bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Multimeter at the Nanoscale
Authors: Voigtländer Bert , Cherepanov Vasily , Coenen Peter 
Published: June 2016

AbstractA multi‐tip scanning tunneling microscope (STM) specifically designed for charge transport measurements at the nanoscale is described. Complementing the instrument with a versatile measurement electronics creates a powerful tool to give insight into fundamental transport properties at the nanoscale. We demonstrate the capabilities of the instrument by measuring resistance profiles along freestanding GaAs nanowires, by the acquisition of nanoscale potential maps, and by the identification of an anisotropy in the surface conductivity at a silicon surface.
Magnetic Resonance Imaging in Patients with Mechanical Low Back Pain Using a Novel Rapid-Acquisition Three-Dimensional SPACE Sequence at 1.5-T: A Pilot Study Comparing Lumbar Stenosis Assessment with Routine Two-Dimensional Magnetic Resonance Sequences
Authors: Swami Vimarsha G. , Katlariwala Mihir , Dhillon Sukhvinder , Jibri Zaid , Jaremko Jacob L. 
Published: May 2016

Purpose To minimize the burden of overutilisation of lumbar spine magnetic resonance imaging (MRI) on a resource-constrained public healthcare system, it may be helpful to image some patients with mechanical low-back pain (LBP) using a simplified rapid MRI screening protocol at 1.5-T. A rapid-acquisition 3-dimensional (3D) SPACE (Sampling Perfection with Application-optimized Contrasts using different flip angle Evolution) sequence can demonstrate common etiologies of LBP. We compared lumbar spinal canal stenosis (LSCS) and neural foraminal stenosis (LNFS) assessment on 3D SPACE against conventional 2-dimensional (2D) MRI. Methods We prospectively performed 3D SPACE and 2D spin-echo MRI sequences (axial or sagittal T1-weighted or T2-weighted) at 1.5-T in 20 patients. Two blinded readers assessed levels L3-4, L4-5 and L5-S1 using: 1) morphologic grading systems, 2) global impression on the presence or absence of clinically significant stenosis (n = 60 disc levels for LSCS, n = 120 foramina for LNFS). Reliability statistics were calculated. Results Acquisition time was ∼5 minutes for SPACE and ∼20 minutes for 2D MRI sequences. Interobserver agreement of LSCS was substantial to near perfect on both sequences (morphologic grading: kappa [k] = 0.71 SPACE, k = 0.69 T2-weighted; global impression: k = 0.85 SPACE, k = 0.78 T2-weighted). LNFS assessment had superior interobserver reliability using SPACE than T1-weighted (k = 0.54 vs 0.37). Intersequence agreement of findings between SPACE and 2D MRI was substantial to near perfect by global impression (LSCS: k = 0.78 Reader 1, k = 0.85 Reader 2; LNFS: k = 0.63 Reader 1, k = 0.66 Reader 2). Conclusions 3D SPACE was acquired in one-quarter the time as the conventional 2D MRI protocol, had excellent agreement with 2D MRI for stenosis assessment, and had interobserver reliability superior to 2D MRI. These results justify future work to explore the role of 3D SPACE in a rapid MRI screening protocol at 1.5-T for mechanical LBP.
Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders
Authors: Kaminsky Natalie , Bihari Ofer , Kanner Sivan , Barzilai Ari 
Published: May 2016

Abstract
The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a “hostile” environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.
Functions of PARylation in DNA Damage Repair Pathways
Authors: Wei Huiting , Yu Xiaochun 
Published: May 2016

Abstract
Protein poly ADP-ribosylation (PARylation) is a widespread post-translational modification at DNA lesions, which is catalyzed by poly(ADP-ribose) polymerases (PARPs). This modification regulates a number of biological processes including chromatin reorganization, DNA damage response (DDR), transcriptional regulation, apoptosis, and mitosis. PARP1, functioning as a DNA damage sensor, can be activated by DNA lesions, forming PAR chains that serve as a docking platform for DNA repair factors with high biochemical complexity. Here, we highlight molecular insights into PARylation recognition, the expanding role of PARylation in DDR pathways, and the functional interaction between PARylation and ubiquitination, which will offer us a better understanding of the biological roles of this unique post-translational modification.
DNA End Resection: Facts and Mechanisms
Authors: Liu Ting , Huang Jun 
Published: May 2016

Abstract
DNA double-strand breaks (DSBs), which arise following exposure to a number of endogenous and exogenous agents, can be repaired by either the homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways in eukaryotic cells. A vital step in HR repair is DNA end resection, which generates a long 3′ single-stranded DNA (ssDNA) tail that can invade the homologous DNA strand. The generation of 3′ ssDNA is not only essential for HR repair, but also promotes activation of the ataxia telangiectasia and Rad3-related protein (ATR). Multiple factors, including the MRN/X complex, C-terminal-binding protein interacting protein (CtIP)/Sae2, exonuclease 1 (EXO1), Bloom syndrome protein (BLM)/Sgs1, DNA2 nuclease/helicase, and several chromatin remodelers, cooperate to complete the process of end resection. Here we review the basic machinery involved in DNA end resection in eukaryotic cells.
Direct versus indirect climate controls on Holocene diatom assemblages in a sub-tropical deep, alpine lake (Lugu Hu, Yunnan, SW China)
Authors: Wang Qian , Yang Xiangdong , Anderson Nicholas John , Dong Xuhui 
Published: May 2016

AbstractThe reconstruction of Holocene environmental changes in lakes on the plateau region of southwest China provides an understanding of how these ecosystems may respond to climate change. Fossil diatom assemblages were investigated from an 11,000-year lake sediment core from a deep, alpine lake (Lugu Hu) in southwest China, an area strongly influenced by the southwest (or the Indian) summer monsoon. Changes in diatom assemblage composition, notably the abundance of the two dominant planktonic species, Cyclotella rhomboideo-elliptica and Cyclostephanos dubius, reflect the effects of climate variability on nutrient dynamics, mediated via thermal stratification (internal nutrient cycling) and catchment-vegetation processes. Statistical analyses of the climateediatom interactions highlight the strong effect of changing orbitally-induced solar radiation during the Holocene, presumably via its effect on the lake’s thermal budget. In a partial redundancy analysis, climate (solar insolation) and proxies reflecting catchment process (pollen percentages, C/N ratio) were the most important drivers of diatom ecological change, showing the strong effects of climateecatchmentevegetation interactions on lake functioning. This diatom record reflects long-term ontogeny of the lake-catchment ecosystem and suggests that climatic changes (both temperature and precipitation) impact lake ecology indirectly through shifts in thermal stratification and catchment nutrient exports.
Rethinking format: An examination of requests
Authors: Fox Barbara , Heinemann Trine 
Published: June 2016

AbstractThis study explores the formulation of requests in an American English-speaking shoe repair shop. Taking prior work on request formats as our starting point, we explore the two primary syntactic moods (declarative and interrogative) in our collection and two of the commonly noted subtypes of these moods,need/want-declaratives andcan-interrogatives. While our findings in very general terms match those of previous studies, we also find significant grammatical variation within each of these formats, and note interactional uses for each variation. Our examination yields insight into facets of requesting that were previously undescribed. We offer an Emergent Grammar perspective on the complexity of lexicosyntax in the social action of requesting. (Requests, formats, Emergent Grammar, Conversation Analysis, American English, service encounters)*
Validation of an instrument to measure registered dietitians’/nutritionists’ knowledge, attitudes and practices of an intuitive eating approach
Authors: Schaefer Julie T , Zullo Melissa D 
Published: June 2016

AbstractObjectiveThe purpose of the present study was to develop and assess the construct validity of a tool to measure knowledge, attitudes and practices of registered dietitians/nutritionists (RD/N) regarding an intuitive eating lifestyle.DesignCross-sectional study design that utilized a survey administered to a random sample and remaining full population of RD/N.SettingA national survey conducted via online survey software.SubjectsA random sample of 10 % of all RD/N in the USA (n8834) was invited to participate. Survey completion rate was 22·2 % (n1897). After initial validation, the survey was distributed to the remaining 90 % of RD/N to confirm validation.ResultsAfter removing items with insufficient factor loadings, results were consistent with a four-factor solution: (i) knowledge of intuitive eating; (ii) attitudes towards intuitive eating; (iii) traditional and restrictive practices; and (iv) non-restrictive and intuitive eating practices. Confirmatory factor analysis provided further evidence of the validity of the four factors and the factors had strong reliability.ConclusionsUnlike the hypothesized three-factor solution (knowledge, attitudes and practices), validation analysis revealed that the survey measures knowledge of intuitive eating, attitudes towards intuitive eating, use of traditional and restrictive weight-management practices, and use of non-restrictive and intuitive eating practices. With the landscape of weight management and health promotion undergoing a shift towards a health centred, size acceptance approach, this instrument will provide valuable information regarding the current knowledge, attitudes and practices of RD/N and other health promotion professionals.
An adapted imaginal exposure approach to traditional methods used within trauma-focused cognitive behavioural therapy, trialled with a veteran population
Authors: Kaur Manveer , Murphy Dominic , Smith Kirsten V. 
Published: June 2016

AbstractTrauma-focused cognitive behavioural therapy (TF-CBT) is beneficial for individuals with post-traumatic stress disorder (PTSD); however, a subset of clients struggle to engage with traditional methods, due to high levels of avoidance and dissociation. This paper aims to describe an adapted approach to imaginal reliving and prolonged exposure, to facilitate subsequent cognitive updating. The paper demonstrates the technique with veterans, who are a client group that may struggle with some aspects of traditionally implemented TF-CBT. Two case studies are described, both with PTSD symptoms stemming from traumatic military experiences. An adapted exposure technique is utilized to address the barriers of high dissociation, poor access to trauma-related cognitions and fixed intrusive imagery. The approach involved three stages: (1) reliving the trauma outdoors, (2) manipulating the perspectives of the imagery, and (3) restructuring the narrative with new perspectives. Both clients showed decreased dissociation and improved toleration of their traumatic imagery. Improvement of PTSD symptoms and quality-of-life functioning was observed for both clients on objective measures. Adapting TF-CBT to have a stronger emphasis on grounding and allocentric processing may be helpful for a subset of patients with PTSD that present with high levels of dissociation and avoidance. Further research and investigation into alternative populations is needed.
Suppressor of IKKɛ is an essential negative regulator of pathological cardiac hypertrophy
Authors: Deng Ke-Qiong , Wang Aibing , Ji Yan-Xiao , Zhang Xiao-Jing , Fang Jing , Zhang Yan , Zhang Peng , Jiang Xi , Gao Lu , Zhu Xue-Yong , Zhao Yichao , Gao Lingchen , Yang Qinglin , Zhu Xue-Hai , Wei Xiang , Pu Jun , Li Hongliang 
Published: June 2016

AbstractAlthough pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide, our understanding of the molecular mechanisms underlying this disease is still poor. Here, we demonstrate that suppressor of IKKɛ (SIKE), a negative regulator of the interferon pathway, attenuates pathological cardiac hypertrophy in rodents and non-human primates in a TANK-binding kinase 1 (TBK1)/AKT-dependent manner. Sike-deficient mice develop cardiac hypertrophy and heart failure, whereas Sike-overexpressing transgenic (Sike-TG) mice are protected from hypertrophic stimuli. Mechanistically, SIKE directly interacts with TBK1 to inhibit the TBK1-AKT signalling pathway, thereby achieving its anti-hypertrophic action. The suppression of cardiac remodelling by SIKE is further validated in rats and monkeys. Collectively, these findings identify SIKE as a negative regulator of cardiac remodelling in multiple animal species due to its inhibitory regulation of the TBK1/AKT axis, suggesting that SIKE may represent a therapeutic target for the treatment of cardiac hypertrophy and heart failure.
Characterizing the boundary lateral to the shear direction of deformation twins in magnesium
Authors: Liu Y. , Li N. , Shao S. , Gong M. , Wang J. , McCabe R. J. , Jiang Y. , Tomé C. N. 
Published: June 2016

AbstractThe three-dimensional nature of twins, especially the atomic structures and motion mechanisms of the boundary lateral to the shear direction of the twin, has never been characterized at the atomic level, because such boundary is, in principle, crystallographically unobservable. We thus refer to it here as the dark side of the twin. Here, using high-resolution transmission electron microscopy and atomistic simulations, we characterize the dark side of "Equation missing" deformation twins in magnesium. It is found that the dark side is serrated and comprised of "Equation missing" coherent twin boundaries and semi-coherent twist prismatic–prismatic "Equation missing" boundaries that control twin growth. The conclusions of this work apply to the same twin mode in other hexagonal close-packed materials, and the conceptual ideas discussed here should hold for all twin modes in crystalline materials.
Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10
Authors: Yang Wang-Yong , Gao Rui , Southern Mark , Sarkar Partha S. , Disney Matthew D. 
Published: June 2016

AbstractRNA is an important target for chemical probes of function and lead therapeutics; however, it is difficult to target with small molecules. One approach to tackle this problem is to identify compounds that target RNA structures and utilize them to multivalently target RNA. Here we show that small molecules can be identified to selectively bind RNA base pairs by probing a library of RNA-focused small molecules. A small molecule that selectively binds AU base pairs informed design of a dimeric compound (2AU-2) that targets the pathogenic RNA, expanded r(AUUCU) repeats, that causes spinocerebellar ataxia type 10 (SCA10) in patient-derived cells. Indeed, 2AU-2 (50 nM) ameliorates various aspects of SCA10 pathology including improvement of mitochondrial dysfunction, reduced activation of caspase 3, and reduction of nuclear foci. These studies provide a first-in-class chemical probe to study SCA10 RNA toxicity and potentially define broadly applicable compounds targeting RNA AU base pairs in cells.
Fast escape of a quantum walker from an integrated photonic maze
Authors: Caruso Filippo , Crespi Andrea , Ciriolo Anna Gabriella , Sciarrino Fabio , Osellame Roberto 
Published: June 2016

AbstractEscaping from a complex maze, by exploring different paths with several decision-making branches in order to reach the exit, has always been a very challenging and fascinating task. Wave field and quantum objects may explore a complex structure in parallel by interference effects, but without necessarily leading to more efficient transport. Here, inspired by recent observations in biological energy transport phenomena, we demonstrate how a quantum walker can efficiently reach the output of a maze by partially suppressing the presence of interference. In particular, we show theoretically an unprecedented improvement in transport efficiency for increasing maze size with respect to purely quantum and classical approaches. In addition, we investigate experimentally these hybrid transport phenomena, by mapping the maze problem in an integrated waveguide array, probed by coherent light, hence successfully testing our theoretical results. These achievements may lead towards future bio-inspired photonics technologies for more efficient transport and computation.
Observation of coherent delocalized phonon-like modes in DNA under physiological conditions
Authors: González-Jiménez Mario , Ramakrishnan Gopakumar , Harwood Thomas , Lapthorn Adrian J. , Kelly Sharon M. , Ellis Elizabeth M. , Wynne Klaas 
Published: June 2016

AbstractUnderdamped terahertz-frequency delocalized phonon-like modes have long been suggested to play a role in the biological function of DNA. Such phonon modes involve the collective motion of many atoms and are prerequisite to understanding the molecular nature of macroscopic conformational changes and related biochemical phenomena. Initial predictions were based on simple theoretical models of DNA. However, such models do not take into account strong interactions with the surrounding water, which is likely to cause phonon modes to be heavily damped and localized. Here we apply state-of-the-art femtosecond optical Kerr effect spectroscopy, which is currently the only technique capable of taking low-frequency (GHz to THz) vibrational spectra in solution. We are able to demonstrate that phonon modes involving the hydrogen bond network between the strands exist in DNA at physiologically relevant conditions. In addition, the dynamics of the solvating water molecules is slowed down by about a factor of 20 compared with the bulk.
Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain
Authors: Kanju Patrick , Chen Yong , Lee Whasil , Yeo Michele , Lee Suk Hee , Romac Joelle , Shahid Rafiq , Fan Ping , Gooden David M. , Simon Sidney A. , Spasojevic Ivan , Mook Robert A. , Liddle Rodger A. , Guilak Farshid , Liedtke Wolfgang B. 
Published: June 2016

AbstractTRPV4 ion channels represent osmo-mechano-TRP channels with pleiotropic function and wide-spread expression. One of the critical functions of TRPV4 in this spectrum is its involvement in pain and inflammation. However, few small-molecule inhibitors of TRPV4 are available. Here we developed TRPV4-inhibitory molecules based on modifications of a known TRPV4-selective tool-compound, GSK205. We not only increased TRPV4-inhibitory potency, but surprisingly also generated two compounds that potently co-inhibit TRPA1, known to function as chemical sensor of noxious and irritant signaling. We demonstrate TRPV4 inhibition by these compounds in primary cells with known TRPV4 expression - articular chondrocytes and astrocytes. Importantly, our novel compounds attenuate pain behavior in a trigeminal irritant pain model that is known to rely on TRPV4 and TRPA1. Furthermore, our novel dual-channel blocker inhibited inflammation and pain-associated behavior in a model of acute pancreatitis – known to also rely on TRPV4 and TRPA1. Our results illustrate proof of a novel concept inherent in our prototype compounds of a drug that targets two functionally-related TRP channels, and thus can be used to combat isoforms of pain and inflammation in-vivo that involve more than one TRP channel. This approach could provide a novel paradigm for treating other relevant health conditions.
Kennicutt-Schmidt Law in the Central Region of NGC 4321 as Seen by ALMA
Authors: Azeez Jazeel H. , Hwang C.-Y. , Abidin Zamri Z. , Ibrahim Zainol A. 
Published: June 2016

AbstractWe present the Atacama Large Millimeter/Sub-millimeter Array (ALMA) cycle-0 science verification data of the CO(1–0) line emission in the central region of NGC 4321 (also known as M100) at the distance of 17.1 Mpc and VLA, L-band data of HI of the same galaxy. We have drawn the center area of M100 in the 12CO(J = 1–0) line with the resolution of (3.87″ × 2.53″) as viewed by ALMA, along with HI and Spitzer 8 and 3.6 μm data. The relationship between the surface density of molecular gas mass ∑H2 and that of star formation rate ∑SFR has been investigated, in addition to the relationship between the surface density of the neutral atomic hydrogen mass and that of ∑SFR (Kennicutt–Schmidt law) in this galaxy with a high spatial resolution. The results indicate that a significant correlation exists between the SFR surface density and the molecular gas mass density in the ~2 kpc region. The power-law index has been determined for three regions: center, upper and lower arms. The value of this index in the center region is 1.13, which follows the traditional (K-S) law and indicates that the molecular gas is affected by star formation.
Polycomb Group Protein Pcgf6 Acts as a Master Regulator to Maintain Embryonic Stem Cell Identity
Authors: Yang Chao-Shun , Chang Kung-Yen , Dang Jason , Rana Tariq M. 
Published: June 2016

AbstractThe polycomb repressive complex 1 (PRC1) is a multi-subunit complex that plays critical roles in the epigenetic modulation of gene expression. Here, we show that the PRC1 component polycomb group ring finger 6 (Pcgf6) is required to maintain embryonic stem cell (ESC) identity. In contrast to canonical PRC1, Pcgf6 acts as a positive regulator of transcription and binds predominantly to promoters bearing active chromatin marks. Pcgf6 is expressed at high levels in ESCs, and knockdown reduces the expression of the core ESC regulators Oct4, Sox2, and Nanog. Conversely, Pcgf6 overexpression prevents downregulation of these factors and impairs differentiation. In addition, Pcgf6 enhanced reprogramming in both mouse and human somatic cells. The genomic binding profile of Pcgf6 is highly similar to that of trithorax group proteins, but not of PRC1 or PRC2 complexes, suggesting that Pcgf6 functions atypically in ESCs. Our data reveal novel roles for Pcgf6 in directly regulating Oct4, Nanog, Sox2, and Lin28 expression to maintain ESC identity.