Astrophysics Data System (ADS)

Ruckert, K. L.; Guan, Y.; Shaffer, G.; Forest, C. E.; Keller, K.

2015-12-01

(Pre-) calibration of a Reduced Complexity Model of the Antarctic Contribution to Sea-level ChangesKelsey L. Ruckert1*, Yawen Guan2, Chris E. Forest1,3,7, Gary Shaffer 4,5,6, and Klaus Keller1,7,81 Department of Geosciences, The Pennsylvania State University, University Park, Pennsylvania, USA 2 Department of Statistics, The Pennsylvania State University, University Park, Pennsylvania, USA 3 Department of Meteorology, The Pennsylvania State University, University Park, Pennsylvania, USA 4 GAIA_Antarctica, University of Magallanes, Punta Arenas, Chile 5 Center for Advanced Studies in Arid Zones, La Serena, Chile 6 Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark 7 Earth and Environmental Systems Institute, The Pennsylvania State University, University Park, Pennsylvania, USA 8 Department of Engineering and Public Policy, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA * Corresponding author. E-mail klr324@psu.eduUnderstanding and projecting future sea-level changes poses nontrivial challenges. Sea-level changes are driven primarily by changes in the density of seawater as well as changes in the size of glaciers and ice sheets. Previous studies have demonstrated that a key source of uncertainties surrounding sea-level projections is the response of the Antarctic ice sheet to warming temperatures. Here we calibrate a previously published and relatively simple model of the Antarctic ice sheet over a hindcast period from the last interglacial period to the present. We apply and compare a range of (pre-) calibration methods, including a Bayesian approach that accounts for heteroskedasticity. We compare the model hindcasts and projections for different levels of model complexity and calibration methods. We compare the projections with the upper bounds from previous studies and find our projections have a narrower range in 2100. Furthermore we discuss the implications for the design of climate risk management strategies.

SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes.

PubMed

Hwang, Grace; Sun, Fengyun; O'Brien, Marilyn; Eppig, John J; Handel, Mary Ann; Jordan, Philip W

2017-05-01

SMC complexes include three major classes: cohesin, condensin and SMC5/6. However, the localization pattern and genetic requirements for the SMC5/6 complex during mammalian oogenesis have not previously been examined. In mouse oocytes, the SMC5/6 complex is enriched at the pericentromeric heterochromatin, and also localizes along chromosome arms during meiosis. The infertility phenotypes of females with a Zp3-Cre -driven conditional knockout (cKO) of Smc5 demonstrated that maternally expressed SMC5 protein is essential for early embryogenesis. Interestingly, protein levels of SMC5/6 complex components in oocytes decline as wild-type females age. When SMC5/6 complexes were completely absent in oocytes during meiotic resumption, homologous chromosomes failed to segregate accurately during meiosis I. Despite what appears to be an inability to resolve concatenation between chromosomes during meiosis, localization of topoisomerase IIα to bivalents was not affected; however, localization of condensin along the chromosome axes was perturbed. Taken together, these data demonstrate that the SMC5/6 complex is essential for the formation of segregation-competent bivalents during meiosis I, and findings suggest that age-dependent depletion of the SMC5/6 complex in oocytes could contribute to increased incidence of oocyte aneuploidy and spontaneous abortion in aging females. © 2017. Published by The Company of Biologists Ltd.

AMMOS2: a web server for protein-ligand-water complexes refinement via molecular mechanics.

PubMed

Labbé, Céline M; Pencheva, Tania; Jereva, Dessislava; Desvillechabrol, Dimitri; Becot, Jérôme; Villoutreix, Bruno O; Pajeva, Ilza; Miteva, Maria A

2017-07-03

AMMOS2 is an interactive web server for efficient computational refinement of protein-small organic molecule complexes. The AMMOS2 protocol employs atomic-level energy minimization of a large number of experimental or modeled protein-ligand complexes. The web server is based on the previously developed standalone software AMMOS (Automatic Molecular Mechanics Optimization for in silico Screening). AMMOS utilizes the physics-based force field AMMP sp4 and performs optimization of protein-ligand interactions at five levels of flexibility of the protein receptor. The new version 2 of AMMOS implemented in the AMMOS2 web server allows the users to include explicit water molecules and individual metal ions in the protein-ligand complexes during minimization. The web server provides comprehensive analysis of computed energies and interactive visualization of refined protein-ligand complexes. The ligands are ranked by the minimized binding energies allowing the users to perform additional analysis for drug discovery or chemical biology projects. The web server has been extensively tested on 21 diverse protein-ligand complexes. AMMOS2 minimization shows consistent improvement over the initial complex structures in terms of minimized protein-ligand binding energies and water positions optimization. The AMMOS2 web server is freely available without any registration requirement at the URL: http://drugmod.rpbs.univ-paris-diderot.fr/ammosHome.php. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review.

PubMed

Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

2016-07-01

According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The use of animal models in homeopathic research--a review of 2010-2014 PubMed indexed papers.

PubMed

Bonamin, Leoni Villano; Cardoso, Thayná Neves; de Carvalho, Aloísio Cunha; Amaral, Juliana Gimenez

2015-10-01

In the 1990s, a study was performed on the effects of highly diluted thyroxine on frog metamorphosis. This model represented one of the most discussed examples of the biological effects of high dilutions over the next two decades. In 2010, another critical conceptual review of the use of animal models in homeopathy and high-dilution research was published. The main contribution of these studies was the elucidation of the biological features and phenomenology of the effects of high dilutions on living systems, representing an important step forward in our understanding of the mechanisms of action of homeopathic medicines. We performed a further review of this line of investigation using the same methods. Fifty-three articles that were indexed in the PubMed database and used 12 different animal species were systematically evaluated. Only a fraction of the studies (29/53) reported herein were performed with "ultra high" dilutions. The other studies were performed with dilutions in ranges below 10(-23) (14/53 articles) or commercial complexes (10/53 articles). Only two articles reported negative results; both used in vivo protocols to test commercial complexes, one in fish and one in bees. The quality of the employed techniques improved in 2010-2014 compared with the studies that were reviewed previously in 2010, with the inclusion of more ethically refined protocols, including in vitro primary cell cultures and ex vivo studies (10/53 articles), often with three or more replicates and analyses of epigenetic mechanisms that were previously unknown in 2010. In our updated review of the past 5 years, we found further demonstrations of the biological effects of homeopathy using more refined animal models and in vitro techniques. Copyright © 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Temporal evolution of mineralization events in the Bohemian Massif inferred from the Re-Os geochronology of molybdenite

NASA Astrophysics Data System (ADS)

Ackerman, Lukáš; Haluzová, Eva; Creaser, Robert A.; Pašava, Jan; Veselovský, František; Breiter, Karel; Erban, Vojtěch; Drábek, Milan

2017-06-01

Molybdenite is a common mineral accompanying Sn-W, Au, and base metal mineralizations located in different geotectonic units of the Bohemian Massif, but it is also widespread in granitoids and/or related quartz veins/pegmatites forming disseminated Mo mineralization. Thirty Re-Os ages were obtained for molybdenite samples from the Bohemian Massif to provide constraints on the timing and duration of mineralization event(s) within the framework of previously published geochronological data for the host and/or associated rocks. The obtained data for Sn-W-(Li) deposits in the Erzgebirge metallogenetic province indicate the predominance of one and/or multiple short-time mineralization events taking place between ˜319 and 323 Ma, with the exception of the Krupka deposit associated with the Altenberg-Teplice caldera where the data may suggest prolonged activity until ˜315 Ma. The ages of the Pb-Zn-(Au-Mo) Hůrky u Rakovníka and Fe-Cu-As Obří důl mineralizations from the exocontacts of the Čistá pluton and Krkonoše-Jizera Plutonic Complex, respectively, provide evidence for synchronous emplacement of the ore and the associated granitic rocks. In contrast, the Padrť Fe-As-Mo mineralization postdates the age of the associated Padrť granite. Disseminated Mo mineralization in Cadomian and Variscan granitoids and/or related to quartz veins/pegmatites provides Re-Os ages that overlap with the previously published geochronological data for the host rocks, suggesting coeval evolution. Molybdenite samples from the Sázava suite granites of the Central Bohemian Plutonic Complex (CBPC) have resolvable younger ages than their host granites, but similar to the age of spatially related Au mineralization which is associated with the latest evolution of the CBPC.

Extended evolution: A conceptual framework for integrating regulatory networks and niche construction

PubMed Central

Renn, Jürgen

2015-01-01

ABSTRACT This paper introduces a conceptual framework for the evolution of complex systems based on the integration of regulatory network and niche construction theories. It is designed to apply equally to cases of biological, social and cultural evolution. Within the conceptual framework we focus especially on the transformation of complex networks through the linked processes of externalization and internalization of causal factors between regulatory networks and their corresponding niches and argue that these are an important part of evolutionary explanations. This conceptual framework extends previous evolutionary models and focuses on several challenges, such as the path‐dependent nature of evolutionary change, the dynamics of evolutionary innovation and the expansion of inheritance systems. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 565–577, 2015. © 2015 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution published by Wiley Periodicals, Inc. PMID:26097188

Ab initio study of the CO-N2 complex: a new highly accurate intermolecular potential energy surface and rovibrational spectrum.

PubMed

Cybulski, Hubert; Henriksen, Christian; Dawes, Richard; Wang, Xiao-Gang; Bora, Neha; Avila, Gustavo; Carrington, Tucker; Fernández, Berta

2018-05-09

A new, highly accurate ab initio ground-state intermolecular potential-energy surface (IPES) for the CO-N2 complex is presented. Thousands of interaction energies calculated with the CCSD(T) method and Dunning's aug-cc-pVQZ basis set extended with midbond functions were fitted to an analytical function. The global minimum of the potential is characterized by an almost T-shaped structure and has an energy of -118.2 cm-1. The symmetry-adapted Lanczos algorithm was used to compute rovibrational energies (up to J = 20) on the new IPES. The RMSE with respect to experiment was found to be on the order of 0.038 cm-1 which confirms the very high accuracy of the potential. This level of agreement is among the best reported in the literature for weakly bound systems and considerably improves on those of previously published potentials.

Approaches to modelling uranium (VI) adsorption on natural mineral assemblages

USGS Publications Warehouse

Waite, T.D.; Davis, J.A.; Fenton, B.R.; Payne, T.E.

2000-01-01

Component additivity (CA) and generalised composite (GC) approaches to deriving a suitable surface complexation model for description of U(VI) adsorption to natural mineral assemblages are pursued in this paper with good success. A single, ferrihydrite-like component is found to reasonably describe uranyl uptake to a number of kaolinitic iron-rich natural substrates at pH > 4 in the CA approach with previously published information on nature of surface complexes, acid-base properties of surface sites and electrostatic effects used in the model. The GC approach, in which little pre-knowledge about generic surface sites is assumed, gives even better fits and would appear to be a method of particular strength for application in areas such as performance assessment provided the model is developed in a careful, stepwise manner with simplicity and goodness of fit as the major criteria for acceptance.

H3K27 methylation and H3S28 phosphorylation-dependent transcriptional regulation by INHAT subunit SET/TAF-Iβ.

PubMed

Kim, Ji-Young; Kim, Kee-Beom; Son, Hye-Ju; Chae, Yun-Cheol; Oh, Si-Taek; Kim, Dong-Wook; Pak, Jhang Ho; Seo, Sang-Beom

2012-09-21

Significant progress has been made in understanding the relationship between histone modifications and 'reader' molecules and their effects on transcriptional regulation. A previously identified INHAT complex subunit, SET/TAF-Iβ, binds to histones and inhibits histone acetylation. To investigate the binding specificities of SET/TAF-Iβ to various histone modifications, we employed modified histone tail peptide array analyses. SET/TAF-Iβ strongly recognized PRC2-mediated H3K27me1/2/3; however, the bindings were completely disrupted by H3S28 phosphorylation. We have demonstrated that SET/TAF-Iβ is sequentially recruited to the target gene promoter ATF3 after the PRC2 complex via H3K27me recognition and may offer additive effects in the repression of the target gene. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

A novel neutron energy spectrum unfolding code using particle swarm optimization

NASA Astrophysics Data System (ADS)

Shahabinejad, H.; Sohrabpour, M.

2017-07-01

A novel neutron Spectrum Deconvolution using Particle Swarm Optimization (SDPSO) code has been developed to unfold the neutron spectrum from a pulse height distribution and a response matrix. The Particle Swarm Optimization (PSO) imitates the bird flocks social behavior to solve complex optimization problems. The results of the SDPSO code have been compared with those of the standard spectra and recently published Two-steps Genetic Algorithm Spectrum Unfolding (TGASU) code. The TGASU code have been previously compared with the other codes such as MAXED, GRAVEL, FERDOR and GAMCD and shown to be more accurate than the previous codes. The results of the SDPSO code have been demonstrated to match well with those of the TGASU code for both under determined and over-determined problems. In addition the SDPSO has been shown to be nearly two times faster than the TGASU code.

Morphological phylogeny of Tradescantia L. (Commelinaceae) sheds light on a new infrageneric classification for the genus and novelties on the systematics of subtribe Tradescantiinae

PubMed Central

Pellegrini, Marco O. O.

2017-01-01

Abstract Throughout the years, three infrageneric classifications were proposed for Tradescantia along with several informal groups and species complexes. The current infrageneric classification accepts 12 sections – with T. sect. Tradescantia being further divided into four series – and assimilates many concepts adopted by previous authors. Recent molecular-based phylogenetic studies indicate that the currently accepted sections might not represent monophyletic groups within Tradescantia. Based on newly gathered morphological data on the group, complemented with available micromorphological, cytological and phytochemical data, I present the first morphology-based evolutionary hypothesis for Tradescantia. Furthermore, I reduce subtribe Thyrsantheminae to a synonym of subtribe Tradescantiinae, and propose a new infrageneric classification for Tradescantia, based on the total evidence of the present morphological phylogeny, in accordance to the previously published molecular data. PMID:29118649

Translation of Genotype to Phenotype by a Hierarchy of Cell Subsystems.

PubMed

Yu, Michael Ku; Kramer, Michael; Dutkowski, Janusz; Srivas, Rohith; Licon, Katherine; Kreisberg, Jason; Ng, Cherie T; Krogan, Nevan; Sharan, Roded; Ideker, Trey

2016-02-24

Accurately translating genotype to phenotype requires accounting for the functional impact of genetic variation at many biological scales. Here we present a strategy for genotype-phenotype reasoning based on existing knowledge of cellular subsystems. These subsystems and their hierarchical organization are defined by the Gene Ontology or a complementary ontology inferred directly from previously published datasets. Guided by the ontology's hierarchical structure, we organize genotype data into an "ontotype," that is, a hierarchy of perturbations representing the effects of genetic variation at multiple cellular scales. The ontotype is then interpreted using logical rules generated by machine learning to predict phenotype. This approach substantially outperforms previous, non-hierarchical methods for translating yeast genotype to cell growth phenotype, and it accurately predicts the growth outcomes of two new screens of 2,503 double gene knockouts impacting DNA repair or nuclear lumen. Ontotypes also generalize to larger knockout combinations, setting the stage for interpreting the complex genetics of disease.

Application of headspace and direct immersion solid-phase microextraction in the analysis of organothiophosphates related to the Chemical Weapons Convention from water and complex matrices.

PubMed

Althoff, Marc André; Bertsch, Andreas; Metzulat, Manfred; Klapötke, Thomas M; Karaghiosoff, Konstantin L

2017-11-01

The successful application of headspace (HS) and direct immersion (DI) solid phase microextraction (SPME) for the unambiguous identification and characterization of a series of toxic thiophosphate esters, such as Amiton (I), from aqueous phases and complex matrices (e.g. grass and foliage) has been demonstrated. A Thermo Scientific gas chromatograph (GC) - tandem mass spectrometer (MS/MS) system with a TriPlus RSH® autosampler and a SPME tool was used to investigate the effect of different parameters that influence the extraction efficiency: e.g. pH of the sample matrix and extraction temperature. The developed methods were employed for the detection of several Amiton derivatives (Schedule II of the CWC) that are structurally closely related to each other; some of which are new and have not been reported in literature previously. In addition, a novel DI SPME method from complex matrices for the analysis of organophosphates related to the CWC was developed. The studies clearly show that DI SPME for complex matrices is superior to HS extraction and can potentially be applied to other related compounds controlled under the CWC. Copyright © 2017. Published by Elsevier B.V.

Crystal Structures of MEK1 Binary and Ternary Complexes with Nucleotides and Inhibitors

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

Fischmann, Thierry O.; Smith, Catherine K.; Mayhood, Todd W.

MEK1 is a member of the MAPK signal transduction pathway that responds to growth factors and cytokines. We have determined that the kinase domain spans residues 35-382 by proteolytic cleavage. The complete kinase domain has been crystallized and its X-ray crystal structure as a complex with magnesium and ATP-{gamma}S determined at 2.1 {angstrom}. Unlike crystals of a truncated kinase domain previously published, the crystals of the intact domain can be grown either as a binary complex with a nucleotide or as a ternary complex with a nucleotide and one of a multitude of allosteric inhibitors. Further, the crystals allow formore » the determination of costructures with ATP competitive inhibitors. We describe the structures of nonphosphorylated MEK1 (npMEK1) binary complexes with ADP and K252a, an ATP-competitive inhibitor (see Table 1), at 1.9 and 2.7 {angstrom} resolution, respectively. Ternary complexes have also been solved between npMEK1, a nucleotide, and an allosteric non-ATP competitive inhibitor: ATP-{gamma}S with compound 1 and ADP with either U0126 or the MEK1 clinical candidate PD325089 at 1.8, 2.0, and 2.5 {angstrom}, respectively. Compound 1 is structurally similar to PD325901. These structures illustrate fundamental differences among various mechanisms of inhibition at the molecular level. Residues 44-51 have previously been shown to play a negative regulatory role in MEK1 activity. The crystal structure of the integral kinase domain provides a structural rationale for the role of these residues. They form helix A and repress enzymatic activity by stabilizing an inactive conformation in which helix C is displaced from its active state position. Finally, the structure provides for the first time a molecular rationale that explains how mutations in MEK may lead to the cardio-facio-cutaneous syndrome.« less

Abstraction and model evaluation in category learning.

PubMed

Vanpaemel, Wolf; Storms, Gert

2010-05-01

Thirty previously published data sets, from seminal category learning tasks, are reanalyzed using the varying abstraction model (VAM). Unlike a prototype-versus-exemplar analysis, which focuses on extreme levels of abstraction only, a VAM analysis also considers the possibility of partial abstraction. Whereas most data sets support no abstraction when only the extreme possibilities are considered, we show that evidence for abstraction can be provided using the broader view on abstraction provided by the VAM. The present results generalize earlier demonstrations of partial abstraction (Vanpaemel & Storms, 2008), in which only a small number of data sets was analyzed. Following the dominant modus operandi in category learning research, Vanpaemel and Storms evaluated the models on their best fit, a practice known to ignore the complexity of the models under consideration. In the present study, in contrast, model evaluation not only relies on the maximal likelihood, but also on the marginal likelihood, which is sensitive to model complexity. Finally, using a large recovery study, it is demonstrated that, across the 30 data sets, complexity differences between the models in the VAM family are small. This indicates that a (computationally challenging) complexity-sensitive model evaluation method is uncalled for, and that the use of a (computationally straightforward) complexity-insensitive model evaluation method is justified.

Mediator complex cooperatively regulates transcription of retinoic acid target genes with Polycomb Repressive Complex 2 during neuronal differentiation.

PubMed

Fukasawa, Rikiya; Iida, Satoshi; Tsutsui, Taiki; Hirose, Yutaka; Ohkuma, Yoshiaki

2015-11-01

The Mediator complex (Mediator) plays key roles in transcription and functions as the nexus for integration of various transcriptional signals. Previously, we screened for Mediator cyclin-dependent kinase (CDK)-interacting factors and identified three proteins related to chromatin regulation. One of them, SUZ12 is required for both stability and activity of Polycomb Repressive Complex 2 (PRC2). PRC2 primarily suppresses gene expression through histone H3 lysine 27 trimethylation, resulting in stem cell maintenance and differentiation; perturbation of this process leads to oncogenesis. Recent work showed that Mediator contributes to the embryonic stem cell state through DNA loop formation, which is strongly associated with chromatin architecture; however, it remains unclear how Mediator regulates gene expression in cooperation with chromatin regulators (i.e. writers, readers and remodelers). We found that Mediator CDKs interact directly with the PRC2 subunit EZH2, as well as SUZ12. Known PRC2 target genes were deregulated by Mediator CDK knockdown during neuronal differentiation, and both Mediator and PRC2 complexes co-occupied the promoters of developmental genes regulated by retinoic acid. Our results provide a mechanistic link between Mediator and PRC2 during neuronal differentiation. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Generation of Long-time Complex Signals for Testing the Instruments for Detection of Voltage Quality Disturbances

NASA Astrophysics Data System (ADS)

Živanović, Dragan; Simić, Milan; Kokolanski, Zivko; Denić, Dragan; Dimcev, Vladimir

2018-04-01

Software supported procedure for generation of long-time complex test sentences, suitable for testing the instruments for detection of standard voltage quality (VQ) disturbances is presented in this paper. This solution for test signal generation includes significant improvements of computer-based signal generator presented and described in the previously published paper [1]. The generator is based on virtual instrumentation software for defining the basic signal parameters, data acquisition card NI 6343, and power amplifier for amplification of output voltage level to the nominal RMS voltage value of 230 V. Definition of basic signal parameters in LabVIEW application software is supported using Script files, which allows simple repetition of specific test signals and combination of more different test sequences in the complex composite test waveform. The basic advantage of this generator compared to the similar solutions for signal generation is the possibility for long-time test sequence generation according to predefined complex test scenarios, including various combinations of VQ disturbances defined in accordance with the European standard EN50160. Experimental verification of the presented signal generator capability is performed by testing the commercial power quality analyzer Fluke 435 Series II. In this paper are shown some characteristic complex test signals with various disturbances and logged data obtained from the tested power quality analyzer.

Biguanides inhibit complex I, II and IV of rat liver mitochondria and modify their functional properties.

PubMed

Drahota, Z; Palenickova, E; Endlicher, R; Milerova, M; Brejchova, J; Vosahlikova, M; Svoboda, P; Kazdova, L; Kalous, M; Cervinkova, Z; Cahova, M

2014-01-01

In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeability transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to previously published data, we found that phenformin, after a 5 min pre-incubation, dose-dependently inhibits not only mitochondrial complex I but also complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potential. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca(2+) ions. Our data might be in agreement with the hypothesis of Schäfer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity.

Broad supernatural punishment but not moralizing high gods precede the evolution of political complexity in Austronesia.

PubMed

Watts, Joseph; Greenhill, Simon J; Atkinson, Quentin D; Currie, Thomas E; Bulbulia, Joseph; Gray, Russell D

2015-04-07

Supernatural belief presents an explanatory challenge to evolutionary theorists-it is both costly and prevalent. One influential functional explanation claims that the imagined threat of supernatural punishment can suppress selfishness and enhance cooperation. Specifically, morally concerned supreme deities or 'moralizing high gods' have been argued to reduce free-riding in large social groups, enabling believers to build the kind of complex societies that define modern humanity. Previous cross-cultural studies claiming to support the MHG hypothesis rely on correlational analyses only and do not correct for the statistical non-independence of sampled cultures. Here we use a Bayesian phylogenetic approach with a sample of 96 Austronesian cultures to test the MHG hypothesis as well as an alternative supernatural punishment hypothesis that allows punishment by a broad range of moralizing agents. We find evidence that broad supernatural punishment drives political complexity, whereas MHGs follow political complexity. We suggest that the concept of MHGs diffused as part of a suite of traits arising from cultural exchange between complex societies. Our results show the power of phylogenetic methods to address long-standing debates about the origins and functions of religion in human society. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Spinal motor neuron involvement in a patient with homozygous PRUNE mutation.

PubMed

Iacomino, Michele; Fiorillo, Chiara; Torella, Annalaura; Severino, Mariasavina; Broda, Paolo; Romano, Catia; Falsaperla, Raffaele; Pozzolini, Giulia; Minetti, Carlo; Striano, Pasquale; Nigro, Vincenzo; Zara, Federico

2018-05-01

In the last few years, whole exome sequencing (WES) allowed the identification of PRUNE mutations in patients featuring a complex neurological phenotype characterized by severe neurodevelopmental delay, microcephaly, epilepsy, optic atrophy, and brain or cerebellar atrophy. We describe an additional patient with homozygous PRUNE mutation who presented with spinal muscular atrophy phenotype, in addition to the already known brain developmental disorder. This novel feature expands the clinical consequences of PRUNE mutations and allow to converge PRUNE syndrome with previous descriptions of neurodevelopmental/neurodegenerative disorders linked to altered microtubule dynamics. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Modeling uranium(VI) adsorption onto montmorillonite under varying carbonate concentrations: A surface complexation model accounting for the spillover effect on surface potential

NASA Astrophysics Data System (ADS)

Tournassat, C.; Tinnacher, R. M.; Grangeon, S.; Davis, J. A.

2018-01-01

The prediction of U(VI) adsorption onto montmorillonite clay is confounded by the complexities of: (1) the montmorillonite structure in terms of adsorption sites on basal and edge surfaces, and the complex interactions between the electrical double layers at these surfaces, and (2) U(VI) solution speciation, which can include cationic, anionic and neutral species. Previous U(VI)-montmorillonite adsorption and modeling studies have typically expanded classical surface complexation modeling approaches, initially developed for simple oxides, to include both cation exchange and surface complexation reactions. However, previous models have not taken into account the unique characteristics of electrostatic surface potentials that occur at montmorillonite edge sites, where the electrostatic surface potential of basal plane cation exchange sites influences the surface potential of neighboring edge sites ('spillover' effect). A series of U(VI) - Na-montmorillonite batch adsorption experiments was conducted as a function of pH, with variable U(VI), Ca, and dissolved carbonate concentrations. Based on the experimental data, a new type of surface complexation model (SCM) was developed for montmorillonite, that specifically accounts for the spillover effect using the edge surface speciation model by Tournassat et al. (2016a). The SCM allows for a prediction of U(VI) adsorption under varying chemical conditions with a minimum number of fitting parameters, not only for our own experimental results, but also for a number of published data sets. The model agreed well with many of these datasets without introducing a second site type or including the formation of ternary U(VI)-carbonato surface complexes. The model predictions were greatly impacted by utilizing analytical measurements of dissolved inorganic carbon (DIC) concentrations in individual sample solutions rather than assuming solution equilibration with a specific partial pressure of CO2, even when the gas phase was laboratory air. Because of strong aqueous U(VI)-carbonate solution complexes, the measurement of DIC concentrations was even important for systems set up in the 'absence' of CO2, due to low levels of CO2 contamination during the experiment.

Species diversity and phylogeographical affinities of the Branchiopoda (Crustacea) of Churchill, Manitoba, Canada.

PubMed

Jeffery, Nicholas W; Elías-Gutiérrez, Manuel; Adamowicz, Sarah J

2011-01-01

The region of Churchill, Manitoba, contains a wide variety of habitats representative of both the boreal forest and arctic tundra and has been used as a model site for biodiversity studies for nearly seven decades within Canada. Much previous work has been done in Churchill to study the Daphnia pulex species complex in particular, but no study has completed a wide-scale survey on the crustacean species that inhabit Churchill's aquatic ecosystems using molecular markers. We have employed DNA barcoding to study the diversity of the Branchiopoda (Crustacea) in a wide variety of freshwater habitats and to determine the likely origins of the Churchill fauna following the last glaciation. The standard animal barcode marker (COI) was sequenced for 327 specimens, and a 3% divergence threshold was used to delineate potential species. We found 42 provisional and valid branchiopod species from this survey alone, including several cryptic lineages, in comparison with the 25 previously recorded from previous ecological works. Using published sequence data, we explored the phylogeographic affinities of Churchill's branchiopods, finding that the Churchill fauna apparently originated from all directions from multiple glacial refugia (including southern, Beringian, and high arctic regions). Overall, these microcrustaceans are very diverse in Churchill and contain multiple species complexes. The present study introduces among the first sequences for some understudied genera, for which further work is required to delineate species boundaries and develop a more complete understanding of branchiopod diversity over a larger spatial scale.

Species Diversity and Phylogeographical Affinities of the Branchiopoda (Crustacea) of Churchill, Manitoba, Canada

PubMed Central

Jeffery, Nicholas W.; Elías-Gutiérrez, Manuel; Adamowicz, Sarah J.

2011-01-01

The region of Churchill, Manitoba, contains a wide variety of habitats representative of both the boreal forest and arctic tundra and has been used as a model site for biodiversity studies for nearly seven decades within Canada. Much previous work has been done in Churchill to study the Daphnia pulex species complex in particular, but no study has completed a wide-scale survey on the crustacean species that inhabit Churchill's aquatic ecosystems using molecular markers. We have employed DNA barcoding to study the diversity of the Branchiopoda (Crustacea) in a wide variety of freshwater habitats and to determine the likely origins of the Churchill fauna following the last glaciation. The standard animal barcode marker (COI) was sequenced for 327 specimens, and a 3% divergence threshold was used to delineate potential species. We found 42 provisional and valid branchiopod species from this survey alone, including several cryptic lineages, in comparison with the 25 previously recorded from previous ecological works. Using published sequence data, we explored the phylogeographic affinities of Churchill's branchiopods, finding that the Churchill fauna apparently originated from all directions from multiple glacial refugia (including southern, Beringian, and high arctic regions). Overall, these microcrustaceans are very diverse in Churchill and contain multiple species complexes. The present study introduces among the first sequences for some understudied genera, for which further work is required to delineate species boundaries and develop a more complete understanding of branchiopod diversity over a larger spatial scale. PMID:21610864

Low-temperature protein dynamics of the B800 molecules in the LH2 light-harvesting complex: spectral hole burning study and comparison with single photosynthetic complex spectroscopy.

PubMed

Grozdanov, Daniel; Herascu, Nicoleta; Reinot, Tõnu; Jankowiak, Ryszard; Zazubovich, Valter

2010-03-18

Previously published and new spectral hole burning (SHB) data on the B800 band of LH2 light-harvesting antenna complex of Rps. acidophila are analyzed in light of recent single photosynthetic complex spectroscopy (SPCS) results (for a review, see Berlin et al. Phys. Life Rev. 2007, 4, 64.). It is demonstrated that, in general, SHB-related phenomena observed for the B800 band are in qualitative agreement with the SPCS data and the protein models involving multiwell multitier protein energy landscapes. Regarding the quantitative agreement, we argue that the single-molecule behavior associated with the fastest spectral diffusion (smallest barrier) tier of the protein energy landscape is inconsistent with the SHB data. The latter discrepancy can be attributed to SPCS probing not only the dynamics of of the protein complex per se, but also that of the surrounding amorphous host and/or of the host-protein interface. It is argued that SHB (once improved models are developed) should also be able to provide the average magnitudes and probability distributions of light-induced spectral shifts and could be used to determine whether SPCS probes a set of protein complexes that are both intact and statistically relevant. SHB results are consistent with the B800 --> B850 energy-transfer models including consideration of the whole B850 density of states.

Using hand proportions to test taxonomic boundaries within the Tupaia glis species complex (Scandentia, Tupaiidae)

USGS Publications Warehouse

Sargos, Eric J.; Woodman, Neal; Reese, Aspen T.; Olson, Link E.

2013-01-01

Treeshrews (order Scandentia) comprise 2 families of squirrel-sized terrestrial, arboreal, and scansorial mammals distributed throughout much of tropical South and Southeast Asia. The last comprehensive taxonomic revision of treeshrews was published in 1913, and a well-supported phylogeny clarifying relationships among all currently recognized extant species within the order has only recently been published. Within the family Tupaiidae, 2 widely distributed species, the northern treeshrew, Tupaia belangeri (Wagner, 1841), and the common treeshrew, T. glis (Diard, 1820), represent a particularly vexing taxonomic complex. These 2 species are currently distinguished primarily based on their respective distributions north and south of the Isthmus of Kra on the Malay Peninsula and on their different mammae counts. This problematic species complex includes 54 published synonyms, many of which represent putative island endemics. The widespread T. glis and T. belangeri collectively comprise a monophyletic assemblage representing the sister lineage to a clade composed of the golden-bellied treeshrew, T. chrysogaster Miller, 1903 (Mentawai Islands), and the long-footed treeshrew, T. longipes (Thomas, 1893) (Borneo). As part of a morphological investigation of the T. glis–T. belangeri complex, we studied the proportions of hand bones, which have previously been shown to be useful in discriminating species of soricids (true shrews). We measured 38 variables from digital X-ray images of 148 museum study skins representing several subspecies of T. glis, T. belangeri, T. chrysogaster, and T. longipes and analyzed these data using principal components and cluster analyses. Manus proportions among these 4 species readily distinguish them, particularly in the cases of T. chrysogaster and T. longipes. We then tested the distinctiveness of several of the populations comprising T. glis and T. longipes. T. longipes longipes and T. l. salatana Lyon, 1913, are distinguishable from each other, and populations of T. "glis" from Bangka Island and Sumatra are distinct from those on the Malay Peninsula, supporting the recognition of T. salatana, T. discolor Lyon, 1906, and T. ferruginea Raffles, 1821 as distinct species in Indonesia. These relatively small, potentially vulnerable treeshrew populations occur in the Sundaland biodiversity hotspot and will require additional study to determine their appropriate conservation status.

Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells.

PubMed

Souquet, Benoit; Freed, Ellen; Berto, Alessandro; Andric, Vedrana; Audugé, Nicolas; Reina-San-Martin, Bernardo; Lacy, Elizabeth; Doye, Valérie

2018-05-22

Nup133 belongs to the Y-complex, a key component of the nuclear pore complex (NPC) scaffold. Studies on a null mutation in mice previously revealed that Nup133 is essential for embryonic development but not for mouse embryonic stem cell (mESC) proliferation. Using single-pore detection and average NE-fluorescence intensity, we find that Nup133 is dispensable for interphase and postmitotic NPC scaffold assembly in pluripotent mESCs. However, loss of Nup133 specifically perturbs the formation of the nuclear basket as manifested by the absence of Tpr in about half of the NPCs combined with altered dynamics of Nup153. We further demonstrate that its central domain mediates Nup133's role in assembling Tpr and Nup153 into a properly configured nuclear basket. Our findings thus revisit the role of the Y-complex in pore biogenesis and provide insights into the interplay between NPC scaffold architecture, nuclear basket assembly, and the generation of heterogeneity among NPCs. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Diversity and potential impact of Calonectria species in Eucalyptus plantations in Brazil

PubMed Central

Alfenas, R.F.; Lombard, L.; Pereira, O.L.; Alfenas, A.C.; Crous, P.W.

2015-01-01

Species in the genus Calonectria (Hypocreales) represent an important group of plant pathogenic fungi that cause serious losses to plant crops in tropical and subtropical climates. Calonectria leaf blight is currently one of the main impediments to Eucalyptus cultivation in Brazil, and various species of Calonectria have been associated with this disease. Since most previous identifications were solely based on morphological characters, much of the published literature needs to be re-evaluated. The aim of this study was thus to identify and determine the phylogenetic relationships among species that occur in the Eucalyptus growing regions of Brazil by using partial sequences of the β-tubulin, calmodulin, translation elongation factor 1-α and histone H3 gene regions. Based on extensive collections from soil and infected eucalypt leaf samples from plantations, phylogenetic inference revealed the Ca. pteridis complex to be the most common species complex present in Eucalyptus plantations in Brazil. By elucidating taxa in the Ca. pteridis, Ca. cylindrospora and Ca. candelabra species complexes, 20 novel Calonectria species were identified, and a new name in Calonectria provided for Cylindrocladium macrosporum as Ca. pseudopteridis. PMID:26955192

Diversity and potential impact of Calonectria species in Eucalyptus plantations in Brazil.

PubMed

Alfenas, R F; Lombard, L; Pereira, O L; Alfenas, A C; Crous, P W

2015-03-01

Species in the genus Calonectria (Hypocreales) represent an important group of plant pathogenic fungi that cause serious losses to plant crops in tropical and subtropical climates. Calonectria leaf blight is currently one of the main impediments to Eucalyptus cultivation in Brazil, and various species of Calonectria have been associated with this disease. Since most previous identifications were solely based on morphological characters, much of the published literature needs to be re-evaluated. The aim of this study was thus to identify and determine the phylogenetic relationships among species that occur in the Eucalyptus growing regions of Brazil by using partial sequences of the β-tubulin, calmodulin, translation elongation factor 1-α and histone H3 gene regions. Based on extensive collections from soil and infected eucalypt leaf samples from plantations, phylogenetic inference revealed the Ca. pteridis complex to be the most common species complex present in Eucalyptus plantations in Brazil. By elucidating taxa in the Ca. pteridis, Ca. cylindrospora and Ca. candelabra species complexes, 20 novel Calonectria species were identified, and a new name in Calonectria provided for Cylindrocladium macrosporum as Ca. pseudopteridis.

A Design Principle for an Autonomous Post-translational Pattern Formation.

PubMed

Sugai, Shuhei S; Ode, Koji L; Ueda, Hiroki R

2017-04-25

Previous autonomous pattern-formation models often assumed complex molecular and cellular networks. This theoretical study, however, shows that a system composed of one substrate with multisite phosphorylation and a pair of kinase and phosphatase can generate autonomous spatial information, including complex stripe patterns. All (de-)phosphorylation reactions are described with a generic Michaelis-Menten scheme, and all species freely diffuse without pre-existing gradients. Computational simulation upon >23,000,000 randomly generated parameter sets revealed the design motifs of cyclic reaction and enzyme sequestration by slow-diffusing substrates. These motifs constitute short-range positive and long-range negative feedback loops to induce Turing instability. The width and height of spatial patterns can be controlled independently by distinct reaction-diffusion processes. Therefore, multisite reversible post-translational modification can be a ubiquitous source for various patterns without requiring other complex regulations such as autocatalytic regulation of enzymes and is applicable to molecular mechanisms for inducing subcellular localization of proteins driven by post-translational modifications. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Reverse membrane bioreactor: Introduction to a new technology for biofuel production.

PubMed

Mahboubi, Amir; Ylitervo, Päivi; Doyen, Wim; De Wever, Heleen; Taherzadeh, Mohammad J

2016-01-01

The novel concept of reverse membrane bioreactors (rMBR) introduced in this review is a new membrane-assisted cell retention technique benefiting from the advantageous properties of both conventional MBRs and cell encapsulation techniques to tackle issues in bioconversion and fermentation of complex feeds. The rMBR applies high local cell density and membrane separation of cell/feed to the conventional immersed membrane bioreactor (iMBR) set up. Moreover, this new membrane configuration functions on basis of concentration-driven diffusion rather than pressure-driven convection previously used in conventional MBRs. These new features bring along the exceptional ability of rMBRs in aiding complex bioconversion and fermentation feeds containing high concentrations of inhibitory compounds, a variety of sugar sources and high suspended solid content. In the current review, the similarities and differences between the rMBR and conventional MBRs and cell encapsulation regarding advantages, disadvantages, principles and applications for biofuel production are presented and compared. Moreover, the potential of rMBRs in bioconversion of specific complex substrates of interest such as lignocellulosic hydrolysate is thoroughly studied. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

U.S. Geological Survey applied research studies of the Cheyenne River system, South Dakota; description and collation of data, water years 1985-86

USGS Publications Warehouse

Goddard, Kimball E.

1988-01-01

The Cheyenne River system in Western South Dakota has been impacted by the discharge of about 100 million metric tons of gold-mill tailings to Whitewood Creek near Lead, South Dakota. In April 1985, the U.S. Geological Survey initiated an extensive series of research studies to investigate the magnitude of the impact and to define important processes acting on the contaminated sediments present in the system. The report presents all data collected during the 1985 and 1986 water years for these research studies. Some of the data included have been published previously. Hydrologic, geochemical, and biologic data are available for sites on Whitewood Creek, the Belle Fourche and Cheyenne Rivers, and for the Cheyenne River arm of Lake Oahe. Data complexity varies from routine discharge and water quality to very complex photon-correlation spectroscopy and energy-dispersive x-ray analysis. Methods for sample collection, handling and preservation, and laboratory analysis are also presented. No interpretations or complex statistical summaries are included. (USGS)

Complexity in the new NHS: longitudinal case studies of CCGs in England.

PubMed

Checkland, Katherine; McDermott, Imelda; Coleman, Anna; Perkins, Neil

2016-01-07

The reform in the English National Health Services (NHS) under the Health and Social Care Act 2012 is unlike previous NHS reorganisations. The establishment of clinical commissioning groups (CCGs) was intended to be 'bottom up' with no central blueprint. This paper sets out to offer evidence about how this process has played out in practice and examines the implications of the complexity and variation which emerged. Detailed case studies in CCGs across England, using interviews, observation and documentary analysis. Using realist framework, we unpacked the complexity of CCG structures. In phase 1 of the study (January 2011 to September 2012), we conducted 96 interviews, 439 h of observation in a wide variety of meetings, 2 online surveys and 38 follow-up telephone interviews. In phase 2 (April 2013 to March 2015), we conducted 42 interviews with general practitioners (GPs) and managers and observation of 48 different types of meetings. Our study has highlighted the complexity inherent in CCGs, arising out of the relatively permissive environment in which they developed. Not only are they very different from one another in size, but also in structure, functions between different bodies and the roles played by GPs. The complexity and lack of uniformity of CCGs is important as it makes it difficult for those who must engage with CCGs to know who to approach at what level. This is of increasing importance as CCGs are moving towards greater integration across health and social care. Our study also suggests that there is little consensus as to what being a 'membership' organisation means and how it should operate. The lack of uniformity in CCG structure and lack of clarity over the meaning of 'membership' raises questions over accountability, which becomes of greater importance as CCG is taking over responsibility for primary care co-commissioning. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A Defined, Glucose-Limited Mineral Medium for the Cultivation of Listeria spp.

PubMed Central

Schneebeli, Rudolf

2013-01-01

Members of the genus Listeria are fastidious bacteria with respect to their nutritional requirements, and several minimal media described in the literature fail to support growth of all Listeria spp. Furthermore, strict limitation by a single nutrient, e.g., the carbon source, has not been demonstrated for any of the published minimal media. This is an important prerequisite for defined studies of growth and physiology, including “omics.” Based on a theoretical analysis of previously published mineral media for Listeria, an improved, well-balanced growth medium was designed. It supports the growth, not only of all tested Listeria monocytogenes strains, but of all other Listeria species, with the exception of L. ivanovii. The growth performance of L. monocytogenes strain Scott A was tested in the newly designed medium; glucose served as the only carbon and energy source for growth, whereas neither the supplied amino acids nor the buffering and complexing components (MOPS [morpholinepropanesulfonic acid] and EDTA) supported growth. Omission of amino acids, trace elements, or vitamins, alone or in combination, resulted in considerably reduced biomass yields. Furthermore, we monitored the specific growth rates of various Listeria strains cultivated in the designed mineral medium and compared them to growth in complex medium (brain heart infusion broth [BHI]). The novel mineral medium was optimized for the commonly used strain L. monocytogenes Scott A to achieve optimum cell yields and maximum specific growth rates. This mineral medium is the first published synthetic medium for Listeria that has been shown to be strictly carbon (glucose) limited. PMID:23377938

Use of complex hydraulic variables to predict the distribution and density of unionids in a side channel of the Upper Mississippi River

USGS Publications Warehouse

Steuer, J.J.; Newton, T.J.; Zigler, S.J.

2008-01-01

Previous attempts to predict the importance of abiotic and biotic factors to unionids in large rivers have been largely unsuccessful. Many simple physical habitat descriptors (e.g., current velocity, substrate particle size, and water depth) have limited ability to predict unionid density. However, more recent studies have found that complex hydraulic variables (e.g., shear velocity, boundary shear stress, and Reynolds number) may be more useful predictors of unionid density. We performed a retrospective analysis with unionid density, current velocity, and substrate particle size data from 1987 to 1988 in a 6-km reach of the Upper Mississippi River near Prairie du Chien, Wisconsin. We used these data to model simple and complex hydraulic variables under low and high flow conditions. We then used classification and regression tree analysis to examine the relationships between hydraulic variables and unionid density. We found that boundary Reynolds number, Froude number, boundary shear stress, and grain size were the best predictors of density. Models with complex hydraulic variables were a substantial improvement over previously published discriminant models and correctly classified 65-88% of the observations for the total mussel fauna and six species. These data suggest that unionid beds may be constrained by threshold limits at both ends of the flow regime. Under low flow, mussels may require a minimum hydraulic variable (Rez.ast;, Fr) to transport nutrients, oxygen, and waste products. Under high flow, areas with relatively low boundary shear stress may provide a hydraulic refuge for mussels. Data on hydraulic preferences and identification of other conditions that constitute unionid habitat are needed to help restore and enhance habitats for unionids in rivers. ?? 2008 Springer Science+Business Media B.V.

Reappraisal of Hydatigera taeniaeformis (Batsch, 1786) (Cestoda: Taeniidae) sensu lato with description of Hydatigera kamiyai n. sp.

PubMed

Lavikainen, Antti; Iwaki, Takashi; Haukisalmi, Voitto; Konyaev, Sergey V; Casiraghi, Maurizio; Dokuchaev, Nikolai E; Galimberti, Andrea; Halajian, Ali; Henttonen, Heikki; Ichikawa-Seki, Madoka; Itagaki, Tadashi; Krivopalov, Anton V; Meri, Seppo; Morand, Serge; Näreaho, Anu; Olsson, Gert E; Ribas, Alexis; Terefe, Yitagele; Nakao, Minoru

2016-05-01

The common cat tapeworm Hydatigera taeniaeformis is a complex of three morphologically cryptic entities, which can be differentiated genetically. To clarify the biogeography and the host spectrum of the cryptic lineages, 150 specimens of H. taeniaeformis in various definitive and intermediate hosts from Eurasia, Africa and Australia were identified with DNA barcoding using partial mitochondrial cytochrome c oxidase subunit 1 gene sequences and compared with previously published data. Additional phylogenetic analyses of selected isolates were performed using nuclear DNA and mitochondrial genome sequences. Based on molecular data and morphological analysis, Hydatigera kamiyai n. sp. Iwaki is proposed for a cryptic lineage, which is predominantly northern Eurasian and uses mainly arvicoline rodents (voles) and mice of the genus Apodemus as intermediate hosts. Hydatigera taeniaeformis sensu stricto (s.s.) is restricted to murine rodents (rats and mice) as intermediate hosts. It probably originates from Asia but has spread worldwide. Despite remarkable genetic divergence between H. taeniaeformis s.s. and H. kamiyai, interspecific morphological differences are evident only in dimensions of rostellar hooks. The third cryptic lineage is closely related to H. kamiyai, but its taxonomic status remains unresolved due to limited morphological, molecular, biogeographical and ecological data. This Hydatigera sp. is confined to the Mediterranean and its intermediate hosts are unknown. Further studies are needed to classify Hydatigera sp. either as a distinct species or a variant of H. kamiyai. According to previously published limited data, all three entities occur in the Americas, probably due to human-mediated introductions. Copyright © 2016 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Model-based analysis of N-glycosylation in Chinese hamster ovary cells

PubMed Central

Krambeck, Frederick J.; Bennun, Sandra V.; Betenbaugh, Michael J.

2017-01-01

The Chinese hamster ovary (CHO) cell is the gold standard for manufacturing of glycosylated recombinant proteins for production of biotherapeutics. The similarity of its glycosylation patterns to the human versions enable the products of this cell line favorable pharmacokinetic properties and lower likelihood of causing immunogenic responses. Because glycan structures are the product of the concerted action of intracellular enzymes, it is difficult to predict a priori how the effects of genetic manipulations alter glycan structures of cells and therapeutic properties. For that reason, quantitative models able to predict glycosylation have emerged as promising tools to deal with the complexity of glycosylation processing. For example, an earlier version of the same model used in this study was used by others to successfully predict changes in enzyme activities that could produce a desired change in glycan structure. In this study we utilize an updated version of this model to provide a comprehensive analysis of N-glycosylation in ten Chinese hamster ovary (CHO) cell lines that include a wild type parent and nine mutants of CHO, through interpretation of previously published mass spectrometry data. The updated N-glycosylation mathematical model contains up to 50,605 glycan structures. Adjusting the enzyme activities in this model to match N-glycan mass spectra produces detailed predictions of the glycosylation process, enzyme activity profiles and complete glycosylation profiles of each of the cell lines. These profiles are consistent with biochemical and genetic data reported previously. The model-based results also predict glycosylation features of the cell lines not previously published, indicating more complex changes in glycosylation enzyme activities than just those resulting directly from gene mutations. The model predicts that the CHO cell lines possess regulatory mechanisms that allow them to adjust glycosylation enzyme activities to mitigate side effects of the primary loss or gain of glycosylation function known to exist in these mutant cell lines. Quantitative models of CHO cell glycosylation have the potential for predicting how glycoengineering manipulations might affect glycoform distributions to improve the therapeutic performance of glycoprotein products. PMID:28486471

A new crystal structure of the bifunctional antibiotic simocyclinone D8 bound to DNA gyrase gives fresh insight into the mechanism of inhibition.

PubMed

Hearnshaw, Stephen J; Edwards, Marcus J; Stevenson, Clare E; Lawson, David M; Maxwell, Anthony

2014-05-15

Simocyclinone D8 (SD8) is an antibiotic produced by Streptomyces antibioticus that targets DNA gyrase. A previous structure of SD8 complexed with the N-terminal domain of the DNA gyrase A protein (GyrA) suggested that four SD8 molecules stabilized a tetramer of the protein; subsequent mass spectrometry experiments suggested that a protein dimer with two symmetry-related SD8s was more likely. This work describes the structures of a further truncated form of the GyrA N-terminal domain fragment with and without SD8 bound. The structure with SD8 has the two SD8 molecules bound within the same GyrA dimer. This new structure is entirely consistent with the mutations in GyrA that confer SD8 resistance and, by comparison with a new apo structure of the GyrA N-terminal domain, reveals the likely conformation changes that occur upon SD8 binding and the detailed mechanism of SD8 inhibition of gyrase. Isothermal titration calorimetry experiments are consistent with the crystallography results and further suggest that a previously observed complex between SD8 and GyrB is ~1000-fold weaker than the interaction with GyrA. Copyright © 2014. Published by Elsevier Ltd.

Intrusive dike complexes, cumulate cores, and the extrusive growth of Hawaiian volcanoes

USGS Publications Warehouse

Flinders, Ashton F.; Ito, Garrett; Garcia, Michael O.; Sinton, John M.; Kauahikaua, Jim; Taylor, Brian

2013-01-01

The Hawaiian Islands are the most geologically studied hot-spot islands in the world yet surprisingly, the only large-scale compilation of marine and land gravity data is more than 45 years old. Early surveys served as reconnaissance studies only, and detailed analyses of the crustal-density structure have been limited. Here we present a new chain-wide gravity compilation that incorporates historical island surveys, recently published work on the islands of Hawai‘i, Kaua‘i, and Ni‘ihau, and >122,000 km of newly compiled marine gravity data. Positive residual gravity anomalies reflect dense intrusive bodies, allowing us to locate current and former volcanic centers, major rift zones, and a previously suggested volcano on Ka‘ena Ridge. By inverting the residual gravity data, we generate a 3-D view of the dense, intrusive complexes and olivine-rich cumulate cores within individual volcanoes and rift zones. We find that the Hāna and Ka‘ena ridges are underlain by particularly high-density intrusive material (>2.85 g/cm3) not observed beneath other Hawaiian rift zones. Contrary to previous estimates, volcanoes along the chain are shown to be composed of a small proportion of intrusive material (<30% by volume), implying that the islands are predominately built extrusively.

Improved modeling of side-chain--base interactions and plasticity in protein--DNA interface design.

PubMed

Thyme, Summer B; Baker, David; Bradley, Philip

2012-06-08

Combinatorial sequence optimization for protein design requires libraries of discrete side-chain conformations. The discreteness of these libraries is problematic, particularly for long, polar side chains, since favorable interactions can be missed. Previously, an approach to loop remodeling where protein backbone movement is directed by side-chain rotamers predicted to form interactions previously observed in native complexes (termed "motifs") was described. Here, we show how such motif libraries can be incorporated into combinatorial sequence optimization protocols and improve native complex recapitulation. Guided by the motif rotamer searches, we made improvements to the underlying energy function, increasing recapitulation of native interactions. To further test the methods, we carried out a comprehensive experimental scan of amino acid preferences in the I-AniI protein-DNA interface and found that many positions tolerated multiple amino acids. This sequence plasticity is not observed in the computational results because of the fixed-backbone approximation of the model. We improved modeling of this diversity by introducing DNA flexibility and reducing the convergence of the simulated annealing algorithm that drives the design process. In addition to serving as a benchmark, this extensive experimental data set provides insight into the types of interactions essential to maintain the function of this potential gene therapy reagent. Published by Elsevier Ltd.

A peptide disrupting the D2R-DAT interaction protects against dopamine neurotoxicity.

PubMed

Su, Ping; Liu, Fang

2017-09-01

Dopamine reuptake from extracellular space to cytosol leads to accumulation of dopamine, which triggers neurotoxicity in dopaminergic neurons. Previous studies have shown that both dopamine D2 receptor (D2R) and dopamine transporter (DAT) are involved in dopamine neurotoxicity. However, blockade of either D2R or DAT causes side effects due to antagonism of other physiological functions of these two proteins. We previously found that DAT can form a protein complex with D2R and its cell surface expression is facilitated via D2R-DAT interaction, which regulates dopamine reuptake and intracellular dopamine levels. Here we found that an interfering peptide (DAT-S1) disrupting the D2R-DAT interaction protects neurons against dopamine neurotoxicity, and this effect is mediated by inhibiting DAT cell surface expression and inhibiting both caspase-3 and PARP-1 cleavage. This study demonstrates the role of the D2R-DAT complex in dopamine neurotoxicity and investigated the potential mechanisms, which might help better understand the mechanisms of dopamine neurotoxicity. The peptide may provide some insights to improve treatments for dopamine neurotoxicity and related diseases, such as Parkinson's disease, as well as methamphetamine- and 3,4-methsylenedioxy methamphetamine-induced neurotoxicity. Copyright © 2017. Published by Elsevier Inc.

Impact of Empire Expansion on Household Diet: The Inka in Northern Chile's Atacama Desert

PubMed Central

Vinton, Sheila Dorsey; Perry, Linda; Reinhard, Karl J.; Santoro, Calogero M.; Teixeira-Santos, Isabel

2009-01-01

The impact of expanding civilization on the health of American indigenous societies has long been studied. Most studies have focused on infections and malnutrition that occurred when less complex societies were incorporated into more complex civilizations. The details of dietary change, however, have rarely been explored. Using the analysis of starch residues recovered from coprolites, here we evaluate the dietary adaptations of indigenous farmers in northern Chile's Atacama Desert during the time that the Inka Empire incorporated these communities into their economic system. This system has been described as “complementarity” because it involves interaction and trade in goods produced at different Andean elevations. We find that as local farming societies adapted to this new asymmetric system, a portion of their labor had to be given up to the Inka elite through a corvée tax system for maize production. In return, the Inka system of complementarity introduced previously rare foods from the Andean highlands into local economies. These changes caused a disruption of traditional communities as they instituted a state-level economic system on local farmers. Combined with previously published infection information for the same populations under Inka rule, the data suggest that there may have been a dual health impact from disruption of nutrition and introduction of crowd disease. PMID:19956668

The Molecular Determinants of Small-Molecule Ligand Binding at P2X Receptors

PubMed Central

Pasqualetto, Gaia; Brancale, Andrea; Young, Mark T.

2018-01-01

P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular ATP—their physiological ligand—is released as a neurotransmitter and in conditions of cell damage such as inflammation, and substantial evidence implicates P2X receptors in diseases including neuropathic pain, cancer, and arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo- state, was published, and this was followed in 2012 by the ATP-bound structure. These structures transformed our understanding of the conformational changes induced by ATP binding and the mechanism of ligand specificity, and enabled homology modeling of mammalian P2X receptors for ligand docking and rational design of receptor modulators. P2X receptors are attractive drug targets, and a wide array of potent, subtype-selective modulators (mostly antagonists) have been developed. In 2016, crystal structures of human P2X3 in complex with the competitive antagonists TNP-ATP and A-317491, and Ailuropoda melanoleuca P2X7 in complex with a series of allosteric antagonists were published, giving fascinating insights into the mechanism of channel antagonism. In this article we not only summarize current understanding of small-molecule modulator binding at P2X receptors, but also use this information in combination with previously published structure-function data and molecular docking experiments, to hypothesize a role for the dorsal fin loop region in differential ATP potency, and describe novel, testable binding conformations for both the semi-selective synthetic P2X7 agonist 2′-(3′)-O-(4-benzoyl)benzoyl ATP (BzATP), and the P2X4-selective positive allosteric modulator ivermectin. We find that the distal benzoyl group of BzATP lies in close proximity to Lys-127, a residue previously implicated in BzATP binding to P2X7, potentially explaining the increased potency of BzATP at rat P2X7 receptors. We also present molecular docking of ivermectin to rat P2X4 receptors, illustrating a plausible binding conformation between the first and second transmembrane domains which not only tallies with previous mutagenesis studies, but would also likely have the effect of stabilizing the open channel structure, consistent with the mode of action of this positive allosteric modulator. From our docking simulations and analysis of sequence homology we propose a series of mutations likely to confer ivermectin sensitivity to human P2X1. PMID:29456508

Reference Accuracy among Research Articles Published in "Research on Social Work Practice"

ERIC Educational Resources Information Center

Wilks, Scott E.; Geiger, Jennifer R.; Bates, Samantha M.; Wright, Amy L.

2017-01-01

Objective: The objective was to examine reference errors in research articles published in Research on Social Work Practice. High rates of reference errors in other top social work journals have been noted in previous studies. Methods: Via a sampling frame of 22,177 total references among 464 research articles published in the previous decade, a…

Immune complexes with cationic antibodies deposit in glomeruli more effectively than cationic antibodies alone.

PubMed

Mannik, M; Gauthier, V J; Stapleton, S A; Agodoa, L Y

1987-06-15

In previously published studies, highly cationized antibodies alone and in immune complexes bound to glomeruli by charge-charge interaction, but only immune complexes persisted in glomeruli. Because normal IgG does not deposit in glomeruli, studies were conducted to determine whether cationized antibodies can be prepared which deposit in glomeruli when bound to antigen but not when free in circulation. A series of cationized rabbit antiHSA was prepared with the number of added amino groups ranging from 13.3 to 60.2 per antibody molecule. Antibodies alone or in preformed soluble immune complexes, prepared at fivefold or 50-fold antigen excess, were administered to mice. With the injection of a fixed dose of 100 micrograms per mouse, antibodies alone did not deposit in glomeruli with less than 29.6 added amino groups by immunofluorescence microscopy. In contrast, 100 micrograms of antibodies with 23.5 added amino groups in immune complexes, made at fivefold antigen excess, formed immune deposits in glomeruli. With selected preparations of cationized, radiolabeled antibodies, deposition in glomeruli was quantified by isolation of mouse glomeruli. These quantitative data were in good agreement with the results of immunofluorescence microscopy. Immune complexes made at 50-fold antigen excess, containing only small-latticed immune complexes with no more than two antibody molecules per complex, deposited in glomeruli similar to antibodies alone. Selected cationized antibodies alone or in immune complexes were administered to mice in varying doses. In these experiments, glomerular deposition of immune complexes, made at fivefold antigen excess, was detected with five- to 10-fold smaller doses than the deposition of the same antibodies alone. These studies demonstrate that antibody molecules in immune complexes are more likely to deposit in glomeruli by charge-charge interactions than antibodies alone.

Finite element models of the human shoulder complex: a review of their clinical implications and modelling techniques.

PubMed

Zheng, Manxu; Zou, Zhenmin; Bartolo, Paulo Jorge Da Silva; Peach, Chris; Ren, Lei

2017-02-01

The human shoulder is a complicated musculoskeletal structure and is a perfect compromise between mobility and stability. The objective of this paper is to provide a thorough review of previous finite element (FE) studies in biomechanics of the human shoulder complex. Those FE studies to investigate shoulder biomechanics have been reviewed according to the physiological and clinical problems addressed: glenohumeral joint stability, rotator cuff tears, joint capsular and labral defects and shoulder arthroplasty. The major findings, limitations, potential clinical applications and modelling techniques of those FE studies are critically discussed. The main challenges faced in order to accurately represent the realistic physiological functions of the shoulder mechanism in FE simulations involve (1) subject-specific representation of the anisotropic nonhomogeneous material properties of the shoulder tissues in both healthy and pathological conditions; (2) definition of boundary and loading conditions based on individualised physiological data; (3) more comprehensive modelling describing the whole shoulder complex including appropriate three-dimensional (3D) representation of all major shoulder hard tissues and soft tissues and their delicate interactions; (4) rigorous in vivo experimental validation of FE simulation results. Fully validated shoulder FE models would greatly enhance our understanding of the aetiology of shoulder disorders, and hence facilitate the development of more efficient clinical diagnoses, non-surgical and surgical treatments, as well as shoulder orthotics and prosthetics. © 2016 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd. © 2016 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

An analysis of the kangaroo care intervention using neonatal EEG complexity: a preliminary study.

PubMed

Kaffashi, F; Scher, M S; Ludington-Hoe, S M; Loparo, K A

2013-02-01

Skin-to-skin contact (SSC) promotes physiological stability and interaction between parents and infants. Temporal analyses of predictability in EEG-sleep time series can elucidate functional brain maturation between SSC and non-SSC cohorts at similar post-menstrual ages (PMAs). Sixteen EEG-sleep studies were performed on eight preterm infants who received 8 weeks of SSC, and compared with two non-SSC cohorts at term (N=126) that include a preterm group corrected to term age and a full term group. Two time series measures of predictability were used for comparisons. The SSC premature neonate group had increased complexity when compared to the non-SSC premature neonate group at the same PMA. Discriminant analysis shows that SSC neonates at 40 weeks PMA are closer to the full term neonate non-SSC group than to the premature non-SSC group at the same PMA; suggesting that the KC intervention accelerates neurophysiological maturation of premature neonates. Based on the hypothesis that EEG-derived complexity increases with neurophysiological maturation as supported by previously published research, SSC accelerates brain maturation in healthy preterm infants as quantified by time series measures of predictability when compared to a similar non-SSC group. Times series methods that quantify predictability of EEG sleep in neonates can provide useful information about altered neural development after developmental care interventions such as SSC. Analyses of this type may be helpful in assessing other neuroprotection strategies. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A Multi-year Search for Transits of Proxima Centauri. I. Light Curves Corresponding to Published Ephemerides

NASA Astrophysics Data System (ADS)

Blank, David L.; Feliz, Dax; Collins, Karen A.; White, Graeme L.; Stassun, Keivan G.; Curtis, Ivan A.; Hart, Rhodes; Kielkopf, John F.; Nelson, Peter; Relles, Howard; Stockdale, Christopher; Jayawardene, Bandupriya; Pennypacker, Carlton R.; Shankland, Paul; Reichart, Daniel E.; Haislip, Joshua B.; Kouprianov, Vladimir V.

2018-06-01

Proxima Centauri has become the subject of intense study since the radial-velocity (RV) discovery by Anglada-Escudé et al. of a planet orbiting this nearby M dwarf every ∼11.2 days. If Proxima Centauri b transits its host star, independent confirmation of its existence is possible, and its mass and radius can be measured in units of the stellar host mass and radius. To date, there have been three independent claims of possible transit-like event detections in light curve observations obtained by the MOST satellite (in 2014–15), the Bright Star Survey Telescope telescope in Antarctica (in 2016), and the Las Campanas Observatory (in 2016). The claimed possible detections are tentative, due in part to the variability intrinsic to the host star, and in the case of the ground-based observations, also due to the limited duration of the light curve observations. Here, we present preliminary results from an extensive photometric monitoring campaign of Proxima Centauri, using telescopes around the globe and spanning from 2006 to 2017, comprising a total of 329 observations. Considering our data that coincide directly and/or phased with the previously published tentative transit detections, we are unable to independently verify those claims. We do, however, verify the previously reported ubiquitous and complex variability of the host star. We discuss possible interpretations of the data in light of the previous claims, and we discuss future analyses of these data that could more definitively verify or refute the presence of transits associated with the RV-discovered planet.

Disclosing victimisation to healthcare professionals in Sweden: a constructivist grounded theory study of experiences among men exposed to interpersonal violence.

PubMed

Simmons, Johanna; Brüggemann, Adrianus Jelmer; Swahnberg, Katarina

2016-06-20

To develop a theoretical model concerning male victims' processes of disclosing experiences of victimisation to healthcare professionals in Sweden. Qualitative interview study. Informants were recruited from the general population and a primary healthcare centre in Sweden. Informants were recruited by means of theoretical sampling among respondents in a previous quantitative study. Eligible for this study were men reporting sexual, physical and/or emotional violence victimisation by any perpetrator and reporting that they either had talked to a healthcare provider about their victimisation or had wanted to do so. Constructivist grounded theory. 12 interviews were performed and saturation was reached after 9. Several factors influencing the process of disclosing victimisation can be recognised from previous studies concerning female victims, including shame, fear of negative consequences of disclosing, specifics of the patient-provider relationship and time constraints within the healthcare system. However, this study extends previous knowledge by identifying strong negative effects of adherence to masculinity norms for victimised men and healthcare professionals on the process of disclosing. It is also emphasised that the process of disclosing cannot be separated from other, even seemingly unrelated, circumstances in the men's lives. The process of disclosing victimisation to healthcare professionals was a complex process involving the men's experiences of victimisation, adherence to gender norms, their life circumstances and the dynamics of the actual healthcare encounter. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Can technical factors explain the volume-outcome relationship in gastric bypass surgery?

PubMed

Smith, Mark D; Patterson, Emma; Wahed, Abdus S; Belle, Steven H; Courcoulas, Anita P; Flum, David; Khandelwal, Saurabh; Mitchell, James E; Pomp, Alfons; Pories, Walter J; Wolfe, Bruce

2013-01-01

The existence of a relationship between surgeon volume and patient outcome has been reported for different complex surgical operations. This relationship has also been confirmed for patients undergoing Roux-en-Y gastric bypass (RYGB) in the Longitudinal Assessment of Bariatric Surgery (LABS) study. Despite multiple studies demonstrating volume-outcome relationships, fewer studies investigate the causes of this relationship. The purpose of the present study is to understand possible explanations for the volume-outcome relationship in LABS. LABS includes a 10-center, prospective study examining 30-day outcomes after bariatric surgery. The relationship between surgeon annual RYGB volume and incidence of a composite endpoint (CE) has been published previously. Technical aspects of RYGB surgery were compared between high and low volume surgeons. The previously published model was adjusted for select technical factors. High-volume surgeons (>100 RYGBs/yr) were more likely to perform a linear stapled gastrojejunostomy, use fibrin sealant, and place a drain at the gastrojejunostomy compared with low-volume surgeons (<25 RYGBs/yr), and less likely to perform an intraoperative leak test. After adjusting for the newly identified technical factors, the relative risk of CE was .93 per 10 RYGB/yr increase in volume, compared with .90 for clinical risk adjustment alone. High-volume surgeons exhibited certain differences in technique compared with low-volume surgeons. After adjusting for these differences, the strength of the volume-outcome relationship previously found was reduced only slightly, suggesting that other factors are also involved. Copyright © 2013 American Society for Bariatric Surgery. All rights reserved.

Revisiting the use of 'place' as an analytic tool for elucidating geographic issues central to Canadian rural palliative care.

PubMed

Giesbrecht, Melissa; Crooks, Valorie A; Castleden, Heather; Schuurman, Nadine; Skinner, Mark W; Williams, Allison M

2016-09-01

In 2010, Castleden and colleagues published a paper in this journal using the concept of 'place' as an analytic tool to understand the nature of palliative care provision in a rural region in British Columbia, Canada. This publication was based upon pilot data collected for a larger research project that has since been completed. With the addition of 40 semi-structured interviews with users and providers of palliative care in four other rural communities located across Canada, we revisit Castleden and colleagues' (2010) original framework. Applying the concept of place to the full dataset confirmed the previously published findings, but also revealed two new place-based dimensions related to experiences of rural palliative care in Canada: (1) borders and boundaries; and (2) 'making' place for palliative care progress. These new findings offer a refined understanding of the complex interconnections between various dimensions of place and palliative care in rural Canada. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of Copper Acyclovir Complexes on Herpes Simplex Virus Type 1 and Type 2 (HSV-1, HSV-2) Infection in Cultured Cells

PubMed Central

Panteva, M.; Varadinova, T.; Turel, I.

1998-01-01

We have found that when copper, zinc or cobalt is bound to a suitable ligand, the appropriate complex exhibited a significant anti-HSV effect (Varadinova et al., 1993; 1996). Recently published data by Sagripanti et al. (1997) also show that the inhibition of HSV by copper was enhanced by reducing agents and that mechanism of the inactivation is similar as for copper-mediated DNA damage (Aruoma, et al. 1991; Dizdaroglu, et al., 1991; Toyokuni and Sagripanti, 1994). Therefore it was interesting to study the efect of Cu(ll) coordination compounds with acyclovir (ACV) on the replication of HSV in cultured cells. The experiments on cytotoxicity as well as on the activity of three different Cu-ACV complexes [Cu(ACV)2Cl2(H2O)2] = (A); [Cu(ACV)2(H2O)3](NO3)2.H2O = (B) and [Cu(ACV)2(H2O)2](NO3)2] = (C) towards virus replication, with special attention on the growth of ACV-resistant strain R-100 were performed on MDBK cells. ACV was used as a reference compound. The following results were obtained: 1) Increased cell’s viability in the presence of 20-40(g/ml ACV and decreased one in the presence of Cu-ACV complexes with relative level (A) >> (B) > (C); 2) Cu-ACV complexes are more cytotoxic than the ligand - ACV and the relative level is (C)>(B)>(A); 3) The anti-HSV effect of ACV can be modulated by copper at levels depending on the specificity of the particular virus strain: (i) for the ACV sensitive strain DA (HSV-1) - ACV ((A) > (C) > (B); (ii) for the ACV sensitive strain Bja (HSV-2) (A) > ACV > (C) > (B); (iii) for strain R-100 (ACVR, TKa) - (A) > ACV > (C) > (B). This findings are consistent with previously published data and undoubtedly show that Cu-ACV complexes could be useful in the treatment of HSV infections, especially when the causative agent is a resistant to ACV mutant. PMID:18475820

Successful treatment of athletic pubalgia in a lacrosse player with ultrasound-guided needle tenotomy and platelet-rich plasma injection: a case report.

PubMed

Scholten, Paul M; Massimi, Stephen; Dahmen, Nick; Diamond, Joanne; Wyss, James

2015-01-01

Athletic pubalgia is a syndrome of persistent groin pain due to chronic repetitive trauma or stress involving the pelvic joints and many musculotendinous structures that cross the anterior pelvis. As a result, the differential diagnosis can be complex, but insertional tendinopathies are the most common. This case report describes a novel approach to the treatment of distal rectus abdominis tendinopathies with ultrasound-guided needle tenotomy and platelet-rich plasma (PRP) injection. After injection, the patient returned to pain-free play at his previous level of intensity. This suggests that PRP may be a useful treatment for this diagnosis. Copyright © 2015. Published by Elsevier Inc.

Tiny, Dusty, Galactic HI Clouds: The GALFA-HI Compact Cloud Catalog

NASA Astrophysics Data System (ADS)

Saul, Destry R.; Putman, M. E.; Peek, J. G.

2013-01-01

The recently published GALFA-HI Compact Cloud Catalog contains 2000 nearby neutral hydrogen clouds under 20' in angular size detected with a machine-vision algorithm in the Galactic Arecibo L-Band Feed Array HI survey (GALFA-HI). At a distance of 1kpc, the compact clouds would typically be 1 solar mass and 1pc in size. We observe that nearly all of the compact clouds that are classified as high velocity (> 90 km/s) are near previously-identified high velocity complexes. We separate the compact clouds into populations based on velocity, linewidth, and position. We have begun to search for evidence of dust in these clouds using IRIS and have detections in several populations.

Single-Molecule Analysis of Pre-mRNA Splicing with Colocalization Single-Molecule Spectroscopy (CoSMoS).

PubMed

Braun, Joerg E; Serebrov, Victor

2017-01-01

Recent development of single-molecule techniques to study pre-mRNA splicing has provided insights into the dynamic nature of the spliceosome. Colocalization single-molecule spectroscopy (CoSMoS) allows following spliceosome assembly in real time at single-molecule resolution in the full complexity of cellular extracts. A detailed protocol of CoSMoS has been published previously (Anderson and Hoskins, Methods Mol Biol 1126:217-241, 2014). Here, we provide an update on the technical advances since the first CoSMoS studies including slide surface treatment, data processing, and representation. We describe various labeling strategies to generate RNA reporters with multiple dyes (or other moieties) at specific locations.

Systematic review of non-surgical therapies for osteoarthritis of the hand: an update.

PubMed

Lue, S; Koppikar, S; Shaikh, K; Mahendira, D; Towheed, T E

2017-09-01

To update our earlier systematic reviews which evaluated all published randomized controlled trials (RCTs) evaluating pharmacological and non-pharmacological therapies in patients with hand osteoarthritis (OA). Surgical therapies were not evaluated. RCTs published between March 2008 and December 2015 were added to the previous systematic reviews. A total of 95 RCTs evaluating various pharmacological and non-pharmacological therapies in hand OA were analyzed in this update. Generally, the methodological quality of these RCTs has improved since the last update, with more studies describing their methods for randomization, blinding, and allocation concealment. However, RCTs continue to be weakened by a lack of consistent case definition and a lack of standardized outcome assessments specific to hand OA. The number and location of evaluated hand joints continues to be underreported, and only 25% of RCTs adequately described the method used to ensure allocation concealment. These remain major weaknesses of published RCTs. A meta-analysis could not be performed because of marked study heterogeneity, insufficient statistical data available in the published RCTs, and a small number of identical comparators. Hand OA is a complex area in which to study the efficacy of therapies. There has been an improvement in the overall design and conduct of RCTs, however, additional large RCTs with a more robust methodological approach specific to hand OA are needed in order to make clinically relevant conclusions about the efficacy of the diverse treatment options available. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Integrating Gene Expression with Summary Association Statistics to Identify Genes Associated with 30 Complex Traits.

PubMed

Mancuso, Nicholas; Shi, Huwenbo; Goddard, Pagé; Kichaev, Gleb; Gusev, Alexander; Pasaniuc, Bogdan

2017-03-02

Although genome-wide association studies (GWASs) have identified thousands of risk loci for many complex traits and diseases, the causal variants and genes at these loci remain largely unknown. Here, we introduce a method for estimating the local genetic correlation between gene expression and a complex trait and utilize it to estimate the genetic correlation due to predicted expression between pairs of traits. We integrated gene expression measurements from 45 expression panels with summary GWAS data to perform 30 multi-tissue transcriptome-wide association studies (TWASs). We identified 1,196 genes whose expression is associated with these traits; of these, 168 reside more than 0.5 Mb away from any previously reported GWAS significant variant. We then used our approach to find 43 pairs of traits with significant genetic correlation at the level of predicted expression; of these, eight were not found through genetic correlation at the SNP level. Finally, we used bi-directional regression to find evidence that BMI causally influences triglyceride levels and that triglyceride levels causally influence low-density lipoprotein. Together, our results provide insight into the role of gene expression in the susceptibility of complex traits and diseases. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Book review: The Wilderness Debate Rages On: Continuing the Great New Wilderness Debate

Treesearch

Peter Landres

2009-01-01

The Wilderness Debate Rages On is a collection of mostly previously published papers about the meaning, value, and role of wilderness and continues the discussion that was propelled by the editors' previous book The Great New Wilderness Debate (also a collection of papers) published in 1998. The editors state that this sequel to their previous book is mandated...

Ethics in Publishing: Complexity Science and Human Factors Offer Insights to Develop a Just Culture.

PubMed

Saurin, Tarcisio Abreu

2016-12-01

While ethics in publishing has been increasingly debated, there seems to be a lack of a theoretical framework for making sense of existing rules of behavior as well as for designing, managing and enforcing such rules. This letter argues that systems-oriented disciplines, such as complexity science and human factors, offer insights into new ways of dealing with ethics in publishing. Some examples of insights are presented. Also, a call is made for empirical studies that unveil the context and details of both retracted papers and the process of writing and publishing academic papers. This is expected to shed light on the complexity of the publication system as well as to support the development of a just culture, in which all participants are accountable.

A selection model for accounting for publication bias in a full network meta-analysis.

PubMed

Mavridis, Dimitris; Welton, Nicky J; Sutton, Alex; Salanti, Georgia

2014-12-30

Copas and Shi suggested a selection model to explore the potential impact of publication bias via sensitivity analysis based on assumptions for the probability of publication of trials conditional on the precision of their results. Chootrakool et al. extended this model to three-arm trials but did not fully account for the implications of the consistency assumption, and their model is difficult to generalize for complex network structures with more than three treatments. Fitting these selection models within a frequentist setting requires maximization of a complex likelihood function, and identification problems are common. We have previously presented a Bayesian implementation of the selection model when multiple treatments are compared with a common reference treatment. We now present a general model suitable for complex, full network meta-analysis that accounts for consistency when adjusting results for publication bias. We developed a design-by-treatment selection model to describe the mechanism by which studies with different designs (sets of treatments compared in a trial) and precision may be selected for publication. We fit the model in a Bayesian setting because it avoids the numerical problems encountered in the frequentist setting, it is generalizable with respect to the number of treatments and study arms, and it provides a flexible framework for sensitivity analysis using external knowledge. Our model accounts for the additional uncertainty arising from publication bias more successfully compared to the standard Copas model or its previous extensions. We illustrate the methodology using a published triangular network for the failure of vascular graft or arterial patency. Copyright © 2014 John Wiley & Sons, Ltd.

On application of kernel PCA for generating stimulus features for fMRI during continuous music listening.

PubMed

Tsatsishvili, Valeri; Burunat, Iballa; Cong, Fengyu; Toiviainen, Petri; Alluri, Vinoo; Ristaniemi, Tapani

2018-06-01

There has been growing interest towards naturalistic neuroimaging experiments, which deepen our understanding of how human brain processes and integrates incoming streams of multifaceted sensory information, as commonly occurs in real world. Music is a good example of such complex continuous phenomenon. In a few recent fMRI studies examining neural correlates of music in continuous listening settings, multiple perceptual attributes of music stimulus were represented by a set of high-level features, produced as the linear combination of the acoustic descriptors computationally extracted from the stimulus audio. NEW METHOD: fMRI data from naturalistic music listening experiment were employed here. Kernel principal component analysis (KPCA) was applied to acoustic descriptors extracted from the stimulus audio to generate a set of nonlinear stimulus features. Subsequently, perceptual and neural correlates of the generated high-level features were examined. The generated features captured musical percepts that were hidden from the linear PCA features, namely Rhythmic Complexity and Event Synchronicity. Neural correlates of the new features revealed activations associated to processing of complex rhythms, including auditory, motor, and frontal areas. Results were compared with the findings in the previously published study, which analyzed the same fMRI data but applied linear PCA for generating stimulus features. To enable comparison of the results, methodology for finding stimulus-driven functional maps was adopted from the previous study. Exploiting nonlinear relationships among acoustic descriptors can lead to the novel high-level stimulus features, which can in turn reveal new brain structures involved in music processing. Copyright © 2018 Elsevier B.V. All rights reserved.

CD147 Induces Epithelial-to-Mesenchymal Transition by Disassembling Cellular Apoptosis Susceptibility Protein/E-Cadherin/β-Catenin Complex in Human Endometriosis.

PubMed

Wang, Chaoqun; Zhang, Jieting; Fok, Kin Lam; Tsang, Lai Ling; Ye, Mei; Liu, Jianni; Li, Fanghong; Zhao, Allan Zijian; Chan, Hsiao Chang; Chen, Hao

2018-04-06

Epithelial-to-mesenchymal transition (EMT) is postulated to be a prerequisite for the establishment of endometriosis (EMS), a common reproductive disorder in women. Our previous studies have demonstrated the elevated expression of transmembrane glycoprotein CD147 and its prosurvival effect on abnormal cells in endometriosis. Intriguingly, CD147 is known to promote EMT in cancers. However, the involvement of CD147 in EMT during the establishment of endometriosis remains incompletely understood. We found that CD147 promotes EMT in human endometrial adenocarcinoma cell line Ishikawa. We identified a novel CD147-interacting partner, cellular apoptosis susceptibility protein (CAS), which stabilized the interaction between E-cadherin (E-cad) and β-catenin (β-cat) by forming the CAS/E-cad/β-cat complex. Down-regulation of CAS led to the release and nuclear translocation of β-cat from E-cad, resulting in the overexpression of the EMT-promoting gene SNAIL. Interestingly, overexpression of CD147 impaired the interaction between CAS and E-cad and triggered the release of β-cat from the CAS/E-cad/β-cat complex, which in turn led to EMT. Furthermore, CAS was down-regulated in EMS, with elevated levels of CD147 and nuclear β-cat. These findings suggest a previously undefined role of CAS in regulating EMT and reveal the involvement of a CD147-induced EMT signaling pathway in pathogenic progression of EMS. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Allometry and Ecology of the Bilaterian Gut Microbiome

PubMed Central

Sherrill-Mix, Scott; McCormick, Kevin; Lauder, Abigail; Bailey, Aubrey; Zimmerman, Laurie; Li, Yingying; Django, Jean-Bosco N.; Bertolani, Paco; Colin, Christelle; Hart, John A.; Hart, Terese B.; Georgiev, Alexander V.; Sanz, Crickette M.; Morgan, David B.; Atencia, Rebeca; Cox, Debby; Muller, Martin N.; Sommer, Volker; Piel, Alexander K.; Stewart, Fiona A.; Speede, Sheri; Roman, Joe; Wu, Gary; Taylor, Josh; Bohm, Rudolf; Rose, Heather M.; Carlson, John; Mjungu, Deus; Schmidt, Paul; Gaughan, Celeste; Bushman, Joyslin I.; Schmidt, Ella; Bittinger, Kyle; Collman, Ronald G.; Hahn, Beatrice H.

2018-01-01

ABSTRACT Classical ecology provides principles for construction and function of biological communities, but to what extent these apply to the animal-associated microbiota is just beginning to be assessed. Here, we investigated the influence of several well-known ecological principles on animal-associated microbiota by characterizing gut microbial specimens from bilaterally symmetrical animals (Bilateria) ranging from flies to whales. A rigorously vetted sample set containing 265 specimens from 64 species was assembled. Bacterial lineages were characterized by 16S rRNA gene sequencing. Previously published samples were also compared, allowing analysis of over 1,098 samples in total. A restricted number of bacterial phyla was found to account for the great majority of gut colonists. Gut microbial composition was associated with host phylogeny and diet. We identified numerous gut bacterial 16S rRNA gene sequences that diverged deeply from previously studied taxa, identifying opportunities to discover new bacterial types. The number of bacterial lineages per gut sample was positively associated with animal mass, paralleling known species-area relationships from island biogeography and implicating body size as a determinant of community stability and niche complexity. Samples from larger animals harbored greater numbers of anaerobic communities, specifying a mechanism for generating more-complex microbial environments. Predictions for species/abundance relationships from models of neutral colonization did not match the data set, pointing to alternative mechanisms such as selection of specific colonists by environmental niche. Taken together, the data suggest that niche complexity increases with gut size and that niche selection forces dominate gut community construction. PMID:29588401

An Ontology-Enabled Natural Language Processing Pipeline for Provenance Metadata Extraction from Biomedical Text (Short Paper).

PubMed

Valdez, Joshua; Rueschman, Michael; Kim, Matthew; Redline, Susan; Sahoo, Satya S

2016-10-01

Extraction of structured information from biomedical literature is a complex and challenging problem due to the complexity of biomedical domain and lack of appropriate natural language processing (NLP) techniques. High quality domain ontologies model both data and metadata information at a fine level of granularity, which can be effectively used to accurately extract structured information from biomedical text. Extraction of provenance metadata, which describes the history or source of information, from published articles is an important task to support scientific reproducibility. Reproducibility of results reported by previous research studies is a foundational component of scientific advancement. This is highlighted by the recent initiative by the US National Institutes of Health called "Principles of Rigor and Reproducibility". In this paper, we describe an effective approach to extract provenance metadata from published biomedical research literature using an ontology-enabled NLP platform as part of the Provenance for Clinical and Healthcare Research (ProvCaRe). The ProvCaRe-NLP tool extends the clinical Text Analysis and Knowledge Extraction System (cTAKES) platform using both provenance and biomedical domain ontologies. We demonstrate the effectiveness of ProvCaRe-NLP tool using a corpus of 20 peer-reviewed publications. The results of our evaluation demonstrate that the ProvCaRe-NLP tool has significantly higher recall in extracting provenance metadata as compared to existing NLP pipelines such as MetaMap.

Complexity and specificity of the maize (Zea mays L.) root hair transcriptome.

PubMed

Hey, Stefan; Baldauf, Jutta; Opitz, Nina; Lithio, Andrew; Pasha, Asher; Provart, Nicholas; Nettleton, Dan; Hochholdinger, Frank

2017-04-01

Root hairs are tubular extensions of epidermis cells. Transcriptome profiling demonstrated that the single cell-type root hair transcriptome was less complex than the transcriptome of multiple cell-type primary roots without root hairs. In total, 831 genes were exclusively and 5585 genes were preferentially expressed in root hairs [false discovery rate (FDR) ≤1%]. Among those, the most significantly enriched Gene Ontology (GO) functional terms were related to energy metabolism, highlighting the high energy demand for the development and function of root hairs. Subsequently, the maize homologs for 138 Arabidopsis genes known to be involved in root hair development were identified and their phylogenetic relationship and expression in root hairs were determined. This study indicated that the genetic regulation of root hair development in Arabidopsis and maize is controlled by common genes, but also shows differences which need to be dissected in future genetic experiments. Finally, a maize root view of the eFP browser was implemented including the root hair transcriptome of the present study and several previously published maize root transcriptome data sets. The eFP browser provides color-coded expression levels for these root types and tissues for any gene of interest, thus providing a novel resource to study gene expression and function in maize roots. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Lessons learned from more than two decades of research on emerging contaminants in the environment.

PubMed

Noguera-Oviedo, Katia; Aga, Diana S

2016-10-05

In the last twenty years, thousands of research papers covering different aspects of emerging contaminants have been published, ranging from environmental occurrence to treatment and ecological effects. Emerging contaminants are environmental pollutants that have been investigated widely only in the last two decades and include anthropogenic and naturally occurring chemicals such as pharmaceuticals and personal care products and their metabolites, illicit drugs, engineered nanomaterials, and antibiotic resistance genes. The advancement in our knowledge on emerging contaminants has been the result of the appearance of highly sensitive and powerful analytical instrumentation that rapidly developed, allowing identification and trace quantification of unknown contaminants in complex environmental matrices. High efficiency chromatographic separations coupled to high-resolution mass spectrometers have become more common in environmental laboratories and are the pillars of environmental research, increasing our awareness and understanding of the presence of emerging contaminants in the environment, their transformation and fate, and the complex ecological consequences that they pose on exposed biological systems. This introductory paper for the Virtual Thematic Issue on Emerging Contaminants presents a brief literature overview on key research milestones in the area of emerging contaminants, focusing on pharmaceuticals and personal care products and endocrine disrupting compounds, and highlighting selected research papers previously published in the Journal of Hazardous Materials during the period of January 2012 to December 2015. Copyright © 2016 Elsevier B.V. All rights reserved.

Treatment planning for spinal radiosurgery : A competitive multiplatform benchmark challenge.

PubMed

Moustakis, Christos; Chan, Mark K H; Kim, Jinkoo; Nilsson, Joakim; Bergman, Alanah; Bichay, Tewfik J; Palazon Cano, Isabel; Cilla, Savino; Deodato, Francesco; Doro, Raffaela; Dunst, Jürgen; Eich, Hans Theodor; Fau, Pierre; Fong, Ming; Haverkamp, Uwe; Heinze, Simon; Hildebrandt, Guido; Imhoff, Detlef; de Klerck, Erik; Köhn, Janett; Lambrecht, Ulrike; Loutfi-Krauss, Britta; Ebrahimi, Fatemeh; Masi, Laura; Mayville, Alan H; Mestrovic, Ante; Milder, Maaike; Morganti, Alessio G; Rades, Dirk; Ramm, Ulla; Rödel, Claus; Siebert, Frank-Andre; den Toom, Wilhelm; Wang, Lei; Wurster, Stefan; Schweikard, Achim; Soltys, Scott G; Ryu, Samuel; Blanck, Oliver

2018-05-25

To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

Effects of linking a soil-water-balance model with a groundwater-flow model

USGS Publications Warehouse

Stanton, Jennifer S.; Ryter, Derek W.; Peterson, Steven M.

2013-01-01

A previously published regional groundwater-flow model in north-central Nebraska was sequentially linked with the recently developed soil-water-balance (SWB) model to analyze effects to groundwater-flow model parameters and calibration results. The linked models provided a more detailed spatial and temporal distribution of simulated recharge based on hydrologic processes, improvement of simulated groundwater-level changes and base flows at specific sites in agricultural areas, and a physically based assessment of the relative magnitude of recharge for grassland, nonirrigated cropland, and irrigated cropland areas. Root-mean-squared (RMS) differences between the simulated and estimated or measured target values for the previously published model and linked models were relatively similar and did not improve for all types of calibration targets. However, without any adjustment to the SWB-generated recharge, the RMS difference between simulated and estimated base-flow target values for the groundwater-flow model was slightly smaller than for the previously published model, possibly indicating that the volume of recharge simulated by the SWB code was closer to actual hydrogeologic conditions than the previously published model provided. Groundwater-level and base-flow hydrographs showed that temporal patterns of simulated groundwater levels and base flows were more accurate for the linked models than for the previously published model at several sites, particularly in agricultural areas.

Ovarian sex cord tumor with annular tubules. Clinicopathologic report of two benign and one malignant cases with long follow-ups.

PubMed

Gloor, E

1979-01-01

The clinicopathologic features of three new cases of ovarian sex cord tumors with annular tubules are presented, thereby increasing to 23 the number of the published cases in the world literature. These three observations, along with another one which was previously published, were found in the files of the Institute of Pathology of the University of Lausanne from 1939 to 1978. Forty-seven granulosa cell tumors and eight Sertoli and/or Leydig cell tumors of the ovary were found during the same 40-year period. The patients were 48, 64 and 71 years of age. No sign of the Peutz-Jeghers syndrome was noticed in the three patients. All three tumors caused metrorrhagias as a cardinal sign. They were bulky, unilateral and were formed by solid tissue with cystic spaces. Histologically, the most characteristic pattern consisted of simple and complex tubular structures as described by Scully in 1970. Two patients, in which the mitotic indexes of the tumors were lower than 5 mitoses per 10 HPF, died without evidence of a recurrence 36 and 37 years after surgical ablation of the tumor. The third patient, whose neoplasm featured fewer well differentiated tubular structures than the two previous ones and had a mitotic index of over 70 mitoses per 10 HPF, died from massive abdominal recurrence after 5 years and 5 months.

Application of Genotyping during an Extensive Outbreak of Waterborne Giardiasis in Bergen, Norway, during Autumn and Winter 2004†

PubMed Central

Robertson, L. J.; Hermansen, L.; Gjerde, B. K.; Strand, E.; Alvsvåg, J. O.; Langeland, N.

2006-01-01

During the autumn and winter of 2004 and 2005, an extensive outbreak of waterborne giardiasis occurred in Bergen, Norway. Over 1,500 patients were diagnosed with giardiasis. Analysis of water from the implicated source revealed low numbers of Giardia cysts, but the initial contamination event probably occurred up to 10 weeks previously. While sewage leakage from a residential area is now considered to be the probable source of contamination, during the episode waste from one particular septic tank was thought to be a possible source. Genotyping of cysts from the septic tank demonstrated that they were assemblage A cysts, although the sequences were not identical to any previously published sequences. For the β-giardin gene, the closest published subgenotype was subgenotype A3; for the gdh gene, the closest published subgenotype was subgenotype A2. Genotyping of cysts from 21 patient samples revealed that they were assemblage B cysts; thus, the septic tank was unlikely to be the contamination source. Sequencing of the β-giardin and gdh genes from patient samples and a comparison of the sequences gave complex results. For the β-giardin gene, three isolates had sequences identical to subgenotype B3 sequences. However, other isolates had between one and four single-nucleotide polymorphisms (SNPs). For the gdh gene, none of the sequences were identical to the sequence published for subgenotype B3, and the sequences had between one and three SNPs. One isolate, which was identical to subgenotype B3 at the β-giardin gene, was more similar to subgenotype B2 at the gdh gene. Grouping the isolates on the basis of SNPs resulted in different groups for the two genes. The results are discussed in relation to giardiasis in Norway and to other Giardia genotyping studies. PMID:16517674

Stable megadalton TOC-TIC supercomplexes as major mediators of protein import into chloroplasts.

PubMed

Chen, Lih-Jen; Li, Hsou-Min

2017-10-01

Preproteins are believed to be imported into chloroplasts through membrane contact sites where the translocon complexes of the outer (TOC) and inner (TIC) envelope membranes are assembled together. However, a single TOC-TIC supercomplex containing preproteins undergoing active import has not yet been directly observed. We optimized the blue native polyacrylamide gel electrophoresis (PAGE) (BN-PAGE) system to detect and resolve megadalton (MD)-sized complexes. Using this optimized system, the outer-membrane channel Toc75 from pea chloroplasts was found in at least two complexes: the 880-kD TOC complex and a previously undetected 1-MD complex. Two-dimensional BN-PAGE immunoblots further showed that Toc75, Toc159, Toc34, Tic20, Tic56 and Tic110 were all located in the 880-kD to 1.3-MD region. During active preprotein import, preproteins were transported mostly through the 1-MD complex and a smaller amount of preproteins was also detected in a complex of 1.25 MD. Antibody-shift assays showed that the 1-MD complex is a TOC-TIC supercomplex containing at least Toc75, Toc159, Toc34 and Tic110. Results from crosslinking and import with Arabidopsis chloroplasts suggest that the 1.25-MD complex is also a supercomplex. Our data provide direct evidence supporting that chloroplast preproteins are imported through TOC-TIC supercomplexes, and also provide the first size estimation of these supercomplexes. Furthermore, unlike in mitochondria where translocon supercomplexes are only transiently assembled during preprotein import, in chloroplasts at least some of the supercomplexes are preassembled stable structures. © 2017 The Authors The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Preliminary investigation of phosphorus adsorption onto two types of iron oxide-organic matter complexes.

PubMed

Yan, Jinlong; Jiang, Tao; Yao, Ying; Lu, Song; Wang, Qilei; Wei, Shiqiang

2016-04-01

Iron oxide (FeO) coated by natural organic matter (NOM) is ubiquitous. The associations of minerals with organic matter (OM) significantly changes their surface properties and reactivity, and thus affect the environmental fate of pollutants, including nutrients (e.g., phosphorus (P)). In this study, ferrihydrite/goethite-humic acid (FH/GE-HA) complexes were prepared and their adsorption characteristics on P at various pH and ionic strength were investigated. The results indicated that the FeO-OM complexes showed a decreased P adsorption capacity in comparison with bare FeO. The maximum adsorption capacity (Qmax) decreased in the order of FH (22.17 mg/g)>FH-HA (5.43 mg/g)>GE (4.67 mg/g)>GE-HA (3.27 mg/g). After coating with HA, the amorphous FH-HA complex still showed higher P adsorption than the crystalline GE-HA complex. The decreased P adsorption observed might be attributed to changes of the FeO surface charges caused by OM association. The dependence of P adsorption on the specific surface area of adsorbents suggests that the FeO component in the complexes is still the main contributor for the adsorption surfaces. The P adsorptions on FeO-HA complexes decreased with increasing initial pH or decreasing initial ionic strength. A strong dependence of P adsorption on ionic strength and pH may demonstrate that outer-sphere complexes between the OM component on the surface and P possibly coexist with inner-sphere surface complexes between the FeO component and P. Therefore, previous over-emphasis on the contributions of original minerals to P immobilization possibly over-estimates the P loading capacity of soils, especially in humic-rich areas. Copyright © 2015. Published by Elsevier B.V.

Mitotic position and morphology of committed precursor cells in the zebrafish retina adapt to architectural changes upon tissue maturation.

PubMed

Weber, Isabell P; Ramos, Ana P; Strzyz, Paulina J; Leung, Louis C; Young, Stephen; Norden, Caren

2014-04-24

The development of complex neuronal tissues like the vertebrate retina requires the tight orchestration of cell proliferation and differentiation. Although the complexity of transcription factors and signaling pathways involved in retinogenesis has been studied extensively, the influence of tissue maturation itself has not yet been systematically explored. Here, we present a quantitative analysis of mitotic events during zebrafish retinogenesis that reveals three types of committed neuronal precursors in addition to the previously known apical progenitors. The identified precursor types present at distinct developmental stages and exhibit different mitotic location (apical versus nonapical), cleavage plane orientation, and morphology. Interestingly, the emergence of nonapically dividing committed bipolar cell precursors can be linked to an increase in apical crowding caused by the developing photoreceptor cell layer. Furthermore, genetic interference with neuronal subset specification induces ectopic divisions of committed precursors, underlining the finding that progressing morphogenesis can effect precursor division position. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Syntactic and semantic restrictions on morphological recomposition: MEG evidence from Greek.

PubMed

Neophytou, K; Manouilidou, C; Stockall, L; Marantz, A

2018-05-16

Complex morphological processing has been extensively studied in the past decades. However, most of this work has either focused on only certain steps involved in this process, or it has been conducted on a few languages, like English. The purpose of the present study is to investigate the spatiotemporal cortical processing profile of the distinct steps previously reported in the literature, from decomposition to re-composition of morphologically complex items, in a relatively understudied language, Greek. Using magnetoencephalography, we confirm the role of the fusiform gyrus in early, form-based morphological decomposition, we relate the syntactic licensing of stem-suffix combinations to the ventral visual processing stream, somewhat independent from lexical access for the stem, and we further elucidate the role of orbitofrontal regions in semantic composition. Thus, the current study offers the most comprehensive test to date of visual morphological processing and additional, crosslinguistic validation of the steps involved in it. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

AESOP: A Python Library for Investigating Electrostatics in Protein Interactions.

PubMed

Harrison, Reed E S; Mohan, Rohith R; Gorham, Ronald D; Kieslich, Chris A; Morikis, Dimitrios

2017-05-09

Electric fields often play a role in guiding the association of protein complexes. Such interactions can be further engineered to accelerate complex association, resulting in protein systems with increased productivity. This is especially true for enzymes where reaction rates are typically diffusion limited. To facilitate quantitative comparisons of electrostatics in protein families and to describe electrostatic contributions of individual amino acids, we previously developed a computational framework called AESOP. We now implement this computational tool in Python with increased usability and the capability of performing calculations in parallel. AESOP utilizes PDB2PQR and Adaptive Poisson-Boltzmann Solver to generate grid-based electrostatic potential files for protein structures provided by the end user. There are methods within AESOP for quantitatively comparing sets of grid-based electrostatic potentials in terms of similarity or generating ensembles of electrostatic potential files for a library of mutants to quantify the effects of perturbations in protein structure and protein-protein association. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Synaptotagmin 11 interacts with components of the RNA-induced silencing complex RISC in clonal pancreatic β-cells.

PubMed

Milochau, Alexandra; Lagrée, Valérie; Benassy, Marie-Noëlle; Chaignepain, Stéphane; Papin, Julien; Garcia-Arcos, Itsaso; Lajoix, Anne; Monterrat, Carole; Coudert, Laetitia; Schmitter, Jean-Marie; Ochoa, Begoña; Lang, Jochen

2014-06-27

Synaptotagmins are two C2 domain-containing transmembrane proteins. The function of calcium-sensitive members in the regulation of post-Golgi traffic has been well established whereas little is known about the calcium-insensitive isoforms constituting half of the protein family. Novel binding partners of synaptotagmin 11 were identified in β-cells. A number of them had been assigned previously to ER/Golgi derived-vesicles or linked to RNA synthesis, translation and processing. Whereas the C2A domain interacted with the Q-SNARE Vti1a, the C2B domain of syt11 interacted with the SND1, Ago2 and FMRP, components of the RNA-induced silencing complex (RISC). Binding to SND was direct via its N-terminal tandem repeats. Our data indicate that syt11 may provide a link between gene regulation by microRNAs and membrane traffic. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat.

PubMed

Atanur, Santosh S; Diaz, Ana Garcia; Maratou, Klio; Sarkis, Allison; Rotival, Maxime; Game, Laurence; Tschannen, Michael R; Kaisaki, Pamela J; Otto, Georg W; Ma, Man Chun John; Keane, Thomas M; Hummel, Oliver; Saar, Kathrin; Chen, Wei; Guryev, Victor; Gopalakrishnan, Kathirvel; Garrett, Michael R; Joe, Bina; Citterio, Lorena; Bianchi, Giuseppe; McBride, Martin; Dominiczak, Anna; Adams, David J; Serikawa, Tadao; Flicek, Paul; Cuppen, Edwin; Hubner, Norbert; Petretto, Enrico; Gauguier, Dominique; Kwitek, Anne; Jacob, Howard; Aitman, Timothy J

2013-08-01

Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and insulin resistance, along with their respective control strains. Altogether, we identified more than 13 million single-nucleotide variants, indels, and structural variants across these rat strains. Analysis of strain-specific selective sweeps and gene clusters implicated genes and pathways involved in cation transport, angiotensin production, and regulators of oxidative stress in the development of cardiovascular disease phenotypes in rats. Many of the rat loci that we identified overlap with previously mapped loci for related traits in humans, indicating the presence of shared pathways underlying these phenotypes in rats and humans. These data represent a step change in resources available for evolutionary analysis of complex traits in disease models. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Short communication: Multidrug-resistant Acinetobacter baumannii-calcoaceticus complex isolated from infant milk formula and utensils in a nursery in Rio de Janeiro, Brazil.

PubMed

Araújo, B C; Moraes, M S; Costa, L E O; Nascimento, J S

2015-04-01

Infant milk formulas are not sterile products, and pathogenic bacteria can survive and multiply in these products. This study was performed, initially, to detect the presence of Salmonella spp. in reconstituted infant milk formula and on utensils previously sanitized used in their preparation or distribution in a nursery of a public hospital in Rio de Janeiro. None of the samples tested carried Salmonellaspp. However, further identification of colonies growing on the selective media revealed the presence of several other gram-negative bacteria. Seventeen isolates were identified as belonging to Acinetobacter baumannii-calcoaceticus complex. Fourteen isolates presented a multidrug-resistance profile, by disc diffusion assays, and one of them--JE4--was also resistant to imipenem. The detection of Acinetobacter isolates in this work demonstrates inadequate hygiene practices in the preparation or distribution of infant milk formula. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Le Fort Fractures: A Collective Review

PubMed Central

Phillips, Bradley J.; Turco, Lauren M.

2017-01-01

Le Fort fractures constitute a pattern of complex facial injury that occurs secondary to blunt facial trauma.  The most common mechanisms of injury for these fractures, which are frequently associated with drug and alcohol use, include motor vehicle collisions, assault, and falls. A thorough search of the world’s literature following PRISMA guidelines was conducted through PubMed and EBSCO databases. Search terms included “Le Fort fracture”, “facial”, “craniofacial”, and “intracranial.”  Articles were selected based on relevance and examined regarding etiology, epidemiology, diagnosis, treatment, complications, and outcomes in adults. The analyzed studies were published between 1980 and 2016. Initial data search yielded 186 results. The search was narrowed to exclude articles lacking in specificity for Le Fort fractures.  Fifty-one articles were selected, the majority of which were large case studies, and collectively reported that Le Fort fractures are most commonly due to high-velocity MVC and that the severity of fracture type sustained occurred with increasing frequency.  It was also found that there is a general lack of published Level I, Level II, and Level III studies regarding Le Fort fracture management, surgical management, and outcomes. The limitation of this study, similar to all PRISMA-guided review articles, is the dependence on previously published research and availability of references as outlined in our methodology. While mortality rates for Le Fort fractures are low, these complex injuries seldom occur in isolation and are associated with other severe injuries to the head and neck. Quick and accurate diagnosis of Le Fort fractures and associated injuries is crucial to the successful management of blunt head trauma. PMID:29177168

Hydrodynamic and Chemical Factors in Clogging by Montmorillonite in Porous Media

PubMed Central

Mays, David C.; Hunt, James R.

2008-01-01

Clogging by colloid deposits is important in water treatment filters, groundwater aquifers, and petroleum reservoirs. The complexity of colloid deposition and deposit morphology preclude models based on first principles, so this study extends an empirical approach to quantify clogging using a simple, one-parameter model. Experiments were conducted with destabilized suspensions of sodium- and calcium-montmorillonite to quantify the hydrodynamic and chemical factors important in clogging. Greater clogging is observed at slower fluid velocity, consistent with previous investigations. However, calcium-montmorillonite causes one order of magnitude less clogging per mass of deposited particles compared to sodium-montmorillonite or a previously published summary of clogging in model granular media. Steady state conditions, in which the permeability and the quantity of deposited material are both constant, were not observed, even though the experimental conditions were optimized for that purpose. These results indicate that hydrodynamic aspects of clogging by these natural materials are consistent with those of simplified model systems, and they demonstrate significant chemical effects on clogging for fully destabilized montmorillonite clay. PMID:17874771

An improved method of measuring heart rate using a webcam

NASA Astrophysics Data System (ADS)

Liu, Yi; Ouyang, Jianfei; Yan, Yonggang

2014-09-01

Measuring heart rate traditionally requires special equipment and physical contact with the subject. Reliable non-contact and low-cost measurements are highly desirable for convenient and comfortable physiological self-assessment. Previous work has shown that consumer-grade cameras can provide useful signals for remote heart rate measurements. In this paper a simple and robust method of measuring the heart rate using low-cost webcam is proposed. Blood volume pulse is extracted by proper Region of Interest (ROI) and color channel selection from image sequences of human faces without complex computation. Heart rate is subsequently quantified by spectrum analysis. The method is successfully applied under natural lighting conditions. Results of experiments show that it takes less time, is much simpler, and has similar accuracy to the previously published and widely used method of Independent Component Analysis (ICA). Benefitting from non-contact, convenience, and low-costs, it provides great promise for popularization of home healthcare and can further be applied to biomedical research.

Hydrodynamic and chemical factors in clogging by montmorillonite in porous media.

PubMed

Mays, David C; Hunt, James R

2007-08-15

Clogging by colloid deposits is important in water treatment filters, groundwater aquifers, and petroleum reservoirs. The complexity of colloid deposition and deposit morphology preclude models based on first principles, so this study extends an empirical approach to quantify clogging using a simple, one-parameter model. Experiments were conducted with destabilized suspensions of sodium- and calcium-montmorillonite to quantify the hydrodynamic and chemical factors important in clogging. Greater clogging is observed at slower fluid velocity, consistent with previous investigations. However, calcium-montmorillonite causes 1 order of magnitude less clogging per mass of deposited particles compared to sodium-montmorillonite or a previously published summary of clogging in model granular media. Steady-state conditions, in which the permeability and the quantity of deposited material are both constant, were not observed, even though the experimental conditions were optimized for that purpose. These results indicate that hydrodynamic aspects of clogging by these natural materials are consistent with those of simplified model systems, and they demonstrate significant chemical effects on clogging for fully destabilized montmorillonite clay.

Simplified and economical 2D IR spectrometer design using a dual acousto-optic modulator

PubMed Central

Skoff, David R.; Laaser, Jennifer E.; Mukherjee, Sudipta S.; Middleton, Chris T.; Zanni, Martin T.

2012-01-01

Over the last decade two-dimensional infrared (2D IR) spectroscopy has proven to be a very useful extension of infrared spectroscopy, yet the technique remains restricted to a small group of specialized researchers because of its experimental complexity and high equipment cost. We report on a spectrometer that is compact, mechanically robust, and is much less expensive than previous designs because it uses a single pixel MCT detector rather than an array detector. Moreover, each axis of the spectrum can be collected in either the time or frequency domain via computer programming. We discuss pulse sequences for scanning the probe axis, which were not previously possible. We present spectra on metal carbonyl compounds at 5 µm and a model peptide at 6 µm. Data collection with a single pixel MCT takes longer than using an array detector, but publishable quality data are still achieved with only a few minutes of averaging. PMID:24659850

Single chamber microbial fuel cell with spiral anode for dairy wastewater treatment.

PubMed

Mardanpour, Mohammad Mahdi; Nasr Esfahany, Mohsen; Behzad, Tayebeh; Sedaqatvand, Ramin

2012-01-01

This study reports on the fabrication of a novel annular single chamber microbial fuel cell (ASCMFC) with spiral anode. The stainless steel mesh anode with graphite coating was used as anode. Dairy wastewater, containing complex organic matter, was used as substrate. ASCMFC had been operated for 450 h and results indicated a high open circuit voltage (about 810 mV) compared with previously published results. The maximum power density of 20.2 W/m(3) obtained in this study is significantly greater than the power densities reported in previous studies. Besides, a maximum coulombic efficiency of 26.87% with 91% COD removal was achieved. Good bacterial adhesion on the spiral anode is clearly shown in SEM micrographs. High power density and a successful performance in wastewater treatment in ASCMFC suggest it as a promising alternative to conventional MFCs for power generation and wastewater treatment. ASCMFC performance as a power generator was characterized based on polarization behavior and cell potentials. Copyright © 2012 Elsevier B.V. All rights reserved.

Fostering Integrity in Research

NASA Astrophysics Data System (ADS)

McNutt, M. K.

2017-12-01

The responsible conduct of research requires that all involved in the research enterprise - researchers, sponsors, reviewers, publishers, and communicators - adhere to a set of integrity principles to protect the public's investment. Given the increasing complexity and globalization of the research enterprise, the National Academies recently re-examined and updated its integrity recommendations for researchers in the report Fostering Integrity in Research, with sponsorship from the National Science Foundation. Major departures from the previous recommendations 25-years earlier are the recognition that practices that were previously classified as merely questionable are indeed detrimental to the responsible conduct of research. Furthermore, the report concludes that there has been insufficient effort to respond to the threats that lapses in research integrity pose to the quality of research products and the reputation of researchers as deserving of the public trust. It recommends the creation of an independent, non-profit entity dedicated to promoting research integrity by serving as a resource and clearing house for expertise, advice, materials, and best practices on fostering research integrity and responding to allegations of research misconduct.

Battery Test Manual For Plug-In Hybrid Electric Vehicles

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

Jeffrey R. Belt

2010-09-01

This battery test procedure manual was prepared for the United States Department of Energy (DOE), Office of Energy Efficiency and Renewable Energy (EERE), Vehicle Technologies Program. It is based on technical targets established for energy storage development projects aimed at meeting system level DOE goals for Plug-in Hybrid Electric Vehicles (PHEV). The specific procedures defined in this manual support the performance and life characterization of advanced battery devices under development for PHEV’s. However, it does share some methods described in the previously published battery test manual for power-assist hybrid electric vehicles. Due to the complexity of some of the proceduresmore » and supporting analysis, a revision including some modifications and clarifications of these procedures is expected. As in previous battery and capacitor test manuals, this version of the manual defines testing methods for full-size battery systems, along with provisions for scaling these tests for modules, cells or other subscale level devices.« less

Battery Test Manual For Plug-In Hybrid Electric Vehicles

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

Jeffrey R. Belt

2010-12-01

This battery test procedure manual was prepared for the United States Department of Energy (DOE), Office of Energy Efficiency and Renewable Energy (EERE), Vehicle Technologies Program. It is based on technical targets established for energy storage development projects aimed at meeting system level DOE goals for Plug-in Hybrid Electric Vehicles (PHEV). The specific procedures defined in this manual support the performance and life characterization of advanced battery devices under development for PHEV’s. However, it does share some methods described in the previously published battery test manual for power-assist hybrid electric vehicles. Due to the complexity of some of the proceduresmore » and supporting analysis, a revision including some modifications and clarifications of these procedures is expected. As in previous battery and capacitor test manuals, this version of the manual defines testing methods for full-size battery systems, along with provisions for scaling these tests for modules, cells or other subscale level devices.« less

The newest international trend about regulation of indoor radon.

PubMed

Bochicchio, Francesco

2011-07-01

On the basis of recent epidemiological findings, many international and national organisations have revised their recommendations and regulations on radon exposure in dwellings and workplaces, or are in the process to do it. In particular, new recommendations and regulations were recently published (or are going to be) by World Health Organization, Nordic Countries, International Commission on Radiological Protection, International, Atomic Energy Agency (and the other international organisations sponsoring the International Basic Safety Standards), European Commission. Although with some differences, these new documents recommend lower radon concentrations in indoor air, especially in dwellings, compared with previous ones. Moreover, preventive measures in all new buildings are more and more considered as one of the most cost-effective way to reduce the radon-related lung cancers, compared with previous approach restricting preventive measures in radon-prone areas only. A comprehensive national action plan, involving several national and local authorities, is generally considered a necessary tool to deal with the many complex actions needed to reduce the risk from radon exposure in an effective way.

The giraffe (Giraffa camelopardalis) rumen microbiome.

PubMed

Roggenbuck, Michael; Sauer, Cathrine; Poulsen, Morten; Bertelsen, Mads F; Sørensen, Søren J

2014-10-01

Recent studies have shown that wild ruminants are sources of previously undescribed microorganisms, knowledge of which can improve our understanding of the complex microbial interactions in the foregut. Here, we investigated the microbial community of seven wild-caught giraffes (Giraffa camelopardalis), three of which were fed natural browse and four were fed Boskos pellets, leafy alfalfa hay, and cut savanna browse, by characterizing the 16S rRNA gene diversity using 454 FLX high-throughput sequencing. The microbial community composition varied according to diet, but differed little between the ruminal fluid and solid fraction. The giraffe rumen contained large levels of the phyla of Firmicutes and Bacteroidetes independent of diet, while Prevotella, Succinclasticium, and Methanobrevibacter accounted for the largest abundant taxonomic assigned genera. However, up to 21% of the generated sequences could not been assigned to any known bacterial phyla, and c. 70% not to genus, revealing that the giraffe rumen hosts a variety of previously undescribed bacteria. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Vertical coherence of deformation in lithosphere in the eastern Himalayan syntaxis using GPS, Quaternary fault slip rates, and shear wave splitting data

NASA Astrophysics Data System (ADS)

Chang, Lijun; Flesch, Lucy M.; Wang, Chun-Yung; Ding, Zhifeng

2015-07-01

We present 59 new SKS/SKKS and combine them with 69 previously published data to infer the mantle deformation field in SE Tibet. The dense set of anisotropy measurements in the eastern Himalayan syntaxis (EHS) are oriented along a NE-SW azimuth and rotate clockwise in the surround regions. We use GPS measurements and geologic data to determine a continuous surface deformation field that is then used to predict shear wave spitting directions at each station. Comparison of splitting observations with predictions yields an average misfit of 11.7° illustrating that deformation is vertically coherent, consistent with previous studies. Within the central EHS in areas directly surrounding the Namche-Barwa metamorphic massif, the average misfit of 11 stations increases to 60.8°, and vertical coherence is no longer present. The complexity of the mantle anisotropy and surface observations argues for local alteration of the strain fields here associated with recent rapid exhumation of the Indian crust.

Crumbs 2 prevents cortical abnormalities in mouse dorsal telencephalon.

PubMed

Dudok, Jacobus J; Murtaza, Mariyam; Henrique Alves, C; Rashbass, Pen; Wijnholds, Jan

2016-07-01

The formation of a functionally integrated nervous system is dependent on a highly organized sequence of events that includes timely division and differentiation of progenitors. Several apical polarity proteins have been shown to play crucial roles during neurogenesis, however, the role of Crumbs 2 (CRB2) in cortical development has not previously been reported. Here, we show that conditional ablation of Crb2 in the murine dorsal telencephalon leads to defects in the maintenance of the apical complex. Furthermore, within the mutant dorsal telencephalon there is premature expression of differentiation proteins. We examined the physiological function of Crb2 on wild type genetic background as well as on background lacking Crb1. Telencephalon lacking CRB2 resulted in reduced levels of PALS1 and CRB3 from the apical complex, an increased number of mitotic cells and expanded neuronal domain. These defects are transient and therefore only result in rather mild cortical abnormalities. We show that CRB2 is required for maintenance of the apical polarity complex during development of the cortex and regulation of cell division, and that loss of CRB2 results in cortical abnormalities. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Management of complex pediatric laryngotracheal stenosis with skin graft reconstruction.

PubMed

Bowe, Sarah N; Wentland, Carissa J; Sandhu, G S; Hartnick, Christopher J

2018-05-01

For pediatric patients with laryngotracheal stenosis, the ultimate goal is creation of a safe, functional airway. Unfortunately, wound healing in a hollow structure can complicate repair attempts, leading to restenosis. Herein, we present our experience using skin-grafting techniques in two complex pediatric laryngotracheal stenosis cases, leading to successful decannulation or speech production. A chart review was performed examining the evaluation and management of two pediatric patients with laryngotracheal stenosis despite prior reconstructive attempts. Patient history, bronchoscopic evaluation, intra-operative technique, post-operative management, treatment outcomes, and complications were noted. Harvesting and preparation of the split-thickness skin grafts (STSG) proceeded in a similar manner for each case. Stenting material varied based on the clinical scenario. Using this technique, our patient with a Type 3 glottic web achieved substantial improvement in exercise tolerance, as well as vocal strength and quality. In addition, our aphonic patient could vocalize for the first time since her laryngotracheal injury. Temporary endoluminal stenting with skin graft lining can reproduce epithelial continuity and provide "biological inhibition" to enhance the wound healing process. When previous reconstructive efforts have failed, use of STSG can be considered in the management of complex pediatric laryngotracheal stenosis. Copyright © 2018. Published by Elsevier B.V.

Heart transplantation in adults with congenital heart disease.

PubMed

Houyel, Lucile; To-Dumortier, Ngoc-Tram; Lepers, Yannick; Petit, Jérôme; Roussin, Régine; Ly, Mohamed; Lebret, Emmanuel; Fadel, Elie; Hörer, Jürgen; Hascoët, Sébastien

2017-05-01

With the advances in congenital cardiac surgery and postoperative care, an increasing number of children with complex congenital heart disease now reach adulthood. There are already more adults than children living with a congenital heart defect, including patients with complex congenital heart defects. Among these adults with congenital heart disease, a significant number will develop ventricular dysfunction over time. Heart failure accounts for 26-42% of deaths in adults with congenital heart defects. Heart transplantation, or heart-lung transplantation in Eisenmenger syndrome, then becomes the ultimate therapeutic possibility for these patients. This population is deemed to be at high risk of mortality after heart transplantation, although their long-term survival is similar to that of patients transplanted for other reasons. Indeed, heart transplantation in adults with congenital heart disease is often challenging, because of several potential problems: complex cardiac and vascular anatomy, multiple previous palliative and corrective surgeries, and effects on other organs (kidney, liver, lungs) of long-standing cardiac dysfunction or cyanosis, with frequent elevation of pulmonary vascular resistance. In this review, we focus on the specific problems relating to heart and heart-lung transplantation in this population, revisit the indications/contraindications, and update the long-term outcomes. Copyright © 2017. Published by Elsevier Masson SAS.

Complex I deficiency related to T10158C mutation ND3 gene: A further definition of the clinical spectrum.

PubMed

Grosso, Salvatore; Carluccio, Maria Alessandra; Cardaioli, Elena; Cerase, Alfonso; Malandrini, Alessandro; Romano, Chiara; Federico, Antonio; Dotti, Maria Teresa

2017-03-01

Complex I deficiency is the most common energy generation disorder which may clinically present at any age with a wide spectrum of symptoms and signs. The T10158C mutation ND3 gene is rare and occurs in patients showing an early rapid neurological deterioration invariably leading to death after a few months. We report a 9year-old boy with a mtDNA T10158C mutation showing a mild MELAS-like phenotype and brain MRI features congruent with both MELAS and Leigh syndrome. Epilepsia partialis continua also occurred in the clinical course and related to a mild cortical atrophy of the left perisylvian area. The present case confirms that the clinical spectrum of Complex I deficiency related to T10158C mutation ND3 gene is wider than previously described. Our observation further suggests that testing mutation in the MT-ND3 gene should be included in the diagnostic work-up of patients presenting with epilepsia partialis continua accompanied by suspicion of mitochondrial disorder. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[Results of revision after failed surgical treatment for traumatic anterior shoulder instability].

PubMed

Lópiz-Morales, Y; Alcobe-Bonilla, J; García-Fernández, C; Francés-Borrego, A; Otero-Fernández, R; Marco-Martínez, F

2013-01-01

Persistent or recurrent glenohumeral instability after a previous operative stabilization can be a complex problem. Our aim is to establish the incidence of recurrence and its revision surgery, and to analyse the functional results of the revision instability surgery, as well as to determine surgical protocols to perform it. A retrospective analysis was conducted on 16 patients with recurrent instability out of 164 patients operated on between 1999 and 2011. The mean follow-up was 57 months and the mean age was 29 years. To evaluate functional outcome we employed Constant, Rowe, UCLA scores and the visual analogue scale. Of the 12 patients who failed the initial arthroscopic surgery, 6 patients underwent an arthroscopic antero-inferior labrum repair technique, 4 using open labrum repair techniques, and 2 coracoid transfer. The two cases of open surgery with recurrences underwent surgery for coracoid transfer. Results of the Constant score were excellent or good in 64% of patients. Surgical revision of instability is a complex surgery essentially for two reasons: the difficulty in recognising the problem, and the technical demand (greater variety and the increasingly complex techniques). Copyright © 2012 SECOT. Published by Elsevier Espana. All rights reserved.

Three-factor models versus time series models: quantifying time-dependencies of interactions between stimuli in cell biology and psychobiology for short longitudinal data.

PubMed

Frank, Till D; Kiyatkin, Anatoly; Cheong, Alex; Kholodenko, Boris N

2017-06-01

Signal integration determines cell fate on the cellular level, affects cognitive processes and affective responses on the behavioural level, and is likely to be involved in psychoneurobiological processes underlying mood disorders. Interactions between stimuli may subjected to time effects. Time-dependencies of interactions between stimuli typically lead to complex cell responses and complex responses on the behavioural level. We show that both three-factor models and time series models can be used to uncover such time-dependencies. However, we argue that for short longitudinal data the three factor modelling approach is more suitable. In order to illustrate both approaches, we re-analysed previously published short longitudinal data sets. We found that in human embryonic kidney 293 cells cells the interaction effect in the regulation of extracellular signal-regulated kinase (ERK) 1 signalling activation by insulin and epidermal growth factor is subjected to a time effect and dramatically decays at peak values of ERK activation. In contrast, we found that the interaction effect induced by hypoxia and tumour necrosis factor-alpha for the transcriptional activity of the human cyclo-oxygenase-2 promoter in HEK293 cells is time invariant at least in the first 12-h time window after stimulation. Furthermore, we applied the three-factor model to previously reported animal studies. In these studies, memory storage was found to be subjected to an interaction effect of the beta-adrenoceptor agonist clenbuterol and certain antagonists acting on the alpha-1-adrenoceptor / glucocorticoid-receptor system. Our model-based analysis suggests that only if the antagonist drug is administer in a critical time window, then the interaction effect is relevant. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Clinicopathological analysis of near-tetraploidy/tetraploidy acute myeloid leukaemia.

PubMed

Pang, Changlee S; Pettenati, Mark J; Pardee, Timothy S

2015-03-01

Near-tetraploidy/tetraploidy (NT/T) is a rare cytogenetic alteration in acute myeloid leukaemia (AML). NT/T-AML is categorised as complex cytogenetics and therefore, presumed to have an unfavourable prognosis. Our aim is to further characterise the clinical, morphological, cytogenetic and prognostic features of NT/T-AML. We searched our cytogenetic laboratory database from 1991 to 2012 to reveal 13 cases of NT/T-AML. Each case was evaluated with regard to its demographics, morphology, immunophenotype and prognosis. Specific morphological features included blast size, irregularity of nuclear contours, cytoplasmic vacuoles, and presence and lineage of dysplasia. Eleven men and two women had a median age of 68 years. Blasts were predominately large (11/13). Eight of 13 patients had AML with myelodysplasia-related changes. Sixty-nine per cent of patients achieved complete remission (CR). Median overall survival (OS) was 8.6 months. CR rate and median OS in cases with ≥ 5 cytogenetic abnormalities were 71% and 6 months, compared with 67% and 18.1 months in cases with <5 abnormalities. NT/T-AML occurs in older males, exhibits large blast size and is associated with myelodysplasia. Unlike previously reported data, our study reveals an overall better prognosis in this older population with NT/T-AML than was expected for a complex karyotype AML. Cytogenetic complexity independent of ploidy status did not greatly affect the high CR rates, but did appear to be a better estimation of prognostic risk in terms of median OS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Computational Model of Gab1/2-Dependent VEGFR2 Pathway to Akt Activation

PubMed Central

Tan, Wan Hua; Popel, Aleksander S.; Mac Gabhann, Feilim

2013-01-01

Vascular endothelial growth factor (VEGF) signal transduction is central to angiogenesis in development and in pathological conditions such as cancer, retinopathy and ischemic diseases. However, no detailed mass-action models of VEGF receptor signaling have been developed. We constructed and validated the first computational model of VEGFR2 trafficking and signaling, to study the opposing roles of Gab1 and Gab2 in regulation of Akt phosphorylation in VEGF-stimulated endothelial cells. Trafficking parameters were optimized against 5 previously published in vitro experiments, and the model was validated against six independent published datasets. The model showed agreement at several key nodes, involving scaffolding proteins Gab1, Gab2 and their complexes with Shp2. VEGFR2 recruitment of Gab1 is greater in magnitude, slower, and more sustained than that of Gab2. As Gab2 binds VEGFR2 complexes more transiently than Gab1, VEGFR2 complexes can recycle and continue to participate in other signaling pathways. Correspondingly, the simulation results show a log-linear relationship between a decrease in Akt phosphorylation and Gab1 knockdown while a linear relationship was observed between an increase in Akt phosphorylation and Gab2 knockdown. Global sensitivity analysis demonstrated the importance of initial-concentration ratios of antagonistic molecular species (Gab1/Gab2 and PI3K/Shp2) in determining Akt phosphorylation profiles. It also showed that kinetic parameters responsible for transient Gab2 binding affect the system at specific nodes. This model can be expanded to study multiple signaling contexts and receptor crosstalk and can form a basis for investigation of therapeutic approaches, such as tyrosine kinase inhibitors (TKIs), overexpression of key signaling proteins or knockdown experiments. PMID:23805312

Random Survival Forest in practice: a method for modelling complex metabolomics data in time to event analysis.

PubMed

Dietrich, Stefan; Floegel, Anna; Troll, Martina; Kühn, Tilman; Rathmann, Wolfgang; Peters, Anette; Sookthai, Disorn; von Bergen, Martin; Kaaks, Rudolf; Adamski, Jerzy; Prehn, Cornelia; Boeing, Heiner; Schulze, Matthias B; Illig, Thomas; Pischon, Tobias; Knüppel, Sven; Wang-Sattler, Rui; Drogan, Dagmar

2016-10-01

The application of metabolomics in prospective cohort studies is statistically challenging. Given the importance of appropriate statistical methods for selection of disease-associated metabolites in highly correlated complex data, we combined random survival forest (RSF) with an automated backward elimination procedure that addresses such issues. Our RSF approach was illustrated with data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, with concentrations of 127 serum metabolites as exposure variables and time to development of type 2 diabetes mellitus (T2D) as outcome variable. Out of this data set, Cox regression with a stepwise selection method was recently published. Replication of methodical comparison (RSF and Cox regression) was conducted in two independent cohorts. Finally, the R-code for implementing the metabolite selection procedure into the RSF-syntax is provided. The application of the RSF approach in EPIC-Potsdam resulted in the identification of 16 incident T2D-associated metabolites which slightly improved prediction of T2D when used in addition to traditional T2D risk factors and also when used together with classical biomarkers. The identified metabolites partly agreed with previous findings using Cox regression, though RSF selected a higher number of highly correlated metabolites. The RSF method appeared to be a promising approach for identification of disease-associated variables in complex data with time to event as outcome. The demonstrated RSF approach provides comparable findings as the generally used Cox regression, but also addresses the problem of multicollinearity and is suitable for high-dimensional data. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Assessing visual function in children with complex disabilities: the Bradford visual function box.

PubMed

Pilling, Rachel F; Outhwaite, Louise; Bruce, Alison

2016-08-01

Assessment of children with complex and severe learning disabilities is challenging and the children may not respond to the monochrome stimuli of traditional tests. The International Association of Scientific Studies on Intellectual Disability recommends that visual function assessment in poorly or non-cooperative children should be undertaken in an objective manner. We have developed a functional visual assessment tool to assess vision in children with complex and multiple disabilities. The Bradford visual function box (BVFB) comprises a selection of items (small toys) of different size and colour, which are presented to the child and the response observed. The aim of this study is to establish its intertester validity in children with severe learning disability. The visual function of 22 children with severe learning disability was assessed using the BVFB. The children were assessed by experienced practitioners on two separate occasions. The assessors were unaware of each other's findings. In 15/22 of the children, no difference was found in the results of the two assessors. The test was shown to have a good intertester agreement, weighted κ=0.768. The results of this clinical study show that the BVFB is a reliable tool for assessing the visual function in children with severe learning disability in whom other tests fail to elicit a response. The need for a tool which is quick to administer and portable has previously been highlighted. The BVFB offers an option for children for whom other formal tests are unsuccessful in eliciting a response. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

15 CFR 10.10 - Review of published standards.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Review of published standards. 10.10... DEVELOPMENT OF VOLUNTARY PRODUCT STANDARDS § 10.10 Review of published standards. (a) Each standard published... considered until a replacement standard is published. (b) Each standard published under these or previous...

Distributed biotin-streptavidin transcription roadblocks for mapping cotranscriptional RNA folding.

PubMed

Strobel, Eric J; Watters, Kyle E; Nedialkov, Yuri; Artsimovitch, Irina; Lucks, Julius B

2017-07-07

RNA folding during transcription directs an order of folding that can determine RNA structure and function. However, the experimental study of cotranscriptional RNA folding has been limited by the lack of easily approachable methods that can interrogate nascent RNA structure at nucleotide resolution. To address this, we previously developed cotranscriptional selective 2΄-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-Seq) to simultaneously probe all intermediate RNA transcripts during transcription by stalling elongation complexes at catalytically dead EcoRIE111Q roadblocks. While effective, the distribution of elongation complexes using EcoRIE111Q requires laborious PCR using many different oligonucleotides for each sequence analyzed. Here, we improve the broad applicability of cotranscriptional SHAPE-Seq by developing a sequence-independent biotin-streptavidin (SAv) roadblocking strategy that simplifies the preparation of roadblocking DNA templates. We first determine the properties of biotin-SAv roadblocks. We then show that randomly distributed biotin-SAv roadblocks can be used in cotranscriptional SHAPE-Seq experiments to identify the same RNA structural transitions related to a riboswitch decision-making process that we previously identified using EcoRIE111Q. Lastly, we find that EcoRIE111Q maps nascent RNA structure to specific transcript lengths more precisely than biotin-SAv and propose guidelines to leverage the complementary strengths of each transcription roadblock in cotranscriptional SHAPE-Seq. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Recombinational hotspot specific to female meiosis in the mouse major histocompatibility complex.

PubMed

Shiroishi, T; Hanzawa, N; Sagai, T; Ishiura, M; Gojobori, T; Steinmetz, M; Moriwaki, K

1990-01-01

The wm7 haplotype of the major histocompatibility complex (MHC), derived from the Japanese wild mouse Mus musculus molossinus, enhances recombination specific to female meiosis in the K/A beta interval of the MHC. We have mapped crossover points of fifteen independent recombinants from genetic crosses of the wm7 and laboratory haplotypes. Most of them were confined to a short segment of approximately 1 kilobase (kb) of DNA between the A beta 3 and A beta 2 genes, indicating the presence of a female-specific recombinational hotspot. Its location overlaps with a sex-independent hotspot previously identified in the Mus musculus castaneus CAS3 haplotype. We have cloned and sequenced DNA fragments surrounding the hotspot from the wm7 haplotype and the corresponding regions from the hotspot-negative B10.A and C57BL/10 strains. There is no significant difference between the sequences of these three strains, or between these and the published sequences of the CAS3 and C57BL/6 strains. However, a comparison of this A beta 3/A beta 2 hotspot with a previously characterized hotspot in the E beta gene revealed that they have a very similar molecular organization. Each hotspot consists of two elements, the consensus sequence of the mouse middle repetitive MT family and the tetrameric repeated sequences, which are separated by 1 kb of DNA.

Effects of OXPHOS complex deficiencies and ESA dysfunction in working intact skeletal muscle: implications for mitochondrial myopathies.

PubMed

Korzeniewski, Bernard

2015-10-01

The effects of inborn oxidative phosphorylation (OXPHOS) complex deficiencies or possible each-step activation (ESA) dysfunction on the bioenergetic system in working intact skeletal muscle are studied using a computer model of OXPHOS published previously. The curves representing the dependencies of V˙O2 and metabolite concentrations on single complex activity, entire OXPHOS activity or ESA intensity exhibit a characteristic threshold at some OXPHOS complex activity/ESA intensity. This threshold for V˙O2 of single complex activities is significantly lower in intact muscle during moderate and heavy work, than in isolated mitochondria in state 3. Metabolite concentrations and pH in working muscle start to change significantly at much higher OXPHOS complex activities/ESA intensities than V˙O2. The effect of entire OXPHOS deficiency or ESA dysfunction is potentially much stronger than the effect of a single complex deficiency. Implications of these findings for the genesis of mitochondrial myopathies are discussed. It is concluded that V˙O2 in state 3 and its dependence on complex activity in isolated mitochondria is not a universal quantitative determinant of the effect of mitochondrial dysfunctions in vivo. Moderate and severe mitochondria dysfunctions are defined: the former affect significantly only metabolite concentrations and pH, while the latter also decrease significantly V˙O2 in intact skeletal muscle during work. The dysfunction-caused decrease in V˙O2/oxidative ATP synthesis flux, disturbance of metabolite homeostasis, elevated ROS production and anaerobic glycolysis recruitment can account for such mitochondrial myopathy symptoms as muscle weakness, exercise intolerance (exertional fatigue) and lactic acidosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Arthropod phylogenetics in light of three novel millipede (myriapoda: diplopoda) mitochondrial genomes with comments on the appropriateness of mitochondrial genome sequence data for inferring deep level relationships.

PubMed

Brewer, Michael S; Swafford, Lynn; Spruill, Chad L; Bond, Jason E

2013-01-01

Arthropods are the most diverse group of eukaryotic organisms, but their phylogenetic relationships are poorly understood. Herein, we describe three mitochondrial genomes representing orders of millipedes for which complete genomes had not been characterized. Newly sequenced genomes are combined with existing data to characterize the protein coding regions of myriapods and to attempt to reconstruct the evolutionary relationships within the Myriapoda and Arthropoda. The newly sequenced genomes are similar to previously characterized millipede sequences in terms of synteny and length. Unique translocations occurred within the newly sequenced taxa, including one half of the Appalachioria falcifera genome, which is inverted with respect to other millipede genomes. Across myriapods, amino acid conservation levels are highly dependent on the gene region. Additionally, individual loci varied in the level of amino acid conservation. Overall, most gene regions showed low levels of conservation at many sites. Attempts to reconstruct the evolutionary relationships suffered from questionable relationships and low support values. Analyses of phylogenetic informativeness show the lack of signal deep in the trees (i.e., genes evolve too quickly). As a result, the myriapod tree resembles previously published results but lacks convincing support, and, within the arthropod tree, well established groups were recovered as polyphyletic. The novel genome sequences described herein provide useful genomic information concerning millipede groups that had not been investigated. Taken together with existing sequences, the variety of compositions and evolution of myriapod mitochondrial genomes are shown to be more complex than previously thought. Unfortunately, the use of mitochondrial protein-coding regions in deep arthropod phylogenetics appears problematic, a result consistent with previously published studies. Lack of phylogenetic signal renders the resulting tree topologies as suspect. As such, these data are likely inappropriate for investigating such ancient relationships.

Review of Sexuality Studies in Africa: Setting a New Post-2015 Research Agenda.

PubMed

Akinyemi, Joshua O; De Wet, Nicole; Odimegwu, Clifford O

2016-03-01

At the nexus between reproductive health, population and development is the subject of sexuality which has generated extensive discourse in the past two decades. In this paper, we review Africa sexuality studies published between 1994 and 2015 with the aim of synthesizing the available evidence and suggesting a new research agenda for post-2015. Review findings showed that previous studies covered the five components of sexuality - practices, partners, pleasure/pressure/pain, procreation and power to different extents. Risky sexual behaviour was prevalent from adolescence till older ages. Literature on pleasure, pain, procreation and power reflect the complex diversity driven by traditional norms, gender roles and attitudes across the continent. Knowledge gaps were highlighted and new agenda suggested for sexuality research.

Quasi-conformal mapping with genetic algorithms applied to coordinate transformations

NASA Astrophysics Data System (ADS)

González-Matesanz, F. J.; Malpica, J. A.

2006-11-01

In this paper, piecewise conformal mapping for the transformation of geodetic coordinates is studied. An algorithm, which is an improved version of a previous algorithm published by Lippus [2004a. On some properties of piecewise conformal mappings. Eesti NSV Teaduste Akademmia Toimetised Füüsika-Matemaakika 53, 92-98; 2004b. Transformation of coordinates using piecewise conformal mapping. Journal of Geodesy 78 (1-2), 40] is presented; the improvement comes from using a genetic algorithm to partition the complex plane into convex polygons, whereas the original one did so manually. As a case study, the method is applied to the transformation of the Spanish datum ED50 and ETRS89, and both its advantages and disadvantages are discussed herein.

Improvements, testing and development of the ADM-τ sub-grid surface tension model for two-phase LES

NASA Astrophysics Data System (ADS)

Aniszewski, Wojciech

2016-12-01

In this paper, a specific subgrid term occurring in Large Eddy Simulation (LES) of two-phase flows is investigated. This and other subgrid terms are presented, we subsequently elaborate on the existing models for those and re-formulate the ADM-τ model for sub-grid surface tension previously published by these authors. This paper presents a substantial, conceptual simplification over the original model version, accompanied by a decrease in its computational cost. At the same time, it addresses the issues the original model version faced, e.g. introduces non-isotropic applicability criteria based on resolved interface's principal curvature radii. Additionally, this paper introduces more throughout testing of the ADM-τ, in both simple and complex flows.

Sam68 Allows Selective Targeting of Human Cancer Stem Cells.

PubMed

Benoit, Yannick D; Mitchell, Ryan R; Risueño, Ruth M; Orlando, Luca; Tanasijevic, Borko; Boyd, Allison L; Aslostovar, Lili; Salci, Kyle R; Shapovalova, Zoya; Russell, Jennifer; Eguchi, Masakatsu; Golubeva, Diana; Graham, Monica; Xenocostas, Anargyros; Trus, Michael R; Foley, Ronan; Leber, Brian; Collins, Tony J; Bhatia, Mickie

2017-07-20

Targeting of human cancer stem cells (CSCs) requires the identification of vulnerabilities unique to CSCs versus healthy resident stem cells (SCs). Unfortunately, dysregulated pathways that support transformed CSCs, such as Wnt/β-catenin signaling, are also critical regulators of healthy SCs. Using the ICG-001 and CWP family of small molecules, we reveal Sam68 as a previously unappreciated modulator of Wnt/β-catenin signaling within CSCs. Disruption of CBP-β-catenin interaction via ICG-001/CWP induces the formation of a Sam68-CBP complex in CSCs that alters Wnt signaling toward apoptosis and differentiation induction. Our study identifies Sam68 as a regulator of human CSC vulnerability. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

FAP finds FGF21 easy to digest.

PubMed

Gillum, Matthew P; Potthoff, Matthew J

2016-05-01

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates carbohydrate and lipid metabolism. In humans, circulating FGF21 is inactivated by proteolytic cleavage of its C-terminus, thereby preventing signalling through a receptor complex. The mechanism for this cleavage event and the factors contributing to the post-translational regulation of FGF21 activity has previously been unknown. In a recent issue of the Biochemical Journal, Zhen et al. have identified fibroblast activation protein (FAP) as the endopeptidase responsible for this site-specific cleavage of human FGF21 (hFGF21), and propose that inhibition of FAP may be a therapeutic strategy to increase endogenous levels of active FGF21. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Gi- and Gs-coupled GPCRs show different modes of G-protein binding.

PubMed

Van Eps, Ned; Altenbach, Christian; Caro, Lydia N; Latorraca, Naomi R; Hollingsworth, Scott A; Dror, Ron O; Ernst, Oliver P; Hubbell, Wayne L

2018-03-06

More than two decades ago, the activation mechanism for the membrane-bound photoreceptor and prototypical G protein-coupled receptor (GPCR) rhodopsin was uncovered. Upon light-induced changes in ligand-receptor interaction, movement of specific transmembrane helices within the receptor opens a crevice at the cytoplasmic surface, allowing for coupling of heterotrimeric guanine nucleotide-binding proteins (G proteins). The general features of this activation mechanism are conserved across the GPCR superfamily. Nevertheless, GPCRs have selectivity for distinct G-protein family members, but the mechanism of selectivity remains elusive. Structures of GPCRs in complex with the stimulatory G protein, G s , and an accessory nanobody to stabilize the complex have been reported, providing information on the intermolecular interactions. However, to reveal the structural selectivity filters, it will be necessary to determine GPCR-G protein structures involving other G-protein subtypes. In addition, it is important to obtain structures in the absence of a nanobody that may influence the structure. Here, we present a model for a rhodopsin-G protein complex derived from intermolecular distance constraints between the activated receptor and the inhibitory G protein, G i , using electron paramagnetic resonance spectroscopy and spin-labeling methodologies. Molecular dynamics simulations demonstrated the overall stability of the modeled complex. In the rhodopsin-G i complex, G i engages rhodopsin in a manner distinct from previous GPCR-G s structures, providing insight into specificity determinants. Copyright © 2018 the Author(s). Published by PNAS.

Deconstructing the simplification of jury instructions: How simplifying the features of complexity affects jurors' application of instructions.

PubMed

Baguley, Chantelle M; McKimmie, Blake M; Masser, Barbara M

2017-06-01

Research consistently shows that techniques currently used to simplify jury instructions do not always improve mock jurors' comprehension. If improvements are observed, these are limited and overall comprehension remains low. It is unclear, however, why this occurs. It is possible that current simplification techniques do not effectively simplify the features of complexity, present in standardized instructions, which have the greatest effect on jurors' comprehension. It is not yet known, however, how much each feature of complexity individually affects jurors' comprehension. To investigate this, the authors used existing data from published empirical studies to examine how simplifying each feature of complexity affects mock jurors' application of instructions, as jurors can only apply instructions to the extent they understand them. The results suggest that reducing the conceptual complexity and proportion of supplementary information was associated with increased application of the instructions; however, reducing both the linguistic complexity and amount of information, and providing the instructions in a written format was not. In addition, results showed an unexpected adverse effect of simplification-reducing the amount of information was associated with an increase in the punitiveness of mock jurors' verdicts, independently of the instruction content. Together, these results suggest a need to make jury instructions comprehensible, highlight the key principles in the decision-process, and identify a way to eliminate the negative effect of reducing the amount of information. Addressing these needs is essential for developing a simplification technique that maximizes jurors' comprehension and application of instructions, while minimizing the previously overlooked negative effects of simplification. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Immediate Flow Disruption as a Prognostic Factor After Flow Diverter Treatment: Long-Term Experience with the Pipeline Embolization Device.

PubMed

Dodier, Philippe; Frischer, Josa M; Wang, Wei-Te; Auzinger, Thomas; Mallouhi, Ammar; Serles, Wolfgang; Gruber, Andreas; Knosp, Engelbert; Bavinzski, Gerhard

2018-05-01

To report long-term results after Pipeline Embolization Device (PED) implantation, characterize complex and standard aneurysms comprehensively, and introduce a modified flow disruption scale. We retrospectively reviewed a consecutive series of 40 patients harboring 59 aneurysms treated with 54 PEDs. Aneurysm complexity was assessed using our proposed classification. Immediate angiographic results were analyzed using previously published grading scales and our novel flow disruption scale. According to our new definition, 46 (78%) aneurysms were classified as complex. Most PED interventions were performed in the paraophthalmic and cavernous internal carotid artery segments. Excellent neurologic outcome (modified Rankin Scale 0 and 1) was observed in 94% of patients. Our data showed low permanent procedure-related mortality (0%) and morbidity (3%) rates. Long-term angiographic follow-up showed complete occlusion in 81% and near-total obliteration in a further 14%. Complete obliteration after deployment of a single PED was achieved in all standard aneurysms with 1-year follow-up. Our new scale was an independent predictor of aneurysm occlusion in a multivariable analysis. All aneurysms with a high flow disruption grade showed complete occlusion at follow-up regardless of PED number or aneurysm complexity. Treatment with the PED should be recognized as a primary management strategy for a highly selected cohort with predominantly complex intracranial aneurysms. We further show that a priori assessment of aneurysm complexity and our new postinterventional angiographic flow disruption scale predict occlusion probability and may help to determine the adequate number of per-aneurysm devices. Copyright © 2018 Elsevier Inc. All rights reserved.

Diversity and Distribution of Cryptic Species of the Bemisia tabaci (Hemiptera: Aleyrodidae) complex in Pakistan.

PubMed

Masood, Mariyam; Amin, Imran; Hassan, Ishtiaq; Mansoor, Shahid; Brown, Judith K; Briddon, Rob W

2017-12-05

Bemisia tabaci (Gennadius; Hempitera: Aleyrodidae) is considered to be a cryptic (sibling) species complex, the members of which exhibit morphological invariability while being genetically and behaviorally distinct. Members of the complex are agricultural pests that cause direct damage by feeding on plants, and indirectly by transmitting viruses that cause diseases leading to reduced crop yield and quality. In Pakistan, cotton leaf curl disease, caused by multiple begomovirus species, is the most economically important viral disease of cotton. In the study outlined here, the diversity and geographic distribution of B. tabaci cryptic species was investigated by analyzing a taxonomically informative fragment of the mitochondrial cytochrome c oxidase 1 gene (mtCOI-3'). The mtCOI-3' sequence was determined for 285 adult whiteflies and found to represent six cryptic species, the most numerous being Asia II-1 and Middle East Asia Minor 1 (MEAM-1), the later also referred to as the B-biotype, which was previously thought to be confined to Sindh province but herein, was also found to be present in the Punjab province. The endemic Asia I was restricted to Sindh province, while an individual in the Asia II-8 was identified in Pakistan for the first time. Also for the first time, samples were collected from northwestern Pakistan and Asia II-1 was identified. Results indicate that in Pakistan the overall diversity of B. tabaci cryptic species is high and, based on comparisons with findings from previous studies, the distribution is dynamic. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Panel-based whole exome sequencing identifies novel mutations in microphthalmia and anophthalmia patients showing complex Mendelian inheritance patterns.

PubMed

Riera, Marina; Wert, Ana; Nieto, Isabel; Pomares, Esther

2017-11-01

Microphthalmia and anophthalmia (MA) are congenital eye abnormalities that show an extremely high clinical and genetic complexity. In this study, we evaluated the implementation of whole exome sequencing (WES) for the genetic analysis of MA patients. This approach was used to investigate three unrelated families in which previous single-gene analyses failed to identify the molecular cause. A total of 47 genes previously associated with nonsyndromic MA were included in our panel. WES was performed in one affected patient from each family using the AmpliSeq TM Exome technology and the Ion Proton TM platform. A novel heterozygous OTX2 missense mutation was identified in a patient showing bilateral anophthalmia who inherited the variant from a parent who was a carrier, but showed no sign of the condition. We also describe a new PAX6 missense variant in an autosomal-dominant pedigree affected by mild bilateral microphthalmia showing high intrafamiliar variability, with germline mosaicism determined to be the most plausible molecular cause of the disease. Finally, a heterozygous missense mutation in RBP4 was found to be responsible in an isolated case of bilateral complex microphthalmia. This study highlights that panel-based WES is a reliable and effective strategy for the genetic diagnosis of MA. Furthermore, using this technique, the mutational spectrum of these diseases was broadened, with novel variants identified in each of the OTX2, PAX6, and RBP4 genes. Moreover, we report new cases of reduced penetrance, mosaicism, and variable phenotypic expressivity associated with MA, further demonstrating the heterogeneity of such disorders. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Structural insights into activation and inhibition of histo-aspartic protease (HAP) from Plasmodium falciparum

PubMed Central

Bhaumik, Prasenjit; Xiao, Huogen; Hidaka, Koushi; Gustchina, Alla; Kiso, Yoshiaki; Yada, Rickey Y.; Wlodawer, Alexander

2012-01-01

Histo-aspartic protease (HAP) from Plasmodium falciparum offers a promising target for the development of novel antimalarial drugs. HAP exhibits high sequence similarity to pepsin-like aspartic proteases, but one of the two catalytic aspartates, Asp32, is replaced by histidine. Crystal structures of the truncated zymogen of HAP and of the complex of the mature enzyme with inhibitor KNI-10395 have been determined at 2.1 and 2.5 Å resolution, respectively. As in other proplasmepsins, the propeptide of the zymogen interacts with the C-terminal domain of the enzyme, forcing the N- and C- terminal domains apart, thereby separating His32 and Asp215 and preventing formation of the mature active site. In the inhibitor complex the enzyme forms a tight domain-swapped dimer, not previously seen in any aspartic proteases. The inhibitor is found in an unprecedented conformation resembling the letter “U”, stabilized by two intramolecular hydrogen bonds. Surprisingly, the location and conformation of the inhibitor are similar to the fragment of helix 2 comprising residues 34p–38p in the prosegments of the zymogens of gastric aspartic proteases; a corresponding helix assumes a vastly different orientation in proplasmepsins. Each inhibitor molecule is in contact with two molecules of HAP, interacting with the carboxylate group of the catalytic Asp215 of one HAP protomer through a water molecule, while also making a direct hydrogen bond to Glu278A′ of the other protomer. A comparison of the shifts in the positions of the catalytic residues in the inhibitor complex presented here with those published previously gives further hints regarding the enzymatic mechanism of HAP. PMID:21928835

Stiffness distribution in insect cuticle: a continuous or a discontinuous profile?

PubMed

Rajabi, H; Jafarpour, M; Darvizeh, A; Dirks, J-H; Gorb, S N

2017-07-01

Insect cuticle is a biological composite with a high degree of complexity in terms of both architecture and material composition. Given the complex morphology of many insect body parts, finite-element (FE) models play an important role in the analysis and interpretation of biomechanical measurements, taken by either macroscopic or nanoscopic techniques. Many previous studies show that the interpretation of nanoindentation measurements of this layered composite material is very challenging. To develop accurate FE models, it is of particular interest to understand more about the variations in the stiffness through the thickness of the cuticle. Considering the difficulties of making direct measurements, in this study, we use the FE method to analyse previously published data and address this issue numerically. For this purpose, sets of continuous or discontinuous stiffness profiles through the thickness of the cuticle were mathematically described. The obtained profiles were assigned to models developed based on the cuticle of three insect species with different geometries and layer configurations. The models were then used to simulate the mechanical behaviour of insect cuticles subjected to nanoindentation experiments. Our results show that FE models with discontinuous exponential stiffness gradients along their thickness were able to predict the stress and deformation states in insect cuticle very well. Our results further suggest that, for more accurate measurements and interpretation of nanoindentation test data, the ratio of the indentation depth to cuticle thickness should be limited to 7% rather than the traditional '10% rule'. The results of this study thus might be useful to provide a deeper insight into the biomechanical consequences of the distinct material distribution in insect cuticle and also to form a basis for more realistic modelling of this complex natural composite. © 2017 The Author(s).

Structural Insights into the Activation and Inhibition of Histo-Aspartic Protease from Plasmodium falciparum

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

Bhaumik, Prasenjit; Xiao, Huogen; Hidaka, Koushi

2012-09-17

Histo-aspartic protease (HAP) from Plasmodium falciparum is a promising target for the development of novel antimalarial drugs. The sequence of HAP is highly similar to those of pepsin-like aspartic proteases, but one of the two catalytic aspartates, Asp32, is replaced with histidine. Crystal structures of the truncated zymogen of HAP and of the complex of the mature enzyme with inhibitor KNI-10395 have been determined at 2.1 and 2.5 {angstrom} resolution, respectively. As in other proplasmepsins, the propeptide of the zymogen interacts with the C-terminal domain of the enzyme, forcing the N- and C-terminal domains apart, thereby separating His32 and Asp215more » and preventing formation of the mature active site. In the inhibitor complex, the enzyme forms a tight domain-swapped dimer, not previously seen in any aspartic proteases. The inhibitor is found in an unprecedented conformation resembling the letter U, stabilized by two intramolecular hydrogen bonds. Surprisingly, the location and conformation of the inhibitor are similar to those of the fragment of helix 2 comprising residues 34p-38p in the prosegments of the zymogens of gastric aspartic proteases; a corresponding helix assumes a vastly different orientation in proplasmepsins. Each inhibitor molecule is in contact with two molecules of HAP, interacting with the carboxylate group of the catalytic Asp215 of one HAP protomer through a water molecule, while also making a direct hydrogen bond to Glu278A' of the other protomer. A comparison of the shifts in the positions of the catalytic residues in the inhibitor complex presented here with those published previously gives further hints regarding the enzymatic mechanism of HAP.« less

Albumin Stimulates the Activity of the Human UDP-Glucuronosyltransferases 1A7, 1A8, 1A10, 2A1 and 2B15, but the Effects Are Enzyme and Substrate Dependent

PubMed Central

Svaluto-Moreolo, Paolo; Dziedzic, Klaudyna; Yli-Kauhaluoma, Jari; Finel, Moshe

2013-01-01

Human UDP-glucuronosyltransferases (UGTs) are important enzymes in metabolic elimination of endo- and xenobiotics. It was recently shown that addition of fatty acid free bovine serum albumin (BSA) significantly enhances in vitro activities of UGTs, a limiting factor in in vitro–in vivo extrapolation. Nevertheless, since only few human UGT enzymes were tested for this phenomenon, we have now performed detailed enzyme kinetic analysis on the BSA effects in six previously untested UGTs, using 2–4 suitable substrates for each enzyme. We also examined some of the previously tested UGTs, but using additional substrates and a lower BSA concentration, only 0.1%. The latter concentration allows the use of important but more lipophilic substrates, such as estradiol and 17-epiestradiol. In five newly tested UGTs, 1A7, 1A8, 1A10, 2A1, and 2B15, the addition of BSA enhanced, to a different degree, the in vitro activity by either decreasing reaction’s K m, increasing its V max, or both. In contrast, the activities of UGT2B17, another previously untested enzyme, were almost unaffected. The results of the assays with the previously tested UGTs, 1A1, 1A6, 2B4, and 2B7, were similar to the published BSA only as far as the BSA effects on the reactions’ K m are concerned. In the cases of V max values, however, our results differ significantly from the previously published ones, at least with some of the substrates. Hence, the magnitude of the BSA effects appears to be substrate dependent, especially with respect to V max increases. Additionally, the BSA effects may be UGT subfamily dependent since K m decreases were observed in members of subfamilies 1A, 2A and 2B, whereas large V max increases were only found in several UGT1A members. The results shed new light on the complexity of the BSA effects on the activity and enzyme kinetics of the human UGTs. PMID:23372764

Modeling Patient Treatment With Medical Records: An Abstraction Hierarchy to Understand User Competencies and Needs.

PubMed

St-Maurice, Justin D; Burns, Catherine M

2017-07-28

Health care is a complex sociotechnical system. Patient treatment is evolving and needs to incorporate the use of technology and new patient-centered treatment paradigms. Cognitive work analysis (CWA) is an effective framework for understanding complex systems, and work domain analysis (WDA) is useful for understanding complex ecologies. Although previous applications of CWA have described patient treatment, due to their scope of work patients were previously characterized as biomedical machines, rather than patient actors involved in their own care. An abstraction hierarchy that characterizes patients as beings with complex social values and priorities is needed. This can help better understand treatment in a modern approach to care. The purpose of this study was to perform a WDA to represent the treatment of patients with medical records. The methods to develop this model included the analysis of written texts and collaboration with subject matter experts. Our WDA represents the ecology through its functional purposes, abstract functions, generalized functions, physical functions, and physical forms. Compared with other work domain models, this model is able to articulate the nuanced balance between medical treatment, patient education, and limited health care resources. Concepts in the analysis were similar to the modeling choices of other WDAs but combined them in as a comprehensive, systematic, and contextual overview. The model is helpful to understand user competencies and needs. Future models could be developed to model the patient's domain and enable the exploration of the shared decision-making (SDM) paradigm. Our work domain model links treatment goals, decision-making constraints, and task workflows. This model can be used by system developers who would like to use ecological interface design (EID) to improve systems. Our hierarchy is the first in a future set that could explore new treatment paradigms. Future hierarchies could model the patient as a controller and could be useful for mobile app development. ©Justin D St-Maurice, Catherine M Burns. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 28.07.2017.

Scedo-Select III: a new semi-selective culture medium for detection of the Scedosporium apiospermum species complex.

PubMed

Pham, Trâm; Giraud, Sandrine; Schuliar, Gaëlle; Rougeron, Amandine; Bouchara, Jean-Philippe

2015-06-01

The Scedosporium apiospermum complex is responsible for a large variety of infections in human. Members of this complex have become emerging fungal pathogens with an increasing occurrence in patients with underlying conditions such as immunosuppression or cystic fibrosis. A better knowledge of these fungi and of the sources of contamination of the patients is required and more accurate detection methods from the environment are needed. In this context, a highly selective culture medium was developed in the present study. Thus, various aliphatic, cyclic, or aromatic compounds were tested as the sole carbon source, in combination with some inorganic nitrogen sources and fungicides. The best results were obtained with 4-hydroxy-benzoate combined with ammonium sulfate and the fungicides dichloran and benomyl. This new culture medium called Scedo-Select III was shown to support growth of all species of the S. apiospermum complex. Subsequently, this new culture medium was evaluated successfully on water and soil samples, exhibiting higher sensitivity and selectivity than the previously described SceSel+ culture medium. Therefore, this easy-to-prepare and synthetic semi-selective culture medium may be useful to clarify the ecology of these fungi and to identify their reservoirs in patients' environment. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A complex mTOR response in habituation paradigms for a social signal in adult songbirds.

PubMed

Ahmadiantehrani, Somayeh; Gores, Elisa O; London, Sarah E

2018-06-01

Nonassociative learning is considered simple because it depends on presentation of a single stimulus, but it likely reflects complex molecular signaling. To advance understanding of the molecular mechanisms of one form of nonassociative learning, habituation, for ethologically relevant signals we examined song recognition learning in adult zebra finches. These colonial songbirds learn the unique song of individuals, which helps establish and maintain mate and other social bonds, and informs appropriate behavioral interactions with specific birds. We leveraged prior work demonstrating behavioral habituation for individual songs, and extended the molecular framework correlated with this behavior by investigating the mechanistic Target of Rapamycin (mTOR) signaling cascade. We hypothesized that mTOR may contribute to habituation because it integrates a variety of upstream signals and enhances associative learning, and it crosstalks with another cascade previously associated with habituation, ERK/ZENK. To begin probing for a possible role for mTOR in song recognition learning, we used a combination of song playback paradigms and bidirectional dysregulation of mTORC1 activation. We found that mTOR demonstrates the molecular signatures of a habituation mechanism, and that its manipulation reveals the complexity of processes that may be invoked during nonassociative learning. These results thus expand the molecular targets for habituation studies and raise new questions about neural processing of complex natural signals. © 2018 Ahmadiantehrani et al.; Published by Cold Spring Harbor Laboratory Press.

Molecular and Behavioral Differentiation among Brazilian Populations of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae)

PubMed Central

Araki, Alejandra S.; Vigoder, Felipe M.; Bauzer, Luiz G. S. R.; Ferreira, Gabriel E. M.; Souza, Nataly A.; Araújo, Izeneide B.; Hamilton, James G. C.; Brazil, Reginaldo P.; Peixoto, Alexandre A.

2009-01-01

Background Lutzomyia longipalpis is the primary vector of American visceral leishmaniasis. There is strong evidence that L. longipalpis is a species complex, but until recently the existence of sibling species among Brazilian populations was considered a controversial issue. In addition, there is still no consensus regarding the number of species occurring in this complex. Methodology/Principal Findings Using period, a gene that controls circadian rhythms and affects interpulse interval periodicity of the male courtship songs in Drosophila melanogaster and close relatives, we analyzed the molecular polymorphism in a number of L. longipalpis samples from different regions in Brazil and compared the results with our previously published data using the same marker. We also studied the male copulation songs and pheromones from some of these populations. The results obtained so far suggest the existence of two main groups of populations in Brazil, one group representing a single species with males producing Burst-type copulation songs and cembrene-1 pheromones; and a second group that is more heterogeneous and probably represents a number of incipient species producing different combinations of Pulse-type songs and pheromones. Conclusions/Significance Our results reveal a high level of complexity in the divergence and gene-flow among Brazilian populations of the L. longipalpis species complex. This raises important questions concerning the epidemiological consequences of this incipient speciation process. PMID:19172187

Health-related fitness profiles in adolescents with complex congenital heart disease.

PubMed

Klausen, Susanne Hwiid; Wetterslev, Jørn; Søndergaard, Lars; Andersen, Lars L; Mikkelsen, Ulla Ramer; Dideriksen, Kasper; Zoffmann, Vibeke; Moons, Philip

2015-04-01

This study investigates whether subgroups of different health-related fitness (HrF) profiles exist among girls and boys with complex congenital heart disease (ConHD) and how these are associated with lifestyle behaviors. We measured the cardiorespiratory fitness, muscle strength, and body composition of 158 adolescents aged 13-16 years with previous surgery for a complex ConHD. Data on lifestyle behaviors were collected concomitantly between October 2010 and April 2013. A cluster analysis was conducted to identify profiles with similar HrF. For comparisons between clusters, multivariate analyses of covariance were used to test the differences in lifestyle behaviors. Three distinct profiles were formed: (1) Robust (43, 27%; 20 girls and 23 boys); (2) Moderately Robust (85, 54%; 37 girls and 48 boys); and (3) Less robust (30, 19%; 9 girls and 21 boys). The participants in the Robust clusters reported leading a physically active lifestyle and participants in the Less robust cluster reported leading a sedentary lifestyle. Diagnoses were evenly distributed between clusters. The cluster analysis attributed some of the variability in cardiorespiratory fitness among adolescents with complex ConHD to lifestyle behaviors and physical activity. Profiling of HrF offers a valuable new option in the management of person-centered health promotion. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

A conceptual model of the role of complexity in the care of patients with multiple chronic conditions.

PubMed

Grembowski, David; Schaefer, Judith; Johnson, Karin E; Fischer, Henry; Moore, Susan L; Tai-Seale, Ming; Ricciardi, Richard; Fraser, James R; Miller, Donald; LeRoy, Lisa

2014-03-01

Effective healthcare for people with multiple chronic conditions (MCC) is a US priority, but the inherent complexity makes both research and delivery of care particularly challenging. As part of AHRQ Multiple Chronic Conditions Research Network (MCCRN) efforts, the Network developed a conceptual model to guide research in this area. To synthesize methodological and topical issues relevant to MCC patient care into a framework that can improve the delivery of care and advance future research about caring for patients with MCC. The Network synthesized essential constructs for MCC research identified from roundtable discussion, input from expert advisors, and previously published models. The AHRQ MCCRN conceptual model defines complexity as the gap between patient needs and healthcare services, taking into account both the multiple considerations that affect the needs of MCC patients, as well as the contextual factors that influence service delivery. The model reframes processes and outcomes to include not only clinical care quality and experience, but also patient health, well being, and quality of life. The single-condition paradigm for treating needs one-by-one falls apart and highlights the need for care systems to address dynamic patient needs. Defining complexity in terms of the misalignment between patient needs and services offers new insights in how to research and develop solutions to patient care needs.

Sorption of trivalent lanthanides and actinides onto montmorillonite: Macroscopic, thermodynamic and structural evidence for ternary hydroxo and carbonato surface complexes on multiple sorption sites.

PubMed

Fernandes, M Marques; Scheinost, A C; Baeyens, B

2016-08-01

The credibility of long-term safety assessments of radioactive waste repositories may be greatly enhanced by a molecular level understanding of the sorption processes onto individual minerals present in the near- and far-fields. In this study we couple macroscopic sorption experiments to surface complexation modelling and spectroscopic investigations, including extended X-ray absorption fine structure (EXAFS) and time-resolved laser fluorescence spectroscopies (TRLFS), to elucidate the uptake mechanism of trivalent lanthanides and actinides (Ln/An(III)) by montmorillonite in the absence and presence of dissolved carbonate. Based on the experimental sorption isotherms for the carbonate-free system, the previously developed 2 site protolysis non electrostatic surface complexation and cation exchange (2SPNE SC/CE) model needed to be complemented with an additional surface complexation reaction onto weak sites. The fitting of sorption isotherms in the presence of carbonate required refinement of the previously published model by reducing the strong site capacity and by adding the formation of Ln/An(III)-carbonato complexes both on strong and weak sites. EXAFS spectra of selected Am samples and TRLFS spectra of selected Cm samples corroborate the model assumptions by showing the existence of different surface complexation sites and evidencing the formation of Ln/An(III) carbonate surface complexes. In the absence of carbonate and at low loadings, Ln/An(III) form strong inner-sphere complexes through binding to three Al(O,OH)6 octahedra, most likely by occupying vacant sites in the octahedral layers of montmorillonite, which are exposed on {010} and {110} edge faces. At higher loadings, Ln/An(III) binds to only one Al octahedron, forming a weaker, edge-sharing surface complex. In the presence of carbonate, we identified a ternary mono- or dicarbonato Ln/An(III) complex binding directly to one Al(O,OH)6 octahedron, revealing that type-A ternary complexes form with the one or two carbonate groups pointing away from the surface into the solution phase. Within the spectroscopically observable concentration range these complexes could only be identified on the weak sites, in line with the small strong site capacity suggested by the refined sorption model. When the solubility of carbonates was exceeded, formation of an Am carbonate hydroxide could be identified. The excellent agreement between the thermodynamic model parameters obtained by fitting the macroscopic data, and the spectroscopically identified mechanisms, demonstrates the mature state of the 2SPNE SC/CE model for predicting and quantifying the retention of Ln/An(III) elements by montmorillonite-rich clay rocks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of a novel high-resolution mapping technology for ablation of recurrent scar-related atrial tachycardias.

PubMed

Anter, Elad; McElderry, Thomas H; Contreras-Valdes, Fernando M; Li, Jianqing; Tung, Patricia; Leshem, Eran; Haffajee, Charles I; Nakagawa, Hiroshi; Josephson, Mark E

2016-10-01

Rhythmia is a new technology capable of rapid and high-resolution mapping. However, its potential advantage over existing technologies in mapping complex scar-related atrial tachycardias (ATs) has not yet been evaluated. The purpose of this study was to examine the utility of Rhythmia for mapping scar-related ATs in patients who had failed previous ablation procedure(s). This multicenter study included 20 patients with recurrent ATs within 2 years after a previous ablation procedure (1.8 ± 0.7 per patient). In all cases, the ATs could not be adequately mapped during the index procedure because of scar with fractionated electrograms, precluding accurate time annotation, frequent change in the tachycardia in response to pacing, and/or degeneration into atrial fibrillation. These patients underwent repeat mapping and ablation procedure with Rhythmia. From a total of 28 inducible ATs, 24 were successfully mapped. Eighteen ATs (75%) terminated during radiofrequency ablation and 4 (16.6%) with catheter pressure or entrainment from the site of origin or isthmus. Two ATs that were mapped to the interatrial septum slowed but did not terminate with ablation. In 21 of 24 ATs the mechanism was macroreentry, while in 3 of 24 the mechanism was focal. Interestingly, in 5 patients with previously failed ablation of an allegedly "focal" tachycardia, high-resolution mapping demonstrated macroreentrant arrhythmia. The mean mapping time was 28.6 ± 17 minutes, and the mean radiofrequency ablation time to arrhythmia termination was 3.2 ± 2.6 minutes. During a mean follow-up of 7.5 ± 3.1 months, 15 of 20 patients (75%) were free of AT recurrences. The Rhythmia mapping system may be advantageous for mapping complex scar-related ATs. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Dopamine D1 receptor agonist treatment attenuates extinction of morphine conditioned place preference while increasing dendritic complexity in the nucleus accumbens core.

PubMed

Kobrin, Kendra L; Arena, Danielle T; Heinrichs, Stephen C; Nguyen, Olivia H; Kaplan, Gary B

2017-03-30

The dopamine D1 receptor (D1R) has a role in opioid reward and conditioned place preference (CPP), but its role in CPP extinction is undetermined. We examined the effect of D1R agonist SKF81297 on the extinction of opioid CPP and associated dendritic morphology in the nucleus accumbens (NAc), a region involved with reward integration and its extinction. During the acquisition of morphine CPP, mice received morphine and saline on alternate days; injections were given immediately before each of eight daily conditioning sessions. Mice subsequently underwent six days of extinction training designed to diminish the previously learned association. Mice were treated with either 0.5mg/kg SKF81297, 0.8mg/kg SKF81297, or saline immediately after each extinction session. There was a dose-dependent effect, with the highest dose of SKF81297 attenuating extinction, as mice treated with this dose had significantly higher CPP scores than controls. Analysis of medium spiny neuron morphology revealed that in the NAc core, but not in the shell, dendritic arbors were significantly more complex in the morphine conditioned, SKF81297-treated mice compared to controls. In separate experiments using mice conditioned with only saline, SKF81297 administration after extinction sessions had no effect on CPP and produced differing effects on dendritic morphology. At the doses used in our experiments, SKF81297 appears to maintain previously learned opioid conditioned behavior, even in the face of new information. The D1R agonist's differential, rather than unidirectional, effects on dendritic morphology in the NAc core suggests that it may be involved in encoding reward information depending on previously learned behavior. Published by Elsevier B.V.

Fractionation of Hydrogen Isotopes by Sulfate- and Nitrate-Reducing Bacteria.

PubMed

Osburn, Magdalena R; Dawson, Katherine S; Fogel, Marilyn L; Sessions, Alex L

2016-01-01

Hydrogen atoms from water and food are incorporated into biomass during cellular metabolism and biosynthesis, fractionating the isotopes of hydrogen-protium and deuterium-that are recorded in biomolecules. While these fractionations are often relatively constant in plants, large variations in the magnitude of fractionation are observed for many heterotrophic microbes utilizing different central metabolic pathways. The correlation between metabolism and lipid δ(2)H provides a potential basis for reconstructing environmental and ecological parameters, but the calibration dataset has thus far been limited mainly to aerobes. Here we report on the hydrogen isotopic fractionations of lipids produced by nitrate-respiring and sulfate-reducing bacteria. We observe only small differences in fractionation between oxygen- and nitrate-respiring growth conditions, with a typical pattern of variation between substrates that is broadly consistent with previously described trends. In contrast, fractionation by sulfate-reducing bacteria does not vary significantly between different substrates, even when autotrophic and heterotrophic growth conditions are compared. This result is in marked contrast to previously published observations and has significant implications for the interpretation of environmental hydrogen isotope data. We evaluate these trends in light of metabolic gene content of each strain, growth rate, and potential flux and reservoir-size effects of cellular hydrogen, but find no single variable that can account for the differences between nitrate- and sulfate-respiring bacteria. The emerging picture of bacterial hydrogen isotope fractionation is therefore more complex than the simple correspondence between δ(2)H and metabolic pathway previously understood from aerobes. Despite the complexity, the large signals and rich variability of observed lipid δ(2)H suggest much potential as an environmental recorder of metabolism.

Literature searches on Ayurveda: An update.

PubMed

Aggithaya, Madhur G; Narahari, Saravu R

2015-01-01

The journals that publish on Ayurveda are increasingly indexed by popular medical databases in recent years. However, many Eastern journals are not indexed biomedical journal databases such as PubMed. Literature searches for Ayurveda continue to be challenging due to the nonavailability of active, unbiased dedicated databases for Ayurvedic literature. In 2010, authors identified 46 databases that can be used for systematic search of Ayurvedic papers and theses. This update reviewed our previous recommendation and identified current and relevant databases. To update on Ayurveda literature search and strategy to retrieve maximum publications. Author used psoriasis as an example to search previously listed databases and identify new. The population, intervention, control, and outcome table included keywords related to psoriasis and Ayurvedic terminologies for skin diseases. Current citation update status, search results, and search options of previous databases were assessed. Eight search strategies were developed. Hundred and five journals, both biomedical and Ayurveda, which publish on Ayurveda, were identified. Variability in databases was explored to identify bias in journal citation. Five among 46 databases are now relevant - AYUSH research portal, Annotated Bibliography of Indian Medicine, Digital Helpline for Ayurveda Research Articles (DHARA), PubMed, and Directory of Open Access Journals. Search options in these databases are not uniform, and only PubMed allows complex search strategy. "The Researches in Ayurveda" and "Ayurvedic Research Database" (ARD) are important grey resources for hand searching. About 44/105 (41.5%) journals publishing Ayurvedic studies are not indexed in any database. Only 11/105 (10.4%) exclusive Ayurveda journals are indexed in PubMed. AYUSH research portal and DHARA are two major portals after 2010. It is mandatory to search PubMed and four other databases because all five carry citations from different groups of journals. The hand searching is important to identify Ayurveda publications that are not indexed elsewhere. Availability information of citations in Ayurveda libraries from National Union Catalogue of Scientific Serials in India if regularly updated will improve the efficacy of hand searching. A grey database (ARD) contains unpublished PG/Ph.D. theses. The AYUSH portal, DHARA (funded by Ministry of AYUSH), and ARD should be merged to form single larger database to limit Ayurveda literature searches.

Peruvian Tropical Glacier May Survive Longer Than Previously Thought: Landsat Image Analysis of Nevado Coropuna Ice Cap, Peru

NASA Astrophysics Data System (ADS)

Kochtitzky, W. H.; Edwards, B. R.; Marino, J.; Manrique, N.

2015-12-01

Nevado Coropuna is a large volcanic complex in southern Peru (15.56°S, 72.62°N; 6,425 m). The complex is approximately 12 km east-west and 8 km north-south with elevation from ~4,500 m at the base to over 6,000 m at the highest points. This ice cap is the largest hosted by a volcano in the tropics, and one of the ten biggest ice masses in the tropics. Previous workers have predicted that the Coropuna ice cap will completely melt by 2050. We present a new analysis of historic satellite imagery to test this hypothesis. In this study, ice and snow are classified based on unique spectral signatures including spectral band thresholds, Normalized Difference Snow Index, and Band 4/5 ratio. Landsat scenes (L2, 4, 5, 7, and 8) from 1975 to present in addition to one SPOT scene (2013) are used. Previous workers used images from June and July, which are peak snow periods in southern Peru, leading to overestimates of ice area. This study uses November and December images when snow is at an annual minimum. Annual equilibrium line altitudes are calculated for each end of year image (November/December). The glaciers of Nevado Coropuna were found to be shrinking at ~0.5 km2/yr, which is ~1/3 the rate previously published. In this study, SPOT (1.5 m resolution) and Landsat 7 ETM scenes from November 23 and 26, 2013 respectively were used to calibrate the spectral band threshold classification. While this study suggests that the ice cap of Coropuna will persist until 2100 given current rates, water quantity and security remains a concern for Peruvian agriculture. Coropuna is an active volcano, so it poses great risk to surrounding inhabitants from lahars, flooding, and debris avalanches. Our new data suggest that these will continue to be risks late into this century.

Hemoparasites in Oregon spotted frogs (Rana pretiosa) from central Oregon, USA.

PubMed

Stenberg, Patricia L; Bowerman, William J

2008-04-01

Between 2001 and 2003, we screened blood smears of 156 Oregon spotted frogs (Rana pretiosa) from three populations in central Oregon for blood parasites. A Lankesterella sp. and a Trypanosoma sp. were detected in 31% and 35% of the frogs, respectively. Parasite loads were generally light, with Lankesterella sporozoites in 1-2% of erythrocytes, and extracellular trypanosomes were seen at rates of about one parasite per 200 fields of view at 1,000x. Little work has been published on hemoparasites of ranids in the western USA in the past 30 yr. Because of the recent taxonomic division of the Rana pretiosa complex, this may be the first published report of blood parasites for R. pretiosa sensu stricto. Both parasites reported here differed in morphologic features and morphometric comparisons from previous descriptions of anuran hemoparasites. Much work remains to sort out the taxonomy of hemoparasites among western USA ranids and to determine the ecological significance of these parasites; both tasks are important steps in understanding and managing these, and related, sensitive and threatened species.

Menthol: putting the pieces together.

PubMed

Lee, Youn Ok; Glantz, Stanton A

2011-05-01

To integrate information on cigarette companies' understanding and use of menthol as summarised in published research based on previously internal tobacco industry documents with results from large population-based surveys of tobacco use and other independent sources. Papers published in this supplement of Tobacco Control, together with papers identified using PubMed searches. Tobacco companies shaped consumer perceptions of menthol cigarettes. Menthol is not just a flavouring agent. Cigarette companies use menthol's ability to mask irritation and provide sensory effects to make menthol cigarettes appeal to youth and health-concerned smokers, in part because menthol makes low-tar cigarettes more palatable. Consistent with targeted marketing, youths, women and African Americans disproportionately smoke menthols. There appear to be complex interactions with addictive effects of nicotine. The ubiquitous addition of menthol by tobacco companies to over 90% of all tobacco products, whether labelled 'menthol' or not, demonstrates that menthol is not simply a flavour or brand. Menthol imparts sensory characteristics to cigarettes and has a complex interaction with nicotine that affects smoking behaviour whether it is perceived or not, or whether cigarettes containing menthol are marketed as 'menthol' or not. Adding menthol increases fine particles in cigarette smoke, which have immediate adverse effects on the risk of heart attack. Information from industry documents, confirmed by independent scientific literature, consistently demonstrates that menthol increases population harm from smoking by increasing initiation and reducing cessation in some groups. Menthol facilitates and increases smoking, which causes disease and death.

Menthol: putting the pieces together

PubMed Central

Lee, Youn Ok

2011-01-01

Objective To integrate information on cigarette companies' understanding and use of menthol as summarised in published research based on previously internal tobacco industry documents with results from large population-based surveys of tobacco use and other independent sources. Data sources Papers published in this supplement of Tobacco Control, together with papers identified using PubMed searches. Results Tobacco companies shaped consumer perceptions of menthol cigarettes. Menthol is not just a flavouring agent. Cigarette companies use menthol's ability to mask irritation and provide sensory effects to make menthol cigarettes appeal to youth and health-concerned smokers, in part because menthol makes low-tar cigarettes more palatable. Consistent with targeted marketing, youths, women and African Americans disproportionately smoke menthols. There appear to be complex interactions with addictive effects of nicotine. The ubiquitous addition of menthol by tobacco companies to over 90% of all tobacco products, whether labelled ‘menthol’ or not, demonstrates that menthol is not simply a flavour or brand. Menthol imparts sensory characteristics to cigarettes and has a complex interaction with nicotine that affects smoking behaviour whether it is perceived or not, or whether cigarettes containing menthol are marketed as ‘menthol’ or not. Adding menthol increases fine particles in cigarette smoke, which have immediate adverse effects on the risk of heart attack. Conclusion Information from industry documents, confirmed by independent scientific literature, consistently demonstrates that menthol increases population harm from smoking by increasing initiation and reducing cessation in some groups. Menthol facilitates and increases smoking, which causes disease and death. PMID:21504926

Highly Reproducible Label Free Quantitative Proteomic Analysis of RNA Polymerase Complexes*

PubMed Central

Mosley, Amber L.; Sardiu, Mihaela E.; Pattenden, Samantha G.; Workman, Jerry L.; Florens, Laurence; Washburn, Michael P.

2011-01-01

The use of quantitative proteomics methods to study protein complexes has the potential to provide in-depth information on the abundance of different protein components as well as their modification state in various cellular conditions. To interrogate protein complex quantitation using shotgun proteomic methods, we have focused on the analysis of protein complexes using label-free multidimensional protein identification technology and studied the reproducibility of biological replicates. For these studies, we focused on three highly related and essential multi-protein enzymes, RNA polymerase I, II, and III from Saccharomyces cerevisiae. We found that label-free quantitation using spectral counting is highly reproducible at the protein and peptide level when analyzing RNA polymerase I, II, and III. In addition, we show that peptide sampling does not follow a random sampling model, and we show the need for advanced computational models to predict peptide detection probabilities. In order to address these issues, we used the APEX protocol to model the expected peptide detectability based on whole cell lysate acquired using the same multidimensional protein identification technology analysis used for the protein complexes. Neither method was able to predict the peptide sampling levels that we observed using replicate multidimensional protein identification technology analyses. In addition to the analysis of the RNA polymerase complexes, our analysis provides quantitative information about several RNAP associated proteins including the RNAPII elongation factor complexes DSIF and TFIIF. Our data shows that DSIF and TFIIF are the most highly enriched RNAP accessory factors in Rpb3-TAP purifications and demonstrate our ability to measure low level associated protein abundance across biological replicates. In addition, our quantitative data supports a model in which DSIF and TFIIF interact with RNAPII in a dynamic fashion in agreement with previously published reports. PMID:21048197

Sensitivity to prediction error in reach adaptation

PubMed Central

Haith, Adrian M.; Harran, Michelle D.; Shadmehr, Reza

2012-01-01

It has been proposed that the brain predicts the sensory consequences of a movement and compares it to the actual sensory feedback. When the two differ, an error signal is formed, driving adaptation. How does an error in one trial alter performance in the subsequent trial? Here we show that the sensitivity to error is not constant but declines as a function of error magnitude. That is, one learns relatively less from large errors compared with small errors. We performed an experiment in which humans made reaching movements and randomly experienced an error in both their visual and proprioceptive feedback. Proprioceptive errors were created with force fields, and visual errors were formed by perturbing the cursor trajectory to create a visual error that was smaller, the same size, or larger than the proprioceptive error. We measured single-trial adaptation and calculated sensitivity to error, i.e., the ratio of the trial-to-trial change in motor commands to error size. We found that for both sensory modalities sensitivity decreased with increasing error size. A reanalysis of a number of previously published psychophysical results also exhibited this feature. Finally, we asked how the brain might encode sensitivity to error. We reanalyzed previously published probabilities of cerebellar complex spikes (CSs) and found that this probability declined with increasing error size. From this we posit that a CS may be representative of the sensitivity to error, and not error itself, a hypothesis that may explain conflicting reports about CSs and their relationship to error. PMID:22773782

Silencing of the pentose phosphate pathway genes influences DNA replication in human fibroblasts.

PubMed

Fornalewicz, Karolina; Wieczorek, Aneta; Węgrzyn, Grzegorz; Łyżeń, Robert

2017-11-30

Previous reports and our recently published data indicated that some enzymes of glycolysis and the tricarboxylic acid cycle can affect the genome replication process by changing either the efficiency or timing of DNA synthesis in human normal cells. Both these pathways are connected with the pentose phosphate pathway (PPP pathway). The PPP pathway supports cell growth by generating energy and precursors for nucleotides and amino acids. Therefore, we asked if silencing of genes coding for enzymes involved in the pentose phosphate pathway may also affect the control of DNA replication in human fibroblasts. Particular genes coding for PPP pathway enzymes were partially silenced with specific siRNAs. Such cells remained viable. We found that silencing of the H6PD, PRPS1, RPE genes caused less efficient enterance to the S phase and decrease in efficiency of DNA synthesis. On the other hand, in cells treated with siRNA against G6PD, RBKS and TALDO genes, the fraction of cells entering the S phase was increased. However, only in the case of G6PD and TALDO, the ratio of BrdU incorporation to DNA was significantly changed. The presented results together with our previously published studies illustrate the complexity of the influence of genes coding for central carbon metabolism on the control of DNA replication in human fibroblasts, and indicate which of them are especially important in this process. Copyright © 2017 Elsevier B.V. All rights reserved.

Duration of a large Mafic intrusion and heat transfer in the lower crust: A SHRIMP U-Pb zircon Study in the Ivrea-Verbano Zone (Western Alps, Italy)

USGS Publications Warehouse

Peressini, G.; Quick, J.E.; Sinigoi, S.; Hofmann, A.W.; Fanning, M.

2007-01-01

The Ivrea-Verbano Zone in the western Italian Alps contains one of the world's classic examples of ponding of mantle-derived, mafic magma in the deep crust. Within it, a voluminous, composite mafic pluton, the Mafic Complex, intruded lower-crustal, high-grade paragneiss of the Kinzigite Formation during Permian-Carboniferous time, and is now exposed in cross-section as a result of Alpine uplift. The age of the intrusion is still debated because the results of geochronological studies in the last three decades on different rock types and with various dating techniques range from 250 to about 300 Ma. Sensitive high-resolution ion microprobe (SHRIMP) U-Pb zircon age determinations on 12 samples from several locations within the Mafic Complex were performed to better constrain the age of the igneous event. The results indicate a long history of magma emplacement and cooling, which reconciles the spread in previously published ages. The main intrusive phase took place at 288 ?? 4 Ma, causing a perturbation of the deep-crustal geotherm, which relaxed to the Sm-Nd closure temperature in garnet-free mafic rocks after about 15-20 Myr of sub-solidus cooling at c. 270 Ma. These results suggest that large, deep crustal plutons, such as those identified geophysically at depths of 10-20 km within extended continental crust (e.g. Yellowstone, Rio Grande Rift, Basin and Range) may have formed rapidly but induced a prolonged thermal perturbation. In addition, the data indicate that a significant thermal event affected the country rock of the Mafic Complex at about 310 Ma. The occurrence of an upper amphibolite- to granulite-facies thermal event in the Kinzigite Formation prior to the main intrusive phase of the Mafic Complex has been postulated by several workers, and is corroborated by other geochronological investigations. However, it remains uncertain whether this event (1) was part of a prolonged perturbation of the deep-crustal geotherm, which started long before the onset of intrusion of the Mafic Complex, or (2) corresponded to the intrusion of the first sills of the Mafic Complex, or (3) was related to an earlier, independent thermal pulse. ?? The Author 2007. Published by Oxford University Press. All rights reserved.

Externalities and article citations: experience of a national public health journal (Gaceta Sanitaria).

PubMed

Ruano-Ravina, Alberto; Álvarez-Dardet, Carlos; Domínguez-Berjón, M Felicitas; Fernández, Esteve; García, Ana M; Borrell, Carme

2016-01-01

The purpose of the study was to analyze the determinants of citations such as publication year, article type, article topic, article selected for a press release, number of articles previously published by the corresponding author, and publication language in a Spanish journal of public health. Observational study including all articles published in Gaceta Sanitaria during 2007-2011. We retrieved the number of citations from the ISI Web of Knowledge database in June 2013 and also information on other variables such as number of articles published by the corresponding author in the previous 5 years (searched through PubMed), selection for a press release, publication language, article type and topic, and others. We included 542 articles. Of these, 62.5% were cited in the period considered. We observed an increased odds ratio of citations for articles selected for a press release and also with the number of articles published previously by the corresponding author. Articles published in English do not seem to increase their citations. Certain externalities such as number of articles published by the corresponding author and being selected for a press release seem to influence the number of citations in national journals. Copyright © 2016 Elsevier Inc. All rights reserved.

Sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer (NMSC): A population-based study.

PubMed

Fischer, Alexander H; Wang, Timothy S; Yenokyan, Gayane; Kang, Sewon; Chien, Anna L

2016-08-01

Individuals with previous nonmelanoma skin cancer (NMSC) are at increased risk for subsequent skin cancer, and should therefore limit ultraviolet exposure. We sought to determine whether individuals with previous NMSC engage in better sun protection than those with no skin cancer history. We pooled self-reported data (2005 and 2010 National Health Interview Surveys) from US non-Hispanic white adults (758 with and 34,161 without previous NMSC). We calculated adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (CI), taking into account the complex survey design. Individuals with previous NMSC versus no history of NMSC had higher rates of frequent use of shade (44.3% vs 27.0%; aPOR 1.41; 95% CI 1.16-1.71), long sleeves (20.5% vs 7.7%; aPOR 1.55; 95% CI 1.21-1.98), a wide-brimmed hat (26.1% vs 10.5%; aPOR 1.52; 95% CI 1.24-1.87), and sunscreen (53.7% vs 33.1%; aPOR 2.11; 95% CI 1.73-2.59), but did not have significantly lower odds of recent sunburn (29.7% vs 40.7%; aPOR 0.95; 95% CI 0.77-1.17). Among those with previous NMSC, recent sunburn was inversely associated with age, sun avoidance, and shade but not sunscreen. Self-reported cross-sectional data and unavailable information quantifying regular sun exposure are limitations. Physicians should emphasize sunburn prevention when counseling patients with previous NMSC, especially younger adults, focusing on shade and sun avoidance over sunscreen. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

The Impact of Guided Notes on Post-Secondary Student Achievement: A Meta-Analysis

ERIC Educational Resources Information Center

Larwin, Karen H.; Larwin, David A.

2013-01-01

The common practice of using of guided notes in the post-secondary classroom is not fully appreciated or understood. In an effort to add to the existing research about this phenomenon, the current investigation expands on previously published research and one previously published meta-analysis that examined the impact of guided notes on…

Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network

PubMed Central

Pendergrass, Sarah A.; Brown-Gentry, Kristin; Dudek, Scott; Frase, Alex; Torstenson, Eric S.; Goodloe, Robert; Ambite, Jose Luis; Avery, Christy L.; Buyske, Steve; Bůžková, Petra; Deelman, Ewa; Fesinmeyer, Megan D.; Haiman, Christopher A.; Heiss, Gerardo; Hindorff, Lucia A.; Hsu, Chu-Nan; Jackson, Rebecca D.; Kooperberg, Charles; Le Marchand, Loic; Lin, Yi; Matise, Tara C.; Monroe, Kristine R.; Moreland, Larry; Park, Sungshim L.; Reiner, Alex; Wallace, Robert; Wilkens, Lynn R.; Crawford, Dana C.; Ritchie, Marylyn D.

2013-01-01

Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), African Americans (AA), Hispanics/Mexican-Americans, and Asian/Pacific Islanders) in PAGE, each site with measurements for multiple traits, associated laboratory measures, and intermediate biomarkers. A total of 83 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) were genotyped across two or more PAGE study sites. Comprehensive tests of association, stratified by race/ethnicity, were performed, encompassing 4,706 phenotypes mapped to 105 phenotype-classes, and association results were compared across study sites. A total of 111 PheWAS results had significant associations for two or more PAGE study sites with consistent direction of effect with a significance threshold of p<0.01 for the same racial/ethnic group, SNP, and phenotype-class. Among results identified for SNPs previously associated with phenotypes such as lipid traits, type 2 diabetes, and body mass index, 52 replicated previously published genotype–phenotype associations, 26 represented phenotypes closely related to previously known genotype–phenotype associations, and 33 represented potentially novel genotype–phenotype associations with pleiotropic effects. The majority of the potentially novel results were for single PheWAS phenotype-classes, for example, for CDKN2A/B rs1333049 (previously associated with type 2 diabetes in EA) a PheWAS association was identified for hemoglobin levels in AA. Of note, however, GALNT2 rs2144300 (previously associated with high-density lipoprotein cholesterol levels in EA) had multiple potentially novel PheWAS associations, with hypertension related phenotypes in AA and with serum calcium levels and coronary artery disease phenotypes in EA. PheWAS identifies associations for hypothesis generation and exploration of the genetic architecture of complex traits. PMID:23382687

Discrimination of Anopheles species of the Arribalzagia series in Colombia using a multilocus approach.

PubMed

Álvarez, Natalí; Gómez, Giovan F; Naranjo-Díaz, Nelson; Correa, Margarita M

2018-06-18

The Arribalzagia Series of the Anopheles Subgenus comprises morphologically similar species or members of species complexes which makes correct species identification difficult. Therefore, the aim of this work was to discriminate the morphospecies of the Arribalzagia Series present in Colombia using a multilocus approach based on ITS2, COI and CAD sequences. Specimens of the Arribalzagia Series collected at 32 localities in nine departments were allocated to seven species. Individual and concatenated Bayesian analyses showed high support for each of the species and reinforced the previous report of the Apicimacula species Complex with distribution in the Pacific Coast and northwestern Colombia. In addition, a new molecular operational taxonomic unit-MOTU was identified, herein denominated near Anopheles peryassui, providing support for the existence of a Peryassui species Complex. Further, the CAD gene, just recently used for Anopheles taxonomy and phylogeny, demonstrated its power in resolving phylogenetic relationships among species of the Arribalzagia Series. The divergence times for these species correspond to the early Pliocene and the Miocene. Considering the epidemiological importance of some species of the Series and their co-occurrence in malaria endemic regions of Colombia, their discrimination constitutes an important step for vector incrimination and control in the country. Copyright © 2018. Published by Elsevier B.V.

L(3)mbt and the LINT complex safeguard cellular identity in the Drosophila ovary.

PubMed

Coux, Rémi-Xavier; Teixeira, Felipe Karam; Lehmann, Ruth

2018-04-04

Maintenance of cellular identity is essential for tissue development and homeostasis. At the molecular level, cell identity is determined by the coordinated activation and repression of defined sets of genes. The tumor suppressor L(3)mbt has been shown to secure cellular identity in Drosophila larval brains by repressing germline-specific genes. Here, we interrogate the temporal and spatial requirements for L(3)mbt in the Drosophila ovary, and show that it safeguards the integrity of both somatic and germline tissues. l(3)mbt mutant ovaries exhibit multiple developmental defects, which we find to be largely caused by the inappropriate expression of a single gene, nanos , a key regulator of germline fate, in the somatic ovarian cells. In the female germline, we find that L(3)mbt represses testis-specific and neuronal genes. At the molecular level, we show that L(3)mbt function in the ovary is mediated through its co-factor Lint-1 but independently of the dREAM complex. Together, our work uncovers a more complex role for L(3)mbt than previously understood and demonstrates that L(3)mbt secures tissue identity by preventing the simultaneous expression of original identity markers and tissue-specific misexpression signatures. © 2018. Published by The Company of Biologists Ltd.

The perception of complex pitch in cochlear implants: A comparison of monopolar and tripolar stimulation.

PubMed

Fielden, Claire A; Kluk, Karolina; Boyle, Patrick J; McKay, Colette M

2015-10-01

Cochlear implant listeners typically perform poorly in tasks of complex pitch perception (e.g., musical pitch and voice pitch). One explanation is that wide current spread during implant activation creates channel interactions that may interfere with perception of temporal fundamental frequency information contained in the amplitude modulations within channels. Current focusing using a tripolar mode of stimulation has been proposed as a way of reducing channel interactions, minimising spread of excitation and potentially improving place and temporal pitch cues. The present study evaluated the effect of mode in a group of cochlear implant listeners on a pitch ranking task using male and female singing voices separated by either a half or a quarter octave. Results were variable across participants, but on average, pitch ranking was at chance level when the pitches were a quarter octave apart and improved when the difference was a half octave. No advantage was observed for tripolar over monopolar mode at either pitch interval, suggesting that previously published psychophysical advantages for focused modes may not translate into improvements in complex pitch ranking. Evaluation of the spectral centroid of the stimulation pattern, plus a lack of significant difference between male and female voices, suggested that participants may have had difficulty in accessing temporal pitch cues in either mode.

Health technology assessment review: Computerized glucose regulation in the intensive care unit - how to create artificial control

PubMed Central

2009-01-01

Current care guidelines recommend glucose control (GC) in critically ill patients. To achieve GC, many ICUs have implemented a (nurse-based) protocol on paper. However, such protocols are often complex, time-consuming, and can cause iatrogenic hypoglycemia. Computerized glucose regulation protocols may improve patient safety, efficiency, and nurse compliance. Such computerized clinical decision support systems (Cuss) use more complex logic to provide an insulin infusion rate based on previous blood glucose levels and other parameters. A computerized CDSS for glucose control has the potential to reduce overall workload, reduce the chance of human cognitive failure, and improve glucose control. Several computer-assisted glucose regulation programs have been published recently. In order of increasing complexity, the three main types of algorithms used are computerized flowcharts, Proportional-Integral-Derivative (PID), and Model Predictive Control (MPC). PID is essentially a closed-loop feedback system, whereas MPC models the behavior of glucose and insulin in ICU patients. Although the best approach has not yet been determined, it should be noted that PID controllers are generally thought to be more robust than MPC systems. The computerized Cuss that are most likely to emerge are those that are fully a part of the routine workflow, use patient-specific characteristics and apply variable sampling intervals. PMID:19849827

The Sharpin interactome reveals a role for Sharpin in lamellipodium formation via the Arp2/3 complex.

PubMed

Khan, Meraj H; Salomaa, Siiri I; Jacquemet, Guillaume; Butt, Umar; Miihkinen, Mitro; Deguchi, Takahiro; Kremneva, Elena; Lappalainen, Pekka; Humphries, Martin J; Pouwels, Jeroen

2017-09-15

Sharpin, a multifunctional adaptor protein, regulates several signalling pathways. For example, Sharpin enhances signal-induced NF-κB signalling as part of the linear ubiquitin assembly complex (LUBAC) and inhibits integrins, the T cell receptor, caspase 1 and PTEN. However, despite recent insights into Sharpin and LUBAC function, a systematic approach to identify the signalling pathways regulated by Sharpin has not been reported. Here, we present the first 'Sharpin interactome', which identifies a large number of novel potential Sharpin interactors in addition to several known ones. These data suggest that Sharpin and LUBAC might regulate a larger number of biological processes than previously identified, such as endosomal trafficking, RNA processing, metabolism and cytoskeleton regulation. Importantly, using the Sharpin interactome, we have identified a novel role for Sharpin in lamellipodium formation. We demonstrate that Sharpin interacts with Arp2/3, a protein complex that catalyses actin filament branching. We have identified the Arp2/3-binding site in Sharpin and demonstrate using a specific Arp2/3-binding deficient mutant that the Sharpin-Arp2/3 interaction promotes lamellipodium formation in a LUBAC-independent fashion.This article has an associated First Person interview with the first author of the paper. © 2017. Published by The Company of Biologists Ltd.

Multi-omics approach identifies molecular mechanisms of plant-fungus mycorrhizal interaction

DOE PAGES

Larsen, Peter E.; Sreedasyam, Avinash; Trivedi, Geetika; ...

2016-01-19

In mycorrhizal symbiosis, plant roots form close, mutually beneficial interactions with soil fungi. Before this mycorrhizal interaction can be established however, plant roots must be capable of detecting potential beneficial fungal partners and initiating the gene expression patterns necessary to begin symbiosis. To predict a plant root – mycorrhizal fungi sensor systems, we analyzed in vitro experiments of Populus tremuloides (aspen tree) and Laccaria bicolor (mycorrhizal fungi) interaction and leveraged over 200 previously published transcriptomic experimental data sets, 159 experimentally validated plant transcription factor binding motifs, and more than 120-thousand experimentally validated protein-protein interactions to generate models of pre-mycorrhizal sensormore » systems in aspen root. These sensor mechanisms link extracellular signaling molecules with gene regulation through a network comprised of membrane receptors, signal cascade proteins, transcription factors, and transcription factor biding DNA motifs. Modeling predicted four pre-mycorrhizal sensor complexes in aspen that interact with fifteen transcription factors to regulate the expression of 1184 genes in response to extracellular signals synthesized by Laccaria. Predicted extracellular signaling molecules include common signaling molecules such as phenylpropanoids, salicylate, and, jasmonic acid. Lastly, this multi-omic computational modeling approach for predicting the complex sensory networks yielded specific, testable biological hypotheses for mycorrhizal interaction signaling compounds, sensor complexes, and mechanisms of gene regulation.« less

Multi-omics approach identifies molecular mechanisms of plant-fungus mycorrhizal interaction

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

Larsen, Peter E.; Sreedasyam, Avinash; Trivedi, Geetika

In mycorrhizal symbiosis, plant roots form close, mutually beneficial interactions with soil fungi. Before this mycorrhizal interaction can be established however, plant roots must be capable of detecting potential beneficial fungal partners and initiating the gene expression patterns necessary to begin symbiosis. To predict a plant root – mycorrhizal fungi sensor systems, we analyzed in vitro experiments of Populus tremuloides (aspen tree) and Laccaria bicolor (mycorrhizal fungi) interaction and leveraged over 200 previously published transcriptomic experimental data sets, 159 experimentally validated plant transcription factor binding motifs, and more than 120-thousand experimentally validated protein-protein interactions to generate models of pre-mycorrhizal sensormore » systems in aspen root. These sensor mechanisms link extracellular signaling molecules with gene regulation through a network comprised of membrane receptors, signal cascade proteins, transcription factors, and transcription factor biding DNA motifs. Modeling predicted four pre-mycorrhizal sensor complexes in aspen that interact with fifteen transcription factors to regulate the expression of 1184 genes in response to extracellular signals synthesized by Laccaria. Predicted extracellular signaling molecules include common signaling molecules such as phenylpropanoids, salicylate, and, jasmonic acid. Lastly, this multi-omic computational modeling approach for predicting the complex sensory networks yielded specific, testable biological hypotheses for mycorrhizal interaction signaling compounds, sensor complexes, and mechanisms of gene regulation.« less

RNA motif search with data-driven element ordering.

PubMed

Rampášek, Ladislav; Jimenez, Randi M; Lupták, Andrej; Vinař, Tomáš; Brejová, Broňa

2016-05-18

In this paper, we study the problem of RNA motif search in long genomic sequences. This approach uses a combination of sequence and structure constraints to uncover new distant homologs of known functional RNAs. The problem is NP-hard and is traditionally solved by backtracking algorithms. We have designed a new algorithm for RNA motif search and implemented a new motif search tool RNArobo. The tool enhances the RNAbob descriptor language, allowing insertions in helices, which enables better characterization of ribozymes and aptamers. A typical RNA motif consists of multiple elements and the running time of the algorithm is highly dependent on their ordering. By approaching the element ordering problem in a principled way, we demonstrate more than 100-fold speedup of the search for complex motifs compared to previously published tools. We have developed a new method for RNA motif search that allows for a significant speedup of the search of complex motifs that include pseudoknots. Such speed improvements are crucial at a time when the rate of DNA sequencing outpaces growth in computing. RNArobo is available at http://compbio.fmph.uniba.sk/rnarobo .

Physical understanding of complex multiscale biochemical models via algorithmic simplification: Glycolysis in Saccharomyces cerevisiae

NASA Astrophysics Data System (ADS)

Kourdis, Panayotis D.; Steuer, Ralf; Goussis, Dimitris A.

2010-09-01

Large-scale models of cellular reaction networks are usually highly complex and characterized by a wide spectrum of time scales, making a direct interpretation and understanding of the relevant mechanisms almost impossible. We address this issue by demonstrating the benefits provided by model reduction techniques. We employ the Computational Singular Perturbation (CSP) algorithm to analyze the glycolytic pathway of intact yeast cells in the oscillatory regime. As a primary object of research for many decades, glycolytic oscillations represent a paradigmatic candidate for studying biochemical function and mechanisms. Using a previously published full-scale model of glycolysis, we show that, due to fast dissipative time scales, the solution is asymptotically attracted on a low dimensional manifold. Without any further input from the investigator, CSP clarifies several long-standing questions in the analysis of glycolytic oscillations, such as the origin of the oscillations in the upper part of glycolysis, the importance of energy and redox status, as well as the fact that neither the oscillations nor cell-cell synchronization can be understood in terms of glycolysis as a simple linear chain of sequentially coupled reactions.

Modeling Dynamic Anisotropic Behaviour and Spall Failure in Commercial Aluminium Alloys AA7010

NASA Astrophysics Data System (ADS)

Mohd Nor, M. K.; Ma'at, N.; Ho, C. S.

2018-04-01

This paper presents a finite strain constitutive model to predict a complex elastoplastic deformation behaviour involves very high pressures and shockwaves in orthotropic materials of aluminium alloys. The previous published constitutive model is used as a reference to start the development in this work. The proposed formulation that used a new definition of Mandel stress tensor to define Hill's yield criterion and a new shock equation of state (EOS) of the generalised orthotropic pressure is further enhanced with Grady spall failure model to closely predict shockwave propagation and spall failure in the chosen commercial aluminium alloy. This hyperelastic-plastic constitutive model is implemented as a new material model in the Lawrence Livermore National Laboratory (LLNL)-DYNA3D code of UTHM's version, named Material Type 92 (Mat92). The implementations of a new EOS of the generalised orthotropic pressure including the spall failure are also discussed in this paper. The capability of the proposed constitutive model to capture the complex behaviour of the selected material is validated against range of Plate Impact Test data at 234, 450 and 895 ms-1 impact velocities.

New investigations of the guanine trichloro cuprate(II) complex crystal

NASA Astrophysics Data System (ADS)

Fabijanić, Ivana; Matković-Čalogović, Dubravka; Pilepić, Viktor; Ivanišević, Irena; Mohaček-Grošev, Vlasta; Sanković, Krešimir

2017-01-01

Crystals of the guanine trichloro cuprate(II) complex, (HGua)2[Cu2Cl6]·2H2O (HGua = protonated guanine), were prepared and analysed by spectroscopic (IR, Raman) and computational methods. A new single-crystal X-ray diffraction analysis was conducted to obtain data with lower standard uncertainties than those in the previously published structure. Raman and IR spectroscopy and quantum-mechanical analysis gave us new insight into the vibrational states of the (HGua)2[Cu2Cl6]·2H2O crystal. The vibrational spectra of the crystal were assigned by performing a normal coordinate analysis for a free dimer with a centre of inversion as the only symmetry element. The stretching vibration observed at 279 cm-1 in the infrared spectrum corresponds to the N-Cu bond. The noncovalent interaction (NCI) plots and quantum theory of atoms in molecules (QTAIM) analysis of the electron density obtained from periodic DFT calculations elucidated the interactions that exist within the crystal structure. Closed-shell ionic attractions, as well as weak and medium strength hydrogen bonds, prevailed in the crystal packing.

Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs.

PubMed

Zhu, Jinwei; Zhou, Qingqing; Shang, Yuan; Li, Hao; Peng, Mengjuan; Ke, Xiao; Weng, Zhuangfeng; Zhang, Rongguang; Huang, Xuhui; Li, Shawn S C; Feng, Guoping; Lu, Youming; Zhang, Mingjie

2017-12-26

The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Shockwave therapy in the management of complex regional pain syndrome in medial femoral condyle of the knee.

PubMed

Notarnicola, Angela; Moretti, Lorenzo; Tafuri, Silvio; Panella, Antonio; Filipponi, Marco; Casalino, Alessio; Panella, Michele; Moretti, Biagio

2010-06-01

The aim of this prospective study was to assess the efficacy of shockwave (SW) therapy in the management of complex regional pain syndrome (CRPS). In this study, 30 patients (pts) who were affected by CRPS of the medial femoral condyle and unresponsive to previous standard physiotherapeutic and pharmacological treatment underwent 3 SW sessions at 72-h intervals, each consisting of 4000 shocks emitted by a MiniLith SL1 Storz electromagnetic generator. An energy flux density (EFD) of 0.035 or 0.09 mJ/mm(2) was used, depending on how well the patient endured the pain during the treatment. Satisfactory results were observed in 76.7% of the cases (23 pts) at the 2-month follow-up (FU) visit, and in 80% (24 pts) at the 6-month FU visit. The therapeutic effects of SW were caused by decreasing pain. The significant improvements we obtained bear witness to the potential value of SW therapy in the management of CRPS. Copyright 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

The expanding role(s) of eosinophils in health and disease

PubMed Central

Jacobsen, Elizabeth A.; Helmers, Richard A.

2012-01-01

Surprisingly, the role(s) of eosinophils in health and disease is often summarized by clinicians and basic research scientists as a pervasive consensus opinion first learned in medical/graduate school. Eosinophils are rare white blood cells whose activities are primarily destructive and are only relevant in parasitic infections and asthma. However, is this consensus correct? This review argues that the wealth of available studies investigating the role(s) of eosinophils in both health and disease demonstrates that the activities of these granulocytes are far more expansive and complex than previously appreciated. In turn, this greater understanding has led to the realization that eosinophils have significant contributory roles in a wide range of diseases. Furthermore, published studies even implicate eosinophil-mediated activities in otherwise healthy persons. We suggest that the collective reports in the literature showing a role for eosinophils in an ever-increasing number of novel settings highlight the true complexity and importance of this granulocyte. Indeed, discussions of eosinophils are no longer simple and more often than not now begin with the question/statement “Did you know …?” PMID:22936660

Fusion Stage of HIV-1 Entry Depends on Virus-Induced Cell Surface Exposure of Phosphatidylserine.

PubMed

Zaitseva, Elena; Zaitsev, Eugene; Melikov, Kamran; Arakelyan, Anush; Marin, Mariana; Villasmil, Rafael; Margolis, Leonid B; Melikyan, Gregory B; Chernomordik, Leonid V

2017-07-12

HIV-1 entry into host cells starts with interactions between the viral envelope glycoprotein (Env) and cellular CD4 receptors and coreceptors. Previous work has suggested that efficient HIV entry also depends on intracellular signaling, but this remains controversial. Here we report that formation of the pre-fusion Env-CD4-coreceptor complexes triggers non-apoptotic cell surface exposure of the membrane lipid phosphatidylserine (PS). HIV-1-induced PS redistribution depends on Ca 2+ signaling triggered by Env-coreceptor interactions and involves the lipid scramblase TMEM16F. Externalized PS strongly promotes Env-mediated membrane fusion and HIV-1 infection. Blocking externalized PS or suppressing TMEM16F inhibited Env-mediated fusion. Exogenously added PS promoted fusion, with fusion dependence on PS being especially strong for cells with low surface density of coreceptors. These findings suggest that cell-surface PS acts as an important cofactor that promotes the fusogenic restructuring of pre-fusion complexes and likely focuses the infection on cells conducive to PS signaling. Published by Elsevier Inc.

Perspective: An Extension of the STROBE Statement for Observational Studies in Nutritional Epidemiology (STROBE-nut): Explanation and Elaboration

PubMed Central

Berg, Christina; Forsum, Elisabet; Larsson, Christel; Sonestedt, Emily; Åkesson, Agneta; Lachat, Carl; Hawwash, Dana; Kolsteren, Patrick; Byrnes, Graham; De Keyzer, Willem; Van Camp, John; Cade, Janet E; Greenwood, Darren C; Slimani, Nadia; Cevallos, Myriam; Egger, Matthias; Huybrechts, Inge; Wirfält, Elisabet

2017-01-01

Nutritional epidemiology is an inherently complex and multifaceted research area. Dietary intake is a complex exposure and is challenging to describe and assess, and links between diet, health, and disease are difficult to ascertain. Consequently, adequate reporting is necessary to facilitate comprehension, interpretation, and generalizability of results and conclusions. The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement is an international and collaborative initiative aiming to enhance the quality of reporting of observational studies. We previously presented a checklist of 24 reporting recommendations for the field of nutritional epidemiology, called “the STROBE-nut.” The STROBE-nut is an extension of the general STROBE statement, intended to complement the STROBE recommendations to improve and standardize the reporting in nutritional epidemiology. The aim of the present article is to explain the rationale for, and elaborate on, the STROBE-nut recommendations to enhance the clarity and to facilitate the understanding of the guidelines. Examples from the published literature are used as illustrations, and references are provided for further reading. PMID:28916567

Topographic effects on infrasound propagation.

PubMed

McKenna, Mihan H; Gibson, Robert G; Walker, Bob E; McKenna, Jason; Winslow, Nathan W; Kofford, Aaron S

2012-01-01

Infrasound data were collected using portable arrays in a region of variable terrain elevation to quantify the effects of topography on observed signal amplitude and waveform features at distances less than 25 km from partially contained explosive sources during the Frozen Rock Experiment (FRE) in 2006. Observed infrasound signals varied in amplitude and waveform complexity, indicating propagation effects that are due in part to repeated local maxima and minima in the topography on the scale of the dominant wavelengths of the observed data. Numerical simulations using an empirically derived pressure source function combining published FRE accelerometer data and historical data from Project ESSEX, a time-domain parabolic equation model that accounted for local terrain elevation through terrain-masking, and local meteorological atmospheric profiles were able to explain some but not all of the observed signal features. Specifically, the simulations matched the timing of the observed infrasound signals but underestimated the waveform amplitude observed behind terrain features, suggesting complex scattering and absorption of energy associated with variable topography influences infrasonic energy more than previously observed. © 2012 Acoustical Society of America.

Zinc finger protein 274 regulates imprinted expression of transcripts in Prader-Willi syndrome neurons.

PubMed

Langouët, Maéva; Glatt-Deeley, Heather R; Chung, Michael S; Dupont-Thibert, Clémence M; Mathieux, Elodie; Banda, Erin C; Stoddard, Christopher E; Crandall, Leann; Lalande, Marc

2018-02-01

Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay and hyperphagia/obesity and is caused by the absence of paternal contribution to chromosome 15q11-q13. Using induced pluripotent stem cell (iPSC) models of PWS, we previously discovered an epigenetic complex that is comprised of the zinc-finger protein ZNF274 and the SET domain bifurcated 1 (SETDB1) histone H3 lysine 9 (H3K9) methyltransferase and that silences the maternal alleles at the PWS locus. Here, we have knocked out ZNF274 and rescued the expression of silent maternal alleles in neurons derived from PWS iPSC lines, without affecting DNA methylation at the PWS-Imprinting Center (PWS-IC). This suggests that the ZNF274 complex is a separate imprinting mark that represses maternal PWS gene expression in neurons and is a potential target for future therapeutic applications to rescue the PWS phenotype. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The geometry of the forisome-sieve element-sieve plate complex in the phloem of Vicia faba L. leaflets.

PubMed

Peters, Winfried S; van Bel, Aart J E; Knoblauch, Michael

2006-01-01

Forisomes are contractile protein bodies that appear to control flux rates in the phloem of faboid legumes by reversibly plugging the sieve tubes. Plugging is triggered by Ca(2+) which induces an anisotropic deformation of forisomes, consisting of a longitudinal contraction and a radial expansion. By conventional light microscopy and confocal laser-scanning microscopy, the three-dimensional geometry of the forisome-sieve element-sieve plate complex in intact sieve tubes of leaflets of Vicia faba L. was reconstructed. Forisomes were mostly located close to sieve plates, and occasionally were observed drifting unrestrainedly along the sieve element, suggesting that they might be utilized as internal markers of flow direction. The diameter of forisomes in the resting state correlated with the diameter of their sieve elements, supporting the idea that radial expansion of forisomes is the geometric basis of reversible sieve tube plugging. Comparison of the present results regarding forisome geometry in situ with previously published data on forisome reactivity in vitro makes it questionable, however, whether forisomes are capable of completely sealing sieve tubes in V. faba leaves.

Theta Neurofeedback Effects on Motor Memory Consolidation and Performance Accuracy: An Apparent Paradox?

PubMed

Reiner, Miriam; Lev, Dror D; Rosen, Amit

2018-05-15

Previous studies have shown that theta neurofeedback enhances motor memory consolidation on an easy-to-learn finger-tapping task. However, the simplicity of the finger-tapping task precludes evaluating the putative effects of elevated theta on performance accuracy. Mastering a motor sequence is classically assumed to entail faster performance with fewer errors. The speed-accuracy tradeoff (SAT) principle states that as action speed increases, motor performance accuracy decreases. The current study investigated whether theta neurofeedback could improve both performance speed and performance accuracy, or would only enhance performance speed at the cost of reduced accuracy. A more complex task was used to study the effects of parietal elevated theta on 45 healthy volunteers The findings confirmed previous results on the effects of theta neurofeedback on memory consolidation. In contrast to the two control groups, in the theta-neurofeedback group the speed-accuracy tradeoff was reversed. The speed-accuracy tradeoff patterns only stabilized after a night's sleep implying enhancement in terms of both speed and accuracy. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Deep sequencing reveals exceptional diversity and modes of transmission for bacterial sponge symbionts.

PubMed

Webster, Nicole S; Taylor, Michael W; Behnam, Faris; Lücker, Sebastian; Rattei, Thomas; Whalan, Stephen; Horn, Matthias; Wagner, Michael

2010-08-01

Marine sponges contain complex bacterial communities of considerable ecological and biotechnological importance, with many of these organisms postulated to be specific to sponge hosts. Testing this hypothesis in light of the recent discovery of the rare microbial biosphere, we investigated three Australian sponges by massively parallel 16S rRNA gene tag pyrosequencing. Here we show bacterial diversity that is unparalleled in an invertebrate host, with more than 250,000 sponge-derived sequence tags being assigned to 23 bacterial phyla and revealing up to 2996 operational taxonomic units (95% sequence similarity) per sponge species. Of the 33 previously described 'sponge-specific' clusters that were detected in this study, 48% were found exclusively in adults and larvae - implying vertical transmission of these groups. The remaining taxa, including 'Poribacteria', were also found at very low abundance among the 135,000 tags retrieved from surrounding seawater. Thus, members of the rare seawater biosphere may serve as seed organisms for widely occurring symbiont populations in sponges and their host association might have evolved much more recently than previously thought. © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd.

Genomewide screening for genes involved in biofilm formation and miconazole susceptibility in Saccharomyces cerevisiae.

PubMed

Vandenbosch, Davy; De Canck, Evelien; Dhondt, Inne; Rigole, Petra; Nelis, Hans J; Coenye, Tom

2013-12-01

Infections related to fungal biofilms are difficult to treat due to the reduced susceptibility of sessile cells to most antifungal agents. Previous research has shown that 1-10% of sessile Candida cells survive treatment with high doses of miconazole (a fungicidal imidazole). The aim of this study was to identify genes involved in fungal biofilm formation and to unravel the mechanisms of resistance of these biofilms to miconazole. To this end, a screening of a Saccharomyces cerevisiae deletion mutant bank was carried out. Our results revealed that genes involved in peroxisomal transport and the biogenesis of the respiratory chain complex IV play an essential role in biofilm formation. On the other hand, genes involved in transcription and peroxisomal and mitochondrial organization seem to highly influence the susceptibility to miconazole of yeast biofilms. Additionally, our data confirm previous findings on genes involved in biofilm formation and in general stress responses. Our data suggest the involvement of peroxisomes in biofilm formation and miconazole resistance in fungal biofilms. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

[External stability of the elbow after surgical treatment of epicondylitis. Presentation of a case].

PubMed

Llop-Corbacho, A; Romero-Ruiz, J; Denia-Alarcón, N

2014-01-01

Elbow instability is a difficult to diagnose condition in certain cases, and could lead to some problems that limit daily functioning, such as joint blocks, bumps, projections, muscle weakness, and persistent pain. A case is presented of a patient with a clinical picture of epicondylitis, with a previous history of a fall on the affected arm. As there was no improvement after performing conventional non-aggressive treatment, surgery was performed on the affected tendon. The outcome of this was persistent pain and clinical instability of the elbow that ended up requiring surgery to reconstruct the ligament over the external complex. In follow-up 6 months after the operation, the clinical instability had disappeared, but there was still external discomfort and a 30° extension deficit. When faced with a picture of epicondylitis with a previous injury that does not respond to conventional therapies, it is important to take into account the possibility of an underlying elbow instability, ruling this out with a correct physical examination and, where necessary, with the appropriate complementary tests. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

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

Rawle, Rachel A.; Hamerly, Timothy; Tripet, Brian P.

Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted ‘omics’ analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized usingmore » interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis–N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. In conclusion, this multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis–N. equitans association. This study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies.« less

Clinical audit of patients hospitalized due to COPD exacerbation. MAG-1 Study.

PubMed

Escarrabill, Joan; Torrente, Elena; Esquinas, Cristina; Hernández, Carme; Monsó, Eduard; Freixas, Montserrat; Almagro, Pere; Tresserras, Ricard

2015-10-01

Hospitalizations for acute exacerbation of COPD (AECOPD) generate high consumption of health resources, frequent readmissions and high mortality. The MAG -1 study aims to identify critical points to improve the care process of severe AECOPD requiring hospitalization. Observational study, with review of clinical records of patients admitted to hospitals of the Catalan public network for AECOPD. The centers were classified into 3 groups according to the number of discharges/year. Demographic and descriptive data of the previous year, pharmacological treatment, care during hospitalization and discharge process and follow-up, mortality and readmission at 30 and 90 days were analyzed. A total of 910 patients (83% male) with a mean age of 74.3 (+10.1) years and a response rate of 70% were included. Smoking habit was determined in only 45% of cases, of which 9% were active smokers. In 31% of cases, no previous lung function data were available. Median hospital stay was 7 days (IQR 4-10), increasing according the complexity of the hospital. Mortality from admission to 90 days was 12.4% with a readmission rate of 49%. An inverse relationship between length of hospital stay and readmission within 90 days was observed. In a large number of medical records, smoking habit and lung function tests were not appropriately reported. Average hospital stay increases with the complexity of the hospital, but longer stays appear to be associated with lower mortality at follow-up. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.

PubMed

Zhang, Di; Wlodawer, Alexander; Lubkowski, Jacek

2016-11-20

The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-λ receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1Å. In this structure, the receptor peptide forms an 85-Å-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. Both domains of JAK1 are generally well ordered, with regions not seen in the crystal structure limited to loops located away from the receptor-binding regions. The structure provides a much more complete and accurate picture of the interactions between JAK1 and IFNLR1 than those given in earlier reports, illuminating the molecular basis of the JAK-cytokine receptor association. A glutamate residue adjacent to the box2 region in IFNLR1 mimics the mode of binding of a phosphotyrosine in classical SH2 domains. It was shown here that a deletion of residues within the box1 region of the receptor abolishes stable interactions with JAK1, although it was previously shown that box2 alone is sufficient to stabilize a similar complex of the interferon-α receptor and TYK2. Published by Elsevier Ltd.

Imino proton exchange and base-pair kinetics in the AMP-RNA aptamer complex.

PubMed

Nonin, S; Jiang, F; Patel, D J

1997-05-02

We report on the dynamics of base-pair opening in the ATP-binding asymmetric internal loop and flanking base-pairs of the AMP-RNA aptamer complex by monitoring the exchange characteristics of the extremely well resolved imino protons in the NMR spectrum of the complex. The kinetics of imino proton exchange as a function of basic pH or added ammonia catalyst are used to measure the apparent base-pair dissociation constants and lifetimes of Watson-Crick and mismatched base-pairs, as well as the solvent accessibility of the unpaired imino protons in the complex. The exchange characteristics of the imino protons identify the existence of four additional hydrogen bonds stabilizing the conformation of the asymmetric ATP-binding internal loop that were not detected by NOEs and coupling constants alone, but are readily accommodated in the previously reported solution structure of the AMP-RNA aptamer complex published from our laboratory. The hydrogen exchange kinetics of the non-Watson-Crick pairs in the asymmetric internal loop of the AMP-RNA aptamer complex have been characterized and yield apparent dissociation constants (alphaKd) that range from 10(-2) to 10(-7). Surprisingly, three of these alphaKd values are amongst the lowest measured for all base-pairs in the AMP-RNA aptamer complex. Comparative studies of hydrogen exchange of the imino protons in the free RNA aptamer and the AMP-RNA aptamer complex establish that complexation stabilizes not only the bases within the ATP-binding asymmetric internal loop, but also the flanking stem base-pairs (two pairs on either side) of the binding site. We also outline some preliminary results related to the exchange properties of a sugar 2'-hydroxyl proton of a guanosine residue involved in a novel hydrogen bond that has been shown to contribute to the immobilization of the bound AMP by the RNA aptamer, and whose resonance is narrow and downfield shifted in the spectrum.

Increasing algal photosynthetic productivity by integrating ecophysiology with systems biology.

PubMed

Peers, Graham

2014-11-01

Oxygenic photosynthesis is the process by which plants, algae, and cyanobacteria convert sunlight and CO2 into chemical energy and biomass. Previously published estimates suggest that algal photosynthesis is, at best, able to convert approximately 5-7% of incident light energy to biomass and there is opportunity for improvement. Recent analyses of in situ photophysiology in mass cultures of algae and cyanobacteria show that cultivation methods can have detrimental effects on a cell's photophysiology - reinforcing the need to understand the complex responses of cell biology to a highly variable environment. A systems-based approach to understanding the stresses and efficiencies associated with light-energy harvesting, CO2 fixation, and carbon partitioning will be necessary to make major headway toward improving photosynthetic yields. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simulations of the Fuel Economy and Emissions of Hybrid Transit Buses over Planned Local Routes

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

Gao, Zhiming; LaClair, Tim J; Daw, C Stuart

2014-01-01

We present simulated fuel economy and emissions city transit buses powered by conventional diesel engines and diesel-hybrid electric powertrains of varying size. Six representative city drive cycles were included in the study. In addition, we included previously published aftertreatment device models for control of CO, HC, NOx, and particulate matter (PM) emissions. Our results reveal that bus hybridization can significantly enhance fuel economy by reducing engine idling time, reducing demands for accessory loads, exploiting regenerative braking, and shifting engine operation to speeds and loads with higher fuel efficiency. Increased hybridization also tends to monotonically reduce engine-out emissions, but trends inmore » the tailpipe (post-aftertreatment) emissions involve more complex interactions that significantly depend on motor size and drive cycle details.« less

Ecologies, outreach, and the evolution of medical libraries.

PubMed

Shen, Bern

2005-10-01

What are some of the forces shaping the evolution of medical libraries, and where might they lead? Published literature in the fields of library and information sciences, technology, health services research, and business was consulted. Medical libraries currently have a modest footprint in most consumers' personal health ecologies, the network of resources and activities they use to improve their health. They also occupy a relatively small space in the health care, information, and business ecologies of which they are a part. Several trends in knowledge discovery, technology, and social organizations point to ways in which the roles of medical libraries might grow and become more complex. As medical libraries evolve and reach out to previously underserved communities, an ecological approach can serve as a useful organizing framework for the forces shaping this evolution.

Small area estimation of obesity prevalence and dietary patterns: a model applied to Rio de Janeiro city, Brazil.

PubMed

Cataife, Guido

2014-03-01

We propose the use of previously developed small area estimation techniques to monitor obesity and dietary habits in developing countries and apply the model to Rio de Janeiro city. We estimate obesity prevalence rates at the Census Tract through a combinatorial optimization spatial microsimulation model that matches body mass index and socio-demographic data in Brazil's 2008-9 family expenditure survey with Census 2010 socio-demographic data. Obesity ranges from 8% to 25% in most areas and affects the poor almost as much as the rich. Male and female obesity rates are uncorrelated at the small area level. The model is an effective tool to understand the complexity of the problem and to aid in policy design. © 2013 Published by Elsevier Ltd.

An initial MRI picture of limbic encephalitis in subacute sclerosing panencephalitis.

PubMed

Lebon, Sébastien; Maeder, Philippe; Maeder-Ingvar, Malin; Poloni, Claudia; Mayor-Dubois, Claire; Roulet-Perez, Eliane; Jeannet, Pierre-Yves

2011-11-01

Subacute sclerosing panencephalitis (SSPE) is a rare and severe long-term complication of measles. Hallmarks of this entity include progressive cognitive decline, myoclonia, a generalized periodic pattern on EEG and deep white matter abnormalities on MRI. However, imaging can be normal in early stages. We report herein the case of a previously healthy 13-years-old girl with an unusual radiological presentation. She presented with unilateral myoclonia, cognitive decline with memory impairment and a first brain MRI with swelling of both hippocampi mimicking limbic encephalitis. Measles antibodies were positive in CSF and the EEG showed slow periodic complexes. This unusual radiological presentation has never been described in SSPE. Relationship between virus and limbic system are discussed. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Oxidation Mechanisms of Toluene and Benzene

NASA Technical Reports Server (NTRS)

Bittker, David A.

1995-01-01

An expanded and improved version of a previously published benzene oxidation mechanism is presented and shown to model published experimental data fairly successfully. This benzene submodel is coupled to a modified version of a toluene oxidation submodel from the recent literature. This complete mechanism is shown to successfully model published experimental toluene oxidation data for a highly mixed flow reactor and for higher temperature ignition delay times in a shock tube. A comprehensive sensitivity analysis showing the most important reactions is presented for both the benzene and toluene reacting systems. The NASA Lewis toluene mechanism's modeling capability is found to be equivalent to that of the previously published mechanism which contains a somewhat different benzene submodel.

Validating internet research: a test of the psychometric equivalence of internet and in-person samples.

PubMed

Meyerson, Paul; Tryon, Warren W

2003-11-01

This study evaluated the psychometric equivalency of Web-based research. The Sexual Boredom Scale was presented via the World-Wide Web along with five additional scales used to validate it. A subset of 533 participants that matched a previously published sample (Watt & Ewing, 1996) on age, gender, and race was identified. An 8 x 8 correlation matrix from the matched Internet sample was compared via structural equation modeling with a similar 8 x 8 correlation matrix from the previously published study. The Internet and previously published samples were psychometrically equivalent. Coefficient alpha values calculated on the matched Internet sample yielded reliability coefficients almost identical to those for the previously published sample. Factors such as computer administration and uncontrollable administration settings did not appear to affect the results. Demographic data indicated an overrepresentation of males by about 6% and Caucasians by about 13% relative to the U.S. Census (2000). A total of 2,230 participants were obtained in about 8 months without remuneration. These results suggest that data collection on the Web is (1) reliable, (2) valid, (3) reasonably representative, (4) cost effective, and (5) efficient.

Statistical methods used in articles published by the Journal of Periodontal and Implant Science.

PubMed

Choi, Eunsil; Lyu, Jiyoung; Park, Jinyoung; Kim, Hae-Young

2014-12-01

The purposes of this study were to assess the trend of use of statistical methods including parametric and nonparametric methods and to evaluate the use of complex statistical methodology in recent periodontal studies. This study analyzed 123 articles published in the Journal of Periodontal & Implant Science (JPIS) between 2010 and 2014. Frequencies and percentages were calculated according to the number of statistical methods used, the type of statistical method applied, and the type of statistical software used. Most of the published articles considered (64.4%) used statistical methods. Since 2011, the percentage of JPIS articles using statistics has increased. On the basis of multiple counting, we found that the percentage of studies in JPIS using parametric methods was 61.1%. Further, complex statistical methods were applied in only 6 of the published studies (5.0%), and nonparametric statistical methods were applied in 77 of the published studies (38.9% of a total of 198 studies considered). We found an increasing trend towards the application of statistical methods and nonparametric methods in recent periodontal studies and thus, concluded that increased use of complex statistical methodology might be preferred by the researchers in the fields of study covered by JPIS.

Molecular determinants of orexin receptor-arrestin-ubiquitin complex formation.

PubMed

Jaeger, Werner C; Seeber, Ruth M; Eidne, Karin A; Pfleger, Kevin D G

2014-01-01

The orexin system regulates a multitude of key physiological processes, particularly involving maintenance of metabolic homeostasis. Consequently, there is considerable potential for pharmaceutical development for the treatment of disorders from narcolepsy to metabolic syndrome. It acts through the hormonal activity of two endogenous peptides, orexin A binding to orexin receptors 1 and 2 (OX₁ and OX₂) with similar affinity, and orexin B binding to OX₂ with higher affinity than OX₁ receptors. We have previously revealed data differentiating orexin receptor subtypes with respect to their relative stability in forming orexin receptor-arrestin-ubiquitin complexes measured by BRET. Recycling and cellular signalling distinctions were also observed. Here, we have investigated, using BRET, the molecular determinants involved in providing OX₂ receptors with greater β-arrestin-ubiquitin complex stability. The contribution of the C-terminal tail of the OX receptors was investigated by bulk substitution and site-specific mutagenesis using BRET and inositol phosphate assays. Replacement of the OX₁ receptor C-terminus with that of the OX₂ receptor did not result in the expected gain of function, indicating a role for intracellular domain configuration in addition to primary structure. Furthermore, two out of the three putative serine/threonine clusters in the C-terminus were found to be involved in OX₂ receptor-β-arrestin-ubiquitin complex formation. This study provides fundamental insights into the molecular elements that influence receptor-arrestin-ubiquitin complex formation. Understanding how and why the orexin receptors can be functionally differentiated brings us closer to exploiting these receptors as drug targets. © 2013 The Authors. British Journal of Pharmacology published by John Wiley &. Sons Ltd on behalf of The British Pharmacological Society.

Exome sequencing identifies complex I NDUFV2 mutations as a novel cause of Leigh syndrome.

PubMed

Cameron, Jessie M; MacKay, Nevena; Feigenbaum, Annette; Tarnopolsky, Mark; Blaser, Susan; Robinson, Brian H; Schulze, Andreas

2015-09-01

Two siblings with hypertrophic cardiomyopathy and brain atrophy were diagnosed with Complex I deficiency based on low enzyme activity in muscle and high lactate/pyruvate ratio in fibroblasts. Whole exome sequencing results of fibroblast gDNA from one sibling was narrowed down to 190 SNPs or In/Dels in 185 candidate genes by selecting non-synonymous coding sequence base pair changes that were not present in the SNP database. Two compound heterozygous mutations were identified in both siblings in NDUFV2, encoding the 24 kDa subunit of Complex I. The intronic mutation (c.IVS2 + 1delGTAA) is disease causing and has been reported before. The other mutation is novel (c.669_670insG, p.Ser224Valfs*3) and predicted to cause a pathogenic frameshift in the protein. Subsequent investigation of 10 probands with complex I deficiency from different families revealed homozygosity for the intronic c.IVS2 + 1delGTAA mutation in a second, consanguineous family. In this family three of five siblings were affected. Interestingly, they presented with Leigh syndrome but no cardiac involvement. The same genotype had been reported previously in a two families but presenting with hypertrophic cardiomyopathy, trunk hypotonia and encephalopathy. We have identified NDUFV2 mutations in two families with Complex I deficiency, including a novel mutation. The diagnosis of Leigh syndrome expands the clinical phenotypes associated with the c.IVS2 + 1delGTAA mutation in this gene. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Involvement of DPP-IV catalytic residues in enzyme–saxagliptin complex formation

PubMed Central

Metzler, William J.; Yanchunas, Joseph; Weigelt, Carolyn; Kish, Kevin; Klei, Herbert E.; Xie, Dianlin; Zhang, Yaqun; Corbett, Martin; Tamura, James K.; He, Bin; Hamann, Lawrence G.; Kirby, Mark S.; Marcinkeviciene, Jovita

2008-01-01

The inhibition of DPP-IV by saxagliptin has been proposed to occur through formation of a covalent but reversible complex. To evaluate further the mechanism of inhibition, we determined the X-ray crystal structure of the DPP-IV:saxagliptin complex. This structure reveals covalent attachment between S630 and the inhibitor nitrile carbon (C–O distance <1.3 Å). To investigate whether this serine addition is assisted by the catalytic His-Asp dyad, we generated two mutants of DPP-IV, S630A and H740Q, and assayed them for ability to bind inhibitor. DPP-IVH740Q bound saxagliptin with an ∼1000-fold reduction in affinity relative to DPP-IVWT, while DPP-IVS630A showed no evidence for binding inhibitor. An analog of saxagliptin lacking the nitrile group showed unchanged binding properties to the both mutant proteins, highlighting the essential role S630 and H740 play in covalent bond formation between S630 and saxagliptin. Further supporting mechanism-based inhibition by saxagliptin, NMR spectra of enzyme–saxagliptin complexes revealed the presence of three downfield resonances with low fractionation factors characteristic of short and strong hydrogen bonds (SSHB). Comparison of the NMR spectra of various wild-type and mutant DPP-IV:ligand complexes enabled assignment of a resonance at ∼14 ppm to H740. Two additional DPP-IV mutants, Y547F and Y547Q, generated to probe potential stabilization of the enzyme–inhibitor complex by this residue, did not show any differences in inhibitor binding either by ITC or NMR. Together with the previously published enzymatic data, the structural and binding data presented here strongly support a histidine-assisted covalent bond formation between S630 hydroxyl oxygen and the nitrile group of saxagliptin. PMID:18227430

Involvement of DPP-IV Catalytic Residues in Enzyme-Saxagliptin Complex Formation

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

Metzler,W.; Yanchunas, J.; Weigelt, C.

The inhibition of DPP-IV by saxagliptin has been proposed to occur through formation of a covalent but reversible complex. To evaluate further the mechanism of inhibition, we determined the X-ray crystal structure of the DPP-IV:saxagliptin complex. This structure reveals covalent attachment between S630 and the inhibitor nitrile carbon (C-O distance <1.3 Angstroms). To investigate whether this serine addition is assisted by the catalytic His-Asp dyad, we generated two mutants of DPP-IV, S630A and H740Q, and assayed them for ability to bind inhibitor. DPP-IVH740Q bound saxagliptin with an {approx}1000-fold reduction in affinity relative to DPP-IVWT, while DPP-IVS630A showed no evidence formore » binding inhibitor. An analog of saxagliptin lacking the nitrile group showed unchanged binding properties to the both mutant proteins, highlighting the essential role S630 and H740 play in covalent bond formation between S630 and saxagliptin. Further supporting mechanism-based inhibition by saxagliptin, NMR spectra of enzyme-saxagliptin complexes revealed the presence of three downfield resonances with low fractionation factors characteristic of short and strong hydrogen bonds (SSHB). Comparison of the NMR spectra of various wild-type and mutant DPP-IV:ligand complexes enabled assignment of a resonance at {approx}14 ppm to H740. Two additional DPP-IV mutants, Y547F and Y547Q, generated to probe potential stabilization of the enzyme-inhibitor complex by this residue, did not show any differences in inhibitor binding either by ITC or NMR. Together with the previously published enzymatic data, the structural and binding data presented here strongly support a histidine-assisted covalent bond formation between S630 hydroxyl oxygen and the nitrile group of saxagliptin.« less

Redox-Active vs Redox-Innocent: A Comparison of Uranium Complexes Containing Diamine Ligands.

PubMed

Pattenaude, Scott A; Mullane, Kimberly C; Schelter, Eric J; Ferrier, Maryline G; Stein, Benjamin W; Bone, Sharon E; Lezama Pacheco, Juan S; Kozimor, Stosh A; Fanwick, Phillip E; Zeller, Matthias; Bart, Suzanne C

2018-05-11

Uranium complexes ( Mes DAE) 2 U(THF) (1-DAE) and Cp 2 U( Mes DAE) (2-DAE) ( Mes DAE = [ArN-CH 2 CH 2 -NAr]; Ar = 2,4,6-trimethylphenyl (Mes)), bearing redox-innocent diamide ligands, have been synthesized and characterized for a full comparison with previously published, redox-active diimine complexes, ( Mes DAB Me ) 2 U(THF) (1-DAB) and Cp 2 U( Mes DAB Me ) (2-DAB) ( Mes DAB Me = [ArN═C(Me)C(Me)═NAr]; Ar = Mes). These redox-innocent analogues maintain an analogous steric environment to their redox-active ligand counterparts to facilitate a study aimed at determining the differing electronic behavior around the uranium center. Structural analysis by X-ray crystallography showed 1-DAE and 2-DAE have a structural environment very similar to 1-DAB and 2-DAB, respectively. The main difference occurs with coordination of the ene-backbone to the uranium center in the latter species. Electronic absorption spectroscopy reveals these new DAE complexes are nearly identical to each other. X-ray absorption spectroscopy suggests all four species contain +4 uranium ions. The data also indicates that there is an electronic difference between the bis(diamide)-THF uranium complexes as opposed to those that only contain one diamide and two cyclopentadienyl rings. Finally, magnetic measurements reveal that all complexes display temperature-dependent behavior consistent with uranium(IV) ions that do not include ligand radicals. Overall, this study determines that there is no significant bonding difference between the redox-innocent and redox-active ligand frameworks on uranium. Furthermore, there are no data to suggest covalent bonding character using the latter ligand framework on uranium, despite what is known for transition metals.

Influence of chelation strength and bacterial uptake of gallium salicylidene acylhydrazide on biofilm formation and virulence of Pseudomonas aeruginosa.

PubMed

Hakobyan, Shoghik; Rzhepishevska, Olena; Björn, Erik; Boily, Jean-François; Ramstedt, Madeleine

2016-07-01

Development of antibiotic resistance in bacteria causes major challenges for our society and has prompted a great need for new and alternative treatment methods for infection. One promising approach is to target bacterial virulence using for example salicylidene acylhydrazides (hydrazones). Hydrazones coordinate metal ions such as Fe(III) and Ga(III) through a five-membered and a six-membered chelation ring. One suggested mode of action is via restricting bacterial Fe uptake. Thus, it was hypothesized that the chelating strength of these substances could be used to predict their biological activity on bacterial cells. This was investigated by comparing Ga chelation strength of two hydrazone complexes, as well as bacterial Ga uptake, biofilm formation, and virulence in the form of production and secretion of a toxin (ExoS) by Pseudomonas aeruginosa. Equilibrium constants for deprotonation and Ga(III) binding of the hydrazone N'-(5-chloro-2-hydroxy-3-methylbenzylidene)-2,4-dihydroxybenzhydrazide (ME0329), with anti-virulence effect against P. aeruginosa, were determined and compared to bacterial siderophores and the previously described Ga(III) 2-oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (Ga-ME0163) and Ga-citrate complexes. In comparison with these two complexes, it was shown that the uptake of Ga(III) was higher from the Ga-ME0329 complex. The results further show that the Ga-ME0329 complex reduced ExoS expression and secretion to a higher extent than Ga-citrate, Ga-ME0163 or the non-coordinated hydrazone. However, the effect against biofilm formation by P. aeruginosa, by the ME0329 complex, was similar to Ga-citrate and lower than what has been reported for Ga-ME0163. Copyright © 2016. Published by Elsevier Inc.

Solution NMR characterization of magnetic/electronic properties of azide and cyanide-inhibited substrate complexes of human heme oxygenase: implications for steric ligand tilt.

PubMed

Peng, Dungeng; Ogura, Hiroshi; Ma, Li-Hua; Evans, John P; de Montellano, Paul R Ortiz; La Mar, Gerd N

2013-04-01

Solution 2D (1)H NMR was carried out on the azide-ligated substrate complex of human heme oxygenase, hHO, to provide information on the active site molecular structure, chromophore electronic/magnetic properties, and the distal H-bond network linked to the exogenous ligand by catalytically relevant oriented water molecules. While 2D NMR exhibited very similar patterns of two-dimensional nuclear Overhauser spectroscopy cross peaks of residues with substrate and among residues as the previously characterized cyanide complex, significant, broadly distributed chemical shift differences were observed for both labile and non-labile protons. The anisotropy and orientation of the paramagnetic susceptibility tensor, χ, were determined for both the azide and cyanide complexes. The most significant difference observed is the tilt of the major magnetic axes from the heme normal, which is only half as large for the azide than cyanide ligand, with each ligand tilted toward the catalytically cleaved α-meso position. The difference in chemical shifts is quantitatively correlated with differences in dipolar shifts in the respective complexes for all but the distal helix. The necessity of considering dipolar shifts, and hence determination of the orientation/anisotropy of χ, in comparing chemical shifts involving paramagnetic complexes, is emphasized. The analysis shows that the H-bond network cannot detect significant differences in H-bond acceptor properties of cyanide versus azide ligands. Lastly, significant retardation of distal helix labile proton exchange upon replacing cyanide with azide indicates that the dynamic stability of the distal helix is increased upon decreasing the steric interaction of the ligand with the distal helix. Copyright © 2013. Published by Elsevier Inc.

Third-order elastic constants of diamond determined from experimental data

DOE PAGES

Winey, J. M.; Hmiel, A.; Gupta, Y. M.

2016-06-01

The pressure derivatives of the second-order elastic constants (SOECs) of diamond were determined by analyzing previous sound velocity measurements under hydrostatic stress [McSkimin and Andreatch, J. Appl. Phys. 43, 294 (1972)]. Furthermore, our analysis corrects an error in the previously reported results.We present a complete and corrected set of third-order elastic constants (TOECs) using the corrected pressure derivatives, together with published data for the nonlinear elastic response of shock compressed diamond [Lang and Gupta, Phys. Rev. Lett. 106, 125502 (2011)] and it differs significantly from TOECs published previously.

The AASM scoring manual: a critical appraisal.

PubMed

Grigg-Damberger, Madeleine M

2009-11-01

Summarize recently published studies and critiques evaluating the effects of the American Academy of Sleep Medicine (AASM) Sleep Scoring Manual. Only a few retrospective studies have been published evaluating the new AASM Scoring Manual. These have shown that when scoring polysomnograms (PSGs) using the AASM rules compared to previous standards and guidelines: increased amount and percentage of sleep time in Non-Rapid Eye Movement Sleep (NREM) 1 (N1) and N3 sleep, and decreased NREM 2 (N2) sleep; improved interscorer reliability when scoring sleep stages in adults; large differences in apnea-hypopnea indexes (AHIs) using different hypopnea scoring definitions; and PSGs scored using the 'recommended' hypopnea definition in the new manual identified no significant sleep disordered breathing in 40% of lean individuals with symptomatic OSA (AHI ≥5/h by 1999 'Chicago' criteria) and a favorable response to treatment. Two years have passed since the AASM Scoring Manual was published, garnering less criticism than was feared by those who developed it. The improvement in interscorer reliability using the Manual is heartening since this goal shaped many of the choices made. The alternative hypopnea rule should be endorsed as a recommended option. The AASM Scoring Manual provides a foundation upon which we all can build rules and methods that quantify the complexity of sleep and its disorders. Multicenter validation and refinement of the Manual is encouraged.

Chloroform molecules donate hydrogen bonds to S, Se, and Te acceptors: evidence from a published series of terminal chalcogenido complexes

NASA Astrophysics Data System (ADS)

Steiner, Thomas

1998-06-01

Structural data on three chalcogenido complexes published by M. C. Kuchta and G. Parkin, J. Chem. Soc., Chem. Commun. (1994) 1351, provide sound evidence that chloroform molecules can donate hydrogen bonds to S, Se and Te acceptors. This is the first documented example of CHżTe hydrogen bonding. The HżTe distance is only 2.67 Å.

Characterization of the Cadherin-Catenin Complex of the Sea Anemone Nematostella vectensis and Implications for the Evolution of Metazoan Cell-Cell Adhesion.

PubMed

Clarke, Donald Nathaniel; Miller, Phillip W; Lowe, Christopher J; Weis, William I; Nelson, William James

2016-08-01

The cadherin-catenin complex (CCC) mediates cell-cell adhesion in bilaterian animals by linking extracellular cadherin-based adhesions to the actin cytoskeleton. However, it is unknown whether the basic organization of the complex is conserved across all metazoans. We tested whether protein interactions and actin-binding properties of the CCC are conserved in a nonbilaterian animal, the sea anemone Nematostella vectensis We demonstrated that N. vectensis has a complete repertoire of cadherin-catenin proteins, including two classical cadherins, one α-catenin, and one β-catenin. Using size-exclusion chromatography and multi-angle light scattering, we showed that α-catenin and β-catenin formed a heterodimer that bound N. vectensis Cadherin-1 and -2. Nematostella vectensis α-catenin bound F-actin with equivalent affinity as either a monomer or an α/β-catenin heterodimer, and its affinity for F-actin was, in part, regulated by a novel insert between the N- and C-terminal domains. Nematostella vectensis α-catenin inhibited Arp2/3 complex-mediated nucleation of actin filaments, a regulatory property previously thought to be unique to mammalian αE-catenin. Thus, despite significant differences in sequence, the key interactions of the CCC are conserved between bilaterians and cnidarians, indicating that the core function of the CCC as a link between cell adhesions and the actin cytoskeleton is ancestral in the eumetazoans. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

β-Estradiol-dependent activation of the JAK/STAT pathway requires p/CIP and CARM1.

PubMed

Coughlan, N; Thillainadesan, G; Andrews, J; Isovic, M; Torchia, J

2013-06-01

The steroid receptor coactivator p/CIP, also known as SRC-3, is an oncogene commonly amplified in breast and ovarian cancers. p/CIP is known to associate with coactivator arginine methyltransferase 1 (CARM1) on select estrogen responsive genes. We have shown, using a ChIP-on-chip approach, that in response to stimulation with 17β-estradiol (E2), the p/CIP/CARM1 complex is recruited to 204 proximal promoters in MCF-7 cells. Many of the complex target genes have been previously implicated in signaling pathways related to oncogenesis. Jak2, a member of the Jak/Stat signaling cascade, is one of the direct E2-dependent targets of the p/CIP/CARM1 complex. Following E2-treatment, histone modifications at the Jak2 promoter are reflective of a transcriptionally permissive gene, and modest changes in RNA and protein expression lead us to suggest that an additional factor(s) may be required for a more notable transcriptional and functional response. Bioinformatic examination of the 204 proximal promoter sequences of p/CIP/CARM1 targets supports the idea that transcription factor crosstalk is likely the favored mechanism of E2-dependent p/CIP/CARM1 complex recruitment. This data may have implications towards understanding the oncogenic role of p/CIP in breast cancer and ultimately allow for the identification of new prognostic indicators and/or viable therapeutic targets. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

The RNA-binding complex ESCRT-II in Xenopus laevis eggs recognizes purine-rich sequences through its subunit Vps25.

PubMed

Emerman, Amy B; Blower, Michael

2018-06-14

RNA-binding proteins (RBPs) are critical regulators of gene expression. Recent studies have uncovered hundreds of mRNA-binding proteins that do not contain annotated RNA-binding domains and have well-established roles in other cellular processes. Investigation of these nonconventional RBPs is critical for revealing novel RNA-binding domains and may disclose connections between RNA regulation and other aspects of cell biology. Endosomal sorting complex required for transport II (ESCRT-II) is a nonconventional RNA-binding complex that has a canonical role in multivesicular body formation. ESCRT-II previously has been identified as an RNA-binding complex in Drosophila oocytes, but whether its RNA-binding properties extend beyond Drosophila is unknown. In this study, we found that the RNA-binding properties of ESCRT-II are conserved in Xenopus eggs, where ESCRT-II interacted with hundreds of mRNAs. Using a UV-crosslinking approach, we demonstrated that ESCRT-II binds directly to RNA through its subunit Vps25. UV-crosslinking and immunoprecipitation (CLIP)-Seq revealed that Vps25 specifically recognizes a polypurine (i.e. GA-rich) motif in RNA. Using purified components, we could reconstitute the selective Vps25-mediated binding of the polypurine motif in vitro. Our results provide insight into the mechanism by which ESCRT-II selectively binds to mRNAs and also suggest an unexpected link between endosome biology and RNA regulation. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Two new species of the Liolaemuselongatus-kriegi complex (Iguania, Liolaemidae) from Andean highlands of southern Chile.

PubMed

Troncoso-Palacios, Jaime; Díaz, Hugo A; Esquerré, Damien; Urra, Felix A

2015-01-01

The elongatus-kriegi complex is one of the most diverse clades of the Liolaemus (sensu stricto) subgenus of lizards. There are currently 29 species recognized in this group distributed between Chile and Argentina. Based on molecular evidence, there seem to be five main clades nested within this complex: the elongatus, leopardinus, kriegi, petrophilus and punmahuida clades. Liolaemusbuergeri and Liolaemuskriegi, both of the kriegi clade, were believed to inhabit the surroundings of the Laja Lagoon, in the Biobío Region of Chile. Moreover, this Chilean population of Liolaemuskriegi was recently recognized as an undescribed taxon called "Liolaemus sp. A" based on molecular phylogenetics. In this work, we studied these two populations of the Laja Lagoon and provided the morphological diagnosis to describe them as two new species: Liolaemusscorialis sp. n. and Liolaemuszabalai sp. n., previously considered Liolaemusbuergeri and "Liolaemuskriegi/Liolaemus sp. A" respectively. Additionally, we identified another population of Liolaemusscorialis in the vicinity of La Mula Lagoon in the Araucanía Region of Chile. Liolaemusscorialis differs from almost all of the species of the elongatus-kriegi complex by its considerably smaller size. Nevertheless, without molecular data we cannot assign it to any particular subclade. Liolaemuszabalai belongs to the kriegi clade based on published molecular phylogenies. Finally, we provide some natural history data on both species and we document for the first time the presence of Liolaemusneuquensis in Chile from a museum specimen from La Mula Lagoon.

Learning a weighted sequence model of the nucleosome core and linker yields more accurate predictions in Saccharomyces cerevisiae and Homo sapiens.

PubMed

Reynolds, Sheila M; Bilmes, Jeff A; Noble, William Stafford

2010-07-08

DNA in eukaryotes is packaged into a chromatin complex, the most basic element of which is the nucleosome. The precise positioning of the nucleosome cores allows for selective access to the DNA, and the mechanisms that control this positioning are important pieces of the gene expression puzzle. We describe a large-scale nucleosome pattern that jointly characterizes the nucleosome core and the adjacent linkers and is predominantly characterized by long-range oscillations in the mono, di- and tri-nucleotide content of the DNA sequence, and we show that this pattern can be used to predict nucleosome positions in both Homo sapiens and Saccharomyces cerevisiae more accurately than previously published methods. Surprisingly, in both H. sapiens and S. cerevisiae, the most informative individual features are the mono-nucleotide patterns, although the inclusion of di- and tri-nucleotide features results in improved performance. Our approach combines a much longer pattern than has been previously used to predict nucleosome positioning from sequence-301 base pairs, centered at the position to be scored-with a novel discriminative classification approach that selectively weights the contributions from each of the input features. The resulting scores are relatively insensitive to local AT-content and can be used to accurately discriminate putative dyad positions from adjacent linker regions without requiring an additional dynamic programming step and without the attendant edge effects and assumptions about linker length modeling and overall nucleosome density. Our approach produces the best dyad-linker classification results published to date in H. sapiens, and outperforms two recently published models on a large set of S. cerevisiae nucleosome positions. Our results suggest that in both genomes, a comparable and relatively small fraction of nucleosomes are well-positioned and that these positions are predictable based on sequence alone. We believe that the bulk of the remaining nucleosomes follow a statistical positioning model.

Learning a Weighted Sequence Model of the Nucleosome Core and Linker Yields More Accurate Predictions in Saccharomyces cerevisiae and Homo sapiens

PubMed Central

Reynolds, Sheila M.; Bilmes, Jeff A.; Noble, William Stafford

2010-01-01

DNA in eukaryotes is packaged into a chromatin complex, the most basic element of which is the nucleosome. The precise positioning of the nucleosome cores allows for selective access to the DNA, and the mechanisms that control this positioning are important pieces of the gene expression puzzle. We describe a large-scale nucleosome pattern that jointly characterizes the nucleosome core and the adjacent linkers and is predominantly characterized by long-range oscillations in the mono, di- and tri-nucleotide content of the DNA sequence, and we show that this pattern can be used to predict nucleosome positions in both Homo sapiens and Saccharomyces cerevisiae more accurately than previously published methods. Surprisingly, in both H. sapiens and S. cerevisiae, the most informative individual features are the mono-nucleotide patterns, although the inclusion of di- and tri-nucleotide features results in improved performance. Our approach combines a much longer pattern than has been previously used to predict nucleosome positioning from sequence—301 base pairs, centered at the position to be scored—with a novel discriminative classification approach that selectively weights the contributions from each of the input features. The resulting scores are relatively insensitive to local AT-content and can be used to accurately discriminate putative dyad positions from adjacent linker regions without requiring an additional dynamic programming step and without the attendant edge effects and assumptions about linker length modeling and overall nucleosome density. Our approach produces the best dyad-linker classification results published to date in H. sapiens, and outperforms two recently published models on a large set of S. cerevisiae nucleosome positions. Our results suggest that in both genomes, a comparable and relatively small fraction of nucleosomes are well-positioned and that these positions are predictable based on sequence alone. We believe that the bulk of the remaining nucleosomes follow a statistical positioning model. PMID:20628623

Experiences of acute pain in children who present to a healthcare facility for treatment: a systematic review of qualitative evidence.

PubMed

Pope, Nicole; Tallon, Mary; McConigley, Ruth; Leslie, Gavin; Wilson, Sally

2017-06-01

Pain is a universal and complex phenomenon that is personal, subjective and specific. Despite growing knowledge in pediatric pain, management of children's pain remains sub-optimal and is linked to negative behavioral and physiological consequences later in life. As there is no synthesis of these studies, it was timely to undertake a systematic review. To identify, evaluate and synthesize the existing qualitative evidence on children's experiences of acute pain, including pain management, within a healthcare facility. Children aged four to 18 years (inclusive) attending a healthcare facility who experienced acute pain associated with any injury, medical condition or treatment. Children's experiences and perceptions of their acute pain, pain management and expectations of others in managing their pain. Studies on children's experiences of pain in the postoperative context were excluded as a systematic review exploring this phenomenon had previously been published. Studies reporting on children's experiences of chronic pain were also excluded. Any healthcare facility including general practitioners' surgeries, hospitals, emergency departments and outpatient clinics. Qualitative studies including phenomenology, grounded theory, ethnography, action research and feminist research designs. Using a three-step search strategy, databases were searched in December 2015 to identify both published and unpublished articles from 2000 to 2015. Studies published in languages other than English were excluded. All studies that met the inclusion criteria were assessed by at least two independent reviewers for methodological quality using a standardized critical appraisal tool from the Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI). Data were extracted from the papers included in the review using standardized data extraction tool from JBI-QARI. Findings were pooled using JBI-QARI. Findings were rated according to their level of credibility and categorized based on similarity in meaning and then were subjected to a meta-synthesis. Four studies were included in this review. Two meta-syntheses were generated from five categories based on 21 findings: first, children can express their pain experiences in terms of cause, location, meaning and quality. Children's pain experiences include both physical and psychological dimensions. Children's pain experiences are influenced by their previous pain experiences, pain expectations and sociocultural factors. Second, children use a range of cognitive/behavioral and sensory/physical self-soothing strategies not only to help manage their pain, but also rely on the actions and presence of others as helpers when they are in pain. Children's pain is a multi-dimensional complex phenomenon relying upon a multi-modal approach to management. Children as young as four years are capable of articulating their pain in terms of location, intensity and depth. The way children perceive, express and respond to pain is shaped by sociocultural factors, previous pain experiences and their expectations of pain. Children, parents and healthcare professionals play an important role in managing children's pain experiences.

Solubility product constants of covellite and a poorly crystalline copper sulfide precipitate at 298 K

NASA Astrophysics Data System (ADS)

Shea, Damian; Helz, George R.

1989-02-01

The equilibrium constant at 25°C for the following reaction has been measured in NaCl media by an indirect method: CuS(cov) + H +(aq) ⇄ Cu 2+(aq) + HS -(qa), Ksp = MCu 2+MHS -(10 +pH) where CuS(cov) designates synthetic covellite. Values of pKsp are 21.39, 21.04 and 20.95 at NaCl = 0.2, 0.7 and 1.0 M, respectively; the uncertainty in these Ksp values is ±0.15. The free energy of formation of covellite, for which published values are discordant, is calculated to be -11.83±0.4 kcal/mole at 298 K (-49.50 ± 1.7 kJ/mole). This value is obtained by extrapolating the meaured pKsp values to infinite dilution with corrections for Cl - complexing. Applying similar Cl - complexing corrections, based on recent measurements by Seward, to previously published solubility data for galena yields a revised pKsp0 for galena of 12.78. A poorly crystalline precipitate, obtained by mixing Cu 2+ and HS - solutions, yielded a reversible solubility product 3 orders of magnitude greater than that of covellite but about 3 orders of magnitude less than that of a truly amorphous phase, super-cooled liquid CuS. The poorly crystalline phase has not been studied previously. Its bulk composition was Cu 1.18S, but microprobe analysis revealed that it was a partially exsolved mixture of roughly Cu 1.11S and Cu 1.32S (similar to known blaubleibender covellites). It was kinetically unstable, and converted to covellite when thermally annealed or when exposed to polysulfide solutions. Because of its instability, a material of this nature is unlikely to account for the amorphous copper sulfide alleged to occur in the Red Sea Brine deposits. However, it is possible that on short time scales dissolved Cu in sulfidic waters is controlled by metastable, rather than stable phases, as is known to be the case with dissolved Fe.

Inelastic Compaction in High-Porosity Limestone Monitored Using Acoustic Emissions

NASA Astrophysics Data System (ADS)

Baud, Patrick; Schubnel, Alexandre; Heap, Michael; Rolland, Alexandra

2017-12-01

We performed a systematic investigation of mechanical compaction and strain localization in Saint-Maximin limestone, a quartz-rich, high-porosity (37%) limestone from France. Our new data show that the presence of a significant proportion of secondary mineral (i.e., quartz) did not impact the mechanical strength of the limestone in both the brittle faulting and cataclastic flow regimes, but that the presence of water exerted a significant weakening effect. In contrast to previously published studies on deformation in limestones, inelastic compaction in Saint-Maximin limestone was accompanied by abundant acoustic emission (AE) activity. The location of AE hypocenters during triaxial experiments revealed the presence of compaction localization. Two failure modes were identified in agreement with microstructural analysis and X-ray computed tomography imaging: compactive shear bands developed at low confinement and complex diffuse compaction bands formed at higher confinement. Microstructural observations on deformed samples suggest that the recorded AE activity associated with inelastic compaction, unusual for a porous limestone, could have been due to microcracking at the quartz grain interfaces. Similar to published data on high-porosity macroporous limestones, the crushing of calcite grains was the dominant micromechanism of inelastic compaction in Saint-Maximin limestone. New P wave velocity data show that the effect of microcracking was dominant near the yield point and resulted in a decrease in P wave velocity, while porosity reduction resulted in a significant increase in P wave velocity beyond a few percent of plastic volumetric strain. These new data highlight the complex interplay between mineralogy, rock microstructure, and strain localization in porous rocks.

An update on the clinical evidence that supports biosimilar approvals in Europe.

PubMed

Mielke, Johanna; Jilma, Bernd; Jones, Byron; Koenig, Franz

2018-03-25

Sponsors and regulators have more than 10 years of experience with the development of biosimilars in Europe. However, the regulatory pathway is still evolving. The present article provides an update on biosimilar development in practice by reviewing the clinical development programmes of recently approved biosimilars in Europe. We used the European public assessment reports (EPARs) which are published by the European Medicines Agency (EMA) for a comparison of the clinical development programmes of the 37 approved biosimilars in Europe. Here, we present novel strategies in the development of biosimilars by focusing specifically on the 17 biosimilars that have gained approval in the last year, but we also compare additional key characteristics for all approved biosimilars. The high variability of the clinical development strategies that we found previously was confirmed in the present analysis. Compared with earlier biosimilar applications, more nonstandard development strategies have been used recently. This includes, for example, applications without any studies in patients, and more complex study designs. During this study, we found that the EPARs for biosimilars seem to be improving; however, we identified important details which were still often missing. We provide a proposal for a checklist of the minimum information that should be included in biosimilar EPARs for giving the general public insights into the rationale for the approval of biosimilars. European regulators still seem to be open to consider approaches that differ from the guidelines or previous applications, as long as justification is provided. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Swedish women's perceptions of and conformity to feminine norms.

PubMed

Kling, Johanna; Holmqvist Gattario, Kristina; Frisén, Ann

2017-06-01

The relatively high gender equality in the Swedish society is likely to exert an influence on gender role construction. Hence, the present research aimed to investigate Swedish women's perceptions of and conformity to feminine norms. A mixed methods approach with two studies was used. In Study 1, young Swedish women's gender role conformity, as measured by the Conformity to Feminine Norms Inventory 45 (CFNI-45), was compared to the results from previously published studies in Canada, the United States, and Slovakia. Overall, Swedish women displayed less conformity than their foreign counterparts, with the largest difference on the subscale Sexual fidelity. In Study 2, focus group interviews with young Swedish women added a more complex picture of feminine norms in the Swedish society. For instance the results indicated that Swedish women, while living in a society with a strong gender equality discourse, are torn between the perceived need to invest in their appearances and the risk of being viewed as non-equal when doing so. In sum, despite the fact that traditional gender roles are less pronounced in Sweden, gender role conformity is still a pressing issue. Since attending to the potential roles of feminine norms in women's lives previously has been proposed to be useful in counseling and therapeutic work, the present research also offers valuable information for both researchers and practitioners. [Correction added on 5 May 2017, after first online publication in April 2017: An incorrect Abstract was inadvertently captured in the published article and has been corrected in this current version.]. © 2017 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

The MC1R and ASIP Coat Color Loci May Impact Behavior in the Horse

PubMed Central

Jacobs, Lauren N.; Staiger, Elizabeth A.; Albright, Julia D.

2016-01-01

Shared signaling pathways utilized by melanocytes and neurons result in pleiotropic traits of coat color and behavior in many mammalian species. For example, in humans polymorphisms at MC1R cause red hair, increased heat sensitivity, and lower pain tolerance. In deer mice, rats, and foxes, ASIP polymorphisms causing black coat color lead to more docile demeanors and reduced activity. Horse (Equus caballus) base coat color is primarily determined by polymorphisms at the Melanocortin-1 Receptor (MC1R) and Agouti Signaling Protein (ASIP) loci, creating a black, bay, or chestnut coat. Our goal was to investigate correlations between genetic loci for coat color and temperament traits in the horse. We genotyped a total of 215 North American Tennessee Walking Horses for the 2 most common alleles at the MC1R (E/e) and ASIP (A/a) loci using previously published PCR and RFLP methods. The horses had a mean age of 10.5 years and comprised 83 geldings, 25 stallions, and 107 mares. To assess behavior, we adapted a previously published survey for handlers to score horses from 1 to 9 on 20 questions related to specific aspects of temperament. We utilized principle component analysis to combine the individual survey scores into 4 factors of variation in temperament phenotype. A factor component detailing self-reliance correlated with genotypes at the ASIP locus; black mares (aa) were more independent than bay mares (A_) (P = 0.0063). These findings illuminate a promising and novel animal model for future study of neuroendocrine mechanisms in complex behavioral phenotypes. PMID:26884605

Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure.

PubMed

Camarata, Andrew S; Switchenko, Jeffrey M; Demidenko, Eugene; Flood, Ann B; Swartz, Harold M; Ali, Arif N

2016-04-01

Current radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose-rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy min. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for the low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures.

Artificial intelligence in neurodegenerative disease research: use of IBM Watson to identify additional RNA-binding proteins altered in amyotrophic lateral sclerosis.

PubMed

Bakkar, Nadine; Kovalik, Tina; Lorenzini, Ileana; Spangler, Scott; Lacoste, Alix; Sponaugle, Kyle; Ferrante, Philip; Argentinis, Elenee; Sattler, Rita; Bowser, Robert

2018-02-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with no effective treatments. Numerous RNA-binding proteins (RBPs) have been shown to be altered in ALS, with mutations in 11 RBPs causing familial forms of the disease, and 6 more RBPs showing abnormal expression/distribution in ALS albeit without any known mutations. RBP dysregulation is widely accepted as a contributing factor in ALS pathobiology. There are at least 1542 RBPs in the human genome; therefore, other unidentified RBPs may also be linked to the pathogenesis of ALS. We used IBM Watson ® to sieve through all RBPs in the genome and identify new RBPs linked to ALS (ALS-RBPs). IBM Watson extracted features from published literature to create semantic similarities and identify new connections between entities of interest. IBM Watson analyzed all published abstracts of previously known ALS-RBPs, and applied that text-based knowledge to all RBPs in the genome, ranking them by semantic similarity to the known set. We then validated the Watson top-ten-ranked RBPs at the protein and RNA levels in tissues from ALS and non-neurological disease controls, as well as in patient-derived induced pluripotent stem cells. 5 RBPs previously unlinked to ALS, hnRNPU, Syncrip, RBMS3, Caprin-1 and NUPL2, showed significant alterations in ALS compared to controls. Overall, we successfully used IBM Watson to help identify additional RBPs altered in ALS, highlighting the use of artificial intelligence tools to accelerate scientific discovery in ALS and possibly other complex neurological disorders.

The use of genetic programming to develop a predictor of swash excursion on sandy beaches

NASA Astrophysics Data System (ADS)

Passarella, Marinella; Goldstein, Evan B.; De Muro, Sandro; Coco, Giovanni

2018-02-01

We use genetic programming (GP), a type of machine learning (ML) approach, to predict the total and infragravity swash excursion using previously published data sets that have been used extensively in swash prediction studies. Three previously published works with a range of new conditions are added to this data set to extend the range of measured swash conditions. Using this newly compiled data set we demonstrate that a ML approach can reduce the prediction errors compared to well-established parameterizations and therefore it may improve coastal hazards assessment (e.g. coastal inundation). Predictors obtained using GP can also be physically sound and replicate the functionality and dependencies of previous published formulas. Overall, we show that ML techniques are capable of both improving predictability (compared to classical regression approaches) and providing physical insight into coastal processes.

Morphological and genetic evolution in eastern populations of the Macrhybopsis aestivalis complex (Cypriniformes: Cyprinidae), with the descriptions of four new species.

PubMed

Gilbert, Carter R; Mayden, Richard L; Powers, Steven L

2017-03-30

For many years the North American cyprinid fish Macrhybopsis aestivalis (common name: Speckled Chub) was regarded as a single widespread and morphologically variable species, occurring in rivers throughout much of the Mississippi Valley and geographically adjacent eastern Gulf slope drainages, west to the Rio Grande basin in Texas, New Mexico, and Mexico. Eisenhour (1997) completed a morphological study of western populations of the Speckled Chub, the results of which appeared thereafter in published form (Eisenhour 1999, 2004). He demonstrated the existence of five valid species west of the Mississippi River (aestivalis, marconis, australis, tetranema, hyostoma), of which the name aestivalis was shown to be restricted to the population occurring in the Rio Grande and the geographically adjacent Rio San Fernando system, in northeastern Mexico. Eisenhour (2004) considered populations throughout the middle Mississippi Valley and its major tributaries to be a single morphologically variable species (hyostoma), and he also indicated that populations of Macrhybopsis from eastern Gulf slope drainages may represent a complex of species. Genetic confirmation of Eisenhour's conclusions regarding western species appeared in the publication by Underwood et al. (2003), who also showed that western populations of M. hyostoma, as presently recognized, are genetically much more complex than previously considered.     Meanwhile, the present authors were involved in a companion study of eastern populations of Macrhybopsis, for which a genetic summary of the eastern Gulf coast species was published by Mayden & Powers (2004). Based on their findings, four species were recognized from southeastern drainages (identified as species A-D), although no formal taxonomic descriptions were included. Their genetic data, in combination with meristic, morphometric and other morphological data presented herein, form the basis for a revised classification of eastern Macrhybopsis populations, including formal descriptions of the four new species from eastern Gulf coast drainages.

Clinical Information Systems as the Backbone of a Complex Information Logistics Process: Findings from the Clinical Information Systems Perspective for 2016.

PubMed

Hackl, W O; Ganslandt, T

2017-08-01

Objective: To summarize recent research and to propose a selection of best papers published in 2016 in the field of Clinical Information Systems (CIS). Method: The query used to retrieve the articles for the CIS section of the 2016 edition of the IMIA Yearbook of Medical Informatics was reused. It again aimed at identifying relevant publications in the field of CIS from PubMed and Web of Science and comprised search terms from the Medical Subject Headings (MeSH) catalog as well as additional free text search terms. The retrieved articles were categorized in a multi-pass review carried out by the two section editors. The final selection of candidate papers was then peer-reviewed by Yearbook editors and external reviewers. Based on the review results, the best papers were then chosen at the selection meeting with the IMIA Yearbook editorial board. Text mining, term co-occurrence mapping, and topic modelling techniques were used to get an overview on the content of the retrieved articles. Results: The query was carried out in mid-January 2017, yielding a consolidated result set of 2,190 articles published in 921 different journals. Out of them, 14 papers were nominated as candidate best papers and three of them were finally selected as the best papers of the CIS field. The content analysis of the articles revealed the broad spectrum of topics covered by CIS research. Conclusions: The CIS field is multi-dimensional and complex. It is hard to draw a well-defined outline between CIS and other domains or other sections of the IMIA Yearbook. The trends observed in the previous years are progressing. Clinical information systems are more than just sociotechnical systems for data collection, processing, exchange, presentation, and archiving. They are the backbone of a complex, trans-institutional information logistics process. Georg Thieme Verlag KG Stuttgart.

Medical students' opportunities to participate and learn from activities at an internal medicine ward: an ethnographic study.

PubMed

Hägg-Martinell, A; Hult, H; Henriksson, P; Kiessling, A

2017-02-14

To optimise medical students' early clerkship is a complex task since it is conducted in a context primarily organised to take care of patients. Previous studies have explored medical students' perceptions of facilitation and hindrance of learning. However, the opportunities for medical student to learn within the culture of acute medicine care have not been fully investigated. This study aimed to explore how medical students approach, interact and socialise in an acute internal medicine ward context, and how spaces for learning are created and used in such a culture. Ethnographic observations were performed of medical students' interactions and learning during early clerkship at an acute internal medicine care ward. Field notes were taken, transcribed and analysed qualitatively. Data analysis was guided by Wenger's theory of communities of practice. 21 medical students and 30 supervisors participated. Two themes were identified: Nervousness and curiosity- students acted nervously and stressed, especially when they could not answer questions. Over time curiosity could evolve. Unexplored opportunities to support students in developing competence to judge and approach more complex patient-related problems were identified. Invited and involved -students were exposed to a huge variation of opportunities to learn, and to interact and to be involved. Short placements seemed to disrupt the learning process. If and how students became involved also depended on supervisors' activities and students' initiatives. This study shed light on how an acute internal medicine ward culture can facilitate medical students' possibilities to participate and learn. Medical students' learning situations were characterised by questions and answers rather than challenging dialogues related to the complexity of presented patient cases. Further, students experienced continuous transfers between learning situations where the potential to be involved differed in a wide variety of ways. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Replication of Simulated Prebiotic Amphiphilic Vesicles in a Finite Environment Exhibits Complex Behavior That Includes High Progeny Variability and Competition

PubMed Central

Armstrong, Don L.; Lancet, Doron

2018-01-01

Abstract We studied the simulated replication and growth of prebiotic vesicles composed of 140 phospholipids and cholesterol using our R-GARD (Real Graded Autocatalysis Replication Domain) formalism that utilizes currently extant lipids that have known rate constants of lipid-vesicle interactions from published experimental data. R-GARD normally modifies kinetic parameters of lipid-vesicle interactions based on vesicle composition and properties. Our original R-GARD model tracked the growth and division of one vesicle at a time in an environment with unlimited lipids at a constant concentration. We explore here a modified model where vesicles compete for a finite supply of lipids. We observed that vesicles exhibit complex behavior including initial fast unrestricted growth, followed by intervesicle competition for diminishing resources, then a second growth burst driven by better-adapted vesicles, and ending with a final steady state. Furthermore, in simulations without kinetic parameter modifications (“invariant kinetics”), the initial replication was an order of magnitude slower, and vesicles' composition variability at the final steady state was much lower. The complex kinetic behavior was not observed either in the previously published R-GARD simulations or in additional simulations presented here with only one lipid component. This demonstrates that both a finite environment (inducing selection) and multiple components (providing variation for selection to act upon) are crucial for portraying evolution-like behavior. Such properties can improve survival in a changing environment by increasing the ability of early protocellular entities to respond to rapid environmental fluctuations likely present during abiogenesis both on Earth and possibly on other planets. This in silico simulation predicts that a relatively simple in vitro chemical system containing only lipid molecules might exhibit properties that are relevant to prebiotic processes. Key Words: Phospholipid vesicles—Prebiotic compartments—Prebiotic vesicle competition—Prebiotic vesicle variability. Astrobiology 18, 419–430. PMID:29634319

40 CFR 721.5325 - Nickel acrylate complex.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Nickel acrylate complex. 721.5325... Substances § 721.5325 Nickel acrylate complex. Link to an amendment published at 79 FR 34637, June 18, 2014... nickel acrylate complex (PMN P-85-1034) is subject to reporting under this section for the significant...

A Systematic Review of Conceptual Frameworks of Medical Complexity and New Model Development.

PubMed

Zullig, Leah L; Whitson, Heather E; Hastings, Susan N; Beadles, Chris; Kravchenko, Julia; Akushevich, Igor; Maciejewski, Matthew L

2016-03-01

Patient complexity is often operationalized by counting multiple chronic conditions (MCC) without considering contextual factors that can affect patient risk for adverse outcomes. Our objective was to develop a conceptual model of complexity addressing gaps identified in a review of published conceptual models. We searched for English-language MEDLINE papers published between 1 January 2004 and 16 January 2014. Two reviewers independently evaluated abstracts and all authors contributed to the development of the conceptual model in an iterative process. From 1606 identified abstracts, six conceptual models were selected. One additional model was identified through reference review. Each model had strengths, but several constructs were not fully considered: 1) contextual factors; 2) dynamics of complexity; 3) patients' preferences; 4) acute health shocks; and 5) resilience. Our Cycle of Complexity model illustrates relationships between acute shocks and medical events, healthcare access and utilization, workload and capacity, and patient preferences in the context of interpersonal, organizational, and community factors. This model may inform studies on the etiology of and changes in complexity, the relationship between complexity and patient outcomes, and intervention development to improve modifiable elements of complex patients.

Preliminary Multivariable Cost Model for Space Telescopes

NASA Technical Reports Server (NTRS)

Stahl, H. Philip

2010-01-01

Parametric cost models are routinely used to plan missions, compare concepts and justify technology investments. Previously, the authors published two single variable cost models based on 19 flight missions. The current paper presents the development of a multi-variable space telescopes cost model. The validity of previously published models are tested. Cost estimating relationships which are and are not significant cost drivers are identified. And, interrelationships between variables are explored

Uses of the Twins UK genetic database.

PubMed

Spector, Tim D

2007-11-01

Tim Spector is a Professor of Genetic Epidemiology at King's College London and Director of the Twin Research and Genetic Epidemiology Unit at St Thomas' Hospital, London. Professor Spector graduated from St Bartholomew's Hospital Medical School, London, in 1982. After working in General Medicine, he completed a MSc in Epidemiology, and his MD degree at the University of London in 1989. He founded the UK Twins Registry of 10,000 twins in 1993, which is one of the largest collections of genotype and phenotype information on twins worldwide, whose breadth of research has expanded to cover a wide range of common complex traits many of which were previously thought to be mainly due to aging and the environment. He has published over 350 research articles on common diseases. He has written several original articles on the genetics of a wide range of diseases and traits including back pain, acne, inflammation, obesity, memory, musical ability and sexuality. He is the principal investigator of the EU Euroclot and Treat OA study, and a partner in five others. He has written several books, focusing on osteoporosis and genetics and, in 2003, he published a popular book on genetics: Your Genes Unzipped.

Graphic facilitation as a novel approach to practice development.

PubMed

Leonard, Angela; Bonaconsa, Candice; Ssenyonga, Lydia; Coetzee, Minette

2017-10-10

The active participation of staff from the outset of any health service or practice improvement process ensures they are more likely to become engaged in the implementation phases that follow initial service analyses. Graphic facilitation is a way of getting participants to develop an understanding of complex systems and articulate solutions from within them. This article describes how a graphic facilitation process enabled the members of a multidisciplinary team at a specialist paediatric neurosurgery hospital in Uganda to understand how their system worked. The large graphic representation the team created helped each team member to visualise their day-to-day practice, understand each person's contribution, celebrate their triumphs and highlight opportunities for service improvement. The process highlighted three features of their practice: an authentic interdisciplinary team approach to care, admission of the primary carer with the child, and previously unrecognised delays in patient flow through the outpatients department. The team's active participation and ownership of the process resulted in sustainable improvements to clinical practice. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function

PubMed Central

Ungar, Daniel; Oka, Toshihiko; Brittle, Elizabeth E.; Vasile, Eliza; Lupashin, Vladimir V.; Chatterton, Jon E.; Heuser, John E.; Krieger, Monty; Waters, M. Gerard

2002-01-01

Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modification. Three complexes that have previously been partially characterized include (a) the Golgi transport complex (GTC), identified in an in vitro membrane transport assay, (b) the ldlCp complex, identified in analyses of CHO cell mutants with defects in Golgi-associated glycosylation reactions, and (c) the mammalian Sec34 complex, identified by homology to yeast Sec34p, implicated in vesicular transport. We show that these three complexes are identical and rename them the conserved oligomeric Golgi (COG) complex. The COG complex comprises four previously characterized proteins (Cog1/ldlBp, Cog2/ldlCp, Cog3/Sec34, and Cog5/GTC-90), three homologues of yeast Sec34/35 complex subunits (Cog4, -6, and -8), and a previously unidentified Golgi-associated protein (Cog7). EM of ldlB and ldlC mutants established that COG is required for normal Golgi morphology. “Deep etch” EM of purified COG revealed an ∼37-nm-long structure comprised of two similarly sized globular domains connected by smaller extensions. Consideration of biochemical and genetic data for mammalian COG and its yeast homologue suggests a model for the subunit distribution within this complex, which plays critical roles in Golgi structure and function. PMID:11980916

Vibrational dynamics of vocal folds using nonlinear normal modes.

PubMed

Pinheiro, Alan P; Kerschen, Gaëtan

2013-08-01

Many previous works involving physical models, excised and in vivo larynges have pointed out nonlinear vibration in vocal folds during voice production. Moreover, theoretical studies involving mechanical modeling of these folds have tried to gain a profound understanding of the observed nonlinear phenomena. In this context, the present work uses the nonlinear normal mode theory to investigate the nonlinear modal behavior of 16 subjects using a two-mass mechanical modeling of the vocal folds. The free response of the conservative system at different energy levels is considered to assess the impact of the structural nonlinearity of the vocal fold tissues. The results show very interesting and complex nonlinear phenomena including frequency-energy dependence, subharmonic regimes and, in some cases, modal interactions, entrainment and bifurcations. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders--updated European recommendations.

PubMed

Dequeker, Els; Stuhrmann, Manfred; Morris, Michael A; Casals, Teresa; Castellani, Carlo; Claustres, Mireille; Cuppens, Harry; des Georges, Marie; Ferec, Claude; Macek, Milan; Pignatti, Pier-Franco; Scheffer, Hans; Schwartz, Marianne; Witt, Michal; Schwarz, Martin; Girodon, Emmanuelle

2009-01-01

The increasing number of laboratories offering molecular genetic analysis of the CFTR gene and the growing use of commercial kits strengthen the need for an update of previous best practice guidelines (published in 2000). The importance of organizing regional or national laboratory networks, to provide both primary and comprehensive CFTR mutation screening, is stressed. Current guidelines focus on strategies for dealing with increasingly complex situations of CFTR testing. Diagnostic flow charts now include testing in CFTR-related disorders and in fetal bowel anomalies. Emphasis is also placed on the need to consider ethnic or geographic origins of patients and individuals, on basic principles of risk calculation and on the importance of providing accurate laboratory reports. Finally, classification of CFTR mutations is reviewed, with regard to their relevance to pathogenicity and to genetic counselling.

Protection of rhesus macaques against inhalational anthrax with a Bacillus anthracis capsule conjugate vaccine.

PubMed

Chabot, Donald J; Ribot, Wilson J; Joyce, Joseph; Cook, James; Hepler, Robert; Nahas, Debbie; Chua, Jennifer; Friedlander, Arthur M

2016-07-25

The efficacy of currently licensed anthrax vaccines is largely attributable to a single Bacillus anthracis immunogen, protective antigen. To broaden protection against possible strains resistant to protective antigen-based vaccines, we previously developed a vaccine in which the anthrax polyglutamic acid capsule was covalently conjugated to the outer membrane protein complex of Neisseria meningitidis serotype B and demonstrated that two doses of 2.5μg of this vaccine conferred partial protection of rhesus macaques against inhalational anthrax . Here, we demonstrate complete protection of rhesus macaques against inhalational anthrax with a higher 50μg dose of the same capsule conjugate vaccine. These results indicate that B. anthracis capsule is a highly effective vaccine component that should be considered for incorporation in future generation anthrax vaccines. Published by Elsevier Ltd.

Literature searches on Ayurveda: An update

PubMed Central

Aggithaya, Madhur G.; Narahari, Saravu R.

2015-01-01

Introduction: The journals that publish on Ayurveda are increasingly indexed by popular medical databases in recent years. However, many Eastern journals are not indexed biomedical journal databases such as PubMed. Literature searches for Ayurveda continue to be challenging due to the nonavailability of active, unbiased dedicated databases for Ayurvedic literature. In 2010, authors identified 46 databases that can be used for systematic search of Ayurvedic papers and theses. This update reviewed our previous recommendation and identified current and relevant databases. Aims: To update on Ayurveda literature search and strategy to retrieve maximum publications. Methods: Author used psoriasis as an example to search previously listed databases and identify new. The population, intervention, control, and outcome table included keywords related to psoriasis and Ayurvedic terminologies for skin diseases. Current citation update status, search results, and search options of previous databases were assessed. Eight search strategies were developed. Hundred and five journals, both biomedical and Ayurveda, which publish on Ayurveda, were identified. Variability in databases was explored to identify bias in journal citation. Results: Five among 46 databases are now relevant – AYUSH research portal, Annotated Bibliography of Indian Medicine, Digital Helpline for Ayurveda Research Articles (DHARA), PubMed, and Directory of Open Access Journals. Search options in these databases are not uniform, and only PubMed allows complex search strategy. “The Researches in Ayurveda” and “Ayurvedic Research Database” (ARD) are important grey resources for hand searching. About 44/105 (41.5%) journals publishing Ayurvedic studies are not indexed in any database. Only 11/105 (10.4%) exclusive Ayurveda journals are indexed in PubMed. Conclusion: AYUSH research portal and DHARA are two major portals after 2010. It is mandatory to search PubMed and four other databases because all five carry citations from different groups of journals. The hand searching is important to identify Ayurveda publications that are not indexed elsewhere. Availability information of citations in Ayurveda libraries from National Union Catalogue of Scientific Serials in India if regularly updated will improve the efficacy of hand searching. A grey database (ARD) contains unpublished PG/Ph.D. theses. The AYUSH portal, DHARA (funded by Ministry of AYUSH), and ARD should be merged to form single larger database to limit Ayurveda literature searches. PMID:27313409

Writing and Publishing Handbook.

ERIC Educational Resources Information Center

Hansen, William F., Ed.

Intended to provide guidance in academic publishing to faculty members, especially younger faculty members, this handbook is a compilation of four previously published essays by different authors. Following a preface and an introduction, the four essays and their authors are as follows: (1) "One Writer's Secrets" (Donald M. Murray); (2)…

Stratigraphic and volcano-tectonic relations of Crater Flat Tuff and some older volcanic units, Nye County, Nevada

USGS Publications Warehouse

Carr, W.J.; Byers, F.M.; Orkild, Paul P.

1984-01-01

The Crater Flat Tuff is herein revised to include a newly recognized lowest unit, the Tram Member, exposed at scattered localities in the southwest Nevada Test Site region, and in several drill holes in the Yucca Mountain area. The overlying Bullfrog and Prow Pass Members are well exposed at the type locality of the formation near the southeast edge of Crater Flat, just north of U.S. Highway 95. In previous work, the Tram Member was thought to be the Bullfrog Member, and therefore was shown as Bullfrog or as undifferentiated Crater Flat Tuff on published maps. The revised Crater Flat Tuff is stratigraphically below the Topopah Spring Member of the Paintbrush Tuff and above the Grouse Canyon Member of the Belted Range Tuff, and is approximately 13.6 m.y. old. Drill holes on Yucca Mountain and near Fortymile Wash penetrate all three members of the Crater Flat as well as an underlying quartz-poor unit, which is herein defined as the Lithic Ridge Tuff from exposures on Lithic Ridge near the head of Topopah Wash. In outcrops between Calico Hills and Yucca Flat, the Lithic Ridge Tuff overlies a Bullfrog-like unit of reverse magnetic polarity that probably correlates with a widespread unit around and under Yucca Flat, referred to previously as Crater Flat Tuff. This unit is here informally designated as the tuff of Yucca Flat. Although older, it may be genetically related to the Crater Flat Tuff. Although the rocks are poorly exposed, geophysical and geologic evidence to date suggests that (1) the source of the Crater Flat Tuff is a caldera complex in the Crater Flat area between Yucca Mountain and Bare Mountain, and (2) there are at least two cauldrons within this complex--one probably associated with eruption of the Tram, the other with the Bullfrog and Prow Pass Members. The complex is named the Crater Flat-Prospector Pass caldera complex. The northern part of the Yucca Mountain area is suggested as the general location of the source of pre-Crater Flat tuffs, but a caldera related to the Lithic Ridge Tuff has not been specifically identified.

Collision-induced dissociative chemical cross-linking reagents and methodology: Applications to protein structural characterization using tandem mass spectrometry analysis.

PubMed

Soderblom, Erik J; Goshe, Michael B

2006-12-01

Chemical cross-linking combined with mass spectrometry is a viable approach to study the low-resolution structure of protein and protein complexes. However, unambiguous identification of the residues involved in a cross-link remains analytically challenging. To enable a more effective analysis across various MS platforms, we have developed a novel set of collision-induced dissociative cross-linking reagents and methodology for chemical cross-linking experiments using tandem mass spectrometry (CID-CXL-MS/MS). These reagents incorporate a single gas-phase cleavable bond within their linker region that can be selectively fragmented within the in-source region of the mass spectrometer, enabling independent MS/MS analysis for each peptide. Initial design concepts were characterized using a synthesized cross-linked peptide complex. Following verification and subsequent optimization of cross-linked peptide complex dissociation, our reagents were applied to homodimeric glutathione S-transferase and monomeric bovine serum albumin. Cross-linked residues identified by our CID-CXL-MS/MS method were in agreement with published crystal structures and previous cross-linking studies using conventional approaches. Common LC/MS/MS acquisition approaches such as data-dependent acquisition experiments using ion trap mass spectrometers and product ion spectral analysis using SEQUEST were shown to be compatible with our CID-CXL-MS/MS reagents, obviating the requirement for high resolution and high mass accuracy measurements to identify both intra- and interpeptide cross-links.

Complex Patterns of Admixture across the Indonesian Archipelago.

PubMed

Hudjashov, Georgi; Karafet, Tatiana M; Lawson, Daniel J; Downey, Sean; Savina, Olga; Sudoyo, Herawati; Lansing, J Stephen; Hammer, Michael F; Cox, Murray P

2017-10-01

Indonesia, an island nation as large as continental Europe, hosts a sizeable proportion of global human diversity, yet remains surprisingly undercharacterized genetically. Here, we substantially expand on existing studies by reporting genome-scale data for nearly 500 individuals from 25 populations in Island Southeast Asia, New Guinea, and Oceania, notably including previously unsampled islands across the Indonesian archipelago. We use high-resolution analyses of haplotype diversity to reveal fine detail of regional admixture patterns, with a particular focus on the Holocene. We find that recent population history within Indonesia is complex, and that populations from the Philippines made important genetic contributions in the early phases of the Austronesian expansion. Different, but interrelated processes, acted in the east and west. The Austronesian migration took several centuries to spread across the eastern part of the archipelago, where genetic admixture postdates the archeological signal. As with the Neolithic expansion further east in Oceania and in Europe, genetic mixing with local inhabitants in eastern Indonesia lagged behind the arrival of farming populations. In contrast, western Indonesia has a more complicated admixture history shaped by interactions with mainland Asian and Austronesian newcomers, which for some populations occurred more than once. Another layer of complexity in the west was introduced by genetic contact with South Asia and strong demographic events in isolated local groups. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Complexity Optimization and High-Throughput Low-Latency Hardware Implementation of a Multi-Electrode Spike-Sorting Algorithm

PubMed Central

Dragas, Jelena; Jäckel, David; Hierlemann, Andreas; Franke, Felix

2017-01-01

Reliable real-time low-latency spike sorting with large data throughput is essential for studies of neural network dynamics and for brain-machine interfaces (BMIs), in which the stimulation of neural networks is based on the networks' most recent activity. However, the majority of existing multi-electrode spike-sorting algorithms are unsuited for processing high quantities of simultaneously recorded data. Recording from large neuronal networks using large high-density electrode sets (thousands of electrodes) imposes high demands on the data-processing hardware regarding computational complexity and data transmission bandwidth; this, in turn, entails demanding requirements in terms of chip area, memory resources and processing latency. This paper presents computational complexity optimization techniques, which facilitate the use of spike-sorting algorithms in large multi-electrode-based recording systems. The techniques are then applied to a previously published algorithm, on its own, unsuited for large electrode set recordings. Further, a real-time low-latency high-performance VLSI hardware architecture of the modified algorithm is presented, featuring a folded structure capable of processing the activity of hundreds of neurons simultaneously. The hardware is reconfigurable “on-the-fly” and adaptable to the nonstationarities of neuronal recordings. By transmitting exclusively spike time stamps and/or spike waveforms, its real-time processing offers the possibility of data bandwidth and data storage reduction. PMID:25415989

Complexity optimization and high-throughput low-latency hardware implementation of a multi-electrode spike-sorting algorithm.

PubMed

Dragas, Jelena; Jackel, David; Hierlemann, Andreas; Franke, Felix

2015-03-01

Reliable real-time low-latency spike sorting with large data throughput is essential for studies of neural network dynamics and for brain-machine interfaces (BMIs), in which the stimulation of neural networks is based on the networks' most recent activity. However, the majority of existing multi-electrode spike-sorting algorithms are unsuited for processing high quantities of simultaneously recorded data. Recording from large neuronal networks using large high-density electrode sets (thousands of electrodes) imposes high demands on the data-processing hardware regarding computational complexity and data transmission bandwidth; this, in turn, entails demanding requirements in terms of chip area, memory resources and processing latency. This paper presents computational complexity optimization techniques, which facilitate the use of spike-sorting algorithms in large multi-electrode-based recording systems. The techniques are then applied to a previously published algorithm, on its own, unsuited for large electrode set recordings. Further, a real-time low-latency high-performance VLSI hardware architecture of the modified algorithm is presented, featuring a folded structure capable of processing the activity of hundreds of neurons simultaneously. The hardware is reconfigurable “on-the-fly” and adaptable to the nonstationarities of neuronal recordings. By transmitting exclusively spike time stamps and/or spike waveforms, its real-time processing offers the possibility of data bandwidth and data storage reduction.

Dbf4-dependent kinase and the Rtt107 scaffold promote Mus81-Mms4 resolvase activation during mitosis.

PubMed

Princz, Lissa N; Wild, Philipp; Bittmann, Julia; Aguado, F Javier; Blanco, Miguel G; Matos, Joao; Pfander, Boris

2017-03-01

DNA repair by homologous recombination is under stringent cell cycle control. This includes the last step of the reaction, disentanglement of DNA joint molecules (JMs). Previous work has established that JM resolving nucleases are activated specifically at the onset of mitosis. In case of budding yeast Mus81-Mms4, this cell cycle stage-specific activation is known to depend on phosphorylation by CDK and Cdc5 kinases. Here, we show that a third cell cycle kinase, Cdc7-Dbf4 (DDK), targets Mus81-Mms4 in conjunction with Cdc5-both kinases bind to as well as phosphorylate Mus81-Mms4 in an interdependent manner. Moreover, DDK-mediated phosphorylation of Mms4 is strictly required for Mus81 activation in mitosis, establishing DDK as a novel regulator of homologous recombination. The scaffold protein Rtt107, which binds the Mus81-Mms4 complex, interacts with Cdc7 and thereby targets DDK and Cdc5 to the complex enabling full Mus81 activation. Therefore, Mus81 activation in mitosis involves at least three cell cycle kinases, CDK, Cdc5 and DDK Furthermore, tethering of the kinases in a stable complex with Mus81 is critical for efficient JM resolution. © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Antenatal Workup of Early Megacystis and Selection of Candidates for Fetal Therapy.

PubMed

Fontanella, Federica; Duin, Leonie; Adama van Scheltema, Phebe N; Cohen-Overbeek, Titia E; Pajkrt, Eva; Bekker, Mireille; Willekes, Christine; Bax, Caroline J; Oepkes, Dick; Bilardo, Catia M

2018-05-17

To investigate the best criteria for discriminating fetuses with isolated posterior urethral valves from those theoretically not eligible for fetal treatment because of complex megacystis, high chance of spontaneous resolution, and urethral atresia. A retrospective national study was conducted in fetuses with megacystis detected before 17 weeks' gestation (early megacystis). In total, 142 cases with fetal megacystis were included in the study: 52 with lower urinary tract obstruction, 29 with normal micturition at birth, and 61 with miscellaneous syndromal associations, chromosomal and multiple structural abnormalities (complex megacystis). Only a nuchal translucency > 95th centile, and not a longitudinal bladder diameter ≤15 mm (p = 0.24), significantly increased the risk of complex megacystis (p < 0.01). Cases with a high chance of spontaneous resolution were identified by using the cut-off of 12 mm, as demonstrated in a previous study, and the finding of an associated umbilical cord cyst carried a high-risk of urethral atresia (odds ratio: 15; p = 0.026), an unfavorable condition for antenatal treatment. An algorithm encompassing these three criteria demonstrated good accuracy in selecting fetuses theoretically eligible for fetal treatment (specificity 73%; sensitivity 92%). Cases theoretically eligible for early fetal therapy are those with normal nuchal translucency, a longitudinal bladder diameter > 12 mm, and without ultrasound evidence of umbilical cord cysts. © 2018 The Author(s) Published by S. Karger AG, Basel.

Crystal structure of botulinum neurotoxin type A in complex with the cell surface co-receptor GT1b-insight into the toxin-neuron interaction.

PubMed

Stenmark, Pål; Dupuy, Jérôme; Imamura, Akihiro; Kiso, Makoto; Stevens, Raymond C

2008-08-15

Botulinum neurotoxins have a very high affinity and specificity for their target cells requiring two different co-receptors located on the neuronal cell surface. Different toxin serotypes have different protein receptors; yet, most share a common ganglioside co-receptor, GT1b. We determined the crystal structure of the botulinum neurotoxin serotype A binding domain (residues 873-1297) alone and in complex with a GT1b analog at 1.7 A and 1.6 A, respectively. The ganglioside GT1b forms several key hydrogen bonds to conserved residues and binds in a shallow groove lined by Tryptophan 1266. GT1b binding does not induce any large structural changes in the toxin; therefore, it is unlikely that allosteric effects play a major role in the dual receptor recognition. Together with the previously published structures of botulinum neurotoxin serotype B in complex with its protein co-receptor, we can now generate a detailed model of botulinum neurotoxin's interaction with the neuronal cell surface. The two branches of the GT1b polysaccharide, together with the protein receptor site, impose strict geometric constraints on the mode of interaction with the membrane surface and strongly support a model where one end of the 100 A long translocation domain helix bundle swing into contact with the membrane, initiating the membrane anchoring event.

Use of an all-suture anchor for re-creation of the anterior talofibular ligament: a case report.

PubMed

Piraino, Jason A; Busch, Elliot L; Sansosti, Laura E; Pettineo, Steven J; Creech, Corine

2015-01-01

The lateral ankle ligament complex is typically injured during athletic activity caused by an inversion force on a plantar flexed foot. Numerous open surgical procedures to reconstruct the lateral ankle complex have been described. In contrast, we present a case report in which an all-suture anchor was used arthroscopically to re-create the anterior talofibular ligament in conjunction with ankle arthroscopy. A retrospective analysis of a 55-year-old male with a work-related inversion ankle sprain was performed with 14 months of follow-up. Objective and subjective assessments were obtained using range of motion measures, a strength assessment, and the Foot Function Index. An all-suture anchor was deployed through the anterolateral portal and secured in both the fibula and talus, re-creating the anterior talofibular ligament at its origin and insertion. Active range of motion physical therapy began at 2 weeks postoperatively. The patient started a neuromuscular re-education program at 5 weeks with minimal pain or discomfort. A return to full duty was achieved at 3 months postoperatively. To our knowledge, the use of an all-suture anchor has not been previously reported for lateral ankle complex re-creation. It is hoped that this approach to anterior talofibular ligament repair will decrease the incidence of complications and improve outcomes. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Computational analysis of aspartic protease plasmepsin II complexed with EH58 inhibitor: a QM/MM MD study.

PubMed

de Farias Silva, Natália; Lameira, Jerônimo; Alves, Cláudio Nahum

2011-10-01

Plasmepsin (PM) II is one of four enzymes in the food vacuole of Plasmodium falciparum. It has become an attractive target for combating malaria through research regarding its importance in the P. falciparum metabolism and life cycle, making it the target of choice for structure-based drug design. This paper reports the results of hybrid quantum mechanics / molecular mechanics (QM/MM) molecular dynamics (MD) simulations employed to study the details of the interactions established between PM II and N-(3-{(2-benzo[1, 3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dihydro-isoindol-2-yl) propionyl]-amino}-1-benzyl-2-(hydroxyl-propyl)-4-benzyloxy-3,5dimethoxy-benzamide (EH58), a well-known potent inhibitor for this enzyme. Electrostatic binding free energy and energy terms decomposition have been computed for PM II complexed with the EH58 inhibitor. The results reveal that there is a strong interaction between Asp34, Val78, Ser79, Tyr192 and Asp214 residues and the EH58 inhibitor. In addition, we have computed the potential of the mean force (PMF) profile in order to assign the protonation state of the two catalytic aspartates in PM II-EH58 complex. The results indicate that the protonation of Asp214 favors a stable active site structure, which is consistent with our electrostatic binding free energy calculation and with previous published works.

Is email a reliable means of contacting authors of previously published papers? A study of the Emergency Medicine Journal for 2001.

PubMed

O'Leary, F

2003-07-01

To determine whether it is possible to contact authors of previously published papers via email. A cross sectional study of the Emergency Medicine Journal for 2001. 118 articles were included in the study. The response rate from those with valid email addresses was 73%. There was no statistical difference between the type of email address used and the address being invalid (p=0.392) or between the type of article and the likelihood of a reply (p=0.197). More responses were obtained from work addresses when compared with Hotmail addresses (86% v 57%, p=0.02). Email is a valid means of contacting authors of previously published articles, particularly within the emergency medicine specialty. A work based email address may be a more valid means of contact than a Hotmail address.

Performance comparison of leading image codecs: H.264/AVC Intra, JPEG2000, and Microsoft HD Photo

NASA Astrophysics Data System (ADS)

Tran, Trac D.; Liu, Lijie; Topiwala, Pankaj

2007-09-01

This paper provides a detailed rate-distortion performance comparison between JPEG2000, Microsoft HD Photo, and H.264/AVC High Profile 4:4:4 I-frame coding for high-resolution still images and high-definition (HD) 1080p video sequences. This work is an extension to our previous comparative study published in previous SPIE conferences [1, 2]. Here we further optimize all three codecs for compression performance. Coding simulations are performed on a set of large-format color images captured from mainstream digital cameras and 1080p HD video sequences commonly used for H.264/AVC standardization work. Overall, our experimental results show that all three codecs offer very similar coding performances at the high-quality, high-resolution setting. Differences tend to be data-dependent: JPEG2000 with the wavelet technology tends to be the best performer with smooth spatial data; H.264/AVC High-Profile with advanced spatial prediction modes tends to cope best with more complex visual content; Microsoft HD Photo tends to be the most consistent across the board. For the still-image data sets, JPEG2000 offers the best R-D performance gains (around 0.2 to 1 dB in peak signal-to-noise ratio) over H.264/AVC High-Profile intra coding and Microsoft HD Photo. For the 1080p video data set, all three codecs offer very similar coding performance. As in [1, 2], neither do we consider scalability nor complexity in this study (JPEG2000 is operating in non-scalable, but optimal performance mode).

Expression of ionotropic receptors in terrestrial hermit crab's olfactory sensory neurons

PubMed Central

Groh-Lunow, Katrin C.; Getahun, Merid N.; Grosse-Wilde, Ewald; Hansson, Bill S.

2015-01-01

Coenobitidae are one out of at least five crustacean lineages which independently succeeded in the transition from water to land. This change in lifestyle required adaptation of the peripheral olfactory organs, the antennules, in order to sense chemical cues in the new terrestrial habitat. Hermit crab olfactory aesthetascs are arranged in a field on the distal segment of the antennular flagellum. Aesthetascs house approximately 300 dendrites with their cell bodies arranged in spindle-like complexes of ca. 150 cell bodies each. While the aesthetascs of aquatic crustaceans have been shown to be the place of odor uptake and previous studies identified ionotropic receptors (IRs) as the putative chemosensory receptors expressed in decapod antennules, the expression of IRs besides the IR co-receptors IR25a and IR93a in olfactory sensory neurons (OSNs) has not been documented yet. Our goal was to reveal the expression and distribution pattern of non-co-receptor IRs in OSNs of Coenobita clypeatus, a terrestrial hermit crab, with RNA in situ hybridization. We expanded our previously published RNAseq dataset, and revealed 22 novel IR candidates in the Coenobita antennules. We then used RNA probes directed against three different IRs to visualize their expression within the OSN cell body complexes. Furthermore we aimed to characterize ligand spectra of single aesthetascs by recording local field potentials and responses from individual dendrites. This also allowed comparison to functional data from insect OSNs expressing antennal IRs. We show that this orphan receptor subgroup with presumably non-olfactory function in insects is likely the basis of olfaction in terrestrial hermit crabs. PMID:25698921

Evolution of design considerations in complex craniofacial reconstruction using patient-specific implants.

PubMed

Peel, Sean; Bhatia, Satyajeet; Eggbeer, Dominic; Morris, Daniel S; Hayhurst, Caroline

2017-06-01

Previously published evidence has established major clinical benefits from using computer-aided design, computer-aided manufacturing, and additive manufacturing to produce patient-specific devices. These include cutting guides, drilling guides, positioning guides, and implants. However, custom devices produced using these methods are still not in routine use, particularly by the UK National Health Service. Oft-cited reasons for this slow uptake include the following: a higher up-front cost than conventionally fabricated devices, material-choice uncertainty, and a lack of long-term follow-up due to their relatively recent introduction. This article identifies a further gap in current knowledge - that of design rules, or key specification considerations for complex computer-aided design/computer-aided manufacturing/additive manufacturing devices. This research begins to address the gap by combining a detailed review of the literature with first-hand experience of interdisciplinary collaboration on five craniofacial patient case studies. In each patient case, bony lesions in the orbito-temporal region were segmented, excised, and reconstructed in the virtual environment. Three cases translated these digital plans into theatre via polymer surgical guides. Four cases utilised additive manufacturing to fabricate titanium implants. One implant was machined from polyether ether ketone. From the literature, articles with relevant abstracts were analysed to extract design considerations. In all, 19 frequently recurring design considerations were extracted from previous publications. Nine new design considerations were extracted from the case studies - on the basis of subjective clinical evaluation. These were synthesised to produce a design considerations framework to assist clinicians with prescribing and design engineers with modelling. Promising avenues for further research are proposed.

Multi-omics analysis provides insight to the Ignicoccus hospitalis - Nanoarchaeum equitans association

DOE PAGES

Rawle, Rachel A.; Hamerly, Timothy; Tripet, Brian P.; ...

2017-06-04

Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted ‘omics’ analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized usingmore » interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis–N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. In conclusion, this multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis–N. equitans association. This study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies.« less

Lessons from the Crystal Structure of the S. aureus Surface Protein Clumping Factor A in Complex With Tefibazumab, an Inhibiting Monoclonal Antibody.

PubMed

Ganesh, Vannakambadi K; Liang, Xiaowen; Geoghegan, Joan A; Cohen, Ana Luisa V; Venugopalan, Nagarajan; Foster, Timothy J; Hook, Magnus

2016-11-01

The Staphylococcus aureus fibrinogen binding MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules), ClfA (clumping factor A) is an important virulence factor in staphylococcal infections and a component of several vaccines currently under clinical evaluation. The mouse monoclonal antibody aurexis (also called 12-9), and the humanized version tefibazumab are therapeutic monoclonal antibodies targeting ClfA that in combination with conventional antibiotics were effective in animal models but showed less impressive efficacy in a limited Phase II clinical trial. We here report the crystal structure and a biochemical characterization of the ClfA/tefibazumab (Fab) complex. The epitope for tefibazumab is located to the "top" of the N3 subdomain of ClfA and partially overlaps with a previously unidentified second binding site for fibrinogen. A high-affinity binding of ClfA to fibrinogen involves both an interaction at the N3 site and the previously identified docking of the C-terminal segment of the fibrinogen γ-chain in the N2N3 trench. Although tefibazumab binds ClfA with high affinity we observe a modest IC 50 value for the inhibition of fibrinogen binding to the MSCRAMM. This observation, paired with a common natural occurring variant of ClfA that is not effectively recognized by the mAb, may partly explain the modest effect tefibazumab showed in the initial clinic trail. This information will provide guidance for the design of the next generation of therapeutic anti-staphylococcal mAbs targeting ClfA. Copyright © 2016. Published by Elsevier B.V.

Variation and Functional Impact of Neanderthal Ancestry in Western Asia.

PubMed

Taskent, Recep Ozgur; Alioglu, Nursen Duha; Fer, Evrim; Melike Donertas, Handan; Somel, Mehmet; Gokcumen, Omer

2017-12-01

Neanderthals contributed genetic material to modern humans via multiple admixture events. Initial admixture events presumably occurred in Western Asia shortly after humans migrated out of Africa. Despite being a focal point of admixture, earlier studies indicate lower Neanderthal introgression rates in some Western Asian populations as compared with other Eurasian populations. To better understand the genome-wide and phenotypic impact of Neanderthal introgression in the region, we sequenced whole genomes of nine present-day Europeans, Africans, and the Western Asian Druze at high depth, and analyzed available whole genome data from various other populations, including 16 genomes from present-day Turkey. Our results confirmed previous observations that contemporary Western Asian populations, on an average, have lower levels of Neanderthal-introgressed DNA relative to other Eurasian populations. Modern Western Asians also show comparatively high variability in Neanderthal ancestry, which may be attributed to the complex demographic history of the region. We further replicated the previously described depletion of putatively functional sequences among Neanderthal-introgressed haplotypes. Still, we find dozens of common Neanderthal-introgressed haplotypes in the Turkish sample associated with human phenotypes, including anthropometric and metabolic traits, as well as the immune response. One of these haplotypes is unusually long and harbors variants that affect the expression of members of the CCR gene family and are associated with celiac disease. Overall, our results paint a complex first picture of the genomic impact of Neanderthal introgression in the Western Asian populations. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Real-time monitoring of high-gravity corn mash fermentation using in situ raman spectroscopy.

PubMed

Gray, Steven R; Peretti, Steven W; Lamb, H Henry

2013-06-01

In situ Raman spectroscopy was employed for real-time monitoring of simultaneous saccharification and fermentation (SSF) of corn mash by an industrial strain of Saccharomyces cerevisiae. An accurate univariate calibration model for ethanol was developed based on the very strong 883 cm(-1) C-C stretching band. Multivariate partial least squares (PLS) calibration models for total starch, dextrins, maltotriose, maltose, glucose, and ethanol were developed using data from eight batch fermentations and validated using predictions for a separate batch. The starch, ethanol, and dextrins models showed significant prediction improvement when the calibration data were divided into separate high- and low-concentration sets. Collinearity between the ethanol and starch models was avoided by excluding regions containing strong ethanol peaks from the starch model and, conversely, excluding regions containing strong saccharide peaks from the ethanol model. The two-set calibration models for starch (R(2)  = 0.998, percent error = 2.5%) and ethanol (R(2)  = 0.999, percent error = 2.1%) provide more accurate predictions than any previously published spectroscopic models. Glucose, maltose, and maltotriose are modeled to accuracy comparable to previous work on less complex fermentation processes. Our results demonstrate that Raman spectroscopy is capable of real time in situ monitoring of a complex industrial biomass fermentation. To our knowledge, this is the first PLS-based chemometric modeling of corn mash fermentation under typical industrial conditions, and the first Raman-based monitoring of a fermentation process with glucose, oligosaccharides and polysaccharides present. Copyright © 2013 Wiley Periodicals, Inc.

Multi-omics analysis provides insight to the Ignicoccus hospitalis-Nanoarchaeum equitans association.

PubMed

Rawle, Rachel A; Hamerly, Timothy; Tripet, Brian P; Giannone, Richard J; Wurch, Louie; Hettich, Robert L; Podar, Mircea; Copié, Valerie; Bothner, Brian

2017-09-01

Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted 'omics' analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized using interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis-N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. This multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis-N. equitans association. Our study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Rapid kinetics of iron responsive element (IRE) RNA/iron regulatory protein 1 and IRE-RNA/eIF4F complexes respond differently to metal ions.

PubMed

Khan, Mateen A; Ma, Jia; Walden, William E; Merrick, William C; Theil, Elizabeth C; Goss, Dixie J

2014-06-01

Metal ion binding was previously shown to destabilize IRE-RNA/IRP1 equilibria and enhanced IRE-RNA/eIF4F equilibria. In order to understand the relative importance of kinetics and stability, we now report rapid rates of protein/RNA complex assembly and dissociation for two IRE-RNAs with IRP1, and quantitatively different metal ion response kinetics that coincide with the different iron responses in vivo. kon, for FRT IRE-RNA binding to IRP1 was eight times faster than ACO2 IRE-RNA. Mn(2+) decreased kon and increased koff for IRP1 binding to both FRT and ACO2 IRE-RNA, with a larger effect for FRT IRE-RNA. In order to further understand IRE-mRNA regulation in terms of kinetics and stability, eIF4F kinetics with FRT IRE-RNA were determined. kon for eIF4F binding to FRT IRE-RNA in the absence of metal ions was 5-times slower than the IRP1 binding to FRT IRE-RNA. Mn(2+) increased the association rate for eIF4F binding to FRT IRE-RNA, so that at 50 µM Mn(2+) eIF4F bound more than 3-times faster than IRP1. IRP1/IRE-RNA complex has a much shorter life-time than the eIF4F/IRE-RNA complex, which suggests that both rate of assembly and stability of the complexes are important, and that allows this regulatory system to respond rapidly to change in cellular iron. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Transcontinental Phylogeography of the Daphnia pulex Species Complex

PubMed Central

Costanzo, Katie S.; Taylor, Derek J.

2012-01-01

Daphnia pulex is quickly becoming an attractive model species in the field of ecological genomics due to the recent release of its complete genome sequence, a wide variety of new genomic resources, and a rich history of ecological data. Sequences of the mitochondrial NADH dehydrogenase subunit 5 and cytochrome c oxidase subunit 1 genes were used to assess the global phylogeography of this species, and to further elucidate its phylogenetic relationship to other members of the Daphnia pulex species complex. Using both newly acquired and previously published data, we analyzed 398 individuals from collections spanning five continents. Eleven strongly supported lineages were found within the D. pulex complex, and one lineage in particular, panarctic D. pulex, has very little phylogeographical structure and a near worldwide distribution. Mismatch distribution, haplotype network, and population genetic analyses are compatible with a North American origin for this lineage and subsequent spatial expansion in the Late Pleistocene. In addition, our analyses suggest that dispersal between North and South America of this and other species in the D. pulex complex has occurred multiple times, and is predominantly from north to south. Our results provide additional support for the evolutionary relationships of the eleven main mitochondrial lineages of the D. pulex complex. We found that the well-studied panarctic D. pulex is present on every continent except Australia and Antarctica. Despite being geographically very widespread, there is a lack of strong regionalism in the mitochondrial genomes of panarctic D. pulex – a pattern that differs from that of most studied cladocerans. Moreover, our analyses suggest recent expansion of the panarctic D. pulex lineage, with some continents sharing haplotypes. The hypothesis that hybrid asexuality has contributed to the recent and unusual geographic success of the panarctic D. pulex lineage warrants further study. PMID:23056371

Transcontinental phylogeography of the Daphnia pulex species complex.

PubMed

Crease, Teresa J; Omilian, Angela R; Costanzo, Katie S; Taylor, Derek J

2012-01-01

Daphnia pulex is quickly becoming an attractive model species in the field of ecological genomics due to the recent release of its complete genome sequence, a wide variety of new genomic resources, and a rich history of ecological data. Sequences of the mitochondrial NADH dehydrogenase subunit 5 and cytochrome c oxidase subunit 1 genes were used to assess the global phylogeography of this species, and to further elucidate its phylogenetic relationship to other members of the Daphnia pulex species complex. Using both newly acquired and previously published data, we analyzed 398 individuals from collections spanning five continents. Eleven strongly supported lineages were found within the D. pulex complex, and one lineage in particular, panarctic D. pulex, has very little phylogeographical structure and a near worldwide distribution. Mismatch distribution, haplotype network, and population genetic analyses are compatible with a North American origin for this lineage and subsequent spatial expansion in the Late Pleistocene. In addition, our analyses suggest that dispersal between North and South America of this and other species in the D. pulex complex has occurred multiple times, and is predominantly from north to south. Our results provide additional support for the evolutionary relationships of the eleven main mitochondrial lineages of the D. pulex complex. We found that the well-studied panarctic D. pulex is present on every continent except Australia and Antarctica. Despite being geographically very widespread, there is a lack of strong regionalism in the mitochondrial genomes of panarctic D. pulex--a pattern that differs from that of most studied cladocerans. Moreover, our analyses suggest recent expansion of the panarctic D. pulex lineage, with some continents sharing haplotypes. The hypothesis that hybrid asexuality has contributed to the recent and unusual geographic success of the panarctic D. pulex lineage warrants further study.

Putative members of the Arabidopsis Nup107-160 nuclear pore sub-complex contribute to pathogen defense.

PubMed

Wiermer, Marcel; Cheng, Yu Ti; Imkampe, Julia; Li, Meilan; Wang, Dongmei; Lipka, Volker; Li, Xin

2012-06-01

In eukaryotic cells, transduction of external stimuli into the nucleus to induce transcription and export of mRNAs for translation in the cytoplasm is mediated by nuclear pore complexes (NPCs) composed of nucleoporin proteins (Nups). We previously reported that Arabidopsis MOS3, encoding the homolog of vertebrate Nup96, is required for plant immunity and constitutive resistance mediated by the de-regulated Toll interleukin 1 receptor/nucleotide-binding/leucine-rich repeat (TNL)-type R gene snc1. In vertebrates, Nup96 is a component of the conserved Nup107-160 nuclear pore sub-complex, and implicated in immunity-related mRNA export. Here, we used a reverse genetics approach to examine the requirement for additional subunits of the predicted Arabidopsis Nup107-160 complex in plant immunity. We show that, among eight putative complex members, beside MOS3, only plants with defects in Nup160 or Seh1 are impaired in basal resistance. Constitutive resistance in the snc1 mutant and immunity mediated by TNL-type R genes also depend on functional Nup160 and have a partial requirement for Seh1. Conversely, resistance conferred by coiled coil-type immune receptors operates largely independently of both genes, demonstrating specific contributions to plant defense signaling. Our functional analysis further revealed that defects in nup160 and seh1 result in nuclear accumulation of poly(A) mRNA, and, in the case of nup160, considerable depletion of EDS1, a key positive regulator of basal and TNL-triggered resistance. These findings suggest that Nup160 is required for nuclear mRNA export and full expression of EDS1-conditioned resistance pathways in Arabidopsis. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome.

PubMed

Lim, Sze Chern; Smith, Katherine R; Stroud, David A; Compton, Alison G; Tucker, Elena J; Dasvarma, Ayan; Gandolfo, Luke C; Marum, Justine E; McKenzie, Matthew; Peters, Heidi L; Mowat, David; Procopis, Peter G; Wilcken, Bridget; Christodoulou, John; Brown, Garry K; Ryan, Michael T; Bahlo, Melanie; Thorburn, David R

2014-02-06

Leigh syndrome (LS) is a severe neurodegenerative disorder with characteristic bilateral lesions, typically in the brainstem and basal ganglia. It usually presents in infancy and is genetically heterogeneous, but most individuals with mitochondrial complex IV (or cytochrome c oxidase) deficiency have mutations in the biogenesis factor SURF1. We studied eight complex IV-deficient LS individuals from six families of Lebanese origin. They differed from individuals with SURF1 mutations in having seizures as a prominent feature. Complementation analysis suggested they had mutation(s) in the same gene but targeted massively parallel sequencing (MPS) of 1,034 genes encoding known mitochondrial proteins failed to identify a likely candidate. Linkage and haplotype analyses mapped the location of the gene to chromosome 19 and targeted MPS of the linkage region identified a homozygous c.3G>C (p.Met1?) mutation in C19orf79. Abolishing the initiation codon could potentially still allow initiation at a downstream methionine residue but we showed that this would not result in a functional protein. We confirmed that mutation of this gene was causative by lentiviral-mediated phenotypic correction. C19orf79 was recently renamed PET100 and predicted to encode a complex IV biogenesis factor. We showed that it is located in the mitochondrial inner membrane and forms a ∼300 kDa subcomplex with complex IV subunits. Previous proteomic analyses of mitochondria had overlooked PET100 because its small size was below the cutoff for annotating bona fide proteins. The mutation was estimated to have arisen at least 520 years ago, explaining how the families could have different religions and different geographic origins within Lebanon. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Environmentally relevant concentrations of aminopolycarboxylate chelating agents mobilize Cd from humic acid.

PubMed

North, Ashley E; Sarpong-Kumankomah, Sophia; Bellavie, Andrew R; White, Wade M; Gailer, Jürgen

2017-07-01

Although Cd is a pollutant of public health relevance, many dietary sources from which it can be absorbed into human tissues remain unknown. While it is well established that the biogeochemical cycle of Cd involves its complexation with environment-derived ligands (e.g., humic acids, HAs) and anthropogenic ones (e.g., chelating agents, CAs), the interaction of Cd with both of these ligands is less well understood. To gain insight, a HA-Cd complex was injected on a size-exclusion chromatography (SEC) column coupled on-line with a flame atomic absorption spectrometer (FAAS) using 10mmol/L Tris buffer (pH8.0) as the mobile phase. This approach allowed us to observe the intact HA-Cd complex and the retention behavior of Cd as a function of 2-20μmol/L concentrations of ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) or methylglycinediacetic acid (MGDA) that were added to the mobile phase. An increase of the retention time of Cd was indicative of a partial or complete abstraction of Cd from HA. Our results revealed that all CAs abstracted Cd from the HA-Cd complex at concentrations of 5μmol/L, while MGDA and DTPA were effective at 2μmol/L. The bioavailability of some of the on-column formed CA-Cd complexes explains the previously reported increased accumulation of Cd in periphyton in the ecosystem downstream of wastewater treatment plants. In addition, our results imply that the use of effluents which contain CAs and Cd for the irrigation of food crops can introduce Cd into the food supply and compromise food safety. Copyright © 2017. Published by Elsevier B.V.

Constants for mercury binding by organic matter isolates from the Florida Everglades

USGS Publications Warehouse

Benoit, J.M.; Mason, R.P.; Gilmour, C.C.; Aiken, G.R.

2001-01-01

Dissolved organic matter (DOM) has been implicated as an important complexing agent for Hg that can affect its mobility and bioavailability in aquatic ecosystems. However, binding constants for natural Hg-DOM complexes are not well known. We employed a competitive ligand approach to estimate conditional stability constants for Hg complexes with DOM isolates collected from Florida Everglades surface waters. The isolates examined were the hydrophobic fraction of DOM from a eutrophic, sulfidic site (F1-HPoA) and the hydrophilic fraction from an oligotrophic, low-sulfide site (2BS-HPiA). Our experimental determinations utilized overall octanol-water partitioning coefficients (Dow) for 203Hg at 0.01 M chloride and across pH and DOM concentration gradients. Use of this radioisotope allowed rapid determinations of Hg concentrations in both water and octanol phases without problems of matrix interference. Conditional stability constants (1 = 0.06, 23??C) were log K??? = 11.8 for F1-HPoA and log K' = 10.6 for 2BS-HPiA. These are similar to previously published stability constants for Hg binding to low-molecular-weight thiols. Further, F1-HPoA showed a pH-dependent decline in Dow that was consistent with models of Hg complexation with thiol groups as the dominant Hg binding sites in DOM. These experiments demonstrate that the DOM isolates are stronger ligands for Hg than chloride ion or ethylenediamine-tetraacetic acid. Speciation calculations indicate that at the DOM concentrations frequently measured in Everglades, 20 to 40 ??M, significant complexation of Hg by DOM would be expected in aerobic (sulfide-free) surface waters. Copyright ?? 2001 Elsevier Science Ltd.

The Linear ubiquitin chain assembly complex acts as a liver tumor suppressor and inhibits hepatocyte apoptosis and hepatitis.

PubMed

Shimizu, Yutaka; Peltzer, Nieves; Sevko, Alexandra; Lafont, Elodie; Sarr, Aida; Draberova, Helena; Walczak, Henning

2017-06-01

Linear ubiquitination is a key posttranslational modification that regulates immune signaling and cell death pathways, notably tumor necrosis factor receptor 1 (TNFR1) signaling. The only known enzyme complex capable of forming linear ubiquitin chains under native conditions to date is the linear ubiquitin chain assembly complex, of which the catalytic core component is heme-oxidized iron regulatory protein 2 ubiquitin ligase-1-interacting protein (HOIP). To understand the underlying mechanisms of maintenance of liver homeostasis and the role of linear ubiquitination specifically in liver parenchymal cells, we investigated the physiological role of HOIP in the liver parenchyma. To do so, we created mice harboring liver parenchymal cell-specific deletion of HOIP (Hoip Δhep mice) by crossing Hoip-floxed mice with albumin-Cre mice. HOIP deficiency in liver parenchymal cells triggered tumorigenesis at 18 months of age preceded by spontaneous hepatocyte apoptosis and liver inflammation within the first month of life. In line with the emergence of inflammation, Hoip Δhep mice displayed enhanced liver regeneration and DNA damage. In addition, consistent with increased apoptosis, HOIP-deficient hepatocytes showed enhanced caspase activation and endogenous formation of a death-inducing signaling complex which activated caspase-8. Unexpectedly, exacerbated caspase activation and apoptosis were not dependent on TNFR1, whereas ensuing liver inflammation and tumorigenesis were promoted by TNFR1 signaling. The linear ubiquitin chain assembly complex serves as a previously undescribed tumor suppressor in the liver, restraining TNFR1-independent apoptosis in hepatocytes which, in its absence, is causative of TNFR1-mediated inflammation, resulting in hepatocarcinogenesis. (Hepatology 2017;65:1963-1978). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Text Mining for Protein Docking

PubMed Central

Badal, Varsha D.; Kundrotas, Petras J.; Vakser, Ilya A.

2015-01-01

The rapidly growing amount of publicly available information from biomedical research is readily accessible on the Internet, providing a powerful resource for predictive biomolecular modeling. The accumulated data on experimentally determined structures transformed structure prediction of proteins and protein complexes. Instead of exploring the enormous search space, predictive tools can simply proceed to the solution based on similarity to the existing, previously determined structures. A similar major paradigm shift is emerging due to the rapidly expanding amount of information, other than experimentally determined structures, which still can be used as constraints in biomolecular structure prediction. Automated text mining has been widely used in recreating protein interaction networks, as well as in detecting small ligand binding sites on protein structures. Combining and expanding these two well-developed areas of research, we applied the text mining to structural modeling of protein-protein complexes (protein docking). Protein docking can be significantly improved when constraints on the docking mode are available. We developed a procedure that retrieves published abstracts on a specific protein-protein interaction and extracts information relevant to docking. The procedure was assessed on protein complexes from Dockground (http://dockground.compbio.ku.edu). The results show that correct information on binding residues can be extracted for about half of the complexes. The amount of irrelevant information was reduced by conceptual analysis of a subset of the retrieved abstracts, based on the bag-of-words (features) approach. Support Vector Machine models were trained and validated on the subset. The remaining abstracts were filtered by the best-performing models, which decreased the irrelevant information for ~ 25% complexes in the dataset. The extracted constraints were incorporated in the docking protocol and tested on the Dockground unbound benchmark set, significantly increasing the docking success rate. PMID:26650466

Validating Automated Measures of Text Complexity

ERIC Educational Resources Information Center

Sheehan, Kathleen M.

2017-01-01

Automated text complexity measurement tools (also called readability metrics) have been proposed as a way to help teachers, textbook publishers, and assessment developers select texts that are closely aligned with the new, more demanding text complexity expectations specified in the Common Core State Standards. This article examines a critical…

GMXPBSA 2.1: A GROMACS tool to perform MM/PBSA and computational alanine scanning

NASA Astrophysics Data System (ADS)

Paissoni, C.; Spiliotopoulos, D.; Musco, G.; Spitaleri, A.

2015-01-01

GMXPBSA 2.1 is a user-friendly suite of Bash/Perl scripts for streamlining MM/PBSA calculations on structural ensembles derived from GROMACS trajectories, to automatically calculate binding free energies for protein-protein or ligand-protein complexes [R.T. Bradshaw et al., Protein Eng. Des. Sel. 24 (2011) 197-207]. GMXPBSA 2.1 is flexible and can easily be customized to specific needs and it is an improvement of the previous GMXPBSA 2.0 [C. Paissoni et al., Comput. Phys. Commun. (2014), 185, 2920-2929]. Additionally, it performs computational alanine scanning (CAS) to study the effects of ligand and/or receptor alanine mutations on the free energy of binding. Calculations require only for protein-protein or protein-ligand MD simulations. GMXPBSA 2.1 performs different comparative analyses, including a posteriori generation of alanine mutants of the wild-type complex, calculation of the binding free energy values of the mutant complexes and comparison of the results with the wild-type system. Moreover, it compares the binding free energy of different complex trajectories, allowing the study of the effects of non-alanine mutations, post-translational modifications or unnatural amino acids on the binding free energy of the system under investigation. Finally, it can calculate and rank relative affinity to the same receptor utilizing MD simulations of proteins in complex with different ligands. In order to dissect the different MM/PBSA energy contributions, including molecular mechanic (MM), electrostatic contribution to solvation (PB) and nonpolar contribution to solvation (SA), the tool combines two freely available programs: the MD simulations software GROMACS [S. Pronk et al., Bioinformatics 29 (2013) 845-854] and the Poisson-Boltzmann equation solver APBS [N.A. Baker et al., Proc. Natl. Acad. Sci. U.S.A 98 (2001) 10037-10041]. All the calculations can be performed in single or distributed automatic fashion on a cluster facility in order to increase the calculation by dividing frames across the available processors. This new version with respect to our previously published GMXPBSA 2.0 fixes some problem and allows additional kind of calculations, such as CAS on single protein in order to individuate the hot-spots, more custom options to perform APBS calculations, improvements of speed calculation of APBS (precF set to 0), possibility to work with multichain systems (see Summary of revisions for more details). The program is freely available under the GPL license.

Absolute protein-protein association rate constants from flexible, coarse-grained Brownian dynamics simulations: the role of intermolecular hydrodynamic interactions in barnase-barstar association.

PubMed

Frembgen-Kesner, Tamara; Elcock, Adrian H

2010-11-03

Theory and computation have long been used to rationalize the experimental association rate constants of protein-protein complexes, and Brownian dynamics (BD) simulations, in particular, have been successful in reproducing the relative rate constants of wild-type and mutant protein pairs. Missing from previous BD studies of association kinetics, however, has been the description of hydrodynamic interactions (HIs) between, and within, the diffusing proteins. Here we address this issue by rigorously including HIs in BD simulations of the barnase-barstar association reaction. We first show that even very simplified representations of the proteins--involving approximately one pseudoatom for every three residues in the protein--can provide excellent reproduction of the absolute association rate constants of wild-type and mutant protein pairs. We then show that simulations that include intermolecular HIs also produce excellent estimates of association rate constants, but, for a given reaction criterion, yield values that are decreased by ∼35-80% relative to those obtained in the absence of intermolecular HIs. The neglect of intermolecular HIs in previous BD simulation studies, therefore, is likely to have contributed to the somewhat overestimated absolute rate constants previously obtained. Consequently, intermolecular HIs could be an important component to include in accurate modeling of the kinetics of macromolecular association events. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.

PubMed

Tragante, Vinicius; Barnes, Michael R; Ganesh, Santhi K; Lanktree, Matthew B; Guo, Wei; Franceschini, Nora; Smith, Erin N; Johnson, Toby; Holmes, Michael V; Padmanabhan, Sandosh; Karczewski, Konrad J; Almoguera, Berta; Barnard, John; Baumert, Jens; Chang, Yen-Pei Christy; Elbers, Clara C; Farrall, Martin; Fischer, Mary E; Gaunt, Tom R; Gho, Johannes M I H; Gieger, Christian; Goel, Anuj; Gong, Yan; Isaacs, Aaron; Kleber, Marcus E; Mateo Leach, Irene; McDonough, Caitrin W; Meijs, Matthijs F L; Melander, Olle; Nelson, Christopher P; Nolte, Ilja M; Pankratz, Nathan; Price, Tom S; Shaffer, Jonathan; Shah, Sonia; Tomaszewski, Maciej; van der Most, Peter J; Van Iperen, Erik P A; Vonk, Judith M; Witkowska, Kate; Wong, Caroline O L; Zhang, Li; Beitelshees, Amber L; Berenson, Gerald S; Bhatt, Deepak L; Brown, Morris; Burt, Amber; Cooper-DeHoff, Rhonda M; Connell, John M; Cruickshanks, Karen J; Curtis, Sean P; Davey-Smith, George; Delles, Christian; Gansevoort, Ron T; Guo, Xiuqing; Haiqing, Shen; Hastie, Claire E; Hofker, Marten H; Hovingh, G Kees; Kim, Daniel S; Kirkland, Susan A; Klein, Barbara E; Klein, Ronald; Li, Yun R; Maiwald, Steffi; Newton-Cheh, Christopher; O'Brien, Eoin T; Onland-Moret, N Charlotte; Palmas, Walter; Parsa, Afshin; Penninx, Brenda W; Pettinger, Mary; Vasan, Ramachandran S; Ranchalis, Jane E; M Ridker, Paul; Rose, Lynda M; Sever, Peter; Shimbo, Daichi; Steele, Laura; Stolk, Ronald P; Thorand, Barbara; Trip, Mieke D; van Duijn, Cornelia M; Verschuren, W Monique; Wijmenga, Cisca; Wyatt, Sharon; Young, J Hunter; Zwinderman, Aeilko H; Bezzina, Connie R; Boerwinkle, Eric; Casas, Juan P; Caulfield, Mark J; Chakravarti, Aravinda; Chasman, Daniel I; Davidson, Karina W; Doevendans, Pieter A; Dominiczak, Anna F; FitzGerald, Garret A; Gums, John G; Fornage, Myriam; Hakonarson, Hakon; Halder, Indrani; Hillege, Hans L; Illig, Thomas; Jarvik, Gail P; Johnson, Julie A; Kastelein, John J P; Koenig, Wolfgang; Kumari, Meena; März, Winfried; Murray, Sarah S; O'Connell, Jeffery R; Oldehinkel, Albertine J; Pankow, James S; Rader, Daniel J; Redline, Susan; Reilly, Muredach P; Schadt, Eric E; Kottke-Marchant, Kandice; Snieder, Harold; Snyder, Michael; Stanton, Alice V; Tobin, Martin D; Uitterlinden, André G; van der Harst, Pim; van der Schouw, Yvonne T; Samani, Nilesh J; Watkins, Hugh; Johnson, Andrew D; Reiner, Alex P; Zhu, Xiaofeng; de Bakker, Paul I W; Levy, Daniel; Asselbergs, Folkert W; Munroe, Patricia B; Keating, Brendan J

2014-03-06

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Homo-trimerization is essential for the transcription factor function of Myrf for oligodendrocyte differentiation.

PubMed

Kim, Dongkyeong; Choi, Jin-Ok; Fan, Chuandong; Shearer, Randall S; Sharif, Mohamed; Busch, Patrick; Park, Yungki

2017-05-19

Myrf is a key transcription factor for oligodendrocyte differentiation and central nervous system myelination. We and others have previously shown that Myrf is generated as a membrane protein in the endoplasmic reticulum (ER), and that it undergoes auto-processing to release its N-terminal fragment from the ER, which enters the nucleus to work as a transcription factor. These previous studies allow a glimpse into the unusual complexity behind the biogenesis and function of the transcription factor domain of Myrf. Here, we report that Myrf N-terminal fragments assemble into stable homo-trimers before ER release. Consequently, Myrf N-terminal fragments are released from the ER only as homo-trimers. Our re-analysis of a previous genetic screening result in Caenorhabditis elegans shows that homo-trimerization is essential for the biological functions of Myrf N-terminal fragment, and that the region adjacent to the DNA-binding domain is pivotal to its homo-trimerization. Further, our computational analysis uncovered a novel homo-trimeric DNA motif that mediates the homo-trimeric DNA binding of Myrf N-terminal fragments. Importantly, we found that homo-trimerization defines the DNA binding specificity of Myrf N-terminal fragments. In sum, our study elucidates the molecular mechanism governing the biogenesis and function of Myrf N-terminal fragments and its physiological significance. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

High intraspecific variability of Echinococcus granulosus sensu stricto in Chile.

PubMed

Alvarez Rojas, Cristian A; Ebi, Dennis; Paredes, Rodolfo; Acosta-Jamett, Gerardo; Urriola, Nicole; Roa, Juan Carlos; Manterola, Carlos; Cortes, Sandra; Romig, Thomas; Scheerlinck, Jean-Pierre; Lightowlers, Marshall W

2017-04-01

Echinococcus granulosus sensu stricto is the major cause of cystic echinococcosis in most human and animal cases in the world and the most widespread species within the E. granulosus sensu lato complex. E. granulosus s.s. remains endemic in South America together with other species of the Echinococcus genus, especially in some areas in Argentina, Brazil, Chile and Peru. Except for a single human case caused by E. canadensis (G6) described in the literature, only E. granulosus s.s. has been found in the Chilean territory. In the current study 1609bp of the cox1 gene from 69 Chilean isolates of E. granulosus s.s. from humans and animals were analysed. In total, 26 cox1 haplotypes were found, including the widespread haplotype EG01 (22 isolates) and also EGp1 (5), EgRUS7 (1), EgAus02 (1) and EgAus03 (2). Twenty-one different haplotype not previously described were identified from 38 Chilean isolates designated EgCL1-EgCL21. Previous work had described low variability of E. granulosus s.s. in South America, based on isolates from Peru. Results obtained in this work challenge the previously described idea of the low diversity of the parasite in South America, and warrant future investigation on the origin and spread of the parasite in the continent after the Spanish arrival. Copyright © 2016. Published by Elsevier B.V.

Mapping the Binding Interface of VEGF and a Monoclonal Antibody Fab-1 Fragment with Fast Photochemical Oxidation of Proteins (FPOP) and Mass Spectrometry

NASA Astrophysics Data System (ADS)

Zhang, Ying; Wecksler, Aaron T.; Molina, Patricia; Deperalta, Galahad; Gross, Michael L.

2017-05-01

We previously analyzed the Fab-1:VEGF (vascular endothelial growth factor) system described in this work, with both native top-down mass spectrometry and bottom-up mass spectrometry (carboxyl-group or GEE footprinting) techniques. This work continues bottom-up mass spectrometry analysis using a fast photochemical oxidation of proteins (FPOP) platform to map the solution binding interface of VEGF and a fragment antigen binding region of an antibody (Fab-1). In this study, we use FPOP to compare the changes in solvent accessibility by quantitating the extent of oxidative modification in the unbound versus bound states. Determining the changes in solvent accessibility enables the inference of the protein binding sites (epitope and paratopes) and a comparison to the previously published Fab-1:VEGF crystal structure, adding to the top-down and bottom-up data. Using this method, we investigated peptide-level and residue-level changes in solvent accessibility between the unbound proteins and bound complex. Mapping these data onto the Fab-1:VEGF crystal structure enabled successful characterization of both the binding region and regions of remote conformation changes. These data, coupled with our previous higher order structure (HOS) studies, demonstrate the value of a comprehensive toolbox of methods for identifying the putative epitopes and paratopes for biotherapeutic antibodies.

An unexpected twist in viral capsid maturation

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

Gertsman, Ilya; Gan, Lu; Guttman, Miklos

2009-04-14

Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsidmore » structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 {angstrom} resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 {angstrom}. A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and -sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol{sup -1} of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic maturation process probably present in many dsDNA bacteriophage and possibly viruses such as herpesvirus, which share the HK97 subunit fold.« less

Phylogenetic investigation of human FGFR-bearing paralogons favors piecemeal duplication theory of vertebrate genome evolution.

PubMed

Ajmal, Wajya; Khan, Hiba; Abbasi, Amir Ali

2014-12-01

Understanding the genetic mechanisms underlying the organismal complexity and origin of novelties during vertebrate history is one of the central goals of evolutionary biology. Ohno (1970) was the first to postulate that whole genome duplications (WGD) have played a vital role in the evolution of new gene functions: permitting an increase in morphological, physiological and anatomical complexity during early vertebrate history. Here, we analyze the evolutionary history of human FGFR-bearing paralogon (human autosome 4/5/8/10) by the phylogenetic analysis of multigene families with triplicate and quadruplicate distribution on these chromosomes. Our results categorized the histories of 21 families into discrete co-duplicated groups. Genes of a particular co-duplicated group exhibit identical evolutionary history and have duplicated in concert with each other, whereas genes belonging to different groups have dissimilar histories and have not duplicated concurrently. Taken together with our previously published data, we submit that there is sufficient empirical evidence to disprove the 1R/2R hypothesis and to support the general prediction that vertebrate genome evolved by relatively small-scale, regional duplication events that spread across the history of life. Copyright © 2014 Elsevier Inc. All rights reserved.

Archaeal fibrillarin-Nop5 heterodimer 2'-O-methylates RNA independently of the C/D guide RNP particle.

PubMed

Tomkuvienė, Miglė; Ličytė, Janina; Olendraitė, Ingrida; Liutkevičiūtė, Zita; Clouet-d'Orval, Béatrice; Klimašauskas, Saulius

2017-09-01

Archaeal fibrillarin (aFib) is a well-characterized S -adenosyl methionine (SAM)-dependent RNA 2'- O -methyltransferase that is known to act in a large C/D ribonucleoprotein (RNP) complex together with Nop5 and L7Ae proteins and a box C/D guide RNA. In the reaction, the guide RNA serves to direct the methylation reaction to a specific site in tRNA or rRNA by sequence complementarity. Here we show that a Pyrococcus abyssi aFib-Nop5 heterodimer can alone perform SAM-dependent 2'- O -methylation of 16S and 23S ribosomal RNAs in vitro independently of L7Ae and C/D guide RNAs. Using tritium-labeling, mass spectrometry, and reverse transcription analysis, we identified three in vitro 2'- O -methylated positions in the 16S rRNA of P. abyssi , positions lying outside of previously reported pyrococcal C/D RNP methylation sites. This newly discovered stand-alone activity of aFib-Nop5 may provide an example of an ancestral activity retained in enzymes that were recruited to larger complexes during evolution. © 2017 Tomkuvienė et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Epidermal growth factor receptor and integrins control force-dependent vinculin recruitment to E-cadherin junctions.

PubMed

Sehgal, Poonam; Kong, Xinyu; Wu, Jun; Sunyer, Raimon; Trepat, Xavier; Leckband, Deborah

2018-03-20

This study reports novel findings that link E-cadherin (also known as CDH1)-mediated force-transduction signaling to vinculin targeting to intercellular junctions via epidermal growth factor receptor (EGFR) and integrins. These results build on previous findings that demonstrated that mechanically perturbed E-cadherin receptors activate phosphoinositide 3-kinase and downstream integrins in an EGFR-dependent manner. Results of this study show that this EGFR-mediated kinase cascade controls the force-dependent recruitment of vinculin to stressed E-cadherin complexes - a key early signature of cadherin-based mechanotransduction. Vinculin targeting requires its phosphorylation at tyrosine 822 by Abl family kinases (hereafter Abl), but the origin of force-dependent Abl activation had not been identified. We now present evidence that integrin activation, which is downstream of EGFR signaling, controls Abl activation, thus linking E-cadherin to Abl through a mechanosensitive signaling network. These findings place EGFR and integrins at the center of a positive-feedback loop, through which force-activated E-cadherin signals regulate vinculin recruitment to cadherin complexes in response to increased intercellular tension.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

DNA-based probes for flow cytometry analysis of endocytosis and recycling.

PubMed

Dumont, Claire; Czuba, Ewa; Chen, Moore; Villadangos, Jose A; Johnston, Angus P R; Mintern, Justine D

2017-04-01

The internalization of proteins plays a key role in cell development, cell signaling and immunity. We have previously developed a specific hybridization internalization probe (SHIP) to quantitate the internalization of proteins and particles into cells. Herein, we extend the utility of SHIP to examine both the endocytosis and recycling of surface receptors using flow cytometry. SHIP was used to monitor endocytosis of membrane-bound transferrin receptor (TFR) and its soluble ligand transferrin (TF). SHIP enabled measurements of the proportion of surface molecules internalized, the internalization kinetics and the proportion and rate of internalized molecules that recycle to the cell surface with time. Using this method, we have demonstrated the internalization and recycling of holo-TF and an antibody against the TFR behave differently. This assay therefore highlights the implications of receptor internalization and recycling, where the internalization of the receptor-antibody complex behaves differently to the receptor-ligand complex. In addition, we observe distinct internalization patterns for these molecules expressed by different subpopulations of primary cells. SHIP provides a convenient and high throughput technique for analysis of trafficking parameters for both cell surface receptors and their ligands. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficient weighting strategy for enhancing synchronizability of complex networks

NASA Astrophysics Data System (ADS)

Wang, Youquan; Yu, Feng; Huang, Shucheng; Tu, Juanjuan; Chen, Yan

2018-04-01

Networks with high propensity to synchronization are desired in many applications ranging from biology to engineering. In general, there are two ways to enhance the synchronizability of a network: link rewiring and/or link weighting. In this paper, we propose a new link weighting strategy based on the concept of the neighborhood subgroup. The neighborhood subgroup of a node i through node j in a network, i.e. Gi→j, means that node u belongs to Gi→j if node u belongs to the first-order neighbors of j (not include i). Our proposed weighting schema used the local and global structural properties of the networks such as the node degree, betweenness centrality and closeness centrality measures. We applied the method on scale-free and Watts-Strogatz networks of different structural properties and show the good performance of the proposed weighting scheme. Furthermore, as model networks cannot capture all essential features of real-world complex networks, we considered a number of undirected and unweighted real-world networks. To the best of our knowledge, the proposed weighting strategy outperformed the previously published weighting methods by enhancing the synchronizability of these real-world networks.

Rifabutin and rifampin resistance levels and associated rpoB mutations in clinical isolates of Mycobacterium tuberculosis complex.

PubMed

Berrada, Zenda L; Lin, Shou-Yean Grace; Rodwell, Timothy C; Nguyen, Duylinh; Schecter, Gisela F; Pham, Lucy; Janda, J Michael; Elmaraachli, Wael; Catanzaro, Antonino; Desmond, Edward

2016-06-01

Cross-resistance in rifamycins has been observed in rifampin (RIF)-resistant Mycobacterium tuberculosis complex isolates; some rpoB mutations do not confer broad in vitro rifamycin resistance. We examined 164 isolates, of which 102 were RIF-resistant, for differential resistance between RIF and rifabutin (RFB). A total of 42 unique single mutations or combinations of mutations were detected. The number of unique mutations identified exceeded that reported in any previous study. RFB and RIF MICs up to 8 μg/mL by MGIT 960 were studied; the cut-off values for susceptibility to RIF and RFB were 1 μg/mL and 0.5 μg/mL, respectively. We identified 31 isolates resistant to RIF but susceptible to RFB with the mutations D516V, D516F, 518 deletion, S522L, H526A, H526C, H526G, H526L, and two dual mutations (S522L + K527R and H526S + K527R). Clinical investigations using RFB to treat multidrug-resistant tuberculosis cases harboring those mutations are recommended. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

NOTCH1 Inhibits Activation of ATM by Impairing the Formation of an ATM-FOXO3a-KAT5/Tip60 Complex.

PubMed

Adamowicz, Marek; Vermezovic, Jelena; d'Adda di Fagagna, Fabrizio

2016-08-23

The DNA damage response (DDR) signal transduction pathway is responsible for sensing DNA damage and further relaying this signal into the cell. ATM is an apical DDR kinase that orchestrates the activation and the recruitment of downstream DDR factors to induce cell-cycle arrest and repair. We have previously shown that NOTCH1 inhibits ATM activation upon DNA damage, but the underlying mechanism remains unclear. Here, we show that NOTCH1 does not impair ATM recruitment to DNA double-strand breaks (DSBs). Rather, NOTCH1 prevents binding of FOXO3a and KAT5/Tip60 to ATM through a mechanism in which NOTCH1 competes with FOXO3a for ATM binding. Lack of FOXO3a binding to ATM leads to the loss of KAT5/Tip60 association with ATM. Moreover, expression of NOTCH1 or depletion of ATM impairs the formation of the FOXO3a-KAT5/Tip60 protein complex. Finally, we show that pharmacological induction of FOXO3a nuclear localization sensitizes NOTCH1-driven cancers to DNA-damage-induced cell death. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Systems and complexity thinking in the general practice literature: an integrative, historical narrative review.

PubMed

Sturmberg, Joachim P; Martin, Carmel M; Katerndahl, David A

2014-01-01

Over the past 7 decades, theories in the systems and complexity sciences have had a major influence on academic thinking and research. We assessed the impact of complexity science on general practice/family medicine. We performed a historical integrative review using the following systematic search strategy: medical subject heading [humans] combined in turn with the terms complex adaptive systems, nonlinear dynamics, systems biology, and systems theory, limited to general practice/family medicine and published before December 2010. A total of 16,242 articles were retrieved, of which 49 were published in general practice/family medicine journals. Hand searches and snowballing retrieved another 35. After a full-text review, we included 56 articles dealing specifically with systems sciences and general/family practice. General practice/family medicine engaged with the emerging systems and complexity theories in 4 stages. Before 1995, articles tended to explore common phenomenologic general practice/family medicine experiences. Between 1995 and 2000, articles described the complex adaptive nature of this discipline. Those published between 2000 and 2005 focused on describing the system dynamics of medical practice. After 2005, articles increasingly applied the breadth of complex science theories to health care, health care reform, and the future of medicine. This historical review describes the development of general practice/family medicine in relation to complex adaptive systems theories, and shows how systems sciences more accurately reflect the discipline's philosophy and identity. Analysis suggests that general practice/family medicine first embraced systems theories through conscious reorganization of its boundaries and scope, before applying empirical tools. Future research should concentrate on applying nonlinear dynamics and empirical modeling to patient care, and to organizing and developing local practices, engaging in community development, and influencing health care reform.

Systems and Complexity Thinking in the General Practice Literature: An Integrative, Historical Narrative Review

PubMed Central

Sturmberg, Joachim P.; Martin, Carmel M.; Katerndahl, David A.

2014-01-01

PURPOSE Over the past 7 decades, theories in the systems and complexity sciences have had a major influence on academic thinking and research. We assessed the impact of complexity science on general practice/family medicine. METHODS We performed a historical integrative review using the following systematic search strategy: medical subject heading [humans] combined in turn with the terms complex adaptive systems, nonlinear dynamics, systems biology, and systems theory, limited to general practice/family medicine and published before December 2010. A total of 16,242 articles were retrieved, of which 49 were published in general practice/family medicine journals. Hand searches and snowballing retrieved another 35. After a full-text review, we included 56 articles dealing specifically with systems sciences and general/family practice. RESULTS General practice/family medicine engaged with the emerging systems and complexity theories in 4 stages. Before 1995, articles tended to explore common phenomenologic general practice/family medicine experiences. Between 1995 and 2000, articles described the complex adaptive nature of this discipline. Those published between 2000 and 2005 focused on describing the system dynamics of medical practice. After 2005, articles increasingly applied the breadth of complex science theories to health care, health care reform, and the future of medicine. CONCLUSIONS This historical review describes the development of general practice/family medicine in relation to complex adaptive systems theories, and shows how systems sciences more accurately reflect the discipline’s philosophy and identity. Analysis suggests that general practice/family medicine first embraced systems theories through conscious reorganization of its boundaries and scope, before applying empirical tools. Future research should concentrate on applying nonlinear dynamics and empirical modeling to patient care, and to organizing and developing local practices, engaging in community development, and influencing health care reform. PMID:24445105

Entropic Movement Complexity Reflects Subjective Creativity Rankings of Visualized Hand Motion Trajectories

PubMed Central

Peng, Zhen; Braun, Daniel A.

2015-01-01

In a previous study we have shown that human motion trajectories can be characterized by translating continuous trajectories into symbol sequences with well-defined complexity measures. Here we test the hypothesis that the motion complexity individuals generate in their movements might be correlated to the degree of creativity assigned by a human observer to the visualized motion trajectories. We asked participants to generate 55 novel hand movement patterns in virtual reality, where each pattern had to be repeated 10 times in a row to ensure reproducibility. This allowed us to estimate a probability distribution over trajectories for each pattern. We assessed motion complexity not only by the previously proposed complexity measures on symbolic sequences, but we also propose two novel complexity measures that can be directly applied to the distributions over trajectories based on the frameworks of Gaussian Processes and Probabilistic Movement Primitives. In contrast to previous studies, these new methods allow computing complexities of individual motion patterns from very few sample trajectories. We compared the different complexity measures to how a group of independent jurors rank ordered the recorded motion trajectories according to their personal creativity judgment. We found three entropic complexity measures that correlate significantly with human creativity judgment and discuss differences between the measures. We also test whether these complexity measures correlate with individual creativity in divergent thinking tasks, but do not find any consistent correlation. Our results suggest that entropic complexity measures of hand motion may reveal domain-specific individual differences in kinesthetic creativity. PMID:26733896

Surgical Management of Complex Lower-Extremity Trauma With a Long Hindfoot Fusion Nail: A Case Report.

PubMed

Jain, Nickul S; Lopez, Gregory D; Bederman, S Samuel; Wirth, Garrett A; Scolaro, John A

2016-08-01

High-energy injuries can result in complete or partial loss of the talus. Ipsilateral fractures to the lower limb increase the complexity of surgical management, and treatment is guided by previous case reports of similar injuries. A case of complex lower-extremity trauma with extruded and missing talar body and ipsilateral type IIIB open tibia fracture is presented. Surgical limb reconstruction and salvage was performed successfully with a single orthopaedic implant in a manner not described previously in the literature. The purpose of this case report is to present the novel use of a single orthopaedic implant for treatment of a complex, open traumatic injury. Previous case reports in the literature have described the management of complete or partial talar loss. We describe the novel use of a long hindfoot fusion nail and staged bone grafting to achieve tibiocalcaneal arthrodesis for the treatment of complex lower-extremity trauma. Therapeutic, Level IV: Case study. © 2015 The Author(s).

Cell differentiation and germ-soma separation in Ediacaran animal embryo-like fossils

NASA Astrophysics Data System (ADS)

Chen, Lei; Xiao, Shuhai; Pang, Ke; Zhou, Chuanming; Yuan, Xunlai

2014-12-01

Phosphorites of the Ediacaran Doushantuo Formation (~600 million years old) yield spheroidal microfossils with a palintomic cell cleavage pattern. These fossils have been variously interpreted as sulphur-oxidizing bacteria, unicellular protists, mesomycetozoean-like holozoans, green algae akin to Volvox, and blastula embryos of early metazoans or bilaterian animals. However, their complete life cycle is unknown and it is uncertain whether they had a cellularly differentiated ontogenetic stage, making it difficult to test their various phylogenetic interpretations. Here we describe new spheroidal fossils from black phosphorites of the Doushantuo Formation that have been overlooked in previous studies. These fossils represent later developmental stages of previously published blastula-like fossils, and they show evidence for cell differentiation, germ-soma separation, and programmed cell death. Their complex multicellularity is inconsistent with a phylogenetic affinity with bacteria, unicellular protists, or mesomycetozoean-like holozoans. Available evidence also indicates that the Doushantuo fossils are unlikely crown-group animals or volvocine green algae. We conclude that an affinity with cellularly differentiated multicellular eukaryotes, including stem-group animals or algae, is likely but more data are needed to constrain further the exact phylogenetic affinity of the Doushantuo fossils.

Cell differentiation and germ-soma separation in Ediacaran animal embryo-like fossils.

PubMed

Chen, Lei; Xiao, Shuhai; Pang, Ke; Zhou, Chuanming; Yuan, Xunlai

2014-12-11

Phosphorites of the Ediacaran Doushantuo Formation (∼600 million years old) yield spheroidal microfossils with a palintomic cell cleavage pattern. These fossils have been variously interpreted as sulphur-oxidizing bacteria, unicellular protists, mesomycetozoean-like holozoans, green algae akin to Volvox, and blastula embryos of early metazoans or bilaterian animals. However, their complete life cycle is unknown and it is uncertain whether they had a cellularly differentiated ontogenetic stage, making it difficult to test their various phylogenetic interpretations. Here we describe new spheroidal fossils from black phosphorites of the Doushantuo Formation that have been overlooked in previous studies. These fossils represent later developmental stages of previously published blastula-like fossils, and they show evidence for cell differentiation, germ-soma separation, and programmed cell death. Their complex multicellularity is inconsistent with a phylogenetic affinity with bacteria, unicellular protists, or mesomycetozoean-like holozoans. Available evidence also indicates that the Doushantuo fossils are unlikely crown-group animals or volvocine green algae. We conclude that an affinity with cellularly differentiated multicellular eukaryotes, including stem-group animals or algae, is likely but more data are needed to constrain further the exact phylogenetic affinity of the Doushantuo fossils.

An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management.

PubMed

Friedman, Melissa A; Fernandez, Mercedes; Backer, Lorraine C; Dickey, Robert W; Bernstein, Jeffrey; Schrank, Kathleen; Kibler, Steven; Stephan, Wendy; Gribble, Matthew O; Bienfang, Paul; Bowen, Robert E; Degrasse, Stacey; Flores Quintana, Harold A; Loeffler, Christopher R; Weisman, Richard; Blythe, Donna; Berdalet, Elisa; Ayyar, Ram; Clarkson-Townsend, Danielle; Swajian, Karen; Benner, Ronald; Brewer, Tom; Fleming, Lora E

2017-03-14

Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties.

An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management

PubMed Central

Friedman, Melissa A.; Fernandez, Mercedes; Backer, Lorraine C.; Dickey, Robert W.; Bernstein, Jeffrey; Schrank, Kathleen; Kibler, Steven; Stephan, Wendy; Gribble, Matthew O.; Bienfang, Paul; Bowen, Robert E.; Degrasse, Stacey; Flores Quintana, Harold A.; Loeffler, Christopher R.; Weisman, Richard; Blythe, Donna; Berdalet, Elisa; Ayyar, Ram; Clarkson-Townsend, Danielle; Swajian, Karen; Benner, Ronald; Brewer, Tom; Fleming, Lora E.

2017-01-01

Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties. PMID:28335428

Federating heterogeneous datasets to enhance data sharing and experiment reproducibility

NASA Astrophysics Data System (ADS)

Prieto, Juan C.; Paniagua, Beatriz; Yatabe, Marilia S.; Ruellas, Antonio C. O.; Fattori, Liana; Muniz, Luciana; Styner, Martin; Cevidanes, Lucia

2017-03-01

Recent studies have demonstrated the difficulties to replicate scientific findings and/or experiments published in past.1 The effects seen in the replicated experiments were smaller than previously reported. Some of the explanations for these findings include the complexity of the experimental design and the pressure on researches to report positive findings. The International Committee of Medical Journal Editors (ICMJE) suggests that every study considered for publication must submit a plan to share the de-identified patient data no later than 6 months after publication. There is a growing demand to enhance the management of clinical data, facilitate data sharing across institutions and also to keep track of the data from previous experiments. The ultimate goal is to assure the reproducibility of experiments in the future. This paper describes Shiny-tooth, a web based application created to improve clinical data acquisition during the clinical trial; data federation of such data as well as morphological data derived from medical images; Currently, this application is being used to store clinical data from an osteoarthritis (OA) study. This work is submitted to the SPIE Biomedical Applications in Molecular, Structural, and Functional Imaging conference.

Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax.

PubMed

Dumetz, Fabien; Jouvion, Grégory; Khun, Huot; Glomski, Ian Justin; Corre, Jean-Philippe; Rougeaux, Clémence; Tang, Wei-Jen; Mock, Michèle; Huerre, Michel; Goossens, Pierre Louis

2011-06-01

Powerful noninvasive imaging technologies enable real-time tracking of pathogen-host interactions in vivo, giving access to previously elusive events. We visualized the interactions between wild-type Bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. We show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. Edema toxin (ET), but not lethal toxin (LT), markedly modified the patterns of bacterial dissemination leading, to apparent direct dissemination to the spleen and provoking apoptosis of lymphoid cells. Each toxin alone provoked particular histological lesions in the spleen. When ET and LT are produced together during infection, a specific temporal pattern of lesion developed, with early lesions typical of LT, followed at a later stage by lesions typical of ET. Our study provides new insights into the complex spatial and temporal effects of B. anthracis toxins in the infected host, suggesting a greater role than previously suspected for ET in anthrax and suggesting that therapeutic targeting of ET contributes to protection. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Worldwide end-of-life practice for patients in ICUs.

PubMed

Wong, Wai-Tat; Phua, Jason; Joynt, Gavin M

2018-04-01

Published data and practice recommendations on end-of-life (EOL) generally reflect Western practice frameworks. Understanding worldwide practices is important because improving economic conditions are promoting rapid expansion of intensive care services in many previously disadvantaged regions, and increasing migration has promoted a new cultural diversity previously predominantly unicultural societies. This review explores current knowledge of similarities and differences in EOL practice between regions and possible causes and implications of these differences. Recent observational and survey data shows a marked variability in the practice of withholding and withdrawing life sustaining therapy worldwide. Some evidence supports the view that culture, religion, and socioeconomic factors influence EOL practice, and individually or together account for differences observed. There are also likely to be commonly desired values and expectations for EOL practice, and recent attempts at establishing where worldwide consensus may lie have improved our understanding of shared values and practices. Awareness of differences, understanding their likely complex causes, and using this knowledge to inform individualized care at EOL is likely to improve the quality of care for patients. Further research should clarify the causes of EOL practice variability, monitor trends, and objectively evaluate the quality of EOL practice worldwide.

Neuronvisio: A Graphical User Interface with 3D Capabilities for NEURON.

PubMed

Mattioni, Michele; Cohen, Uri; Le Novère, Nicolas

2012-01-01

The NEURON simulation environment is a commonly used tool to perform electrical simulation of neurons and neuronal networks. The NEURON User Interface, based on the now discontinued InterViews library, provides some limited facilities to explore models and to plot their simulation results. Other limitations include the inability to generate a three-dimensional visualization, no standard mean to save the results of simulations, or to store the model geometry within the results. Neuronvisio (http://neuronvisio.org) aims to address these deficiencies through a set of well designed python APIs and provides an improved UI, allowing users to explore and interact with the model. Neuronvisio also facilitates access to previously published models, allowing users to browse, download, and locally run NEURON models stored in ModelDB. Neuronvisio uses the matplotlib library to plot simulation results and uses the HDF standard format to store simulation results. Neuronvisio can be viewed as an extension of NEURON, facilitating typical user workflows such as model browsing, selection, download, compilation, and simulation. The 3D viewer simplifies the exploration of complex model structure, while matplotlib permits the plotting of high-quality graphs. The newly introduced ability of saving numerical results allows users to perform additional analysis on their previous simulations.

Pleiotrophin is downregulated in human keloids.

PubMed

Lee, Dong Hun; Jin, Cheng Long; Kim, Yeji; Shin, Mi Hee; Kim, Ji Eun; Kim, Minji; Lee, Min Jung; Cho, Soyun

2016-10-01

Keloid is an abnormal hyperproliferative scarring process with involvement of complex genetic and triggering environmental factors. Previously published dysregulated gene expression profile of keloids includes genes involved in tumor formation. Pleiotrophin (PTN) is a secreted, heparin-binding growth factor which is involved in various biological functions such as cell growth, differentiation, and tumor progression. Although PTN expression was reported to be increased in hypertrophic scars, there is no study on PTN expression in keloids, and previous microarray results are controversial. To clarify differential expression of PTN in keloids, we investigated the expression of PTN and its interacting molecules in keloid and control fibroblasts, and performed immunohistochemical staining of PTN using tissue arrays. The expressions of PTN, its upstream regulator platelet-derived growth factor subunit B (PDGF-B) and corresponding PDGF receptors were significantly downregulated in keloid fibroblasts compared to normal human fibroblasts, and the decreased PTN protein expression was confirmed by immunohistochemistry as well as Western blot. Moreover, functional downstream receptor protein tyrosine phosphatase β/ζ was significantly upregulated in keloid fibroblasts, supporting overall downregulation of PTN signaling pathway. The lowered PTN expression in keloids suggests a different pathomechanism from that of hypertrophic scars.

AHRQ series on complex intervention systematic reviews-paper 6: PRISMA-CI extension statement and checklist.

PubMed

Guise, Jeanne-Marie; Butler, Mary E; Chang, Christine; Viswanathan, Meera; Pigott, Terri; Tugwell, Peter

2017-10-01

Complex interventions are widely used in health systems, public health, education, and communities and are increasingly the subject of systematic reviews. Oversimplification and inconsistencies in reporting about complex interventions can limit the usability of review findings. Although guidance exists to ensure that reports of individual studies and systematic reviews adhere to accepted scientific standards, their design-specific focus leaves important reporting gaps relative to complex interventions in health care. This paper provides a stand-alone extension to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting tool for complex interventions-PRISMA-CI-to help authors, publishers, and readers understand and apply to systematic reviews of complex interventions. PRISMA-CI development followed the Enhancing the QUAlity and Transparency Of health Research Network guidance for extensions and focused on adding or modifying only essential items that are truly unique to complex interventions and are not covered by broader interpretation of current PRISMA guidance. PRISMA-CI provides an important structure and guidance for systematic reviews and meta-analyses for the highly prevalent and dynamic field of complex interventions. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Testing complex networks of interaction at the onset of the Near Eastern Neolithic using modelling of obsidian exchange.

PubMed

Ibáñez, Juan José; Ortega, David; Campos, Daniel; Khalidi, Lamya; Méndez, Vicenç

2015-06-06

In this paper, we explore the conditions that led to the origins and development of the Near Eastern Neolithic using mathematical modelling of obsidian exchange. The analysis presented expands on previous research, which established that the down-the-line model could not explain long-distance obsidian distribution across the Near East during this period. Drawing from outcomes of new simulations and their comparison with archaeological data, we provide results that illuminate the presence of complex networks of interaction among the earliest farming societies. We explore a network prototype of obsidian exchange with distant links which replicates the long-distance movement of ideas, goods and people during the Early Neolithic. Our results support the idea that during the first (Pre-Pottery Neolithic A) and second (Pre-Pottery Neolithic B) phases of the Early Neolithic, the complexity of obsidian exchange networks gradually increased. We propose then a refined model (the optimized distant link model) whereby long-distance exchange was largely operated by certain interconnected villages, resulting in the appearance of a relatively homogeneous Neolithic cultural sphere. We hypothesize that the appearance of complex interaction and exchange networks reduced risks of isolation caused by restricted mobility as groups settled and argue that these networks partially triggered and were crucial for the success of the Neolithic Revolution. Communities became highly dynamic through the sharing of experiences and objects, while the networks that developed acted as a repository of innovations, limiting the risk of involution. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Two new species of the Liolaemus elongatus-kriegi complex (Iguania, Liolaemidae) from Andean highlands of southern Chile

PubMed Central

Troncoso-Palacios, Jaime; Díaz, Hugo A.; Esquerré, Damien; Urra, Felix A.

2015-01-01

Abstract The elongatus-kriegi complex is one of the most diverse clades of the Liolaemus (sensu stricto) subgenus of lizards. There are currently 29 species recognized in this group distributed between Chile and Argentina. Based on molecular evidence, there seem to be five main clades nested within this complex: the elongatus, leopardinus, kriegi, petrophilus and punmahuida clades. Liolaemus buergeri and Liolaemus kriegi, both of the kriegi clade, were believed to inhabit the surroundings of the Laja Lagoon, in the Biobío Region of Chile. Moreover, this Chilean population of Liolaemus kriegi was recently recognized as an undescribed taxon called “Liolaemus sp. A” based on molecular phylogenetics. In this work, we studied these two populations of the Laja Lagoon and provided the morphological diagnosis to describe them as two new species: Liolaemus scorialis sp. n. and Liolaemus zabalai sp. n., previously considered Liolaemus buergeri and “Liolaemus kriegi/Liolaemus sp. A” respectively. Additionally, we identified another population of Liolaemus scorialis in the vicinity of La Mula Lagoon in the Araucanía Region of Chile. Liolaemus scorialis differs from almost all of the species of the elongatus-kriegi complex by its considerably smaller size. Nevertheless, without molecular data we cannot assign it to any particular subclade. Liolaemus zabalai belongs to the kriegi clade based on published molecular phylogenies. Finally, we provide some natural history data on both species and we document for the first time the presence of Liolaemus neuquensis in Chile from a museum specimen from La Mula Lagoon. PMID:25987873

Speciation in Indo-Pacific swiftlets (Aves: Apodidae): integrating molecular and phenotypic data for a new provisional taxonomy of the Collocalia esculenta complex.

PubMed

Rheindt, Frank E; Christidis, Les; Norman, Janette A; Eaton, James A; Sadanandan, Keren R; Schodde, Richard

2017-04-07

White-bellied swiftlets of the Collocalia esculenta complex constitute a radiation of colony-breeding swifts distributed throughout the tropical Indo-Pacific region. Resolution of their taxonomy is challenging due to their morphological uniformity. To analyze the evolutionary history of this complex, we combine new biometric measurements and results from plumage assessment of museum specimens with novel as well as previously published molecular data. Together, this body of information constitutes the largest systematic dataset for white-bellied swiftlets yet compiled, drawn from 809 individuals belonging to 32 taxa for which new molecular, biometric, and/or plumage data are presented. We propose changing the classification of white-bellied swiftlets, for which two species are currently recognized, to elevate eight regional forms to species level, and we also describe two new subspecies. The ten taxa we recommend recognizing at the species level are: Collocalia linchi (Java to Lombok, Sumatran hills), C. dodgei (montane Borneo), C. natalis (Christmas Island), C. affinis (Greater Sundas, including the Thai-Malay Peninsula and Andaman-Nicobar Islands), C. marginata (Philippines), C. isonota (Philippines), C. sumbawae (west Lesser Sundas), C. neglecta (east Lesser Sundas), C. esculenta (Sulawesi, Moluccas, New Guinea, Bismarck Archipelago, Solomon Islands), and C. uropygialis (Vanuatu, New Caledonia). Future molecular and morphological work is needed to resolve questions of speciation and population affinities in the Philippines, Christmas Island, Wallacea and central Melanesia, and to shed light on historic diversification and patterns of gene flow in the complex.

Surveillance Systems from Public Health Institutions and Scientific Societies for Antimicrobial Resistance and Healthcare-Associated Infections in Europe (SUSPIRE): protocol for a systematic review.

PubMed

Núñez-Núñez, María; Navarro, María Dolores; Gkolia, Panagiota; Babu Rajendran, Nithya; Del Toro, María Dolores; Voss, Andreas; Sharland, Mike; Sifakis, Frangiscos; Tacconelli, Evelina; Rodríguez-Baño, Jesús

2017-03-27

The worldwide spread of antimicrobial resistance is now recognised as a global public health threat. Owing to the geographical heterogeneity, complexity and continuously evolving dynamics of resistant organisms and genes, surveillance is a key tool for understanding, measuring and informing actions in the fight against this problem. To date there is no harmonisation of key indicators or of methodologies used to obtain them. The main objective of this project is to systematically review and analyse the current publicly available surveillance activities on antimicrobial resistance and healthcare-associated infections in Europe. Eligible activities are those endorsed by regional, national or transnational health organisations and scientific societies providing data on a periodic basis. Grey and peer-reviewed literature will be searched with no language restrictions. Three independent reviewers will perform a two-step selection process using a previously piloted, tailored electronic data extraction form. Descriptive summaries and tables of all relevant findings will be performed and reported according to PRISMA guidelines. We did not seek ethical approval for this study because the data to be collected are not linked to individuals. Data will be presented at international conferences and published in peer-reviewed journals. CRD42016033867. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Resilience and the population history of the Kuril Islands, Northwest Pacific: A study in complex human ecodynamics

PubMed Central

Fitzhugh, Ben; Gjesfjeld, Erik; Brown, William; Hudson, Mark J.; Shaw, Jennie D.

2016-01-01

Living in remote places can strain the adaptive capacities of human settlers. It can also protect communities from external social, political and economic forces. In this paper, we present an archaeological population history of the Kuril Islands. This string of small volcanic islands on the margins of the Northwest Pacific was occupied by maritime hunting, fishing and gathering communities from the mid-Holocene to recent centuries. We bring together (1) 380 new and previously published archaeological radiocarbon dates, (2) a new paleodemographic model based on a radiocarbon-timestamped temporal frequency distribution of archaeological deposits, (3) recently published paleoclimate trends, and (4) recently published archaeological proxy evidence for changes in the extent of social networks. We demonstrate that, over the last two millennia, inhabitants of the Kuril Islands underwent dramatic demographic fluctuations. Explanations of these fluctuations are considered in the context of environmental hazards, social networks and the emergence of an East Asian “World System”, elucidating the tension between local and external adaptive strategies to social and ecological uncertainty. Results suggest that population resilience to local climate and environmental variability was achieved by virtue of social networks that maintained non-local support in times of crisis. Conversely, the expansion of the East Asian political economy into neighboring regions of the southern margin of the Kuril Islands perhaps in conjunction with exposure to epidemic diseases appears to have undermined the adaptive strategies, resulting in an increase in the vulnerability of Kuril populations to environmental fluctuations. PMID:28066132

Quantifying reproducibility in computational biology: the case of the tuberculosis drugome.

PubMed

Garijo, Daniel; Kinnings, Sarah; Xie, Li; Xie, Lei; Zhang, Yinliang; Bourne, Philip E; Gil, Yolanda

2013-01-01

How easy is it to reproduce the results found in a typical computational biology paper? Either through experience or intuition the reader will already know that the answer is with difficulty or not at all. In this paper we attempt to quantify this difficulty by reproducing a previously published paper for different classes of users (ranging from users with little expertise to domain experts) and suggest ways in which the situation might be improved. Quantification is achieved by estimating the time required to reproduce each of the steps in the method described in the original paper and make them part of an explicit workflow that reproduces the original results. Reproducing the method took several months of effort, and required using new versions and new software that posed challenges to reconstructing and validating the results. The quantification leads to "reproducibility maps" that reveal that novice researchers would only be able to reproduce a few of the steps in the method, and that only expert researchers with advance knowledge of the domain would be able to reproduce the method in its entirety. The workflow itself is published as an online resource together with supporting software and data. The paper concludes with a brief discussion of the complexities of requiring reproducibility in terms of cost versus benefit, and a desiderata with our observations and guidelines for improving reproducibility. This has implications not only in reproducing the work of others from published papers, but reproducing work from one's own laboratory.

Retracted articles in surgery journals. What are surgeons doing wrong?

PubMed

Cassão, Bruna Dell'Acqua; Herbella, Fernando A M; Schlottmann, Francisco; Patti, Marco G

2018-06-01

Retraction of previously published scientific articles is an important mechanism to preserve the integrity of scientific work. This study analyzed retractions of previously published articles from surgery journals. We searched for retracted articles in the 100 surgery journals with the highest SJR2 indicator grades. We found 130 retracted articles in 49 journals (49%). Five or more retracted articles were published in 8 journals (8%). The mean time between publication and retraction was 26 months (range 1 to 158 months). The United States, China, Germany, Japan, and the United Kingdom accounted for more than 3 out of 4 of the retracted articles. The greatest number of retractions came from manuscripts about orthopedics and traumatology, general surgery, anesthesiology, cardiothoracic surgery, and plastic surgery. Nonsurgeons were responsible for 16% of retractions in these surgery journals. The main reasons for retraction were duplicate publication (42%), plagiarism (16%), absence of proven integrity of the study (14%), incorrect data (13%), data published without authorization (12%), violation of research ethics (11%), documented fraud (11%), request of an author(s) (5%), and unknown (3%). In 25% of the retracted articles, other publications by the same authors also had been retracted. Retraction of published articles does not occur frequently in surgery journals. Some form of scientific misconduct was present in the majority of retractions, especially duplication of publication and plagiarism. Retractions of previously published articles were most frequent from countries with the greatest number of publications; some authors showed recidivism. Copyright © 2018 Elsevier Inc. All rights reserved.

Proteomic and Biochemical Comparison of the Cellular Interaction Partners of Human VPS33A and VPS33B.

PubMed

Hunter, Morag R; Hesketh, Geoffrey G; Benedyk, Tomasz H; Gingras, Anne-Claude; Graham, Stephen C

2018-05-17

Multi-subunit tethering complexes control membrane fusion events in eukaryotic cells. Class C core vacuole/endosome tethering (CORVET) and homotypic fusion and vacuole protein sorting (HOPS) are two such complexes, both containing the Sec1/Munc18 protein subunit VPS33A. Metazoans additionally possess VPS33B, which has considerable sequence similarity to VPS33A but does not integrate into CORVET or HOPS complexes and instead stably interacts with VIPAR. It has been recently suggested that VPS33B and VIPAR comprise two subunits of a novel multi-subunit tethering complex (named "CHEVI"), perhaps analogous in configuration to CORVET and HOPS. We utilized the BioID proximity biotinylation assay to compare and contrast the interactomes of VPS33A and VPS33B. Overall, few proteins were identified as associating with both VPS33A and VPS33B, suggesting that these proteins have distinct sub-cellular localizations. Consistent with previous reports, we observed that VPS33A was co-localized with many components of class III phosphatidylinositol 3-kinase (PI3KC3) complexes: PIK3C3, PIK3R4, NRBF2, UVRAG and RUBICON. Although VPS33A clearly co-localized with several subunits of CORVET and HOPS in this assay, no proteins with the canonical CORVET/HOPS domain architecture were found to co-localize with VPS33B. Instead, we identified that VPS33B interacts directly with CCDC22, a member of the CCC complex. CCDC22 does not co-fractionate with VPS33B and VIPAR in gel filtration of human cell lysates, suggesting that CCDC22 interacts transiently with VPS33B/VIPAR rather than forming a stable complex with these proteins in cells. We also observed that the protein complex containing VPS33B and VIPAR is considerably smaller than CORVET/HOPS, suggesting that the CHEVI complex comprises just VPS33B and VIPAR. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

37 CFR 381.10 - Cost of living adjustment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... determined by the Consumer Price Index (all consumers, all items) during the period from the most recent Index published prior to December 1, 2006, to the most recent Index published prior to December 1, 2007... the cost of living during the period from the most recent index published prior to the previous notice...

37 CFR 253.10 - Cost of living adjustment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... determined by the Consumer Price Index (all consumers, all items) during the period from the most recent Index published prior to December 1, 2002, to the most recent Index published prior to December 1, 2003... cost of living during the period from the most recent index published prior to the previous notice, to...

37 CFR 381.10 - Cost of living adjustment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... determined by the Consumer Price Index (all consumers, all items) during the period from the most recent Index published prior to December 1, 2012, to the most recent Index published prior to December 1, 2013... change in the cost of living during the period from the most recent index published prior to the previous...

37 CFR 381.10 - Cost of living adjustment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... determined by the Consumer Price Index (all consumers, all items) during the period from the most recent Index published prior to December 1, 2006, to the most recent Index published prior to December 1, 2007... the cost of living during the period from the most recent index published prior to the previous notice...

37 CFR 381.10 - Cost of living adjustment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... determined by the Consumer Price Index (all consumers, all items) during the period from the most recent Index published prior to December 1, 2012, to the most recent Index published prior to December 1, 2013... change in the cost of living during the period from the most recent index published prior to the previous...

37 CFR 253.10 - Cost of living adjustment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... determined by the Consumer Price Index (all consumers, all items) during the period from the most recent Index published prior to December 1, 2002, to the most recent Index published prior to December 1, 2003... cost of living during the period from the most recent index published prior to the previous notice, to...

37 CFR 253.10 - Cost of living adjustment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... determined by the Consumer Price Index (all consumers, all items) during the period from the most recent Index published prior to December 1, 2002, to the most recent Index published prior to December 1, 2003... cost of living during the period from the most recent index published prior to the previous notice, to...

37 CFR 253.10 - Cost of living adjustment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... determined by the Consumer Price Index (all consumers, all items) during the period from the most recent Index published prior to December 1, 2002, to the most recent Index published prior to December 1, 2003... cost of living during the period from the most recent index published prior to the previous notice, to...

37 CFR 381.10 - Cost of living adjustment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... determined by the Consumer Price Index (all consumers, all items) during the period from the most recent Index published prior to December 1, 2006, to the most recent Index published prior to December 1, 2007... the cost of living during the period from the most recent index published prior to the previous notice...

The Genetic Architecture of Complex Traits in Teosinte (Zea mays ssp. parviglumis): New Evidence from Association Mapping

USDA-ARS?s Scientific Manuscript database

Our previous association analyses showed that variation at major regulatory genes contributes to standing variation for complex traits in Balsas teosinte, the progenitor of maize. This study expands our previous association mapping effort in teosinte by testing 123 markers in 52 candidate genes for ...

Adverse outcome pathway networks II: Network analytics.

PubMed

Villeneuve, Daniel L; Angrish, Michelle M; Fortin, Marie C; Katsiadaki, Ioanna; Leonard, Marc; Margiotta-Casaluci, Luigi; Munn, Sharon; O'Brien, Jason M; Pollesch, Nathan L; Smith, L Cody; Zhang, Xiaowei; Knapen, Dries

2018-06-01

Toxicological responses to stressors are more complex than the simple one-biological-perturbation to one-adverse-outcome model portrayed by individual adverse outcome pathways (AOPs). Consequently, the AOP framework was designed to facilitate de facto development of AOP networks that can aid in the understanding and prediction of pleiotropic and interactive effects more common to environmentally realistic, complex exposure scenarios. The present study introduces nascent concepts related to the qualitative analysis of AOP networks. First, graph theory-based approaches for identifying important topological features are illustrated using 2 example AOP networks derived from existing AOP descriptions. Second, considerations for identifying the most significant path(s) through an AOP network from either a biological or risk assessment perspective are described. Finally, approaches for identifying interactions among AOPs that may result in additive, synergistic, or antagonistic responses (or previously undefined emergent patterns of response) are introduced. Along with a companion article (part I), these concepts set the stage for the development of tools and case studies that will facilitate more rigorous analysis of AOP networks, and the utility of AOP network-based predictions, for use in research and regulatory decision-making. The present study addresses one of the major themes identified through a Society of Environmental Toxicology and Chemistry Horizon Scanning effort focused on advancing the AOP framework. Environ Toxicol Chem 2018;37:1734-1748. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2007 update.

PubMed

O'Donnell, Denis E; Aaron, Shaw; Bourbeau, Jean; Hernandez, Paul; Marciniuk, Darcy D; Balter, Meyer; Ford, Gordon; Gervais, Andre; Goldstein, Rogers; Hodder, Rick; Kaplan, Alan; Keenan, Sean; Lacasse, Yves; Maltais, Francois; Road, Jeremy; Rocker, Graeme; Sin, Don; Sinuff, Tasmin; Voduc, Nha

2007-09-01

Chronic obstructive pulmonary disease (COPD) is a major respiratory illness in Canada that is both preventable and treatable. Our understanding of the pathophysiology of this complex condition continues to grow and our ability to offer effective treatment to those who suffer from it has improved considerably. The purpose of the present educational initiative of the Canadian Thoracic Society (CTS) is to provide up to date information on new developments in the field so that patients with this condition will receive optimal care that is firmly based on scientific evidence. Since the previous CTS management recommendations were published in 2003, a wealth of new scientific information has become available. The implications of this new knowledge with respect to optimal clinical care have been carefully considered by the CTS Panel and the conclusions are presented in the current document. Highlights of this update include new epidemiological information on mortality and prevalence of COPD, which charts its emergence as a major health problem for women; a new section on common comorbidities in COPD; an increased emphasis on the meaningful benefits of combined pharmacological and nonpharmacological therapies; and a new discussion on the prevention of acute exacerbations. A revised stratification system for severity of airway obstruction is proposed, together with other suggestions on how best to clinically evaluate individual patients with this complex disease. The results of the largest randomized clinical trial ever undertaken in COPD have recently been published, enabling the Panel to make evidence-based recommendations on the role of modern pharmacotherapy. The Panel hopes that these new practice guidelines, which reflect a rigorous analysis of the recent literature, will assist caregivers in the diagnosis and management of this common condition.

Surgical patient selection and counseling.

PubMed

Ziegelmann, Matt; Köhler, Tobias S; Bailey, George C; Miest, Tanner; Alom, Manaf; Trost, Landon

2017-08-01

The objectives of patient selection and counseling are ultimately to enhance successful outcomes. However, the definition for success is often narrowly defined in published literature (ability to complete surgery, complications, satisfaction) and fails to account for patient desires and expectations, temporal changes, natural history of underlying diseases, or independent validation. Factors associated with satisfaction and dissatisfaction are often surgery-specific, although correlation with pre-operative expectations, revisions, and complications are common with most procedures. The process of appropriate patient selection is determined by the integration of patient and surgeon factors, including psychological capacity to handle unsatisfactory results, baseline expectations, complexity of case, and surgeon volume and experience. Using this model, a high-risk scenario includes one in which a low-volume surgeon performs a complex case in a patient with limited psychological capacity and high expectations. In contrast, a high-volume surgeon performing a routine case in a male with low expectations and abundant psychiatric reserve is more likely to achieve a successful outcome. To further help identify patients who are at high risk for dissatisfaction, a previously published mnemonic is recommended: CURSED Patient (compulsive/obsessive, unrealistic, revision, surgeon shopping, entitled, denial, and psychiatric). Appropriate patient counseling includes setting appropriate expectations, reviewing the potential and anticipated risks of surgery, post-operative instruction to limit complications, and long-term follow-up. As thorough counseling is often a time-consuming endeavor, busy practices may elect to utilize various resources including educational materials, advanced practice providers, or group visits, among others. The consequences for poor patient selection and counseling may range from poor surgical outcomes and patient dissatisfaction to lawsuits, loss of credibility, or even significant patient or personal harm.

Monte Carlo kinetics simulations of ice-mantle formation on interstellar grains

NASA Astrophysics Data System (ADS)

Garrod, Robin

2015-08-01

The majority of interstellar dust-grain chemical kinetics models use rate equations, or alternative population-based simulation methods, to trace the time-dependent formation of grain-surface molecules and ice mantles. Such methods are efficient, but are incapable of considering explicitly the morphologies of the dust grains, the structure of the ices formed thereon, or the influence of local surface composition on the chemistry.A new Monte Carlo chemical kinetics model, MIMICK, is presented here, whose prototype results were published recently (Garrod 2013, ApJ, 778, 158). The model calculates the strengths and positions of the potential mimima on the surface, on the fly, according to the individual pair-wise (van der Waals) bonds between surface species, allowing the structure of the ice to build up naturally as surface diffusion and chemistry occur. The prototype model considered contributions to a surface particle's potential only from contiguous (or "bonded") neighbors; the full model considers contributions from surface constituents from short to long range. Simulations are conducted on a fully 3-D user-generated dust-grain with amorphous surface characteristics. The chemical network has also been extended from the simple water system previously published, and now includes 33 chemical species and 55 reactions. This allows the major interstellar ice components to be simulated, such as water, methane, ammonia and methanol, as well as a small selection of more complex molecules, including methyl formate (HCOOCH3).The new model results indicate that the porosity of interstellar ices are dependent on multiple variables, including gas density, the dust temperature, and the relative accretion rates of key gas-phase species. The results presented also have implications for the formation of complex organic molecules on dust-grain surfaces at very low temperatures.

Habitat selection and movements of Piping Plover broods suggest a tradeoff between breeding stages

USGS Publications Warehouse

Wiltermuth, Mark T.; Anteau, Michael J.; Sherfy, Mark H.; Pearse, Aaron T.

2015-01-01

In precocial birds, adults select breeding areas using cues associated with habitat characteristics that are favorable for nesting success and chick survival, but there may be tradeoffs in habitat selection between these breeding stages. Here we describe habitat selection and intra-territory movements of 53 Piping Plover (Charadrius melodus) broods (320 observations) during the 2007–2008 breeding seasons on mainland- and island-shoreline habitats at Lake Sakakawea, North Dakota, USA. We used remotely sensed habitat characteristics to separately examine habitat selection and movements at two spatiotemporal scales to account for potential confounding effects of nest-site selection on brood-rearing habitat used. The scales used were (1) the entire brood-rearing period within available brood-rearing areas and (2) 2-day observation intervals within age-specific discrete habitat selection choice sets. Analyses at both scales indicated that broods selected areas which were non-vegetated, moderately level, and nearer to the shoreline. Rate of brood movement increased with age up to 5 days, then stabilized; broods that hatched >50 m away from the shoreline moved toward the shoreline. Brood movements were greater when they were in vegetated areas, when the brood-rearing area was of greater topographic complexity, and when broods aged 6–25 days were further away from the shoreline. Using inferences from our results and those of previously published work, we postulate how a potential tradeoff in habitat selection between nesting and brood-rearing can contribute to an ecological trap in a novel habitat. This work, in the context of published works, suggests that plover breeding habitat is a complex of both nesting and brood-rearing habitats and provides a basis for making remotely sensed abundance estimates of suitable breeding habitat for Piping Plovers.

Surgical patient selection and counseling

PubMed Central

Ziegelmann, Matt; Köhler, Tobias S.; Bailey, George C.; Miest, Tanner; Alom, Manaf

2017-01-01

The objectives of patient selection and counseling are ultimately to enhance successful outcomes. However, the definition for success is often narrowly defined in published literature (ability to complete surgery, complications, satisfaction) and fails to account for patient desires and expectations, temporal changes, natural history of underlying diseases, or independent validation. Factors associated with satisfaction and dissatisfaction are often surgery-specific, although correlation with pre-operative expectations, revisions, and complications are common with most procedures. The process of appropriate patient selection is determined by the integration of patient and surgeon factors, including psychological capacity to handle unsatisfactory results, baseline expectations, complexity of case, and surgeon volume and experience. Using this model, a high-risk scenario includes one in which a low-volume surgeon performs a complex case in a patient with limited psychological capacity and high expectations. In contrast, a high-volume surgeon performing a routine case in a male with low expectations and abundant psychiatric reserve is more likely to achieve a successful outcome. To further help identify patients who are at high risk for dissatisfaction, a previously published mnemonic is recommended: CURSED Patient (compulsive/obsessive, unrealistic, revision, surgeon shopping, entitled, denial, and psychiatric). Appropriate patient counseling includes setting appropriate expectations, reviewing the potential and anticipated risks of surgery, post-operative instruction to limit complications, and long-term follow-up. As thorough counseling is often a time-consuming endeavor, busy practices may elect to utilize various resources including educational materials, advanced practice providers, or group visits, among others. The consequences for poor patient selection and counseling may range from poor surgical outcomes and patient dissatisfaction to lawsuits, loss of credibility, or even significant patient or personal harm. PMID:28904893

Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis

PubMed Central

Hinks, Anne; Eyre, Steve; Ke, Xiayi; Barton, Anne; Martin, Paul; Flynn, Edward; Packham, Jon; Worthington, Jane; Thomson, Wendy

2010-01-01

Background Genome-wide association studies (GWAS) have been extremely successful in the search for susceptibility risk factors for complex genetic autoimmune diseases. As more studies are published, evidence is emerging of considerable overlap of loci between these diseases. In juvenile idiopathic arthritis (JIA), another complex genetic autoimmune disease, the strategy of using information from autoimmune disease GWAS or candidate gene studies to help in the search for novel JIA susceptibility loci has been successful, with confirmed association with two genes, PTPN22 and IL2RA. Rheumatoid arthritis (RA) is an autoimmune disease that shares similar clinical and pathological features with JIA and, therefore, recently identified confirmed RA susceptibility loci are also excellent JIA candidate loci. Objective To determine the overlap of disease susceptibility loci for RA and JIA. Methods Fifteen single nucleotide polymorphisms (SNPs) at nine RA-associated loci were genotyped in Caucasian patients with JIA (n=1054) and controls (n=3531) and tested for association with JIA. Allele and genotype frequencies were compared between cases and controls using the genetic analysis software, PLINK. Results Two JIA susceptibility loci were identified, one of which was a novel JIA association (STAT4) and the second confirmed previously published associations of the TRAF1/C5 locus with JIA. Weak evidence of association of JIA with three additional loci (Chr6q23, KIF5A and PRKCQ) was also obtained, which warrants further investigation. Conclusion All these loci are good candidates in view of the known pathogenesis of JIA, as genes within these regions (TRAF1, STAT4, TNFAIP3, PRKCQ) are known to be involved in T-cell receptor signalling or activation pathways. PMID:19674979

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease – 2007 update

PubMed Central

O’Donnell, Denis E; Aaron, Shawn; Bourbeau, Jean; Hernandez, Paul; Marciniuk, Darcy D; Balter, Meyer; Ford, Gordon; Gervais, Andre; Goldstein, Roger; Hodder, Rick; Kaplan, Alan; Keenan, Sean; Lacasse, Yves; Maltais, Francois; Road, Jeremy; Rocker, Graeme; Sin, Don; Sinuff, Tasmin; Voduc, Nha

2007-01-01

Chronic obstructive pulmonary disease (COPD) is a major respiratory illness in Canada that is both preventable and treatable. Our understanding of the pathophysiology of this complex condition continues to grow and our ability to offer effective treatment to those who suffer from it has improved considerably. The purpose of the present educational initiative of the Canadian Thoracic Society (CTS) is to provide up to date information on new developments in the field so that patients with this condition will receive optimal care that is firmly based on scientific evidence. Since the previous CTS management recommendations were published in 2003, a wealth of new scientific information has become available. The implications of this new knowledge with respect to optimal clinical care have been carefully considered by the CTS Panel and the conclusions are presented in the current document. Highlights of this update include new epidemiological information on mortality and prevalence of COPD, which charts its emergence as a major health problem for women; a new section on common comorbidities in COPD; an increased emphasis on the meaningful benefits of combined pharmacological and nonpharmacological therapies; and a new discussion on the prevention of acute exacerbations. A revised stratification system for severity of airway obstruction is proposed, together with other suggestions on how best to clinically evaluate individual patients with this complex disease. The results of the largest randomized clinical trial ever undertaken in COPD have recently been published, enabling the Panel to make evidence-based recommendations on the role of modern pharmacotherapy. The Panel hopes that these new practice guidelines, which reflect a rigorous analysis of the recent literature, will assist caregivers in the diagnosis and management of this common condition. PMID:17885691

Genetic variation in Tunisia in the context of human diversity worldwide.

PubMed

Cherni, Lotfi; Pakstis, Andrew J; Boussetta, Sami; Elkamel, Sarra; Frigi, Sabeh; Khodjet-El-Khil, Houssein; Barton, Alison; Haigh, Eva; Speed, William C; Ben Ammar Elgaaied, Amel; Kidd, Judith R; Kidd, Kenneth K

2016-09-01

North Africa has a complex demographic history of migrations from within Africa, Europe, and the Middle East. However, population genetic studies, especially for autosomal genetic markers, are few relative to other world regions. We examined autosomal markers for eight Tunisian and Libyan populations in order to place them in a global context. Data were collected by TaqMan on 399 autosomal single nucleotide polymorphisms on 331 individuals from Tunisia and Libya. These data were combined with data on the same SNPs previously typed on 2585 individuals from 57 populations from around the world. Where meaningful, close by SNPs were combined into multiallelic haplotypes. Data were evaluated by clustering, principal components, and population tree analyses. For a subset of 102 SNPs, data from the literature on seven additional North African populations were included in analyses. Average heterozygosity of the North African populations is high relative to our global samples, consistent with a complex demographic history. The Tunisian and Libyan samples form a discrete cluster in the global and regional views and can be separated from sub-Sahara, Middle East, and Europe. Within Tunisia the Nebeur and Smar are outlier groups. Across North Africa, pervasive East-West geographical patterns were not found. Known historical migrations and invasions did not displace or homogenize the genetic variation in the region but rather enriched it. Even a small region like Tunisia contains considerable genetic diversity. Future studies across North Africa have the potential to increase our understanding of the historical demographic factors influencing the region. Am J Phys Anthropol 161:62-71, 2016. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc. © 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

REMARK checklist elaborated to improve tumor prognostician

Cancer.gov

Experts have elaborated on a previously published checklist of 20 items -- including descriptions of design, methods, and analysis -- that researchers should address when publishing studies of prognostic markers. These markers are indicators that enable d

Higher Levels of Neanderthal Ancestry in East Asians than in Europeans

PubMed Central

Wall, Jeffrey D.; Yang, Melinda A.; Jay, Flora; Kim, Sung K.; Durand, Eric Y.; Stevison, Laurie S.; Gignoux, Christopher; Woerner, August; Hammer, Michael F.; Slatkin, Montgomery

2013-01-01

Neanderthals were a group of archaic hominins that occupied most of Europe and parts of Western Asia from ∼30,000 to 300,000 years ago (KYA). They coexisted with modern humans during part of this time. Previous genetic analyses that compared a draft sequence of the Neanderthal genome with genomes of several modern humans concluded that Neanderthals made a small (1–4%) contribution to the gene pools of all non-African populations. This observation was consistent with a single episode of admixture from Neanderthals into the ancestors of all non-Africans when the two groups coexisted in the Middle East 50–80 KYA. We examined the relationship between Neanderthals and modern humans in greater detail by applying two complementary methods to the published draft Neanderthal genome and an expanded set of high-coverage modern human genome sequences. We find that, consistent with the recent finding of Meyer et al. (2012), Neanderthals contributed more DNA to modern East Asians than to modern Europeans. Furthermore we find that the Maasai of East Africa have a small but significant fraction of Neanderthal DNA. Because our analysis is of several genomic samples from each modern human population considered, we are able to document the extent of variation in Neanderthal ancestry within and among populations. Our results combined with those previously published show that a more complex model of admixture between Neanderthals and modern humans is necessary to account for the different levels of Neanderthal ancestry among human populations. In particular, at least some Neanderthal–modern human admixture must postdate the separation of the ancestors of modern European and modern East Asian populations. PMID:23410836

egs_brachy: a versatile and fast Monte Carlo code for brachytherapy

NASA Astrophysics Data System (ADS)

Chamberland, Marc J. P.; Taylor, Randle E. P.; Rogers, D. W. O.; Thomson, Rowan M.

2016-12-01

egs_brachy is a versatile and fast Monte Carlo (MC) code for brachytherapy applications. It is based on the EGSnrc code system, enabling simulation of photons and electrons. Complex geometries are modelled using the EGSnrc C++ class library and egs_brachy includes a library of geometry models for many brachytherapy sources, in addition to eye plaques and applicators. Several simulation efficiency enhancing features are implemented in the code. egs_brachy is benchmarked by comparing TG-43 source parameters of three source models to previously published values. 3D dose distributions calculated with egs_brachy are also compared to ones obtained with the BrachyDose code. Well-defined simulations are used to characterize the effectiveness of many efficiency improving techniques, both as an indication of the usefulness of each technique and to find optimal strategies. Efficiencies and calculation times are characterized through single source simulations and simulations of idealized and typical treatments using various efficiency improving techniques. In general, egs_brachy shows agreement within uncertainties with previously published TG-43 source parameter values. 3D dose distributions from egs_brachy and BrachyDose agree at the sub-percent level. Efficiencies vary with radionuclide and source type, number of sources, phantom media, and voxel size. The combined effects of efficiency-improving techniques in egs_brachy lead to short calculation times: simulations approximating prostate and breast permanent implant (both with (2 mm)3 voxels) and eye plaque (with (1 mm)3 voxels) treatments take between 13 and 39 s, on a single 2.5 GHz Intel Xeon E5-2680 v3 processor core, to achieve 2% average statistical uncertainty on doses within the PTV. egs_brachy will be released as free and open source software to the research community.

Exploring Canadian Women's Multiple Abortion Experiences: Implications for Reducing Stigma and Improving Patient-Centered Care.

PubMed

LaRoche, Kathryn J; Foster, Angel M

2018-05-24

Roughly one-third of all abortions in Canada are subsequent abortions. However, few published reports showcase women's voices or explore women's experiences on this topic. Our study aimed to understand better the ways that women who have had multiple abortions talk about and view those experiences. Between 2012 and 2016, we conducted in-depth interviews with 41 Canadian women who had a total of 87 abortions in the 5 years preceding the interviews. We audio-recorded and transcribed all English- and French-language interviews and analyzed our data for content and themes using a multiphased iterative approach and inductive and deductive techniques. Women described their abortion experiences as unique life events, even in cases when the overarching circumstances surrounding the pregnancies were similar. Participants recalled multiple factors that influenced their decisions to terminate, including their relationship status; level of support from family and friends; financial situation; health status; previous reproductive health, pregnancy, and abortion experiences; and desire to parent. In general, a previous abortion demystified the abortion process but did not play a significant role in decision making. Women described intensified feelings of shame and both internalized and externalized stigma surrounding their decision to have more than one abortion. However, the overwhelming majority were confident in their decisions. The often-used phase "repeat abortion" fails to capture women's experiences and the complex decision making surrounding each pregnancy. Efforts to reframe the narrative of multiple abortions, including among health care providers, could help reduce the amplified stigma associated with having more than one lifetime abortion. Copyright © 2018 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Literature Review of Benign Müllerian Papilloma Contrasted With Vaginal Rhabdomyosarcoma.

PubMed

McQuillan, Sarah K; Grover, Sonia R; Pyman, Jan; Jayasinghe, Yasmin L

2016-08-01

Benign müllerian papillomas of the genital tract are rare and, hence, can be mistaken for vaginal rhabdomyosarcoma on initial clinical review. This review of the literature will consolidate the previous cases of müllerian papilloma reported and looks for clues to differentiate the 2 entities. We provide a case report and literature review, with patients from a pediatric adolescent gynecology clinic in a tertiary center. We conducted a search of English-language publications from 1951 (the first case report) until January 2014 by using the search words "Müllerian papilloma" and "prepubertal bleeding." References from previous published reports were also obtained for completeness. Literature review of benign müllerian papilloma. Since 1951, 56 cases of müllerian papilloma were reported, including 4 cases at our institution. Comorbid conditions were found in 31.5% of cases (with 3 cases associated with mesenchymal tumors). The average length of time from onset of symptoms (primarily vaginal bleeding) to diagnosis was 6.7 months (range, 1 day to 3 years), with only 1 case diagnosed incidentally. Median age of presentation was 5 years (range, 1 day to 52 years). Most cases were localized and resected with ease. Histology reveals complex papillary lesions without cytologic atypia. Benign müllerian papilloma is distinguished from the more significant diagnosis of vaginal rhabdomyosarcoma by initial length of vaginal bleeding at presentation, lack of vaginal wall extension, ease of resection, and histopathology. This is compared with vaginal rhabdomyosarcoma which commonly exhibits both localized and distant spread. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

egs_brachy: a versatile and fast Monte Carlo code for brachytherapy.

PubMed

Chamberland, Marc J P; Taylor, Randle E P; Rogers, D W O; Thomson, Rowan M

2016-12-07

egs_brachy is a versatile and fast Monte Carlo (MC) code for brachytherapy applications. It is based on the EGSnrc code system, enabling simulation of photons and electrons. Complex geometries are modelled using the EGSnrc C++ class library and egs_brachy includes a library of geometry models for many brachytherapy sources, in addition to eye plaques and applicators. Several simulation efficiency enhancing features are implemented in the code. egs_brachy is benchmarked by comparing TG-43 source parameters of three source models to previously published values. 3D dose distributions calculated with egs_brachy are also compared to ones obtained with the BrachyDose code. Well-defined simulations are used to characterize the effectiveness of many efficiency improving techniques, both as an indication of the usefulness of each technique and to find optimal strategies. Efficiencies and calculation times are characterized through single source simulations and simulations of idealized and typical treatments using various efficiency improving techniques. In general, egs_brachy shows agreement within uncertainties with previously published TG-43 source parameter values. 3D dose distributions from egs_brachy and BrachyDose agree at the sub-percent level. Efficiencies vary with radionuclide and source type, number of sources, phantom media, and voxel size. The combined effects of efficiency-improving techniques in egs_brachy lead to short calculation times: simulations approximating prostate and breast permanent implant (both with (2 mm) 3 voxels) and eye plaque (with (1 mm) 3 voxels) treatments take between 13 and 39 s, on a single 2.5 GHz Intel Xeon E5-2680 v3 processor core, to achieve 2% average statistical uncertainty on doses within the PTV. egs_brachy will be released as free and open source software to the research community.

Cystic Fibrosis Diagnostic Challenges over 4 Decades: Historical Perspectives and Lessons Learned.

PubMed

Farrell, Philip M; White, Terry B; Derichs, Nico; Castellani, Carlo; Rosenstein, Beryl J

2017-02-01

Because cystic fibrosis (CF) can be difficult to diagnose, and because information about the genetic complexities and pathologic basis of the disease has grown so rapidly over the decades, several consensus conferences have been held by the US CF Foundation, and a variety of other efforts to improve diagnostic practices have been organized by the European CF Society. Despite these efforts, the application of diagnostic criteria has been variable and caused confusion. To improve diagnosis and achieve standardization in terms and definitions worldwide, the CF Foundation in 2015 convened a committee of 32 experts in the diagnosis of CF from 9 countries. As part of the process, all previous consensus-seeking exercises sponsored by the CF Foundation, along with the important efforts of the European CF Society, were comprehensively and critically reviewed. The goal was to better understand why consensus conferences and their publications have not led to the desired results. Lessons learned from previous diagnosis consensus processes and products were identified. It was decided that participation in developing a consensus was generally not inclusive enough for global impact. It was also found that many efforts to address sweat test issues were valuable but did not always improve clinical practices as CF diagnostic testing evolved. It also became clear from this review that premature applications of potential diagnostic tests such as nasal potential difference and intestinal current measurement should be avoided until validation and standardization occur. Finally, we have learned that due to the significant and growing number of cases that are challenging to diagnose, an associated continuing medical education program is both desirable and necessary. It is necessary but not sufficient to organize and publish CF diagnosis consensus processes. Follow-up implementation efforts and monitoring practices seem essential. Copyright © 2016. Published by Elsevier Inc.

Impact and Cost-effectiveness of 3 Doses of 9-Valent Human Papillomavirus (HPV) Vaccine Among US Females Previously Vaccinated With 4-Valent HPV Vaccine.

PubMed

Chesson, Harrell W; Laprise, Jean-François; Brisson, Marc; Markowitz, Lauri E

2016-06-01

We estimated the potential impact and cost-effectiveness of providing 3-doses of nonavalent human papillomavirus (HPV) vaccine (9vHPV) to females aged 13-18 years who had previously completed a series of quadrivalent HPV vaccine (4vHPV), a strategy we refer to as "additional 9vHPV vaccination." We used 2 distinct models: (1) the simplified model, which is among the most basic of the published dynamic HPV models, and (2) the US HPV-ADVISE model, a complex, stochastic, individual-based transmission-dynamic model. When assuming no 4vHPV cross-protection, the incremental cost per quality-adjusted life-year (QALY) gained by additional 9vHPV vaccination was $146 200 in the simplified model and $108 200 in the US HPV-ADVISE model ($191 800 when assuming 4vHPV cross-protection). In 1-way sensitivity analyses in the scenario of no 4vHPV cross-protection, the simplified model results ranged from $70 300 to $182 000, and the US HPV-ADVISE model results ranged from $97 600 to $118 900. The average cost per QALY gained by additional 9vHPV vaccination exceeded $100 000 in both models. However, the results varied considerably in sensitivity and uncertainty analyses. Additional 9vHPV vaccination is likely not as efficient as many other potential HPV vaccination strategies, such as increasing primary 9vHPV vaccine coverage. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

[Psychotherapies for the Treatment of Phantom Limb Pain].

PubMed

Cárdenas, Katherine; Aranda, Mariana

The phantom limb pain has been described as a condition in which patients experience a feeling of itching, spasm or pain in a limb or body part that has been previously amputated. Such pain can be induced by a conflict between the representation of the visual and proprioceptive feedback of the previously healthy limb. The phantom limb pain occurs in at least 42 to 90% of amputees. Regular drug treatment of phantom limb pain is almost never effective. A systematic review of the literature was conducted in Medline and Cochrane using the MESH terms "phantom limb pain" and "psychotherapy", published in the last 10 years, in English and Spanish, finding 49 items. After reviewing the abstracts, 25 articles were excluded for not being related to the objective of the research. Additionally cross references of included articles and literature were reviewed. To describe the psychotherapies used in the management of phantom limb pain, their effectiveness and clinical application reported in the literature. The mechanisms underlying phantom limb pain were initially explained, as were the published studies on the usefulness of some psychotherapies such as mirror visual feedback and immersive virtual reality, visual imagery, desensitization and reprocessing eye movements and hypnosis. The phantom limb pain is a complex syndrome that requires pharmacological and psychotherapeutic intervention. The psychotherapies that have been used the most as adjuvants in the treatment of phantom limb pain are mirror visual feedback, desensitization and reprocessing eye movements, imagery and hypnosis. Studies with more representative samples, specifically randomized trials are required. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Polymerin and lignimerin, as humic acid-like sorbents from vegetable waste, for the potential remediation of waters contaminated with heavy metals, herbicides, or polycyclic aromatic hydrocarbons.

PubMed

Capasso, Renato; De Martino, Antonio

2010-10-13

Polymerin is a humic acid-like polymer, which we previously recovered for the first time from olive oil mill waste waters (OMWW) only, and chemically and physicochemically characterized. We also previously investigated its versatile sorption capacity for toxic inorganic and organic compounds. Therefore, a review is presented on the removal, from simulated polluted waters, of cationic heavy metals [Cu(II), Zn, Cr(III)] and anionic ones [Cr(VI)) and As(V)] by sorption on this natural organic sorbent in comparison with its synthetic derivatives, K-polymerin, a ferrihydrite-polymerin complex and with ferrihydrite. An overview is also performed of the removal of ionic herbicides (2,4-D, paraquat, MCPA, simazine, and cyhalofop) by sorption on polymerin, ferrihydrite, and their complex and of the removal of phenanthrene, as a representative of polycyclic aromatic hydrocarbons, by sorption on this sorbent and its complexes with micro- or nanoparticles of aluminum oxide, pointing out the employment of all these sorbents in biobed systems, which might allow the remediation of water and protection of surface and groundwater. In addition, a short review is also given on the removal of Cu(II) and Zn from simulated contaminated waters, by sorption on the humic acid-like organic fraction, named lignimerin, which we previously isolated for the first time, in collaboration with a Chilean group, from cellulose mill Kraft waste waters (KCMWW) only. More specifically, the production methods and the characterization of the two natural sorbents (polymerin and lignimerin) and their derivatives (K-polymerin ferrihydrite-polymerin, polymerin-microAl(2)O(3) and -nanoAl(2)O(3), and H-lignimerin, respectively) as well as their sorption data and mechanism are reviewed. Published and original results obtained by the cyclic sorption on all of the considered sorbents for the removal of the above-mentioned toxic compounds from simulated waste waters are also reported. Moreover, sorption capacity and mechanism of the considered compounds on polymerins and lignimerins are evaluated in comparison with other known natural sorbents, especially of humic acid nature and other organic matter. Some of their technical aspects and relative costs are also considered. Finally, the possible large-scale application of the considered sorption systems for water remediation is briefly discussed.

CFD: A Castle in the Sand?

NASA Technical Reports Server (NTRS)

Kleb, William L.; Wood, William A.

2004-01-01

The computational simulation community is not routinely publishing independently verifiable tests to accompany new models or algorithms. A survey reveals that only 22% of new models published are accompanied by tests suitable for independently verifying the new model. As the community develops larger codes with increased functionality, and hence increased complexity in terms of the number of building block components and their interactions, it becomes prohibitively expensive for each development group to derive the appropriate tests for each component. Therefore, the computational simulation community is building its collective castle on a very shaky foundation of components with unpublished and unrepeatable verification tests. The computational simulation community needs to begin publishing component level verification tests before the tide of complexity undermines its foundation.

[New design of the Health Survey of Catalonia (Spain, 2010-2014): a step forward in health planning and evaluation].

PubMed

Alcañiz-Zanón, Manuela; Mompart-Penina, Anna; Guillén-Estany, Montserrat; Medina-Bustos, Antonia; Aragay-Barbany, Josep M; Brugulat-Guiteras, Pilar; Tresserras-Gaju, Ricard

2014-01-01

This article presents the genesis of the Health Survey of Catalonia (Spain, 2010-2014) with its semiannual subsamples and explains the basic characteristics of its multistage sampling design. In comparison with previous surveys, the organizational advantages of this new statistical operation include rapid data availability and the ability to continuously monitor the population. The main benefits are timeliness in the production of indicators and the possibility of introducing new topics through the supplemental questionnaire as a function of needs. Limitations consist of the complexity of the sample design and the lack of longitudinal follow-up of the sample. Suitable sampling weights for each specific subsample are necessary for any statistical analysis of micro-data. Accuracy in the analysis of territorial disaggregation or population subgroups increases if annual samples are accumulated. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Modal parameter identification using the log decrement method and band-pass filters

NASA Astrophysics Data System (ADS)

Liao, Yabin; Wells, Valana

2011-10-01

This paper presents a time-domain technique for identifying modal parameters of test specimens based on the log-decrement method. For lightly damped multidegree-of-freedom or continuous systems, the conventional method is usually restricted to identification of fundamental-mode parameters only. Implementation of band-pass filters makes it possible for the proposed technique to extract modal information of higher modes. The method has been applied to a polymethyl methacrylate (PMMA) beam for complex modulus identification in the frequency range 10-1100 Hz. Results compare well with those obtained using the Least Squares method, and with those previously published in literature. Then the accuracy of the proposed method has been further verified by experiments performed on a QuietSteel specimen with very low damping. The method is simple and fast. It can be used for a quick estimation of the modal parameters, or as a complementary approach for validation purposes.

Transgenic over expression of nicotinic receptor alpha 5, alpha 3, and beta 4 subunit genes reduces ethanol intake in mice.

PubMed

Gallego, Xavier; Ruiz-Medina, Jessica; Valverde, Olga; Molas, Susanna; Robles, Noemí; Sabrià, Josefa; Crabbe, John C; Dierssen, Mara

2012-05-01

Abuse of alcohol and smoking are extensively co-morbid. Some studies suggest partial commonality of action of alcohol and nicotine mediated through nicotinic acetylcholine receptors (nAChRs). We tested mice with transgenic over expression of the alpha 5, alpha 3, beta 4 receptor subunit genes, which lie in a cluster on human chromosome 15, that were previously shown to have increased nicotine self-administration, for several responses to ethanol. Transgenic and wild-type mice did not differ in sensitivity to several acute behavioral responses to ethanol. However, transgenic mice drank less ethanol than wild-type in a two-bottle (ethanol vs. water) preference test. These results suggest a complex role for this receptor subunit gene cluster in the modulation of ethanol's as well as nicotine's effects. Copyright © 2012. Published by Elsevier Inc.

Comment on “The role of interbasin groundwater transfers in geologically complex terranes, demonstrated by the Great Basin in the western United States”: report published in Hydrogeology Journal (2014) 22:807–828, by Stephen T. Nelson and Alan L. Mayo

USGS Publications Warehouse

Masbruch, Melissa D.; Brooks, Lynette E.; Heilweil, Victor M.; Sweetkind, Donald S.

2015-01-01

The subject article (Nelson and Mayo 2014) presents an overview of previous reports of interbasin flow in the Great Basin of the western United States. This Comment is presented by authors of a cited study (comprising chapters in one large report) on the Great Basin carbonate and alluvial aquifer system (GBCAAS; Heilweil and Brooks 2011; Masbruch et al. 2011; Sweetkind et al. 2011a, b), who agree that water budget imbalances alone are not enough to accurately quantify interbasin flow; however, it is proposed that statements made in the subject article about the GBCAAS report are inaccurate. The Comment authors appreciate the opportunity to clarify some statements made about the work.

Patient- and family-centered care of children in the emergency department.

PubMed

O'Malley, Patricia J; Brown, Kathleen; Krug, Steven E

2008-08-01

Patient- and family-centered care is an innovative approach to the planning, delivery, and evaluation of health care that is grounded in a mutually beneficial partnership among patients, families, and health care professionals. Providing patient- and family-centered care to children in the emergency department setting presents many opportunities and challenges. This technical report draws on previously published policy statements and reports, reviews the current literature, and describes the present state of practice and research regarding patient- and family-centered care for children in the emergency department setting as well as some of the complexities of providing such care. This technical report has been endorsed by the Academic Pediatric Association (formerly the Ambulatory Pediatric Association), the American College of Osteopathic Emergency Physicians, the National Association of Emergency Medical Technicians, the Institute for Family-Centered Care, and the American College of Emergency Physicians. This report is also supported by the Emergency Nurses Association.

In-situ characterization of laser-powder interaction and cooling rates through high-speed imaging of powder bed fusion additive manufacturing

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

Scipioni Bertoli, Umberto; Guss, Gabe; Wu, Sheldon

We report detailed understanding of the complex melt pool physics plays a vital role in predicting optimal processing regimes in laser powder bed fusion additive manufacturing. In this work, we use high framerate video recording of Selective Laser Melting (SLM) to provide useful insight on the laser-powder interaction and melt pool evolution of 316 L powder layers, while also serving as a novel instrument to quantify cooling rates of the melt pool. The experiment was performed using two powder types – one gas- and one water-atomized – to further clarify how morphological and chemical differences between these two feedstock materialsmore » influence the laser melting process. Finally, experimentally determined cooling rates are compared with values obtained through computer simulation, and the relationship between cooling rate and grain cell size is compared with data previously published in the literature.« less

Treatment of Calcaneal Fracture With Severe Soft Tissue Injury and Osteomyelitis: A Case Report.

PubMed

Karns, Michael; Dailey, Steven K; Archdeacon, Michael T

2015-01-01

Advancements in surgical technique have resulted in the ability to reconstruct lower extremity injuries that would have previously been treated by amputation. Currently, a paucity of data is available specifically addressing limb amputation versus reconstruction for calcaneal fractures with severe soft tissue compromise. Reconstruction leaves the patient with their native limb; however, multiple surgeries, infections, chronic pain, and a poor functional outcome are very real possibilities. We present the case of a complex calcaneal fracture complicated by soft tissue injury and osteomyelitis that highlights the importance of shared decision-making between patient and surgeon when considering reconstruction versus amputation. This case exemplifies the need for open communication concerning the risks and benefits of treatment modalities while simultaneously considering the patient's expectations and desired outcomes. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Pretty and powerless: nurses in advertisements, 1930-1950.

PubMed

Lusk, B

2000-06-01

Images of nurses in pictorial advertisements from all issues of hospital administration journals published in 1930, 1940, and 1950 (N = 598) were examined. Content analysis of the data was based on Goffman's classic 1979 study on gender advertisements. Nurses also were compared with other figures in the advertisements and nursing activities were described. Nurses were predominantly portrayed as female, young, eager to please, and without the appearance of wisdom. In group scenes, nurses were placed as subordinate to physicians and hospital administrators. Nurses in 1940 performed more complex, autonomous activities than in 1930 and 1950. These findings support previous research focused on more recent portrayals of women and nurses in communication media. The overt and subtle subordinate representation of nurses in these advertisements, compared with physicians and administrators, reveals one facet of nursing's heritage as a woman's profession. Copyright 2000 John Wiley & Sons, Inc.

[Private health insurance in Brazil: approaches to public/private patterns in healthcare].

PubMed

Sestelo, José Antonio de Freitas; Souza, Luis Eugenio Portela Fernandes de; Bahia, Lígia

2013-05-01

This article draws on a previous review of 270 articles on private health plans published from 2000 to 2010 and selects 17 that specifically address the issue of the relationship between the public and private healthcare sectors. Content analysis considered the studies' concepts and terms, related theoretical elements, and predominant lines of argument. A reading of the argumentative strategies detected the existence of a critical view of the modus operandi in the public/private relationship based on Social Medicine and the theoretical tenets of the Brazilian Health Reform Movement. The study also identified contributions based on neoliberal business approaches that focus strictly on economic issues to discuss private health insurance. Understanding the public/private link in healthcare obviously requires the development of a solid empirical base, analyzed with adequate theoretical assumptions due to the inherent degree of complexity in the public/private healthcare interface.

Electron-ion dissociative recombination rate constants relevant to the Titan atmosphere and the Interstellar Medium

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

Osborne, David; Lawson, Patrick; Adams, Nigel, E-mail: ngadams@uga.edu

Following the arrival of Cassini at Titan in 2004, the Titan atmosphere has been shown to contain large complex polycyclic-aromatic hydrocarbons. Since Cassini has provided a great deal of data, there exists a need for kinetic rate data to help with modeling this atmosphere. One type of kinetic data needed is electron-ion dissociative recombination (e-IDR) rate constants. These data are not readily available for larger compounds, such as naphthalene, or oxygen containing compounds, such as 1,4 dioxane or furan. Here, the rate constants for naphthalene, 1,4 dioxane, and furan have been measured and their temperature dependencies are determined when possible,more » using the University of Georgia's Variable Temperature Flowing Afterglow. The rate constants are compared with those previously published for other compounds; these show trends which illustrate the effects which multi-rings and oxygen heteroatoms substitutions have upon e-IDR rate constants.« less

Spumaretroviruses: Updated taxonomy and nomenclature.

PubMed

Khan, Arifa S; Bodem, Jochen; Buseyne, Florence; Gessain, Antoine; Johnson, Welkin; Kuhn, Jens H; Kuzmak, Jacek; Lindemann, Dirk; Linial, Maxine L; Löchelt, Martin; Materniak-Kornas, Magdalena; Soares, Marcelo A; Switzer, William M

2018-03-01

Spumaretroviruses, commonly referred to as foamy viruses, are complex retroviruses belonging to the subfamily Spumaretrovirinae, family Retroviridae, which naturally infect a variety of animals including nonhuman primates (NHPs). Additionally, cross-species transmissions of simian foamy viruses (SFVs) to humans have occurred following exposure to tissues of infected NHPs. Recent research has led to the identification of previously unknown exogenous foamy viruses, and to the discovery of endogenous spumaretrovirus sequences in a variety of host genomes. Here, we describe an updated spumaretrovirus taxonomy that has been recently accepted by the International Committee on Taxonomy of Viruses (ICTV) Executive Committee, and describe a virus nomenclature that is generally consistent with that used for other retroviruses, such as lentiviruses and deltaretroviruses. This taxonomy can be applied to distinguish different, but closely related, primate (e.g., human, ape, simian) foamy viruses as well as those from other hosts. This proposal accounts for host-virus co-speciation and cross-species transmission. Published by Elsevier Inc.

Refractive-index measurement and inverse correction using optical coherence tomography.

PubMed

Stritzel, Jenny; Rahlves, Maik; Roth, Bernhard

2015-12-01

We describe a novel technique for determination of the refractive index of hard biological tissue as well as nonopaque technical samples based on optical coherence tomography (OCT). Our method relies on an inverse refractive-index correction (I-RIC), which matches a measured feature geometry distorted due to refractive-index boundaries to its real geometry. For known feature geometry, the refractive index can be determined with high precision from the best match between the distorted and corrected images. We provide experimental data for refractive-index measurements on a polymethylmethacrylate (PMMA) and on an ex vivo porcine cranial-bone, which are compared to reference measurements and previously published data. Our method is potentially capable of in vivo measurements on rigid biological tissue such as bone as, for example, is required to improve guidance in robot-aided surgical interventions and also for retrieving complex refractive-index profiles of compound materials.

A composite computational model of liver glucose homeostasis. I. Building the composite model.

PubMed

Hetherington, J; Sumner, T; Seymour, R M; Li, L; Rey, M Varela; Yamaji, S; Saffrey, P; Margoninski, O; Bogle, I D L; Finkelstein, A; Warner, A

2012-04-07

A computational model of the glucagon/insulin-driven liver glucohomeostasis function, focusing on the buffering of glucose into glycogen, has been developed. The model exemplifies an 'engineering' approach to modelling in systems biology, and was produced by linking together seven component models of separate aspects of the physiology. The component models use a variety of modelling paradigms and degrees of simplification. Model parameters were determined by an iterative hybrid of fitting to high-scale physiological data, and determination from small-scale in vitro experiments or molecular biological techniques. The component models were not originally designed for inclusion within such a composite model, but were integrated, with modification, using our published modelling software and computational frameworks. This approach facilitates the development of large and complex composite models, although, inevitably, some compromises must be made when composing the individual models. Composite models of this form have not previously been demonstrated.

International Dengue Vaccine Communication and Advocacy: Challenges and Way Forward.

PubMed

Carvalho, Ana; Van Roy, Rebecca; Andrus, Jon

2016-01-01

Dengue vaccine introduction will likely occur soon. However, little has been published on international dengue vaccine communication and advocacy. More effort at the international level is required to review, unify and strategically disseminate dengue vaccine knowledge to endemic countries' decision makers and potential donors. Waiting to plan for the introduction of new vaccines until licensure may delay access in developing countries. Concerted efforts to communicate and advocate for vaccines prior to licensure are likely challenged by unknowns of the use of dengue vaccines and the disease, including uncertainties of vaccine impact, vaccine access and dengue's complex pathogenesis and epidemiology. Nevertheless, the international community has the opportunity to apply previous best practices for vaccine communication and advocacy. The following key strategies will strengthen international dengue vaccine communication and advocacy: consolidating existing coalitions under one strategic umbrella, urgently convening stakeholders to formulate the roadmap for integrated dengue prevention and control, and improving the dissemination of dengue scientific knowledge.

Description of the tadpoles of two endemic frogs: the Phu Luang cascade frog Odorrana aureola (Anura: Ranidae) and the Isan big-headed frog Limnonectes isanensis (Anura: Dicroglossidae) from northeastern Thailand.

PubMed

Ampai, Natee; Rujirawan, Attapol; Arkajag, Jirachai; Mcleod, David S; Aowphol, Anchalee

2015-07-07

We describe the external morphology of the tadpoles of two frogs endemic to Thailand: the Phu Luang cascade frog    (Odorrana aureola) and the Isan big-headed frog (Limnonectes isanensis) from the type localities in the Phu Luang Wildlife Sanctuary, Loei Province, northeastern Thailand. Morphological and genetic characters (16S rRNA) were used to identify specimen and match tadpoles to the adults. Detailed descriptions of external morphology and coloration in life are provided for both species. We provide a brief discussion of the ecology of these tadpoles and a comparison to previously published data from tadpoles of closely related taxa. Additionally, we provide evidence for the utility of larval morphology in resolving the taxonomic puzzles presented by cryptic species complexes.

Emerging treatments for primary sclerosing cholangitis.

PubMed

Rodriguez, Eduardo A; Carey, Elizabeth J; Lindor, Keith D

2017-05-01

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic, idiopathic liver disease that can progress to end-stage liver disease, cirrhosis and cholangiocarcinoma. PSC is an uncommon and highly heterogeneous disease, associated with inflammatory bowel disease and a complex pathophysiology. To date, no medical therapies have proved effective. The only available treatment for end-stage PSC is liver transplant, but recurrence is a significant complication. Areas covered: This review will explore previously tested treatments, discuss current treatment strategies and present viewpoints about future emerging therapies in PSC. We searched PubMed using the noted keywords. We included data from full-text articles published in English. Further relevant articles were identified from the reference lists of review articles. Expert commentary: The development of new therapies in PSC has been challenging. However, with greater awareness of the disease nowadays, new insights into the disease may help in the design of future therapeutic agents in PSC and ultimately in effective therapies.

Bipolar Disorder and Cognitive Dysfunction: A Complex Link.

PubMed

Cipriani, Gabriele; Danti, Sabrina; Carlesi, Cecilia; Cammisuli, Davide Maria; Di Fiorino, Mario

2017-10-01

The aim of this article was to describe the current evidence regarding phenomenon of cognitive functioning and dementia in bipolar disorder (BD). Cochrane Library and PubMed searches were conducted for relevant articles, chapters, and books published before 2016. Search terms used included "bipolar disorder," "cognitive dysfunction," and "dementia." At the end of the selection process, 159 studies were included in our qualitative synthesis. As result, cognitive impairments in BD have been previously considered as infrequent and limited to the affective episodes. Nowadays, there is evidence of stable and lasting cognitive dysfunctions in all phases of BD, including remission phase, particularly in the following domains: attention, memory, and executive functions. The cause of cognitive impairment in BD raises the question if it subtends a neurodevelopmental or a neurodegenerative process. Impaired cognitive functioning associated with BD may contribute significantly to functional disability, in addition to the distorted affective component usually emphasized.

Nerve Entrapment in Ankle and Foot: Ultrasound Imaging.

PubMed

Chari, Basavaraj; McNally, Eugene

2018-07-01

Peripheral nerve entrapment of the ankle and foot is relatively uncommon and often underdiagnosed because electrophysiologic studies may not contribute to the diagnosis. Anatomy of the peripheral nerves is variable and complex, and along with a comprehensive physical examination, a thorough understanding of the applied anatomy is essential. Several studies have helped identify specific areas in which nerves are commonly compressed. Identified secondary causes of nerve compression include previous trauma, osteophytes, ganglion cysts, edema, accessory muscles, tenosynovitis, vascular lesions, and a primary nerve tumor. Imaging plays a key role in identifying primary and secondary causes of nerve entrapment, specifically ultrasound (US) and magnetic resonance imaging. US is a dynamic imaging modality that is cost effective and offers excellent resolution. Symptoms of nerve entrapment may mimic other common foot and ankle conditions such as plantar fasciitis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

On chirality of slime mould.

PubMed

Dimonte, Alice; Adamatzky, Andrew; Erokhin, Victor; Levin, Michael

2016-02-01

Left-right patterning and lateralised behaviour is an ubiquitous aspect of plants and animals. The mechanisms linking cellular chirality to the large-scale asymmetry of multicellular structures are incompletely understood, and it has been suggested that the chirality of living cells is hardwired in their cytoskeleton. We examined the question of biased asymmetry in a unique organism: the slime mould Physarum polycephalum, which is unicellular yet possesses macroscopic, complex structure and behaviour. In laboratory experiment using a T-shape, we found that Physarum turns right in more than 74% of trials. The results are in agreement with previously published studies on asymmetric movement of muscle cells, neutrophils, liver cells and growing neural filaments, and for the first time reveal the presence of consistently-biased laterality in the fungi kingdom. Exact mechanisms of the slime mould's direction preference remain unknown. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Electron-ion dissociative recombination rate constants relevant to the Titan atmosphere and the Interstellar Medium

NASA Astrophysics Data System (ADS)

Osborne, David; Lawson, Patrick; Adams, Nigel

2014-01-01

Following the arrival of Cassini at Titan in 2004, the Titan atmosphere has been shown to contain large complex polycyclic-aromatic hydrocarbons. Since Cassini has provided a great deal of data, there exists a need for kinetic rate data to help with modeling this atmosphere. One type of kinetic data needed is electron-ion dissociative recombination (e-IDR) rate constants. These data are not readily available for larger compounds, such as naphthalene, or oxygen containing compounds, such as 1,4 dioxane or furan. Here, the rate constants for naphthalene, 1,4 dioxane, and furan have been measured and their temperature dependencies are determined when possible, using the University of Georgia's Variable Temperature Flowing Afterglow. The rate constants are compared with those previously published for other compounds; these show trends which illustrate the effects which multi-rings and oxygen heteroatoms substitutions have upon e-IDR rate constants.

A graphical method to evaluate predominant geochemical processes occurring in groundwater systems for radiocarbon dating

USGS Publications Warehouse

Han, Liang-Feng; Plummer, Niel; Aggarwal, Pradeep

2012-01-01

A graphical method is described for identifying geochemical reactions needed in the interpretation of radiocarbon age in groundwater systems. Graphs are constructed by plotting the measured 14C, δ13C, and concentration of dissolved inorganic carbon and are interpreted according to specific criteria to recognize water samples that are consistent with a wide range of processes, including geochemical reactions, carbon isotopic exchange, 14C decay, and mixing of waters. The graphs are used to provide a qualitative estimate of radiocarbon age, to deduce the hydrochemical complexity of a groundwater system, and to compare samples from different groundwater systems. Graphs of chemical and isotopic data from a series of previously-published groundwater studies are used to demonstrate the utility of the approach. Ultimately, the information derived from the graphs is used to improve geochemical models for adjustment of radiocarbon ages in groundwater systems.

Stratiform chromite deposit model

USGS Publications Warehouse

Schulte, Ruth F.; Taylor, Ryan D.; Piatak, Nadine M.; Seal, Robert R.

2010-01-01

Stratiform chromite deposits are of great economic importance, yet their origin and evolution remain highly debated. Layered igneous intrusions such as the Bushveld, Great Dyke, Kemi, and Stillwater Complexes, provide opportunities for studying magmatic differentiation processes and assimilation within the crust, as well as related ore-deposit formation. Chromite-rich seams within layered intrusions host the majority of the world's chromium reserves and may contain significant platinum-group-element (PGE) mineralization. This model of stratiform chromite deposits is part of an effort by the U.S. Geological Survey's Mineral Resources Program to update existing models and develop new descriptive mineral deposit models to supplement previously published models for use in mineral-resource and mineral-environmental assessments. The model focuses on features that may be common to all stratiform chromite deposits as a way to gain insight into the processes that gave rise to their emplacement and to the significant economic resources contained in them.

Analysis of waveguides containing EMCs (electromagnetic conductors) or PEMCs (perfect electromagnetic conductors)

NASA Astrophysics Data System (ADS)

Prudêncio, Filipa R.; Matos, Sérgio A.; Paiva, Carlos R.

2014-11-01

The concept of a perfect electromagnetic conductor (PEMC) was introduced to generalize and unify two well-known and apparently disjoint concepts in electromagnetics: the perfect electric conductor (PEC) and the perfect magnetic conductor (PMC). Although the PEMC has proven a fertile tool in electromagnetic analyses dealing with new and complex boundaries, its corresponding definition as a medium has, nevertheless, raised several problems. In fact, according to its initial 3D definition, the PEMC cannot be considered a unique and well-defined medium: it leads to extraneous fields without physical meaning. By using a previously published generalization of a PEMC that regards this concept both as a boundary and as a medium - which was dubbed an MIM (Minkowskian isotropic medium) and acts, in practice, as an actual electromagnetic conductor (EMC) - it is herein presented a straightforward analysis of waveguides containing PEMCs that readily and systematically follows from the general framework of waveguides containing EMCs.

In-situ characterization of laser-powder interaction and cooling rates through high-speed imaging of powder bed fusion additive manufacturing

DOE PAGES

Scipioni Bertoli, Umberto; Guss, Gabe; Wu, Sheldon; ...

2017-09-21

We report detailed understanding of the complex melt pool physics plays a vital role in predicting optimal processing regimes in laser powder bed fusion additive manufacturing. In this work, we use high framerate video recording of Selective Laser Melting (SLM) to provide useful insight on the laser-powder interaction and melt pool evolution of 316 L powder layers, while also serving as a novel instrument to quantify cooling rates of the melt pool. The experiment was performed using two powder types – one gas- and one water-atomized – to further clarify how morphological and chemical differences between these two feedstock materialsmore » influence the laser melting process. Finally, experimentally determined cooling rates are compared with values obtained through computer simulation, and the relationship between cooling rate and grain cell size is compared with data previously published in the literature.« less

Percolation behaviour in the magnetic permeability and electrical conductivity in conducting magnetic - Insulating non magnetic binary composites

NASA Astrophysics Data System (ADS)

McLachlan, David S.; Doyle, Terence B.; Sauti, Godfrey

2018-07-01

Experimental results of the complex magnetic permeability (μ) and the electrical conductivity (σ) of a granular paramagnetic Gadolinium Gallium Garnet (GGG: 0.3-26 vol%) and Teflon (PTFE) system are presented and discussed in relation to previously published (conductivity) and unpublished (permeability) studies on granular Fe3O4 - talc and Ni - talc wax systems. In these systems plots of the real conductivity (σm‧) against the volume fraction (φ) lie on characteristic sigmoid curves that when fitted to the Two Exponent Phenomenological Percolation Equation (TEPPE) confirm the existence of "percolation microstructures" with critical volume fractions (φc). The plots of the real and imaginary permeability (μm‧) and (μm″) satisfactorily fit to the TEPPE using the φc obtained in each case from the "conductivity" measurements. In all three cases the conductivity results gave the exponent t > 2, and the permeability results gave t < 1.

Hydraulic containment: analytical and semi-analytical models for capture zone curve delineation

NASA Astrophysics Data System (ADS)

Christ, John A.; Goltz, Mark N.

2002-05-01

We present an efficient semi-analytical algorithm that uses complex potential theory and superposition to delineate the capture zone curves of extraction wells. This algorithm is more flexible than previously published techniques and allows the user to determine the capture zone for a number of arbitrarily positioned extraction wells pumping at different rates. The algorithm is applied to determine the capture zones and optimal well spacing of two wells pumping at different flow rates and positioned at various orientations to the direction of regional groundwater flow. The algorithm is also applied to determine capture zones for non-colinear three-well configurations as well as to determine optimal well spacing for up to six wells pumping at the same rate. We show that the optimal well spacing is found by minimizing the difference in the stream function evaluated at the stagnation points.

Player Types, Play Styles, and Play Complexity: Updating the Entertainment Grid

ERIC Educational Resources Information Center

Rademacher Mena, Ricardo Javier

2012-01-01

In a previous work the author created the Education and Entertainment Grid by combining various taxonomies from the fields of play and learning. In this paper, a section of this grid known as the Entertainment Grid will be extended by including previously unused elements of Richard Bartle's online player types and Robert Caillois' play complexity.…

A BIBLIOGRAPHY OF BIOLOGICAL APPLICATIONS OF AUTORADIOGRAPHY, 1958 THROUGH 1959

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

Johnston, M.E.

1959-08-01

This bibliography of 281 reports and published literature references on biological applications of autoradiography is a supplement to the one published July 1958 as UCRL-8400. References previously omitted are included. (J.E. D.)

A second chance for authors of hijacked journals to publish in legitimate journals.

PubMed

Jalalian, Mehrdad

2015-01-01

This article proposes the republication of articles that have previously been published in counterfeit websites of hijacked journals. The paper also discusses the technical and ethical aspects of republishing such articles.

Publisher Correction: Measuring progress from nationally determined contributions to mid-century strategies

NASA Astrophysics Data System (ADS)

Iyer, Gokul; Ledna, Catherine; Clarke, Leon; Edmonds, James; McJeon, Haewon; Kyle, Page; Williams, James H.

2018-03-01

In the version of this Article previously published, technical problems led to the wrong summary appearing on the homepage, and an incorrect Supplementary Information file being uploaded. Both errors have now been corrected.

Army Digital Systems Complexity

DTIC Science & Technology

2008-05-22

recently published Chamber of Commerce report entitled Defense Trade: Keeping America Secure in March of 2007, indicates that the defense industry employs... Chamber of Commerce published report indicated that the national defense expenditures totaled $474.4 billion in 2005 and represented 3.8 percent of U.S...from the U.S. Chamber of Commerce , published in March 2007, shows total direct defense expenditure projections

Combined qualitative and quantitative research designs.

PubMed

Seymour, Jane

2012-12-01

Mixed methods research designs have been recognized as important in addressing complexity and are recommended particularly in the development and evaluation of complex interventions. This article reports a review of studies in palliative care published between 2010 and March 2012 that combine qualitative and quantitative approaches. A synthesis of approaches to mixed methods research taken in 28 examples of published research studies of relevance to palliative and supportive care is provided, using a typology based on a classic categorization put forward in 1992. Mixed-method studies are becoming more frequently employed in palliative care research and resonate with the complexity of the palliative care endeavour. Undertaking mixed methods research requires a sophisticated understanding of the research process and recognition of some of the underlying complexities encountered when working with different traditions and perspectives on issues of: sampling, validity, reliability and rigour, different sources of data and different data collection and analysis techniques.

A New Method to Develop Human Dental Pulp Cells and Platelet-rich Fibrin Complex.

PubMed

He, Xuan; Chen, Wen-Xia; Ban, Guifei; Wei, Wei; Zhou, Jun; Chen, Wen-Jin; Li, Xian-Yu

2016-11-01

Platelet-rich fibrin (PRF) has been used as a scaffold material in various tissue regeneration studies. In the previous methods to combine seed cells with PRF, the structure of PRF was damaged, and the manipulation time in vitro was also increased. The objective of this in vitro study was to explore an appropriate method to develop a PRF-human dental pulp cell (hDPC) complex to maintain PRF structure integrity and to find out the most efficient part of PRF. The PRF-hDPC complex was developed at 3 different time points during PRF preparation: (1) the before centrifugation (BC) group, the hDPC suspension was added to the venous blood before blood centrifugation; (2) the immediately after centrifugation (IAC) group, the hDPC suspension was added immediately after blood centrifugation; (3) the after centrifugation (AC) group, the hDPC suspension was added 10 minutes after blood centrifugation; and (4) the control group, PRF without hDPC suspension. The prepared PRF-hDPC complexes were cultured for 7 days. The samples were fixed for histologic, immunohistochemistry, and scanning electron microscopic evaluation. Real-time polymerase chain reaction was performed to evaluate messenger RNA expression of alkaline phosphatase and dentin sialophosphoprotein. Enzyme-linked immunosorbent assay quantification for growth factors was performed within the different parts of the PRF. Histologic, immunohistochemistry, and scanning electron microscopic results revealed that hDPCs were only found in the BC group and exhibited favorable proliferation. Real-time polymerase chain reaction revealed that alkaline phosphatase and dentin sialophosphoprotein expression increased in the cultured PRF-hDPC complex. The lower part of the PRF released the maximum quantity of growth factors. Our new method to develop a PRF-hDPCs complex maintained PRF structure integrity. The hDPCs were distributed in the buffy coat, which might be the most efficient part of PRF. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Hydrous partial melting in the sheeted dike complex at fast spreading ridges: experimental and natural observations

NASA Astrophysics Data System (ADS)

France, Lydéric; Koepke, Juergen; Ildefonse, Benoit; Cichy, Sarah B.; Deschamps, Fabien

2010-11-01

In ophiolites and in present-day oceanic crust formed at fast spreading ridges, oceanic plagiogranites are commonly observed at, or close to the base of the sheeted dike complex. They can be produced either by differentiation of mafic melts, or by hydrous partial melting of the hydrothermally altered sheeted dikes. In addition, the hydrothermally altered base of the sheeted dike complex, which is often infiltrated by plagiogranitic veins, is usually recrystallized into granoblastic dikes that are commonly interpreted as a result of prograde granulitic metamorphism. To test the anatectic origin of oceanic plagiogranites, we performed melting experiments on a natural hydrothermally altered dike, under conditions that match those prevailing at the base of the sheeted dike complex. All generated melts are water saturated, transitional between tholeiitic and calc-alkaline, and match the compositions of oceanic plagiogranites observed close to the base of the sheeted dike complex. Newly crystallized clinopyroxene and plagioclase have compositions that are characteristic of the same minerals in granoblastic dikes. Published silicic melt compositions obtained in classical MORB fractionation experiments also broadly match the compositions of oceanic plagiogranites; however, the compositions of the coexisting experimental minerals significantly deviate from those of the granoblastic dikes. Our results demonstrate that hydrous partial melting is a likely common process in the root zone of the sheeted dike complex, starting at temperatures exceeding 850°C. The newly formed melt can either crystallize to form oceanic plagiogranites or may be recycled within the melt lens resulting in hybridized and contaminated MORB melts. It represents the main MORB crustal contamination process. The residue after the partial melting event is represented by the granoblastic dikes. Our results support a model with a dynamic melt lens that has the potential to trigger hydrous partial melting reactions in the previously hydrothermally altered sheeted dikes. A new thermometer using the Al content of clinopyroxene is also elaborated.

The Application of COMSOL Multiphysics Package on the Modelling of Complex 3-D Lithospheric Electrical Resistivity Structures - A Case Study from the Proterozoic Orogenic belt within the North China Craton

NASA Astrophysics Data System (ADS)

Guo, L.; Yin, Y.; Deng, M.; Guo, L.; Yan, J.

2017-12-01

At present, most magnetotelluric (MT) forward modelling and inversion codes are based on finite difference method. But its structured mesh gridding cannot be well adapted for the conditions with arbitrary topography or complex tectonic structures. By contrast, the finite element method is more accurate in calculating complex and irregular 3-D region and has lower requirement of function smoothness. However, the complexity of mesh gridding and limitation of computer capacity has been affecting its application. COMSOL Multiphysics is a cross-platform finite element analysis, solver and multiphysics full-coupling simulation software. It achieves highly accurate numerical simulations with high computational performance and outstanding multi-field bi-directional coupling analysis capability. In addition, its AC/DC and RF module can be used to easily calculate the electromagnetic responses of complex geological structures. Using the adaptive unstructured grid, the calculation is much faster. In order to improve the discretization technique of computing area, we use the combination of Matlab and COMSOL Multiphysics to establish a general procedure for calculating the MT responses for arbitrary resistivity models. The calculated responses include the surface electric and magnetic field components, impedance components, magnetic transfer functions and phase tensors. Then, the reliability of this procedure is certificated by 1-D, 2-D and 3-D and anisotropic forward modeling tests. Finally, we establish the 3-D lithospheric resistivity model for the Proterozoic Wutai-Hengshan Mts. within the North China Craton by fitting the real MT data collected there. The reliability of the model is also verified by induced vectors and phase tensors. Our model shows more details and better resolution, compared with the previously published 3-D model based on the finite difference method. In conclusion, COMSOL Multiphysics package is suitable for modeling the 3-D lithospheric resistivity structures under complex tectonic deformation backgrounds, which could be a good complement to the existing finite-difference inversion algorithms.

Dissociation of a Dynamic Protein Complex Studied by All-Atom Molecular Simulations.

PubMed

Zhang, Liqun; Borthakur, Susmita; Buck, Matthias

2016-02-23

The process of protein complex dissociation remains to be understood at the atomic level of detail. Computers now allow microsecond timescale molecular-dynamics simulations, which make the visualization of such processes possible. Here, we investigated the dissociation process of the EphA2-SHIP2 SAM-SAM domain heterodimer complex using unrestrained all-atom molecular-dynamics simulations. Previous studies on this system have shown that alternate configurations are sampled, that their interconversion can be fast, and that the complex is dynamic by nature. Starting from different NMR-derived structures, mutants were designed to stabilize a subset of configurations by swapping ion pairs across the protein-protein interface. We focused on two mutants, K956D/D1235K and R957D/D1223R, with attenuated binding affinity compared with the wild-type proteins. In contrast to calculations on the wild-type complexes, the majority of simulations of these mutants showed protein dissociation within 2.4 μs. During the separation process, we observed domain rotation and pivoting as well as a translation and simultaneous rolling, typically to alternate and weaker binding interfaces. Several unsuccessful recapturing attempts occurred once the domains were moderately separated. An analysis of protein solvation suggests that the dissociation process correlates with a progressive loss of protein-protein contacts. Furthermore, an evaluation of internal protein dynamics using quasi-harmonic and order parameter analyses indicates that changes in protein internal motions are expected to contribute significantly to the thermodynamics of protein dissociation. Considering protein association as the reverse of the separation process, the initial role of charged/polar interactions is emphasized, followed by changes in protein and solvent dynamics. The trajectories show that protein separation does not follow a single distinct pathway, but suggest that the mechanism of dissociation is common in that it initially involves transitions to surfaces with fewer, less favorable contacts compared with those seen in the fully formed complex. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature.

PubMed

Abou Jamra, Rami; Philippe, Orianne; Raas-Rothschild, Annick; Eck, Sebastian H; Graf, Elisabeth; Buchert, Rebecca; Borck, Guntram; Ekici, Arif; Brockschmidt, Felix F; Nöthen, Markus M; Munnich, Arnold; Strom, Tim M; Reis, Andre; Colleaux, Laurence

2011-06-10

Intellectual disability inherited in an autosomal-recessive fashion represents an important fraction of severe cognitive-dysfunction disorders. Yet, the extreme heterogeneity of these conditions markedly hampers gene identification. Here, we report on eight affected individuals who were from three consanguineous families and presented with severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. Using a combination of autozygosity mapping and either Sanger sequencing of candidate genes or next-generation exome sequencing, we identified one mutation in each of three genes encoding adaptor protein complex 4 (AP4) subunits: a nonsense mutation in AP4S1 (NM_007077.3: c.124C>T, p.Arg42(∗)), a frameshift mutation in AP4B1 (NM_006594.2: c.487_488insTAT, p.Glu163_Ser739delinsVal), and a splice mutation in AP4E1 (NM_007347.3: c.542+1_542+4delGTAA, r.421_542del, p.Glu181Glyfs(∗)20). Adaptor protein complexes (AP1-4) are ubiquitously expressed, evolutionarily conserved heterotetrameric complexes that mediate different types of vesicle formation and the selection of cargo molecules for inclusion into these vesicles. Interestingly, two mutations affecting AP4M1 and AP4E1 have recently been found to cause cerebral palsy associated with severe intellectual disability. Combined with previous observations, these results support the hypothesis that AP4-complex-mediated trafficking plays a crucial role in brain development and functioning and demonstrate the existence of a clinically recognizable syndrome due to deficiency of the AP4 complex. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

77 FR 7609 - Policy Letter 11-01, Performance of Inherently Governmental and Critical Functions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... Regulation. The corrections below should be used in place of text previously published in the September 12, 2011 notice. All other information from the published Final Policy remains unchanged. The full text of...

Device SEE Susceptibility Update: 1996-1998

NASA Technical Reports Server (NTRS)

Coss, J. R.; Miyahira, T. F.; Swift, G. M.

1998-01-01

This eighth Compendium continues the previous work of Nichols, et al, on single event effects (SEE) first published in 1985. Because the compendium has grown so voluminous, this update only presents data not publised in previous compendia.

1. GENERAL VIEW OF COMPLEX (drawing from History of San ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. GENERAL VIEW OF COMPLEX (drawing from History of San Diego County, California, published 1883. Photocopy 1975 by Bert Shankland, San Diego). - Johnson-Taylor Ranch House, Black Mountain Road vicinity, Rancho Penasquitos, San Diego County, CA

An updated checklist of mosquito species (Diptera: Culicidae) from Madagascar.

PubMed

Tantely, Michaël Luciano; Le Goff, Gilbert; Boyer, Sébastien; Fontenille, Didier

2016-01-01

An updated checklist of 235 mosquito species from Madagascar is presented. The number of species has increased considerably compared to previous checklists, particularly the last published in 2003 (178 species). This annotated checklist provides concise information on endemism, taxonomic position, developmental stages, larval habitats, distribution, behavior, and vector-borne diseases potentially transmitted. The 235 species belong to 14 genera: Aedeomyia (3 species), Aedes (35 species), Anopheles (26 species), Coquillettidia (3 species), Culex (at least 50 species), Eretmapodites (4 species), Ficalbia (2 species), Hodgesia (at least one species), Lutzia (one species), Mansonia (2 species), Mimomyia (22 species), Orthopodomyia (8 species), Toxorhynchites (6 species), and Uranotaenia (73 species). Due to non-deciphered species complexes, several species remain undescribed. The main remarkable characteristic of Malagasy mosquito fauna is the high biodiversity with 138 endemic species (59%). Presence and abundance of species, and their association, in a given location could be a bio-indicator of environmental particularities such as urban, rural, forested, deforested, and mountainous habitats. Finally, taking into account that Malagasy culicidian fauna includes 64 species (27%) with a known medical or veterinary interest in the world, knowledge of their biology and host preference summarized in this paper improves understanding of their involvement in pathogen transmission in Madagascar. © M.L. Tantely et al., published by EDP Sciences, 2016.

Three dimensional microstructural network of elastin, collagen, and cells in Achilles tendons.

PubMed

Pang, Xin; Wu, Jian-Ping; Allison, Garry T; Xu, Jiake; Rubenson, Jonas; Zheng, Ming-Hao; Lloyd, David G; Gardiner, Bruce; Wang, Allan; Kirk, Thomas Brett

2017-06-01

Similar to most biological tissues, the biomechanical, and functional characteristics of the Achilles tendon are closely related to its composition and microstructure. It is commonly reported that type I collagen is the predominant component of tendons and is mainly responsible for the tissue's function. Although elastin has been found in varying proportions in other connective tissues, previous studies report that tendons contain very small quantities of elastin. However, the morphology and the microstructural relationship among the elastic fibres, collagen, and cells in tendon tissue have not been well examined. We hypothesize the elastic fibres, as another fibrillar component in the extracellular matrix, have a unique role in mechanical function and microstructural arrangement in Achilles tendons. It has been shown that elastic fibres present a close connection with the tenocytes. The close relationship of the three components has been revealed as a distinct, integrated and complex microstructural network. Notably, a "spiral" structure within fibril bundles in Achilles tendons was observed in some samples in specialized regions. This study substantiates the hierarchical system of the spatial microstructure of tendon, including the mapping of collagen, elastin and tenocytes, with 3-dimensional confocal images. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1203-1214, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

An induction or flare of arthritis and/or sacroiliitis by vedolizumab in inflammatory bowel disease: a case series.

PubMed

Varkas, G; Thevissen, K; De Brabanter, G; Van Praet, L; Czul-Gurdian, F; Cypers, H; De Kock, J; Carron, P; De Vos, M; Hindryckx, P; Arts, J; Vanneuville, I; Schoenaers, P; Claerhout, B; Abreu, M; Van den Bosch, F; Elewaut, D

2017-05-01

In inflammatory bowel disease (IBD), a new biological therapy has recently been approved. Vedolizumab is a humanised IgG1 monoclonal antibody to α4β7 integrin that modulates gut lymphocyte trafficking. Although an exclusively local effect of vedolizumab could be expected based on the restricted presence of the α4β7-mucosal vascular addressin cell adhesion molecule 1 complex in the gut, past combined success with anti-tumour necrosis factor, and previous demonstration of α4β7 integrin in the joint, led to the expectation of a therapeutic efficacy in spondyloarthritis. Nonetheless, the effect of vedolizumab on extraintestinal manifestations-and especially the joint-has not been reported so far. A series of five patients with IBD who were treated with vedolizumab and promptly developed new onset or exacerbation of sacroiliitis or arthritis are reported. Vedolizumab therapy does not seem to show any efficacy in and might even induce arthritis and/or sacroiliitis. However, larger cohort studies are needed to provide information on the prevalence, the evolution and underlying mechanism. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Caspase-8 Deficiency Presenting as Late-Onset Multi-Organ Lymphocytic Infiltration with Granulomas in two Adult Siblings.

PubMed

Niemela, Julie; Kuehn, Hye Sun; Kelly, Corin; Zhang, Mingchang; Davies, Joie; Melendez, Jose; Dreiling, Jennifer; Kleiner, David; Calvo, Katherine; Oliveira, João B; Rosenzweig, Sergio D

2015-05-01

Caspase-8 deficiency (CED) was originally described in 2002 in two pediatric patients presenting with clinical manifestations resembling autoimmune lymphoproliferative syndrome (ALPS) accompanied by infections, and T, B and NK cell defects. Since then, no new CED patients were published. Here we report two adult siblings (Pt1 and Pt2) presenting in their late thirties with pulmonary hypertension leading to lung transplant (Pt1), and a complex neurological disease leading to multiple cranial nerves palsies (Pt2) as their main manifestations. A thorough clinical and immunological evaluation was performed at the Primary Immunodeficiency Clinic at NIH, followed by whole exome sequencing. The patients had multiorgan lymphocytic infiltration and granulomas, as well as clinical signs of immune deficiency/ immune dysregulation. Both siblings carried homozygous mutations in CASP8, c.1096C > T, p.248R > W. This was the same mutation described on the previously published CED patients, to whom these new patients were likely distantly related. We report two new CED patients presenting during adulthood with life-threatening end-organ lymphocyte infiltrates affecting the lungs, liver, spleen, bone marrow and central nervous system. This phenotype broadens the clinical spectrum of manifestations associated with this disease and warrants the search of CASP8 mutations in other cohorts of patients.

A Systematic Literature Review on Evaluation of Digital Tools for Authoring Evidence-Based Clinical Guidelines.

PubMed

Khodambashi, Soudabeh; Nytrø, Øystein

2017-01-01

To facilitate the clinical guideline (GL) development process, different groups of researchers have proposed tools that enable computer-supported tools for authoring and publishing GLs. In a previous study we interviewed GL authors in different Norwegian institutions and identified tool shortcomings. In this follow-up study our goal is to explore to what extent GL authoring tools have been evaluated by researchers, guideline organisations, or GL authors. This article presents results from a systematic literature review of evaluation (including usability) of GL authoring tools. A controlled database search and backward snow-balling were used to identify relevant articles. From the 12692 abstracts found, 188 papers were fully reviewed and 26 papers were identified as relevant. The GRADEPro tool has attracted some evaluation, however popular tools and platforms such as DECIDE, Doctor Evidence, JBI-SUMARI, G-I-N library have not been subject to specific evaluation from an authoring perspective. Therefore, we found that little attention was paid to the evaluation of the tools in general. We could not find any evaluation relevant to how tools integrate and support the complex GL development workflow. The results of this paper are highly relevant to GL authors, tool developers and GL publishing organisations in order to improve and control the GL development and maintenance process.

Coronary artery disease concomitant with chronic obstructive pulmonary disease.

PubMed

Roversi, Sara; Roversi, Pietro; Spadafora, Giuseppe; Rossi, Rosario; Fabbri, Leonardo M

2014-01-01

Numerous epidemiologic studies have linked the presence of chronic obstructive pulmonary disease (COPD) to coronary artery disease (CAD). However, prevalence, pathological processes, clinical manifestations and therapy are still debated, as progress towards uncovering the link between these two disorders has been hindered by the complex nature of multimorbidity. Articles targeting CAD in patients with COPD were identified from the searches of MEDLINE and EMBASE databases in July 2013. Three authors reviewed available evidence, focusing on the latest development on disease prevalence, pathogenesis, clinical manifestations and therapeutic strategies. Both clinical trial and previous reviews have been included in this work. The most accredited hypothesis asserts that the main common risk factors, that is, cigarette smoke and ageing, elicit a chronic low-grade systemic inflammatory response, which affects both cardiovascular endothelial cells and airways/lung parenchyma. The development of CAD in patients with COPD potentiates the morbidity of COPD, leading to increased hospitalizations, mortality and health costs. Moreover, correct diagnosis is challenging and therapies are not clearly defined. Evidence from recently published articles highlights the importance of multimorbidity in patient management and future research. Moreover, many authors emphasize the importance of low-grade systemic inflammation as a common pathological mechanism and a possible future therapeutic target. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

Genome editing of bread wheat using biolistic delivery of CRISPR/Cas9 in vitro transcripts or ribonucleoproteins.

PubMed

Liang, Zhen; Chen, Kunling; Zhang, Yi; Liu, Jinxing; Yin, Kangquan; Qiu, Jin-Long; Gao, Caixia

2018-03-01

This protocol is an extension to: Nat. Protoc. 9, 2395-2410 (2014); doi:10.1038/nprot.2014.157; published online 18 September 2014In recent years, CRISPR/Cas9 has emerged as a powerful tool for improving crop traits. Conventional plant genome editing mainly relies on plasmid-carrying cassettes delivered by Agrobacterium or particle bombardment. Here, we describe DNA-free editing of bread wheat by delivering in vitro transcripts (IVTs) or ribonucleoprotein complexes (RNPs) of CRISPR/Cas9 by particle bombardment. This protocol serves as an extension of our previously published protocol on genome editing in bread wheat using CRISPR/Cas9 plasmids delivered by particle bombardment. The methods we describe not only eliminate random integration of CRISPR/Cas9 into genomic DNA, but also reduce off-target effects. In this protocol extension article, we present detailed protocols for preparation of IVTs and RNPs; validation by PCR/restriction enzyme (RE) and next-generation sequencing; delivery by biolistics; and recovery of mutants and identification of mutants by pooling methods and Sanger sequencing. To use these protocols, researchers should have basic skills and experience in molecular biology and biolistic transformation. By using these protocols, plants edited without the use of any foreign DNA can be generated and identified within 9-11 weeks.

Surgical, ethical, and psychosocial considerations in human head transplantation.

PubMed

Furr, Allen; Hardy, Mark A; Barret, Juan P; Barker, John H

2017-05-01

Transplanting a head and brain is perhaps the final frontier of organ transplantation. The goal of body-to-head transplantation (BHT) is to sustain the life of individuals who suffer from terminal disease, but whose head and brain are healthy. Ideally BHT could provide a lifesaving treatment for several conditions where none currently exists. BHT is no ordinary experiment, to transfer a head to another body involves extraordinarily complex medical challenges as well as ethical and existential dilemmas that were previously confined to the imagination of writers of fiction. The possibility of replacing an incurably ill body with a healthy one tests not only our surgical limits, but also the social and psychological boundaries of physical life and alters what we recognize life to be. The purpose of this target article, the complementary manuscript focused on immunological issues in BHT, and the accompanying Commentaries by scholars and practitioners in medicine, immunology, and bioethics is to review major surgical and psychosocial-ethical and immunological considerations surrounding body-to-head transplantation. We hope that together these ideas will provide readers with a comprehensive overview of the possibilities and challenges associated with BHT and initiate professional discussion and debate through which this new frontier in medicine is considered and approached. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

A versatile modular bioreactor platform for Tissue Engineering.

PubMed

Schuerlein, Sebastian; Schwarz, Thomas; Krziminski, Steffan; Gätzner, Sabine; Hoppensack, Anke; Schwedhelm, Ivo; Schweinlin, Matthias; Walles, Heike; Hansmann, Jan

2017-02-01

Tissue Engineering (TE) bears potential to overcome the persistent shortage of donor organs in transplantation medicine. Additionally, TE products are applied as human test systems in pharmaceutical research to close the gap between animal testing and the administration of drugs to human subjects in clinical trials. However, generating a tissue requires complex culture conditions provided by bioreactors. Currently, the translation of TE technologies into clinical and industrial applications is limited due to a wide range of different tissue-specific, non-disposable bioreactor systems. To ensure a high level of standardization, a suitable cost-effectiveness, and a safe graft production, a generic modular bioreactor platform was developed. Functional modules provide robust control of culture processes, e.g. medium transport, gas exchange, heating, or trapping of floating air bubbles. Characterization revealed improved performance of the modules in comparison to traditional cell culture equipment such as incubators, or peristaltic pumps. By combining the modules, a broad range of culture conditions can be achieved. The novel bioreactor platform allows using disposable components and facilitates tissue culture in closed fluidic systems. By sustaining native carotid arteries, engineering a blood vessel, and generating intestinal tissue models according to a previously published protocol the feasibility and performance of the bioreactor platform was demonstrated. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Creation and Statistical Evaluation of a Deterministic Model of the Human Bronchial Tree from HRCT Images.

PubMed

Montesantos, Spyridon; Katz, Ira; Pichelin, Marine; Caillibotte, Georges

2016-01-01

A quantitative description of the morphology of lung structure is essential prior to any form of predictive modeling of ventilation or aerosol deposition implemented within the lung. The human lung is a very complex organ, with airway structures that span two orders of magnitude and having a multitude of interfaces between air, tissue and blood. As such, current medical imaging protocols cannot provide medical practitioners and researchers with in-vivo knowledge of deeper lung structures. In this work a detailed algorithm for the generation of an individualized 3D deterministic model of the conducting part of the human tracheo-bronchial tree is described. Distinct initial conditions were obtained from the high-resolution computed tomography (HRCT) images of seven healthy volunteers. The algorithm developed is fractal in nature and is implemented as a self-similar space sub-division procedure. The expansion process utilizes physiologically realistic relationships and thresholds to produce an anatomically consistent human airway tree. The model was validated through extensive statistical analysis of the results and comparison of the most common morphological features with previously published morphometric studies and other equivalent models. The resulting trees were shown to be in good agreement with published human lung geometric characteristics and can be used to study, among other things, structure-function relationships in simulation studies.

Comparative proteomic profiling of the choline transporter-like1 (CHER1) mutant provides insights into plasmodesmata composition of fully developed Arabidopsis thaliana leaves.

PubMed

Kraner, Max E; Müller, Carmen; Sonnewald, Uwe

2017-11-01

In plants, intercellular communication and exchange are highly dependent on cell wall bridging structures between adhering cells, so-called plasmodesmata (PD). In our previous genetic screen for PD-deficient Arabidopsis mutants, we described choline transporter-like 1 (CHER1) being important for PD genesis and maturation. Leaves of cher1 mutant plants have up to 10 times less PD, which do not develop to complex structures. Here we utilize the T-DNA insertion mutant cher1-4 and report a deep comparative proteomic workflow for the identification of cell-wall-embedded PD-associated proteins. Analyzing triplicates of cell-wall-enriched fractions in depth by fractionation and quantitative high-resolution mass spectrometry, we compared > 5000 proteins obtained from fully developed leaves. Comparative data analysis and subsequent filtering generated a list of 61 proteins being significantly more abundant in Col-0. This list was enriched for previously described PD-associated proteins. To validate PD association of so far uncharacterized proteins, subcellular localization analyses were carried out by confocal laser-scanning microscopy. This study confirmed the association of PD for three out of four selected candidates, indicating that the comparative approach indeed allowed identification of so far undescribed PD-associated proteins. Performing comparative cell wall proteomics of Nicotiana benthamiana tissue, we observed an increase in abundance of these three selected candidates during sink to source transition. Taken together, our comparative proteomic approach revealed a valuable data set of potential PD-associated proteins, which can be used as a resource to unravel the molecular composition of complex PD and to investigate their function in cell-to-cell communication. © 2017 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Brain White Matter Shape Changes in Amyotrophic Lateral Sclerosis (ALS): A Fractal Dimension Study

PubMed Central

Allexandre, Didier; Zhang, Luduan; Wang, Xiao-Feng; Pioro, Erik P.; Yue, Guang H.

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder. Current diagnosis time is about 12-months due to lack of objective methods. Previous brain white matter voxel based morphometry (VBM) studies in ALS reported inconsistent results. Fractal dimension (FD) has successfully been used to quantify brain WM shape complexity in various neurological disorders and aging, but not yet studied in ALS. Therefore, we investigated WM morphometric changes using FD analyses in ALS patients with different clinical phenotypes. We hypothesized that FD would better capture clinical features of the WM morphometry in different ALS phenotypes than VBM analysis. High resolution MRI T1-weighted images were acquired in controls (n = 11), and ALS patients (n = 89). ALS patients were assigned into four subgroups based on their clinical phenotypes.VBM analysis was carried out using SPM8. FD values were estimated for brain WM skeleton, surface and general structure in both controls and ALS patients using our previously published algorithm. No significant VBM WM changes were observed between controls and ALS patients and among the ALS subgroups. In contrast, significant (p<0.05) FD reductions in skeleton and general structure were observed between ALS with dementia and other ALS subgroups. No significant differences in any of the FD measures were observed between control and ALS patients. FD correlated significantly with revised ALS functional rating scale (ALSFRS-R) score a clinical measure of function. Results suggest that brain WM shape complexity is more sensitive to ALS disease process when compared to volumetric VBM analysis and FD changes are dependent on the ALS phenotype. Correlation between FD and clinical measures suggests that FD could potentially serve as a biomarker of ALS pathophysiology, especially after confirmation by longitudinal studies. PMID:24040000

Added value of cardiac magnetic resonance in etiological diagnosis of ventricular arrhythmias.

PubMed

Cabanelas, Nuno; Vidigal Ferreira, Maria João; Donato, Paulo; Gaspar, António; Pinto, Joana; Caseiro-Alves, Filipe; Providência, Luís Augusto

2013-10-01

Cardiac magnetic resonance (CMR) imaging is increasingly important in the diagnostic work-up of a wide range of heart diseases, including those with arrhythmogenic potential. To assess the added value of CMR in etiological diagnosis of ventricular arrhythmias after an inconclusive conventional investigation. Patients undergoing CMR between 2005 and 2011 for investigation of ventricular arrhythmias were included (n=113). All had documented arrhythmias. Those with a definite diagnosis from a previous investigation and those with evidence of coronary artery disease (acute coronary syndrome, typical angina symptoms, increase in biomarkers or positive stress test) were excluded. CMR results were considered relevant when they fulfilled diagnostic criteria. Of the 113 patients, 57.5% were male and mean age was 41.7 ± 16.2 years. Regarding the initial arrhythmia, 38.1% had ventricular fibrillation/sustained ventricular tachycardia (VF/VT) and 61.9% had less complex ventricular ectopy. CMR imaging showed criteria of a specific diagnosis in 42.5% of patients, was totally normal in 36.3%, and showed non-specific alterations in the remainder. In VF/VT patients, specific criteria were found in 60.4%, and in 31.4% of those with less complex ectopy. The most frequent diagnoses were arrhythmogenic right ventricular dysplasia, ventricular non-compaction and myopericarditis. It is worth noting that, although there was no evidence of previous coronary artery disease, 6.2% of patients had a late gadolinium enhancement distribution pattern compatible with myocardial infarction. CMR gives additional and important information in the diagnostic work-up of ventricular arrhythmias after an inconclusive initial investigation. The proportion of patients with diagnostic criteria was 42.5% (60.0% in those with VF/VT), and CMR was completely normal in 36.6%. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Initial laparoscopic basic skills training shortens the learning curve of laparoscopic suturing and is cost-effective.

PubMed

Stefanidis, Dimitrios; Hope, William W; Korndorffer, James R; Markley, Sarah; Scott, Daniel J

2010-04-01

Laparoscopic suturing is an advanced skill that is difficult to acquire. Simulator-based skills curricula have been developed that have been shown to transfer to the operating room. Currently available skills curricula need to be optimized. We hypothesized that mastering basic laparoscopic skills first would shorten the learning curve of a more complex laparoscopic task and reduce resource requirements for the Fundamentals of Laparoscopic Surgery suturing curriculum. Medical students (n = 20) with no previous simulator experience were enrolled in an IRB-approved protocol, pretested on the Fundamentals of Laparoscopic Surgery suturing model, and randomized into 2 groups. Group I (n = 10) trained (unsupervised) until proficiency levels were achieved on 5 basic tasks; Group II (n = 10) received no basic training. Both groups then trained (supervised) on the Fundamentals of Laparoscopic Surgery suturing model until previously reported proficiency levels were achieved. Two weeks later, they were retested to evaluate their retention scores, training parameters, instruction requirements, and cost between groups using t-test. Baseline characteristics and performance were similar for both groups, and 9 of 10 subjects in each group achieved the proficiency levels. The initial performance on the simulator was better for Group I after basic skills training, and their suturing learning curve was shorter compared with Group II. In addition, Group I required less active instruction. Overall time required to finish the curriculum was similar for both groups; but the Group I training strategy cost less, with a savings of $148 per trainee. Teaching novices basic laparoscopic skills before a more complex laparoscopic task produces substantial cost savings. Additional studies are needed to assess the impact of such integrated curricula on ultimate educational benefit. Copyright (c) 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Methylprednisolone prevents nerve injury-induced hyperalgesia in neprilysin knockout mice.

PubMed

He, Lan; Uçeyler, Nurcan; Krämer, Heidrun H; Colaço, Maria Nandini; Lu, Bao; Birklein, Frank; Sommer, Claudia

2014-03-01

The pathophysiology of the complex regional pain syndrome involves enhanced neurogenic inflammation mediated by neuropeptides. Neutral endopeptidase (neprilysin, NEP) is a key enzyme in neuropeptide catabolism. Our previous work revealed that NEP knock out (ko) mice develop more severe hypersensitivity to thermal and mechanical stimuli after chronic constriction injury (CCI) of the sciatic nerve than wild-type (wt) mice. Because treatment with glucocorticoids is effective in early complex regional pain syndrome, we investigated whether methylprednisolone (MP) reduces pain and sciatic nerve neuropeptide content in NEP ko and wt mice with nerve injury. After CCI, NEP ko mice developed more severe thermal and mechanical hypersensitivity and hind paw edema than wt mice, confirming previous findings. Hypersensitivity was prevented by MP treatment in NEP ko but not in wt mice. MP treatment had no effect on protein levels of calcitonin-gene related peptide, substance P, and bradykinin in sciatic nerves of NEP ko mice. Endothelin-1 (ET-1) levels were higher in naïve and nerve-injured NEP ko than in wt mice, without an effect of MP treatment. Gene expression of the ET-1 receptors ETAR and ETBR was not different between genotypes and was not altered after CCI, but was increased after additional MP treatment. The ETBR agonist IRL-1620 was analgesic in NEP ko mice after CCI, and the ETBR antagonist BQ-788 showed a trend to reduce the analgesic effect of MP. The results provide evidence that MP reduces CCI-induced hyperalgesia in NEP ko mice, and that this may be related to ET-1 via analgesic actions of ETBR. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Pinniped Hearing in Complex Acoustic Environments

DTIC Science & Technology

2013-09-30

published] Mulsow, J. & Reichmuth, C. (2013). The binaural click-evoked auditory brainstem response of the California sea lion (Zalophus...California sea lion can keep the beat : Motor entrainment to rhythmic auditory stimuli in a non vocal mimic. Journal of Comparative Psychology, online first. [published

A methodology for the design of experiments in computational intelligence with multiple regression models.

PubMed

Fernandez-Lozano, Carlos; Gestal, Marcos; Munteanu, Cristian R; Dorado, Julian; Pazos, Alejandro

2016-01-01

The design of experiments and the validation of the results achieved with them are vital in any research study. This paper focuses on the use of different Machine Learning approaches for regression tasks in the field of Computational Intelligence and especially on a correct comparison between the different results provided for different methods, as those techniques are complex systems that require further study to be fully understood. A methodology commonly accepted in Computational intelligence is implemented in an R package called RRegrs. This package includes ten simple and complex regression models to carry out predictive modeling using Machine Learning and well-known regression algorithms. The framework for experimental design presented herein is evaluated and validated against RRegrs. Our results are different for three out of five state-of-the-art simple datasets and it can be stated that the selection of the best model according to our proposal is statistically significant and relevant. It is of relevance to use a statistical approach to indicate whether the differences are statistically significant using this kind of algorithms. Furthermore, our results with three real complex datasets report different best models than with the previously published methodology. Our final goal is to provide a complete methodology for the use of different steps in order to compare the results obtained in Computational Intelligence problems, as well as from other fields, such as for bioinformatics, cheminformatics, etc., given that our proposal is open and modifiable.

Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly

PubMed Central

Cook, Jeremy D.; Kondapalli, Kalyan C.; Rawat, Swati; Childs, William C.; Murugesan, Yogapriya; Dancis, Andrew; Stemmler, Timothy L.

2010-01-01

Frataxin, a conserved nuclear encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich’s ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two: Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone n the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural module to better understand the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry (ITC). Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into a Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly. PMID:20815377

A methodology for the design of experiments in computational intelligence with multiple regression models

PubMed Central

Gestal, Marcos; Munteanu, Cristian R.; Dorado, Julian; Pazos, Alejandro

2016-01-01

The design of experiments and the validation of the results achieved with them are vital in any research study. This paper focuses on the use of different Machine Learning approaches for regression tasks in the field of Computational Intelligence and especially on a correct comparison between the different results provided for different methods, as those techniques are complex systems that require further study to be fully understood. A methodology commonly accepted in Computational intelligence is implemented in an R package called RRegrs. This package includes ten simple and complex regression models to carry out predictive modeling using Machine Learning and well-known regression algorithms. The framework for experimental design presented herein is evaluated and validated against RRegrs. Our results are different for three out of five state-of-the-art simple datasets and it can be stated that the selection of the best model according to our proposal is statistically significant and relevant. It is of relevance to use a statistical approach to indicate whether the differences are statistically significant using this kind of algorithms. Furthermore, our results with three real complex datasets report different best models than with the previously published methodology. Our final goal is to provide a complete methodology for the use of different steps in order to compare the results obtained in Computational Intelligence problems, as well as from other fields, such as for bioinformatics, cheminformatics, etc., given that our proposal is open and modifiable. PMID:27920952

Impact of choice of future climate change projection on growth chamber experimental outcomes: a preliminary study in potato.

PubMed

Leisner, Courtney P; Wood, Joshua C; Vaillancourt, Brieanne; Tang, Ying; Douches, Dave S; Robin Buell, C; Winkler, Julie A

2018-04-01

Understanding the impacts of climate change on agriculture is essential to ensure adequate future food production. Controlled growth experiments provide an effective tool for assessing the complex effects of climate change. However, a review of the use of climate projections in 57 previously published controlled growth studies found that none considered within-season variations in projected future temperature change, and few considered regional differences in future warming. A fixed, often arbitrary, temperature perturbation typically was applied for the entire growing season. This study investigates the utility of employing more complex climate change scenarios in growth chamber experiments. A case study in potato was performed using three dynamically downscaled climate change projections for the mid-twenty-first century that differ in terms of the timing during the growing season of the largest projected temperature changes. The climate projections were used in growth chamber experiments for four elite potato cultivars commonly planted in Michigan's major potato growing region. The choice of climate projection had a significant influence on the sign and magnitude of the projected changes in aboveground biomass and total tuber count, whereas all projections suggested an increase in total tuber weight and a decrease in specific gravity, a key market quality trait for potato, by mid-century. These results demonstrate that the use of more complex climate projections that extend beyond a simple incremental change can provide additional insights into the future impacts of climate change on crop production and the accompanying uncertainty.

Crystal Structure of Botulinum Neurotoxin Type a in Complex With the Cell Surface Co-Receptor GT1b-Insight Into the Toxin-Neuron Interaction

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

Stenmark, P.; Dupuy, J.; Inamura, A.

2009-05-26

Botulinum neurotoxins have a very high affinity and specificity for their target cells requiring two different co-receptors located on the neuronal cell surface. Different toxin serotypes have different protein receptors; yet, most share a common ganglioside co-receptor, GT1b. We determined the crystal structure of the botulinum neurotoxin serotype A binding domain (residues 873-1297) alone and in complex with a GT1b analog at 1.7 A and 1.6 A, respectively. The ganglioside GT1b forms several key hydrogen bonds to conserved residues and binds in a shallow groove lined by Tryptophan 1266. GT1b binding does not induce any large structural changes in themore » toxin; therefore, it is unlikely that allosteric effects play a major role in the dual receptor recognition. Together with the previously published structures of botulinum neurotoxin serotype B in complex with its protein co-receptor, we can now generate a detailed model of botulinum neurotoxin's interaction with the neuronal cell surface. The two branches of the GT1b polysaccharide, together with the protein receptor site, impose strict geometric constraints on the mode of interaction with the membrane surface and strongly support a model where one end of the 100 A long translocation domain helix bundle swing into contact with the membrane, initiating the membrane anchoring event.« less

Molecular Details of the Yeast Frataxin-Isu1 Interaction during Mitochondrial Fe-S Cluster Assembly

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

Cook, J.; Kondapalli, K; Rawat, S

2010-01-01

Frataxin, a conserved nuclear-encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich's ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone in the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural modulemore » to improve our understanding of the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry. Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into an Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly.« less

Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly.

PubMed

Cook, Jeremy D; Kondapalli, Kalyan C; Rawat, Swati; Childs, William C; Murugesan, Yogapriya; Dancis, Andrew; Stemmler, Timothy L

2010-10-12

Frataxin, a conserved nuclear-encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich's ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone in the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural module to improve our understanding of the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry. Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into an Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly.

Long term results of diode laser cycloablation in complex glaucoma using the Zeiss Visulas II system

PubMed Central

Ataullah, S; Biswas, S; Artes, P H; O'Donoghue, E; Ridgway, A E A; Spencer, A F

2002-01-01

Aim: To investigate the safety and efficacy of the Zeiss Visulas II diode laser system in the reduction of intraocular pressure (IOP) in patients with complex glaucoma. Methods: The authors analysed the medical records of patients who underwent trans-scleral diode laser cycloablation (TDC) at the Manchester Royal Eye Hospital during a 34 month period. 55 eyes of 53 patients with complex glaucoma were followed up for a period of 12–52 months (mean 23.1 months) after initial treatment with the Zeiss Visulas II diode laser system. Results: Mean pretreatment IOP was 35.8 mm Hg (range 22–64 mm Hg). At the last examination, mean IOP was 17.3 mm Hg (range 0–40 mm Hg). After treatment, 45 eyes (82%) had an IOP between 5 and 22 mm Hg; in 46 eyes (84%) the preoperative IOP had been reduced by 30% or more. The mean number of treatment sessions was 1.7 (range 1–6). At the last follow up appointment, the mean number of glaucoma medications was reduced from 2.1 to 1.6 (p<0.05). In 10 eyes (18%), post-treatment visual acuity (VA) was worse than pretreatment VA by 2 or more lines. Conclusions: Treatment with the Zeiss Visulas II diode laser system can be safely repeated in order to achieve the target IOP. Treatment outcomes in this study were similar to those from previously published work using the Iris Medical Oculight SLx laser. PMID:11801501

High Spatial Resolution 40Ar/39Ar Geochronology of Lunar Impact Melt Rocks

NASA Astrophysics Data System (ADS)

Mercer, Cameron Mark

Impact cratering has played a key role in the evolution of the solid surfaces of Solar System bodies. While much of Earth’s impact record has been erased, its Moon preserves an extensive history of bombardment. Quantifying the timing of lunar impact events is crucial to understanding how impacts have shaped the evolution of early Earth, and provides the basis for estimating the ages of other cratered surfaces in the Solar System. Many lunar impact melt rocks are complex mixtures of glassy and crystalline “melt” materials and inherited clasts of pre-impact minerals and rocks. If analyzed in bulk, these samples can yield complicated incremental release 40Ar/39Ar spectra, making it challenging to uniquely interpret impact ages. Here, I have used a combination of high-spatial resolution 40Ar/39Ar geochronology and thermal-kinetic modeling to gain new insights into the impact histories recorded by such lunar samples. To compare my data to those of previous studies, I developed a software tool to account for differences in the decay, isotopic, and monitor age parameters used for different published 40Ar/39Ar datasets. Using an ultraviolet laser ablation microprobe (UVLAMP) system I selectively dated melt and clast components of impact melt rocks collected during the Apollo 16 and 17 missions. UVLAMP 40Ar/39Ar data for samples 77135, 60315, 61015, and 63355 show evidence of open-system behavior, and provide new insights into how to interpret some complexities of published incremental heating 40Ar/39Ar spectra. Samples 77115, 63525, 63549, and 65015 have relatively simple thermal histories, and UVLAMP 40Ar/39Ar data for the melt components of these rocks indicate the timing of impact events—spanning hundreds of millions of years—that influenced the Apollo 16 and 17 sites. My modeling and UVLAMP 40Ar/39Ar data for sample 73217 indicate that some impact melt rocks can quantitatively retain evidence for multiple melt-producing impact events, and imply that such polygenetic rocks should be regarded as high-value sampling opportunities during future exploration missions to cratered planetary surfaces. Collectively, my results complement previous incremental heating 40Ar/39Ar studies, and support interpretations that the Moon experienced a prolonged period of heavy bombardment early in its history.

Ultra-deep sequencing of ribosome-associated poly-adenylated RNA in early Drosophila embryos reveals hundreds of conserved translated sORFs.

PubMed

Li, Hongmei; Hu, Chuansheng; Bai, Ling; Li, Hua; Li, Mingfa; Zhao, Xiaodong; Czajkowsky, Daniel M; Shao, Zhifeng

2016-12-01

There is growing recognition that small open reading frames (sORFs) encoding peptides shorter than 100 amino acids are an important class of functional elements in the eukaryotic genome, with several already identified to play critical roles in growth, development, and disease. However, our understanding of their biological importance has been hindered owing to the significant technical challenges limiting their annotation. Here we combined ultra-deep sequencing of ribosome-associated poly-adenylated RNAs with rigorous conservation analysis to identify a comprehensive population of translated sORFs during early Drosophila embryogenesis. In total, we identify 399 sORFs, including those previously annotated but without evidence of translational capacity, those found within transcripts previously classified as non-coding, and those not previously known to be transcribed. Further, we find, for the first time, evidence for translation of many sORFs with different isoforms, suggesting their regulation is as complex as longer ORFs. Furthermore, many sORFs are found not associated with ribosomes in late-stage Drosophila S2 cells, suggesting that many of the translated sORFs may have stage-specific functions during embryogenesis. These results thus provide the first comprehensive annotation of the sORFs present during early Drosophila embryogenesis, a necessary basis for a detailed delineation of their function in embryogenesis and other biological processes. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Improved determination of particulate absorption from combined filter pad and PSICAM measurements.

PubMed

Lefering, Ina; Röttgers, Rüdiger; Weeks, Rebecca; Connor, Derek; Utschig, Christian; Heymann, Kerstin; McKee, David

2016-10-31

Filter pad light absorption measurements are subject to two major sources of experimental uncertainty: the so-called pathlength amplification factor, β, and scattering offsets, o, for which previous null-correction approaches are limited by recent observations of non-zero absorption in the near infrared (NIR). A new filter pad absorption correction method is presented here which uses linear regression against point-source integrating cavity absorption meter (PSICAM) absorption data to simultaneously resolve both β and the scattering offset. The PSICAM has previously been shown to provide accurate absorption data, even in highly scattering waters. Comparisons of PSICAM and filter pad particulate absorption data reveal linear relationships that vary on a sample by sample basis. This regression approach provides significantly improved agreement with PSICAM data (3.2% RMS%E) than previously published filter pad absorption corrections. Results show that direct transmittance (T-method) filter pad absorption measurements perform effectively at the same level as more complex geometrical configurations based on integrating cavity measurements (IS-method and QFT-ICAM) because the linear regression correction compensates for the sensitivity to scattering errors in the T-method. This approach produces accurate filter pad particulate absorption data for wavelengths in the blue/UV and in the NIR where sensitivity issues with PSICAM measurements limit performance. The combination of the filter pad absorption and PSICAM is therefore recommended for generating full spectral, best quality particulate absorption data as it enables correction of multiple errors sources across both measurements.

Ultraviolet filters in stomatopod crustaceans: diversity, ecology and evolution.

PubMed

Bok, Michael J; Porter, Megan L; Cronin, Thomas W

2015-07-01

Stomatopod crustaceans employ unique ultraviolet (UV) optical filters in order to tune the spectral sensitivities of their UV-sensitive photoreceptors. In the stomatopod species Neogonodactylus oerstedii, we previously found four filter types, produced by five distinct mycosporine-like amino acid pigments in the crystalline cones of their specialized midband ommatidial facets. This UV-spectral tuning array produces receptors with at least six distinct spectral sensitivities, despite expressing only two visual pigments. Here, we present a broad survey of these UV filters across the stomatopod order, examining their spectral absorption properties in 21 species from seven families in four superfamilies. We found that UV filters are present in three of the four superfamilies, and evolutionary character reconstruction implies that at least one class of UV filter was present in the ancestor of all modern stomatopods. Additionally, postlarval stomatopods were observed to produce the UV filters simultaneously alongside development of the adult eye. The absorbance properties of the filters are consistent within a species; however, between species we found a great deal of diversity, both in the number of filters and in their spectral absorbance characteristics. This diversity correlates with the habitat depth ranges of these species, suggesting that species living in shallow, UV-rich environments may tune their UV spectral sensitivities more aggressively. We also found additional, previously unrecognized UV filter types in the crystalline cones of the peripheral eye regions of some species, indicating the possibility for even greater stomatopod visual complexity than previously thought. © 2015. Published by The Company of Biologists Ltd.

Retrieval of volcanic ash height from satellite-based infrared measurements

NASA Astrophysics Data System (ADS)

Zhu, Lin; Li, Jun; Zhao, Yingying; Gong, He; Li, Wenjie

2017-05-01

A new algorithm for retrieving volcanic ash cloud height from satellite-based measurements is presented. This algorithm, which was developed in preparation for China's next-generation meteorological satellite (FY-4), is based on volcanic ash microphysical property simulation and statistical optimal estimation theory. The MSG satellite's main payload, a 12-channel Spinning Enhanced Visible and Infrared Imager, was used as proxy data to test this new algorithm. A series of eruptions of Iceland's Eyjafjallajökull volcano during April to May 2010 and the Puyehue-Cordón Caulle volcanic complex eruption in the Chilean Andes on 16 June 2011 were selected as two typical cases for evaluating the algorithm under various meteorological backgrounds. Independent volcanic ash simulation training samples and satellite-based Cloud-Aerosol Lidar with Orthogonal Polarization data were used as validation data. It is demonstrated that the statistically based volcanic ash height algorithm is able to rapidly retrieve volcanic ash heights, globally. The retrieved ash heights show comparable accuracy with both independent training data and the lidar measurements, which is consistent with previous studies. However, under complicated background, with multilayers in vertical scale, underlying stratus clouds tend to have detrimental effects on the final retrieval accuracy. This is an unresolved problem, like many other previously published methods using passive satellite sensors. Compared with previous studies, the FY-4 ash height algorithm is independent of simultaneous atmospheric profiles, providing a flexible way to estimate volcanic ash height using passive satellite infrared measurements.

Orbital Plotting of WDS 04545-0314 and WDS 04478+5318

NASA Astrophysics Data System (ADS)

Smith, Nick; Foster, Chris; Myers, Blake; Sepulveda, Barbel; Genet, Russell

2016-01-01

Students at Lincoln High School used the PlateSolve 3 program to obtain the position angle and separation of two double stars, WDS 04545-0314 and WDS 04478+5318. Both stars were observed at Kitt Peak on October 20, 2013. A java-based program developed by the team was used to plot the new data on the previously published orbital paths. It was determined that WDS 04545-0314 is maintaining the previously published orbital solution but that the orbit of WDS 04478+5318 may need to be revised.

The presentation and management of complex female genital malformations.

PubMed

Acién, Pedro; Acién, Maribel

2016-01-01

Common uterine anomalies are important owing to their impact on fertility, and complex mesonephric anomalies and certain Müllerian malformations are particularly important because they cause serious clinical symptoms and affect woman's quality of life, in addition to creating fertility problems. In these cases of complex female genital tract malformations, a correct diagnosis is essential to avoid inappropriate and/or unnecessary surgery. Therefore, acquiring and applying the appropriate embryological knowledge, management and therapy is a challenge for gynaecologists. Here, we considered complex malformations to be obstructive anomalies and/or those associated with cloacal and urogenital sinus anomalies, urinary and/or extragenital anomalies, or other clinical implications or symptoms creating a difficult differential diagnosis. A diligent and comprehensive search of PubMed and Scopus was performed for all studies published from 1 January 2011 to 15 April 2015 (then updated up to September 2015) using the following search terms: 'management' in combination with either 'female genital malformations' or 'female genital tract anomalies' or 'Müllerian anomalies'. The MeSH terms 'renal agenesis', 'hydrocolpos', 'obstructed hemivagina' 'cervicovaginal agenesis or atresia', 'vaginal agenesis or atresia', 'Herlyn-Werner-Wunderlich syndrome', 'uterine duplication' and 'cloacal anomalies' were also used to compile a list of all publications containing these terms since 2011. The basic embryological considerations for understanding female genitourinary malformations were also revealed. Based on our experience and the updated literature review, we studied the definition and classification of the complex malformations, and we analysed the clinical presentation and different therapeutic strategies for each anomaly, including the embryological and clinical classification of female genitourinary malformations. From 755 search retrieved references, 230 articles were analysed and 120 studied in detail. They were added to those included in a previous systematic review. Here, we report the clinical presentation and management of: agenesis or hypoplasia of one urogenital ridge; unilateral renal agenesis and ipsilateral blind or obstructed hemivagina or unilateral cervicovaginal agenesis; cavitated and non-communicating uterine horns and Müllerian atresias or agenesis, including Rokitansky syndrome; anomalies of the cloaca and urogenital sinus, including congenital vagino-vesical fistulas and cloacal anomalies; malformative combinations and other complex malformations. The clinical symptoms and therapeutic strategies for each complex genitourinary malformation are discussed. In general, surgical techniques to correct genital malformations depend on the type of anomaly, its complexity, the patient's symptoms and the correct embryological interpretation of the anomaly. Most anomalies can typically be resolved vaginally or by hysteroscopy, but laparoscopy or laparotomy is often required as well. We also include additional discussion of the catalogue and classification systems for female genital malformations, the systematic association between renal agenesis and ipsilateral genital malformation, and accessory and cavitated uterine masses. Knowledge of the correct genitourinary embryology is essential for the understanding, study, diagnosis and subsequent treatment of genital malformations, especially complex ones and those that lead to gynaecological and reproductive problems, particularly in young patients. Some anomalies may require complex surgery involving multiple specialties, and patients should therefore be referred to centres that have experience in treating complex genital malformations. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.

PubMed

Fenwick, Aimee L; Kliszczak, Maciej; Cooper, Fay; Murray, Jennie; Sanchez-Pulido, Luis; Twigg, Stephen R F; Goriely, Anne; McGowan, Simon J; Miller, Kerry A; Taylor, Indira B; Logan, Clare; Bozdogan, Sevcan; Danda, Sumita; Dixon, Joanne; Elsayed, Solaf M; Elsobky, Ezzat; Gardham, Alice; Hoffer, Mariette J V; Koopmans, Marije; McDonald-McGinn, Donna M; Santen, Gijs W E; Savarirayan, Ravi; de Silva, Deepthi; Vanakker, Olivier; Wall, Steven A; Wilson, Louise C; Yuregir, Ozge Ozalp; Zackai, Elaine H; Ponting, Chris P; Jackson, Andrew P; Wilkie, Andrew O M; Niedzwiedz, Wojciech; Bicknell, Louise S

2016-07-07

DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The phylogenetic utility of acetyltransferase (ARD1) and glutaminyl tRNA synthetase (QtRNA) for reconstructing Cenozoic relationships as exemplified by the large Australian cicada Pauropsalta generic complex.

PubMed

Owen, Christopher L; Marshall, David C; Hill, Kathy B R; Simon, Chris

2015-02-01

The Pauropsalta generic complex is a large group of cicadas (72 described spp.; >82 undescribed spp.) endemic to Australia. No previous molecular work on deep level relationships within this complex has been conducted, but a recent morphological revision and phylogenetic analysis proposed relationships among the 11 genera. We present here the first comprehensive molecular phylogeny of the complex using five loci (1 mtDNA, 4 nDNA), two of which are from nuclear genes new to cicada systematics. We compare the molecular phylogeny to the morphological phylogeny. We evaluate the phylogenetic informativeness of the new loci to traditional cicada systematics loci to generate a baseline of performance and behavior to aid in gene choice decisions in future systematic and phylogenomic studies. Our maximum likelihood and Bayesian inference phylogenies strongly support the monophyly of most of the newly described genera; however, relationships among genera differ from the morphological phylogeny. A comparison of phylogenetic informativeness among all loci revealed that COI 3rd positions dominate the informativeness profiles relative to all other loci but exhibit some among taxon nucleotide bias. After removing COI 3rd positions, COI 1st positions dominate near the terminals, while the period intron has the most phylogenetic informativeness near the root. Among the nuclear loci, ARD1 and QtRNA have lower phylogenetic informativeness than period intron and elongation factor 1 alpha intron, but the informativeness increases at you move from the tips to the root. The increase in phylogenetic informativeness deeper in the tree suggests these loci may be useful for resolving older relationships. Copyright © 2015. Published by Elsevier Inc.

Comparative study of the Aristotle Comprehensive Complexity and the Risk Adjustment in Congenital Heart Surgery scores.

PubMed

Bojan, Mirela; Gerelli, Sébastien; Gioanni, Simone; Pouard, Philippe; Vouhé, Pascal

2011-09-01

The Aristotle Comprehensive Complexity (ACC) and the Risk Adjustment in Congenital Heart Surgery (RACHS-1) scores have been proposed for complexity adjustment in the analysis of outcome after congenital heart surgery. Previous studies found RACHS-1 to be a better predictor of outcome than the Aristotle Basic Complexity score. We compared the ability to predict operative mortality and morbidity between ACC, the latest update of the Aristotle method and RACHS-1. Morbidity was assessed by length of intensive care unit stay. We retrospectively enrolled patients undergoing congenital heart surgery. We modeled each score as a continuous variable, mortality as a binary variable, and length of stay as a censored variable. We compared performance between mortality and morbidity models using likelihood ratio tests for nested models and paired concordance statistics. Among all 1,384 patients enrolled, 30-day mortality rate was 3.5% and median length of intensive care unit stay was 3 days. Both scores strongly related to mortality, but ACC made better prediction than RACHS-1; c-indexes 0.87 (0.84, 0.91) vs 0.75 (0.65, 0.82). Both scores related to overall length of stay only during the first postoperative week, but ACC made better predictions than RACHS-1; U statistic=0.22, p<0.001. No significant difference was noted after adjusting RACHS-1 models on age, prematurity, and major extracardiac abnormalities. The ACC was a better predictor of operative mortality and length of intensive care unit stay than RACHS-1. In order to achieve similar performance, regression models including RACHS-1 need to be further adjusted on age, prematurity, and major extracardiac abnormalities. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Werner complex deficiency in cells disrupts the Nuclear Pore Complex and the distribution of lamin B1.

PubMed

Li, Zhi; Zhu, Yizhou; Zhai, Yujia; R Castroagudin, Michelle; Bao, Yifei; White, Tommy E; Glavy, Joseph S

2013-12-01

From the surrounding shell to the inner machinery, nuclear proteins provide the functional plasticity of the nucleus. This study highlights the nuclear association of Pore membrane (POM) protein NDC1 and Werner protein (WRN), a RecQ helicase responsible for the DNA instability progeria disorder, Werner Syndrome. In our previous publication, we connected the DNA damage sensor Werner's Helicase Interacting Protein (WHIP), a binding partner of WRN, to the NPC. Here, we confirm the association of the WRN/WHIP complex and NDC1. In established WRN/WHIP knockout cell lines, we further demonstrate the interdependence of WRN/WHIP and Nucleoporins (Nups). These changes do not completely abrogate the barrier of the Nuclear Envelope (NE) but do affect the distribution of FG Nups and the RAN gradient, which are necessary for nuclear transport. Evidence from WRN/WHIP knockout cell lines demonstrates changes in the processing and nucleolar localization of lamin B1. The appearance of "RAN holes" void of RAN corresponds to regions within the nucleolus filled with condensed pools of lamin B1. From WRN/WHIP knockout cell line extracts, we found three forms of lamin B1 that correspond to mature holoprotein and two potential post-translationally modified forms of the protein. Upon treatment with topoisomerase inhibitors lamin B1 cleavage occurs only in WRN/WHIP knockout cells. Our data suggest the link of the NDC1 and WRN as one facet of the network between the nuclear periphery and genome stability. Loss of WRN complex leads to multiple alterations at the NPC and the nucleolus. © 2013. Published by Elsevier B.V. All rights reserved.

Identifying and Quantifying Chemical Forms of Sediment-Bound Ferrous Iron.

NASA Astrophysics Data System (ADS)

Kohler, M.; Kent, D. B.; Bekins, B. A.; Cozzarelli, I.; Ng, G. H. C.

2015-12-01

Aqueous Fe(II) produced by dissimilatory iron reduction comprises only a small fraction of total biogenic Fe(II) within an aquifer. Most biogenic Fe(II) is bound to sediments on ion exchange sites; as surface complexes and, possibly, surface precipitates; or incorporated into solid phases (e.g., siderite, magnetite). Different chemical forms of sediment-bound Fe(II) have different reactivities (e.g., with dissolved oxygen) and their formation or destruction by sorption/desorption and precipitation/dissolution is coupled to different solutes (e.g., major cations, H+, carbonate). We are quantifying chemical forms of sediment-bound Fe(II) using previously published extractions, novel extractions, and experimental studies (e.g., Fe isotopic exchange). Sediments are from Bemidji, Minnesota, where biodegradation of hydrocarbons from a burst oil pipeline has driven extensive dissimilatory Fe(III) reduction, and sites potentially impacted by unconventional oil and gas development. Generally, minimal Fe(II) was mobilized from ion exchange sites (batch desorption with MgCl2 and repeated desorption with NH4Cl). A < 2mm sediment fraction from the iron-reducing zone at Bemidji had 1.8umol/g Fe(II) as surface complexes or carbonate phases (sodium acetate at pH 5) of which ca. 13% was present as surface complexes (FerroZine extractions). Total bioavailable Fe(III) and biogenic Fe(II) (HCl extractions) was 40-50 umole/g on both background and iron-reducing zone sediments . Approximately half of the HCl-extractable Fe from Fe-reducing zone sediments was Fe(II) whereas 12 - 15% of Fe extracted from background sediments was present as Fe(II). One-third to one-half of the total biogenic Fe(II) extracted from sediments collected from a Montana prairie pothole located downgradient from a produced-water disposal pit was present as surface-complexed Fe(II).

Mixed-complexity artificial grammar learning in humans and macaque monkeys: evaluating learning strategies.

PubMed

Wilson, Benjamin; Smith, Kenny; Petkov, Christopher I

2015-03-01

Artificial grammars (AG) can be used to generate rule-based sequences of stimuli. Some of these can be used to investigate sequence-processing computations in non-human animals that might be related to, but not unique to, human language. Previous AG learning studies in non-human animals have used different AGs to separately test for specific sequence-processing abilities. However, given that natural language and certain animal communication systems (in particular, song) have multiple levels of complexity, mixed-complexity AGs are needed to simultaneously evaluate sensitivity to the different features of the AG. Here, we tested humans and Rhesus macaques using a mixed-complexity auditory AG, containing both adjacent (local) and non-adjacent (longer-distance) relationships. Following exposure to exemplary sequences generated by the AG, humans and macaques were individually tested with sequences that were either consistent with the AG or violated specific adjacent or non-adjacent relationships. We observed a considerable level of cross-species correspondence in the sensitivity of both humans and macaques to the adjacent AG relationships and to the statistical properties of the sequences. We found no significant sensitivity to the non-adjacent AG relationships in the macaques. A subset of humans was sensitive to this non-adjacent relationship, revealing interesting between- and within-species differences in AG learning strategies. The results suggest that humans and macaques are largely comparably sensitive to the adjacent AG relationships and their statistical properties. However, in the presence of multiple cues to grammaticality, the non-adjacent relationships are less salient to the macaques and many of the humans. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Kissing loop interaction in adenine riboswitch: insights from umbrella sampling simulations.

PubMed

Di Palma, Francesco; Bottaro, Sandro; Bussi, Giovanni

2015-01-01

Riboswitches are cis-acting regulatory RNA elements prevalently located in the leader sequences of bacterial mRNA. An adenine sensing riboswitch cis-regulates adeninosine deaminase gene (add) in Vibrio vulnificus. The structural mechanism regulating its conformational changes upon ligand binding mostly remains to be elucidated. In this open framework it has been suggested that the ligand stabilizes the interaction of the distal "kissing loop" complex. Using accurate full-atom molecular dynamics with explicit solvent in combination with enhanced sampling techniques and advanced analysis methods it could be possible to provide a more detailed perspective on the formation of these tertiary contacts. In this work, we used umbrella sampling simulations to study the thermodynamics of the kissing loop complex in the presence and in the absence of the cognate ligand. We enforced the breaking/formation of the loop-loop interaction restraining the distance between the two loops. We also assessed the convergence of the results by using two alternative initialization protocols. A structural analysis was performed using a novel approach to analyze base contacts. Contacts between the two loops were progressively lost when larger inter-loop distances were enforced. Inter-loop Watson-Crick contacts survived at larger separation when compared with non-canonical pairing and stacking interactions. Intra-loop stacking contacts remained formed upon loop undocking. Our simulations qualitatively indicated that the ligand could stabilize the kissing loop complex. We also compared with previously published simulation studies. Kissing complex stabilization given by the ligand was compatible with available experimental data. However, the dependence of its value on the initialization protocol of the umbrella sampling simulations posed some questions on the quantitative interpretation of the results and called for better converged enhanced sampling simulations.

Structural basis for the metal-selective activation of the manganese transport regulator of Bacillus subtilis.

PubMed

Kliegman, Joseph I; Griner, Sarah L; Helmann, John D; Brennan, Richard G; Glasfeld, Arthur

2006-03-21

The manganese transport regulator (MntR) of Bacillus subtilis is activated by Mn(2+) to repress transcription of genes encoding transporters involved in the uptake of manganese. MntR is also strongly activated by cadmium, both in vivo and in vitro, but it is poorly activated by other metal cations, including calcium and zinc. The previously published MntR.Mn(2+) structure revealed a binuclear complex of manganese ions with a metal-metal separation of 3.3 A (herein designated the AB conformer). Analysis of four additional crystal forms of MntR.Mn(2+) reveals that the AB conformer is only observed in monoclinic crystals at 100 K, suggesting that this conformation may be stabilized by crystal packing forces. In contrast, monoclinic crystals analyzed at room temperature (at either pH 6.5 or pH 8.5), and a second hexagonal crystal form (analyzed at 100 K), all reveal the shift of one manganese ion by 2.5 A, thereby leading to a newly identified conformation (the AC conformer) with an internuclear distance of 4.4 A. Significantly, the cadmium and calcium complexes of MntR also contain binuclear complexes with a 4.4 A internuclear separation. In contrast, the zinc complex of MntR contains only one metal ion per subunit, in the A site. Isothermal titration calorimetry confirms the stoichiometry of Mn(2+), Cd(2+), and Zn(2+) binding to MntR. We propose that the specificity of MntR activation is tied to productive binding of metal ions at two sites; the A site appears to act as a selectivity filter, determining whether the B or C site will be occupied and thereby fully activate MntR.

Functional MRI evidence for the importance of visual short-term memory in logographic reading.

PubMed

Koyama, Maki S; Stein, John F; Stoodley, Catherine J; Hansen, Peter C

2011-02-01

Logographic symbols are visually complex, and thus children's abilities for visual short-term memory (VSTM) predict their reading competence in logographic systems. In the present study, we investigated the importance of VSTM in logographic reading in adults, both behaviorally and by means of fMRI. Outside the scanner, VSTM predicted logographic Kanji reading in native Japanese adults (n=45), a finding consistent with previous observations in Japanese children. In the scanner, participants (n=15) were asked to perform a visual one-back task. For this fMRI experiment, we took advantage of the unique linguistic characteristic of the Japanese writing system, whereby syllabic Kana and logographic Kanji can share the same sound and meaning, but differ only in the complexity of their visual features. Kanji elicited greater activation than Kana in the cerebellum and two regions associated with VSTM, the lateral occipital complex and the superior intraparietal sulcus, bilaterally. The same regions elicited the highest activation during the control condition (an unfamiliar, unpronounceable script to the participants), presumably due to the increased VSTM demands for processing the control script. In addition, individual differences in VSTM performance (outside the scanner) significantly predicted blood oxygen level-dependent signal changes in the identified VSTM regions, during the Kanji and control conditions, but not during the Kana condition. VSTM appears to play an important role in reading logographic words, even in skilled adults, as evidenced at the behavioral and neural level, most likely due to the increased VSTM/visual attention demands necessary for processing complex visual features inherent in logographic symbols. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.

Petrogenesis and tectonics of the Acasta Gneiss Complex derived from integrated petrology and 142Nd and 182W extinct nuclide-geochemistry

NASA Astrophysics Data System (ADS)

Reimink, Jesse R.; Chacko, Thomas; Carlson, Richard W.; Shirey, Steven B.; Liu, Jingao; Stern, Richard A.; Bauer, Ann M.; Pearson, D. Graham; Heaman, Larry M.

2018-07-01

The timing and mechanisms of continental crust formation represent major outstanding questions in the Earth sciences. Extinct-nuclide radioactive systems offer the potential to evaluate the temporal relations of a variety of differentiation processes on the early Earth, including crust formation. Here, we investigate the whole-rock 182W/184W and 142Nd/144Nd ratios and zircon Δ17O values of a suite of well-studied and lithologically-homogeneous meta-igneous rocks from the Acasta Gneiss Complex, Northwest Territories, Canada, including the oldest-known zircon-bearing rocks on Earth. In the context of previously published geochemical data and petrogenetic models, the new 142Nd/144Nd data indicate that formation of the Hadean-Eoarchean Acasta crust was ultimately derived from variable sources, both in age and composition. Although 4.02 Ga crust was extracted from a nearly bulk-Earth source, heterogeneous μ142Nd signatures indicate that Eoarchean rocks of the Acasta Gneiss Complex were formed by partial melting of hydrated, Hadean-age mafic crust at depths shallower than the garnet stability field. By ∼3.6 Ga, granodioritic-granitic rocks were formed by partial melting of Archean hydrated mafic crust that was melted at greater depth, well into the garnet stability field. Our 182W results indicate that the sources to the Acasta Gneiss Complex had homogeneous, high-μ182W on the order of +10 ppm-a signature ubiquitous in other Eoarchean terranes. No significant deviation from the terrestrial mass fractionation line was found in the triple oxygen isotope (16O-17O-18O) compositions of Acasta zircons, confirming homogeneous oxygen isotope compositions in Earth's mantle by 4.02 Ga.

The Health and Sport Engagement (HASE) Intervention and Evaluation Project: protocol for the design, outcome, process and economic evaluation of a complex community sport intervention to increase levels of physical activity.

PubMed

Mansfield, Louise; Anokye, Nana; Fox-Rushby, Julia; Kay, Tess

2015-10-26

Sport is being promoted to raise population levels of physical activity for health. National sport participation policy focuses on complex community provision tailored to diverse local users. Few quality research studies exist that examine the role of community sport interventions in raising physical activity levels and no research to date has examined the costs and cost-effectiveness of such provision. This study is a protocol for the design, outcome, process and economic evaluation of a complex community sport intervention to increase levels of physical activity, the Health and Sport Engagement (HASE) project part of the national Get Healthy Get Active programme led by Sport England. The HASE study is a collaborative partnership between local community sport deliverers and sport and public health researchers. It involves designing, delivering and evaluating community sport interventions. The aim is to engage previously inactive people in sustained sporting activity for 1×30 min a week and to examine associated health and well-being outcomes. The study uses mixed methods. Outcomes (physical activity, health, well-being costs to individuals) will be measured by a series of self-report questionnaires and attendance data and evaluated using interrupted time series analysis controlling for a range of sociodemographic factors. Resource use will be identified and measured using diaries, interviews and records and presented alongside effectiveness data as incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. A longitudinal process evaluation (focus groups, structured observations, in-depth interview methods) will examine the efficacy of the project for achieving its aim using the principles of thematic analysis. The results of this study will be disseminated through peer-reviewed publications, academic conference presentations, Sport England and national public health organisation policy conferences, and practice-based case studies. Ethical approval was obtained through Brunel University London's research ethics committee (reference number RE33-12). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

New Luminescence Ages for the Galería Complex Archaeological Site: Resolving Chronological Uncertainties on the Acheulean Record of the Sierra de Atapuerca, Northern Spain

PubMed Central

Demuro, Martina; Arnold, Lee J.; Parés, Josep M.; Pérez-González, Alfredo; Ortega, Ana I.; Arsuaga, Juan L.; Bermúdez de Castro, José M.; Carbonell, Eudald

2014-01-01

The archaeological karstic infill site of Galería Complex, located within the Atapuerca system (Spain), has produced a large faunal and archaeological record (Homo sp. aff. heidelbergensis fossils and Mode II lithic artefacts) belonging to the Middle Pleistocene. Extended-range luminescence dating techniques, namely post-infrared infrared stimulated luminescence (pIR-IR) dating of K-feldspars and thermally transferred optically stimulated luminescence (TT-OSL) dating of individual quartz grains, were applied to fossil-bearing sediments at Galería. The luminescence dating results are in good agreement with published chronologies derived using alternative radiometric dating methods (i.e., ESR and U-series dating of bracketing speleothems and combined ESR/U-series dating of herbivore teeth), as well as biochronology and palaeoenvironmental reconstructions inferred from proxy records (e.g., pollen data). For the majority of samples dated, however, the new luminescence ages are significantly (∼50%) younger than previously published polymineral thermoluminescence (TL) chronologies, suggesting that the latter may have overestimated the true burial age of the Galería deposits. The luminescence ages obtained indicate that the top of the basal sterile sands (GIb) at Galería have an age of up to ∼370 thousand years (ka), while the lowermost sub-unit containing Mode II Acheulean lithics (base of unit GIIa) was deposited during MIS 9 (mean age = 313±14 ka; n = 4). The overlying units GIIb-GIV, which contain the richest archaeopalaeontological remains, were deposited during late MIS 8 or early MIS 7 (∼240 ka). Galería Complex may be correlative with other Middle Pleistocene sites from Atapuerca, such as Gran Dolina level TD10 and unit TE19 from Sima del Elefante, but the lowermost archaeological horizons are ∼100 ka younger than the hominin-bearing clay breccias at the Sima de los Huesos site. Our results suggest that both pIR-IR and single-grain TT-OSL dating are suitable for resolving Middle Pleistocene chronologies for the Sierra de Atapuerca karstic infill sequences. PMID:25338076

New luminescence ages for the Galería Complex archaeological site: resolving chronological uncertainties on the acheulean record of the Sierra de Atapuerca, northern Spain.

PubMed

Demuro, Martina; Arnold, Lee J; Parés, Josep M; Pérez-González, Alfredo; Ortega, Ana I; Arsuaga, Juan L; Bermúdez de Castro, José M; Carbonell, Eudald

2014-01-01

The archaeological karstic infill site of Galería Complex, located within the Atapuerca system (Spain), has produced a large faunal and archaeological record (Homo sp. aff. heidelbergensis fossils and Mode II lithic artefacts) belonging to the Middle Pleistocene. Extended-range luminescence dating techniques, namely post-infrared infrared stimulated luminescence (pIR-IR) dating of K-feldspars and thermally transferred optically stimulated luminescence (TT-OSL) dating of individual quartz grains, were applied to fossil-bearing sediments at Galería. The luminescence dating results are in good agreement with published chronologies derived using alternative radiometric dating methods (i.e., ESR and U-series dating of bracketing speleothems and combined ESR/U-series dating of herbivore teeth), as well as biochronology and palaeoenvironmental reconstructions inferred from proxy records (e.g., pollen data). For the majority of samples dated, however, the new luminescence ages are significantly (∼50%) younger than previously published polymineral thermoluminescence (TL) chronologies, suggesting that the latter may have overestimated the true burial age of the Galería deposits. The luminescence ages obtained indicate that the top of the basal sterile sands (GIb) at Galería have an age of up to ∼370 thousand years (ka), while the lowermost sub-unit containing Mode II Acheulean lithics (base of unit GIIa) was deposited during MIS 9 (mean age = 313±14 ka; n = 4). The overlying units GIIb-GIV, which contain the richest archaeopalaeontological remains, were deposited during late MIS 8 or early MIS 7 (∼240 ka). Galería Complex may be correlative with other Middle Pleistocene sites from Atapuerca, such as Gran Dolina level TD10 and unit TE19 from Sima del Elefante, but the lowermost archaeological horizons are ∼100 ka younger than the hominin-bearing clay breccias at the Sima de los Huesos site. Our results suggest that both pIR-IR and single-grain TT-OSL dating are suitable for resolving Middle Pleistocene chronologies for the Sierra de Atapuerca karstic infill sequences.

Self-management programmes for people living with chronic obstructive pulmonary disease: a call for a reconceptualisation.

PubMed

Jonsdottir, Helga

2013-03-01

To synthesise findings from previously published studies on the effectiveness of self-management programmes for people with chronic obstructive pulmonary disease. Self-management is a widely valued concept to address contemporary issues of chronic health problems. Yet, findings of self-management programmes for people with chronic obstructive pulmonary disease are indecisive. Literature review of (1) previously published systematic reviews and (2) an integrative literature review. Synthesis of findings from previously published systematic reviews (n = 4) of the effectiveness of self-management programmes for people with chronic obstructive pulmonary disease and an integrated review that was performed on papers published between January 2007-June 2012 (n = 9). Findings demonstrate that there are few studies on the effectiveness of self-management programmes on people with chronic obstructive pulmonary disease despite more than a decade of research activities. Outcomes of the studies reveal some increase in health-related quality of life and reduction in use of healthcare resources. The methodological approaches vary, and the sample size is primarily small. Families are not acknowledged. Features of patient-centredness exist in self-management programmes, particularly in the more recent articles. The effectiveness of self-management programmes for people with chronic obstructive pulmonary disease remains indecisive. A reconceptualisation of self-management programmes is called for with attention to a family-centred, holistic and relational care focusing on living with and minimising the handicapping consequences of the health problems in their entirety. © 2013 Blackwell Publishing Ltd.

Modulation of in vivo distribution through chelator: Synthesis and evaluation of a 2-nitroimidazole-dipicolylamine-(99m)Tc(CO)3 complex for detecting tumor hypoxia.

PubMed

Mallia, Madhava B; Mittal, Sweety; Sarma, Haladhar D; Banerjee, Sharmila

2016-01-01

Previous studies have clearly demonstrated strong correlation between in vivo distribution and blood clearance of radiopharmaceuticals for the detection of hypoxia. Present study describes an attempt to improve the in vivo distribution of a previously reported 2-nitroimidazole-(99m)Tc(CO)3 complex by tuning its blood clearance pattern through structural modification of the ligand. Herein, a 2-nitroimidazole-dipicolylamine ligand (2-nitroimidazole-DPA) was synthesized in a two-step procedure and radiolabeled with (99m)Tc(CO)3 core. Subsequently, the complex was evaluated in Swiss mice bearing fibrosarcoma tumor. As intended by its design, 2-nitroimidazole-DPA-(99m)Tc(CO)3 complex was more lipophilic than previously reported 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex (DETA-diethylenetriamine) and showed slower blood clearance. Consequently it showed higher tumor uptake than 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex. Significantly, despite structural modifications, other parameters such as the tumor to blood ratio and tumor to muscle ratio of the 2-nitroimidazole-DPA-(99m)Tc(CO)3 complex remained comparable to that of 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex. Present study demonstrates the feasibility of structural modifications for improving in vivo tumor uptake of hypoxia detecting radiopharmaceuticals. This might encourage researchers to improve suboptimal properties of a potential radiopharmaceuticals rather than ignoring it altogether. Copyright © 2015 Elsevier Ltd. All rights reserved.

Complex and open fractures: a straightforward approach to management in the cat.

PubMed

Corr, Sandra

2012-01-01

Cats often present with traumatic injuries of the limbs, including complex and open fractures, frequently as a result of road traffic accidents. On initial assessment, complex and open fractures may appear to require expertise beyond the experience of the general practitioner and, in some cases, referral to a specialist may be indicated or amputation should be considered. Many cases, however, can be managed using straightforward principles. This review describes a logical and practical approach to treating such injuries. It discusses general principles of fracture management, highlights the treatment of open fractures, and describes the use of external skeletal fixation for stabilisation of both open and complex fractures. Most fractures can be stabilised using equipment and expertise available in general practice if the basic principles of fracture fixation are understood and rigorously applied. Many textbooks and journal articles have been published on the management of fractures in companion animals, presenting case studies, case series and original biomechanical research. The simple strategy for managing complex injuries that is provided in this review is based on the published literature and the author's clinical experience.

The role of activity complexes in the distribution of solar magnetic fields.

NASA Astrophysics Data System (ADS)

García de La Rosa, J. I.; Reyes, R. C.

Using published data on the large-scale distribution of solar activity, the authors conclude that the longlived coronal holes are formed and maintained by the unbalanced magnetic flux which developes at both extremes of the complexes of activity.

Aprotinin; friend or foe? A review of recent medical literature.

PubMed

Royston, D; van Haaften, N; De Vooght, P

2007-01-01

Recent articles published in peer review journals have questioned the safety of using aprotinin in patients having heart surgery. Also, evidence has been published to suggest an increase in renal events in patients given aprotinin when compared to those where tranexamic acid was used. The present review will focus principally on the first of these articles in relation to previously published data and experience.

Why do smokers try to quit without medication or counselling? A qualitative study with ex-smokers.

PubMed

Smith, Andrea L; Carter, Stacy M; Chapman, Simon; Dunlop, Sally M; Freeman, Becky

2015-04-30

When tobacco smokers quit, between half and two-thirds quit unassisted: that is, they do not consult their general practitioner (GP), use pharmacotherapy (nicotine-replacement therapy, bupropion or varenicline), or phone a quitline. We sought to understand why smokers quit unassisted. Qualitative grounded theory study (in-depth interviews, theoretical sampling, concurrent data collection and data analysis). 21 Australian adult ex-smokers (aged 28-68 years; 9 males and 12 females) who quit unassisted within the past 6 months to 2 years. 12 participants had previous experience of using assistance to quit; 9 had never previously used assistance. Community, Australia. Along with previously identified barriers to use of cessation assistance (cost, access, lack of awareness or knowledge of assistance, including misperceptions about effectiveness or safety), our study produced new explanations of why smokers quit unassisted: (1) they prioritise lay knowledge gained directly from personal experiences and indirectly from others over professional or theoretical knowledge; (2) their evaluation of the costs and benefits of quitting unassisted versus those of using assistance favours quitting unassisted; (3) they believe quitting is their personal responsibility; and (4) they perceive quitting unassisted to be the 'right' or 'better' choice in terms of how this relates to their own self-identity or self-image. Deep-rooted personal and societal values such as independence, strength, autonomy and self-control appear to be influencing smokers' beliefs and decisions about quitting. The reasons for smokers' rejection of the conventional medical model for smoking cessation are complex and go beyond modifiable or correctable problems relating to misperceptions or treatment barriers. These findings suggest that GPs could recognise and respect smokers' reasons for rejecting assistance, validate and approve their choices, and modify brief interventions to support their preference for quitting unassisted, where preferred. Further research and translation may assist in developing such strategies for use in practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis.

PubMed

Kori, Medi; Aydın, Busra; Unal, Semra; Arga, Kazim Yalcin; Kazan, Dilek

2016-11-01

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) lack robust diagnostics and prognostic biomarkers. Metabolomics is a postgenomics field that offers fresh insights for biomarkers of common complex as well as rare diseases. Using data on metabolite-disease associations published in the previous decade (2006-2016) in PubMed, ScienceDirect, Scopus, and Web of Science, we identified 101 metabolites as putative biomarkers for these three neurodegenerative diseases. Notably, uric acid, choline, creatine, L-glutamine, alanine, creatinine, and N-acetyl-L-aspartate were the shared metabolite signatures among the three diseases. The disease-metabolite-pathway associations pointed out the importance of membrane transport (through ATP binding cassette transporters), particularly of arginine and proline amino acids in all three neurodegenerative diseases. When disease-specific and common metabolic pathways were queried by using the pathway enrichment analyses, we found that alanine, aspartate, glutamate, and purine metabolism might act as alternative pathways to overcome inadequate glucose supply and energy crisis in neurodegeneration. These observations underscore the importance of metabolite-based biomarker research in deciphering the elusive pathophysiology of neurodegenerative diseases. Future research investments in metabolomics of complex diseases might provide new insights on AD, PD, and ALS that continue to place a significant burden on global health.

A high-performance liquid chromatography method for the serotonin release assay is equivalent to the radioactive method.

PubMed

Sono-Koree, N K; Crist, R A; Frank, E L; Rodgers, G M; Smock, K J

2016-02-01

The serotonin release assay (SRA) is considered the gold standard laboratory test for heparin-induced thrombocytopenia (HIT). The historic SRA method uses platelets loaded with radiolabeled serotonin to evaluate platelet activation by HIT immune complexes. However, a nonradioactive method is desirable. We report the performance characteristics of a high-performance liquid chromatography (HPLC) SRA method. We validated the performance characteristics of an HPLC-SRA method, including correlation with a reference laboratory using the radioactive method. Serotonin released from reagent platelets was quantified by HPLC using fluorescent detection. Results were expressed as % release and classified as positive, negative, or indeterminate based on previously published cutoffs. Serum samples from 250 subjects with suspected HIT were tested in the HPLC-SRA and with the radioactive method. Concordant classifications were observed in 230 samples (92%). Sera from 41 healthy individuals tested negative. Between-run imprecision studies showed standard deviation of <6 (% release) for positive, weak positive, and negative serum pools. Stability studies demonstrated stability after two freeze-thaw cycles or up to a week of refrigeration. The HPLC-SRA has robust performance characteristics, equivalent to the historic radioactive method, but avoids the complexities of working with radioactivity. © 2015 John Wiley & Sons Ltd.

α-dystroglycan is a potential target of matrix metalloproteinase MMP-2.

PubMed

Sbardella, Diego; Sciandra, Francesca; Gioia, Magda; Marini, Stefano; Gori, Alessandro; Giardina, Bruno; Tarantino, Umberto; Coletta, Massimo; Brancaccio, Andrea; Bozzi, Manuela

2015-01-01

Dystroglycan (DG) is a member of the glycoprotein complex associated to dystrophin and composed by two subunits, the β-DG, a transmembrane protein, and the α-DG, an extensively glycosylated extracellular protein. The β-DG ectodomain degradation by the matrix metallo-proteinases (i.e., MMP-2 and MMP-9) in both, pathological and physiological conditions, has been characterized in detail in previous publications. Since the amounts of α-DG and β-DG at the cell surface decrease when gelatinases are up-regulated, we investigated the degradation of α-DG subunit by MMP-2. Present data show, for the first time, that the proteolysis of α-DG indeed occurs on a native glycosylated molecule enriched from rabbit skeletal muscle. In order to characterize the α-DG portion, which is more prone to cleavage by MMP-2, we performed different degradations on tailored recombinant domains of α-DG spanning the whole subunit. The overall bulk of results casts light on a relevant susceptibility of the α-DG to MMP-2 degradation with particular reference to its C-terminal domain, thus opening a new scenario on the role of gelatinases (in particular of MMP-2) in the degradation of this glycoprotein complex, taking place in the course of pathological processes. Copyright © 2014. Published by Elsevier B.V.

Prostaglandin E2 is an endogenous modulator of cerebellar development and complex behavior during a sensitive postnatal period.

PubMed

Dean, Shannon L; Knutson, Jessica F; Krebs-Kraft, Desiree L; McCarthy, Margaret M

2012-04-01

Prostaglandins are lipid-derived molecules that mediate the generation of fever in the central nervous system. In addition to their proinflammatory role, prostaglandins also impact neuronal development and synaptic plasticity, sometimes in a sex-specific manner. The cerebellum has a high expression of prostaglandin receptors during development, but the role that these molecules play during normal cerebellar maturation is unknown. We demonstrate here that disrupting prostaglandin synthesis with cyclo-oxygenase inhibitors during a time-sensitive window in early postnatal life alters cerebellar Purkinje cell development in rats, resulting in initially increased dendritic growth in both sexes. We show that this results in later cerebellar atrophy in males only, resulting in a sex-specific loss of cerebellar volume. Further, although performance in motor tasks is spared, social interaction and the sensory threshold are altered in males developmentally exposed to cyclo-oxygenase inhibitors. This work demonstrates a previously unknown role for prostaglandins in cerebellar development and emphasizes the role that the cerebellum plays outside motor tasks, in cognitive and sensory domains that may help to explain its connection to complex neurodevelopmental disorders such as autism. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling.

PubMed

Wachter, Franziska; Grunert, Michaela; Blaj, Cristina; Weinstock, David M; Jeremias, Irmela; Ehrhardt, Harald

2013-04-17

The p53 protein is the best studied target in human cancer. For decades, p53 has been believed to act mainly as a tumor suppressor and by transcriptional regulation. Only recently, the complex and diverse function of p53 has attracted more attention. Using several molecular approaches, we studied the impact of different p53 variants on extrinsic and intrinsic apoptosis signaling. We reproduced the previously published results within intrinsic apoptosis induction: while wild-type p53 promoted cell death, different p53 mutations reduced apoptosis sensitivity. The prediction of the impact of the p53 status on the extrinsic cell death induction was much more complex. The presence of p53 in tumor cell lines and primary xenograft tumor cells resulted in either augmented, unchanged or reduced cell death. The substitution of wild-type p53 by mutant p53 did not affect the extrinsic apoptosis inducing capacity. In summary, we have identified a non-expected impact of p53 on extrinsic cell death induction. We suggest that the impact of the p53 status of tumor cells on extrinsic apoptosis signaling should be studied in detail especially in the context of therapeutic approaches that aim to restore p53 function to facilitate cell death via the extrinsic apoptosis pathway.

A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia.

PubMed

Foxler, Daniel E; Bridge, Katherine S; Foster, John G; Grevitt, Paul; Curry, Sean; Shah, Kunal M; Davidson, Kathryn M; Nagano, Ai; Gadaleta, Emanuela; Rhys, Hefin I; Kennedy, Paul T; Hermida, Miguel A; Chang, Ting-Yu; Shaw, Peter E; Reynolds, Louise E; McKay, Tristan R; Wang, Hsei-Wei; Ribeiro, Paulo S; Plevin, Michael J; Lagos, Dimitris; Lemoine, Nicholas R; Rajan, Prabhakar; Graham, Trevor A; Chelala, Claude; Hodivala-Dilke, Kairbaan M; Spendlove, Ian; Sharp, Tyson V

2018-06-21

The adaptive cellular response to low oxygen tensions is mediated by the hypoxia-inducible factors (HIFs), a family of heterodimeric transcription factors composed of HIF-α and HIF-β subunits. Prolonged HIF expression is a key contributor to cellular transformation, tumorigenesis and metastasis. As such, HIF degradation under hypoxic conditions is an essential homeostatic and tumour-suppressive mechanism. LIMD1 complexes with PHD2 and VHL in physiological oxygen levels (normoxia) to facilitate proteasomal degradation of the HIF-α subunit. Here, we identify LIMD1 as a HIF-1 target gene, which mediates a previously uncharacterised, negative regulatory feedback mechanism for hypoxic HIF-α degradation by modulating PHD2-LIMD1-VHL complex formation. Hypoxic induction of LIMD1 expression results in increased HIF-α protein degradation, inhibiting HIF-1 target gene expression, tumour growth and vascularisation. Furthermore, we report that copy number variation at the LIMD1 locus occurs in 47.1% of lung adenocarcinoma patients, correlates with enhanced expression of a HIF target gene signature and is a negative prognostic indicator. Taken together, our data open a new field of research into the aetiology, diagnosis and prognosis of LIMD1 -negative lung cancers. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

A case of complex regional pain syndrome with agnosia for object orientation.

PubMed

Robinson, Gail; Cohen, Helen; Goebel, Andreas

2011-07-01

This systematic investigation of the neurocognitive correlates of complex regional pain syndrome (CRPS) in a single case also reports agnosia for object orientation in the context of persistent CRPS. We report a patient (JW) with severe long-standing CRPS who had no difficulty identifying and naming line drawings of objects presented in 1 of 4 cardinal orientations. In contrast, he was extremely poor at reorienting these objects into the correct upright orientation and in judging whether an object was upright or not. Moreover, JW made orientation errors when copying drawings of objects, and he also showed features of mirror reversal in writing single words and reading single letters. The findings are discussed in relation to accounts of visual processing. Agnosia for object orientation is the term for impaired knowledge of an object's orientation despite good recognition and naming of the same misoriented object. This defect has previously only been reported in patients with major structural brain lesions. The neuroanatomical correlates are discussed. The patient had no structural brain lesion, raising the possibility that nonstructural reorganisation of cortical networks may be responsible for his deficits. Other patients with CRPS may have related neurocognitive defects. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Microgravity effects on water supply and substrate properties in porous matrix root support systems

NASA Technical Reports Server (NTRS)

Bingham, G. E.; Jones, S. B.; Or, D.; Podolski, I. G.; Levinskikh, M. A.; Sytchov, V. N.; Ivanova, T.; Kostov, P.; Sapunova, S.; Dandolov, I.;

A new fast algorithm for solving the minimum spanning tree problem based on DNA molecules computation.

PubMed

Wang, Zhaocai; Huang, Dongmei; Meng, Huajun; Tang, Chengpei

2013-10-01

The minimum spanning tree (MST) problem is to find minimum edge connected subsets containing all the vertex of a given undirected graph. It is a vitally important NP-complete problem in graph theory and applied mathematics, having numerous real life applications. Moreover in previous studies, DNA molecular operations usually were used to solve NP-complete head-to-tail path search problems, rarely for NP-hard problems with multi-lateral path solutions result, such as the minimum spanning tree problem. In this paper, we present a new fast DNA algorithm for solving the MST problem using DNA molecular operations. For an undirected graph with n vertex and m edges, we reasonably design flexible length DNA strands representing the vertex and edges, take appropriate steps and get the solutions of the MST problem in proper length range and O(3m+n) time complexity. We extend the application of DNA molecular operations and simultaneity simplify the complexity of the computation. Results of computer simulative experiments show that the proposed method updates some of the best known values with very short time and that the proposed method provides a better performance with solution accuracy over existing algorithms. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.