bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaffolding of Cystine‐Stabilized Miniproteins
Authors: Sankaran Shrikrishnan , Stojanovic Ivan , Barendregt Arjan , Heck Albert J.R. , Schasfoort Richard B.M. , Jonkheijm Pascal 
Published: April 2016

AbstractBiomolecular scaffolds were engineered by genetically fusing robust miniproteins in a sequence, like a chain. By fusing these miniprotein chains to a teal fluorescent protein (TFP), an efficient strategy was devised for their production in E. coli. Miniproteins that bind β‐trypsin, VEGF and HIV‐1 Nef proteins were used to make 4 individual chains, each with 3 miniproteins arranged in different orders. Their stability and binding properties were analyzed with native ESI‐mass spectrometry, microscale thermophoresis, surface plasmon resonance imaging and a trypsin activity assay. Miniproteins within the chains were found to be functional and significantly robust. The trypsin activity assay showed that miniprotein chains containing two β‐trypsin inhibitors clearly inhibit β‐trypsin more than two fold stronger compared to chains containing only one β‐trypsin inhibitor indicating that multivalent interactions occurs. SPR imaging results indicated that these constructs had the potential to simultaneously bind multiple target proteins. However, each miniprotein chain exhibited different binding affinities towards the target proteins, especially VEGF and HIV‐1 Nef possibly due to issues dealing with folding, miniprotein orientations, non‐specific adhesion and slow proteolytic degradation of the miniproteins. Analysis of these issues provided insights into parameters that need to be taken into consideration while designing such multi‐specific protein constructs. By careful optimization, such constructs have the potential to be used in a very versatile manner for various molecular engineering applications.
Electrophysiology of cerebral ischemia and reperfusion: First evidence for the role of synapse in ischemic tolerance
Authors: Haghani Masoud , Keshavarz Somaye , Nazari Maryam , Rafati Ali 
Published: April 2016

ABSTRACTObjective: The subthreshold brain‐damaging stimulus may protect the brain from subsequent ischemia; this phenomenon has been named “ischemic tolerance” (IT). We focused on the synaptic properties of the neurons after mild and severe ischemia to determine the association between IT and synaptic efficacy. Experimental design: Adult male rats were randomly divided into four experimental groups including control, sham, permanent ischemia (pI/R), and mild ischemia (mI/R). Middle cerebral artery occlusion (MCAO) method was applied to induce brain ischemia. Seven days after the insult, long‐term potentiation (LTP) induced by high‐frequency stimulation (HFS) and paired‐pulse ratio (PPR) were monitored before and after the HFS delivery. Results: The field potential recording demonstrated that mild ischemia significantly increased the basal synaptic transmission. Additionally, the HFS produced a significant potentiation compared to its baseline level in the mI/R group. Moreover, mild ischemia prevented depression of PPR by HFS. This effect was accompanied by a significant increase in the normalized PPR (PPR after HFS/PPR before HFS) in this group. Conclusions: Our data indicated that a mild reduction in brain perfusion without permanent lesion can dramatically increase the basal synaptic transmission. This effect may be associated with an increase in the neurotransmitter content of the pre‐synaptic neurons. This hypothesis could provide a new insight into the relationship between IT and synaptic efficacy. Synapse 70:351–360, 2016. © 2016 Wiley Periodicals, Inc.
Intraneuronal aggregation of the β-CTF fragment of APP (C99) induces Aβ-independent lysosomal-autophagic pathology
Authors: Lauritzen Inger , Pardossi-Piquard Raphaëlle , Bourgeois Alexandre , Pagnotta Sophie , Biferi Maria-Grazia , Barkats Martine , Lacor Pascale , Klein William , Bauer Charlotte , Checler Frederic 
Published: April 2016

AbstractEndosomal-autophagic-lysosomal (EAL) dysfunction is an early and prominent neuropathological feature of Alzheimers’s disease, yet the exact molecular mechanisms contributing to this pathology remain undefined. By combined biochemical, immunohistochemical and ultrastructural approaches, we demonstrate a link between EAL pathology and the intraneuronal accumulation of the β-secretase-derived βAPP fragment (C99) in two in vivo models, 3xTgAD mice and adeno-associated viral-mediated C99-infected mice. We present a pathological loop in which the accumulation of C99 is both the effect and causality of impaired lysosomal-autophagic function. The deleterious effect of C99 was found to be linked to its aggregation within EAL-vesicle membranes leading to disrupted lysosomal proteolysis and autophagic impairment. This effect was Aβ independent and was even exacerbated when γ-secretase was pharmacologically inhibited. No effect was observed in inhibitor-treated wild-type animals suggesting that lysosomal dysfunction was indeed directly linked to C99 accumulation. In some brain areas, strong C99 expression also led to inflammatory responses and synaptic dysfunction. Taken together, this work demonstrates a toxic effect of C99 which could underlie some of the early-stage anatomical hallmarks of Alzheimer’s disease pathology. Our work also proposes molecular mechanisms likely explaining some of the unfavorable side-effects associated with γ-secretase inhibitor-directed therapies.
Similarity Estimation Between DNA Sequences Based on Local Pattern Histograms of Binary Images
Authors: Kobori Yusei , Mizuta Satoshi 
Published: April 2016

Abstract
Graphical representation of DNA sequences is one of the most popular techniques for alignment-free sequence comparison. Here, we propose a new method for the feature extraction of DNA sequences represented by binary images, by estimating the similarity between DNA sequences using the frequency histograms of local bitmap patterns of images. Our method shows linear time complexity for the length of DNA sequences, which is practical even when long sequences, such as whole genome sequences, are compared. We tested five distance measures for the estimation of sequence similarities, and found that the histogram intersection and Manhattan distance are the most appropriate ones for phylogenetic analyses.
A framework for similarity recognition of CAD models
Authors: Zehtaban Leila , Elazhary Omar , Roller Dieter 
Published: April 2016

Abstract
A designer is mainly supported by two essential factors in design decisions. These two factors are intelligence and experience aiding the designer by predicting the interconnection between the required design parameters. Through classification of product data and similarity recognition between new and existing designs, it is partially possible to replace the required experience for an inexperienced designer. Given this context, the current paper addresses a framework for recognition and flexible retrieval of similar models in product design. The idea is to establish an infrastructure for transferring design as well as the required PLM (Product Lifecycle Management) know-how to the design phase of product development in order to reduce the design time. Furthermore, such a method can be applied as a brainstorming method for a new and creative product development as well. The proposed framework has been tested and benchmarked while showing promising results.
Highlights Developing a knowledge-based framework to assist the designer in design decisions. Opitz feature recognition and code generation from STEP for data standardization. An efficient similarity recognition algorithm to retrieve models from database.
Determining an optimal hierarchical forecasting model based on the characteristics of the data set: Technical note
Authors: Nenova Zlatana D. , May Jerrold H. 
Published: April 2016

AbstractThe efficient flow of goods and services involves addressing multilevel forecast questions, and careful consideration when aggregating or disaggregating hierarchical estimates. Assessing all possible aggregation alternatives helps to determine the statistically most accurate way of consolidating multilevel forecasts. However, doing so in a multilevel and multiproduct supply chain may prove to be a very computationally intensive and time‐consuming task. In this paper, we present a new, two‐level oblique linear discriminant tree model, which identifies the optimal hierarchical forecast technique for a given hierarchical database in a very time‐efficient manner. We induced our model from a real‐world dataset, and it separates all historical time series into the four aggregation mechanisms considered. The separation process is a function of both the positive and negative correlation groups' variances at the lowest level of the hierarchical datasets. Our primary contributions are: (1) establishing a clear‐cut relationship between the correlation metrics at the lowest level of the hierarchy and the optimal aggregation mechanism for a product/service hierarchy, and (2) developing an analytical model for personalized forecast aggregation decisions, based on characteristics of a hierarchical dataset.
Schizophrenia interactome with 504 novel protein–protein interactions
Authors: Ganapathiraju Madhavi K , Thahir Mohamed , Handen Adam , Sarkar Saumendra N , Sweet Robert A , Nimgaonkar Vishwajit L , Loscher Christine E , Bauer Eileen M , Chaparala Srilakshmi 
Published: April 2016

AbstractGenome-wide association studies of schizophrenia (GWAS) have revealed the role of rare and common genetic variants, but the functional effects of the risk variants remain to be understood. Protein interactome-based studies can facilitate the study of molecular mechanisms by which the risk genes relate to schizophrenia (SZ) genesis, but protein–protein interactions (PPIs) are unknown for many of the liability genes. We developed a computational model to discover PPIs, which is found to be highly accurate according to computational evaluations and experimental validations of selected PPIs. We present here, 365 novel PPIs of liability genes identified by the SZ Working Group of the Psychiatric Genomics Consortium (PGC). Seventeen genes that had no previously known interactions have 57 novel interactions by our method. Among the new interactors are 19 drug targets that are targeted by 130 drugs. In addition, we computed 147 novel PPIs of 25 candidate genes investigated in the pre-GWAS era. While there is little overlap between the GWAS genes and the pre-GWAS genes, the interactomes reveal that they largely belong to the same pathways, thus reconciling the apparent disparities between the GWAS and prior gene association studies. The interactome including 504 novel PPIs overall, could motivate other systems biology studies and trials with repurposed drugs. The PPIs are made available on a webserver, called Schizo-Pi at http://severus.dbmi.pitt.edu/schizo-pi with advanced search capabilities.
The transcriptomics of an experimentally evolved plant-virus interaction
Authors: Hillung Julia , García-García Francisco , Dopazo Joaquín , Cuevas José M. , Elena Santiago F. 
Published: April 2016

AbstractModels of plant-virus interaction assume that the ability of a virus to infect a host genotype depends on the matching between virulence and resistance genes. Recently, we evolved tobacco etch potyvirus (TEV) lineages on different ecotypes ofArabidopsis thaliana, and found that some ecotypes selected for specialist viruses whereas others selected for generalists. Here we sought to evaluate the transcriptomic basis of such relationships. We have characterized the transcriptomic responses of five ecotypes infected with the ancestral and evolved viruses. Genes and functional categories differentially expressed by plants infected with local TEV isolates were identified, showing heterogeneous responses among ecotypes, although significant parallelism existed among lineages evolved in the same ecotype. Although genes involved in immune responses were altered upon infection, other functional groups were also pervasively over-represented, suggesting that plant resistance genes were not the only drivers of viral adaptation. Finally, the transcriptomic consequences of infection with the generalist and specialist lineages were compared. Whilst the generalist induced very similar perturbations in the transcriptomes of the different ecotypes, the perturbations induced by the specialist were divergent. Plant defense mechanisms were activated when the infecting virus was specialist but they were down-regulated when infecting with generalist.
Comparative study on the spectral properties of boron clusters Bn0/−1(n = 38–40)
Authors: Li Shixiong , Zhang Zhengping , Long Zhengwen , Sun Guangyu , Qin Shuijie 
Published: April 2016

AbstractThe all-boron fullerenes B40−1 and B39−1 discovered in recent experiments are characterized and revealed using photoelectron spectroscopy. Except for the photoelectron spectroscopy, one may identify such boron clusters with other spectroscopic techniques, such as infrared spectra and Raman spectra. Insight into the spectral properties of boron clusters is important to understand the boron clusters and find their potential applications. In this work, density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations are carried out to comparatively study the vibrational frequencies, infrared spectra, Raman spectra and electronic absorption spectra of boron clusters Bn0/−1(n = 38–40). The numerical simulations show that such boron clusters have different and meaningful spectral features. These spectral features are readily compared with future spectroscopy measurements and can be used as fingerprints to distinguish the boron clusters Bn0/−1 with different structures (cage structure or quasi-planar structure) and with different sizes (n = 38–40).
Rigorous Approach for Design of Differential Coupled-Line Directional Couplers Applicable in Integrated Circuits and Substrate-Embedded Networks
Authors: Staszek Kamil , Wincza Krzysztof , Gruszczynski Slawomir 
Published: April 2016

AbstractWe report rigorous approach for the design of differential coupled-line directional couplers in multilayer dielectric structures. In the proposed procedure numerically calculated per-unit-length parameters of coupled transmission lines are utilized for derivation of differential couplers’ properties. The known description technique with multimode scattering parameters has been extended to the eight-ports considered in the paper and the properties resulting from symmetry of the considered networks have been shown. Exemplary 3-dB and 8-dB coupled-line directional couplers have been designed and experimentally evaluated. Nodal to mixed-mode conversion of scattering parameters has been applied to allow for measurements of the physically realized models. Results of measurements are shown to confirm the presented theoretical considerations.
Neural mechanisms to predict subjective level of fatigue in the future: a magnetoencephalography study
Authors: Ishii Akira , Tanaka Masaaki , Watanabe Yasuyoshi 
Published: April 2016

AbstractFatigue is a major contributor to workplace accidents, morbidity and mortality. To prevent the disruption of homeostasis and to concurrently accomplish an assigned workload, it is essential to control the level of workload based on the subjective estimation of the level of fatigue that will be experienced in the near future. In this study, we aimed to clarify the neural mechanisms related to predicting subjective levels of fatigue that would be experienced 60 min later, using magnetoencephalography. Sixteen healthy male volunteers participated in this study. In relation to the prediction, a decrease of alpha band power in the right Brodmann’s area (BA) 40 and BA 9 at 1200 to 1350 ms and that in the right BA 9 at 1350 to 1500 ms and a decrease of gamma band power in the right BA 10 at 1500 to 1650 ms were observed. In addition, the decreased level of alpha band power in BA 9 at 1200 to 1350 ms was positively associated with the daily level of fatigue. These findings may help increase our understanding of the neural mechanisms activated to indicate the need to take a rest based on the prediction of the subjective fatigue in the future.
A dynamic interaction process between KaiA and KaiC is critical to the cyanobacterial circadian oscillator
Authors: Dong Pei , Fan Ying , Sun Jianqiang , Lv Mengting , Yi Ming , Tan Xiao , Liu Sen 
Published: April 2016

AbstractThe core circadian oscillator of cyanobacteria consists of three proteins, KaiA, KaiB, and KaiC. This circadian oscillator could be functionally reconstituted in vitro with these three proteins, and therefore has been a very important model in circadian rhythm research. KaiA can bind to KaiC and then stimulate its phosphorylation, but their interaction mechanism remains elusive. In this study, we followed the “second-site suppressor” strategy to investigate the interaction mechanism of KaiA and KaiC. Using protein sequence analyses, we showed that there exist co-varying residues in the binding interface of KaiA and KaiC. The followed mutagenesis study verified that these residues are important to the functions of KaiA and KaiC, but their roles could not be fully explained by the reported complex structures of KaiA and KaiC derived peptides. Combining our data with previous reports, we suggested a dynamic interaction mechanism in KaiA-KaiC interaction, in which both KaiA and the intrinsically disordered tail of KaiC undergo significant structural changes through conformational selection and induced fit during the binding process. At last, we presented a mathematic model to support this hypothesis and explained the importance of this interaction mechanism for the KaiABC circadian oscillator.
Preparation of Nickel Cobalt Sulfide Hollow Nanocolloids with Enhanced Electrochemical Property for Supercapacitors Application
Authors: Chen Zhenhua , Wan Zhanghui , Yang Tiezhu , Zhao Mengen , Lv Xinyan , Wang Hao , Ren Xiuli , Mei Xifan 
Published: April 2016

AbstractNanostructured functional materials with hollow interiors are considered to be good candidates for a variety of advanced applications. However, synthesis of uniform hollow nanocolloids with porous texture via wet chemistry method is still challenging. In this work, nickel cobalt precursors (NCP) in sub-micron sized spheres have been synthesized by a facile solvothermal method. The subsequent sulfurization process in hydrothermal system has changed the NCP to nickel cobalt sulfide (NCS) with porous texture. Importantly, the hollow interiors can be tuned through the sulfurization process by employing different dosage of sulfur source. The derived NCS products have been fabricated into supercapacitor electrodes and their electrochemical performances are measured and compared, where promising results were found for the next-generation high-performance electrochemical capacitors.
Dissociating the therapeutic effects of environmental enrichment and exercise in a mouse model of anxiety with cognitive impairment
Authors: Rogers J , Vo U , Buret LS , Pang TY , Meiklejohn H , Zeleznikow-Johnston A , Churilov L , van den Buuse M , Hannan AJ , Renoir T 
Published: April 2016

AbstractClinical evidence indicates that serotonin-1A receptor (5-HT1AR) gene polymorphisms are associated with anxiety disorders and deficits in cognition. In animal models, exercise (Ex) and environmental enrichment (EE) can change emotionality-related behaviours, as well as enhance some aspects of cognition and hippocampal neurogenesis. We investigated the effects of Ex and EE (which does not include running wheels) on cognition and anxiety-like behaviours in wild-type (WT) and 5-HT1AR knock-out (KO) mice. Using an algorithm-based classification of search strategies in the Morris water maze, we report for we believe the first time that Ex increased the odds for mice to select more hippocampal-dependent strategies. In the retention probe test, Ex (but not EE) corrected long-term spatial memory deficits displayed by KO mice. In agreement with these findings, only Ex increased hippocampal cell survival and BDNF protein levels. However, only EE (but not Ex) modified anxiety-like behaviours, demonstrating dissociation between improvements in cognition and innate anxiety. EE enhanced hippocampal cell proliferation in WT mice only, suggesting a crucial role for intact serotonergic signalling in mediating this effect. Together, these results demonstrate differential effects of Ex vs EE in a mouse model of anxiety with cognitive impairment. Overall, the 5-HT1AR does not seem to be critical for those behavioural effects to occur. These findings will have implications for our understanding of how Ex and EE enhance experience-dependent plasticity, as well as their differential impacts on anxiety and cognition.
1,8-Cineole potentiates IRF3-mediated antiviral response in human stem cells and in an ex vivo model of rhinosinusitis
Authors: Müller Janine , Greiner Johannes F.W. , Zeuner Marie , Brotzmann Viktoria , Schäfermann Johanna , Wieters Frederique , Widera Darius , Sudhoff Holger , Kaltschmidt Barbara , Kaltschmidt Christian 
Published: April 2016

The common cold is one of the most frequent human inflammatory diseases caused by viruses and can facilitate bacterial superinfections, resulting in sinusitis or pneumonia. The active ingredient of the drug Soledum, 1,8-cineole, is commonly applied for treating inflammatory diseases of the respiratory tract. However, the potential for 1,8-cineole to treat primary viral infections of the respiratory tract remains unclear. In the present study, we demonstrate for the first time that 1,8-cineole potentiates poly(I:C)-induced activity of the antiviral transcription factor interferon regulatory factor 3 (IRF3), while simultaneously reducing proinflammatory nuclear factor (NF)-κB activity in human cell lines, inferior turbinate stem cells (ITSCs) and in ex vivo cultivated human nasal mucosa. Co-treatment of cell lines with poly(I:C) and 1,8-cineole resulted in significantly increased IRF3 reporter gene activity compared with poly(I:C) alone, whereas NF-κB activity was reduced. Accordingly, 1,8-cineole- and poly(I:C) treatment led to increased nuclear translocation of IRF3 in ITSCs and a human ex vivo model of rhinosinusitis compared with the poly(I:C) treatment approach. Nuclear translocation of IRF3 was significantly increased in ITSCs and slice cultures treated with lipopolysaccharide (LPS) and 1,8-cineole compared with the LPS-treated cells mimicking bacterial infection. Our findings strongly suggest that 1,8-cineole potentiates the antiviral activity of IRF3 in addition to its inhibitory effect on proinflammatory NF-κB signalling, and may thus broaden its field of application.
Injury and Illness Rates During Ultratrail Running
Authors: Vernillo G. , Savoldelli A. , La Torre A. , Skafidas S. , Bortolan L. , Schena F. 
Published: April 2016

AbstractThis study aimed to describe injury/illness rates in ultratrail runners competing in a 65-km race to build a foundation for injury prevention and help race organizers to plan medical provision for these events. Prospectively transcribed medical records were analysed for 77 athletes at the end of the race. Number of injuries/illnesses per 1 000 runners and per 1 000-h run, overall injury/illness rate and 90% confidence intervals and rates for major and minor illnesses, musculoskeletal injuries, and skin disorders were analysed. A total of 132 injuries/illnesses were encountered during the race. The overall injuries/illnesses were 1.9 per runner and 187.9 per 1000-h run. Medical illnesses were the most prominent medical diagnoses encountered (50.3%), followed by musculoskeletal injuries (32.8%), and skin-related disorders (16.9%). Despite the ultra-long nature of the race, the majority of injuries/illnesses were minor in nature. Medical staff and runners should prepare to treat all types of injuries and illnesses, especially the fatigue arising throughout the course of an ultratrail run and injuries to the lower limbs. Future studies should attempt to systematically identify injury locations and mechanisms in order to better direct injury prevention strategies and plan more accurate medical care.