bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants
Authors: Rotroff D M , Corum D G , Motsinger-Reif A , Fiehn O , Bottrel N , Drevets W C , Singh J , Salvadore G , Kaddurah-Daouk R 
Published: September 2016

AbstractKetamine, at sub-anesthetic doses, is reported to rapidly decrease depression symptoms in patients with treatment-resistant major depressive disorder (MDD). Many patients do not respond to currently available antidepressants, (for example, serotonin reuptake inhibitors), making ketamine and its enantiomer, esketamine, potentially attractive options for treatment-resistant MDD. Although mechanisms by which ketamine/esketamine may produce antidepressant effects have been hypothesized on the basis of preclinical data, the neurobiological correlates of the rapid therapeutic response observed in patients receiving treatment have not been established. Here we use a pharmacometabolomics approach to map global metabolic effects of these compounds in treatment-refractory MDD patients upon 2 h from infusion with ketamine (n=33) or its S-enantiomer, esketamine (n=20). The effects of esketamine on metabolism were retested in the same subjects following a second exposure administered 4 days later. Two complementary metabolomics platforms were used to provide broad biochemical coverage. In addition, we investigated whether changes in particular metabolites correlated with treatment outcome. Both drugs altered metabolites related to tryptophan metabolism (for example, indole-3-acetate and methionine) and/or the urea cycle (for example, citrulline, arginine and ornithine) at 2 h post infusion (q<0.25). In addition, we observed changes in glutamate and circulating phospholipids that were significantly associated with decreases in depression severity. These data provide new insights into the mechanism underlying the rapid antidepressant effects of ketamine and esketamine, and constitute some of the first detailed metabolomics mapping for these promising therapies.
White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults
Authors: Beydoun M A , Beydoun H A , Dore G A , Canas J-A , Fanelli-Kuczmarski M T , Evans M K , Zonderman A B 
Published: September 2016

AbstractTotal white blood cell count (TWBCC) and percentage (%) composition of lymphocytes (PL) or neutrophils (PN) are linked to mid- and late-life depression, though sex-specific temporal relationships between those inflammatory markers and depressive symptoms remain unclear. The association between inflammation and depressive symptoms in longitudinal data on ethnically and socioeconomically diverse urban adults was examined with two hypotheses. In hypothesis 1, we examined the relationship between TWBCC, PL and PN with change in level of depressive symptoms from baseline to follow-up, stratifying by sex. In hypothesis 2, we examined reverse causality, by testing the relationship of depressive symptoms with change in TWBCC, PL and PN. Multiple linear mixed-effects regression models were performed to examine both the hypotheses. The sample sizes of participants (n) and repeated observations (n’) were: Hypothesis 1 (n=2009; n’=3501); Hypothesis 2 (n=2081; n’=3560). Among key findings (Hypothesis 1), in women, higher TWBCC was linked to a faster increase in depressive symptom total score (γ1112±s.e.: +0.81±0.28, P=0.003), with a slower increase over time in the positive affect subdomain coupled with faster increases in depressed affect and somatic complaints. Among women, baseline score on somatic complaints was positively associated with low PN (γ01a=+1.61±0.48, P<0.001) and high PL (γ01a=+1.16±0.45, P=0.011), whereas baseline score on positive affect was inversely related to higher PL (γ01a=−0.69±0.28, P=0.017). Results among men indicated that there was a positive cross-sectional relationship between low TWBCC and depressive symptoms, depressed affect and an inverse cross-sectional relationship with positive affect. However, over time, a low TWBCC in men was linked to a higher score on positive affect. There was no evidence of a bi-directional relationship between WBC parameters and depressive symptoms (Hypothesis 2). In sum, TWBCC and related markers were linked to depressive symptoms, mostly among women. Further longitudinal studies are needed to replicate this sex-specific association.
Serelaxin improves the therapeutic efficacy of RXFP1-expressing human amnion epithelial cells in experimental allergic airway disease
Authors: Royce Simon G. , Tominaga Anna M. , Shen Matthew , Patel Krupesh P. , Huuskes Brooke M. , Lim Rebecca , Ricardo Sharon D. , Samuel Chrishan S. 
Published: September 2016

Current asthma therapies primarily target airway inflammation (AI) and suppress episodes of airway hyperresponsiveness (AHR) but fail to treat airway remodelling (AWR), which can develop independently of AI and contribute to irreversible airway obstruction. The present study compared the anti-remodelling and therapeutic efficacy of human bone marrow-derived mesenchymal stem cells (MSCs) to that of human amnion epithelial stem cells (AECs) in the setting of chronic allergic airways disease (AAD), in the absence or presence of an anti-fibrotic (serelaxin; RLX). Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA)-induced chronic AAD, were either vehicle-treated (OVA alone) or treated with MSCs or AECs alone [intranasally (i.n.)-administered with 1×106 cells once weekly], RLX alone (i.n.-administered with 0.8 mg/ml daily) or a combination of MSCs or AECs and RLX from weeks 9–11 (n=6/group). Measures of AI, AWR and AHR were then assessed. OVA alone exacerbated AI, epithelial damage/thickness, sub-epithelial extracellular matrix (ECM) and total collagen deposition, markers of collagen turnover and AHR compared with that in saline-treated counterparts (all P&lt;0.01 compared with saline-treated controls). RLX or AECs (but not MSCs) alone normalized epithelial thickness and partially diminished the OVA-induced fibrosis and AHR by ∼40–50% (all P&lt;0.05 compared with OVA alone). Furthermore, the combination treatments normalized epithelial thickness, measures of fibrosis and AHR to that in normal mice, and significantly decreased AI. Although AECs alone demonstrated greater protection against the AAD-induced AI, AWR and AHR, compared with that of MSCs alone, combining RLX with MSCs or AECs reversed airway fibrosis and AHR to an even greater extent.
10 Mbps 0.3 nJ/bit OQPSK transceiver IC for 400–450 MHz medical telemetry
Authors: Jiang Hanjun , Weng Zhaoyang , Li Yang , Dong Jingjing , Rhee Woogeun , Wang Zhihua 
Published: September 2016

A 10 Mbps OQPSK transceiver working in the 400–450 MHz frequency range is designed for medical telemetry applications requiring wireless communication with both high data rate and low power consumption. An inverter based phase‐switching transmitter has been proposed to lower the transmitter power consumption. Moreover, a digital‐assisted DC offset calibration (DCOC) technique that combines the PGA‐gain‐uncorrelated DCOC method and a lookup table is adopted to enable an zero‐IF receiver architecture. Fabricated in 65 nm CMOS process, both the transmitter and the receiver consumes ∼3 mW from 1 V supply at 10 Mbps data rate. The transceiver energy efficiency is ∼0.3 nJ/bit, which outperforms the similar designs in recent literature.
Providing a “challenge function”: Government social researchers in the UK’s Department of Energy and Climate Change (2010–2015)
Authors: Kattirtzi Michael 
Published: September 2016

AbstractRecent research in Science and Technology Studies (STS) and related fields has scrutinized UK policy institutions’ governance of technical policy domains, revealing the prevalence of naïve assumptions about citizens’ engagement with science and technology. Government officials are characterized as wedded to institutional commitments and averse to criticism. From that perspective, technical policy issues such as energy and climate change are addressed without the sufficient interrogation of assumptions about citizens. This study, based on an analysis of 15 interviews with civil servants and over 40 documents (including evidence reviews, policy reports, stakeholder publications and parliamentary records), presents a more varied picture within the Department of Energy and Climate Change (DECC) during the years of the Conservative and Liberal Democrat Coalition Government (2010–2015). It focuses on two priority policy areas of the time: the Green Deal and the installation of smart meters in UK homes. It is shown that government social researchers in DECC have aided policy officials to rethink their understandings of citizens. Social researchers have achieved this through their institutionalized commitment to providing an evidence-based “challenge function”. I conclude that policy development on technical topics is more likely to be effective if policy officials engage with social researchers at an early stage, and if social researchers receive senior civil service representation and support. This article is published as part of a collection on scientific advice to governments.
Mechanical approach to chemical transport
Authors: Kocherginsky Nikolai , Gruebele Martin 
Published: September 2016

Significance
It is useful to have a systematic and simple framework to describe transport and equilibrium in chemical systems. Here, we present a general Lagrangian-based approach to describe transport phenomena, while remaining consistent with chemical thermodynamics. Although we neglect heat flow independent of transport, the ease with which transport and equilibrium relations can be derived for any type of driving factors (electromagnetic, thermal, pressure, surface tension, etc.) should make this approach useful in physics, chemistry, biophysics, engineering, and even economics and social sciences.
Direct brain recordings reveal hippocampal rhythm underpinnings of language processing
Authors: Piai Vitória , Anderson Kristopher L. , Lin Jack J. , Dewar Callum , Parvizi Josef , Dronkers Nina F. , Knight Robert T. 
Published: September 2016

Significance
Language is viewed as a predominantly perisylvian function typically studied in isolation from memory. We demonstrate that the same neuronal computations used by the hippocampus for memory function also subserve online language usage. Our findings specify that the hippocampal complex contributes to language in an active fashion, relating incoming words to stored semantic knowledge, a necessary process in the generation of sentence meaning. These findings represent a major step in integrating the studies of language and memory, significantly expanding the role of hippocampal theta oscillations and adding hippocampal structures to the neural network supporting language.
Ultradonut topology of the nuclear envelope
Authors: Torbati Mehdi , Lele Tanmay P. , Agrawal Ashutosh 
Published: September 2016

Significance
Lipid membranes exhibit a variety of morphologies tailored to perform specific functions of cells and their organelles. A unique lipid structure is the nuclear envelope which houses the genome and plays a vital role in genome organization and signaling pathways. The nuclear envelope is composed of two fused membranes with thousands of toroid-shaped pores with extremely high curvatures, the origin of which remains an open question in biology. Here, we show that the architecture of this “ultradonut” may be generated by nanoscale buckling instabilities triggered by membrane stresses during nuclei growth. Our findings may help understand the impact of membrane mechanics on the geometry and the functionality of the nucleus and more generally, other double-membrane organelles in cells.
Spin and valence dependence of iron partitioning in Earth’s deep mantle
Authors: Piet Hélène , Badro James , Nabiei Farhang , Dennenwaldt Teresa , Shim Sang-Heon , Cantoni Marco , Hébert Cécile , Gillet Philippe 
Published: September 2016

Significance
We studied high-pressure and high-temperature phase equilibria using state-of-the-art microanalytical techniques to measure iron partitioning and valence in iron-bearing lower-mantle rocks. Our data allow us to reconcile the discrepancies observed in previous reports, and to propose a comprehensive model of the evolution of iron partitioning in the lower mantle. We reveal an intricate interplay between spin and valence states. Our results suggest a mineral physics basis for rheological variations in the deep lower mantle as a process for stabilizing large thermochemical piles and large low-shear-velocity provinces.
Mechanism of inhibition of the tumor suppressor Patched by Sonic Hedgehog
Authors: Tukachinsky Hanna , Petrov Kostadin , Watanabe Miyako , Salic Adrian 
Published: September 2016

Significance
The Hedgehog-signaling pathway plays key roles in animal development and physiology. Insufficient Hedgehog signaling causes birth defects, whereas uncontrolled signaling is implicated in cancer. Signaling is triggered by the secreted protein, Sonic Hedgehog, which inhibits the membrane protein Patched1, leading to pathway activation. Despite its fundamental importance, we do not understand how Sonic Hedgehog inhibits Patched1. Here, we uncover a critical interaction between the fatty-acid–modified N-terminal portion of Sonic Hedgehog and Patched1, and we demonstrate that it is necessary and sufficient for Patched1 inhibition during Hedgehog signaling. This interaction explains impairment of a Sonic Hedgehog mutant causing a congenital brain malformation (holoprosencephaly) and oncogenic activity of Patched1 mutants responsible for a human cancer syndrome.
Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma
Authors: Zheng Hong , Dai Wei , Cheung Arthur Kwok Leung , Ko Josephine Mun Yee , Kan Rebecca , Wong Bonnie Wing Yan , Leong Merrin Man Long , Deng Mingdan , Kwok Tommy Chin Tung , Chan Jimmy Yu-Wai , Kwong Dora Lai-Wan , Lee Anne Wing-Mui , Ng Wai Tong , Ngan Roger Kai Cheong , Yau Chun Chung , Tung Stewart , Lee Victor Ho-fun , Lam Ka-On , Kwan Chung Kong , Li Wing Sum , Yau Stephen , Chan Kwok-Wah , Lung Maria Li 
Published: September 2016

SignificanceHost genetics, environmental factors, and EBV infection together contribute to nasopharyngeal carcinoma (NPC) development. A number of critical genetic and epigenetic events contributing to tumor development has been reported. However, the genomic alterations in NPC have not been completely deciphered. We used the whole-exome sequencing approach to study the somatic mutations in NPC, and an APOBEC-mediated mutagenesis signature was revealed. Importantly, multiple loss-of-function mutations in the NF-κB–negative regulators (NFKBIA,CYLD, andTNFAIP3) were discovered in NPC tumors, and we functionally confirmed that theNFKBIAloss-of-function mutations induce damaging effects on the WT proteins. Detection of these mutations emphasizes the critical role of NF-κB signaling in NPC tumorigenesis and provides perspectives for targeting this pathway in NPC treatment.
Calmodulin in complex with the first IQ motif of myosin-5a functions as an intact calcium sensor
Authors: Shen Mei , Zhang Ning , Zheng Sanduo , Zhang Wen-Bo , Zhang Hai-Man , Lu Zekuan , Su Qian Peter , Sun Yujie , Ye Keqiong , Li Xiang-dong 
Published: September 2016

Significance
Myosin-5a is a molecular motor that functions as a cargo transporter in cells. The motor function of myosin-5a is regulated by calcium via the calmodulin bound to the first isoleucine-glutamine (IQ) motif (IQ1) of myosin-5a. Here, we solve the crystal structure of a truncated myosin-5a containing the motor domain and the IQ1 complexed with calcium-bound calmodulin. Comparison of the structures of the IQ1 complexed with calmodulin with or without bound calcium reveals the calcium-induced conformational changes of calmodulin. We demonstrated that calmodulin continuously associates with the IQ1 during that calcium transition and that the IQ1 binding substantially changes the thermodynamic and kinetics of calcium transition in calmodulin. These findings provide insight into the mechanism by which calcium regulates myosin-5a.
Evaluation of a Long‐Term Predator Removal Program: Abundance and Population Dynamics of Invasive Northern Pike in the Yampa River, Colorado
Authors: Zelasko Koreen A. , Bestgen Kevin R. , Hawkins John A. , White Gary C. 
Published: September 2016

AbstractThe Northern Pike Esox lucius is invasive in the upper Green and Yampa River basins of Colorado and Utah and impedes endangered fish recovery in the upper Colorado River basin. Mechanical removal was implemented in 2004, but Northern Pike population dynamics and removal efficacy were not well understood. We analyzed mark–recapture records from 8,929 individual Northern Pike captured during 2004–2010 from three reaches of the Yampa River: Hayden to Craig (upstream reach), South Beach–Little Yampa Canyon–Juniper (middle reach), and Maybell–Sunbeam (downstream reach), encompassing 175 river kilometers. Annual survival rates for Northern Pike of the mean TL (465 mm) were highest downstream (mean = 0.54; range = 0.36–0.71) and lowest upstream (mean = 0.25; range = 0.12–0.38). Annual abundance exhibited the opposite pattern, as it was highest upstream (annual range = 1,144–4,078 fish) and lowest downstream (range = 232–746 fish). After removal occurred each year, Northern Pike abundance increased annually by nearly 1,000% in the upstream reach, over 875% in the middle reach, and over 375% in the downstream reach due to recruitment and immigration. Resulting densities were 4–58 times higher than those for a native apex predator, the endangered Colorado Pikeminnow Ptychocheilus lucius. Northern Pike movement was mostly (90%) downstream and sometimes extensive, which may have promoted establishment of additional populations. Removal rates were inadequate to reduce Northern Pike abundance in the Yampa River because recruitment and immigration exceeded removal and mortality. Investigation of reproduction and recruitment, along with source management, spawning disruption, and increased removal, are needed to further reduce Northern Pike abundance and to aid recovery of native and endangered fishes. These findings underscore the need for sustained, comprehensive, and often costly removal efforts—including evaluation of their effects—in the face of the expanding distribution and abundance of invasive predator species.Received April 16, 2015; accepted March 29, 2016Published online September 19, 2016
Production of high activity Aspergillus niger BCC4525 β-mannanase in Pichia pastoris and its application for mannooligosaccharides production from biomass hydrolysis
Authors: Harnpicharnchai Piyanun , Pinngoen Waraporn , Teanngam Wanwisa , Sornlake Warasirin , Sae-Tang Kittapong , Manitchotpisit Pennapa , Tanapongpipat Sutipa 
Published: September 2016

Abstract
A cDNA encoding β-mannanase was cloned from Aspergillus niger BCC4525 and expressed in Pichia pastoris KM71. The secreted enzyme hydrolyzed locust bean gum substrate with very high activity (1625 U/mL) and a relatively high kcat/Km (461 mg−1 s−1 mL). The enzyme is thermophilic and thermostable with an optimal temperature of 70 °C and 40% retention of endo-β-1,4-mannanase activity after preincubation at 70 °C. In addition, the enzyme exhibited broad pH stability with an optimal pH of 5.5. The recombinant enzyme hydrolyzes low-cost biomass, including palm kernel meal (PKM) and copra meal, to produce mannooligosaccharides, which is used as prebiotics to promote the growth of beneficial microflora in animals. An in vitro digestibility test simulating the gastrointestinal tract system of broilers suggested that the recombinant β-mannanase could effectively liberate reducing sugars from PKM-containing diet. These characteristics render this enzyme suitable for utilization as a feed additive to improve animal performance.
Final report on COOMET supplementary comparison of inductance at 10 mH and 100 mH at 1 kHz (COOMET.EM-S14)
Authors: Velychko O , Shevkun S 
Published: September 2016

An inter-comparison of 10 mH and 100 mH inductance standards has taken place within the framework of COOMET. The inter-comparison, piloted by State Enterprise 'Ukrmetrteststandard'-UMTS (Ukraine), has involved four laboratories, including one who is a member of another regional metrological organization - EURAMET (GUM, Poland). The results presented in this report show that there are significant differences between some laboratory representations of the henry. However, the agreement demonstrated by the inter-comparison provides confidence in maintaining traceability for the henry.
KEY WORDS FOR SEARCH
Inter-comparison, inductance standard, traceability, regional metrological organization

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.
The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Key comparison SIM.EM.RF-K5b.CL: scattering coefficients by broad-band methods, 2 GHz–18 GHz — type N connector
Authors: Silva H , Monasterios G 
Published: September 2016

The first key comparison in microwave frequencies within the SIM (Sistema Interamericano de Metrología) region has been carried out. The measurands were the S-parameters of 50 ohm coaxial devices with Type-N connectors and were measured at 2 GHz, 9 GHz and 18 GHz. SIM.EM.RF-K5b.CL was the identification assigned and it was based on a parent CCEM key comparison named CCEM.RF-K5b.CL. For this reason, the measurements standards and their nominal values were selected accordingly, i.e. two one-port devices (a matched and a mismatched load) to cover low and high reflection coefficients and two attenuators (3dB and 20 dB) to cover low and high transmission coefficients. This key comparison has met the need for ensuring traceability in high-frequency measurements across America by linking SIM's results to CCEM. Six NMIs have participated in this comparison which was piloted by the Instituto Nacional de Tecnología Industrial (Argentina). A linking method of multivariate values was proposed and implemented in order to allow the linking of 2-dimensional results.
KEY WORDS FOR SEARCH

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.
The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).