bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arguing for Transcendental Idealism: Lucy Allais on Manifest Reality
Authors: Guyer Paul 
Published: June 2016

AbstractI endorse Allais’s ‘moderate metaphysical’ approach to transcendental idealism, but find tension between her concept of ‘manifest reality’ and her relational interpretation of the doctrine. And I think her reconstruction of Kant’s argument for transcendental idealism fails to block the famous ‘missing alternative’ objection, although in my view Kant’s fundamental argument for the position was intended precisely to block such an objection.
Non-Conceptualism and Knowledge in Lucy Allais’s Manifest Reality
Authors: Newton Alexandra 
Published: June 2016

AbstractLucy Allais’s Manifest Reality presents a systematic discussion of the role that Kant assigns to concepts in making knowledge of objects possible. In this paper, I ascribe to Allais a version of non-conceptualism, according to which knowledge is a ‘hybrid’ or loose unity of concept and intuition; concept relates to intuition as form relates to matter in an artefact. I will show how this view has trouble accommodating the distinction between knowledge and accidentally true belief, and how it leads to objectionable forms of idealism.
Diverse genetic architectures lead to the same cryptic phenotype in a yeast cross
Authors: Taylor Matthew B. , Phan Joann , Lee Jonathan T. , McCadden Madelyn , Ehrenreich Ian M. 
Published: June 2016

AbstractCryptic genetic variants that do not typically influence traits can interact epistatically with each other and mutations to cause unexpected phenotypes. To improve understanding of the genetic architectures and molecular mechanisms that underlie these interactions, we comprehensively dissected the genetic bases of 17 independent instances of the same cryptic colony phenotype in a yeast cross. In eight cases, the phenotype resulted from a genetic interaction between a de novo mutation and one or more cryptic variants. The number and identities of detected cryptic variants depended on the mutated gene. In the nine remaining cases, the phenotype arose without a de novo mutation due to two different classes of higher-order genetic interactions that only involve cryptic variants. Our results may be relevant to other species and disease, as most of the mutations and cryptic variants identified in our study reside in components of a partially conserved and oncogenic signalling pathway.
Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice
Authors: Beglopoulos V. , Tulloch J. , Roe A. D. , Daumas S. , Ferrington L. , Watson R. , Fan Z. , Hyman B. T. , Kelly P. A. T. , Bard F. , Morris R. G. M. 
Published: June 2016

AbstractEarlier diagnosis and treatment of Alzheimer’s disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory task normally and displaying normal brain glucose uptake, they display faster forgetting after a long delay following performance to a criterion, together with a strong impairment of brain glucose uptake at the time of attempted memory retrieval. Preliminary observations suggest that these deficits, likely caused by an impairment in systems consolidation, could be rescued by immunotherapy with an anti-β-amyloid antibody. Our data suggest a biomarker strategy for the early detection of β-amyloid-related abnormalities.
Germline hemizygous deletion of CDKN2A–CDKN2B locus in a patient presenting with Li–Fraumeni syndrome
Authors: Chan Sock Hoai , Lim Weng Khong , Michalski Scott T , Lim Jing Quan , Ishak Nur Diana Binte , Met-Domestici Marie , Young Cedric Ng Chuan , Vikstrom Karen , Esplin Edward D , Fulbright Jennifer , Ang Mei Kim , Wee Joseph , Sittampalam Kesavan , Farid Mohamad , Lincoln Stephen E , Itahana Koji , Abdullah Syafiq , Teh Bin Tean , Ngeow Joanne 
Published: June 2016

AbstractLi–Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome usually associated with TP53 germline alterations. Its genetic basis in TP53 wild-type pedigrees is less understood. Using whole-genome sequencing, we identified a germline hemizygous deletion ablating CDKN2A–CDKN2B in a TP53 wild-type patient presenting with high-grade sarcoma, laryngeal squamous cell carcinoma and a family history suggestive of LFS. Patient-derived cells demonstrated reduced basal gene and protein expression of the CDKN2A-encoded tumour suppressors p14ARF and p16INK4A with concomitant decrease in p21 and faster cell proliferation, implying potential deregulation of p53-mediated cell cycle control. Review of 13 additional patients with pathogenic CDKN2A variants suggested associations of germline CDKN2A mutations with an expanded spectrum of non-melanoma familial cancers. To our knowledge, this is the first report of a germline gross deletion of the CDKN2A–CDKN2B locus in an LFS family. These findings highlight the potential contribution of germline CDKN2A deletions to cancer predisposition and the importance of interrogating the full extent of CDKN2A locus in clinical testing gene panels.
Sustained Resistive Switching in a Single Cu:7,7,8,8-tetracyanoquinodimethane Nanowire: A Promising Material for Resistive Random Access Memory
Authors: Basori Rabaya , Kumar Manoranjan , Raychaudhuri Arup K. 
Published: June 2016

AbstractWe report a new type of sustained and reversible unipolar resistive switching in a nanowire device made from a single strand of Cu:7,7,8,8-tetracyanoquinodimethane (Cu:TCNQ) nanowire (diameter <100 nm) that shows high ON/OFF ratio (~103), low threshold voltage of switching (~3.5 V) and large cycling endurance (>103). This indicates a promising material for high density resistive random access memory (ReRAM) device integration. Switching is observed in Cu:TCNQ single nanowire devices with two different electrode configuration: symmetric (C-Pt/Cu:TCNQ/C-Pt) and asymmetric (Cu/Cu:TCNQ/C-Pt), where contacts connecting the nanowire play an important role. This report also developed a method of separating out the electrode and material contributions in switching using metal-semiconductor-metal (MSM) device model along with a direct 4-probe resistivity measurement of the nanowire in the OFF as well as ON state. The device model was followed by a phenomenological model of current transport through the nanowire device which shows that lowering of potential barrier at the contacts likely occur due to formation of Cu filaments in the interface between nanowire and contact electrodes. We obtain quantitative agreement of numerically analyzed results with the experimental switching data.
Quantum uncertainty switches on or off the error-disturbance tradeoff
Authors: Zhang Yu-Xiang , Su Zu-En , Zhu Xuanmin , Wu Shengjun , Chen Zeng-Bing 
Published: June 2016

AbstractThe indeterminacy of quantum mechanics was originally presented by Heisenberg through the tradeoff between the measuring error of the observable A and the consequential disturbance to the value of another observable B. This tradeoff now has become a popular interpretation of the uncertainty principle. However, the historic idea has never been exactly formulated previously and is recently called into question. A theory built upon operational and state-relevant definitions of error and disturbance is called for to rigorously reexamine the relationship. Here by putting forward such natural definitions, we demonstrate both theoretically and experimentally that there is no tradeoff if the outcome of measuring B is more uncertain than that of A. Otherwise, the tradeoff will be switched on and well characterized by the Jensen-Shannon divergence. Our results reveal the hidden effect of the uncertain nature possessed by the measured state, and conclude that the state-relevant relation between error and disturbance is not almosteverywhere a tradeoff as people usually believe.
Threatened by mining, polymetallic nodules are required to preserve abyssal epifauna
Authors: Vanreusel Ann , Hilario Ana , Ribeiro Pedro A. , Menot Lenaick , Arbizu Pedro Martínez 
Published: June 2016

AbstractPolymetallic nodule mining at abyssal depths in the Clarion Clipperton Fracture Zone (Eastern Central Pacific) will impact one of the most remote and least known environments on Earth. Since vast areas are being targeted by concession holders for future mining, large-scale effects of these activities are expected. Hence, insight into the fauna associated with nodules is crucial to support effective environmental management. In this study video surveys were used to compare the epifauna from sites with contrasting nodule coverage in four license areas. Results showed that epifaunal densities are more than two times higher at dense nodule coverage (>25 versus ≤10 individuals per 100 m2) and that taxa such as alcyonacean and antipatharian corals are virtually absent from nodule-free areas. Furthermore, surveys conducted along tracks from trawling or experimental mining simulations up to 37 years old, suggest that the removal of epifauna is almost complete and that its full recovery is slow. By highlighting the importance of nodules for the epifaunal biodiversity of this abyssal area, we urge for cautious consideration of the criteria for determining future preservation zones.
Enhanced immunoregulation of mesenchymal stem cells by IL-10-producing type 1 regulatory T cells in collagen-induced arthritis
Authors: Lim Jung-Yeon , Im Keon-Il , Lee Eun-Sol , Kim Nayoun , Nam Young-Sun , Jeon Young-Woo , Cho Seok-Goo 
Published: June 2016

AbstractMesenchymal stem cells (MSCs) possess immunomodulatory properties and have potential, however, there have been conflicting reports regarding their effects in rheumatoid arthritis (RA), which causes inflammation and destruction of the joints. Through a comparative analysis of regulatory T (Treg) and IL-10-producing type 1 regulatory T (Tr1) cells, we hypothesized that Tr1 cells enhance the immunoregulatory functions of MSCs, and that a combinatorial approach to cell therapy may exert synergistic immunomodulatory effects in an experimental animal model of rheumatoid arthritis (RA). A combination of MSCs and Tr1 cells prevented the development of destructive arthritis compared to single cell therapy. These therapeutic effects were associated with an increase in type II collagen (CII)-specific CD4+CD25+Foxp3+ Treg cells and inhibition of CII-specific CD4+IL-17+ T cells. We observed that Tr1 cells produce high levels of IL-10-dependent interferon (IFN)-β, which induces toll-like receptor (TLR) 3 expression in MSCs. Moreover, induction of indoleamine 2,3-dioxygenase (IDO) by TLR3 involved an autocrine IFN-β that was dependent on STAT1 signaling. Furthermore, we observed that production of IFN-β and IL-10 in Tr1 cells synergistically induces IDO in MSCs through the STAT1 pathway. These findings suggest co-administration of MSCs and Tr1 cells to be a novel therapeutic modality for clinical autoimmune diseases.
Exploring ecological modelling to investigate factors governing the colonization success in nosocomial environment of Candida albicans and other pathogenic yeasts
Authors: Corte Laura , Roscini Luca , Colabella Claudia , Tascini Carlo , Leonildi Alessandro , Sozio Emanuela , Menichetti Francesco , Merelli Maria , Scarparo Claudio , Meyer Wieland , Cardinali Gianluigi , Bassetti Matteo 
Published: June 2016

AbstractTwo hundred seventy seven strains from eleven opportunistic species of the genus Candida, isolated from two Italian hospitals, were identified and analyzed for their ability to form biofilm in laboratory conditions. The majority of Candida albicans strains formed biofilm while among the NCAC species there were different level of biofilm forming ability, in accordance with the current literature. The relation between the variables considered, i.e. the departments and the hospitals or the species and their ability to form biofilm, was tested with the assessment of the probability associated to each combination. Species and biofilm forming ability appeared to be distributed almost randomly, although some combinations suggest a potential preference of some species or of biofilm forming strains for specific wards. On the contrary, the relation between biofilm formation and species isolation frequency was highly significant (R2 around 0.98). Interestingly, the regression analyses carried out on the data of the two hospitals separately were rather different and the analysis on the data merged together gave a much lower correlation. These findings suggest that, harsh environments shape the composition of microbial species significantly and that each environment should be considered per se to avoid less significant statistical treatments.
Electrocatalytic oxidation of Epinephrine and Norepinephrine at metal oxide doped phthalocyanine/MWCNT composite sensor
Authors: Mphuthi Ntsoaki G. , Adekunle Abolanle S. , Ebenso Eno E. 
Published: June 2016

AbstractGlassy carbon electrode (GCE) was modified with metal oxides (MO = Fe3O4, ZnO) nanoparticles doped phthalocyanine (Pc) and functionalized MWCNTs and the electrocatalytic properties were studied. Successful synthesis of the metal oxide nanoparticles and the MO/Pc/MWCNT composite were confirmed using FTIR, Raman and SEM techniques. The electrodes were characterized using cyclic voltammetry (CV) technique. The electrocatalytic behaviour of the electrode towards epinephrine (EP) and norepinephrine (NE) oxidation was investigated using CV and DPV. Result showed that GCE-MWCNT/Fe3O4/2,3-Nc, GCE-MWCNT/Fe3O429H,31H-Pc, GCE-MWCNT/ZnO/2,3-Nc and GCE-MWCNT/ZnO/29H,31H-Pc electrodes gave enhanced EP and NE current response. Stability study indicated that the four GCE-MWCNT/MO/Pc modified electrodes were stable against electrode fouling effect with the percentage NE current drop of 5.56–5.88% after 20 scans. GCE-MWCNT/Fe3O4/29H,31H-Pc gave the lowest limit of detection (4.6 μM) towards EP while MWCNT/ZnO/29H,31H-Pc gave the lowest limit of detection (1.7 μM) towards NE. The limit of detection and sensitivity of the electrodes compared well with literature. Electrocatalytic oxidation of EP and NE on GCE-MWCNT/MO/Pc electrodes was diffusion controlled with some adsorption of electro-oxidation reaction intermediates products. The electrodes were found to be electrochemically stable, reusable and can be used for the analysis of EP and NE in real life samples.
Targeted next-generation sequencing reveals multiple deleterious variants in OPLL-associated genes
Authors: Chen Xin , Guo Jun , Cai Tao , Zhang Fengshan , Pan Shengfa , Zhang Li , Wang Shaobo , Zhou Feifei , Diao Yinze , Zhao Yanbin , Chen Zhen , Liu Xiaoguang , Chen Zhongqiang , Liu Zhongjun , Sun Yu , Du Jie 
Published: June 2016

AbstractOssification of the posterior longitudinal ligament of the spine (OPLL), which is characterized by ectopic bone formation in the spinal ligaments, can cause spinal-cord compression. To date, at least 11 susceptibility genes have been genetically linked to OPLL. In order to identify potential deleterious alleles in these OPLL-associated genes, we designed a capture array encompassing all coding regions of the target genes for next-generation sequencing (NGS) in a cohort of 55 unrelated patients with OPLL. By bioinformatics analyses, we successfully identified three novel and five extremely rare variants (MAF < 0.005). These variants were predicted to be deleterious by commonly used various algorithms, thereby resulting in missense mutations in four OPLL-associated genes (i.e., COL6A1, COL11A2, FGFR1 and BMP2). Furthermore, potential effects of the patient with p.Q89E of BMP2 were confirmed by a markedly increased BMP2 level in peripheral blood samples. Notably, seven of the variants were found to be associated with the patients with continuous subtype changes by cervical spinal radiological analyses. Taken together, our findings revealed for the first time that deleterious coding variants of the four OPLL-associated genes are potentially pathogenic in the patients with OPLL.
Microbiological profiles of sputum and gastric juice aspirates in Cystic Fibrosis patients
Authors: Al-momani H. , Perry A. , Stewart C. J. , Jones R. , Krishnan A. , Robertson A. G. , Bourke S. , Doe S. , Cummings S. P. , Anderson A. , Forrest T. , Griffin S. M. , Brodlie M. , Pearson J. , Ward C. 
Published: June 2016

AbstractGastro-Oesophageal Reflux (GOR) is a key problem in Cystic Fibrosis (CF), but the relationship between lung and gastric microbiomes is not well understood. We hypothesised that CF gastric and lung microbiomes are related. Gastric and sputum cultures were obtained from fifteen CF patients receiving percutaneous endoscopic gastrostomy feeding. Non-CF gastric juice data was obtained through endoscopy from 14 patients without lung disease. Bacterial and fungal isolates were identified by culture. Molecular bacterial profiling used next generation sequencing (NGS) of the 16S rRNA gene. Cultures grew bacteria and/or fungi in all CF gastric juice and sputa and in 9/14 non-CF gastric juices. Pseudomonas aeruginosa(Pa) was present in CF sputum in 11 patients, 4 had identical Pa strains in the stomach. NGS data from non-CF gastric juice samples were significantly more diverse compared to CF samples. NGS showed CF gastric juice had markedly lower abundance of normal gut bacteria; Bacteroides and Faecalibacterium, but increased Pseudomonas compared with non-CF. Multivariate partial least squares discriminant analysis demonstrated similar bacterial profiles of CF sputum and gastric juice samples, which were distinct from non-CF gastric juice. We provide novel evidence suggesting the existence of an aerodigestive microbiome in CF, which may have clinical relevance.
Orientation selectivity in a multi-gated organic electrochemical transistor
Authors: Gkoupidenis Paschalis , Koutsouras Dimitrios A. , Lonjaret Thomas , Fairfield Jessamyn A. , Malliaras George G. 
Published: June 2016

AbstractNeuromorphic devices offer promising computational paradigms that transcend the limitations of conventional technologies. A prominent example, inspired by the workings of the brain, is spatiotemporal information processing. Here we demonstrate orientation selectivity, a spatiotemporal processing function of the visual cortex, using a poly(3,4ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) organic electrochemical transistor with multiple gates. Spatially distributed inputs on a gate electrode array are found to correlate with the output of the transistor, leading to the ability to discriminate between different stimuli orientations. The demonstration of spatiotemporal processing in an organic electronic device paves the way for neuromorphic devices with new form factors and a facile interface with biology.
The Sp1-mediaded allelic regulation of MMP13 expression by an ESCC susceptibility SNP rs2252070
Authors: Shi Meng , Xia Jianhong , Xing Huaixin , Yang Wenjun , Xiong Xiangyu , Pan Wenting , Han Sichong , Shang Jinhua , Zhou Changchun , Zhou Liqing , Yang Ming 
Published: June 2016

AbstractMetallopeptidase 13 (MMP13), a well-known and highly regulated zinc-dependent MMP collagenase, plays a crucial part in development and progression of esophageal squamous cell carcinoma (ESCC). Therefore, we examined associations between ESCC susceptibility and four haplotype-tagging single nucleotide polymorphisms (htSNPs) using a two stage case-control strategy. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed by logistic regression model. After analyzing 1588 ESCC patients and frequency-matched 1600 unaffected controls, we found that MMP13 rs2252070 G > A genetic polymorphism is significantly associated with ESCC risk in Chinese Han populations (GA: OR = 0.63, 95% CI = 0.54–0.74, P = 1.7 × 10−6, AA: OR = 0.73, 95% CI = 0.66–0.81, P = 1.8 × 10−6). Interestingly, the rs2252070 G-to-A change was shown to diminish a Sp1-binding site in ESCC cells. Reporter gene assays indicated that the rs2252070 A allele locating in a potential MMP13 promoter has low promoter activities. After measuring MMP13 gene expression in sixty-six pairs of esophageal cancer and normal tissues, we observed that the rs2252070 A protective allele carriers showed decreased oncogene MMP13 expression. Results of these analyses underline the support of the notion that MMP13 might function as a key oncogene in esophageal carcinogenesis.
Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT
Authors: Jung Yookyung , Klein Oliver J. , Wang Hequn , Evans Conor L. 
Published: June 2016

AbstractThree-dimensional in vitro tumor models are highly useful tools for studying tumor growth and treatment response of malignancies such as ovarian cancer. Existing viability and treatment assessment assays, however, face shortcomings when applied to these large, complex and heterogeneous culture systems. Optical coherence tomography (OCT) is a noninvasive, label-free, optical imaging technique that can visualize live cells and tissues over time with subcellular resolution and millimeters of optical penetration depth. Here, we show that OCT is capable of carrying out high-content, longitudinal assays of 3D culture treatment response. We demonstrate the usage and capability of OCT for the dynamic monitoring of individual and combination therapeutic regimens in vitro, including both chemotherapy drugs and photodynamic therapy (PDT) for ovarian cancer. OCT was validated against the standard LIVE/DEAD Viability/Cytotoxicity Assay in small tumor spheroid cultures, showing excellent correlation with existing standards. Importantly, OCT was shown to be capable of evaluating 3D spheroid treatment response even when traditional viability assays failed. OCT 3D viability imaging revealed synergy between PDT and the standard-of-care chemotherapeutic carboplatin that evolved over time. We believe the efficacy and accuracy of OCT in vitro drug screening will greatly contribute to the field of cancer treatment and therapy evaluation.
Association of Non-alcoholic Fatty Liver Disease with Metabolic Syndrome Independently of Central Obesity and Insulin Resistance
Authors: Yang Kuen Cheh , Hung Hui-Fang , Lu Chia-Wen , Chang Hao-Hsiang , Lee Long-Teng , Huang Kuo-Chin 
Published: June 2016

AbstractNon-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease that may lead to liver cirrhosis and hepatocellular carcinoma. We aimed to determine the association between the prevalence of metabolic syndrome (MetS) and NAFLD severity using semi-quantitative ultrasonography (US). A total of 614 participants were recruited from the community. NAFLD was evaluated according to the ultrasonographic Fatty Liver Indicator (US-FLI), which is a semi-quantitative liver ultrasound score. Insulin resistance was estimated with the homeostasis model assessment index for insulin resistance (HOMA-IR). NAFLD and MetS were found in 53.7 and 17.3% of the participants, respectively. Linear relationships were found between the severity of NAFLD and waist circumference, fasting glucose, HOMA-IR, triglycerides, HDL-C and blood pressure. After adjusting for confounding factors, i.e., body mass index and HOMA-IR, the odds ratios for MetS were 3.64 (95% confidence interval (CI): 1.5–8.83) for those with mild NAFLD and 9.4 (95% CI: 3.54–24.98) for those with moderate-to-severe NAFLD compared to those without NAFLD. The combination of the HOMA-IR and US-FLI scores better differentiated MetS than the HOMA-IR alone. In addition to obesity, the severity of NAFLD and the HOMA-IR both play important roles in MetS. Whether NAFLD is a component of MetS warrants further research.