bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target
Authors: Chiba Shuntaro , Ikeda Kazuyoshi , Ishida Takashi , Gromiha M. Michael , Taguchi Y-h. , Iwadate Mitsuo , Umeyama Hideaki , Hsin Kun-Yi , Kitano Hiroaki , Yamamoto Kazuki , Sugaya Nobuyoshi , Kato Koya , Okuno Tatsuya , Chikenji George , Mochizuki Masahiro , Yasuo Nobuaki , Yoshino Ryunosuke , Yanagisawa Keisuke , Ban Tomohiro , Teramoto Reiji , Ramakrishnan Chandrasekaran , Thangakani A. Mary , Velmurugan D. , Prathipati Philip , Ito Junichi , Tsuchiya Yuko , Mizuguchi Kenji , Honma Teruki , Hirokawa Takatsugu , Akiyama Yutaka , Sekijima Masakazu 
Published: November 2015

AbstractA search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective.
Formation of Nanotwin Networks during High-Temperature Crystallization of Amorphous Germanium
Authors: Sandoval Luis , Reina Celia , Marian Jaime 
Published: November 2015

AbstractGermanium is an extremely important material used for numerous functional applications in many fields of nanotechnology. In this paper, we study the crystallization of amorphous Ge using atomistic simulations of critical nano-metric nuclei at high temperatures. We find that crystallization occurs by the recurrent transfer of atoms via a diffusive process from the amorphous phase into suitably-oriented crystalline layers. We accompany our simulations with a comprehensive thermodynamic and kinetic analysis of the growth process, which explains the energy balance and the interfacial growth velocities governing grain growth. For the 〈111〉 crystallographic orientation, we find a degenerate atomic rearrangement process, with two zero-energy modes corresponding to a perfect crystalline structure and the formation of a Σ3 twin boundary. Continued growth in this direction results in the development a twin network, in contrast with all other growth orientations, where the crystal grows defect-free. This particular mechanism of crystallization from amorphous phases is also observed during solid-phase epitaxial growth of 〈111〉 semiconductor crystals, where growth is restrained to one dimension. We calculate the equivalent X-ray diffraction pattern of the obtained nanotwin networks, providing grounds for experimental validation.
A chimeolysin with extended-spectrum streptococcal host range found by an induced lysis-based rapid screening method
Authors: Yang Hang , Linden Sara B. , Wang Jing , Yu Junping , Nelson Daniel C. , Wei Hongping 
Published: November 2015

AbstractThe increasing emergence of multi-drug resistant streptococci poses a serious threat to public health worldwide. Bacteriophage lysins are promising alternatives to antibiotics; however, their narrow lytic spectrum restricted to closely related species is a central shortcoming to their translational development. Here, we describe an efficient method for rapid screening of engineered chimeric lysins and report a unique “chimeolysin”, ClyR, with robust activity and an extended-spectrum streptococcal host range against most streptococcal species, including S. pyogenes, S. agalactiae, S. dysgalactiae, S. equi, S. mutans, S. pneumoniae, S. suis and S. uberis, as well as representative enterococcal and staphylococcal species (including MRSA and VISA). ClyR is the first lysin that demonstrates activity against the dominant dental caries-causing pathogen as well as the first lysin that kills all four of the bovine mastitis-causing pathogens. This study demonstrates the success of the screening method resulting in a powerful lysin with potential for treating most streptococcal associated infections.
The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines
Authors: Canham Maurice A. , Van Deusen Amy , Brison Daniel R. , De Sousa Paul A. , Downie Janet , Devito Liani , Hewitt Zoe A. , Ilic Dusko , Kimber Susan J. , Moore Harry D. , Murray Helen , Kunath Tilo 
Published: November 2015

AbstractThe application of human embryonic stem cell (hESC) derivatives to regenerative medicine is now becoming a reality. Although the vast majority of hESC lines have been derived for research purposes only, about 50 lines have been established under Good Manufacturing Practice (GMP) conditions. Cell types differentiated from these designated lines may be used as a cell therapy to treat macular degeneration, Parkinson’s, Huntington’s, diabetes, osteoarthritis and other degenerative conditions. It is essential to know the genetic stability of the hESC lines before progressing to clinical trials. We evaluated the molecular karyotype of 25 clinical-grade hESC lines by whole-genome single nucleotide polymorphism (SNP) array analysis. A total of 15 unique copy number variations (CNVs) greater than 100 kb were detected, most of which were found to be naturally occurring in the human population and none were associated with culture adaptation. In addition, three copy-neutral loss of heterozygosity (CN-LOH) regions greater than 1 Mb were observed and all were relatively small and interstitial suggesting they did not arise in culture. The large number of available clinical-grade hESC lines with defined molecular karyotypes provides a substantial starting platform from which the development of pre-clinical and clinical trials in regenerative medicine can be realised.
Identification of a novel cathelicidin antimicrobial peptide from ducks and determination of its functional activity and antibacterial mechanism
Authors: Gao Wei , Xing Liwei , Qu Pei , Tan Tingting , Yang Na , Li Dan , Chen Huixian , Feng Xingjun 
Published: November 2015

AbstractThe family of antimicrobial peptide, cathelicidins, which plays important roles against infections in animals, has been identified from many species. Here, we identified a novel avian cathelicidin ortholog from ducks and named dCATH. The cDNA sequence of dCATH encodes a predicted 146-amino-acid polypeptide composed of a 17-residue signal peptide, a 109-residue conserved cathelin domain and a 20-residue mature peptide. Phylogenetic analysis demonstrated that dCATH is highly divergent from other avian peptides. The α-helical structure of the peptide exerted strong antimicrobial activity against a broad range of bacteria in vitro, with most minimum inhibitory concentrations in the range of 2 to 4 μM. Moreover, dCATH also showed cytotoxicity, lysing 50% of mammalian erythrocytes in the presence or absence of 10% fetal calf serum at concentrations of 32 μM or 20 μM and killing 50% HaCaT cells at a concentration of 10 μM. The effects on bacterial outer and inner membranes, as examined by scanning electron microscope and transmission electron microscopy, indicate that dCATH kills microbial cells by increasing permeability, causing a loss of membrane integrity.
A community split among dolphins: the effect of social relationships on the membership of new communities
Authors: Nishita Miki , Shirakihara Miki , Amano Masao 
Published: November 2015

AbstractLittle is known about community splitting among dolphins because such events are rare in dolphin populations. A case of a community split was confirmed in a population of Indo-Pacific bottlenose dolphins (Tursiops aduncus) in Japan, where a group of approximately 30 dolphins moved to a new habitat some 60 km from the original habitat. We examined the associations among the dolphins before the community split to determine whether the new community members were already socially different before the split, using 7-year identification data. Before the split, the males in the same community after the split more often associated with each other than they did with those in different community. In contrast, the association patterns among females and between sexes showed no relationships with their post-split community membership. These results indicate that the males of new community were socially different from the other males for a long time before the split, but the females might not have been different. Our findings suggest that at time of the community split, the factors determining the memberships of the subsequent communities are sex-linked. The long-term social relationships among males could be maintained in the subsequent communities.
In-depth proteomic analysis of shell matrix proteins of Pinctada fucata
Authors: Liu Chuang , Li Shiguo , Kong Jingjing , Liu Yangjia , Wang Tianpeng , Xie Liping , Zhang Rongqing 
Published: November 2015

AbstractThe shells of pearl oysters, Pinctada fucata, are composed of calcite and aragonite and possess remarkable mechanical properties. These shells are formed under the regulation of macromolecules, especially shell matrix proteins (SMPs). Identification of diverse SMPs will lay a foundation for understanding biomineralization process. Here, we identified 72 unique SMPs using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of proteins extracted from the shells of P. fucata combined with a draft genome. Of 72 SMPs, 17 SMPs are related to both the prismatic and nacreous layers. Moreover, according to the diverse domains found in the SMPs, we hypothesize that in addition to controlling CaCO3 crystallization and crystal organization, these proteins may potentially regulate the extracellular microenvironment and communicate between cells and the extracellular matrix (ECM). Immunohistological localization techniques identify the SMPs in the mantle, shells and synthetic calcite. Together, these proteomic data increase the repertoires of the shell matrix proteins in P. fucata and suggest that shell formation in P. fucata may involve tight regulation of cellular activities and the extracellular microenvironment.
The distribution and characteristics of LDL receptor mutations in China: A systematic review
Authors: Jiang Long , Sun Li-Yuan , Dai Yan-Fang , Yang Shi-Wei , Zhang Feng , Wang Lu-Ya 
Published: November 2015

AbstractFamilial hypercholesterolemia (FH) is a common and serious dominant genetic disease and its main pathogenic gene is the low-density lipoprotein receptor (LDLR) gene. This study aimed to perform a systematic review of LDLR mutations in China. Using PubMed, Embase, Wanfang (Chinese), the Chinese National Knowledge Infrastructure (Chinese) and the Chinese Biological and Medical database (Chinese), public data were limited to December 2014. The Medical Subject Headings terms and the following key words were used: “familial hypercholesterolemia”, “Chinese”, “China”, “Hong Kong” and “Taiwan”. A total of 74 studies including 295 probands with 131 LDLR mutations were identified. Most of the mutations were located in exon 4 of LDLR and approximately 60% of the mutations were missense mutations. Thirty new mutations that were not recorded in the LDLR databases were found. In silico analysis revealed that most of the mutations were pathogenic. The primary LDLR mutations were C308Y, H562Y and A606T and all of the mutations had functional significance. Prevalence data suggest that there are nearly 3.8 million FH patients in China, although reported numbers are much smaller, suggesting that FH is widely misunderstood. This systematic review provides information that is specific to China for inclusion in the international FH database.
Enhancing Localized Evaporation through Separated Light Absorbing Centers and Scattering Centers
Authors: Zhao Dengwu , Duan Haoze , Yu Shengtao , Zhang Yao , He Jiaqing , Quan Xiaojun , Tao Peng , Shang Wen , Wu Jianbo , Song Chengyi , Deng Tao 
Published: November 2015

AbstractThis report investigates the enhancement of localized evaporation via separated light absorbing particles (plasmonic absorbers) and scattering particles (polystyrene nanoparticles). Evaporation has been considered as one of the most important phase-change processes in modern industries. To improve the efficiency of evaporation, one of the most feasible methods is to localize heat at the top water layer rather than heating the bulk water. In this work, the mixture of purely light absorptive plasmonic nanostructures such as gold nanoparticles and purely scattering particles (polystyrene nanoparticles) are employed to confine the incident light at the top of the solution and convert light to heat. Different concentrations of both the light absorbing centers and the light scattering centers were evaluated and the evaporation performance can be largely enhanced with the balance between absorbing centers and scattering centers. The findings in this study not only provide a new way to improve evaporation efficiency in plasmonic particle-based solution, but also shed lights on the design of new solar-driven localized evaporation systems.
Fitting Proportional Odds Model to Case-Control data with Incorporating Hardy-Weinberg Equilibrium
Authors: Zhang Wei , Zhang Zehui , Li Xinmin , Li Qizhai 
Published: November 2015

AbstractGenetic association studies have been proved to be an efficient tool to reveal the aetiology of many human complex diseases and traits. When the phenotype is binary, the logistic regression model is commonly employed to evaluate the association strength of the genetic variants predispose to human diseases because the maximum likelihood estimator of the odds ratio based on case-control data is equivalent to that from the same model by taking the data as being arisen prospectively. This equivalence does not hold for the proportional odds model and using it to analyze the case-control data directly often results in a substantial bias. Through putting a parameter of the minor allele frequency in the modified likelihood function under the condition that the Hardy-Weinberg equilibrium law holds within controls, a consistent estimator is obtained. On the basis of it, we construct a score test statistic to test whether the genetic variant is associated with the diseases. Simulation studies show that the proposed estimator has smaller mean squared error than the existing methods when the genetic effect size is away from zero and the proposed test statistic has a good control of type I error rate and is more powerful than the existing procedures. Application to 45 single nucleotide polymorphisms located in the region of TRAF1-C5 genes for the association with four-level anticyclic citrullinated protein antibody from Genetic Analysis Workshop 16 further demonstrates its performance.
Demonstrating 1 nm‐oxide‐equivalent‐thickness La2O3 and HfO2 multi‐layer composite oxides on In0.53Ga0.47As MOS capacitor
Authors: Wu Wen‐Hao , Lin Yueh‐Chin , Hou Tzu‐Ching , Lin Tai‐Wei , Hsu Hisang‐Hua , Wong Yuen‐Yee , Iwai Hiroshi , Kakushima Kuniyuki , Chang Edward Yi 
Published: November 2015

The use of a high k composite dielectric composed of La2O3 and HfO2 layers as the gate dielectric for In0.53Ga0.47As MOS application is proposed. Two multi‐layer structures of La2O3 (1 nm)/HfO2 (1 nm) and La2O3 (0.5 nm)/HfO2 (0.5 nm) were deposited and annealed at 450 and 500°C for device performance comparison. X‐ray photoelectron spectroscopy, TEM and C–V measurements were used for the interface analysis between the oxide and the semiconductor. Finally, a 1 nm equivalent‐oxide‐thickness dielectric with small hysteresis of 88 mV and Dit of 1.9 × 1012 cm−2 eV−1 was achieved for six layers of an La2O3 (0.5 nm)/HfO2 (0.5 nm) composite oxide structure on an In0.53Ga0.47As MOS capacitor with a post‐deposition annealing temperature of 450°C.
Wideband out‐of‐phase power divider using tightly coupled lines and microstrip to slotline transitions
Authors: Ahmed U.T. , Abbosh A.M. 
Published: November 2015

A broadband out‐of‐phase power divider in a compact structure employing a microstrip technology is presented. The proposed power divider consists of a T‐junction of microstrip to slotline transition at the input ports along with a pair of tightly coupled microstrip lines at the two output ports. The main features of the proposed device are the employment of a dumbbell‐shaped slot terminated with a chip resistor under the tightly coupled lines to improve the isolation between the output ports and shunt open‐ended stubs at the output ports to improve their impedance matching. The overall size of the structure is 30 × 60 mm using the substrate Rogers RO4003C with a dielectric constant of 3.38 and thickness of 0.4 mm. The simulated and experimental results of the developed device show wide bandwidths (120% fractional bandwidth) with isolation >15 dB across the investigated band 1–4 GHz. In addition, the output ports are out‐of‐phase with <1° phase imbalance across the whole frequency band.
200 μm APD OEIC in 0.35 μm BiCMOS
Authors: Jukić T. , Steindl B. , Enne R. , Zimmermann H. 
Published: November 2015

An optoelectronic integrated circuit (OEIC) in a 0.35 μm BiCMOS technology is presented. The receiver designed for optical wireless communication and communication over plastic optical fibre for data rates up to 2 Gbit/s has a 200 μm diameter avalanche photodiode (APD). Thanks to a thick intrinsic zone the APD has a low capacitance of 0.5 pF. The chip requires a supply voltage of 3.3 V and has a current consumption of 76 mA. The OEIC provides a single‐ended output swing of 550 mV on 50 Ω and a total transimpedence of 260 kΩ with a bandwidth of 1.08 GHz. The OEIC achieves a sensitivity of −32.2 dBm at a BER of 10−9 for a data rate of 2 Gbit/s.
Surgeon Specialty Influences Referral Rate for Osteoporosis Management following Vertebral Compression Fractures
Authors: Daffner Scott D. , Karnes Jonathan M. , Watkins Colleen M. 
Published: November 2015

Study Design Retrospective chart review. Objective To evaluate the referral rate for long-term osteoporosis management following vertebral compression fracture treated by different specialties at a single academic institution. Methods Patients undergoing vertebral cement augmentation for painful osteoporotic compression fractures from 2009 to 2014 were identified. Medical records were reviewed to determine if the treating surgeon discussed and/or referred the patient for long-term osteoporosis management. Any referral for or mention of medical long-term osteoporosis management was counted as a positive response. Results were statistically analyzed with chi-square test. Results Two hundred fourteen patients underwent vertebral cement augmentation; 150 met inclusion criteria. Orthopedic surgeons treated 88 patients, neurosurgeons treated 39, and interventional radiology or pain management physicians treated 23. Orthopedic surgeons referred 82% of patients for osteoporosis management, neurosurgeons referred 36%, and interventional radiology/pain management referred 17%. The referral rate was significantly higher for orthopedic surgeons compared with either of the other two groups; there was no significant difference between neurosurgery and interventional radiology/pain management. Conclusions Among physicians who treat osteoporotic vertebral compression fractures, orthopedic surgeons more frequently address osteoporosis or refer patients for osteoporosis management compared with neurosurgeons and interventional radiologists or pain management physicians. The results of this study shed light on the disparity in how different specialties approach treatment of osteoporosis in patients with fractures painful enough to require surgery and highlight potential areas for improvement in osteoporosis awareness training.
The Application of the Revised Condyle–C1 Interval Method to Diagnose Traumatic Atlanto-occipital Dissociation in Adults
Authors: Dahdaleh Nader S. , Khanna Ryan , Menezes Arnold H. , Smith Zachary A. , Viljoen Stephanus V. , Koski Tyler R. , Hitchon Patrick W. , Dlouhy Brian J. 
Published: November 2015

Study Design Retrospective study. Objective Traumatic atlanto-occipital dissociation (AOD) remains a diagnostic challenge, and delay in diagnosis is associated with catastrophic outcomes. Recently, a revised version of the condyl–C1 interval (CCI) utilizing parasagittal computed tomography (CT) reconstruction was used successfully with unilateral dislocation of 2.5 mm at the level of that joint diagnostic of AOD. We report the utility of this simple technique in the diagnosis of six patients with AOD. Methods Two blinded neurosurgeons assessed CTs of six patients with AOD and 30 patients without AOD. The following methodologies were applied: basion–dens interval (BDI), basion–axial interval (BAI), Lee X-lines, Powers ratio, CCI, and revised CCI. The average sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) as well as the kappa statistic indicating interrater reliability of each method were investigated. Results The average sensitivity for BDI, BAI, Lee X-lines, Power ratio, CCI, and revised CCI was 0.75, 0.33, 0.67, 0.50, 1.00, and 1.00, respectively. The average specificity was 1.00, 1.00, 0.50, 1.00, 0.94, and 1.00, respectively. The average PPV was 1.00, 1.00, 0.25, 1.00, 0.80, and 1.00, respectively. The average NPV was 0.96, 0.88, 0.89, 0.91, 1.00, and 1.00, respectively, and the kappa statistic was 0.57, 0.25, 0.25, 0.20, 1.00, and 1.00, respectively. Conclusion Based on this study, the revised CCI method is simple yet the most sensitive and reliable technique for the diagnosis of AOD.
STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity
Authors: Demaria Olivier , De Gassart Aude , Coso Sanja , Gestermann Nicolas , Di Domizio Jeremy , Flatz Lukas , Gaide Olivier , Michielin Olivier , Hwu Patrick , Petrova Tatiana V. , Martinon Fabio , Modlin Robert L. , Speiser Daniel E. , Gilliet Michel 
Published: November 2015

Significance
Tumor recognition by the immune system can occur spontaneously but has usually little impact on tumor growth. However, the cellular and molecular mechanisms that drive these responses could be exploited therapeutically to generate efficacious antitumor immunity. Here, we show that stimulator of IFN genes (STING), a molecule involved in cytosolic DNA sensing and required for the generation of spontaneous antitumor immune responses, can be targeted by intratumoral injection of cGAMP to boost antitumor immunity and to control tumor growth. The immune response induced by therapeutic but also spontaneous STING activation was dependent on type I IFN produced by endothelial cells in the tumor microenvironment, unraveling an unexpected role of the tumor vasculature in the initiation of spontaneous and therapeutic antitumor immunity via STING.
Temporal fate mapping reveals age-linked heterogeneity in naive T lymphocytes in mice
Authors: Hogan Thea , Gossel Graeme , Yates Andrew J. , Seddon Benedict 
Published: November 2015

Significance
T cells are essential components of vertebrate immune systems, but the mechanisms by which they are maintained are still poorly defined. Existing methods infer cell lifetimes and division rates using DNA labeling of dividing cells, but do not resolve heterogeneity in population dynamics well. We present a novel experimental system that, when combined with mathematical models, yields kinetic parameters and allows us to measure the effect of a cell’s age on its ability to survive and divide. Our approach quantifies lymphocyte dynamics over a year of a mouse’s life and reveals a first-in, last-out structure in which subpopulations of naive T cells generated early in life persist with slower kinetics and resist displacement by newer specificities.