bluuebunny/crossref_metadata_2025 huggingface dataset:
Supporting wellbeing in motor neurone disease for patients, carers, social networks, and health professionals: A scoping review and synthesis
Authors: Harris Melanie , Thomas Geoff , Thomas Mary , Cafarella Paul , Stocks Allegra , Greig Julia , McEvoy R. Doug
Published: August 2017

Objective:

Disease management in motor neurone disease (MND) is focused on preserving quality of life. However, the emphasis has so far been on physical symptoms and functioning and not psychosocial wellbeing. MND affects the wellbeing of carers, of family and social network members, and of healthcare providers, as well as of the patients. We therefore aimed to assess and synthesize the knowledge about maximizing MND-related psychosocial wellbeing across all these groups.

Method:

We used a systematic search and selection process to assess the scope of the literature along with a narrative synthesis of recent high-quality reviews.

Results:

The original studies were mainly observational studies of patients and, to a lesser extent, of carers. There were few interventional studies, mainly of patients. There were very few studies of any type on wellbeing in their wider social network or in healthcare professionals. All the review literature looked at MND patient or carer wellbeing, with some covering both. No reviews were found of wellbeing in other family members, patients' social networks, or their healthcare professionals. The reviews demonstrated wellbeing problems for patients linked to psychosocial issues. Carer wellbeing is also compromised. Psychotherapies, social supports, improved decision supports, and changes to healthcare delivery are among the suggested strategies for improved patient and carer wellbeing, but no proven interventions were identified for either. Early access to palliative care, also not well-tested but recommended, is poorly implemented.

Significance of results:

Work on interventions to deal with well-established wellbeing problems for patients and carers is now a research priority. Explicit use of current methods for patient and public involvement and for design and testing of interventions provide a toolkit for this research. Observational research is needed in other groups. There is a potential in considering needs across patients' social networks rather than looking individually at particular groups.
Sideshows at the Center - British Campaigns in the Middle East during the Great War
Authors: Satia Priya
Published: August 2017

This article places the Middle East campaigns at the heart of the effort to understand the First World War's cultural impact in Britain. By doing so, it shows that the effects typically attributed to the western front—loss of faith in technology and heroism—were mediated in important ways by lessons emerging from the Middle Eastern fronts in Palestine and Mesopotamia, where the British found their faith in technology strengthened. By incorporating that cultural legacy, we can better understand why Britons remained committed to the war and why they maintained their faith in industrial development and imperial warfare after the war had ended. The heroic image of T. E. Lawrence and of the infrastructural development undertaken by the British military in Mesopotamia bolstered faith in technology and imperialism just when the western front was revealing their darker side. The article begins with a study of the unique military tactics the British adopted in the region, shaped by particular cultural notions about a largely imaginary “Arabia”: deception, irregular warfare, and airpower were used to an unprecedented degree in these campaigns. It goes on to show how the British government strove to capitalize on the propaganda effects of these “sideshows” as they became successful. In particular, they stressed the notion that the empire could find redemption in the restoration of the ancient “cradle of civilization.” Such ideas sustained idealistic notions even as the western front unleashed a new kind of cynicism.
Engineering New Foundations for a Thawing Arctic
Authors: Poppick Laura
Published: August 2017

Researchers experiment with new building supports to prepare the Arctic for rapid shifts in permafrost and ground stability.
Large-scale comparative metagenomics of Blastocystis, a common member of the human gut microbiome
Authors: Beghini Francesco , Pasolli Edoardo , Truong Tin Duy , Putignani Lorenza , Cacciò Simone M , Segata Nicola
Published: August 2017

The influence of unicellular eukaryotic microorganisms on human gut health and disease is still largely unexplored. Blastocystis spp. commonly colonize the gut, but its clinical significance and ecological role are currently unsettled. We have developed a high-sensitivity bioinformatic pipeline to detect Blastocystis subtypes (STs) from shotgun metagenomics, and applied it to 12 large data sets, comprising 1689 subjects of different geographic origin, disease status and lifestyle. We confirmed and extended previous observations on the high prevalence the microrganism in the population (14.9%), its non-random and ST-specific distribution, and its ability to cause persistent (asymptomatic) colonization. These findings, along with the higher prevalence observed in non-westernized individuals, the lack of positive association with any of the disease considered, and decreased presence in individuals with dysbiosis associated with colorectal cancer and Crohn’s disease, strongly suggest that Blastocystis is a component of the healthy gut microbiome. Further, we found an inverse association between body mass index and Blastocystis, and strong co-occurrence with archaeal organisms (Methanobrevibacter smithii) and several bacterial species. The association of specific microbial community structures with Blastocystis was confirmed by the high predictability (up to 0.91 area under the curve) of the microorganism colonization based on the species-level composition of the microbiome. Finally, we reconstructed and functionally profiled 43 new draft Blastocystis genomes and discovered a higher intra subtype variability of ST1 and ST2 compared with ST3 and ST4. Altogether, we provide an in-depth epidemiologic, ecological, and genomic analysis of Blastocystis, and show how metagenomics can be crucial to advance population genomics of human parasites.
Thermally-drawn fibers with spatially-selective porous domains
Authors: Grena Benjamin , Alayrac Jean-Baptiste , Levy Etgar , Stolyarov Alexander M. , Joannopoulos John D. , Fink Yoel
Published: August 2017

The control of mass transport using porous fibers is ubiquitous, with applications ranging from filtration to catalysis. Yet, to date, porous fibers have been made of single materials in simple geometries, with limited function. Here we report the fabrication and characterization of thermally drawn multimaterial fibers encompassing internal porous domains alongside non-porous insulating and conductive materials, in highly controlled device geometries. Our approach utilizes phase separation of a polymer solution during the preform-to-fiber drawing process, generating porosity as the fiber is drawn. Engineering the preform structure grants control over the geometry and materials architecture of the final porous fibers. Electrical conductivity of the selectrolyte-filled porous domains is substantiated through ionic conductivity measurements using electrodes thermally drawn in the cross-section. Pore size tunability between 500 nm–10 µm is established by regulating the phase separation kinetics. We further demonstrate capillary breakup of cylindrical porous structures porous microspheres within the fiber core.
A qualitative study of GP, nurse and practice manager views on using targeted case-finding to identify patients with COPD in primary care
Authors: Summers Rachael H. , Sharmeen Taniya , Lippiett Kate , Gillett Kate , Astles Carla , Vu Linh , Stafford-Watson Mark , Bruton Anne , Thomas Mike , Wilkinson Tom
Published: August 2017

‘Finding the missing millions’ with chronic obstructive pulmonary disease became part of the Department of Health strategy for England in 2010. Targeted case-finding within primary care is one potential pro-active strategy, but currently little is known about the views of healthcare professionals on this approach. In this study, 36 healthcare professionals (12 GPs, 14 nurses, and 10 practice managers) from 34 UK practices participated in semi-structured telephone interviews about targeted case-finding. Interviews followed an interview guide, were audio-recorded, transcribed verbatim, coded and analysed using ‘Framework Approach’. Most of those interviewed practiced opportunistic case-finding. The main perceived barriers to wider case-finding programmes were the resource implications associated with running such programmes and identifying more chronic obstructive pulmonary disease patients. Financial incentives, support from specialist clinicians, and comprehensive guidance were viewed as facilitators. While targeted case-finding is conceptually accepted by primary care staff, scepticism surrounding (1) the value of identifying those with mild disease and (2) the availability of effective targeted case-finding methods, may lead some to favour an opportunistic approach. Key concerns were a lack of unequivocal evidence for the relative benefits vs. disadvantages of diagnosing patients earlier, and resource constraints in an already over-burdened system. Barriers to practical implementation of case-finding studies may be addressed with financial, human and educational resources, such as additional staff to undertake searches and perform spirometry tests, and practical and educational support from specialist teams.
Comparative genomics of Australian and international isolates of Salmonella Typhimurium: correlation of core genome evolution with CRISPR and prophage profiles
Authors: Fu Songzhe , Hiley Lester , Octavia Sophie , Tanaka Mark M. , Sintchenko Vitali , Lan Ruiting
Published: August 2017

Salmonella enterica subsp enterica serovar Typhimurium (S. Typhimurium) is a serovar with broad host range. To determine the genomic diversity of S. Typhimurium, we sequenced 39 isolates (37 Australian and 2 UK isolates) representing 14 Repeats Groups (RGs) determined primarily by clustered regularly interspaced short palindromic repeats (CRISPR). Analysis of single nucleotide polymorphisms (SNPs) among the 39 isolates yielded an average of 1,232 SNPs per isolate, ranging from 128 SNPs to 11,339 SNPs relative to the reference strain LT2. Phylogenetic analysis of the 39 isolates together with 66 publicly available genomes divided the 105 isolates into five clades and 19 lineages, with the majority of the isolates belonging to clades I and II. The composition of CRISPR profiles correlated well with the lineages, showing progressive deletion and occasional duplication of spacers. Prophage genes contributed nearly a quarter of the S. Typhimurium accessory genome. Prophage profiles were found to be correlated with lineages and CRISPR profiles. Three new variants of HP2-like P2 prophage, several new variants of P22 prophage and a plasmid-like genomic island StmGI_0323 were found. This study presents evidence of horizontal transfer from other serovars or species and provides a broader understanding of the global genomic diversity of S. Typhimurium.
Cell-permeable capsids as universal antigen carrier for the induction of an antigen-specific CD8+ T-cell response
Authors: Akhras Sami , Toda Masako , Boller Klaus , Himmelsbach Kiyoshi , Elgner Fabian , Biehl Marlene , Scheurer Stephan , Gratz Meike , Vieths Stefan , Hildt Eberhard
Published: August 2017

Vaccine platforms that can be flexibly loaded with antigens can contribute to decrease response time to emerging infections. For many pathogens and chronic infections, induction of a robust cytotoxic T lymphocytes-mediated response is desirable to control infection. Antigen delivery into the cytoplasm of antigen presenting cells favors induction of cytotoxic T cells. By fusion of the cell-permeable translocation motif (TLM)-peptide to the capsid-forming core protein of hepatitis B virus, and by insertion of the strep-tag in the spike tip (a domain that protrudes from the surface of the capsid), cell-permeable carrier capsids were generated that can be flexibly loaded with various antigens. Loading with antigens was demonstrated by electron microscopy, density gradient centrifugation and surface plasmon resonance spectroscopy. Confocal immunofluorescence microscopy showed that cell-permeable carrier capsids mediate transfer of cargo antigen into the cytoplasm. Using cell-permeable carrier capsids loaded with ovalbumin as model antigen, activation of antigen presenting cells and ovalbumin-specific CD8+T-cells, which correlates with enhanced specific killing activity, was found. This demonstrates the capacity of TLM-carrier-capsids to serve as universal antigen carrier to deliver antigens into the cytoplasm of antigen presenting cells, which leads to enhanced MHC class I-mediated presentation and induction of antigen-specific cytotoxic T lymphocytes response.
Segregating Top-Down Selective Attention from Response Inhibition in a Spatial Cueing Go/NoGo Task: An ERP and Source Localization Study
Authors: Hong Xiangfei , Wang Yao , Sun Junfeng , Li Chunbo , Tong Shanbao
Published: August 2017

Successfully inhibiting a prepotent response tendency requires the attentional detection of signals which cue response cancellation. Although neuroimaging studies have identified important roles of stimulus-driven processing in the attentional detection, the effects of top-down control were scarcely investigated. In this study, scalp EEG was recorded from thirty-two participants during a modified Go/NoGo task, in which a spatial-cueing approach was implemented to manipulate top-down selective attention. We observed classical event-related potential components, including N2 and P3, in the attended condition of response inhibition. While in the ignored condition of response inhibition, a smaller P3 was observed and N2 was absent. The correlation between P3 and CNV during the foreperiod suggested an inhibitory role of P3 in both conditions. Furthermore, source analysis suggested that P3 generation was mainly localized to the midcingulate cortex, and the attended condition showed increased activation relative to the ignored condition in several regions, including inferior frontal gyrus, middle frontal gyrus, precentral gyrus, insula and uncus, suggesting that these regions were involved in top-down attentional control rather than inhibitory processing. Taken together, by segregating electrophysiological correlates of top-down selective attention from those of response inhibition, our findings provide new insights in understanding the neural mechanisms of response inhibition.
Graphene/h-BN Heterostructures for Vertical Architecture of RRAM Design
Authors: Huang Yi-Jen , Lee Si-Chen
Published: August 2017

The development of RRAM is one of the mainstreams for next generation non-volatile memories to replace the conventional charge-based flash memory. More importantly, the simpler structure of RRAM makes it feasible to be integrated into a passive crossbar array for high-density memory applications. By stacking up the crossbar arrays, the ultra-high density of 3D horizontal RRAM (3D-HRAM) can be realized. However, 3D-HRAM requires critical lithography and other process for every stacked layer, and this fabrication cost overhead increases linearly with the number of stacks. Here, it is demonstrated that the 2D material-based vertical RRAM structure composed of graphene plane electrode/multilayer h-BN insulating dielectric stacked layers, AlOx/TiOx resistive switching layer and ITO pillar electrode exhibits reliable device performance including forming-free, low power consumption (Pset = ~2 μW and Preset = ~0.2 μW), and large memory window (>300). The scanning transmission electron microscopy indicates that the thickness of multilayer h-BN is around 2 nm. Due to the ultrathin-insulating dielectric and naturally high thermal conductivity characteristics of h-BN, the vertical structure combining the graphene plane electrode with multilayer h-BN insulating dielectric can pave the way toward a new area of ultra high-density memory integration in the future.
Human antigen R-regulated CCL20 contributes to osteolytic breast cancer bone metastasis
Authors: Lee Sun Kyoung , Park Kwang-Kyun , Kim Hyun-Jeong , Park Junhee , Son Seung Hwa , Kim Ki Rim , Chung Won-Yoon
Published: August 2017

Breast cancer mainly spreads to bone, causing decreased survival of patient. Human antigen R (HuR) and chemokines are important molecules associated with mRNA stability and cell-cell interaction in cancer biology. Here, HuR knockdown inhibited bone metastasis and osteolysis of metastatic breast cancer cells in mice and HuR expression promoted the metastatic ability of cancer cells via CCL20 and GM-CSF. In contrast with the findings for GM-CSF, ELAVL1 and CCL20 expressions were markedly increased in breast tumor tissues and ELAVL1 expression showed a strong positive correlation with CCL20 expression in breast cancer subtypes, particularly the basal-like subtype. Metastasis-free survival and overall survival were decreased in the breast cancer patients with high CCL20 expression. We further confirmed the role of CCL20 in breast cancer bone metastasis. Intraperitoneal administration of anti-CCL20 antibodies inhibited osteolytic breast cancer bone metastasis in mice. Treatment with CCL20 noticeably promoted cell invasion and the secretion of MMP-2/9 in the basal-like triple-negative breast cancer cell lines, not the luminal. Moreover, CCL20 elevated the receptor activator of nuclear factors kappa-B ligand/osteoprotegerin ratio in breast cancer and osteoblastic cells and mediated the crosstalk between these cells. Collectively, HuR-regulated CCL20 may be an attractive therapeutic target for breast cancer bone metastasis.
Towards Noise Simulation in Interacting Nonequilibrium Systems Strongly Coupled to Baths
Authors: Miwa Kuniyuki , Chen Feng , Galperin Michael
Published: August 2017

Progress in experimental techniques at nanoscale makes measurements of noise in molecular junctions possible. These data are important source of information not accessible through average flux measurements. The emergence of optoelectronics, the recently shown possibility of strong light-matter couplings, and developments in the field of quantum thermodynamics are making measurements of transport statistics even more important. Theoretical methods for noise evaluation in first principles simulations can be roughly divided into approaches for weak intra-system interactions, and those treating strong interactions for systems weakly coupled to baths. We argue that due to structure of its diagrammatic expansion, and the use of many-body states as a basis of its formulation, the recently introduced nonequilibrium diagrammatic technique for Hubbard Green functions is a relatively inexpensive method suitable for evaluation of noise characteristics in first principles simulations over a wide range of parameters. We illustrate viability of the approach by simulations of noise and noise spectrum within generic models for non-, weakly and strongly interacting systems. Results of the simulations are compared to exact data (where available) and to simulations performed within approaches best suited for each of the three parameter regimes.
Prevalence of Rare Genetic Variations and Their Implications in NGS-data Interpretation
Authors: Cho Yangrae , Lee Chul-Ho , Jeong Eun-Goo , Kim Min-Ho , Hong Jong Hui , Ko Younhee , Lee Bomnun , Yun Gilly , Kim Byong Joon , Jung Jongcheol , Jung Jongsun , Lee Jin-Sung
Published: August 2017

Next-generation sequencing (NGS) technology has improved enough to discover mutations associated with genetic diseases. Our study evaluated the feasibility of targeted NGS as a primary screening tool to detect causal variants and subsequently predict genetic diseases. We performed parallel computations on 3.7-megabase-targeted regions to detect disease-causing mutations in 103 participants consisting of 81 patients and 22 controls. Data analysis of the participants took about 6 hours using local databases and 200 nodes of a supercomputer. All variants in the selected genes led on average to 3.6 putative diseases for each patient while variants restricted to disease-causing genes identified the correct disease. Notably, only 12% of predicted causal variants were recorded as causal mutations in public databases: 88% had no or insufficient records. In this study, most genetic diseases were caused by rare mutations and public records were inadequate. Most rare variants, however, were not associated with genetic diseases. These data implied that novel, rare variants should not be ignored but interpreted in conjunction with additional clinical data. This step is needed so appropriate advice can be given to primary doctors and parents, thus fulfilling the purpose of this method as a primary screen for rare genetic diseases.
Response to Alternating Electric Fields of Tubulin Dimers and Microtubule Ensembles in Electrolytic Solutions
Authors: Santelices Iara B. , Friesen Douglas E. , Bell Clayton , Hough Cameron M. , Xiao Jack , Kalra Aarat , Kar Piyush , Freedman Holly , Rezania Vahid , Lewis John D. , Shankar Karthik , Tuszynski Jack A.
Published: August 2017

Microtubules (MTs), which are cylindrical protein filaments that play crucial roles in eukaryotic cell functions, have been implicated in electrical signalling as biological nanowires. We report on the small-signal AC (“alternating current”) conductance of electrolytic solutions containing MTs and tubulin dimers, using a microelectrode system. We find that MTs (212 nM tubulin) in a 20-fold diluted BRB80 electrolyte increase solution conductance by 23% at 100 kHz, and this effect is directly proportional to the concentration of MTs in solution. The frequency response of MT-containing electrolytes exhibits a concentration-independent peak in the conductance spectrum at 111 kHz (503 kHz FWHM that decreases linearly with MT concentration), which appears to be an intrinsic property of MT ensembles in aqueous environments. Conversely, tubulin dimers (42 nM) decrease solution conductance by 5% at 100 kHz under similar conditions. We attribute these effects primarily to changes in the mobility of ionic species due to counter-ion condensation effects, and changes in the solvent structure and solvation dynamics. These results provide insight into MTs’ ability to modulate the conductance of aqueous electrolytes, which in turn, has significant implications for biological information processing, especially in neurons, and for intracellular electrical communication in general.
Feeling stiffness in the back: a protective perceptual inference in chronic back pain
Authors: Stanton Tasha R. , Moseley G. Lorimer , Wong Arnold Y. L. , Kawchuk Gregory N.
Published: August 2017

Does feeling back stiffness actually reflect having a stiff back? This research interrogates the long-held question of what informs our subjective experiences of bodily state. We propose a new hypothesis: feelings of back stiffness are a protective perceptual construct, rather than reflecting biomechanical properties of the back. This has far-reaching implications for treatment of pain/stiffness but also for our understanding of bodily feelings. Over three experiments, we challenge the prevailing view by showing that feeling stiff does not relate to objective spinal measures of stiffness and objective back stiffness does not differ between those who report feeling stiff and those who do not. Rather, those who report feeling stiff exhibit self-protective responses: they significantly overestimate force applied to their spine, yet are better at detecting changes in this force than those who do not report feeling stiff. This perceptual error can be manipulated: providing auditory input in synchrony to forces applied to the spine modulates prediction accuracy in both groups, without altering actual stiffness, demonstrating that feeling stiff is a multisensory perceptual inference consistent with protection. Together, this presents a compelling argument against the prevailing view that feeling stiff is an isomorphic marker of the biomechanical characteristics of the back.
Proteomic and network analysis of human serum albuminome by integrated use of quick crosslinking and two-step precipitation
Authors: Liu Zhao , Li Shuiming , Wang Haiyang , Tang Min , Zhou Mi , Yu Jia , Bai Shunjie , Li Pengfei , Zhou Jian , Xie Peng
Published: August 2017

Affinity- and chemical-based methods are usually employed to prepare human serum albuminome; however, these methods remain technically challenging. Herein, we report the development of a two-step precipitation (TSP) method by combined use of polyethylene glycol (PEG) and ethanol. PEG precipitation was newly applied to remove immunoglobulin G for albuminome preparation, which is simple, cost effective, efficient and compatible with downstream ethanol precipitation. Nonetheless, chemical extraction using TSP may disrupt weak and transient protein interactions with human serum albumin (HSA) leading to an incomplete albuminome. Accordingly, rapid fixation based on formaldehyde crosslinking (FC) was introduced into the TSP procedure. The developed FC-TSP method increased the number of identified proteins, probably by favouring real-time capture of weakly bound proteins in the albuminome. A total of 171 proteins excluding HSA were identified from the fraction obtained with FC-TSP. Further interaction network and cluster analyses revealed 125 HSA-interacting proteins and 14 highly-connected clusters. Compared with five previous studies, 55 new potential albuminome proteins including five direct and 50 indirect binders were only identified by our strategy and 12 were detected as common low-abundance proteins. Thus, this new strategy has the potential to effectively survey the human albuminome, especially low-abundance proteins of clinical interest.
Observation of Third-order Nonlinearities in Graphene Oxide Film at Telecommunication Wavelengths
Authors: Xu Xiaochuan , Zheng Xiaorui , He Feng , Wang Zheng , Subbaraman Harish , Wang Yaguo , Jia Baohua , Chen Ray T.
Published: August 2017

All-optical switches have been considered as a promising solution to overcome the fundamental speed limit of the current electronic switches. However, the lack of a suitable third-order nonlinear material greatly hinders the development of this technology. Here we report the observation of ultrahigh third-order nonlinearity about 0.45 cm2/GW in graphene oxide thin films at the telecommunication wavelength region, which is four orders of magnitude higher than that of single crystalline silicon. Besides, graphene oxide is water soluble and thus easy to process due to the existence of oxygen containing groups. These unique properties can potentially significantly advance the performance of all-optical switches.
Neural glycoprotein M6a is released in extracellular vesicles and modulated by chronic stressors in blood
Authors: Monteleone Melisa C. , Billi Silvia C. , Brocco Marcela A. , Frasch Alberto C.
Published: August 2017

Membrane neuronal glycoprotein M6a is highly expressed in the brain and contributes to neural plasticity promoting neurite growth and spine and synapse formation. We have previously showed that chronic stressors alter hippocampal M6a mRNA levels in rodents and tree shrews. We now show that M6a glycoprotein can be detected in mouse blood. M6a is a transmembrane glycoprotein and, as such, unlikely to be free in blood. Here we demonstrate that, in blood, M6a is transported in extracellular vesicles (EVs). It is also shown that M6a-containing EVs are delivered from cultured primary neurons as well as from M6a-transfected COS-7 cells. Released EVs containing M6a can be incorporated into COS-7 cells changing its phenotype through formation of membrane protrusions. Thus, M6a-containing EVs might contribute to maintain cellular plasticity. M6a presence in blood was used to monitor stress effects. Chronic restraint stress modulated M6a protein level in a sex dependent manner. Analysis of individual animals indicated that M6a level variations depend on the stressor applied. The response to stressors in blood makes M6a amenable to further studies in the stress disorder field.
Lipopolysaccharide-binding protein (LBP) reverses the amyloid state of fibrin seen in plasma of type 2 diabetics with cardiovascular co-morbidities
Authors: Pretorius Etheresia , Mbotwe Sthembile , Kell Douglas B.
Published: August 2017

Type 2 diabetes (T2D) has many cardiovascular complications, including a thrombotic propensity. Many such chronic, inflammatory diseases are accompanied (and may be exacerbated, and possibly even largely caused) by amyloid fibril formation. Recognising that there are few strong genetic associations underpinning T2D, but that amyloidogenesis of amylin is closely involved, we have been seeking to understand what might trigger the disease. Serum levels of bacterial lipopolysaccharide are raised in T2D, and we recently showed that fibrin(ogen) polymerisation during blood clotting can be affected strongly by LPS. The selectivity was indicated by the regularisation of clotting by lipopolysaccharide-binding protein (LBP). Since coagulopathies are a hallmark of T2D, we wondered whether they might too be caused by LPS (and reversed by LBP). We show here, using SEM and confocal microscopy, that platelet-poor-plasma from subjects with T2D had a much greater propensity for hypercoagulability and for amyloidogenesis, and that these could both be reversed by LBP. These data imply that coagulopathies are an important feature of T2D, and may be driven by ‘hidden’ LPS. Given the prevalence of amyloid formation in the sequelae of diabetes, this opens up novel strategies for both the prevention and treatment of T2D.
Effects of H2 High-pressure Annealing on HfO2/Al2O3/In0.53Ga0.47As Capacitors: Chemical Composition and Electrical Characteristics
Authors: Choi Sungho , An Youngseo , Lee Changmin , Song Jeongkeun , Nguyen Manh-Cuong , Byun Young-Chul , Choi Rino , McIntyre Paul C. , Kim Hyoungsub
Published: August 2017

We studied the impact of H2 pressure during post-metallization annealing on the chemical composition of a HfO2/Al2O3 gate stack on a HCl wet-cleaned In0.53Ga0.47As substrate by comparing the forming gas annealing (at atmospheric pressure with a H2 partial pressure of 0.04 bar) and H2 high-pressure annealing (H2-HPA at 30 bar) methods. In addition, the effectiveness of H2-HPA on the passivation of the interface states was compared for both p- and n-type In0.53Ga0.47As substrates. The decomposition of the interface oxide and the subsequent out-diffusion of In and Ga atoms toward the high-k film became more significant with increasing H2 pressure. Moreover, the increase in the H2 pressure significantly improved the capacitance‒voltage characteristics, and its effect was more pronounced on the p-type In0.53Ga0.47As substrate. However, the H2-HPA induced an increase in the leakage current, probably because of the out-diffusion and incorporation of In/Ga atoms within the high-k stack.
Correlation between particle size/domain structure and magnetic properties of highly crystalline Fe3O4 nanoparticles
Authors: Li Qing , Kartikowati Christina W. , Horie Shinji , Ogi Takashi , Iwaki Toru , Okuyama Kikuo
Published: August 2017

Highly crystalline single-domain magnetite Fe3O4nanoparticles (NPs) are important, not only for fundamental understanding of magnetic behaviour, but also for their considerable potential applications in biomedicine and industry. Fe3O4NPs with sizes of 10–300 nm were systematically investigated to reveal the fundamental relationship between the crystal domain structure and the magnetic properties. The examined Fe3O4NPs were prepared under well-controlled crystal growth conditions using a large-scale liquid precipitation method. The crystallite size of cube-like NPs estimated from X-ray diffraction pattern increased linearly as the particle size (estimated by transmission electron microscopy) increased from 10 to 64.7 nm, which indicates that the NPs have a single-domain structure. This was further confirmed by the uniform lattice fringes. The critical size of approximately 76 nm was obtained by correlating particle size with both crystallite size and magnetic coercivity; this was reported for the first time in this study. The coercivity of cube-like Fe3O4NPs increased to a maximum of 190 Oe at the critical size, which suggests strong exchange interactions during spin alignment. Compared with cube-like NPs, sphere-like NPs have lower magnetic coercivity and remanence values, which is caused by the different orientations of their polycrystalline structure.
Melatonin ameliorates restraint stress-induced oxidative stress and apoptosis in testicular cells via NF-κB/iNOS and Nrf2/ HO-1 signaling pathway
Authors: Guo Ying , Sun Junyan , Li Ting , Zhang Qiuwan , Bu Shixia , Wang Qian , Lai Dongmei
Published: August 2017

Decline in semen quality has become a global public health concern. Psychological stress is common in the current modern society and is associated with semen decline. Increasing evidence demonstrated that melatonin has anti-apoptotic and antioxidant functions. Whether melatonin can ameliorate the damage in testes induced by psychological stress has never been investigated. Here, a mouse model of restraint stress demonstrated that melatonin normalized the sperm density decline, testicular cells apoptosis, and testicular oxidative stress in stressed male mice. Melatonin decreased reactive oxygen species (ROS) level, increased superoxide dismutase (SOD) and glutathione (GSH) activities, and downregulated inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) activities in stressed mice testes. Furthermore, melatonin reduced the stress-induced activation of the NF-κB signaling pathway by decreasing the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and p65 nuclear translocation. In addition, melatonin upregulated the expression of anti-oxidant proteins including nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Meanwhile,in vitrostudies also demonstrated melatonin could reduce oxidative apoptosis of testicular cells. Collectively, melatonin mitigated psychological stress-induced spermatogenic damage, which provides evidence for melatonin as a therapy against sperm impairment associated with psychological stress.
A rapid evaluation of acute hydrogen sulfide poisoning in blood based on DNA-Cu/Ag nanocluster fluorescence probe
Authors: Ding Yanjun , Li Xingmei , Chen Ceng , Ling Jiang , Li Weichen , Guo Yadong , Yan Jie , Zha Lagabaiyla , Cai Jifeng
Published: August 2017

Hydrogen sulfide (H2S) is a highly toxic gas as a cause of inhalational death. Accurate detection of H2S poisoning concentration is valuable and vital for forensic workers to estimate the cause of death. But so far, it is no uniform and reliable standard method to measure sulfide concentrations in H2S poisoning blood for forensic identification. This study introduces a fluorescence sensing technique into forensic research, in which a DNA-templated copper/silver nanocluster (DNA-Cu/AgNCs) fluorescence probe has been proposed to selective detection of S2−. Under an optimized condition, the proposed method can allow for determination of S2− in the concentration range of 10 pM to 1 mM with a linear equation: y = −0.432 lg[S2−] + 0.675 (R2 = 0.9844), with the limit of detection of 3.75 pM. Moreover, acute H2S poisoning mouse models were established by intraperitoneally injected different doses of Na2S, and the practical feasibility of the proposed fluorescence sensor has been demonstrated by 35 poisoning blood samples. This proposed method is proved to be quite simple and straightforward for the detection of H2S poisoning blood. Also it may provide a basis ﻿for sulfide metabolizing study in body﻿, and it woul﻿d be m﻿eaningful to further pus﻿h﻿ forensic toxicology identification and clinical laboratory research.
The histidine-rich peptide LAH4-L1 strongly promotes PAMAM-mediated transfection at low nitrogen to phosphorus ratios in the presence of serum
Authors: Liu Nan , Bechinger Burkhard , Süss Regine
Published: August 2017

Non-viral vectors are widely used and investigated for the delivery of genetic material into cells. However, gene delivery barriers like lysosomal degradation, serum inhibition and transient gene expression so far still limit their clinical applications. Aiming to overcome these limitations, a pH-sensitive hybrid gene vector (PSL complex) was designed by self-assembly of poly(amidoamine) (PAMAM) dendrimers, the histidine-rich peptide LAH4-L1 and the sleeping beauty transposon system (SB transposon system, a plasmid system capable of efficient and precise genomic insertion). Transfection studies revealed that PSL complexes achieved excellent efficiency in all investigated cell lines (higher than 90% in HeLa cells and over 30% in MDCK cells, a difficult-to-transfect cell line). Additionally, the PSL complexes showed high serum tolerance and exhibited outstanding transfection efficiency even in medium containing 50% serum (higher than 90% in HeLa cells). Moreover, a high level of long-term gene expression (over 30% in HeLa cells) was observed. Furthermore, PSL complexes not only resulted in high endocytosis, but also showed enhanced ability of endosomal escape compared to PAMAM/DNA complexes. These results demonstrate that simple association of PAMAM dendrimers, LAH4-L1 peptides and the SB transposon system by self-assembly is a general and promising strategy for efficient and safe gene delivery.
Multipoint Tissue Circulation Monitoring with a Flexible Optical Probe
Authors: Tomioka Yoko , Enomoto Shintaro , Gu Jian , Kaneko Akiko , Saito Itsuro , Inoue Yusuke , Woo Taeseong , Koshima Isao , Yoshimura Kotaro , Someya Takao , Sekino Masaki
Published: August 2017

Compromised circulation is a potential complication during the postoperative period following tissue transplantation. The use of a monitoring device allows physicians to detect compromised circulation immediately. Such monitoring devices need to be continuously usable, wearable, and area-detectable. However, existing devices fail to satisfy all of these requirements simultaneously. We developed a wearable, multipoint pulse wave-monitoring device. An array of reflective optical sensors implemented on a thin film substrate was used as a lightweight and flexible probe. As a model of tissue transplantation, an inguinal flap in a Wistar rat was dissected and freed from all subcutaneous tissue. By ligating the artery or vein, ischemia or congestion was induced in the tissue. In a human study, ischemia or congestion was induced in the palm by pressing the feeding artery or cutaneous vein, respectively. The amplitude of the pulse wave was evaluated using the power spectrum of Fourier transformed signals. Pulse wave amplitude significantly decreased under compromised circulation in both animal and human models. Moreover, we accomplished 1 week of continuous wireless monitoring in healthy subjects. These results demonstrated the potential utility of the developed device in postoperative blood-flow monitoring to improve the rescue rate of transplanted tissue.
TGF-β participates choroid neovascularization through Smad2/3-VEGF/TNF-α signaling in mice with Laser-induced wet age-related macular degeneration
Authors: Wang Xiaolei , Ma Wei , Han Song , Meng Zhaoyang , Zhao Lu , Yin Yi , Wang Yanling , Li Junfa
Published: August 2017

Choroidal neovascularization(CNV) is the most severe complication in Age-related macular degeneration(AMD) and the most common cause of irreversible blindness in the elderly in developed world. The aim of this study was to identify the effect of transforming growth factor-β(TGF-β) and Smad2/3-VEGF/TNF-α signaling on CNV angiopoiesis, and to explore TGF-β inhibitors on the development of CNV in a CNV mouse model. Fundus fluorescein angiography(FFA) was used to evaluate the laser-induced CNV formation. The histology of CNV lesions stained with hematoxylin-eosin(HE) was obtained. The immunofluorescent staining was performed to determine TGF-β protein expression. The expressions of TGF-β, phosphorylated Smad2/3, VEGF and TNF-α were determined by using Western blot analysis. The CNV areas were analyzed by using fluorescein stain on RPE/choroid-sclera flat mounts. We found the levels of TGF-β protein expression increasingly reached the peak till 3rd week during the CNV development. The protein levels of VEGF and TNF-α also increased significantly in CNV mice, which were inhibited by a synthetic TGF-β inhibitor LY2157299 or a natural TGF-β inhibitor Decorin. The phosphorylated Smad2/3 levels increased significantly in CNV mice, but this response was profoundly suppressed by the TGF-β inhibitors. Here we have demonstrated that TGF-β/Smad signaling plays an important role in Laser-induced CNV formation through down-regulation of VEGF and TNF-α expressions, suggesting TGF-β inhibitors may provide an alternative to traditional methods in wet AMD treatment.
CD271 determines migratory properties of melanoma cells
Authors: Radke Josefine , Roßner Florian , Redmer Torben
Published: August 2017

Melanoma cell expression of the nerve growth factor receptor CD271 is associated with stem-like properties. However, the contributing role of the receptor in melanoma cell migration is elusive. Here, we explored extracranial (skin, soft tissue, lymph node and liver, n = 13) and matched brain metastases (BM, n = 12) and observed a heterogeneous distribution of phenotypically distinct subsets of CD271+ cells. In addition, we observed that CD271 expression gradually rises along with melanoma progression and metastasis by exploration of publicly available expression data of nevi, primary melanoma (n = 31) and melanoma metastases (n = 54). Furthermore, we observed highest levels of CD271 in BM. Sub-clustering identified 99 genes differentially expressed among CD271high and CD271low (p < 0.05) BM-subgroups. Comparative analysis of subsets revealed increased ( ≥ 1.5fold, log2) expression of migration-associated genes and enrichment of CD271-responsible genes involved in DNA-repair and stemness. Live cell-imaging based scratch-wound assays of melanoma cells with stable knock-down of CD271 revealed a significantly reduced cell migration (3.9fold, p = 1.2E-04) and a reduced expression of FGF13, CSPG4, HMGA2 and AKT3 major candidate regulatory genes of melanoma cell migration. In summary, we provide new insights in melanoma cell migration and suggest that CD271 serves as a candidate regulator, sufficient to determine cellular properties of melanoma brain metastatic cells.
Sensitivity-controllable refractive index sensor based on reflective θ-shaped microfiber resonator cooperated with Vernier effect
Authors: Xu Zhilin , Luo Yiyang , Liu Deming , Shum Perry Ping , Sun Qizhen
Published: August 2017

In this paper, we report a sensitivity-controllable refractive index (RI) sensor based on a reflective θ-shaped microfiber resonator cooperated with Vernier effect. The θ-shaped microfiber resonator is a reflective all-fiber device with comb spectrum under weak coupling condition. By cascading it with a fiber Fabry-Perot interferometer, Vernier effect is generated to demodulate surrounding RI with enhanced sensitivity. Theoretical analysis reveals that RI sensitivity of the combined structure with Vernier effect is m times higher than the sensitivity of singular θ-shaped microfiber resonator. Moreover, by adjusting cavity length of the θ-shaped microfiber resonator, magnification factor M = (m + 1) can be tuned which enables the RI sensitivity to be controlled. Experimental result demonstrates that the RI sensitivity can be widely tuned from 311.77 nm/RIU (Reflective index unit) to 2460.07 nm/RIU when the cavity length of the θ-shaped microfiber resonator is adjusted from 9.4 mm to 8.7 mm. The θ-shaped microfiber resonator based all-fiber RI sensor featuring controllable sensitivity and compact size can be widely used for chemical and biological detections. The proposed scheme of generating Vernier effect also offers a universal idea to increase measurement sensitivity for optical fiber sensing structures with comb spectrum.
Health risk assessment of rare earth elements in cereals from mining area in Shandong, China
Authors: Zhuang Maoqiang , Wang Liansen , Wu Guangjian , Wang Kebo , Jiang Xiaofeng , Liu Taibin , Xiao Peirui , Yu Lianlong , Jiang Ying , Song Jian , Zhang Junli , Zhou Jingyang , Zhao Jinshan , Chu Zunhua
Published: August 2017

To investigate the concentrations of rare earth elements in cereals and assess human health risk through cereal consumption, a total of 327 cereal samples were collected from rare earth mining area and control area in Shandong, China. The contents of 14 rare earth elements were determined by Inductively Coupled Plasma—Mass Spectrometry (ICP—MS). The medians of total rare earth elements in cereals from mining and control areas were 74.22 μg/kg and 47.83 μg/kg, respectively, and the difference was statistically significant (P < 0.05). The wheat had the highest rare earth elements concentrations (109.39 μg/kg and 77.96 μg/kg for mining and control areas, respectively) and maize had the lowest rare earth elements concentrations (42.88 μg/kg and 30.25 μg/kg for mining and control areas, respectively). The rare earth elements distribution patterns for both areas were characterized by enrichment of light rare earth elements. The health risk assessment demonstrated that the estimated daily intakes of rare earth elements through cereal consumption were considerably lower than the acceptable daily intake (70 μg/kg bw). The damage to adults can be neglected, but more attention should be paid to the effects of continuous exposure to rare earth elements on children.
Novel evidence for complement system activation in chick myopia and hyperopia models: a meta-analysis of transcriptome datasets
Authors: Riddell Nina , Crewther Sheila G.
Published: August 2017

Myopia (short-sightedness) and hyperopia (long-sightedness) occur when the eye grows too long or short, respectively, for its refractive power. There are currently approximately 1.45 billion myopes worldwide and prevalence is rising dramatically. Although high myopia significantly increases the risk of developing a range of sight-threatening disorders, the molecular mechanisms underlying ocular growth regulation and its relationship to these secondary complications remain poorly understood. Thus, this study meta-analyzed transcriptome datasets collected in the commonly used chick model of optically-induced refractive error. Fifteen datasets (collected across five previous studies) were obtained from GEO, preprocessed in Bioconductor, and divided into 4 conditions representing early (≤1 day) and late (>1 day) myopia and hyperopia induction. Differentially expressed genes in each condition were then identified using Rank Product meta-analysis. The results provide novel evidence for transcriptional activation of the complement system during both myopia and hyperopia induction, and confirm existing literature implicating cell signaling, mitochondrial, and structural processes in refractive error. Further comparisons demonstrated that the meta-analysis results also significantly improve concordance with broader omics data types (i.e., human genetic association and animal proteomics studies) relative to previous transcriptome studies, and show extensive similarities with the genes linked to age-related macular degeneration, choroidal neovascularization, and cataract.