bluuebunny/crossref_metadata_2025 huggingface dataset:
THERE IS NO SUCH THING AS IDEAL THEORY
Authors: Levy Jacob T.
Published: December 2016

In this essay, I argue against the bright-line distinction between ideal and nonideal normative political theory, a distinction used to distinguish “stages” of theorizing such that ideal political principles can be deduced and examined before compromises with the flawed political world are made. The distinction took on its familiar form in Rawls and has enjoyed a resurgence of interest in the past few years. I argue that the idea of a categorical distinction — the kind that could allow for a sequencing of stages of theorizing — is misconceived, because wholly “ideal” normative political theory is a conceptual mistake, the equivalent of taking the simplifying models of introductory physics (“frictionless movement in a vacuum”) and trying to develop an ideal theory of aerodynamics. Political organization and justice are about moral friction in the first instance. I examine both logical and epistemological arguments for the position that we need the uniquely idealizing assumptions of ideal theory in order to arrive at, or to know, a genuine theory of justice or political morality; and I find them wanting. Such assumptions as full compliance, consensus, and the publicity principle of universal knowledge about consensus can sometimes be useful, if used carefully and with justification; but they are not categorically different from other idealizing and abstracting assumptions in generating normative theory. What is referred to as “nonideal” theory is all that there is, and it is many kinds of theory, not one — the many ways in which we learn about justice and injustice, and seek to answer questions of practical reason about what ought to be done in our political world.
A PHILOSOPHER OF SCIENCE LOOKS AT IDEALIZATION IN POLITICAL THEORY
Authors: Ismael Jenann
Published: December 2016

Rawls ignited a debate in political theory when he introduced a division between the ideal and nonideal parts of a theory of justice. In the ideal part of the theory, one presents a positive conception of justice in a setting that assumes perfect compliance with the rules of justice. In the nonideal part, one addresses the question of what happens under departures from compliance. Critics of Rawls have attacked his focus on ideal theory as a form of utopianism, and have argued that political theory should be focused instead on providing solutions to the manifest injustices of the real world. In this essay, I offer a defense of the ideal/nonideal theory distinction according to which it amounts to nothing more than a division of labor, and explore some scientific analogies. Rawls’s own focus on the ideal part of the theory, I argue, stems from a felt need to clarify the foundations of justice, rather than a utopian neglect of real world problems.
Differential gene expression of BMP2 and BMP receptors in chick retina & choroid induced by imposed optical defocus
Authors: ZHANG YAN , LIU YUE , HANG ABRAHAM , PHAN EILEEN , WILDSOET CHRISTINE F.
Published: December 2016

Recent studies have demonstrated the defocus sign-dependent, bidirectional gene expression regulation of bone morphogenetic proteins, BMP2, 4 and 7 in chick RPE. In this study, we examined the effects of imposed positive (+10 D) and negative (−10 D) lenses on the gene expression of these BMPs and BMP receptors (BMPR1A, BMPR1B, BMPR2) in chick retina and choroid after monocular lens treatment for 2 or 48 h, as indicators of the roles of retinal and choroidal BMPs and receptors in postnatal eye growth regulation. In retina, although all genes were expressed, neither +10 nor −10 D lenses, worn for either 2 or 48 h, significantly altered gene expression. In contrast, treatment-related differential gene expression was detected in the choroid for both BMPs and their receptors, although interestingly, with the +10 D lens, BMP2 was up-regulated by 156.7 ± 19.7% after 2 h, while BMPR1A was down-regulated to 82.3 ± 12.5% only after 48 h. With the −10 D lens, only the gene expression of BMPR1B was significantly altered, being up-regulated by 162.3 ± 21.2% after 48 h. Untreated birds showed no difference in expression between their two eyes, for any of the genes examined. The finding that retinal gene expression for BMP2, 4, 7 and their receptors are not affected by short-term optical defocus contrasts with previous observations of sign-dependent expression changes for the same genes in the RPE. The latter changes were also larger and more consistent in direction than the choroidal gene expression changes reported here. The interrelationship between these various changes and their biological significance for eye growth regulation are yet to be elucidated.
Planting Colourings Silently
Authors: BAPST VICTOR , COJA-OGHLAN AMIN , EFTHYMIOU CHARILAOS
Published: December 2016

Letk⩾ 3 be a fixed integer and letZk(G) be the number ofk-colourings of the graphG. For certain values of the average degree, the random variableZk(G(n,m)) is known to be concentrated in the sense that$\tfrac{1}{n}(\ln Z_k(G(n,m))-\ln\Erw[Z_k(G(n,m))])$converges to 0 in probability (Achlioptas and Coja-Oghlan,Proc. FOCS 2008). In the present paper we prove a significantly stronger concentration result. Namely, we show that for a wide range of average degrees,$\tfrac{1}{\omega}(\ln Z_k(G(n,m))-\ln\Erw[Z_k(G(n,m))])$converges to 0 in probability foranydiverging function$\omega=\omega(n)\ra\infty$. Forkexceeding a certain constantk0this result covers all average degrees up to the so-calledcondensation phase transitiondk,con, and this is best possible. As an application, we show that the experiment of choosing ak-colouring of the random graphG(n,m) uniformly at random is contiguous with respect to the so-called ‘planted model’.
Effects of vitrification on blastomere viability and cytoskeletal integrity in mouse embryos
Authors: Oikonomou Zenon , Chatzimeletiou Katerina , Sioga Antonia , Oikonomou Louisa , Tarlatzis Basil C. , Kolibianakis Efstratios
Published: December 2016

Vitrification is widely used to cryopreserve supernumerary embryos following in vitro fertilization (IVF). The mouse model was used to investigate the effects of vitrification on blastomere viability, using viability markers, and on the cytoskeleton, by analysing spindle/chromosome configurations, using confocal scanning microscopy. Ninety cleavage and morula stage dimethyl sulphoxide (DMSO)/EG vitrified mouse embryos were either processed immediately following warming for viability assessment by labelling with the fluorescent markers carboxyfluorescein-diacetate succinimidylester (CFSE) and propidium iodide (PI) or were cultured to the blastocyst stage and immunostained with α-tubulin antibody to visualize microtubules and DAPI or PI to visualize DNA. Sixty-five fresh embryos were also used as the control. Vitrified embryos showed high survival rates following warming, but they had a higher incidence of damaged blastomeres compared with fresh embryos. Most mitotic spindles examined in all groups were normal, but multivariable analysis revealed that the proportion of abnormal spindles was significantly higher in vitrified/warmed embryos (P < 0.05). This study is the first to examine the immediate effects of vitrification on blastomere viability, using fluorescent markers and shows that although vitrification results in a higher incidence of damaged blastomeres, vitrified embryos may compensate for this limited number of damaged/abnormal cells, as development to the blastocyst stage was not compromised.
Pre-pregnancy BMI, gestational weight gain and breast-feeding: a cohort study in China
Authors: Tao Xing-Yong , Huang Kun , Yan Shuang-Qin , Zuo A-Zhu , Tao Rui-Wen , Cao Hui , Gu Chun-Li , Tao Fang-Biao
Published: December 2016

Objective

The purpose of the present study was to examine the influence of maternal pre-pregnancy BMI and gestational weight gain (GWG) on initiation and duration of infant breast-feeding in a prospective birth cohort study.

Design

Breast-feeding information was collected at 1, 3, 6 and 12 months postpartum. The association of pre-pregnancy BMI and GWG with delayed lactogenesis II and termination of exclusive breast-feeding was assessed with logistic regression analysis. The risk of early termination of any breast-feeding during the first year postpartum was assessed with Cox proportional hazards models.

Setting

Urban city in China.

Subjects

Women with infants from the Ma’anshan Birth Cohort Study (n 3196).

Results

The median duration of any breast-feeding in this cohort was 7·0 months. Pre-pregnancy obese women had higher risks of delayed lactogenesis II (risk ratio=1·89; 95 % CI 1·04, 3·43) and early termination of any breast-feeding (hazard ratio=1·38; 95 % CI 1·09, 1·75) adjusted for potential maternal and infant confounders, when compared with normal-weight women. No differences in breast-feeding initiation or duration of exclusive breast-feeding according to pre-pregnancy BMI were found. Moreover, GWG was not associated with any poor breast-feeding outcomes.

Conclusions

The present study indicated that pre-pregnancy obesity increases the risks of delayed lactogenesis II and early termination of any breast-feeding in Chinese women.
Non-adherence to Psychotropic Medication Among Adolescents – A Systematic Review of the Literature
Authors: Häge Alexander , Weymann Lisa , Bliznak Lucia , Märker Viktoria , Mechler Konstantin , Dittmann Ralf W.
Published: December 2016

Abstract. Introduction: Whether patients take their medication as prescribed is of increasing importance in adolescent psychiatry since both the number of efficacious pharmaceutical treatments and the rate of prescriptions of psychotropic compounds are on the rise. Previous research showed high rates of medication nonadherence among both adolescents with medical disorders and adult patients with psychiatric disorders. Methods: The present review was performed according to PRISMA guidelines and evaluates existing scientific literature concerning adherence to psychotropic medication among adolescents. The goal was to determine rates of nonadherence in this age group as well as the factors associated with it. Therefore, we conducted a comprehensive literature search of PubMed from its inception until 15 September 2015 using the keywords “adherence,” “compliance,” “adolescent,” and “psychotropic medication.” Results: A total of 607 pertinent articles were collected and screened; 15 publications were selected for detailed review. The studies differed, among other things, regarding sample characteristics, medication type, and indications. Furthermore, the definitions of what constitutes nonadherence and the methods used to assess it varied widely. Nonadherence rates ranged from 6 % to 62 % (median 33 %). Conclusion: Nonadherence to psychotropic medication is a clinically relevant problem among adolescents. Because of the methodological heterogeneity across studies and partially contradictory results, no conclusions could be drawn concerning the influence of factors such as psychopathology, medication type, side effects, the effectiveness of treatment, or family-related factors. Well-designed long-term studies of large patient samples and a consensus regarding definitions are therefore warranted. Such research would facilitate the design of tailored strategies to improve adherence in these patients.
Downregulation of ASPP2 improves hepatocellular carcinoma cells survival via promoting BECN1-dependent autophagy initiation
Authors: Chen Rui , Wang Hao , Liang Beibei , Liu Guoke , Tang Min , Jia Rongjie , Fan Xiaoyu , Jing Wei , Zhou Xuyu , Wang Huajing , Yang Yang , Wei Huafeng , Li Bohua , Zhao Jian
Published: December 2016

Autophagy is an important catabolic process, which sustains intracellular homeostasis and lengthens cell survival under stress. Here we identify the ankyrin-repeat-containing, SH3-domain-containing, and proline-rich region-containing protein 2 (ASPP2), a haploinsufficient tumor suppressor, as a molecular regulator of starvation-induced autophagy in hepatocellular carcinoma (HCC). ASPP2 expression is associated with an autophagic response upon nutrient deprivation and downregulation of ASPP2 facilitates autophagic flux, whereas overexpression of ASPP2 blocks this starvation-induced autophagy in HCC cells. Mechanistically, ASPP2 inhibits autophagy through regulating BECN1 transcription and formation of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) complex. Firstly, ASPP2 inhibits p65/RelA-induced transcription of BECN1, directly by an ASPP2-p65/RelA-IκBα complex which inhibits phosphorylation of IκBα and the translocation of p65/RelA into the nucleus. Secondly, ASPP2 binds to BECN1, leading to decreased binding of PIK3C3 and UV radiation resistance-associated gene (UVRAG), and increased binding of Rubicon in PIK3C3 complex. Downregulation of ASPP2 enhances the pro-survival and chemoresistant property via autophagy in HCC cells in vitro and in vivo. Decreased ASPP2 expression was associated with increased BECN1 and poor survival in HCC patients. Therefore, ASPP2 is a key regulator of BECN1-dependent autophagy, and decreased ASPP2 may contribute to tumor progression and chemoresistance via promoting autophagy.
Water striders adjust leg movement speed to optimize takeoff velocity for their morphology
Authors: Yang Eunjin , Son Jae Hak , Lee Sang-im , Jablonski Piotr G. , Kim Ho-Young
Published: December 2016

Water striders are water-walking insects that can jump upwards from the water surface. Quick jumps allow striders to avoid sudden dangers such as predators’ attacks, and therefore their jumping is expected to be shaped by natural selection for optimal performance. Related species with different morphological constraints could require different jumping mechanics to successfully avoid predation. Here we show that jumping striders tune their leg rotation speed to reach the maximum jumping speed that water surface allows. We find that the leg stroke speeds of water strider species with different leg morphologies correspond to mathematically calculated morphology-specific optima that maximize vertical takeoff velocity by fully exploiting the capillary force of water. These results improve the understanding of correlated evolution between morphology and leg movements in small jumping insects, and provide a theoretical basis to develop biomimetic technology in semi-aquatic environments.
Pressure-induced nano-crystallization of silicate garnets from glass
Authors: Irifune T. , Kawakami K. , Arimoto T. , Ohfuji H. , Kunimoto T. , Shinmei T.
Published: December 2016

Transparent ceramics are important for scientific and industrial applications because of the superior optical and mechanical properties. It has been suggested that optical transparency and mechanical strength are substantially enhanced if transparent ceramics with nano-crystals are available. However, synthesis of the highly transparent nano-crystalline ceramics has been difficult using conventional sintering techniques at relatively low pressures. Here we show direct conversion from bulk glass starting material in mutianvil high-pressure apparatus leads to pore-free nano-polycrystalline silicate garnet at pressures above ∼10 GPa in a limited temperature range around 1,400 °C. The synthesized nano-polycrystalline garnet is optically as transparent as the single crystal for almost the entire visible light range and harder than the single crystal by ∼30%. The ultrahigh-pressure conversion technique should provide novel functional ceramics having various crystal structures, including those of high-pressure phases, as well as ideal specimens for some mineral physics applications.
CRISPR/Cas9-based genetic correction for recessive dystrophic epidermolysis bullosa
Authors: Webber Beau R , Osborn Mark J , McElroy Amber N , Twaroski Kirk , Lonetree Cara-lin , DeFeo Anthony P , Xia Lily , Eide Cindy , Lees Christopher J , McElmurry Ron T , Riddle Megan J , Kim Chong Jai , Patel Dharmeshkumar D , Blazar Bruce R , Tolar Jakub
Published: December 2016

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe disorder caused by mutations to the COL7A1 gene that deactivate production of a structural protein essential for skin integrity. Haematopoietic cell transplantation can ameliorate some of the symptoms; however, significant side effects from the allogeneic transplant procedure can occur and unresponsive areas of blistering persist. Therefore, we employed genome editing in patient-derived cells to create an autologous platform for multilineage engineering of therapeutic cell types. The clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system facilitated correction of an RDEB-causing COL7A1 mutation in primary fibroblasts that were then used to derive induced pluripotent stem cells (iPSCs). The resulting iPSCs were subsequently re-differentiated into keratinocytes, mesenchymal stem cells (MSCs) and haematopoietic progenitor cells using defined differentiation strategies. Gene-corrected keratinocytes exhibited characteristic epithelial morphology and expressed keratinocyte-specific genes and transcription factors. iPSC-derived MSCs exhibited a spindle morphology and expression of CD73, CD90 and CD105 with the ability to undergo adipogenic, chondrogenic and osteogenic differentiation in vitro in a manner indistinguishable from bone marrow-derived MSCs. Finally, we used a vascular induction strategy to generate potent definitive haematopoietic progenitors capable of multilineage differentiation in methylcellulose-based assays. In totality, we have shown that CRISPR/Cas9 is an adaptable gene-editing strategy that can be coupled with iPSC technology to produce multiple gene-corrected autologous cell types with therapeutic potential for RDEB.
Widening perspectives on regenerative processes through growth
Authors: Nowotarski Stephanie H , Sánchez Alvarado Alejandro
Published: December 2016

Defining the basic mechanisms behind regeneration requires comparison to both development and homeostasis. How is organ size achieved in animals during normal development, and how is it reconstituted in animals capable of regenerating organs and body parts lost to injury? Are the mechanisms regulating size and allometry evolutionarily conserved? In recent years, discoveries in the fields of signalling, physiology, developmental biology and regeneration using a growing and diverse collection of model organisms have begun to shed mechanistic insight into these problems. Growth, central to embryonic development, tissue homeostasis and regeneration, was the unifying concept at the recent Molecular and Cellular Basis for Growth and Regeneration Keystone meeting.
Cardiac Specific Overexpression of Mitochondrial Omi/HtrA2 Induces Myocardial Apoptosis and Cardiac Dysfunction
Authors: Wang Ke , Yuan Yuexing , Liu Xin , Lau Wayne Bond , Zuo Lin , Wang Xiaoliang , Ma Lu , Jiao Kun , Shang Jianyu , Wang Wen , Ma Xinliang , Liu Huirong
Published: December 2016

Myocardial apoptosis is a significant problem underlying ischemic heart disease. We previously reported significantly elevated expression of cytoplasmic Omi/HtrA2, triggers cardiomyocytes apoptosis. However, whether increased Omi/HtrA2 within mitochondria itself influences myocardial survival in vivo is unknown. We aim to observe the effects of mitochondria-specific, not cytoplasmic, Omi/HtrA2 on myocardial apoptosis and cardiac function. Transgenic mice overexpressing cardiac-specific mitochondrial Omi/HtrA2 were generated and they had increased myocardial apoptosis, decreased systolic and diastolic function, and decreased left ventricular remodeling. Transiently or stably overexpression of mitochondria Omi/HtrA2 in H9C2 cells enhance apoptosis as evidenced by elevated caspase-3, -9 activity and TUNEL staining, which was completely blocked by Ucf-101, a specific Omi/HtrA2 inhibitor. Mechanistic studies revealed mitochondrial Omi/HtrA2 overexpression degraded the mitochondrial anti-apoptotic protein HAX-1, an effect attenuated by Ucf-101. Additionally, transfected cells overexpressing mitochondrial Omi/HtrA2 were more sensitive to hypoxia and reoxygenation (H/R) induced apoptosis. Cyclosporine A (CsA), a mitochondrial permeability transition inhibitor, blocked translocation of Omi/HtrA2 from mitochondrial to cytoplasm, and protected transfected cells incompletely against H/R-induced caspase-3 activation. We report in vitro and in vivo overexpression of mitochondrial Omi/HtrA2 induces cardiac apoptosis and dysfunction. Thus, strategies to directly inhibit Omi/HtrA2 or its cytosolic translocation from mitochondria may protect against heart injury.
Experimental Demonstration of Printed Graphene Nano-flakes Enabled Flexible and Conformable Wideband Radar Absorbers
Authors: Huang Xianjun , Pan Kewen , Hu Zhirun
Published: December 2016

In this work, we have designed, fabricated and experimentally characterized a printed graphene nano-flakes enabled flexible and conformable wideband radar absorber. The absorber covers both X (8–12 GHz) and Ku (12–18 GHz) bands and is printed on flexible substrate using graphene nano-flakes conductive ink through stencil printing method. The measured results show that an effective absorption (above 90%) bandwidth spans from 10.4 GHz to 19.7 GHz, namely a 62% fraction bandwidth, with only 2 mm thickness. The flexibility of the printed graphene nano-flakes enables the absorber conformably bending and attaching to a metal cylinder. The radar cross section (RCS) of the cylinder with and without absorber attachment has been compared and excellent absorption has been obtained. Only 3.6% bandwidth reduction has been observed comparing to that of un-bended absorber. This work has demonstrated unambiguously that printed graphene can provide flexible and conformable wideband radar absorption, which extends the graphene’s application to practical RCS reductions.
A central cavity within the holo-translocon suggests a mechanism for membrane protein insertion
Authors: Botte Mathieu , Zaccai Nathan R. , Nijeholt Jelger Lycklama à. , Martin Remy , Knoops Kèvin , Papai Gabor , Zou Juan , Deniaud Aurélien , Karuppasamy Manikandan , Jiang Qiyang , Roy Abhishek Singha , Schulten Klaus , Schultz Patrick , Rappsilber Juri , Zaccai Giuseppe , Berger Imre , Collinson Ian , Schaffitzel Christiane
Published: December 2016

The conserved SecYEG protein-conducting channel and the accessory proteins SecDF-YajC and YidC constitute the bacterial holo-translocon (HTL), capable of protein-secretion and membrane-protein insertion. By employing an integrative approach combining small-angle neutron scattering (SANS), low-resolution electron microscopy and biophysical analyses we determined the arrangement of the proteins and lipids within the super-complex. The results guided the placement of X-ray structures of individual HTL components and allowed the proposal of a model of the functional translocon. Their arrangement around a central lipid-containing pool conveys an unexpected, but compelling mechanism for membrane-protein insertion. The periplasmic domains of YidC and SecD are poised at the protein-channel exit-site of SecY, presumably to aid the emergence of translocating polypeptides. The SecY lateral gate for membrane-insertion is adjacent to the membrane ‘insertase’ YidC. Absolute-scale SANS employing a novel contrast-match-point analysis revealed a dynamic complex adopting open and compact configurations around an adaptable central lipid-filled chamber, wherein polytopic membrane-proteins could fold, sheltered from aggregation and proteolysis.
Arctic lakes show strong decadal trend in earlier spring ice-out
Authors: Šmejkalová Tereza , Edwards Mary E. , Dash Jadunandan
Published: December 2016

The timing of the seasonal freeze-thaw cycle of arctic lakes affects ecological processes and land-atmosphere energy fluxes. We carried out detailed ice-phenology mapping of arctic lakes, based on daily surface-reflectance time series for 2000–2013 from MODIS at 250 m spatial resolution. We used over 13,300 lakes, area >1 km2, in five study areas distributed evenly across the circumpolar Arctic — the first such phenological dataset. All areas showed significant trends towards an earlier break-up, stronger than previously reported. The mean shift in break-up start ranged from −0.10 days/year (Northern Europe) to −1.05 days/year (central Siberia); the shift in break-up end was between −0.14 and −0.72 days/year. Finally, we explored the effect of temperature on break-up timing and compared results among study areas. The 0 °C isotherm shows the strongest relationship (r = 0.56–0.81) in all study areas. If the trend in early break-up continues, rapidly changing ice phenology will likely generate significant, arctic-wide impacts.
Replicatively senescent human fibroblasts reveal a distinct intracellular metabolic profile with alterations in NAD+ and nicotinamide metabolism
Authors: James Emma L. , Lane James A. E. , Michalek Ryan D. , Karoly Edward D. , Parkinson E. Kenneth
Published: December 2016

Cellular senescence occurs by proliferative exhaustion (PEsen) or following multiple cellular stresses but had not previously been subject to detailed metabolomic analysis. Therefore, we compared PEsen fibroblasts with proliferating and transiently growth arrested controls using a combination of different mass spectroscopy techniques. PEsen cells showed many specific alterations in both the NAD+ de novo and salvage pathways including striking accumulations of nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) in the amidated salvage pathway despite no increase in nicotinamide phosphoribosyl transferase or in the NR transport protein, CD73. Extracellular nicotinate was depleted and metabolites of the deamidated salvage pathway were reduced but intracellular NAD+ and nicotinamide were nevertheless maintained. However, sirtuin 1 was downregulated and so the accumulation of NMN and NR was best explained by reduced flux through the amidated arm of the NAD+ salvage pathway due to reduced sirtuin activity. PEsen cells also showed evidence of increased redox homeostasis and upregulated pathways used to generate energy and cellular membranes; these included nucleotide catabolism, membrane lipid breakdown and increased creatine metabolism. Thus PEsen cells upregulate several different pathways to sustain their survival which may serve as pharmacological targets for the elimination of senescent cells in age-related disease.
Differential stimulation of the retina with subretinally injected exogenous neurotransmitter: A biomimetic alternative to electrical stimulation
Authors: Rountree Corey M. , Inayat Samsoon , Troy John B. , Saggere Laxman
Published: December 2016

Subretinal stimulation of the retina with neurotransmitters, the normal means of conveying visual information, is a potentially better alternative to electrical stimulation widely used in current retinal prostheses for treating blindness from photoreceptor degenerative diseases. Yet, no subretinal electrical or chemical stimulation study has stimulated the OFF and ON pathways differentially through inner retinal activation. Here, we demonstrate the feasibility of differentially stimulating retinal ganglion cells (RGCs) through the inner nuclear layer of the retina with glutamate, a primary neurotransmitter chemical, in a biomimetic way. We show that controlled pulsatile delivery of glutamate into the subsurface of explanted wild-type rat retinas elicits highly localized simultaneous inhibitory and excitatory spike rate responses in OFF and ON RGCs. We also present the spatiotemporal characteristics of RGC responses to subretinally injected glutamate and the therapeutic stimulation parameters. Our findings could pave the way for future development of a neurotransmitter-based subretinal prosthesis offering more naturalistic vision and better visual acuity than electrical prostheses.
Tunable electron heating induced giant magnetoresistance in the high mobility GaAs/AlGaAs 2D electron system
Authors: Wang Zhuo , Samaraweera R. L. , Reichl C. , Wegscheider W. , Mani R. G.
Published: December 2016

Electron-heating induced by a tunable, supplementary dc-current (Idc) helps to vary the observed magnetoresistance in the high mobility GaAs/AlGaAs 2D electron system. The magnetoresistance at B = 0.3 T is shown to progressively change from positive to negative with increasing Idc, yielding negative giant-magnetoresistance at the lowest temperature and highest Idc. A two-term Drude model successfully fits the data at all Idc and T. The results indicate that carrier heating modifies a conductivity correction σ1, which undergoes sign reversal from positive to negative with increasing Idc, and this is responsible for the observed crossover from positive- to negative- magnetoresistance, respectively, at the highest B.
High-performance SERS substrate based on hybrid structure of graphene oxide/AgNPs/Cu film@pyramid Si
Authors: Li Zhe , Xu Shi Cai , Zhang Chao , Liu Xiao Yun , Gao Sai Sai , Hu Li Tao , Guo Jia , Ma Yong , Jiang Shou Zhen , Si Hai Peng
Published: December 2016

We present a novel surface-enhanced Raman scattering (SERS) substrate based on graphene oxide/silver nanoparticles/copper film covered silicon pyramid arrays (GO/AgNPs/PCu@Si) by a low-cost and simple method. The GO/AgNPs/PCu@Si substrate presents high sensitivity, good homogeneity and well stability with R6G molecules as a probe. The detected concentration of Rhodamine 6 G (R6G) is as low as 10−15 M. These sensitive SERS behaviors are also confirmed in theory via a commercial COMSOL software, the electric field enhancement is not only formed between the AgNPs, but also formed between the AgNPs and Cu film. And the GO/AgNPs/PCu@Si substrates also present good property on practical application for the detection of methylene blue (MB) and crystal violet (CV). This work may offer a novel and practical method to facilitate the SERS applications in areas of medicine, food safety and biotechnology.
Spotted phenotypes in horses lost attractiveness in the Middle Ages
Authors: Wutke Saskia , Benecke Norbert , Sandoval-Castellanos Edson , Döhle Hans-Jürgen , Friederich Susanne , Gonzalez Javier , Hallsson Jón Hallsteinn , Hofreiter Michael , Lõugas Lembi , Magnell Ola , Morales-Muniz Arturo , Orlando Ludovic , Pálsdóttir Albína Hulda , Reissmann Monika , Ruttkay Matej , Trinks Alexandra , Ludwig Arne
Published: December 2016

Horses have been valued for their diversity of coat colour since prehistoric times; this is especially the case since their domestication in the Caspian steppe in ~3,500 BC. Although we can assume that human preferences were not constant, we have only anecdotal information about how domestic horses were influenced by humans. Our results from genotype analyses show a significant increase in spotted coats in early domestic horses (Copper Age to Iron Age). In contrast, medieval horses carried significantly fewer alleles for these phenotypes, whereas solid phenotypes (i.e., chestnut) became dominant. This shift may have been supported because of (i) pleiotropic disadvantages, (ii) a reduced need to separate domestic horses from their wild counterparts, (iii) a lower religious prestige, or (iv) novel developments in weaponry. These scenarios may have acted alone or in combination. However, the dominance of chestnut is a remarkable feature of the medieval horse population.
Structure and dynamics of a constitutively active neurotensin receptor
Authors: Krumm Brian E. , Lee Sangbae , Bhattacharya Supriyo , Botos Istvan , White Courtney F. , Du Haijuan , Vaidehi Nagarajan , Grisshammer Reinhard
Published: December 2016

Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3 Å crystal structure of a constitutively active, agonist-bound neurotensin receptor (NTSR1) and molecular dynamics simulations of agonist-occupied and ligand-free receptor. Comparison with the structure of a NTSR1 variant that has little constitutive activity reveals uncoupling of the ligand-binding domain from conserved connector residues, that effect conformational changes during GPCR activation. Furthermore, molecular dynamics simulations show strong contacts between connector residue side chains and increased flexibility at the intracellular receptor face as features that coincide with robust signalling in cells. The loss of correlation between the binding pocket and conserved connector residues, combined with altered receptor dynamics, possibly explains the reduced neurotensin efficacy in the constitutively active NTSR1 and a facilitated initial engagement with G protein in the absence of agonist.
Excitatory Post-Synaptic Potential Mimicked in Indium-Zinc-Oxide Synaptic Transistors Gated by Methyl Cellulose Solid Electrolyte
Authors: Guo Liqiang , Wen Juan , Ding Jianning , Wan Changjin , Cheng Guanggui
Published: December 2016

The excitatory postsynaptic potential (EPSP) of biological synapses is mimicked in indium-zinc-oxide synaptic transistors gated by methyl cellulose solid electrolyte. These synaptic transistors show excellent electrical performance at an operating voltage of 0.8 V, Ion/off ratio of 2.5 × 106, and mobility of 38.4 cm2/Vs. After this device is connected to a resistance of 4 MΩ in series, it exhibits excellent characteristics as an inverter. A threshold potential of 0.3 V is achieved by changing the gate pulse amplitude, width, or number, which is analogous to biological EPSP.
Baseline neutrophil–lymphocyte ratio is associated with baseline and subsequent presence of brain metastases in advanced non-small-cell lung cancer
Authors: Koh Young Wha , Choi Jin-Hyuk , Ahn Mi Sun , Choi Yong Won , Lee Hyun Woo
Published: December 2016

We examined the predictive value of neutrophil–lymphocyte ratio (NLR) by examining their association with the baseline presence and subsequent development of brain metastases in patients with stage IV non-small cell lung cancer (NSCLC). We examined the predictive value of NLR for brain metastasis in 260 stage IV NSCLC. Logistic regression models and competing risk analysis were used to determine the association of NLR with baseline and subsequent presence of brain metastases. Multivariate analysis reveals that patients with high NLR (≥4.95) had significantly more brain metastases at diagnosis than those with low NLR (Odds Ratio = 2.59, P = 0.01). In patients who had no baseline brain metastasis, competing risks analysis revealed that patients with high NLR showed higher cumulative incidence of subsequent brain metastases, compared to those with low NLR (P = 0.017). A high NLR was associated with the baseline presence or the subsequent development of brain metastases, particularly in the group with adenocarcinoma (P = 0.013 and P = 0.044, respectively). Furthermore, an increase in NLR during treatment was associated with subsequent brain metastases (P = 0.004). The NLR is an independent predictive factor for the baseline presence of brain metastases and subsequent brain metastases in stage IV NSCLC.
All-Silicon Ultra-Broadband Infrared Light Absorbers
Authors: Gorgulu Kazim , Gok Abdullah , Yilmaz Mehmet , Topalli Kagan , Bıyıklı Necmi , Okyay Ali K.
Published: December 2016

Absorbing infrared radiation efficiently is important for critical applications such as thermal imaging and infrared spectroscopy. Common infrared absorbing materials are not standard in Si VLSI technology. We demonstrate ultra-broadband mid-infrared absorbers based purely on silicon. Broadband absorption is achieved by the combined effects of free carrier absorption, and vibrational and plasmonic absorption resonances. The absorbers, consisting of periodically arranged silicon gratings, can be fabricated using standard optical lithography and deep reactive ion etching techniques, allowing for cost-effective and wafer-scale fabrication of micro-structures. Absorption wavebands in excess of 15 micrometers (5–20 μm) are demonstrated with more than 90% average absorptivity. The structures also exhibit broadband absorption performance even at large angles of incidence (θ = 50°), and independent of polarization.
NADPH oxidase 4 deficiency increases tubular cell death during acute ischemic reperfusion injury
Authors: Nlandu-Khodo Stellor , Dissard Romain , Hasler Udo , Schäfer Matthias , Pircher Haymo , Jansen-Durr Pidder , Krause Karl Heinz , Martin Pierre-Yves , de Seigneux Sophie
Published: December 2016

NADPH oxidase 4 (NOX4) is highly expressed in kidney proximal tubular cells. NOX4 constitutively produces hydrogen peroxide, which may regulate important pro-survival pathways. Renal ischemia reperfusion injury (IRI) is a classical model mimicking human ischemic acute tubular necrosis. We hypothesized that NOX4 plays a protective role in kidney IRI. In wild type (WT) animals subjected to IRI, NOX4 protein expression increased after 24 hours. NOX4 KO (knock-out) and WT littermates mice were subjected to IRI. NOX4 KO mice displayed decreased renal function and more severe tubular apoptosis, decreased Bcl-2 expression and higher histologic damage scores compared to WT. Activation of NRF2 was decreased in NOX4 KO mice in response to IRI. This was related to decreased KEAP1 oxidation leading to decreased NRF2 stabilization. This resulted in decreased glutathione levels. In vitro silencing of NOX4 in cells showed an enhanced propensity to apoptosis, with reduced expression of NRF2, glutathione content and Bcl-2 expression, similar to cells derived from NOX4 KO mice. Overexpression of a constitutively active form of NRF2 (caNRF2) in NOX4 depleted cells rescued most of this phenotype in cultured cells, implying that NRF2 regulation by ROS issued from NOX4 may play an important role in its anti-apoptotic property.
New principle for measuring arterial blood oxygenation, enabling motion-robust remote monitoring
Authors: van Gastel Mark , Stuijk Sander , de Haan Gerard
Published: December 2016

Finger-oximeters are ubiquitously used for patient monitoring in hospitals worldwide. Recently, remote measurement of arterial blood oxygenation (SpO2) with a camera has been demonstrated. Both contact and remote measurements, however, require the subject to remain static for accurate SpO2 values. This is due to the use of the common ratio-of-ratios measurement principle that measures the relative pulsatility at different wavelengths. Since the amplitudes are small, they are easily corrupted by motion-induced variations. We introduce a new principle that allows accurate remote measurements even during significant subject motion. We demonstrate the main advantage of the principle, i.e. that the optimal signature remains the same even when the SNR of the PPG signal drops significantly due to motion or limited measurement area. The evaluation uses recordings with breath-holding events, which induce hypoxemia in healthy moving subjects. The events lead to clinically relevant SpO2 levels in the range 80–100%. The new principle is shown to greatly outperform current remote ratio-of-ratios based methods. The mean-absolute SpO2-error (MAE) is about 2 percentage-points during head movements, where the benchmark method shows a MAE of 24 percentage-points. Consequently, we claim ours to be the first method to reliably measure SpO2 remotely during significant subject motion.
Deep sub-wavelength nanofocusing of UV-visible light by hyperbolic metamaterials
Authors: Kim Minkyung , So Sunae , Yao Kan , Liu Yongmin , Rho Junsuk
Published: December 2016

Confining light into a sub-wavelength area has been challenging due to the natural phenomenon of diffraction. In this paper, we report deep sub-wavelength focusing via dispersion engineering based on hyperbolic metamaterials. Hyperbolic metamaterials, which can be realized by alternating layers of metal and dielectric, are materials showing opposite signs of effective permittivity along the radial and the tangential direction. They can be designed to exhibit a nearly-flat open isofrequency curve originated from the large-negative permittivity in the radial direction and small-positive one in the tangential direction. Thanks to the ultraflat dispersion relation and curved geometry of the multilayer stack, hyperlens can magnify or demagnify an incident beam without diffraction depending on the incident direction. We numerically show that hyperlens-based nanofocusing device can compress a Gaussian beam down to tens-of-nanometers of spot size in the ultraviolet (UV) and visible frequency range. We also report four types of hyperlenses using different material combinations to span the entire range of visible frequencies. The nanofocusing device based on the hyperlens, unlike conventional lithography, works under ordinary light source without complex optics system, giving rise to practical applications including truly nanoscale lithography and deep sub-wavelength scale confinement.
Transcriptomic characterization and curation of candidate neuropeptides regulating reproduction in the eyestalk ganglia of the Australian crayfish, Cherax quadricarinatus
Authors: Nguyen Tuan Viet , Cummins Scott F. , Elizur Abigail , Ventura Tomer
Published: December 2016

The Australian redclaw crayfish (Cherax quadricarinatus) has recently received attention as an emerging candidate for sustainable aquaculture production in Australia and worldwide. More importantly, C. quadricarinatus serves as a good model organism for the commercially important group of decapod crustaceans as it is distributed worldwide, easy to maintain in the laboratory and its reproductive cycle has been well documented. In order to better understand the key reproduction and development regulating mechanisms in decapod crustaceans, the molecular toolkit available for model organisms such as C. quadricarinatus must be expanded. However, there has been no study undertaken to establish the C. quadricarinatus neuropeptidome. Here we report a comprehensive study of the neuropeptide genes expressed in the eyestalk in the Australian crayfish C. quadricarinatus. We characterised 53 putative neuropeptide-encoding transcripts based on key features of neuropeptides as characterised in other species. Of those, 14 neuropeptides implicated in reproduction regulation were chosen for assessment of their tissue distribution using RT-PCR. Further insights are discussed in relation to current knowledge of neuropeptides in other species and potential follow up studies. Overall, the resulting data lays the foundation for future gene-based neuroendocrinology studies in C. quadricarinatus.
Size Specific Transfection to Mammalian Cells by Micropillar Array Electroporation
Authors: Zu Yingbo , Huang Shuyan , Lu Yang , Liu Xuan , Wang Shengnian
Published: December 2016

Electroporation serves as a promising non-viral gene delivery approach, while its current configuration carries several drawbacks associated with high-voltage electrical pulses and heterogeneous treatment on individual cells. Here we developed a new micropillar array electroporation (MAE) platform to advance the electroporation-based delivery of DNA and RNA probes into mammalian cells. By introducing well-patterned micropillar array texture on the electrode surface, the number of pillars each cell faces varies with its plasma membrane surface area, despite their large population and random locations. In this way, cell size specific electroporation is conveniently carried out, contributing to a 2.5~3 fold increase on plasmid DNA transfection and an additional 10–55% transgene knockdown with siRNA probes, respectively. The delivery efficiency varies with the number and size of micropillars as well as their pattern density. As MAE works like many single cell electroporation are carried out in parallel, the electrophysiology response of individual cells is representative, which has potentials to facilitate the tedious, cell-specific protocol screening process in current bulk electroporation (i.e., electroporation to a large population of cells). Its success might promote the wide adoption of electroporation as a safe and effective non-viral gene delivery approach needed in many biological research and clinical treatments.
Relationship between Salivary Oxytocin Levels and Generosity in Preschoolers
Authors: Fujii Takayuki , Schug Joanna , Nishina Kuniyuki , Takahashi Taiki , Okada Hiroyuki , Takagishi Haruto
Published: December 2016

This study examined the association between salivary oxytocin (sOT) levels and generosity in preschoolers. Fifty preschoolers played two dictator games (DG) by deciding how to allocate 10 chocolates between themselves and another child, who was either from the same class as the participant (ingroup member), or an unknown child from another class (outgroup member). sOT levels were assessed in saliva collected from the children immediately prior to the DG tasks. While sOT levels were negatively associated with allocations made to both ingroup and outgroup members by boys, among girl sOT levels were positively related to allocations made to ingroup members, and unrelated to allocations made to outgroup members. These results suggest sex differences in the association between salivary oxytocin and generosity.
The efficacy of Mycophenolate mofetil for the treatment of Chinese Takayasu’s arteritis
Authors: Li Jing , Yang Yunjiao , Zhao Jiuliang , Li Mengtao , Tian Xinping , Zeng Xiaofeng
Published: December 2016

To investigate the therapeutic effect of mycophenolate mofetil(MMF) on Chinese Takayasu’s arteritis(TAK) patients. Thirty consecutive TAK outpatients were prospectively enrolled during 2013 to 2015. MMF combined with glucocorticoid was the primary treatment regimen. If clinical stable disease could not be reached, another traditional immunosuppressive agent could be added. All patients were evaluated and followed up every 3 months and vascular image studies by Doppler ultrasonography were repeated every 6 months. The effectiveness of MMF was defined as:(1) ESR < 20 mm/hr;(2) CRP < 10 mg/L or hs-CRP<3 mg/L;(3) stable or improved in vascular image studies;(4) clinical assessment is stable, improved or in remission;(5) the dosage of glucocorticoid could be tapered to less than 15 mg/day. ESR < 40 mm/hr, CRP < 20 mg/L or hs-CRP < 6 mg/L, but meet the other three criteria is defined as partial effectiveness. MMF alone combined with corticosteroid was effective in 12(40.0%) patients. When MMF combined with methotrexate less than 15 mg/week, the effective rate was 30.0%(9/30), including partial effective in 3 patients. When MMF combined with azathioprine 100–150 mg/day, the effective rate was 10.0%(3/30), including partial effective in 1 patient. Four patients withdrew due to side effects. Two patients failed to show response. The overall effective rate of therapy including MMF in treating TAK is 80%.
Enhancing steel properties through in situ formation of ultrahard ceramic surface
Authors: Pahlevani Farshid , Kumar Rahul , Gorjizadeh Narjes , Hossain Rumana , Cholake Sagar T , Privat Karen , Sahajwalla Veena
Published: December 2016

Abrasion and corrosion resistant steel has attracted considerable interest for industrial application as a means of minimising the costs associated with product/component failures and/or short replacement cycles. These classes of steels contain alloying elements that increase their resistance to abrasion and corrosion. Their benefits, however, currently come at a potentially prohibitive cost; such high performance steel products are both more technically challenging and more expensive to produce. Although these methods have proven effective in improving the performance of more expensive, high-grade steel components, they are not economically viable for relatively low cost steel products. New options are needed. In this study, a complex industrial waste stream has been transformed in situ via precisely controlled high temperature reactions to produce an ultrahard ceramic surface on steel. This innovative ultrahard ceramic surface increases both the hardness and compressive strength of the steel. Furthermore, by modifying the composition of the waste input and the processing parameters, the ceramic surface can be effectively customised to match the intended application of the steel. This economical new approach marries industry demands for more cost-effective, durable steel products with global imperatives to address resource depletion and environmental degradation through the recovery of resources from waste.