bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Velocity Layer Characterization in the Niger Delta: Implications for Seismic Reflection Data Quality
Authors: Opara A. I. , Agoha C. C. , Okereke C. N. , Adiela U. P. , Onwubuariri C. N. , Okpono J. O. , Nosiri O. P.
Published: September 2017

The problems of poor data quality and statics in seismic surveys have been attributed to lack of proper understanding of the low velocity layer characteristics of the area from which such data was acquired. Downhole seismic refraction survey was therefore conducted at twenty (20) borehole locations within parts of Niger Delta, Nigeria to determine the low velocity layer characteristics of the area using the Geometrics Stratavisor NZ11 instrument. The data was processed using Udysys software with spatial representation of the results presented. Static corrections were carried out on reflection seismic data acquired from the study area using Geoscribe II software to determine the effects of the low velocity layer on reflection seismic data in the area. Results of the study revealed that the velocity of the low velocity layer ranged between 144 and 996m/s with a regional average of 407m/s. The thickness of the low velocity layer varied between 3.0 and 9.6m with a mean value of 5.0m. Similarly, the velocity of the consolidated layer ranged between 1449 and 1812m/s with a mean value of 1738m/s. Results of the static correction carried out on the seismic reflection data revealed a substantial improvement in the resolution of the data after static correction. Based on these findings, it is therefore, recommended that shots for reflection seismic survey should be located at a minimum depth of 9.6m in the area to eliminate the effects associated with the low velocity layer.
MRPN Technique for Assessment of Working Risks in Underground Coal Mines
Authors: Behraftar S. , Hossaini S. M. F. , Bakhtavar E.
Published: September 2017

Accidents in underground collieries, under geological and geotechnical uncertainties, cause some irrecoverable consequences for workers. Recognizing and studying the effective factors in the occurrence of such accidents have a very crucial impact on improving worker safety and reducing mining costs. This paper introduces a new and beneficial technique named “modified risk priority number (MRPN)” for recognizing and assessing those risks which may cause working accidents in Iranian underground collieries. The available qualitative data from the mines was quantified using standard tables established for risk assessment. The technique was exemplified using data from mine accidents in Kerman and East-Alborz regions. Roof-fall was found to be the most significant risk factor in the mines that were investigated.
Assessment of Uranium in Correlation with Physico-chemical Properties of Drinking Water of Northern Rajasthan
Authors: Mittal Sudhir , Rani Asha , Mehra Rohit , Balaram V. , Satyanarayanan M. , Sawant S. S.
Published: September 2017

In the present study, analysis of 238U concentration in 40 drinking water samples collected from different locations of Jodhpur, Nagaur, Bikaner and Jhunjhunu districts of Rajasthan, India has been carried out by using high resolution inductively coupled plasma mass spectroscopy (HR-ICP-MS) technique. The water samples were taken from hand pumps and tube wells having depths ranging from 50 to 800 feet. The measured uranium concentration lies in the range from 0.89 to 166.89 μg l−1 with the mean value of 31.72 μg l−1. The measured uranium content in twelve water samples was found to be higher than the safe limit of 30 μg l−1 as recommended by World Health Organization (WHO, 2011) and US Environmental Protection Agency (USEPA, 2011). Radiological risk calculated in the form of annual effective dose estimated from annual uranium intake ranges from 0.66 to 138.63 μSv y−1 with the mean value of 26.28 μSv y−1. The annual effective dose in two drinking water samples was found to be greater than WHO (2004) recommended level of 100 μSv y−1. Chemical risk calculated in the form of lifetime average daily dose (LAAD) estimated from the water samples varies from 0.02 to 4.57 μg kg−1 d−1 with the mean value of 0.87 μg kg−1 d−1. The lifetime average daily dose (LAAD) of ten drinking water samples was found to be greater than WHO (2011) recommended level of 1 μg kg−1 d−1. The corresponding values of hazard quotient of 48% water samples were found to be greater than unity. A good positive correlation of uranium concentration with total dissolved solids (TDS) and conductance has been observed. However no correlation of uranium concentration with pH was observed. The results revels that uranium concentration in drinking water samples of the study area can cause radiological and chemical threat to the inhabitants.
An Integrative Review of the Hands‐Free Technique in the OR
Authors: Linzer Pamela B. , Clarke Sean P.
Published: September 2017

Sharps injury rates are proportionally higher in perioperative areas than in other practice settings. The hands‐free technique (HFT) has been shown to decrease the hazards of sharps injuries when passing sharps during surgery. We reviewed and synthesized research studies regarding compliance with the HFT and factors facilitating its use using a key word search of online databases and a secondary search of references. We reviewed English language studies published since 2001 regarding HFT compliance rates or related factors using the Johns Hopkins Nursing Evidence‐Based Practice Model and Guidelines. We found 14 articles reporting a wide range of HFT compliance rates (ie, 5% to 84%), which identified that a number of organizational factors and health care workers’ perceptions of infection risks influenced the use of the HFT.
Neural correlates of affective and non-affective cognition in obsessive compulsive disorder: A meta-analysis of functional imaging studies
Authors: Rasgon A. , Lee W.H. , Leibu E. , Laird A. , Glahn D. , Goodman W. , Frangou S.
Published: September 2017

Obsessive compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive ritualistic behaviors and has been associated with diverse functional brain abnormalities. We sought to synthesize current evidence from functional magnetic resonance imaging (fMRI) studies and examine their alignment to pathogenetic models of OCD. Following systematic review, we identified 54 task-fMRI studies published in the last decade comparing adults with OCD (n = 1186) to healthy adults (n = 1159) using tasks of affective and non-affective cognition. We used voxel-based quantitative meta-analytic methods to combine primary data on anatomical coordinates of case-control differences, separately for affective and non-affective tasks. We found that functional abnormalities in OCD cluster within cortico-striatal thalamic circuits. Within these circuits, the abnormalities identified showed significant dependence on the affective or non-affective nature of the tasks employed as circuit probes. In studies using affective tasks, patients overactivated regions involved in salience, arousal and habitual responding (anterior cingulate cortex, insula, caudate head and putamen) and underactivated regions implicated in cognitive and behavioral control (medial prefrontal cortex, posterior caudate). In studies using non-affective cognitive tasks, patients overactivated regions involved in self-referential processing (precuneus, posterior cingulate cortex) and underactivated subcortical regions that support goal-directed cognition and motor control (pallidum, ventral anterior thalamus, posterior caudate). The overall pattern suggests that OCD-related brain dysfunction involves increased affective and self-referential processing, enhanced habitual responding and blunted cognitive control.
Pérdida de productividad en el lugar de trabajo relacionada con el estrés financiero
Authors: Mejía Córdova Guillermo
Published: September 2017

El propósito de esta investigación fue relacionar el nivel de estrés causado por problemas financieros en la productividad de los empleados dePetróleos Mexicanos en el sureste de México. Esta investigación utilizó un modelo de ecuaciones estructurales para probar la hipótesis. De acuerdocon los resultados, se comprueba la relación entre el estrés financiero con la productividad de los empleados.© 2017 Universidad Nacional Autónoma de México, Asociación Mexicana de Comportamiento y Salud. Este es un artículo Open Access bajo lalicencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Weed Abundance and Community Composition following a Long-Term Organic Vegetable Cropping Systems Experiment
Authors: Jernigan Ashley B. , Caldwell Brian A. , Cordeau Stéphane , DiTommaso Antonio , Drinkwater Laurie E. , Mohler Charles L. , Ryan Matthew R.
Published: September 2017

Weed management is a major constraint in organic cropping systems. In 2004, the Cornell Organic Vegetable Cropping Systems Experiment was established in central New York state using a split-plot randomized complete block design with two crop rotation entry points (split-plot factor). Four organic vegetable cropping systems that varied in cropping intensity and tillage (main plot factor) were compared: (1) intensive, (2) intermediate, (3) bio-extensive, and (4) ridge tillage. The basic crop rotation was cabbage, lettuce, potato, and winter squash, with additional short-season crops in the intensive system and with cover crops and fallow substituted for cabbage and potato in the bio-extensive system. In 2014, two uniformity trials were conducted in which oat and then a mixture of sorghum-sudangrass plus Japanese millet were grown uniformly over the entire experiment. Prior to sowing oat, soil samples were collected from each plot and an emergence bioassay was conducted to assess the soil weed seedbank. Crop biomass, weed density, and weed biomass were sampled in the uniformity crops. Soil weed seedbank density was three to four times greater in the intensive, intermediate, and ridge-tillage systems than in the bio-extensive system. The bio-extensive system also had lower weed density and weed biomass in the oat uniformity trial compared with the other three systems. Oat biomass did not differ between the cropping systems. Weed density and biomass in oat were also affected by the crop rotation entry point. Cropping system legacy effects on weed abundance and community composition were greater in the oat than in the sorghum-sudangrass plus Japanese millet uniformity trial. Our results illustrate the effects of different organic vegetable production practices on weed community structure and highlight the value of tilled fallow periods, cover crops, and prevention of weed seed rain for reducing weed populations.
Prognostic implications of abnormalities of chromosome 13 and the presence of multiple cytogenetic high-risk abnormalities in newly diagnosed multiple myeloma
Authors: Binder M , Rajkumar S V , Ketterling R P , Greipp P T , Dispenzieri A , Lacy M Q , Gertz M A , Buadi F K , Hayman S R , Hwa Y L , Zeldenrust S R , Lust J A , Russell S J , Leung N , Kapoor P , Go R S , Gonsalves W I , Kyle R A , Kumar S K
Published: September 2017

Fluorescencein situhybridization evaluation is essential for initial risk stratification in multiple myeloma. While the presence of specific cytogenetic high-risk abnormalities (HRA) is known to confer a poor prognosis, less is known about the cumulative effect of multiple HRA. We studied 1181 patients with newly diagnosed multiple myeloma who received novel agents as first-line therapy. High-risk abnormalities were defined as t(4;14), t(14;16), t(14;20) and del(17p). There were 884 patients (75%) without any HRA and 297 patients (25%) with HRA, including 262 (22%) with one HRA and 35 (3%) with two HRA. The presence of one HRA (versus zero, hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.32–2.05,p<0.001) and the presence of two HRA (versus zero, HR 3.15, 95% CI 2.00–4.96,p<0.001) were of prognostic significance after adjusting for other prognostic factors. Abnormalities of chromosome 13 were of prognostic significance independent of the established HRA: Monosomy 13 (HR 1.27, 95% CI 1.04–1.56,P=0.022) and del(13q) (HR 0.48, 95% CI 0.28–0.81,P=0.006) with opposite effects. Patients with HRA experienced worse overall survival suggesting a cumulative adverse effect of multiple HRA. Abnormalities of chromosome 13 were of prognostic significance after adjusting for other prognostic factors.
CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients
Authors: Matsushita M , Ozawa K , Suzuki T , Nakamura M , Nakano N , Kanchi S , Ichikawa D , Matsuki E , Sakurai M , Karigane D , Kasahara H , Tsukamoto N , Shimizu T , Mori T , Nakajima H , Okamoto S , Kawakami Y , Hattori Y
Published: September 2017

Although the introduction of tyrosine kinase inhibitors (TKIs) has improved overall survival of patients with chronic myeloid leukemia (CML), about half of the patients eventually relapse after cessation of TKIs. In contrast, the remainder of the patients maintain molecular remission without TKIs, indicating that the patients’ immune system could control proliferation of TKI-resistant leukemic stem cells (LSCs). However, the precise mechanism of immunity against CML-LSCs is not fully understood. We have identified a novel immune target, CXorf48, expressed in LSCs of CML patients. Cytotoxic T cells (CTLs) induced by the epitope peptide derived from CXorf48 recognized CD34+CD38− cells obtained from the bone marrow of CML patients. We detected CXorf48-specific CTLs in the peripheral blood mononuclear cells from CML patients who have discontinued imatinib after maintaining complete molecular remission for more than 2 years. Significantly, the relapse rate of CXorf48-specific CTL-negative patients was 63.6%, compared to 0% in CXorf48-specific CTL-positive patients. These results indicate that CXorf48 could be a promising therapeutic target of LSCs for immunotherapy to obtain durable treatment-free remission in CML patients.
On the role of initial velocities in pair dispersion in a microfluidic chaotic flow
Authors: Afik Eldad , Steinberg Victor
Published: September 2017

Chaotic flows drive mixing and efficient transport in fluids, as well as the associated beautiful complex patterns familiar to us from our every day life experience. Generating such flows at small scales where viscosity takes over is highly challenging from both the theoretical and engineering perspectives. This can be overcome by introducing a minuscule amount of long flexible polymers, resulting in a chaotic flow dubbed ‘elastic turbulence’. At the basis of the theoretical frameworks for its study lie the assumptions of a spatially smooth and random-in-time velocity field. Previous measurements of elastic turbulence have been limited to two-dimensions. Using a novel three-dimensional particle tracking method, we conduct a microfluidic experiment, allowing us to explore elastic turbulence from the perspective of particles moving with the flow. Our findings show that the smoothness assumption breaks already at scales smaller than a tenth of the system size. Moreover, we provide conclusive experimental evidence that ‘ballistic’ separation prevails in the dynamics of pairs of tracers over long times and distances, exhibiting a memory of the initial separation velocities. The ballistic dispersion is universal, yet it has been overlooked so far in the context of small scales chaotic flows.
Genetic correlations reveal the shared genetic architecture of transcription in human peripheral blood
Authors: Lukowski Samuel W. , Lloyd-Jones Luke R. , Holloway Alexander , Kirsten Holger , Hemani Gibran , Yang Jian , Small Kerrin , Zhao Jing , Metspalu Andres , Dermitzakis Emmanouil T. , Gibson Greg , Spector Timothy D. , Thiery Joachim , Scholz Markus , Montgomery Grant W. , Esko Tonu , Visscher Peter M. , Powell Joseph E.
Published: September 2017

Transcript co-expression is regulated by a combination of shared genetic and environmental factors. Here, we estimate the proportion of co-expression that is due to shared genetic variance. To do so, we estimated the genetic correlations between each pairwise combination of 2469 transcripts that are highly heritable and expressed in whole blood in 1748 unrelated individuals of European ancestry. We identify 556 pairs with a significant genetic correlation of which 77% are located on different chromosomes, and report 934 expression quantitative trait loci, identified in an independent cohort, with significant effects on both transcripts in a genetically correlated pair. We show significant enrichment for transcription factor control and physical proximity through chromatin interactions as possible mechanisms of shared genetic control. Finally, we construct networks of interconnected transcripts and identify their underlying biological functions. Using genetic correlations to investigate transcriptional co-regulation provides valuable insight into the nature of the underlying genetic architecture of gene regulation.
Prophage-triggered membrane vesicle formation through peptidoglycan damage in Bacillus subtilis
Authors: Toyofuku Masanori , Cárcamo-Oyarce Gerardo , Yamamoto Tatsuya , Eisenstein Fabian , Hsiao Chien-Chi , Kurosawa Masaharu , Gademann Karl , Pilhofer Martin , Nomura Nobuhiko , Eberl Leo
Published: September 2017

Bacteria release membrane vesicles (MVs) that play important roles in various biological processes. However, the mechanisms of MV formation in Gram-positive bacteria are unclear, as these cells possess a single cytoplasmic membrane that is surrounded by a thick cell wall. Here we use live cell imaging and electron cryo-tomography to describe a mechanism for MV formation in Bacillus subtilis. We show that the expression of a prophage-encoded endolysin in a sub-population of cells generates holes in the peptidoglycan cell wall. Through these openings, cytoplasmic membrane material protrudes into the extracellular space and is released as MVs. Due to the loss of membrane integrity, the induced cells eventually die. The vesicle-producing cells induce MV formation in neighboring cells by the enzymatic action of the released endolysin. Our results support the idea that endolysins may be important for MV formation in bacteria, and this mechanism may potentially be useful for the production of MVs for applications in biomedicine and nanotechnology.
Fas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function
Authors: Item Flurin , Wueest Stephan , Lemos Vera , Stein Sokrates , Lucchini Fabrizio C. , Denzler Rémy , Fisser Muriel C. , Challa Tenagne D. , Pirinen Eija , Kim Youngsoo , Hemmi Silvio , Gulbins Erich , Gross Atan , O’Reilly Lorraine A. , Stoffel Markus , Auwerx Johan , Konrad Daniel
Published: September 2017

Nonalcoholic fatty liver disease is one of the most prevalent metabolic disorders and it tightly associates with obesity, type 2 diabetes, and cardiovascular disease. Reduced mitochondrial lipid oxidation contributes to hepatic fatty acid accumulation. Here, we show that the Fas cell surface death receptor (Fas/CD95/Apo-1) regulates hepatic mitochondrial metabolism. Hepatic Fas overexpression in chow-fed mice compromises fatty acid oxidation, mitochondrial respiration, and the abundance of mitochondrial respiratory complexes promoting hepatic lipid accumulation and insulin resistance. In line, hepatocyte-specific ablation of Fas improves mitochondrial function and ameliorates high-fat-diet-induced hepatic steatosis, glucose tolerance, and insulin resistance. Mechanistically, Fas impairs fatty acid oxidation via the BH3 interacting-domain death agonist (BID). Mice with genetic or pharmacological inhibition of BID are protected from Fas-mediated impairment of mitochondrial oxidation and hepatic steatosis. We suggest Fas as a potential novel therapeutic target to treat obesity-associated fatty liver and insulin resistance.
Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis
Authors: Müller-Fielitz Helge , Stahr Marcus , Bernau Mareike , Richter Marius , Abele Sebastian , Krajka Victor , Benzin Anika , Wenzel Jan , Kalies Kathrin , Mittag Jens , Heuer Heike , Offermanns Stefan , Schwaninger Markus
Published: September 2017

The hypothalamic–pituitary–thyroid (HPT) axis maintains circulating thyroid hormone levels in a narrow physiological range. As axons containing thyrotropin-releasing hormone (TRH) terminate on hypothalamic tanycytes, these specialized glial cells have been suggested to influence the activity of the HPT axis, but their exact role remained enigmatic. Here, we demonstrate that stimulation of the TRH receptor 1 increases intracellular calcium in tanycytes of the median eminence via Gαq/11 proteins. Activation of Gαq/11 pathways increases the size of tanycyte endfeet that shield pituitary vessels and induces the activity of the TRH-degrading ectoenzyme. Both mechanisms may limit the TRH release to the pituitary. Indeed, blocking TRH signaling in tanycytes by deleting Gαq/11 proteins in vivo enhances the response of the HPT axis to the chemogenetic activation of TRH neurons. In conclusion, we identify new TRH- and Gαq/11-dependent mechanisms in the median eminence by which tanycytes control the activity of the HPT axis.
Ultrawide thermal free-carrier tuning of dielectric antennas coupled to epsilon-near-zero substrates
Authors: Iyer Prasad P. , Pendharkar Mihir , Palmstrøm Chris J. , Schuller Jon A.
Published: September 2017

The principal challenge for achieving reconfigurable optical antennas and metasurfaces is the need to generate continuous and large tunability of subwavelength, low-Q resonators. We demonstrate continuous and steady-state refractive index tuning at mid-infrared wavelengths using temperature-dependent control over the low-loss plasma frequency in III–V semiconductors. In doped InSb we demonstrate nearly two-fold increase in the electron effective mass leading to a positive refractive index shift (Δn > 1.5) that is an order of magnitude greater than conventional thermo-optic effects. In undoped films we demonstrate more than 10-fold change in the thermal free-carrier concentration producing a near-unity negative refractive index shift. Exploiting both effects within a single resonator system—intrinsic InSb wires on a heavily doped (epsilon-near-zero) InSb substrate—we demonstrate dynamically steady-state tunable Mie resonances. The observed line-width resonance shifts (Δλ > 1.7 μm) suggest new avenues for highly tunable and steady-state mid-infrared semiconductor antennas.
Tau exacerbates excitotoxic brain damage in an animal model of stroke
Authors: Bi Mian , Gladbach Amadeus , van Eersel Janet , Ittner Arne , Przybyla Magdalena , van Hummel Annika , Chua Sook Wern , van der Hoven Julia , Lee Wei S. , Müller Julius , Parmar Jasneet , Jonquieres Georg von , Stefen Holly , Guccione Ernesto , Fath Thomas , Housley Gary D. , Klugmann Matthias , Ke Yazi D. , Ittner Lars M.
Published: September 2017

Neuronal excitotoxicity induced by aberrant excitation of glutamatergic receptors contributes to brain damage in stroke. Here we show that tau-deficient (tau−/−) mice are profoundly protected from excitotoxic brain damage and neurological deficits following experimental stroke, using a middle cerebral artery occlusion with reperfusion model. Mechanistically, we show that this protection is due to site-specific inhibition of glutamate-induced and Ras/ERK-mediated toxicity by accumulation of Ras-inhibiting SynGAP1, which resides in a post-synaptic complex with tau. Accordingly, reducing SynGAP1 levels in tau−/− mice abolished the protection from pharmacologically induced excitotoxicity and middle cerebral artery occlusion-induced brain damage. Conversely, over-expression of SynGAP1 prevented excitotoxic ERK activation in wild-type neurons. Our findings suggest that tau mediates excitotoxic Ras/ERK signaling by controlling post-synaptic compartmentalization of SynGAP1.
The Ca2+ influx through the mammalian skeletal muscle dihydropyridine receptor is irrelevant for muscle performance
Authors: Dayal Anamika , Schrötter Kai , Pan Yuan , Föhr Karl , Melzer Werner , Grabner Manfred
Published: September 2017

Skeletal muscle excitation–contraction (EC) coupling is initiated by sarcolemmal depolarization, which is translated into a conformational change of the dihydropyridine receptor (DHPR), which in turn activates sarcoplasmic reticulum (SR) Ca2+ release to trigger muscle contraction. During EC coupling, the mammalian DHPR embraces functional duality, as voltage sensor and l-type Ca2+ channel. Although its unique role as voltage sensor for conformational EC coupling is firmly established, the conventional function as Ca2+ channel is still enigmatic. Here we show that Ca2+ influx via DHPR is not necessary for muscle performance by generating a knock-in mouse where DHPR-mediated Ca2+ influx is eliminated. Homozygous knock-in mice display SR Ca2+ release, locomotor activity, motor coordination, muscle strength and susceptibility to fatigue comparable to wild-type controls, without any compensatory regulation of multiple key proteins of the EC coupling machinery and Ca2+ homeostasis. These findings support the hypothesis that the DHPR-mediated Ca2+ influx in mammalian skeletal muscle is an evolutionary remnant.
Efficient post-acceleration of protons in helical coil targets driven by sub-ps laser pulses
Authors: Ahmed H. , Kar S. , Cantono G. , Hadjisolomou P. , Poye A. , Gwynne D. , Lewis C. L. S. , Macchi A. , Naughton K. , Nersisyan G. , Tikhonchuk V. , Willi O. , Borghesi M.
Published: September 2017

The characteristics of laser driven proton beams can be efficiently controlled and optimised by employing a recently developed helical coil technique, which exploits the transient self-charging of solid targets irradiated by intense laser pulses. Here we demonstrate a well collimated (<1° divergence) and narrow bandwidth (~10% energy spread) proton beamlet of ~107 particles at 10 ± 0.5 MeV obtained by irradiating helical coil targets with a few joules, sub-ps laser pulses at an intensity of ~2 × 1019 W cm−2. The experimental data are in good agreement with particle tracing simulations suggesting post-acceleration of protons inside the coil at a rate ~0.7 MeV/mm, which is comparable to the results obtained from a similar coil target irradiated by a fs class laser at an order of magnitude higher intensity, as reported in S. Kar et al., Nat. Commun, 7, 10792 (2016). The dynamics of hot electron escape from the laser irradiated target was studied numerically for these two irradiation regimes, which shows that the target self-charging can be optimised at a pulse duration of few hundreds of fs. This information is highly beneficial for maximising the post-acceleration gradient in future experiments.
Comparison of APACHE IV with APACHE II, SAPS 3, MELD, MELD-Na, and CTP scores in predicting mortality after liver transplantation
Authors: Lee Hannah , Yoon Susie , Oh Seung-Young , Shin Jungho , Kim Jeongsoo , Jung Chul-Woo , Ryu Ho Geol
Published: September 2017

The Acute Physiology and Chronic Health Evaluation (APACHE) IV score and Simplified Acute Physiology Score (SAPS) 3 include liver transplantation as a diagnostic category. The performance of APACHE IV-liver transplantation (LT) specific predicted mortality, SAPS 3, APACHE II, Model for End-stage Liver Disease (MELD)-Na, MELD, and CTP scores in predicting in-hospital and 1 year mortality in liver transplant patients was compared using 590 liver transplantations in a single university hospital. In-hospital mortality and 1 year mortality were 2.9% and 4.2%, respectively. The APACHE IV-LT specific predicted mortality showed better performance in predicting in-hospital mortality (AUC 0.91, 95% CI [0.86–0.96]) compared to SAPS 3 (AUC 0.78, 95% CI [0.66–0.90], p = 0.01), MELD-Na (AUC 0.74, 95% CI [0.57–0.86], p = 0.01), and CTP (AUC 0.68, 95% CI [0.54–0.81], p = 0.01). The APACHE IV-LT specific predicted mortality showed better performance in predicting 1 year mortality (AUC 0.83, 95% CI [0.76–0.9]) compared to MELD-Na (AUC 0.67, 95% CI [0.55–0.79], p = 0.04) and CTP (AUC 0.64, 95% CI [0.53–0.75], p = 0.03), and also in all MELD groups and in both living and deceased donor transplantation. The APACHE IV-LT specific predicted mortality showed better performance in predicting in-hospital and 1 year mortality after liver transplantation.
Loss of brain inter-frequency hubs in Alzheimer's disease
Authors: Guillon J. , Attal Y. , Colliot O. , La Corte V. , Dubois B. , Schwartz D. , Chavez M. , De Vico Fallani F.
Published: September 2017

Alzheimer’s disease (AD) causes alterations of brain network structure and function. The latter consists of connectivity changes between oscillatory processes at different frequency channels. We proposed a multi-layer network approach to analyze multiple-frequency brain networks inferred from magnetoencephalographic recordings during resting-states in AD subjects and age-matched controls. Main results showed that brain networks tend to facilitate information propagation across different frequencies, as measured by the multi-participation coefficient (MPC). However, regional connectivity in AD subjects was abnormally distributed across frequency bands as compared to controls, causing significant decreases of MPC. This effect was mainly localized in association areas and in the cingulate cortex, which acted, in the healthy group, as a true inter-frequency hub. MPC values significantly correlated with memory impairment of AD subjects, as measured by the total recall score. Most predictive regions belonged to components of the default-mode network that are typically affected by atrophy, metabolism disruption and amyloid-β deposition. We evaluated the diagnostic power of the MPC and we showed that it led to increased classification accuracy (78.39%) and sensitivity (91.11%). These findings shed new light on the brain functional alterations underlying AD and provide analytical tools for identifying multi-frequency neural mechanisms of brain diseases.
Plasma exosomal miR-223 expression regulates inflammatory responses during cardiac surgery with cardiopulmonary bypass
Authors: Poon Kin-Shing , Palanisamy Kalaiselvi , Chang Shih-Sheng , Sun Kuo-Ting , Chen Kuen-Bao , Li Ping-Chun , Lin Tso-Chou , Li Chi-Yuan
Published: September 2017

Cardiopulmonary bypass (CPB) induces inflammatory responses, and effective endogenous homeostasis is important for preventing systemic inflammation. We assessed whether plasma exosomal microRNAs in patients undergoing cardiac surgery with CPB are involved in the regulation of inflammatory responses. Plasma samples were isolated from CPB patients (n = 21) at 5 specified time points: pre-surgery, pre-CPB and 2 hours (h), 4 h and 24 h after CPB began. Plasma TNF-α expression was increased after CPB began compared to that in the pre-surgery samples. Plasma IL-8 and IL-6 expression peaked at 4 h after CPB began but was downregulated at 24 h. The number of plasma exosomes collected at 2 h (55.1 ± 8.3%), 4 h (63.8 ± 10.1%) and 24 h (83.5 ± 3.72%) after CPB began was significantly increased compared to that in the pre-CPB samples (42.8 ± 0.11%). These exosomes had a predominantly parental cellular origin from RBCs and platelets. Additionally, the plasma exosomal miR-223 levels were significantly increased after CPB began compared to those in the pre-CPB samples. Further, exosomal miR-223 from plasma collected after CPB began downregulated IL-6 and NLRP3 expression in the monocytes. Here, we present the novel findings that increased plasma exosomal miR-223 expression during cardiac surgery with CPB might play homeostatic roles in downregulating inflammatory responses through intercellular communication.
Combining Biomarkers with EMR Data to Identify Patients in Different Phases of Sepsis
Authors: Taneja Ishan , Reddy Bobby , Damhorst Gregory , Dave Zhao Sihai , Hassan Umer , Price Zachary , Jensen Tor , Ghonge Tanmay , Patel Manish , Wachspress Samuel , Winter Jackson , Rappleye Michael , Smith Gillian , Healey Ryan , Ajmal Muhammad , Khan Muhammad , Patel Jay , Rawal Harsh , Sarwar Raiya , Soni Sumeet , Anwaruddin Syed , Davis Benjamin , Kumar James , White Karen , Bashir Rashid , Zhu Ruoqing
Published: September 2017

Sepsis is a leading cause of death and is the most expensive condition to treat in U.S. hospitals. Despite targeted efforts to automate earlier detection of sepsis, current techniques rely exclusively on using either standard clinical data or novel biomarker measurements. In this study, we apply machine learning techniques to assess the predictive power of combining multiple biomarker measurements from a single blood sample with electronic medical record data (EMR) for the identification of patients in the early to peak phase of sepsis in a large community hospital setting. Combining biomarkers and EMR data achieved an area under the receiver operating characteristic (ROC) curve (AUC) of 0.81, while EMR data alone achieved an AUC of 0.75. Furthermore, a single measurement of six biomarkers (IL-6, nCD64, IL-1ra, PCT, MCP1, and G-CSF) yielded the same predictive power as collecting an additional 16 hours of EMR data(AUC of 0.80), suggesting that the biomarkers may be useful for identifying these patients earlier. Ultimately, supervised learning using a subset of biomarker and EMR data as features may be capable of identifying patients in the early to peak phase of sepsis in a diverse population and may provide a tool for more timely identification and intervention.
New Late Permian tectonic model for South Africa’s Karoo Basin: foreland tectonics and climate change before the end-Permian crisis
Authors: Viglietti Pia A. , Rubidge Bruce S. , Smith Roger M. H.
Published: September 2017

Late Permian Karoo Basin tectonics in South Africa are reflected as two fining-upward megacycles in the Balfour and upper Teekloof formations. Foreland tectonics are used to explain the cyclic nature and distribution of sedimentation, caused by phases of loading and unloading in the southern source areas adjacent to the basin. New data supports this model, and identifies potential climatic effects on the tectonic regime. Diachronous second-order subaerial unconformities (SU) are identified at the base and top of the Balfour Formation. One third-order SU identified coincides ﻿with﻿ a faunal turnover which could be related to the Permo-Triassic mass extinction (PTME). The SU are traced, for the first time, to the western portion of the basin (upper Teekloof Formation). Their age determinations support the foreland basin model as they coincide with dated paroxysms. A condensed distal (northern) stratigraphic record is additional support for this tectonic regime because orogenic loading and unloading throughout the basin was not equally distributed, nor was it in-phase. This resulted in more frequent non-deposition with increased distance from the tectonically active source. Refining basin dynamics allows us to distinguish between tectonic and climatic effects and how they have influenced ancient ecosystems and sedimentation through time.
Mechanism and DNA-based detection of field-evolved resistance to transgenic Bt corn in fall armyworm (Spodoptera frugiperda)
Authors: Banerjee Rahul , Hasler James , Meagher Robert , Nagoshi Rodney , Hietala Lucas , Huang Fangneng , Narva Kenneth , Jurat-Fuentes Juan Luis
Published: September 2017

Evolution of resistance threatens sustainability of transgenic crops producing insecticidal proteins from the bacterium Bacillus thuringiensis (Bt). The fall armyworm (Spodoptera frugiperda) is a devastating pest of corn in the Western Hemisphere initially controlled by transgenic Bt corn producing the Cry1Fa insecticidal protein (event TC1507). However field-evolved resistance to TC1507 was observed in Puerto Rico in 2007 and has subsequently been reported in a number of locations in North and South America. Early studies on Puerto Rico fall armyworm populations found that the resistance phenotype was associated with reduced expression of alkaline phosphatase. However, in this work we show that field-evolved resistance to Cry1Fa Bt corn in Puerto Rico is closely linked to a mutation in an ATP Binding Cassette subfamily C2 (ABCC2) gene that functions as a Cry1Fa receptor in susceptible insects. Furthermore, we report a DNA-based genotyping test used to demonstrate the presence of the resistant (SfABCC2mut) allele in Puerto Rico populations in 2007, coincident with the first reports of damage to TC1507 corn. These DNA-based field screening data provide strong evidence that resistance to TC1507 in fall armyworm maps to the SfABCC2 gene and provides a useful molecular marker for detecting the SfABCC2mut allele in resistant fall armyworm.
Disseminated tuberculosis among hospitalised HIV patients in South Africa: a common condition that can be rapidly diagnosed using urine-based assays
Authors: Kerkhoff Andrew D. , Barr David A. , Schutz Charlotte , Burton Rosie , Nicol Mark P. , Lawn Stephen D. , Meintjes Graeme
Published: September 2017

HIV-associated disseminated TB (tuberculosis) has been under-recognised and poorly characterised. Blood culture is the gold-standard diagnostic test, but is expensive, slow, and may under-diagnose TB dissemination. In a cohort of hospitalised HIV patients, we aimed to report the prevalence of TB-blood-culture positivity, performance of rapid diagnostics as diagnostic surrogates, and better characterise the clinical phenotype of disseminated TB. HIV-inpatients were systematically investigated using sputum, urine and blood testing. Overall, 132/410 (32.2%) patients had confirmed TB; 41/132 (31.1%) had a positive TB blood culture, of these 9/41 (22.0%) died within 90-days. In contrast to sputum diagnostics, urine Xpert and urine-lipoarabinomannan (LAM) combined identified 88% of TB blood-culture-positive patients, including 9/9 who died within 90-days. For confirmed-TB patients, half the variation in major clinical variables was captured on two principle components (PCs). Urine Xpert, urine LAM and TB-blood-culture positive patients clustered similarly on these axes, distinctly from patients with localised disease. Total number of positive tests from urine Xpert, urine LAM and MTB-blood-culture correlated with PCs (p < 0.001 for both). PC1&PC2 independently predicted 90-day mortality (ORs 2.6, 95%CI = 1.3–6.4; and 2.4, 95%CI = 1.3–4.5, respectively). Rather than being a non-specific diagnosis, disseminated TB is a distinct, life-threatening condition, which can be diagnosed using rapid urine-based tests, and warrants specific interventional trials.
Stacking-fault strengthening of biomedical Co–Cr–Mo alloy via multipass thermomechanical processing
Authors: Yamanaka Kenta , Mori Manami , Sato Shigeo , Chiba Akihiko
Published: September 2017

The strengthening of metallic biomaterials, such as Co–Cr–Mo and titanium alloys, is of crucial importance to the improvement of the durability of orthopedic implants. In the present study, we successfully developed a face-centered cubic (fcc) Co–Cr–Mo alloy with an extremely high yield strength (1400 MPa) and good ductility (12%) by multipass hot-rolling, which is suitable for industrial production, and examined the relevant strengthening mechanisms. Using an X-ray diffraction line-profile analysis, we revealed that a substantial increase in the number of stacking faults (SFs) in the fcc γ-matrix occurred at a greater height reduction (r), while physical modeling demonstrated that the contribution of the accumulated SFs (i.e., the reduction in SF spacing) with an increase inrsuccessfully explains the entire strengthening behavior of the hot-rolled alloy. The present study sheds light on the importance of the SF strengthening mechanism, and will help to guide the design and manufacturing strategy for the high-strength Co–Cr–Mo alloys used in highly durable medical devices.
Antibiotic treatment for Tuberculosis induces a profound dysbiosis of the microbiome that persists long after therapy is completed
Authors: Wipperman Matthew F. , Fitzgerald Daniel W. , Juste Marc Antoine Jean , Taur Ying , Namasivayam Sivaranjani , Sher Alan , Bean James M. , Bucci Vanni , Glickman Michael S.
Published: September 2017

Mycobacterium tuberculosis, the cause of Tuberculosis (TB), infects one third of the world’s population and causes substantial mortality worldwide. In its shortest format, treatment of TB requires six months of multidrug therapy with a mixture of broad spectrum and mycobacterial specific antibiotics, and treatment of multidrug resistant TB is longer. The widespread use of this regimen makes this one of the largest exposures of humans to antimicrobials, yet the effects of TB treatment on intestinal microbiome composition and long-term stability are unknown. We compared the microbiome composition, assessed by both 16S rDNA and metagenomic DNA sequencing, of TB cases during antimycobacterial treatment and following cure by 6 months of antibiotics. TB treatment does not perturb overall diversity, but nonetheless dramatically depletes multiple immunologically significant commensal bacteria. The microbiomic perturbation of TB therapy can persist for at least 1.2 years, indicating that the effects of TB treatment are long lasting. These results demonstrate that TB treatment has dramatic effects on the intestinal microbiome and highlight unexpected durable consequences of treatment for the world’s most common infection on human ecology.
In search of a small molecule agonist of the relaxin receptor RXFP1 for the treatment of liver fibrosis
Authors: McBride Andrew , Hoy Anna M. , Bamford Mark J. , Mossakowska Danuta E. , Ruediger Martin P. , Griggs Jeremy , Desai Sapna , Simpson Kate , Caballero-Hernandez Ivan , Iredale John P. , Pell Theresa , Aucott Rebecca L. , Holmes Duncan S. , Webster Scott P. , Fallowfield Jonathan A.
Published: September 2017

The peptide hormone human relaxin-2 (H2-RLX) has emerged as a potential therapy for cardiovascular and fibrotic diseases, but its short in vivo half-life is an obstacle to long-term administration. The discovery of ML290 demonstrated that it is possible to identify small molecule agonists of the cognate G-protein coupled receptor for H2-RLX (relaxin family peptide receptor-1 (RXFP1)). In our efforts to generate a new medicine for liver fibrosis, we sought to identify improved small molecule functional mimetics of H2-RLX with selective, full agonist or positive allosteric modulator activity against RXFP1. First, we confirmed expression of RXFP1 in human diseased liver. We developed a robust cellular cAMP reporter assay of RXFP1 signaling in HEK293 cells transiently expressing RXFP1. A high-throughput screen did not identify further specific agonists or positive allosteric modulators of RXFP1, affirming the low druggability of this receptor. As an alternative approach, we generated novel ML290 analogues and tested their activity in the HEK293-RXFP1 cAMP assay and the human hepatic cell line LX-2. Differences in activity of compounds on cAMP activation compared with changes in expression of fibrotic markers indicate the need to better understand cell- and tissue-specific signaling mechanisms and their disease-relevant phenotypes in order to enable drug discovery.
Plant litter dynamics in the forest-stream interface: precipitation is a major control across tropical biomes
Authors: Tonin Alan M. , Gonçalves José F. , Bambi Paulino , Couceiro Sheyla R. M. , Feitoza Lorrane A. M. , Fontana Lucas E. , Hamada Neusa , Hepp Luiz U. , Lezan-Kowalczuk Vânia G. , Leite Gustavo F. M. , Lemes-Silva Aurea L. , Lisboa Leonardo K. , Loureiro Rafael C. , Martins Renato T. , Medeiros Adriana O. , Morais Paula B. , Moretto Yara , Oliveria Patrícia C. A. , Pereira Evelyn B. , Ferreira Lidiane P. , Pérez Javier , Petrucio Mauricio M. , Reis Deusiano F. , S. Rezende Renan , Roque Nadia , Santos Luiz E. P. , Siegloch Ana E. , Tonello Gabriela , Boyero Luz
Published: September 2017

Riparian plant litter is a major energy source for forested streams across the world and its decomposition has repercussions on nutrient cycling, food webs and ecosystem functioning. However, we know little about plant litter dynamics in tropical streams, even though the tropics occupy 40% of the Earth’s land surface. Here we investigated spatial and temporal (along a year cycle) patterns of litter inputs and storage in multiple streams of three tropical biomes in Brazil (Atlantic forest, Amazon forest and Cerrado savanna), predicting major differences among biomes in relation to temperature and precipitation regimes. Precipitation explained most of litter inputs and storage, which were generally higher in more humid biomes (litterfall: 384, 422 and 308 g m−2 y−1, storage: 55, 113 and 38 g m−2, on average in Atlantic forest, Amazon and Cerrado, respectively). Temporal dynamics varied across biomes in relation to precipitation and temperature, with uniform litter inputs but seasonal storage in Atlantic forest streams, seasonal inputs in Amazon and Cerrado streams, and aseasonal storage in Amazon streams. Our findings suggest that litter dynamics vary greatly within the tropics, but point to the major role of precipitation, which contrasts with the main influence of temperature in temperate areas.
QTL mapping using an ultra-high-density SNP map reveals a major locus for grain yield in an elite rice restorer R998
Authors: Zhu Manshan , Liu Dilin , Liu Wuge , Li Dan , Liao Yilong , Li Jinhua , Fu Chongyun , Fu Fuhong , Huang Huijun , Zeng Xueqin , Ma Xiaozhi , Wang Feng
Published: September 2017

To dissect the genetic basis of yield formation in restorer line of hybrid rice, we conducted QTL analysis for 6 yield traits including panicles per plant (PPP), grains per panicle (GPP), grain yield per plant (GY), thousand-grain weight (TGW), above-ground biomass (AGB), and harvest index (HI) using SNP markers in a recombinant inbred lines (RILs) population derived from a cross between a tropical japonica inbred Francis and an elite indica restorer Guanghui 998 (R998). A total of 26 QTLs were detected using a high density genetic map consisting of 3016 bin markers. Nineteen out of the 26 QTL alleles from R998 had a beneficial effect on yield traits. Most of the QTLs were co-located with previously reported rice QTLs. qAGB6 and qHI9, controlling AGB and HI respectively, were detected as novel QTLs. Four QTLs for GY were repeatedly detected across two years, with all the beneficial alleles from R998. Notably, qGY8 explained over 20% of the yield variance in both years. Moreover, qGY8 together with qTGW8 and qHI8 formed a QTL cluster. Markers tightly linked with qGY8 were developed. Cloning of qGY8 will facilitate its further exploitation in high-yield breeding.
A reminder before extinction strengthens episodic memory via reconsolidation but fails to disrupt generalized threat responses
Authors: Kroes Marijn C. W. , Dunsmoor Joseph E. , Lin Qi , Evans Michael , Phelps Elizabeth A.
Published: September 2017

A reminder can temporarily renew flexibility of consolidated memories, referred to as reconsolidation. Pavlovian threat-conditioning studies suggest that a reminder can renew flexibility of threat responses but that episodic memories remain stable. In contrast, outside the threat-conditioning domain, studies testing memory for word lists or stories find that a reminder can renew flexibility of episodic memory. This discrepancy in findings leaves it unclear if episodic memories reconsolidate, or only Pavlovian responses. Here we unite the different approaches in the field and show that a reminder can retroactively strengthen episodic memory for Pavlovian threat-conditioned events, but that, in contrast to threat-conditioning studies with simple sensory stimuli, extinction after a reminder fails to prevent recovery of generalized threat responses. Our results indicate the episodic memories also reconsolidate, allowing strengthening of relevant memories. These findings also suggest that generalized threat responses and episodic memories are less susceptible to be modified by reminder-interventions procedures.