bluuebunny/crossref_metadata_2025 huggingface dataset:
Free‐Blockage Mesoporous Anticancer Nanoparticles Based on ROS‐Responsive Wetting Behavior of Nanopores
Authors: Cheng Yaya , Jiao Xiangyu , Xu Tailin , Wang Wenqian , Cao Yu , Wen Yongqiang , Zhang Xueji
Published: August 2017

To achieve an excellent delivery effect of drug, stimuli‐responsive nano “gate” with physical blockage units is usually constructed on the surface of the mesoporous silica nanocarriers (MSNs). In nature, the aquaporins in cell membrane can control the transport of water molecules by regulating the channel wettability, which is resulted from the conformational change of amino acids in the channel. Inspired by this phonomenon, herein a new concept of free‐blockage controlled release system is proposed, which is achieved by controlling the wettability of the internal surface of nanopores on MSNs. Such a new system is different from the physical‐blockage controlled release system, which bypasses the use of nano “gate” and overcomes the limitations of traditional physical blockage system. Moreover, further studies have shown that the system can selectively release the entrapped doxorubicin in human breast adenocarcinoma (MCF‐7) cells triggered by intracellular reactive oxygen species (ROS) but not in normalhuman umbilical vein endothelial cells (HUVECs) containing ROS with low levels. The wettability‐determined free‐blockage controlled release system is simple and effective, and it can also be triggered by intracellular biological stimuli, which provides a new approach for the future practical application of drug delivery and cancer therapy.
An empirical assessment of technical debt practices in industry
Authors: Codabux Zadia , Williams Byron J. , Bradshaw Gary L. , Cantor Murray
Published: August 2017

Context

Technical debt refers to the consequences of taking shortcuts when developing software. These consequences can impede the software growth and have financial implications. The software engineering research community needs to explore technical debt further from a practitioner standpoint.

Objective

This study gathers insights from practitioners on key components of technical debt such as its definition, characterization, consequences, benefits, and how it is communicated.

Method

We conducted semi‐structured interviews with a convenience sample of 17 practitioners and a survey of 67 participants.

Results

Despite the lack of consensus, we identified the most commonly accepted definition, method to measure technical debt (as person hours), and method to reduce debt (by allocating time in iterations to address the debt). Defects were also identified as type of debt and the cost of technical debt is more than the cost to make changes to source code. Three distinct company profiles emerged.

Conclusion

Despite increasing research on technical debt, the field lacks consensus on its many facets. One interesting outcome of this study is how to assess the risks of technical debt by evaluating liabilities beyond costs of directly handling debt.
Plantain flour: A potential nutraceutical ingredient to increase fiber and reduce starch digestibility of gluten‐free cookies
Authors: García‐Solís Sandra E. , Bello‐Pérez Luis A. , Agama‐Acevedo Edith , Flores‐Silva Pamela C.
Published: August 2017

There is interest in the production of gluten‐free foods with high dietary fibre content and low caloric supply. It is well known that gluten‐free foods present a poor matrix due to the absence of gluten, a protein that builds the network which provides the accepted textural characteristics of bakery products and pasta. Moreover, gluten‐free products have a low dietary fibre content due to the use of starch or refined flours. The aim of this study was to evaluate the use of unripe plantain flour (UPF) to prepare gluten‐free cookies with high dietary fibre content. A commercial high dietary fibre ingredient (Hi‐Maize 260®) was used for comparison. The hardness, chemical composition, and starch digestibility of the cookies were assessed. The texture and the proximal composition of both cookies was similar, but the dietary fibre content of the cookie with UPF was 100% higher than that of Hi‐Maize 260®, and the former showed a lower predicted glycaemic index. These results indicated that unripe plantain flour can be used as a substitute for commercial ingredients to produce gluten‐free cookies with high dietary fibre content and a low predicted glycaemic index.
Morphological and physicochemical properties of starches isolated from three taro bulbs
Authors: Zhu Xiaowei , Cui Wenxue , Zhang Erjin , Sheng Jieyue , Yu Xurun , Xiong Fei
Published: August 2017

Taro [Colocasia esculenta (L.) Schott] is an edible underground bulb crop belonging to the family Araceae, and its main component is starch. We systematically studied and compared the morphological and physicochemical characteristics of the starches isolated from bulbs of three taro varieties with high output and quality. Viscosity analysis showed that the starches from Xiangsha and Longxiang displayed the highest and lowest peak, trough, breakdown, and final viscosity, respectively. Xiangsha presented the highest proportion of crystalline region and V‐type single helical components, whereas the opposite was observed in Longxiang. When hydrolyzed by porcine pancreatic α‐amylase, amyloglucosidase, and hydrochloric acid, Longxiang and Xiangsha ultimately presented the highest and lowest hydrolysis degrees, respectively. The results indicate that starches from the three taro bulbs significantly differed in morphological and physicochemical characteristics, and these results may provide valuable information for the exploitation and utilization of taro starch in food and non‐food industries.
New nonlinear dynamic response model of squat/slender flanged/non‐flanged reinforced concrete walls
Authors: Allouzi Rabab , Alkloub Amer
Published: August 2017

The response of reinforced concrete (RC) shear wall as a lateral resisting member has been studied extensively, but it still demands a general practical model that identifies the envelope within which load–drift paths occur during cyclic loading. Such a broad model is vital to ensure adequate lateral strength to resist reversal loadings imposed on these walls during earthquake events and ductility to measure inelastic deformation capabilities. A new model to define the backbone curve is developed in this paper for squat, intermediate, and slender flanged and non‐flanged RC walls. The most common failure modes observed in the field and laboratory experiments are investigated and incorporated in the proposed model to estimate the response of these walls from elastic range until ultimate failure. The main parameters controlling the estimation of drifts that features the backbone curve thresholds are presented in this paper. The results of proposed model are compared with the outcomes of 117 specimens experimentally tested by other researchers. Also, the results are compared with Federal Emergency Management Agency (FEMA) 356, the updated American Society of Civil Engineers (ASCE)/Structural Engineering Institute (SEI) 41, and Eurocode (EC8 and EC2) provisions which reveal that only one general model, proposed in this paper, can capture the response of RC structural walls with an aspect ratio ranging from 0.35 to 2.5 and an axial load ratio from 0 to 0.4 with good agreement with experimental outcomes.
Validity evidence for a learning progression of scientific explanation
Authors: Yao Jian‐Xin , Guo Yu‐Ying
Published: August 2017

Providing scientific explanations for natural phenomena is a fundamental aim of science; therefore, scientific explanation has been selected as one of the key practices in science education policy documents around the world. To further elaborate on existing educational frameworks of scientific explanation in K–12, we propose a learning progression of scientific explanation based on the Phenomenon‐Theory‐Data‐Reasoning (PTDR) framework. To examine the validation of the PTDR framework for scientific explanation and the learning progression based on it, we developed the Scientific Explanation Progression Assessment to investigate students’ performance (Grades 8–12 students, N = 4,554) on scientific explanations. A Rasch analysis and other statistical tests together indicated the validity of the PTDR framework for scientific explanation and the learning progression derived from this framework. We end with a discussion of the implications for future design of instruction and assessment. © 2017 Wiley Periodicals, Inc. J Res Sci Teach 55: 299–317, 2018
Advances in metabolome information retrieval: turning chemistry into biology. Part II: biological information recovery
Authors: Tebani Abdellah , Afonso Carlos , Bekri Soumeya
Published: August 2017

This work reports the second part of a review intending to give the state of the art of major metabolic phenotyping strategies. It particularly deals with inherent advantages and limits regarding data analysis issues and biological information retrieval tools along with translational challenges. This Part starts with introducing the main data preprocessing strategies of the different metabolomics data. Then, it describes the main data analysis techniques including univariate and multivariate aspects. It also addresses the challenges related to metabolite annotation and characterization. Finally, functional analysis including pathway and network strategies are discussed. The last section of this review is devoted to practical considerations and current challenges and pathways to bring metabolomics into clinical environments.
Use of specialists on audit engagements: A research synthesis and directions for future research
Authors: Hux Candice T.
Published: August 2017

This synthesis covers academic research on the use of valuation, tax, information technology (IT), and forensic specialists on audit engagements. The importance and role of specialists on audit engagements have recently increased, and specialist use has garnered significant attention from regulators and academics. Given the PCAOB’s (2017b) recent proposal to revise auditing standards regarding specialists’ involvement, it is important to review the specialist literature as a whole. By integrating research across these four domains, I identify commonalities and differences related to: (1) factors associated with the use of specialists on audit engagements (including the nature, timing, and extent of use); (2) factors impacting auditors’ interactions with specialists (including specialists contracted by the auditor or management); and (3) outcomes associated with the use of specialists. This integrated analysis of the specialist literatures shows variation in the use of specialists, and various factors affecting both if and how they are involved and whether auditors use specialists internal or external to the audit firm. Additionally, research has sometimes (but not always) linked specialist involvement to higher audit quality. The commonalities and areas of variation identified are informative to audit research and practice, particularly as regulators and audit firms look to improve the quality of audits using specialists. Throughout the synthesis, I also provide a number of directions for future research.
Backing into the future: pharmacological approaches to the management of resistant depression
Authors: Cowen P. J.
Published: August 2017

Pragmatic studies indicate that a substantial number of depressed patients do not remit with current first-line antidepressant treatments and after two failed treatment steps the chance of remission with subsequent therapies is around 15%. This paper focuses on current evidence for pharmacological treatments in resistant depression as well as possible future developments. For patients who have failed to respond to two antidepressant trials, augmentation with atypical antipsychotic drugs, specifically quetiapine and aripiprazole, has the best evidence for efficacy, though older treatments such as lithium and triiodothyronine still have utility. The striking antidepressant effect of ketamine in resistant depression has stimulated research into glutamatergic compounds; however, capturing the efficacy of ketamine with drugs suitable for continuous use has proved challenging. Growing knowledge of the pathophysiological role of inflammation in depression offers great opportunities for future treatment in terms of repurposing anti-inflammatory agents from general medicine and pre-treatment stratification of those depressed patients in whom such interventions are likely to be beneficial. Finally an older drug, the dopamine receptor agonist pramipexole, if used carefully may well improve the prospects of depressed patients who are refractory to current approaches.
VICTORIAN ECOCRITICISM FOR THE ANTHROPOCENE
Authors: Williams Daniel
Published: August 2017

How might literary and cultural spheresintersect with the Anthropocene, the epoch — however defined — of humanity's detectable influence at geological scale? What forms, genres, objects, and methodological lenses might prove most fertile in mediating between the concept's abstraction and its concrete entailments for literary and cultural history? Such questions have already commissioned a range of critical projects that attempt to reframe the Anthropocene itself: as a trope of science fiction, given how humans are “terraforming” the planet (Heise 215–20); as an object for media archaeology, considering the “signatures” that our aggregate actions are leaving in the physical strata of the earth (Boes and Marshall 64–67); and as a challenge to the categorical distinctions by which historical study is practiced, with its blurring of “human history” and “natural history” (Chakrabarty 201–07).
Percutaneous sclerotherapy for spongiform venous malformations – analysis of patient-evaluated outcome and satisfaction
Authors: Clemens Robert Karl , Baumann Frederic , Husmann Marc , Meier Thomas Oleg , Thalhammer Christoph , MacCallum Gail , Amann-Vesti Beatrice Ruth , Alomari Ahmad Ibrahim
Published: August 2017

Abstract. Background: Congenital venous malformations are frequently treated with sclerotherapy. Primary treatment goal is to control the often size-related symptoms. Functional impairment and aesthetical aspects as well as satisfaction have rarely been evaluated. Patients and methods: Medical records of patients who underwent sclerotherapy of spongiform venous malformations were reviewed and included in this retrospective study. The outcome of sclerotherapy as self-reported by patients was assessed in a 21 item questionnaire. Results: Questionnaires were sent to 166 patients with a total of 327 procedures. Seventy-seven patients (48 %) with a total of 159 procedures (50 %) responded to the survey. Fifty-seven percent of patients were male. The age ranged from 1 to 38.1 years with a median age of 16.4 years. The lower extremities were the most common treated area. Limitations caused by the venous malformation improved in the majority of patients (e.g. pain improvement 87 %, improvement of swelling 83 %) but also worsening of symptoms occurred in a minority of cases. Seventy-seven per cent would undergo sclerotherapy again. Conclusions: Sclerotherapy for treatment of venous malformations results in significant reduction of symptoms. Multiple treatments are often needed, but patients are willing to undergo them.
Giovanni: The Bridge Between Data and Science
Authors: Liu Zhong , Acker James
Published: August 2017

Using satellite remote sensing data sets can be a daunting task. Giovanni, a Web-based tool, facilitates access, visualization, and exploration for many of NASA’s Earth science data sets.
How Can We Best Manage Shared Resources?
Authors: Witman Sarah
Published: August 2017

Researchers develop a mathematical model to shed light on the social, economic, and ecological challenges of governing resources such as fisheries, forests, grazing lands, and the atmosphere.
Direct observation of localized surface plasmon field enhancement by Kelvin probe force microscopy
Authors: Li Da-Bing , Sun Xiao-Juan , Jia Yu-Ping , Stockman Mark I , Paudel Hari P , Song Hang , Jiang Hong , Li Zhi-Ming
Published: August 2017

A surface plasmon (SP) is a fundamental excitation state that exists in metal nanostructures. Over the past several years, the performance of optoelectronic devices has been improved greatly via the SP enhancement effect. In our previous work, the responsivity of GaN ultraviolet detectors was increased by over 30 times when using Ag nanoparticles. However, the physics of the SP enhancement effect has not been established definitely because of the lack of experimental evidence. To reveal the physical origin of this enhancement, Kelvin probe force microscopy (KPFM) was used to observe the SP-induced surface potential reduction in the vicinity of Ag nanoparticles on a GaN epilayer. Under ultraviolet illumination, the localized field enhancement induced by the SP forces the photogenerated electrons to drift close to the Ag nanoparticles, leading to a reduction of the surface potential around the Ag nanoparticles on the GaN epilayer. For an isolated Ag nanoparticle with a diameter of ~200 nm, the distribution of the SP localized field is located within 60 nm of the boundary of the Ag nanoparticle. For a dimer of Ag nanoparticles, the localized field enhancement between the nanoparticles was the strongest. The results presented here provide direct experimental proof of the localized field enhancement. These results not only explain the high performance of GaN detectors observed with the use of Ag nanoparticles but also reveal the physical mechanism of SP enhancement in optoelectronic devices, which will help us further understand and improve the performance of SP-based optoelectronic devices in the future.
Expression of Thyroid Hormone Responsive SPOT 14 Gene Is Regulated by Estrogen in Chicken (Gallus gallus)
Authors: Ren Junxiao , Xu Naiyi , Zheng Hang , Tian Weihua , Li Hong , Li Zhuanjian , Wang Yanbin , Tian Yadong , Kang Xiangtao , Liu Xiaojun
Published: August 2017

Thyroid hormone responsive spot 14 (THRSP) is a small nuclear protein that responds rapidly to thyroid hormone. It has been shown that THRSP is abundant in lipogenic tissues such as liver, fat and the mammary gland in mammals. The THRSP gene acts as a key lipogenic activator and can be activated by thyroid hormone triiodothyronine (T3), glucose, carbohydrate and insulin. Here we report that chicken THRSP is also abundant in lipogenic tissues including the liver and the abdominal fat, and its expression levels increased with sex maturation and reached the highest level at the peak of egg production. Structure analysis of the THRSP gene indicates that there is a conscious estrogen response element (ERE) located in the −2390 – −2402 range of the gene promoter region. Further studies by ChIP-qPCR proved that the ERα interacts with the putative ERE site. In addition, THRSP was significantly upregulated (P < 0.05) when chickens or chicken primary hepatocytes were treated with 17β-estradiol in both the in vivo and in vitro conditions. We therefore conclude that THRSP is directly regulated by estrogen and is involved in the estrogen regulation network in chicken.
Optical spin noise spectra of Rb atomic gas with homogeneous and inhomogeneous broadening
Authors: Ma Jian , Shi Ping , Qian Xuan , Shang Yaxuan , Ji Yang
Published: August 2017

We study the optical spin noise spectra of Rb atomic gas with different broadening mechanisms. The first is homogeneous broadening using 250 Torr nitrogen buffer gas, while the other mechanism is inhomogeneous broadening via the Doppler effect without buffer gas. Spin noise signals are measured by the typical spin noise spectroscopy geometry (single-pass geometry) and the saturated absorption spectroscopy geometry (double-pass geometry). In the homogeneously broadened system, the line shape of the optical spin noise spectra shows a pronounced dip that vanishes at the center of the band in both geometries. In the inhomogeneously broadened system, however, a peak in the single-pass geometry and a dip in the double-pass geometry at the band center are observed. The difference between the optical spin noise spectra from these two systems arises from their different level-broadening mechanisms.
Bi-directional plasticity: Rotifer prey adjust spine length to different predator regimes
Authors: Zhang Huan , Hollander Johan , Hansson Lars-Anders
Published: August 2017

Numerous prey organisms, including many rotifers, exhibit inducible defensive plasticity, such as spines, in response to predators. Here, we test the hypothesis that prey modify their defence response to different predator sizes with a bi-directional adjustment in spine length. First, we show experimentally, that large-sized predators induce a reduction in prey spine length. Second, we conducted a complementary field monitoring study showing that the spine length of the prey rotifer Keratella cochlearis changed in opposite directions, in response to the shift in dominance between small-sized and large-sized predators. Third, in order to test the generality of our novel findings, we conducted a meta-analysis covering a wide array of rotifer prey taxa, strengthening the conclusions from our experimental and field studies. Hence, by combining evidence from experiments and studies in the field with a meta-analysis, we, for the first time, demonstrate that rotifer prey distinguish between predators and adjust their protective spine length accordingly, i.e. rapidly adjust spine length to escape either below or above the dominant predator’s gape size window. In a broader perspective, our conclusions advance our knowledge on observed spatial and temporal variations in protective morphologies among prey organisms.
CXCR3 plays a critical role for host protection against Salmonellosis
Authors: Chami Belal , Yeung Amanda , Buckland Michael , Liu Hongjun , M. Fong Genevieve , Tao Kun , Bao Shisan
Published: August 2017

CXCR3 and its ligands are heavily associated with inflammation and have been implicated in numerous inflammatory diseases. CXCR3 plays an important role in recruiting pro-inflammatory cells, specifically neutrophils, in a model of sterile colitis whereby CXCR3−/− mice showed an attenuated course of colitis with markedly reduced host-tissue damage in the inflamed caecum. The role of CXCR3 during infectious colitis, however, is unclear and therefore in this study, we investigated the role of CXCR3 in the regulation of the immune response during acute and chronic gastrointestinal infection, using a murine model of Salmonella enterica serovar Enteritidis. During acute infection with Salmonella, we observed significantly increased Salmonella loading in the caecum and dissemination to the spleen and liver in CXCR3−/− mice, but not in Wt counterparts. During chronic infection, increased pathological features of inflammation were noted in the spleen and liver, with significantly increased levels of apoptosis in the liver of CXCR3−/− mice, when compared to Wt counterparts. In addition, compromised intestinal IgA levels, CD4+ helper T cells and neutrophil recruitment were observed in CXCR3−/− challenged with Salmonella, when compared to Wt counterparts. Our data suggests that CXCR3 is a key molecule in host intestinal immunity against Salmonellosis via regulating neutrophils chemotaxis.
Epigenetic Regulation of PLIN
1 in Obese Women and its Relation to Lipolysis
Authors: Bialesova Lucia , Kulyté Agné , Petrus Paul , Sinha Indranil , Laurencikiene Jurga , Zhao Chunyan , Wright Karin Dahlman , Arner Peter , Dahlman Ingrid
Published: August 2017

Increased adipocyte lipolysis links obesity to insulin resistance. The lipid droplet coating-protein Perilipin participates in regulation of lipolysis and is implicated in obesity. In the present study we investigate epigenetic regulation of the PLIN1 gene by correlating PLIN1 CpG methylation to gene expression and lipolysis, and functionally evaluating PLIN1 promoter methylation. PLIN1 CpG methylation in adipocytes and gene expression in white adipose tissue (WAT) was quantified in two cohorts by array. Basal lipolysis in WAT explants and adipocytes was quantified by measuring glycerol release. CpG-methylation of the PLIN1 promoter in adipocytes from obese women was higher as compared to never-obese women. PLIN1 promoter methylation was inversely correlated with PLIN1 mRNA expression and the lipolytic activity. Human mesenchymal stem cells (hMSCs) differentiated in vitro into adipocytes and harboring methylated PLIN1 promoter displayed decreased reporter gene activity as compared to hMSCs harboring unmethylated promoter. Treatment of hMSCs differentiated in vitro into adipocytes with a DNA methyltransferase inhibitor increased levels of PLIN1 mRNA and protein. In conclusion, the PLIN1 gene is epigenetically regulated and promoter methylation is inversely correlated with basal lipolysis in women suggesting that epigenetic regulation of PLIN1 is important for increased adipocyte lipolysis in insulin resistance states.
Learning performance is linked to procedural memory consolidation across both sleep and wakefulness
Authors: Rångtell Frida H. , Karamchedu Swathy , Andersson Peter , van Egmond Lieve , Hultgren Tyra , Broman Jan-Erik , Cedernaes Jonathan , Benedict Christian
Published: August 2017

We investigated whether learning performance in a procedural finger tapping task ﻿﻿before nocturnal sleep﻿﻿ would﻿ predict performance gains after sleep in 60 young adults. Gains were defined as change in correctly tapped digit sequences between learning (12 trials﻿ ad﻿minist﻿er﻿ed in the evening) and retesting (3 ﻿trials﻿ administere﻿d in the morning after sleep). The same task was also administered to a separate wake group (N = 54 young adults), which learned in the morning and was retested in the evening.﻿ Learning performance was determined by either using the average performance on the last three learning trials or the a﻿verage performance on the best three learning trials. Our results demonstrated an inverse association between learning performance and gains in procedural skill, i.e., good learners exhibited smaller performance gains﻿ across ﻿both wakefulness and sleep than poor learners. Regardless of learning performance, gains in finger tapping skills were greater after sleep than daytime wakefulness. Importantly, some of our findings were influenced by how learning performance was estimated. Collectively, these results suggest that learning performance and the method through which it is estimated may influence performance gains in finger tapping skills across both sleep and wakefulness.
A Two-Step Growth Pathway for High Sb Incorporation in GaAsSb Nanowires in the Telecommunication Wavelength Range
Authors: Ahmad Estiak , Karim Md Rezaul , Hafiz Shihab Bin , Reynolds C Lewis , Liu Yang , Iyer Shanthi
Published: August 2017

Self-catalyzed growth of axial GaAs1−xSbx nanowire (NW) arrays with bandgap tuning corresponding to the telecommunication wavelength of 1.3 µm poses a challenge, as the growth mechanism for axial configuration is primarily thermodynamically driven by the vapor-liquid-solid growth process. A systematic study carried out on the effects of group V/III beam equivalent (BEP) ratios and substrate temperature (Tsub) on the chemical composition in NWs and NW density revealed the efficacy of a two-step growth temperature sequence (initiating the growth at relatively higher Tsub = 620 °C and then continuing the growth at lower Tsub) as a promising approach for obtaining high-density NWs at higher Sb compositions. The dependence of the Sb composition in the NWs on the growth parameters investigated has been explained by an analytical relationship between the effective vapor composition and NW composition using relevant kinetic parameters. A two-step growth approach along with a gradual variation in Ga-BEP for offsetting the consumption of the droplets has been explored to realize long NWs with homogeneous Sb composition up to 34 at.% and photoluminescence emission reaching 1.3 µm at room temperature.
Neuroblastoma patient-derived xenograft cells cultured in stem-cell promoting medium retain tumorigenic and metastatic capacities but differentiate in serum
Authors: Persson Camilla U. , von Stedingk Kristoffer , Bexell Daniel , Merselius My , Braekeveldt Noémie , Gisselsson David , Arsenian-Henriksson Marie , Påhlman Sven , Wigerup Caroline
Published: August 2017

Cultured cancer cells serve as important models for preclinical testing of anti-cancer compounds. However, the optimal conditions for retaining original tumor features during in vitro culturing of cancer cells have not been investigated in detail. Here we show that serum-free conditions are critical for maintaining an immature phenotype of neuroblastoma cells isolated from orthotopic patient-derived xenografts (PDXs). PDX cells could be grown either as spheres or adherent on laminin in serum-free conditions with retained patient-specific genomic aberrations as well as tumorigenic and metastatic capabilities. However, addition of serum led to morphological changes, neuronal differentiation and reduced cell proliferation. The epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were central for PDX cell proliferation and MYCN expression, and also hindered the serum-induced differentiation. Although serum induced a robust expression of neurotrophin receptors, stimulation with their cognate ligands did not induce further sympathetic differentiation, which likely reflects a block in PDX cell differentiation capacity coupled to their tumor genotype. Finally, PDX cells cultured as spheres or adherent on laminin responded similarly to various cytotoxic drugs, suggesting that both conditions are suitable in vitro screening models for neuroblastoma-targeting compounds.
The paradox of highly effective sofosbuvir-based combination therapy despite slow viral decline: can we still rely on viral kinetics?
Authors: Nguyen Thi Huyen Tram , Guedj Jérémie , Uprichard Susan L. , Kohli Anita , Kottilil Shyam , Perelson Alan S.
Published: August 2017

High sustained virologic response (SVR) rates have been observed after 6 weeks of anti-HCV treatment using sofosbuvir, ledipasvir and a non-nucleoside polymerase-inhibitor (GS-9669) or a protease-inhibitor (GS-9451) and after 12 weeks with sofosbuvir + ledipasvir. Here we analyze the viral kinetics observed during these treatments to decipher the origin of the rapid cure and to evaluate the possibility of further reducing treatment duration. We found that viral kinetics were surprisingly slow in all treatment groups and could not reproduce the high SVR rates observed. Based on experimental results suggesting that NS5A- or protease-inhibitors can generate non-infectious virus, we incorporated this effect into a mathematical model. We found that to predict observed SVR rates it was necessary to assume that ledipasvir, GS-9669 and GS-9451 rapidly reduce virus infectivity. We predicted with this model that 4 weeks of triple therapy could be sufficient to achieve SVR in patients with undetectable viremia at week 1, but would be suboptimal in general. In conclusion, the rapid cure rate achieved with these combinations is largely disconnected from viral loads measured during treatment. A model assuming that rapid cure is due to a drug effect of generating non-infectious virus could be a basis for future response guided therapy.
Intracellular Chloride Regulation in AVP+ and VIP+ Neurons of the Suprachiasmatic Nucleus
Authors: Klett Nathan J. , Allen Charles N.
Published: August 2017

Several reports have described excitatory GABA transmission in the suprachiasmatic nucleus (SCN), the master pacemaker of circadian physiology. However, there is disagreement regarding the prevalence, timing, and neuronal location of excitatory GABA transmission in the SCN. Whether GABA is inhibitory or excitatory depends, in part, on the intracellular concentration of chloride ([Cl−]i). Here, using ratiometric Cl− imaging, we have investigated intracellular chloride regulation in AVP and VIP-expressing SCN neurons and found evidence suggesting that [Cl−]i is higher during the day than during the night in both AVP+ and VIP+ neurons. We then investigated the contribution of the cation chloride cotransporters to setting [Cl−]i in these SCN neurons and found that the chloride uptake transporter NKCC1 contributes to [Cl−]i regulation in SCN neurons, but that the KCCs are the primary regulators of [Cl−]i in SCN neurons. Interestingly, we observed that [Cl−]i is differentially regulated between AVP+ and VIP+ neurons-a low concentration of the loop diuretic bumetanide had differential effects on AVP+ and VIP+ neurons, while blocking the KCCs with VU0240551 had a larger effect on VIP+ neurons compared to AVP+ neurons.
The First Call Note Plays a Crucial Role in Frog Vocal Communication
Authors: Yue Xizi , Fan Yanzhu , Xue Fei , Brauth Steven E. , Tang Yezhong , Fang Guangzhan
Published: August 2017

Vocal Communication plays a crucial role in survival and reproductive success in most amphibian species. Although amphibian communication sounds are often complex consisting of many temporal features, we know little about the biological significance of each temporal component. The present study examined the biological significance of notes of the male advertisement calls of the Emei music frog (Babina daunchina) using the optimized electroencephalogram (EEG) paradigm of mismatch negativity (MMN). Music frog calls generally contain four to six notes separated approximately by 150 millisecond intervals. A standard stimulus (white noise) and five deviant stimuli (five notes from one advertisement call) were played back to each subject while simultaneously recording multi-channel EEG signals. The results showed that the MMN amplitude for the first call note was significantly larger than for that of the others. Moreover, the MMN amplitudes evoked from the left forebrain and midbrain were typically larger than those from the right counterpart. These results are consistent with the ideas that the first call note conveys more information than the others for auditory recognition and that there is left-hemisphere dominance for processing information derived from conspecific calls in frogs.
Ecological and functional adaptations to water management in a semiarid agroecosystem: a soil metaproteomics approach
Authors: Starke Robert , Bastida Felipe , Abadía Joaquín , García Carlos , Nicolás Emilio , Jehmlich Nico
Published: August 2017

Climate change models point to a decrease in water availability in semiarid areas that would compromise the maintenance of sustainable agriculture. Here, we used a grapefruit agroecosystem model to evaluate the responses of the active soil microbial community – as a microbial subset directly involved in soil functionality- undergoing strategies to cope with the low water availability in south-east Spain. For this purpose, we tested the impacts of: (i) water quality: transfer-water from a river (TW) or reclaimed-water from a wastewater-treatment plant (RW); and (ii) water quantity: continuous optimal amount of water or reduced irrigation (RDI) in the temporal frame when the crop is less sensitive; and their interactions. Metaproteomics revealed that the phylogenetic diversity of the active community and its functional diversity were lowered in soils with RW. RDI lowered soil respiration and functional diversity while the phylogenetic diversity remained constant. The reestablishment of full irrigation after RDI led to a recovery of soil respiration that was accompanied by an enhanced abundance of resilient bacterial populations. Bacterial populations displayed molecular mechanisms against water stress that have been conserved evolutionarily in plants. Protein-based studies shed light on ecological and functional mechanisms that govern the adaptive responses of soil microbial communities to climate-change friendly water management.
Rapid Fabrication of Graphene Field-Effect Transistors with Liquid-metal Interconnects and Electrolytic Gate Dielectric Made of Honey
Authors: Ordonez Richard C. , Hayashi Cody K. , Torres Carlos M. , Melcher Jordan L. , Kamin Nackieb , Severa Godwin , Garmire David
Published: August 2017

Historically, graphene-based transistor fabrication has been time-consuming due to the high demand for carefully controlled Raman spectroscopy, physical vapor deposition, and lift-off processes. For the first time in a three-terminal graphene field-effect transistor embodiment, we introduce a rapid fabrication technique that implements non-toxic eutectic liquid-metal Galinstan interconnects and an electrolytic gate dielectric comprised of honey. The goal is to minimize cost and turnaround time between fabrication runs; thereby, allowing researchers to focus on the characterization of graphene phenomena that drives innovation rather than a lengthy device fabrication process that hinders it. We demonstrate characteristic Dirac peaks for a single-gate graphene field-effect transistor embodiment that exhibits hole and electron mobilities of 213 ± 15 and 166 ± 5 cm2/V·s respectively. We discuss how our methods can be used for the rapid determination of graphene quality and can complement Raman Spectroscopy techniques. Lastly, we explore a PN junction embodiment which further validates that our fabrication techniques can rapidly adapt to alternative device architectures and greatly broaden the research applicability.
Ultra-broad Mid-IR Supercontinuum Generation in Single, Bi and Tri Layer Graphene Nano-Plasmonic waveguides pumping at Low Input Peak Powers
Authors: Bobba Swetha S. , Agrawal Arti
Published: August 2017

This article presents four different plasmonic structures using Graphene which yielded an efficient plasmonic mode with low loss for Supercontinuum(SC) generation. At an operating wavelength of 1550 nm in these structures, we generated a multi-octave broadband SC spectrum ranging from 1.5 um–25 um at a low input peak power of 1 W. Due to pumping in the anomalous dispersion region with two Zero Dispersion Wavelengths (ZDWs) and the process of cross phase modulation with soliton fission, red-shifted dispersive waves were generated which led to large broadening from 1.5 um–25 um. Two other Supercontinua ranging from 1–10 um and 0.85–2.2 um also at low input peak powers of 2 W and 0.1 W respectively were generated. These three supercontinua are useful for applications in the fields of biomedical sensors, spectroscopy, fluorescence lifetime imaging and in the design of many other new optical devices. Furthermore, we have also discussed our results on behaviour of Graphene as a metal, even without the negative real value of dielectric constant.
Architecture for Directed Transport of Superparamagnetic Microbeads in a Magnetic Domain Wall Routing Network
Authors: Rapoport Elizabeth , Beach Geoffrey S. D.
Published: August 2017

Directed transport of biological species across the surface of a substrate is essential for realizing lab-on-chip technologies. Approaches that utilize localized magnetic fields to manipulate magnetic particles carrying biological entities are attractive owing to their sensitivity, selectivity, and minimally disruptive impact on biomaterials. Magnetic domain walls in magnetic tracks produce strong localized fields and can be used to capture, transport, and detect individual superparamagnetic microbeads. The dynamics of magnetic microbead transport by domain walls has been well studied. However, demonstration of more complex functions such as selective motion and sorting using continuously driven domain walls in contiguous magnetic tracks is lacking. Here, a junction architecture is introduced that allows for branching networks in which superparamagnetic microbeads can be routed along dynamically-selected paths by a combination of rotating in-plane field for translation, and a pulsed out-of-plane field for path selection. Moreover, experiments and modeling show that the select-field amplitude is bead-size dependent, which allows for digital sorting of multiple bead populations using automated field sequences. This work provides a simple means to implement complex routing networks and selective transport functionalities in chip-based devices using magnetic domain wall conduits.
Predicting the Ionic Product of Water
Authors: Perlt Eva , von Domaros Michael , Kirchner Barbara , Ludwig Ralf , Weinhold Frank
Published: August 2017

We present a first-principles calculation and mechanistic characterization of the ion product of liquid water (K
W
), based on Quantum Cluster Equilibrium (QCE) theory with a variety of ab initio and density functional methods. The QCE method is based on T-dependent Boltzmann weighting of different-sized clusters and consequently enables the observation of thermodynamically less favored and therefore low populated species such as hydronium and hydroxide ions in water. We find that common quantum chemical methods achieve semi-quantitative accuracy in predicting K
W
and its T-dependence. Dominant ion-pair water clusters of the QCE equilibrium distribution are found to exhibit stable 2-coordinate buttress-type motifs, all with maximally Grotthus-ordered H-bond patterns that successfully prevent recombination of hydronium and hydroxide ions at 3-coordinate bridgehead sites. We employ standard quantum chemistry techniques to describe kinetic and mechanistic aspects of ion-pair formation, and we obtain NBO-based bonding indices to characterize other electronic, structural, spectroscopic, and reactive properties of cluster-mediated ionic dissociation.
Gene expression analysis of whole blood RNA from pigs infected with low and high pathogenic African swine fever viruses
Authors: Jaing Crystal , Rowland Raymond R. R. , Allen Jonathan E. , Certoma Andrea , Thissen James B. , Bingham John , Rowe Brenton , White John R. , Wynne James W. , Johnson Dayna , Gaudreault Natasha N. , Williams David T.
Published: August 2017

African swine fever virus (ASFV) is a macrophage-tropic virus responsible for ASF, a transboundary disease that threatens swine production world-wide. Since there are no vaccines available to control ASF after an outbreak, obtaining an understanding of the virus-host interaction is important for developing new intervention strategies. In this study, a whole transcriptomic RNA-Seq method was used to characterize differentially expressed genes in pigs infected with a low pathogenic ASFV isolate, OUR T88/3 (OURT), or the highly pathogenic Georgia 2007/1 (GRG). After infection, pigs infected with OURT showed no or few clinical signs; whereas, GRG produced clinical signs consistent with acute ASF. RNA-Seq detected the expression of ASFV genes from the whole blood of the GRG, but not the OURT pigs, consistent with the pathotypes of these strains and the replication of GRG in circulating monocytes. Even though GRG and OURT possess different pathogenic properties, there was significant overlap in the most upregulated host genes. A small number of differentially expressed microRNAs were also detected in GRG and OURT pigs. These data confirm previous studies describing the response of macrophages and lymphocytes to ASFV infection, as well as reveal unique gene pathways upregulated in response to infection with GRG.
Long-term PGC1β overexpression leads to apoptosis, autophagy and muscle wasting
Authors: Sopariwala Danesh H. , Yadav Vikas , Badin Pierre-Marie , Likhite Neah , Sheth Megha , Lorca Sabina , Vila Isabelle K. , Kim Eun Ran , Tong Qingchun , Song Min Sup , Rodney George G. , Narkar Vihang A.
Published: August 2017

Skeletal muscle wasting is prevalent in many chronic diseases, necessitating inquiries into molecular regulation of muscle mass. Nuclear receptor co-activator peroxisome proliferator-activated receptor co-activator 1 alpha (PGC1α) and its splice variant PGC1α4 increase skeletal muscle mass. However, the effect of the other PGC1 sub-type, PGC1β, on muscle size is unclear. In transgenic mice selectively over-expressing PGC1β in the skeletal muscle, we have found that PGC1β progressively decreases skeletal muscle mass predominantly associated with loss of type 2b fast-twitch myofibers. Paradoxically, PGC1β represses the ubiquitin-proteolysis degradation pathway genes resulting in ubiquitinated protein accumulation in muscle. However, PGC1β overexpression triggers up-regulation of apoptosis and autophagy genes, resulting in robust activation of these cell degenerative processes, and a concomitant increase in muscle protein oxidation. Concurrently, PGC1β up-regulates apoptosis and/or autophagy transcriptional factors such as E2f1, Atf3, Stat1, and Stat3, which may be facilitating myopathy. Therefore, PGC1β activation negatively affects muscle mass over time, particularly fast-twitch muscles, which should be taken into consideration along with its known aerobic effects in the skeletal muscle.
Pupillary responses to light are not affected by narrow irido-corneal angles
Authors: Rukmini A. V. , Najjar Raymond P. , Atalay Eray , Sharma Sourabh , Lock Jing Zhan , Baskaran Mani , Nongpiur Monisha , Gooley Joshua J. , Aung Tin , Milea Dan
Published: August 2017

Chromatic pupillometry is an emerging method for evaluating ocular health that relies upon the differential stimulation of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it has been investigated in conditions affecting the outer or inner retina, there is a paucity of studies in conditions where the anterior chamber of the eye is affected. Primary angle closure suspects (PACS) are defined as eyes with narrow anterior chamber angles and intact retina. PACS patients are at risk of developing primary angle closure glaucoma and are prophylactically treated by performing laser peripheral iridotomy (LPI). Here we evaluated pupillary responses to monchromatic lights in 18 PACS before and after LPI, and compared the results with those of 36 age-matched controls who had gonioscopically open angles. Dose response curves for pupillary constriction were similar between PACS patients and controls (p = 0.98 for blue and 0.90 for red light) and within subjects pre- and post-LPI (p = 0.58 for blue and 0.20 for red light). Baseline-adjusted pupillary constriction responses to blue and red lights were similar in controls and PACS, and not altered after LPI. Our findings suggest that narrow irido-corneal angles and LPI do not influence pupillary responses in PACS.
High-performance metal mesh/graphene hybrid films using prime-location and metal-doped graphene
Authors: Min Jung-Hong , Jeong Woo-Lim , Kwak Hoe-Min , Lee Dong-Seon
Published: August 2017

We introduce high-performance metal mesh/graphene hybrid transparent conductive layers (TCLs) using prime-location and metal-doped graphene in near-ultraviolet light-emitting diodes (NUV LEDs). Despite the transparency and sheet resistance values being similar for hybrid TCLs, there were huge differences in the NUV LEDs’ electrical and optical properties depending on the location of the graphene layer. We achieved better physical stability and current spreading when the graphene layer was located beneath the metal mesh, in direct contact with the p-GaN layer. We further improved the contact properties by adding a very thin Au mesh between the thick Ag mesh and the graphene layer to produce a dual-layered metal mesh. The Au mesh effectively doped the graphene layer to create a p-type electrode. Using Raman spectra, work function variations, and the transfer length method (TLM), we verified the effect of doping the graphene layer after depositing a very thin metal layer on the graphene layers. From our results, we suggest that the nature of the contact is an important criterion for improving the electrical and optical performance of hybrid TCLs, and the method of doping graphene layers provides new opportunities for solving contact issues in other semiconductor devices.