bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-sensitive protein detection via Single Molecule Arrays towards early stage cancer monitoring
Authors: Schubert Stephanie M. , Arendt Lisa M. , Zhou Wenhui , Baig Shazia , Walter Stephanie R. , Buchsbaum Rachel J. , Kuperwasser Charlotte , Walt David R. 
Published: June 2015

AbstractThe early diagnosis of cancers and continued monitoring of tumor growth would be greatly facilitated by the development of a blood-based, non-invasive, screening technique for early cancer detection. Current technologies for cancer screening and detection typically rely on imaging techniques or blood tests that are not accurate or sensitive enough to definitively diagnose cancer at its earliest stages or predict biologic outcomes. By utilizing Single Molecule Arrays (SiMoA), an ultra-sensitive enzyme-linked immunosorbent assay (ELISA) technique, we were able to measure increasing levels of prostate specific antigen (PSA) within murine serum over time, which we attribute to tumor development. The measured concentrations of PSA were well below the detectable limits of both a leading clinical diagnostic PSA ELISA assay as well as a commercial ultra-sensitive PSA assay. Our work benchmarks the role of SiMoA as a vital tool in monitoring previously non-detectable protein biomarkers in serum for early cancer detection and offers significant potential as a non-invasive platform for the monitoring of early stage cancer.
Course of neurological soft signs in first-episode schizophrenia: Relationship with negative symptoms and cognitive performances
Authors: Chan Raymond C. K. , Geng Fu-lei , Lui Simon S. Y. , Wang Ya , Ho Karen K. Y. , Hung Karen S. Y. , Gur Raquel E. , Gur Ruben C. , Cheung Eric F. C. 
Published: June 2015

AbstractThis prospective study examined the course of neurological soft signs (NSS) in patients with first-episode schizophrenia and its relationship with negative symptoms and cognitive functions. One hundred and forty-five patients with first-episode schizophrenia were recruited, 29 were classified as having prominent negative symptoms. NSS and neuropsychological measures were administered to all patients and 62 healthy controls at baseline. Patients were then followed-up prospectively at six-month intervals for up to a year. Patients with prominent negative symptoms exhibited significantly more motor coordination signs and total NSS than patients without prominent negative symptoms. Patients with prominent negative symptoms performed worse than patients without negative symptoms in working memory functions but not other fronto-parietal or fronto-temporal functions. Linear growth model for binary data showed that the prominent negative symptoms were stable over time. Despite general improvement in NSS and neuropsychological functions, the prominent negative symptoms group still exhibited poorer motor coordination and higher levels of NSS, as well as poorer working memory than patients without prominent negative symptoms. Two distinct subtypes of first-episode patients could be distinguished by NSS and prominent negative symptoms.
Do nuclear-encoded core subunits of mitochondrial complex I confer genetic susceptibility to schizophrenia in Han Chinese populations?
Authors: Li Xiao , Zhang Wen , Tang Jinsong , Tan Liwen , Luo Xiong-jian , Chen Xiaogang , Yao Yong-Gang 
Published: June 2015

AbstractSchizophrenia is one of the most prevalent psychiatric disorders with complex genetic etiology. Accumulating evidence suggests that energy metabolism and oxidative stress play important roles in the pathophysiology of schizophrenia. Dysfunction of mitochondrial respiratory chain and altered expression of complex I subunits were frequently reported in schizophrenia. To investigate whether nuclear-encoded core subunit genes of mitochondrial complex I are associated with schizophrenia, we performed a genetic association study in Han Chinese. In total, 46 tag single nucleotide polymorphisms (SNPs) from 7 nuclear-encoded core genes of mitochondrial complex I were genotyped in 918 schizophrenia patients and 1042 healthy controls. We also analyzed these SNPs in a large sample mainly composed of Europeans through using the available GWAS datasets from the Psychiatric Genomics Consortium (PGC). No significant associations were detected between these SNPs and schizophrenia in Han Chinese and the PGC data set. However, we observed nominal significant associations of 2 SNPs in the NDUFS1 gene and 4 SNPs in the NDUFS2 gene with early onset schizophrenia (EOS), but none of these associations survived the Bonferroni correction. Taken together, our results suggested that common SNPs in the nuclear-encoded core subunit genes of mitochondrial complex I may not confer genetic susceptibility to schizophrenia.
The Clinical Features and Bacteriological Characterizations of Bone and Joint Tuberculosis in China
Authors: Chen Su-Ting , Zhao Li-Ping , Dong Wei-Jie , Gu Yun-Ting , Li Yun-Xu , Dong Ling-Ling , Ma Yi-Feng , Qin Shi-Bing , Huang Hai-Rong 
Published: June 2015

AbstractBone and Joint tuberculosis (BJTB) constitutes about 10% of total extra-pulmonary TB cases. Since the BJTB is a paucibacillary condition, there has been no systematic study on the bacterial characterization, especially the epidemiological feature. Here we collected the mycobacterial clinical isolates, analyzed the clinical features and the bacteriological characteristics from 113 BJTB cases reported in China. The mean age of the cases was 40.33 years while most of the patients fell into the 20–29 year age group; local pain was the most common onset symptom of BJTB cases; mean time from symptom onset to BJTB diagnosis was 13.16 months. 31 isolates were defined as drug resistant, including 15 multidrug resistant (MDR) and 2 extensively drug resistant (XDR) isolates according to the drug susceptibility test outcomes; after spoligotyping, 87.6% (99/113) isolates were categorized as Beijing family. In contrast to the isolates from pulmonary tuberculosis patients, here the MIRU-VNTR assay did not find anything significant. A prolonged time span for BJTB diagnosis highlights the requirement of paying further attention to BJTB infection in China. This study provides essential insights into the demographic and microbial characteristics of BJTB cases in China.
Focusing on Plates: Controlling Guided Waves using Negative Refraction
Authors: Philippe Franck D. , Murray Todd W. , Prada Claire 
Published: June 2015

AbstractElastic waves are guided along finite structures such as cylinders, plates, or rods through reflection, refraction and mode conversion at the interfaces. Such wave propagation is ubiquitous in the world around us and studies of elastic waveguides first emerged in the later part of the 19th century. Early work on elastic waveguides revealed the presence of backward propagating waves, in which the phase velocity and group velocity are anti-parallel. While backward wave propagation exists naturally in very simple finite elastic media, there has been remarkably little attention paid to this phenomenon. Here we report the development of a tunable acoustic lens in an isotropic elastic plate showing negative refraction over a finite acoustic frequency bandwidth. As compared to engineered acoustic materials such as phononic crystals and metamaterials, the design of the acoustic lens is very simple, with negative refraction obtained through thickness changes rather than internal periodicity or sub-wavelength resonant structures. A new class of acoustic devices, including resonators, filters, lenses and cloaks, may be possible through topography optimization of elastic waveguide structures to exploit the unique properties of backward waves.
Structural and Dynamic Features of F-recruitment Site Driven Substrate Phosphorylation by ERK2
Authors: Piserchio Andrea , Ramakrishan Venkatesh , Wang Hsin , Kaoud Tamer S. , Arshava Boris , Dutta Kaushik , Dalby Kevin N. , Ghose Ranajeet 
Published: June 2015

AbstractThe F-recruitment site (FRS) of active ERK2 binds F-site (Phe-x-Phe-Pro) sequences found downstream of the Ser/Thr phospho-acceptor on cellular substrates. Here we apply NMR methods to analyze the interaction between active ERK2 (ppERK2) and a 13-residue F-site-bearing peptide substrate derived from its cellular target, the transcription factor Elk-1. Our results provide detailed insight into previously elusive structural and dynamic features of FRS/F-site interactions and FRS-driven substrate phosphorylation. We show that substrate F-site engagement significantly quenches slow dynamics involving the ppERK2 activation-loop and the FRS. We also demonstrate that the F-site phenylalanines make critical contacts with ppERK2, in contrast to the proline whose cis-trans isomerization has no significant effect on F-site recognition by the kinase FRS. Our results support a mechanism where phosphorylation of the disordered N-terminal phospho-acceptor is facilitated by its increased productive encounters with the ppERK2 active site due to docking of the proximal F-site at the kinase FRS.
Metabolic engineering for the high-yield production of isoprenoid-based C5 alcohols in E. coli
Authors: George Kevin W. , Thompson Mitchell G. , Kang Aram , Baidoo Edward , Wang George , Chan Leanne Jade G. , Adams Paul D. , Petzold Christopher J. , Keasling Jay D. , Soon Lee Taek 
Published: June 2015

AbstractBranched five carbon (C5) alcohols are attractive targets for microbial production due to their desirable fuel properties and importance as platform chemicals. In this study, we engineered a heterologous isoprenoid pathway in E. coli for the high-yield production of 3-methyl-3-buten-1-ol, 3-methyl-2-buten-1-ol and 3-methyl-1-butanol, three C5 alcohols that serve as potential biofuels. We first constructed a pathway for 3-methyl-3-buten-1-ol, where metabolite profiling identified NudB, a promiscuous phosphatase, as a likely pathway bottleneck. We achieved a 60% increase in the yield of 3-methyl-3-buten-1-ol by engineering the Shine-Dalgarno sequence of nudB, which increased protein levels by 9-fold and reduced isopentenyl diphosphate (IPP) accumulation by 4-fold. To further optimize the pathway, we adjusted mevalonate kinase (MK) expression and investigated MK enzymes from alternative microbes such as Methanosarcina mazei. Next, we expressed a fusion protein of IPP isomerase and the phosphatase (Idi1~NudB) along with a reductase (NemA) to diversify production to 3-methyl-2-buten-1-ol and 3-methyl-1-butanol. Finally, we used an oleyl alcohol overlay to improve alcohol recovery, achieving final titers of 2.23 g/L of 3-methyl-3-buten-1-ol (~70% of pathway-dependent theoretical yield), 150 mg/L of 3-methyl-2-buten-1-ol and 300 mg/L of 3-methyl-1-butanol.
Far-field subwavelength imaging with near-field resonant metalens scanning at microwave frequencies
Authors: Wang Ren , Wang Bing-Zhong , Gong Zhi-Shuang , Ding Xiao 
Published: June 2015

AbstractA method for far-field subwavelength imaging at microwave frequencies using near-field resonant metalens scanning is proposed. The resonant metalens is composed of switchable split-ring resonators (SRRs). The on-SRR has a strong magnetic coupling ability and can convert evanescent waves into propagating waves using the localized resonant modes. In contrast, the off-SRR cannot achieve an effective conversion. By changing the switch status of each cell, we can obtain position information regarding the subwavelength source targets from the far field. Because the spatial response and Green’s function do not need to be measured and evaluated and only a narrow frequency band is required for the entire imaging process, this method is convenient and adaptable to various environment. This method can be used for many applications, such as subwavelength imaging, detection and electromagnetic monitoring, in both free space and complex environments.
Photocatalytic generation of hydrogen by core-shell WO3/BiVO4 nanorods with ultimate water splitting efficiency
Authors: Pihosh Yuriy , Turkevych Ivan , Mawatari Kazuma , Uemura Jin , Kazoe Yutaka , Kosar Sonya , Makita Kikuo , Sugaya Takeyoshi , Matsui Takuya , Fujita Daisuke , Tosa Masahiro , Kondo Michio , Kitamori Takehiko 
Published: June 2015

AbstractEfficient photocatalytic water splitting requires effective generation, separation and transfer of photo-induced charge carriers that can hardly be achieved simultaneously in a single material. Here we show that the effectiveness of each process can be separately maximized in a nanostructured heterojunction with extremely thin absorber layer. We demonstrate this concept on WO3/BiVO4+CoPi core-shell nanostructured photoanode that achieves near theoretical water splitting efficiency. BiVO4 is characterized by a high recombination rate of photogenerated carriers that have much shorter diffusion length than the thickness required for sufficient light absorption. This issue can be resolved by the combination of BiVO4 with more conductive WO3 nanorods in a form of core-shell heterojunction, where the BiVO4 absorber layer is thinner than the carrier diffusion length while it’s optical thickness is reestablished by light trapping in high aspect ratio nanostructures. Our photoanode demonstrates ultimate water splitting photocurrent of 6.72 mA cm−2 under 1 sun illumination at 1.23 VRHE that corresponds to ~90% of the theoretically possible value for BiVO4. We also demonstrate a self-biased operation of the photoanode in tandem with a double-junction GaAs/InGaAsP photovoltaic cell with stable water splitting photocurrent of 6.56 mA cm−2 that corresponds to the solar to hydrogen generation efficiency of 8.1%.
Internalization of silver nanoparticles into mouse spermatozoa results in poor fertilization and compromised embryo development
Authors: Yoisungnern Ton , Choi Yun-Jung , Woong Han Jae , Kang Min-Hee , Das Joydeep , Gurunathan Sangiliyandi , Kwon Deug-Nam , Cho Ssang-Goo , Park Chankyu , Kyung Chang Won , Chang Byung-Soo , Parnpai Rangsun , Kim Jin-Hoi 
Published: June 2015

AbstractSilver nanoparticles (AgNPs) have many features that make them attractive as medical devices, especially in therapeutic agents and drug delivery systems. Here we have introduced AgNPs into mouse spermatozoa and then determined the cytotoxic effects of AgNPs on sperm function and subsequent embryo development. Scanning electron microscopy and transmission electron microscopy analyses showed that AgNPs could be internalized into sperm cells. Furthermore, exposure to AgNPs inhibited sperm viability and the acrosome reaction in a dose-dependent manner, whereas sperm mitochondrial copy numbers, morphological abnormalities and mortality due to reactive oxygen species were significantly increased. Likewise, sperm abnormalities due to AgNPs internalization significantly decreased the rate of oocyte fertilization and blastocyst formation. Blastocysts obtained from AgNPs-treated spermatozoa showed lower expression of trophectoderm-associated and pluripotent marker genes. Overall, we propose that AgNPs internalization into spermatozoa may alter sperm physiology, leading to poor fertilization and embryonic development. Such AgNPs-induced reprotoxicity may be a valuable tool as models for testing the safety and applicability of medical devices using AgNPs.
Estimating variability in grain legume yields across Europe and the Americas
Authors: Cernay Charles , Ben-Ari Tamara , Pelzer Elise , Meynard Jean-Marc , Makowski David 
Published: June 2015

AbstractGrain legume production in Europe has recently come under scrutiny. Although legume crops are often promoted to provide environmental services, European farmers tend to turn to non-legume crops. It is assumed that high variability in legume yields explains this aversion, but so far this hypothesis has not been tested. Here, we estimate the variability of major grain legume and non-legume yields in Europe and the Americas from yield time series over 1961–2013. Results show that grain legume yields are significantly more variable than non-legume yields in Europe. These differences are smaller in the Americas. Our results are robust at the level of the statistical methods. In all regions, crops with high yield variability are allocated to less than 1% of cultivated areas. Although the expansion of grain legumes in Europe may be hindered by high yield variability, some species display risk levels compatible with the development of specialized supply chains.
Functional Identification of Target by Expression Proteomics (FITExP) reveals protein targets and highlights mechanisms of action of small molecule drugs
Authors: Chernobrovkin Alexey , Marin-Vicente Consuelo , Visa Neus , Zubarev Roman A. 
Published: June 2015

AbstractPhenomenological screening of small molecule libraries for anticancer activity yields potentially interesting candidate molecules, with a bottleneck in the determination of drug targets and the mechanism of anticancer action. We have found that, for the protein target of a small-molecule drug, the abundance change in late apoptosis is exceptional compared to the expectations based on the abundances of co-regulated proteins. Based on this finding, a novel method to drug target deconvolution is proposed. In a proof of principle experiment, the method yielded known targets of several common anticancer agents among a few (often, just one) likely candidates identified in an unbiased way from cellular proteome comprising more than 4,000 proteins. A validation experiment with a different set of cells and drugs confirmed the findings. As an additional benefit, mapping most specifically regulated proteins on known protein networks highlighted the mechanism of drug action. The new method, if proven to be general, can significantly shorten drug target identification and thus facilitate the emergence of novel anticancer treatments.
Intracerebroventricular administration of leptin increase physical activity but has no effect on thermogenesis in cold-acclimated rats
Authors: Tang Gang-Bin , Tang Xiang-Fang , Li Kui , Wang De-Hua 
Published: June 2015

AbstractMost small homotherms display low leptin level in response to chronic cold exposure. Cold-induced hypoleptinemia was proved to induce hyperphagia. However, it is still not clear whether hypoleptinemia regulates energy expenditure in cold condition. We try to answer this question in chronic cold-acclimated rats. Results showed that 5-day intracerebroventricular(ICV) infusion of leptin (5 μg/day) had no effects on basal and adaptive thermogenesis and uncoupling protein 1 expression. Physical activity was increased by leptin treatment. We further determined whether ghrelin could reverse the increasing effect of leptin on physical activity. Coadministration of ghrelin (1.2 μg/day) completely reversed the effect of leptin on physical activity. Collectively, this study indicated the regulation of leptin on energy expenditure during cold acclimation may be mainly mediated by physical activity but not by thermogenesis. Our study outlined behavioral role of leptin during the adaptation to cold, which adds some new knowledge to promote our understanding of cold-induced metabolic adaptation.
Biomimetic Intrafibrillar Mineralization of Type I Collagen with Intermediate Precursors-loaded Mesoporous Carriers
Authors: Zhang Wei , Luo Xiao-juan , Niu Li-na , Yang Hong-ye , Yiu Cynthia K.Y. , Wang Tian-da , Zhou Li-qun , Mao Jing , Huang Cui , Pashley David H. , Tay Franklin R. 
Published: June 2015

AbstractLimited continuous replenishment of the mineralization medium is a restriction for in-situ solution-based remineralization of hypomineralized body tissues. Here, we report a process that generated amine-functionalized mesoporous silica nanoparticles for sustained release of biomimetic analog-stabilized amorphous calcium phosphate precursors. Both two-dimensional and three-dimensional collagen models can be intrafibrillarly mineralized with these released fluidic intermediate precursors. This represents an important advance in the translation of biomineralization concepts into regimes for in-situ remineralization of bone and teeth.
Mutational Analysis of Intracellular Loops Identify Cross Talk with Nucleotide Binding Domains of Yeast ABC Transporter Cdr1p
Authors: Shah Abdul Haseeb , Rawal Manpreet Kaur , Dhamgaye Sanjiveeni , Komath Sneha Sudha , Saxena Ajay Kumar , Prasad Rajendra 
Published: June 2015

AbstractThe ABC transporter Cdr1 protein (Cdr1p) of Candida albicans, which plays a major role in antifungal resistance, has two transmembrane domains (TMDs) and two nucleotide binding domains (NBDs) that are interconnected by extracellular (ECLs) and intracellular (ICLs) loops. To examine the communication interface between the NBDs and ICLs of Cdr1p, we subjected all four ICLs to alanine scanning mutagenesis, replacing each of the 85 residues with an alanine. The resulting ICL mutant library was analyzed by biochemical and phenotypic mapping. Only 18% of the mutants from this library displayed enhanced drug susceptibility. Most of the drug-susceptible mutants displayed uncoupling between ATP hydrolysis and drug transport. The two drug-susceptible ICL1 mutants (I574A and S593A) that lay within or close to the predicted coupling helix yielded two chromosomal suppressor mutations that fall near the Q-loop of NBD2 (R935) and in the Walker A motif (G190) of NBD1. Based on a 3D homology model and kinetic analysis of drug transport, our data suggest that large distances between ICL residues and their respective chromosomal suppressor mutations rule out a direct interaction between them. However, they impact the transport cycle by restoring the coupling interface via indirect downstream signaling.
Vertical split-ring resonator based anomalous beam steering with high extinction ratio
Authors: Hsu Wei-Lun , Wu Pin Chieh , Chen Jia-Wern , Chen Ting-Yu , Cheng Bo Han , Chen Wei Ting , Huang Yao-Wei , Liao Chun Yen , Sun Greg , Tsai Din Ping 
Published: June 2015

AbstractMetasurfaces created artificially with metal nanostructures that are patterned on surfaces of different media have shown to possess “unusual” abilities to manipulate light. Limited by nanofabrication difficulties, so far most reported works have been based on 2D metal structures. We have recently developed an advanced e-beam process that allowed for the deposition of 3D nanostructures, namely vertical split-ring resonators (VSRRs), which opens up another degree of freedom in the metasurface design. Here we explore the functionality of beam steering with phase modulation by tuning only the vertical dimension of the VSRRs and show that anomalous steering reflection of a wide range of angles can be accomplished with high extinction ratio using the finite-difference-time-domain simulation. We also demonstrate that metasurfaces made of 3D VSRRs can be made with roughly half of the footprint compared to that of 2D nano-rods, enabling high density integration of metal nanostructures.