bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of HSP90 inhibitors as a novel class of senolytics
Authors: Fuhrmann-Stroissnigg Heike , Ling Yuan Yuan , Zhao Jing , McGowan Sara J. , Zhu Yi , Brooks Robert W. , Grassi Diego , Gregg Siobhan Q. , Stripay Jennifer L. , Dorronsoro Akaitz , Corbo Lana , Tang Priscilla , Bukata Christina , Ring Nadja , Giacca Mauro , Li Xuesen , Tchkonia Tamara , Kirkland James L. , Niedernhofer Laura J. , Robbins Paul D. 
Published: August 2017

AbstractAging is the main risk factor for many chronic degenerative diseases and cancer. Increased senescent cell burden in various tissues is a major contributor to aging and age-related diseases. Recently, a new class of drugs termed senolytics were demonstrated to extending healthspan, reducing frailty and improving stem cell function in multiple murine models of aging. To identify novel and more optimal senotherapeutic drugs and combinations, we established a senescence associated β-galactosidase assay as a screening platform to rapidly identify drugs that specifically affect senescent cells. We used primary Ercc1−/− murine embryonic fibroblasts with reduced DNA repair capacity, which senesce rapidly if grown at atmospheric oxygen. This platform was used to screen a small library of compounds that regulate autophagy, identifying two inhibitors of the HSP90 chaperone family as having significant senolytic activity in mouse and human cells. Treatment of Ercc1−/∆ mice, a mouse model of a human progeroid syndrome, with the HSP90 inhibitor 17-DMAG extended healthspan, delayed the onset of several age-related symptoms and reduced p16INK4a expression. These results demonstrate the utility of our screening platform to identify senotherapeutic agents as well as identified HSP90 inhibitors as a promising new class of senolytic drugs.
Orbital bistatic radar observations of asteroid Vesta by the Dawn mission
Authors: Palmer Elizabeth M. , Heggy Essam , Kofman Wlodek 
Published: August 2017

AbstractWe present orbital bistatic radar observations of a small-body, acquired during occultation by the Dawn spacecraft at asteroid Vesta. The radar forward-scattering properties of different reflection sites are used to assess the textural properties of Vesta’s surface at centimeter-to-decimeter scales and are compared to subsurface hydrogen concentrations observed by Dawnʼs Gamma Ray and Neutron Detector to assess potential volatile occurrence in the surface and shallow subsurface. We observe significant differences in surface radar reflectivity, implying substantial spatial variations in centimeter-to-decimeter-scale surface roughness. Our results suggest that unlike the Moon, Vesta’s surface roughness variations cannot be explained by cratering processes only. In particular, the occurrence of heightened hydrogen concentrations within large smoother terrains (over hundreds of square kilometers) suggests that potential ground-ice presence may have contributed to the formation of Vesta’s current surface texture. Our observations are consistent with geomorphological evidence of transient water flow from Dawn Framing Camera images.
Demonstration of sub-luminal propagation of single-cycle terahertz pulses for particle acceleration
Authors: Walsh D. A. , Lake D. S. , Snedden E. W. , Cliffe M. J. , Graham D. M. , Jamison S. P. 
Published: August 2017

AbstractThe sub-luminal phase velocity of electromagnetic waves in free space is generally unobtainable, being closely linked to forbidden faster than light group velocities. The requirement of sub-luminal phase-velocity in laser-driven particle acceleration schemes imposes a limit on the total acceleration achievable in free space, and necessitates the use of dispersive structures or waveguides for extending the field-particle interaction. We demonstrate a travelling source approach that overcomes the sub-luminal propagation limits. The approach exploits ultrafast optical sources with slow group velocity propagation, and a group-to-phase front conversion through nonlinear optical interaction. The concept is demonstrated with two terahertz generation processes, nonlinear optical rectification and current-surge rectification. We report measurements of longitudinally polarised single-cycle electric fields with phase and group velocity between 0.77c and 1.75c. The ability to scale to multi-megavolt-per-metre field strengths is demonstrated. Our approach paves the way towards the realisation of cheap and compact particle accelerators with femtosecond scale control of particles.
Ethnic differences in smoking intensity and COPD risk: an observational study in primary care
Authors: Gilkes Alexander , Hull Sally , Durbaba Stevo , Schofield Peter , Ashworth Mark , Mathur Rohini , White Patrick 
Published: August 2017

AbstractChronic obstructive pulmonary disease risk is lower in black and south Asian people than white people, when adjusting for age, sex, deprivation and smoking status. The role of smoking intensity was assessed for its contribution to ethnic differences in chronic obstructive pulmonary disease risk, a relationship not previously investigated. This cross-sectional study included routinely collected primary care data from four multi-ethnic London boroughs. Smoking intensity (estimated by cigarettes per day) was compared between ethnic groups. Chronic obstructive pulmonary disease risk was compared between ethnic groups using multiple logistic regression, controlling for age, sex, deprivation, asthma and both smoking status and smoking intensity, examined independently. In all, 1,000,388 adults were included. Smoking prevalence and intensity were significantly higher in the white British/Irish groups than other ethnic groups. Higher smoking intensity was associated with higher chronic obstructive pulmonary disease risk. Chronic obstructive pulmonary disease risk was significantly lower in all ethnic groups compared with white British/Irish after adjustment for either smoking status or smoking intensity, with lowest risk in black Africans (odds ratio 0.33; confidence interval 0.28–0.38). Ethnic differences in chronic obstructive pulmonary disease risk were not explained in this study by ethnic differences in smoking prevalence or smoking intensity. Other causes of ethnic differences in chronic obstructive pulmonary disease risk should be sought, including ethnic differences in smoking behaviour, environmental factors, repeated respiratory infections, immigrant status, metabolism and addictiveness of nicotine and differential susceptibility to the noxious effects of cigarette smoke.
Schizophrenia genetics in the genome-wide era: a review of Japanese studies
Authors: Kanazawa Tetsufumi , Bousman Chad A. , Liu Chenxing , Everall Ian P. 
Published: August 2017

AbstractThe introduction of the genome-wide association study transformed schizophrenia genetics research and has promoted a genome-wide mindset that has stimulated the development of genomic technology, enabling departures from the traditional candidate gene approach. As result, we have witnessed a decade of major discoveries in schizophrenia genetics and the development of genome-wide approaches to the study of copy number variants. These genomic technologies have primarily been applied in populations of European descent. However, more recently both genome-wide association study and copy number variant studies in Asian populations have begun to emerge. In this invited review, we provide concise summaries of the schizophrenia genome-wide association study and copy number variant literature with specific focus on studies conducted in the Japanese population. When applicable, we compare findings observed in the Japanese population with those found in other populations. We conclude with recommendations for future research in schizophrenia genetics, relevant to Japan and beyond.
Conjoint and dissociated structural and functional abnormalities in first-episode drug-naive patients with major depressive disorder: a multimodal meta-analysis
Authors: Wang Weina , Zhao Youjin , Hu Xinyu , Huang Xiaoqi , Kuang Weihong , Lui Su , Kemp Graham J. , Gong Qiyong 
Published: August 2017

AbstractPublished MRI evidence of structural and resting-state functional brain abnormalities in MDD has been inconsistent. To eliminate interference by repeated disease episodes and antidepressant treatment, we conducted the first multimodal voxel-wise meta-analysis of studies of voxel-based morphometry (VBM) and the amplitude of low-frequency fluctuation (ALFF) in first-episode drug-naive MDD patients, using the Seed-based d Mapping method (SDM). Fifteen VBM data sets and 11 ALFF data sets were included. SDM-based multimodal meta-analysis was used to highlight brain regions with both structural and functional abnormalities. This identified conjoint structural and functional abnormalities in left lateral orbitofrontal cortex and right supplementary motor area, and also dissociated abnormalities of structure (decreased grey matter in right dorsolateral prefrontal cortex and right inferior temporal gyrus; increased grey matter in right insula, right putamen, left temporal pole, and bilateral thalamus) and function (increased brain activity in left supplementary motor area, left parahippocampal gyrus, and hippocampus; decreased brain activity in right lateral orbitofrontal cortex). This study reveals a complex pattern of conjoint and dissociated structural and functional abnormalities, supporting the involvement of basal ganglia-thalamocortical circuits, representing emotional, cognitive and psychomotor abnormalities, in the pathophysiology of early-stage MDD. Specifically, this study adds to Psychoradiology, an emerging subspecialty of radiology, which seems primed to play a major clinical role in guiding diagnostic and treatment planning decisions in patients with mental disorder.
Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities
Authors: Sadeghi-Naini Ali , Sannachi Lakshmanan , Tadayyon Hadi , Tran William T. , Slodkowska Elzbieta , Trudeau Maureen , Gandhi Sonal , Pritchard Kathleen , Kolios Michael C. , Czarnota Gregory J. 
Published: August 2017

AbstractAnti-cancer therapies including chemotherapy aim to induce tumour cell death. Cell death introduces alterations in cell morphology and tissue micro-structures that cause measurable changes in tissue echogenicity. This study investigated the effectiveness of quantitative ultrasound (QUS) parametric imaging to characterize intra-tumour heterogeneity and monitor the pathological response of breast cancer to chemotherapy in a large cohort of patients (n = 100). Results demonstrated that QUS imaging can non-invasively monitor pathological response and outcome of breast cancer patients to chemotherapy early following treatment initiation. Specifically, QUS biomarkers quantifying spatial heterogeneities in size, concentration and spacing of acoustic scatterers could predict treatment responses of patients with cross-validated accuracies of 82 ± 0.7%, 86 ± 0.7% and 85 ± 0.9% and areas under the receiver operating characteristic (ROC) curve of 0.75 ± 0.1, 0.80 ± 0.1 and 0.89 ± 0.1 at 1, 4 and 8 weeks after the start of treatment, respectively. The patients classified as responders and non-responders using QUS biomarkers demonstrated significantly different survivals, in good agreement with clinical and pathological endpoints. The results form a basis for using early predictive information on survival-linked patient response to facilitate adapting standard anti-cancer treatments on an individual patient basis.
Miltefosine Resistant Field Isolate From Indian Kala-Azar Patient Shows Similar Phenotype in Experimental Infection
Authors: Khanra Supriya , Sarraf Nibedeeta R. , Das Anjan K. , Roy Syamal , Manna Madhumita 
Published: August 2017

AbstractEmergence of resistance to drugs used to treat the Indian Kala-azar patients makes control strategy shattered. In this bleak situation, Miltefosine (MIL) was introduced to treat mainly antimonial unresponsive cases. Within years, resistance to MIL has been reported. While checking the MIL sensitivity of the recent KA clinical isolates (n = 26), we came across one isolate which showed four times more EC50 for MIL than that of MIL-Sensitive (MIL-S) isolates and considered as putative MIL-Resistant (MIL-R). The expressions of LdMT and LdRos3 genes of this isolate were found down regulated. Th1/Th2 cytokines, ROS and NO, FACS dot plots and mitochondrial trans membrane potential measurement were performed. In vivo hamster model with this MIL-R isolate showed much lesser reduction in liver weight (17.5%) compared to average reduction in liver weight (40.2%) of the animals infected with MIL-S isolates. The splenic and hepatic stamps smears of MIL-R infected hamsters revealed the retention of parasite load of about 51.45%. The splenocytes of these animals failed to proliferate anti leishmanial T-cells and lack of cell mediated immunity hampered recovery. Thus, these phenotypic expressions of experimental model may be considered similar to that of the MIL unresponsive patients. This is first such kind of report.
Effect of Correlations in Swarms on Collective Response
Authors: Mateo David , Kuan Yoke Kong , Bouffanais Roland 
Published: August 2017

AbstractSocial interaction increases significantly the performance of a wide range of cooperative systems. However, evidence that natural swarms limit the number of interactions suggests potentially detrimental consequences of excessive interaction. Using a canonical model of collective motion, we find that the collective response to a dynamic localized perturbation–emulating a predator attack–is hindered when the number of interacting neighbors exceeds a certain threshold. Specifically, the effectiveness in avoiding the predator is enhanced by large integrated correlations, which are known to peak at a given level of interagent interaction. From the network-theoretic perspective, we uncover the same interplay between number of connections and effectiveness in group-level response for two distinct decision-making models of distributed consensus operating over a range of static networks. The effect of the number of connections on the collective response critically depends on the dynamics of the perturbation. While adding more connections improves the response to slow perturbations, the opposite is true for fast ones. These results have far-reaching implications for the design of artificial swarms or interaction networks.
Zoonotic intestinal helminths interact with the canine immune system by modulating T cell responses and preventing dendritic cell maturation
Authors: Junginger Johannes , Raue Katharina , Wolf Karola , Janecek Elisabeth , Stein Veronika M. , Tipold Andrea , Günzel-Apel Anne-Rose , Strube Christina , Hewicker-Trautwein Marion 
Published: August 2017

AbstractParasite co-evolution alongside the mammalian immune system gave rise to several modulatory strategies by which they prevent exaggerated pathology and facilitate a longer worm survival. As little is known about the immunoregulatory potential of the zoonotic canine parasites Ancylostoma caninum and Toxocara canis in the natural host, the present study aimed to investigate whether their larval excretory-secretory (ES) products can modulate the canine immune system. We demonstrated TcES to increase the frequency of CD4+ Foxp3high T cells, while both AcES and TcES were associated with elevated Helios expression in Foxp3high lymphocytes. ES products were further capable of inducing IL-10 production by lymphocytes, which was mainly attributed to CD8+ T cells. ES treatment of PBMCs prior to mitogen stimulation inhibited polyclonal proliferation of CD4+ and CD8+ T cells. Moreover, monocyte-derived ES-pulsed dendritic cells reduced upregulation of MHC-II and CD80 in response to lipopolysaccharide. The data showed that regulation of the canine immune system by A. caninum and T. canis larvae comprises the modification of antigen-specific and polyclonal T cell responses and dendritic cell maturation.
Cell Division Cycle 42 plays a Cell type-Specific role in Lung Tumorigenesis
Authors: Zheng Chao , Wang Yuetong , Yang Liu , Zhou Shuhua , Gao Yijun , Li Fuming , Feng Yan , Wang Zuoyun , Zhan Lixing , Yan Qin , Zhu Xueliang , Wong Kwok-Kin , Chen Zhengjun , Ji Hongbin 
Published: August 2017

AbstractCell division cycle 42 (CDC42) plays important roles in polarity establishment and maintenance as well as cell cycle progression and cell division. Although disruption of cell polarity is a prerequisite in epithelial tumor initiation, the roles of CDC42 in tumorigenesis are still poorly understood. Here we find that Cdc42 deficiency inhibits the Kras
G12D
-induced lung alveoli tumor formation, while conversely promotes bronchiole tumor formation in mice. Bronchial Cdc42 loss destroys contact inhibition potentially through cell polarity disruption, and results in increased tumor formation. In contrast, deletion of Cdc42 in alveoli cells prevents Kras
G12D
-induced cell proliferation, which leads to reduced tumor formation. Further analyses of clinical specimens uncover a significant positive correlation between CDC42 and type II alveolar epithelial cells marker SP-A, indicating the potential importance of CDC42 in this specific subset of lung cancer. Collectively, we identify the lineage-specific function of CDC42 in lung tumorigenesis potentially through the regulation of cell polarity integrity.
Digital holographic high-speed 3D imaging for the vibrometry of fast-occurring phenomena
Authors: Kakue Takashi , Endo Yutaka , Nishitsuji Takashi , Shimobaba Tomoyoshi , Masuda Nobuyuki , Ito Tomoyoshi 
Published: August 2017

AbstractDigital holography allows production of high-speed three-dimensional images at rates over 100,000 frames per second; however, simultaneously obtaining suitable performance and levels of accuracy using digital holography is difficult. This problem prevents high-speed three-dimensional imaging from being used for vibrometry. In this paper, we propose and test a digital holography method that can produce vibration measurements. The method is based on single-shot phase-shifting interferometry. Herein, we imaged the surface of a loudspeaker diaphragm and measured its displacement due to the vibrations produced by a frequency sweep signal. We then analyzed the frequency of the experimental data and confirmed that the frequency spectra inferred from the reconstructed images agreed well with the spectra produced by the sound recorded by a microphone. This method can be used for measuring vibrations with three-dimensional imaging for loudspeakers, microelectromechanical systems, surface acoustic wave filters, and biological tissues and organs.
A novel inducible mutagenesis screen enables to isolate and clone both embryonic and adult zebrafish mutants
Authors: Ma Zhipeng , Zhu Peipei , Pang Meijun , Guo Liwei , Chang Nannan , Zheng Jiyuan , Zhu Xiaojun , Gao Ce , Huang Honghui , Cui Zongbin , Xiong Jing-Wei , Peng Jinrong , Chen Jun 
Published: August 2017

AbstractConventional genetic screens for recessive mutants are inadequate for studying biological processes in the adult vertebrate due to embryonic lethality. Here, we report that a novel inducible mutagenesis system enables to study gene function in both embryonic and adult zebrafish. This system yields genetic mutants with conditional ectopic over- or under-expression of genes in F1 heterozygotes by utilizing inducible Tet-On transcriptional activation of sense or anti-sense transcripts from entrapped genes by Tol2 transposase-meditated transgenesis. Pilot screens identified 37 phenotypic mutants displaying embryonic defects (34 lines), adult fin regeneration defects (7 lines), or defects at both stages (4 lines). Combination of various techniques (such as: generating a new mutant allele, injecting gene specific morpholino or mRNA etc) confirms that Dox-induced embryonic abnormalities in 10 mutants are due to dysfunction of entrapped genes; and that Dox-induced under-expression of 6 genes causes abnormal adult fin regeneration. Together, this work presents a powerful mutagenesis system for genetic analysis from zebrafish embryos to adults in particular and other model organisms in general.
A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis
Authors: Maheshwari Vaibhav , Thijssen Stephan , Tao Xia , Fuertinger Doris , Kappel Franz , Kotanko Peter 
Published: August 2017

AbstractProtein-bound uremic toxins (PBUTs) are difficult to remove by conventional hemodialysis; a high degree of protein binding reduces the free fraction of toxins and decreases their diffusion across dialyzer membranes. Mechanistic understanding of PBUT kinetics can open new avenues to improve their dialytic removal. We developed a comprehensive model of PBUT kinetics that comprises: (1) a three-compartment patient model, (2) a dialyzer model. The model accounts for dynamic equilibrium between protein, toxin, and the protein-toxin complex. Calibrated and validated using clinical and experimental data from the literature, the model predicts key aspects of PBUT kinetics, including the free and bound concentration profiles for PBUTs and the effects of dialysate flow rate and dialyzer size on PBUT removal. Model simulations suggest that an increase in dialysate flow rate improves the reduction ratio (and removal) of strongly protein-bound toxins, namely, indoxyl sulfate and p-cresyl sulfate, while for weakly bound toxins, namely, indole-3-acetic acid and p-cresyl glucuronide, an increase in blood flow rate is advantageous. With improved dialyzer performance, removal of strongly bound PBUTs improves gradually, but marginally. The proposed model can be used for optimizing the dialysis regimen and for in silico testing of novel approaches to enhance removal of PBUTs.
Capturing PM2.5 Emissions from 3D Printing via Nanofiber-based Air Filter
Authors: Rao Chengchen , Gu Fu , Zhao Peng , Sharmin Nusrat , Gu Haibing , Fu Jianzhong 
Published: August 2017

AbstractThis study investigated the feasibility of using polycaprolactone (PCL) nanofiber-based air filters to capture PM2.5 particles emitted from fused deposition modeling (FDM) 3D printing. Generation and aggregation of emitted particles were investigated under different testing environments. The results show that: (1) the PCL nanofiber membranes are capable of capturing particle emissions from 3D printing, (2) relative humidity plays a signification role in aggregation of the captured particles, (3) generation and aggregation of particles from 3D printing can be divided into four stages: the PM2.5 concentration and particles size increase slowly (first stage), small particles are continuously generated and their concentration increases rapidly (second stage), small particles aggregate into more large particles and the growth of concentration slows down (third stage), the PM2.5 concentration and particle aggregation sizes increase rapidly (fourth stage), and (4) the ultrafine particles denoted as “building unit” act as the fundamentals of the aggregated particles. This work has tremendous implications in providing measures for controlling the particle emissions from 3D printing, which would facilitate the extensive application of 3D printing. In addition, this study provides a potential application scenario for nanofiber-based air filters other than laboratory theoretical investigation.