bluuebunny/crossref_metadata_2025 huggingface dataset:
A minimal double quantum dot
Authors: Zheng Hao , Zhang Junyi , Berndt Richard
Published: September 2017

Double quantum dots (DQDs) are a versatile platform for solid-state physics, quantum computation and nanotechnology. The micro-fabrication techniques commonly used to fabricate DQDs are difficult to extend to the atomic scale. Using an alternative approach, which relies on scanning tunneling microscopy and spectroscopy, we prepared a minimal DQD in a wide band-gap semiconductor matrix. It is comprised of a pair of strongly coupled donor atoms that can each be doubly charged. The donor excitation diagram of this system mimicks the charge stability diagram observed in transport measurements of DQDs. We furthermore illustrate how the charge and spin degrees of freedom of the minimal DQD may be used to obtain a single quantum bit and to prepare a Bell state. The results open an intriguing perspective for quantum electronics with atomic-scale structures.
Analysis of Bioactive Amino Acids from Fish Hydrolysates with a New Bioinformatic Intelligent System Approach
Authors: Elaziz Mohamed Abd , Hemdan Ahmed Monem , Hassanien AboulElla , Oliva Diego , Xiong Shengwu
Published: September 2017

The current economics of the fish protein industry demand rapid, accurate and expressive prediction algorithms at every step of protein production especially with the challenge of global climate change. This help to predict and analyze functional and nutritional quality then consequently control food allergies in hyper allergic patients. As, it is quite expensive and time-consuming to know these concentrations by the lab experimental tests, especially to conduct large-scale projects. Therefore, this paper introduced a new intelligent algorithm using adaptive neuro-fuzzy inference system based on whale optimization algorithm. This algorithm is used to predict the concentration levels of bioactive amino acids in fish protein hydrolysates at different times during the year. The whale optimization algorithm is used to determine the optimal parameters in adaptive neuro-fuzzy inference system. The results of proposed algorithm are compared with others and it is indicated the higher performance of the proposed algorithm.
BMP-2 induced Dspp transcription is mediated by Dlx3/Osx signaling pathway in odontoblasts
Authors: Yang Guobin , Yuan Guohua , MacDougall Mary , Zhi Chen , Chen Shuo
Published: September 2017

Dentin sialophosphoprotein (Dspp) as a differentiation marker of odontoblasts is regulated by BMP-2. However, the intimate mechanism is still unknown. Transcription factors Dlx3 and Osx are essential for odontoblasts differentiation. We hypothesized that BMP-2 regulation of Dspp transcription was mediated by Dlx3 and/or Osx in odontoblasts. In the present investigation, we found that BMP-2 stimulated expression and nuclear translocation of Dlx3 and Osx in odontoblasts both in vitro and in vivo. Osx was a downstream target of Dlx3 and both of them stimulated Dsp expression. Both Dlx3 and Osx were able to activate Dspp promoter from nucleotides (nt) −318 to +54 by transfections of luciferase reports containing different lengths of mouse Dspp promoters. The binding of Dlx3 and Osx with nt −318 to +54 of Dspp promoter was verified by chromatin immunoprecipitation in vivo. Two Dlx3 binding sites and one Osx binding site on Dspp promoter were found by EMSA. Furthermore, the exact biological function of these binding sites was confirmed by site-directed mutagenesis. At last, the protein-protein interaction between Dlx3 and Osx in odontoblasts was detected by co-immunoprecipitation. In conclusion, in this study we found a novel signaling pathway in which BMP-2 activates Dspp gene transcription via Dlx3/Osx pathway.
Synthesis, high-throughput screening and pharmacological characterization of β–lactam derivatives as TRPM8 antagonists
Authors: de la Torre-Martínez Roberto , Bonache M. Angeles , Llabrés-Campaner Pedro J. , Balsera Beatriz , Fernández-Carvajal Asia , Fernández-Ballester Gregorio , Ferrer-Montiel Antonio , Pérez de Vega M. Jesús , González-Muñiz Rosario
Published: September 2017

The mammalian transient receptor potential melastatin channel 8 (TRPM8), highly expressed in trigeminal and dorsal root ganglia, mediates the cooling sensation and plays an important role in the cold hypersensitivity characteristic of some types of neuropathic pain, as well as in cancer. Consequently, the identification of selective and potent ligands for TRPM8 is of great interest. Here, a series of compounds, having a β-lactam central scaffold, were prepared to explore the pharmacophore requirements for TRPM8 modulation. Structure-activity studies indicate that the minimal requirements for potent β-lactam-based TRPM8 blockers are hydrophobic groups (benzyl preferentially or
t
Bu) on R1, R2, R3 and R5 and a short N-alkyl chain (≤3 carbons). The best compounds in the focused library (41 and 45) showed IC50 values of 46 nM and 83 nM, respectively, in electrophysiology assays. These compounds selectively blocked all modalities of TRPM8 activation, i.e. menthol, voltage, and temperature. Molecular modelling studies using a homology model of TRPM8 identified two putative binding sites, involving networks of hydrophobic interactions, and suggesting a negative allosteric modulation through the stabilization of the closed state. Thus, these β-lactams provide a novel pharmacophore scaffold to evolve TRPM8 allosteric modulators to treat TRPM8 channel dysfunction.
Spatially-resolved optical and structural properties of semi-polar $$\mathrm{(11}\bar{2}\mathrm{2)}$$ Al
x
Ga1−x
N with x up to 0.56
Authors: Bruckbauer Jochen , Li Zhi , Naresh-Kumar G. , Warzecha Monika , Edwards Paul R. , Jiu Ling , Gong Yipin , Bai Jie , Wang Tao , Trager-Cowan Carol , Martin Robert W.
Published: September 2017

Pushing the emission wavelength of efficient ultraviolet (UV) emitters further into the deep-UV requires material with high crystal quality, while also reducing the detrimental effects of built-in electric fields. Crack-free semi-polar $$\mathrm{(11}\bar{2}\mathrm{2)}$$
(11

2
¯

2)
Al
x
Ga1−x
N epilayers with AlN contents up to x = 0.56 and high crystal quality were achieved using an overgrowth method employing GaN microrods on m-sapphire. Two dominant emission peaks were identified using cathodoluminescence hyperspectral imaging. The longer wavelength peak originates near and around chevron-shaped features, whose density is greatly increased for higher contents. The emission from the majority of the surface is dominated by the shorter wavelength peak, influenced by the presence of basal-plane stacking faults (BSFs). Due to the overgrowth technique BSFs are bunched up in parallel stripes where the lower wavelength peak is broadened and hence appears slightly redshifted compared with the higher quality regions in-between. Additionally, the density of threading dislocations in these region is one order of magnitude lower compared with areas affected by BSFs as ascertained by electron channelling contrast imaging. Overall, the luminescence properties of semi-polar AlGaN epilayers are strongly influenced by the overgrowth method, which shows that reducing the density of extended defects improves the optical performance of high AlN content AlGaN structures.
Identification of 2-hydroxyisocaproic acid production in lactic acid bacteria and evaluation of microbial dynamics during kimchi ripening
Authors: Park Boyeon , Hwang Hyelyeon , Chang Ji Yoon , Hong Sung Wook , Lee Se Hee , Jung Min Young , Sohn Sung-Oh , Park Hae Woong , Lee Jong-Hee
Published: September 2017

Lactic acid bacteria produce diverse functional metabolites in fermented foods. However, little is known regarding the metabolites and the fermentation process in kimchi. In this study, the culture broth from Leuconostoc lactis, a lactic acid bacterium isolated from kimchi, was analysed by liquid chromatography-tandem mass spectrometry and identified by the MS-DIAL program. The MassBank database was used to analyse the metabolites produced during fermentation. A mass spectrum corresponding to 2-hydroxyisocaproic acid (HICA) was validated based on a collision-induced dissociation (CID) fragmentation pattern with an identified m/z value of 131.07. HICA production by lactic acid bacteria was monitored and showed a positive correlation with hydroxyisocaproate dehydrogenases (HicDs), which play a key role in the production of HICA from leucine and ketoisocaproic acid. Interestingly, the HICA contents of kimchi varied with Leuconostoc and Lactobacillus content during the early stage of fermentation, and the addition of lactic acid bacteria enhanced the HICA content of kimchi. Our results suggest that HICA production in kimchi is dependent on the lactic acid bacterial composition.
MiR-338-5p enhances the radiosensitivity of esophageal squamous cell carcinoma by inducing apoptosis through targeting survivin
Authors: Park Misun , Yoon Hyeon-joon , Kang Moon Chul , Kwon Junhye , Lee Hae Won
Published: September 2017

Radioresistance is a challenge in the treatment of esophageal squamous cell carcinoma (ESCC). MicroRNAs (miRNAs) are known to play an important role in the functional modification of cancer cells and recent studies have reported miRNA-mediated radiotherapy resistance. However, further research is necessary to reveal the regulation mechanisms, and treatment strategies using miRNA are yet to be established for ESCC. We compared the miRNA expression profiles of ESCC parental (TE-4) and acquired radioresistance (TE-4R) cell lines using a miRNA microarray and qRT-PCR. Our data showed that miR-338-5p, one of the target miRNA biomarkers, was significantly downregulated in TE-4R. Ectopic overexpression of miR-338-5p induced apoptosis and sensitivity to radiation treatment by interfering with survivin, which is a known inhibitor of apoptosis. Overexpression of survivin reversed miR-338-5p-induced apoptosis. Tumor xenograft experiments indicated that therapeutic delivery of the miR-338-5p mimics via direct injection into tumor mass increased sensitivity to radiation therapy. In conclusion, our findings suggest that miR-338-5p is a potential radiosensitizer and may be a therapeutic biomarker for radioresistant in ESCC.
In situ characterization of mixed-wettability in a reservoir rock at subsurface conditions
Authors: Alhammadi Amer M. , AlRatrout Ahmed , Singh Kamaljit , Bijeljic Branko , Blunt Martin J.
Published: September 2017

We used X-ray micro-tomography to image the in situ wettability, the distribution of contact angles, at the pore scale in calcite cores from a producing hydrocarbon reservoir at subsurface conditions. The contact angle was measured at hundreds of thousands of points for three samples after twenty pore volumes of brine flooding.We found a wide range of contact angles with values both above and below 90°. The hypothesized cause of wettability alteration by an adsorbed organic layer on surfaces contacted by crude oil after primary drainage was observed with Scanning Electron Microscopy (SEM) and identified using Energy Dispersive X-ray (EDX) analysis. However, not all oil-filled pores were altered towards oil-wet conditions, which suggests that water in surface roughness, or in adjacent micro-porosity, can protect the surface from a strong wettability alteration. The lowest oil recovery was observed for the most oil-wet sample, where the oil remained connected in thin sheet-like layers in the narrower regions of the pore space. The highest recovery was seen for the sample with an average contact angle close to 90°, with an intermediate recovery in a more water-wet system, where the oil was trapped in ganglia in the larger regions of the pore space.
Development of new experimental platform ‘MARS’—Multiple Artificial-gravity Research System—to elucidate the impacts of micro/partial gravity on mice
Authors: Shiba Dai , Mizuno Hiroyasu , Yumoto Akane , Shimomura Michihiko , Kobayashi Hiroe , Morita Hironobu , Shimbo Miki , Hamada Michito , Kudo Takashi , Shinohara Masahiro , Asahara Hiroshi , Shirakawa Masaki , Takahashi Satoru
Published: September 2017

This Japan Aerospace Exploration Agency project focused on elucidating the impacts of partial gravity (partial g) and microgravity (μg) on mice using newly developed mouse habitat cage units (HCU) that can be installed in the Centrifuge-equipped Biological Experiment Facility in the International Space Station. In the first mission, 12 C57BL/6 J male mice were housed under μg or artificial earth-gravity (1 g). Mouse activity was monitored daily via downlinked videos; μg mice floated inside the HCU, whereas artificial 1 g mice were on their feet on the floor. After 35 days of habitation, all mice were returned to the Earth and processed. Significant decreases were evident in femur bone density and the soleus/gastrocnemius muscle weights of μg mice, whereas artificial 1 g mice maintained the same bone density and muscle weight as mice in the ground control experiment, in which housing conditions in the flight experiment were replicated. These data indicate that these changes were particularly because of gravity. They also present the first evidence that the addition of gravity can prevent decreases in bone density and muscle mass, and that the new platform ‘MARS’ may provide novel insights on the molecular-mechanisms regulating biological processes controlled by partial g/μg.
Penicilliumin B, a novel sesquiterpene methylcyclopentenedione from a deep sea-derived Penicillium strain with renoprotective activities
Authors: Lin Xiuping , Wu Qinyu , Yu Yuying , Liang Zhi , Liu Yonghong , Zhou Lili , Tang Lan , Zhou Xuefeng
Published: September 2017

A novel sesquiterpene methylcyclopentenedione, penicilliumin B (1), was obtained from a deep sea-derived fungus Penicillium sp. F00120, together with three known sesquiterpene cyclohexenones (2–4). Penicilliumin B (1), presenting the first example with the sesquiterpene cyclopentenedione skeleton as natural products, was structurally determined by analysis of the NMR and MS spectroscopic data, while the absolute configurations were assigned by single-crystal X-ray experiments. The plausible biosynthetic pathway of the unusual cyclopentenone skeleton of 1 was proposed. Penicilliumin B (1), with low toxicity, was showed significant potential to inhibit the kidney fibrogenic action in vitro, by a mechanism dependent on disruption of oxidative stress, presenting a new type of promising renoprotective agent.
Biomass burning in the Amazon region causes DNA damage and cell death in human lung cells
Authors: de Oliveira Alves Nilmara , Vessoni Alexandre Teixeira , Quinet Annabel , Fortunato Rodrigo Soares , Kajitani Gustavo Satoru , Peixoto Milena Simões , Hacon Sandra de Souza , Artaxo Paulo , Saldiva Paulo , Menck Carlos Frederico Martins , Batistuzzo de Medeiros Silvia Regina
Published: September 2017

Most of the studies on air pollution focus on emissions from fossil fuel burning in urban centers. However, approximately half of the world's population is exposed to air pollution caused by biomass burning emissions. In the Brazilian Amazon population, over 10 million people are directly exposed to high levels of pollutants resulting from deforestation and agricultural fires. This work is the first study to present an integrated view of the effects of inhalable particles present in emissions of biomass burning. Exposing human lung cells to particulate matter smaller than 10 µm (PM10), significantly increased the level of reactive oxygen species (ROS), inflammatory cytokines, autophagy, and DNA damage. Continued PM10 exposure activated apoptosis and necrosis. Interestingly, retene, a polycyclic aromatic hydrocarbon present in PM10, is a potential compound for the effects of PM10, causing DNA damage and cell death. The PM10 concentrations observed during Amazon biomass burning were sufficient to induce severe adverse effects in human lung cells. Our study provides new data that will help elucidate the mechanism of PM10-mediated lung cancer development. In addition, the results of this study support the establishment of new guidelines for human health protection in regions strongly impacted by biomass burning.
The Oceanic Biological Pump: Rapid carbon transfer to depth at Continental Margins during Winter
Authors: Thomsen Laurenz , Aguzzi Jacopo , Costa Corrado , De Leo Fabio , Ogston Andrea , Purser Autun
Published: September 2017

The oceanic biological pump is responsible for the important transfer of CO2-C as POC “Particulate Organic Carbon” to the deep sea. It plays a decisive role in the Earth’s carbon cycle and significant effort is spent to quantify its strength. In this study we used synchronized daily time-series data of surface chlorophyll-a concentrations from the NASA’s MODIS satellite in combination with hourly to daily observations from sea surface buoys and from an Internet Operated Vehicle (IOV) on the seafloor within Barkley Canyon (Northeast Pacific) to investigate the importance of winter processes in the export of fresh phytodetritus. The results indicate that phytoplankton pulses during winter can be as important in POC transfer to depth as the pulses associated with spring and summer blooms. Short winter phytoplankton pulses were observed to disappear from surface waters after low-pressure systems affected the area. Pulses of chlorophyll reached the IOV, at 870 m depth on the canyon seafloor, 12–72 hours later. These observed short pulses of biological carbon production regularly observed in the region from December to March have not been considered a significant component of the biological pump when compared with the denser summer productivity blooms.
Association Between Body Mass Index Combined with Albumin: creatinine Ratio and All-cause Mortality in Chinese Population
Authors: Xiong Jiachuan , Wang Jinwei , Zhao Jinghong , Zhang Luxia
Published: September 2017

The association between body mass index (BMI) combined with albumin: creatinine ratio (ACR) and all-cause mortality in the general population has not been established. To address this, we examined a representative sample from the general population of China. The study included 46,854 participants with a follow-up of 4.6 years. Compared to the normal weight with ACR <10 mg/g group (the reference group), the crude hazard ratios (HRs) for all-cause mortality for the underweight with ACR >10 mg/g, normal weight with ACR >10 mg/g, overweight with ACR >10 mg/g, and obese with ACR >10 mg/g groups, were 2.22 (95% CI, 1.41 to 3.49), 1.70 (95% CI, 1.42 to 2.04), 1.52 (95% CI, 1.22 to 1.89), and 2.05 (95% CI, 1.45 to 2.89), respectively. After multivariable adjustments for age, race, comorbidities, and baseline eGFR, the HRs for the underweight with ACR >10 mg/g and normal weight with ACR >10 mg/g groups were 1.85 (95% CI, 1.17 to 2.91) and 1.36 (95% CI, 1.13 to 1.63), respectively. The results indicate that BMI combined with ACR can better predict all-cause mortality than BMI alone in the general Chinese population. Underweight and normal weight people with elevated ACR are at a higher risk of all-cause mortality than those in the same BMI category with ACR <10 mg/g.
Astrocytes and oligodendrocytes in grey and white matter regions of the brain metabolize fatty acids
Authors: Hofmann Kristina , Rodriguez-Rodriguez Rosalia , Gaebler Anne , Casals Núria , Scheller Anja , Kuerschner Lars
Published: September 2017

The grey and white matter regions of the mammalian brain consist of both neurons and neuroglial cells. Among the neuroglia, the two macroglia oligodendrocytes and astrocytes are the most abundant cell types. While the major function of oligodendrocytes is the formation of the lipid-rich myelin structure, the heterogeneous group of astrocytes fulfils a multitude of important roles in cerebral development and homeostasis. Brain lipid homeostasis involves the synthesis of a specific cerebral lipidome by local lipid metabolism. In this study we have investigated the fatty acid uptake and lipid biosynthesis in grey and white matter regions of the murine brain. Key findings were: (i) white matter oligodendrocytes and astrocytes take up saturated and unsaturated fatty acids, (ii) different grey matter regions show varying lipid labelling intensities, (iii) the medial habenula, an epithalamic grey matter structure, and the oligodendrocytes and astrocytes therein are targeted by fatty acids, and (iv) in the medial habenula, the neutral lipid containing lipid droplets are found in cells facing the ventricle but undetectable in the habenular parenchyma. Our data indicate a role for oligodendrocytes and astrocytes in local lipid metabolism of white and grey matter regions in the brain.
Channel Formation and Membrane Deformation via Sterol-Aided Polymorphism of Amphidinol 3
Authors: Iwamoto Masayuki , Sumino Ayumi , Shimada Eri , Kinoshita Masanao , Matsumori Nobuaki , Oiki Shigetoshi
Published: September 2017

Amphidinol 3 (AM3) is an anti-fungal polyene extracted from a marine dinoflagellate. Here, we examined the ion channel activity and membrane-embedded structure of AM3 using a lipid bilayer method and atomic force microscopy (AFM). AM3 exhibited large-conductance (~1 nS) and non-selective single-channel activity only when sterols were present in the membrane leaflet of the AM3-added side. The variable conductance suggests the formation of a multimeric barrel-stave pore. At high AM3 concentrations, giant-conductance “jumbo” channels (~40 nS) emerged. AFM revealed a thicker raft-like membrane phase with the appearance of a wrinkled surface, in which phase pores (diameter: ~10 nm) were observed. The flip-flop of ergosterol occurred only after the appearance of the jumbo channel, indicating that the jumbo channel induced a continuity between the outer and inner leaflets of the membrane: a feature characteristic of toroidal-like pores. Thus, AM3 forms different types of sterol-aided polymorphic channels in a concentration dependent manner.
Virulence of current German PEDV strains in suckling pigs and investigation of protective effects of maternally derived antibodies
Authors: Leidenberger S. , Schröder Ch. , Zani L. , Auste A. , Pinette M. , Ambagala A. , Nikolin V. , de Smit H. , Beer M. , Blome S.
Published: September 2017

Porcine epidemic diarrhea (PED) has caused tremendous losses to the United States pig industry since 2013. From 2014, outbreaks were also reported from Central Europe. To characterize the Central European PEDV strains regarding their virulence in suckling piglets, and to assess the protective effect of maternally derived antibodies (MDA), four trial groups were randomly assigned, each consisting of two pregnant sows and their litter. To induce MDA in a subset of piglets, two sows received a cell culture-adapted PEDV strain, and another two sows were inoculated with field material from German PED outbreaks. Four sows stayed naïve. Subsequently, all piglets were inoculated with the corresponding PEDV strains at an age of 3 to 6 days, and virus shedding, clinical signs and occurrence of specific antibodies were assessed. Piglets without MDA showed a morbidity of 100% and low lethality, while almost all MDA-positive piglets stayed clinically healthy and showed considerably lower virus shedding. Taken together, the Central European PEDV strains showed rather low virulence under experimental conditions, and pre-inoculation of sows led to a solid protection of their offspring. The latter is the prerequisite for a sow vaccination concept that could help to prevent PED induced losses in the piglet sector.
A method for estimating intracellular ion concentration using optical nanosensors and ratiometric imaging
Authors: Rong Guoxin , Kim Eric H. , Poskanzer Kira E. , Clark Heather A.
Published: September 2017

Optical nanoparticle (NP)-based sensors have been widely implemented as tools for detection of targeted ions and biomolecules. The NP sensing platform offer a modular design that can incorporate different sensing components for greater target specificity and the ability to tune the dynamic range, as well as encapsulation of multiple dyes to generate a ratiometric signal with varying spectra. Despite these advantages, demonstrating quantitative ion imaging for intracellular measurement still possess a major challenge. Here, we describe fundamentals that enable intracellular validation of this approach using ion-selective nanosensors for investigating calcium (Ca2+) as a model ion. While conventional indicators can improve individual aspects of indicator performance such as Kd, wavelength, and ratiometric measurements, the use of NP sensors can achieve combined benefits of addressing these issues simultaneously. The nanosensor incorporates highly calcium-selective ionophores and two fluorescence indicators that act as signal transducers to facilitate quantitative ratiometric imaging. For intracellular Ca2+ application, the sensors are fine-tuned to physiological sensing range, and live-cell imaging and quantification are demonstrated in HeLa cells loaded with nanosensors and their responsiveness to carbachol-evoked store release (~400 nM). The current nanosensor design thus provides a promising sensing platform for real-time detection and optical determination of intracellular ions.
In situ disordering of monoclinic titanium monoxide Ti5O5 studied by transmission electron microscope TEM
Authors: Rempel А. А. , Van Renterghem W. , Valeeva А. А. , Verwerft M. , Van den Berghe S.
Published: September 2017

The superlattice and domain structures exhibited by ordered titanium monoxide Ti5O5 are disrupted by low energy electron beam irradiation. The effect is attributed to the disordering of the oxygen and titanium sublattices. This disordering is caused by the displacement of both oxygen and titanium atoms by the incident electrons and results in a phase transformation of the monoclinic phase Ti5O5 into cubic B1 titanium monoxide. In order to determine the energies required for the displacement of titanium or oxygen atoms, i.e. threshold displacement energies, a systematic study of the disappearance of superstructure reflections with increasing electron energy and electron bombardment dose has been performed in situ in a transmission electron microscope (TEM). An incident electron energy threshold between 120 and 140 keV has been observed. This threshold can be ascribed to the displacements of titanium atoms with 4 as well as with 5 oxygen atoms as nearest neighbors. The displacement threshold energy of titanium atoms in Ti5O5 corresponding with the observed incident electron threshold energy lies between 6.0 and 7.5 eV. This surprisingly low value can be explained by the presence of either one or two vacant oxygen lattice sites in the nearest neighbors of all titanium atoms.
Effect of Metabolic Syndrome on the Functional Outcome of Corticosteroid Injection for Lateral Epicondylitis: Retrospective Matched Case-Control Study
Authors: Roh Young Hak , Oh Minjoon , Noh Jung Ho , Gong Hyun Sik , Baek Goo Hyun
Published: September 2017

Both obesity and diabetes mellitus are well-known risk factors for tendinopathies. We retrospectively compared the efficacy of single corticosteroid injections in treating lateral epicondylitis in patients with and without metabolic syndrome (MetS). Fifty-one patients with lateral epicondylitis and MetS were age- and sex-matched with 51 controls without MetS. Pain severity, Disability of the Arm, Shoulder, and Hand score, and grip strength were assessed at base line and at 6, 12 and 24 weeks post-injection. The pain scores in the MetS group were greater than those in the control group at 6 and 12 weeks. The disability scores and grip strength in the MetS group were significantly worse than those of the control group at 6 weeks. However, there were no significant differences at 24 weeks between the groups in terms of pain, disability scores and grip strengths. After 24 weeks, three patients (6%) in the control group and five patients (10%) in the MetS group had surgical decompression (p = 0.46). Patients with MetS are at risk for poor functional outcome after corticosteroid injection for lateral epicondylitis in the short term, but in the long term there was no difference in outcomes of steroid injection in patients with and without MetS.
Pedestrian collective motion in competitive room evacuation
Authors: Garcimartín A. , Pastor J. M. , Martín-Gómez C. , Parisi D. , Zuriguel I.
Published: September 2017

When a sizable number of people evacuate a room, if the door is not large enough, an accumulation of pedestrians in front of the exit may take place. This is the cause of emerging collective phenomena where the density is believed to be the key variable determining the pedestrian dynamics. Here, we show that when sustained contact among the individuals exists, density is not enough to describe the evacuation, and propose that at least another variable –such as the kinetic stress– is required. We recorded evacuation drills with different degrees of competitiveness where the individuals are allowed to moderately push each other in their way out. We obtain the density, velocity and kinetic stress fields over time, showing that competitiveness strongly affects them and evidencing patterns which have been never observed in previous (low pressure) evacuation experiments. For the highest competitiveness scenario, we detect the development of sudden collective motions. These movements are related to a notable increase of the kinetic stress and a reduction of the velocity towards the door, but do not depend on the density.
Potential Systematic Interception Errors are Avoided When Tracking the Target with One’s Eyes
Authors: Malla Cristina de la , Smeets Jeroen B. J. , Brenner Eli
Published: September 2017

Directing our gaze towards a moving target has two known advantages for judging its trajectory: the spatial resolution with which the target is seen is maximized, and signals related to the eyes’ movements are combined with retinal cues to better judge the target’s motion. We here explore whether tracking a target with one’s eyes also prevents factors that are known to give rise to systematic errors in judging retinal speeds from resulting in systematic errors in interception. Subjects intercepted white or patterned disks that moved from left to right across a large screen at various constant velocities while either visually tracking the target or fixating the position at which they were required to intercept the target. We biased retinal motion perception by moving the pattern within the patterned targets. This manipulation led to large systematic errors in interception when subjects were fixating, but not when they were tracking the target. The reduction in the errors did not depend on how smoothly the eyes were tracking the target shortly before intercepting it. We propose that tracking targets with one’s eyes when one wants to intercept them makes one less susceptible to biases in judging their motion.
Conditions for Eltonian Pyramids in Lotka-Volterra Food Chains
Authors: Jonsson Tomas
Published: September 2017

In ecological communities consumers (excluding parasites and parasitoids) are in general larger and less numerous than their resource. This results in a well-known observation known as ‘Eltonian pyramids’ or the ‘pyramid of numbers’, and metabolic arguments suggest that this pattern is independent of the number of trophic levels in a system. At the same time, Lotka-Volterra (LV) consumer-resource models are a frequently used tool to study many questions in community ecology, but their capacity to produce Eltonian pyramids has not been formally analysed. Here, I address this knowledge gap by investigating if and when LV food chain models give rise to Eltonian pyramids. I show that Eltonian pyramids are difficult to reproduce without density-dependent mortality in the consumers, unless biologically plausible relationships between mortality rate and interaction strength are taken into account.
Stretchable Dual-Capacitor Multi-Sensor for Touch-Curvature-Pressure-Strain Sensing
Authors: Jin Hanbyul , Jung Sungchul , Kim Junhyung , Heo Sanghyun , Lim Jaeik , Park Wonsang , Chu Hye Yong , Bien Franklin , Park Kibog
Published: September 2017

We introduce a new type of multi-functional capacitive sensor that can sense several different external stimuli. It is fabricated only with polydimethylsiloxane (PDMS) films and silver nanowire electrodes by using selective oxygen plasma treatment method without photolithography and etching processes. Differently from the conventional single-capacitor multi-functional sensors, our new multi-functional sensor is composed of two vertically-stacked capacitors (dual-capacitor). The unique dual-capacitor structure can detect the type and strength of external stimuli including curvature, pressure, strain, and touch with clear distinction, and it can also detect the surface-normal directionality of curvature, pressure, and touch. Meanwhile, the conventional single-capacitor sensor has ambiguity in distinguishing curvature and pressure and it can detect only the strength of external stimulus. The type, directionality, and strength of external stimulus can be determined based on the relative capacitance changes of the two stacked capacitors. Additionally, the logical flow reflected on a tree structure with its branches reaching the direction and strength of the corresponding external stimulus unambiguously is devised. This logical flow can be readily implemented in the sensor driving circuit if the dual-capacitor sensor is commercialized actually in the future.
Urine to highly porous heteroatom-doped carbons for supercapacitor: A value added journey for human waste
Authors: Razmjooei Fatemeh , Singh Kiranpal , Kang Tong Hyun , Chaudhari Nitin , Yuan Jinliang , Yu Jong-Sung
Published: September 2017

Obtaining functionalized carbonaceous materials, with well-developed pores and doped heteroatoms, from waste precursors using environmentally friendly processes has always been of great interest. Herein, a simple template-free approach is devised to obtain porous and heteroatom-doped carbon, by using the most abundant human waste, “urine”. Removal of inherent mineral salts from the urine carbon (URC) makes it to possess large quantity of pores. Synergetic effect of the heteroatom doping and surface properties of the URC is exploited by carrying out energy storage application for the first time. Suitable heteroatom content and porous structure can enhance the pseudo-capacitance and electric double layer capacitance, eventually generating superior capacitance from the URC. The optimal carbon electrode obtained particularly at 900 °C (URC-900) possesses high BET surface area (1040.5 m2g−1), good conductivity, and efficient heteroatom doping of N, S, and P, illustrating high specific capacitance of 166 Fg−1at 0.5 Ag−1for three-electrode system in inorganic electrolyte. Moreover, the URC-900 delivers outstanding cycling stability with only 1.7% capacitance decay over 5,000 cycles at 5 Ag−1. Present work suggests an economical approach based on easily available raw waste material, which can be utilized for large-scale production of new age multi-functional carbon nanomaterials for various energy applications.
Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis
Authors: Takahashi Nozomi , Harada Miyuki , Hirota Yasushi , Nose Emi , Azhary Jerilee MK , Koike Hiroshi , Kunitomi Chisato , Yoshino Osamu , Izumi Gentaro , Hirata Tetsuya , Koga Kaori , Wada-Hiraike Osamu , Chang R. Jeffrey , Shimasaki Shunichi , Fujii Tomoyuki , Osuga Yutaka
Published: September 2017

Recent studies report the involvement of intra-ovarian factors, such as inflammation and oxidative stress, in the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder of reproductive age women. Endoplasmic reticulum (ER) stress is a local factor that affects various cellular events during a broad spectrum of physiological and pathological conditions. It may also be an important determinant of pro-fibrotic remodeling during tissue fibrosis. In the present study, we showed that ER stress was activated in granulosa cells of PCOS patients as well as in a well-established PCOS mouse model. Pharmacological inducers of ER stress, tunicamycin and thapsigargin, were found to increase the expression of pro-fibrotic growth factors, including transforming growth factor (TGF)-β1, in human granulosa cells, and their expression also increased in granulosa cells of PCOS patients. By contrast, treatment of PCOS mice with an ER stress inhibitor, tauroursodeoxycholic acid or BGP-15, decreased interstitial fibrosis and collagen deposition in ovaries, accompanied by a reduction in TGF-β1 expression in granulosa cells. These findings suggest that ER stress in granulosa cells of women with PCOS contributes to the induction of pro-fibrotic growth factors during ovarian fibrosis, and that ER stress may serve as a therapeutic target in PCOS.
Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations
Authors: Bringas Mauro , Petruk Ariel A. , Estrin Darío A. , Capece Luciana , Martí Marcelo A.
Published: September 2017

Human hemoglobin (Hb) is a benchmark protein of structural biology that shaped our view of allosterism over 60 years ago, with the introduction of the MWC model based on Perutz structures of the oxy(R) and deoxy(T) states and the more recent Tertiary Two-State model that proposed the existence of individual subunit states -“r” and “t”-, whose structure is yet unknown. Cooperative oxygen binding is essential for Hb function, and despite decades of research there are still open questions related to how tertiary and quaternary changes regulate oxygen affinity. In the present work, we have determined the free energy profiles of oxygen migration and for HisE7 gate opening, with QM/MM calculations of the oxygen binding energy in order to address the influence of tertiary differences in the control of oxygen affinity. Our results show that in the α subunit the low to high affinity transition is achieved by a proximal effect that mostly affects oxygen dissociation and is the driving force of the allosteric transition, while in the β subunit the affinity change results from a complex interplay of proximal and distal effects, including an increase in the HE7 gate opening, that as shown by free energy profiles promotes oxygen uptake.
The circadian clock in immune cells controls the magnitude of Leishmania parasite infection
Authors: Kiessling Silke , Dubeau-Laramée Geneviève , Ohm Hyejee , Labrecque Nathalie , Olivier Martin , Cermakian Nicolas
Published: September 2017

The intracellular parasite Leishmania uses neutrophils and macrophages as host cells upon infection. These immune cells harbour their own intrinsic circadian clocks, known to influence many aspects of their functions. Therefore, we tested whether the host circadian clocks regulate the magnitude of Leishmania major infection in mice. The extent of parasitic infection varied over 24 h in bone marrow-derived macrophages in vitro and in two different in vivo models, footpad and peritoneal cavity infection. In vivo this was paralleled by time of day-dependent neutrophil and macrophage infiltration to the infection site and rhythmic chemokine expression. Thus, rhythmic parasitic infection observed in vivo was likely initiated by the circadian expression of chemoattractants and the subsequent rhythmic infiltration of neutrophils and macrophages. Importantly, all rhythms were abolished in clock-deficient macrophages and when mice lacking the circadian clock in immune cells were infected. Therefore we demonstrated a critical role for the circadian clocks in immune cells in modulating the magnitude of Leishmania infection. To our knowledge this is the first report showing that the circadian clock controls infection by protozoan parasites in mammals. Understanding the timed regulation of host-parasite interactions will allow developing better prophylactic and therapeutic strategies to fight off vector-borne diseases.
New compounds identified through in silico approaches reduce the α-synuclein expression by inhibiting prolyl oligopeptidase in vitro
Authors: Kumar Raj , Bavi Rohit , Jo Min Gi , Arulalapperumal Venkatesh , Baek Ayoung , Rampogu Shailima , Kim Myeong Ok , Lee Keun Woo
Published: September 2017

Prolyl oligopeptidase (POP) is a serine protease that is responsible for the maturation and degradation of short neuropeptides and peptide hormones. The inhibition of POP has been demonstrated in the treatment of α-synucleinopathies and several neurological conditions. Therefore, ligand-based and structure-based pharmacophore models were generated and validated in order to identify potent POP inhibitors. Pharmacophore-based and docking-based virtual screening of a drug-like database resulted in 20 compounds. The in vitro POP assays indicated that the top scoring compounds obtained from virtual screening, Hit 1 and Hit 2 inhibit POP activity at a wide range of concentrations from 0.1 to 10 µM. Moreover, treatment of the hit compounds significantly reduced the α-synuclein expression in SH-SY5Y human neuroblastoma cells, that is implicated in Parkinson’s disease. Binding modes of Hit 1 and Hit 2 compounds were explored through molecular dynamics simulations. A detailed investigation of the binding interactions revealed that the hit compounds exhibited hydrogen bond interactions with important active site residues and greater electrostatic and hydrophobic interactions compared to those of the reference inhibitors. Finally, our findings indicated the potential of the identified compounds for the treatment of synucleinopathies and CNS related disorders.
Factor Xa Mediates Calcium Flux in Endothelial Cells and is Potentiated by Igg From Patients With Lupus and/or Antiphospholipid Syndrome
Authors: Artim-Esen Bahar , Smoktunowicz Natalia , McDonnell Thomas , Ripoll Vera M. , Pericleous Charis , Mackie Ian , Robinson Eifion , Isenberg David , Rahman Anisur , Ioannou Yiannis , Chambers Rachel C. , Giles Ian
Published: September 2017

Factor (F) Xa reactive IgG isolated from patients with antiphospholipid syndrome (APS) display higher avidity binding to FXa with greater coagulant effects compared to systemic lupus erythematosus (SLE) non APS IgG. FXa signalling via activation of protease-activated receptors (PAR) leads to increased intracellular calcium (Ca2+). Therefore, we measured alterations in Ca2+levels in human umbilical vein endothelial cells (HUVEC) following FXa-mediated PAR activation and investigated whether FXa reactive IgG from patients with APS or SLE/APS- alter these responses. We observed concentration-dependent induction of Ca2+release by FXa that was potentiated by APS-IgG and SLE/APS- IgG compared to healthy control subjects’ IgG, and FXa alone. APS-IgG and SLE/APS- IgG increased FXa mediated NFκB signalling and this effect was fully-retained in the affinity purified anti-FXa IgG sub-fraction. Antagonism of PAR-1 and PAR-2 reduced FXa-induced Ca2+release. Treatment with a specific FXa inhibitor, hydroxychloroquine or fluvastatin significantly reduced FXa-induced and IgG-potentiated Ca2+release. In conclusion, PAR-1 and PAR-2 are involved in FXa-mediated intracellular Ca2+release in HUVEC and FXa reactive IgG from patients with APS and/or SLE potentiate this effect. Further work is required to explore the potential use of IgG FXa reactivity as a novel biomarker to stratify treatment with FXa inhibitors in these patients.
Overexpression of Insig-2 inhibits atypical antipsychotic-induced adipogenic differentiation and lipid biosynthesis in adipose-derived stem cells
Authors: Chen Chien-Chih , Hsu Li-Wen , Huang Kuang-Tzu , Goto Shigeru , Chen Chao-Long , Nakano Toshiaki
Published: September 2017

Atypical antipsychotics (AAPs) are considered to possess superior efficacy for treating both the positive and negative symptoms of schizophrenia; however, AAP use often causes excessive weight gain and metabolic abnormalities. Recently, several reports have demonstrated that AAPs activate sterol regulatory element-binding protein (SREBP). SREBP, SREBP cleavage-activating protein (SCAP) and insulin-induced gene (Insig) regulate downstream cholesterol and fatty acid biosynthesis. In this study, we explored the effects of clozapine, olanzapine and risperidone on SREBP signaling and downstream lipid biosynthesis genes in the early events of adipogenic differentiation in adipose-derived stem cells (ASCs). After the induction of adipogenic differentiation for 2 days, all AAPs, notably clozapine treatment for 3 and 7 days, enhanced the expression of SREBP-1 and its downstream lipid biosynthesis genes without dexamethasone and insulin supplementation. Simultaneously, protein level of SREBP-1 was significantly enhanced via inhibition of Insig-2 expression. By contrast, SREBP-1 activation was suppressed when Insig-2 expression was upregulated by transfection with Insig-2 plasmid DNA. In summary, our results indicate that AAP treatment, notably clozapine treatment, induces early-stage lipid biosynthesis in ASCs. Such abnormal lipogenesis can be reversed when Insig-2 expression was increased, suggesting that Insig/SCAP/SREBP signaling may be a therapeutic target for AAP-induced weight gain and metabolic abnormalities.
Inter-subject Functional Correlation Reveal a Hierarchical Organization of Extrinsic and Intrinsic Systems in the Brain
Authors: Ren Yudan , Nguyen Vinh Thai , Guo Lei , Guo Christine Cong
Published: September 2017

The brain is constantly monitoring and integrating both cues from the external world and signals generated intrinsically. These extrinsically and intrinsically-driven neural processes are thought to engage anatomically distinct regions, which are thought to constitute the extrinsic and intrinsic systems of the brain. While the specialization of extrinsic and intrinsic system is evident in primary and secondary sensory cortices, a systematic mapping of the whole brain remains elusive. Here, we characterized the extrinsic and intrinsic functional activities in the brain during naturalistic movie-viewing. Using a novel inter-subject functional correlation (ISFC) analysis, we found that the strength of ISFC shifts along the hierarchical organization of the brain. Primary sensory cortices appear to have strong inter-subject functional correlation, consistent with their role in processing exogenous information, while heteromodal regions that attend to endogenous processes have low inter-subject functional correlation. Those brain systems with higher intrinsic tendency show greater inter-individual variability, likely reflecting the aspects of brain connectivity architecture unique to individuals. Our study presents a novel framework for dissecting extrinsically- and intrinsically-driven processes, as well as examining individual differences in brain function during naturalistic stimulation.
Genome-wide identification and co-expression network analysis provide insights into the roles of auxin response factor gene family in chickpea
Authors: Singh Vikash K. , Rajkumar Mohan Singh , Garg Rohini , Jain Mukesh
Published: September 2017

Auxin response factors (ARFs) are the transcription factors that regulate auxin responses in various aspects of plant growth and development. Although genome-wide analysis of ARF gene family has been done in some species, no information is available regarding ARF genes in chickpea. In this study, we identified 28 ARF genes (CaARF) in the chickpea genome. Phylogenetic analysis revealed that CaARFs can be divided into four different groups. Duplication analysis revealed that 50% of CaARF genes arose from duplication events. We analyzed expression pattern of CaARFs in various developmental stages. CaARF16.3, CaARF17.1 and CaARF17.2 showed highest expression at initial stages of flower bud development, while CaARF6.2 had higher expression at later stages of flower development. Further, CaARF4.2, CaARF9.2, CaARF16.2 and CaARF7.1 exhibited differential expression under different abiotic stress conditions, suggesting their role in abiotic stress responses. Co-expression network analysis among CaARF, CaIAA and CaGH3 genes enabled us to recognize components involved in the regulatory network associated with CaARFs. Further, we identified microRNAs that target CaARFs and TAS3 locus that trigger production of trans-acting siRNAs targeting CaARFs. The analyses presented here provide comprehensive information on ARF family members and will help in elucidating their exact function in chickpea.