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Nuclear spin hyperpolarization techniques, such as dynamic nuclear polarization (DNP) and parahydrogen-induced polarization (PHIP), have revolutionized nuclear magnetic resonance and magnetic resonance imaging. In these methods, a readily available source of high spin order, either electron spins in DNP or singlet states in hydrogen for PHIP, is brought into close proximity with nuclear spin targets, enabling efficient transfer of spin order under external quantum control. Despite vast disparities in energy scales and interaction mechanisms between electron spins in DNP and nuclear singlet states in PHIP, a pseudo-spin formalism allows us to establish an intriguing equivalence. As a result, the important low-field polarization transfer regime of PHIP can be mapped onto an analogous system equivalent to pulsed-DNP. This establishes a correspondence between key polarization transfer sequences in PHIP and DNP, facilitating the transfer of sequence development concepts. This promises fresh insights and significant cross-pollination between DNP and PHIP polarization sequence developers. [Display omitted] • Translation framework for polarization sequences between PHIP and DNP identified. • New robust and efficient sequences for Para-Hydrogen Induced Polarization. • Comparing polarization sequences in theory and experiment. [ABSTRACT FROM AUTHOR]

Abstract The binary Constraint Satisfaction Problem (CSP) is to decide whether there exists an assignment to a set of variables which satisfies specified constraints between pairs of variables. A binary CSP instance can be presented as a labelled graph encoding both the forms of the constraints and where they are imposed. We consider subproblems defined by restricting the allowed form of this graph. One type of restriction is to forbid certain specified substructures (patterns). This captures some tractable classes of the CSP, but does not capture classes defined by language restrictions, or the well-known structural property of acyclicity. We extend the notion of pattern and introduce the notion of a topological minor of a binary CSP instance. By forbidding a finite set of patterns from occurring as topological minors we obtain a compact mechanism for expressing novel tractable subproblems of the CSP, including new generalisations of the class of acyclic instances. [ABSTRACT FROM AUTHOR]

We examined the use of automated voice recognition (AVR) messages targeting smokers from primary care practices located in underserved urban and rural communities to promote smoking cessation. We partnered with urban and rural primary care medical offices (n = 7) interested in offering this service to patients. Current smokers, 18 years and older, who had completed an office visit within the previous 12 months, from these sites were used to create a smoker's registry. Smokers were recruited within an eight county region of western New York State between June 2012 and August 2013. Participants were contacted over six month intervals using the AVR system. Among 5812 smokers accrued 1899 (32%) were reached through the AVR system and 55% (n = 1049) continued to receive calls. Smokers with race other than white or African American were less likely to be reached (OR = 0.71, 0.57-0.90), while smokers ages 40 and over were more likely to be reached. Females (OR = 0.78, 0.65-0.95) and persons over age 40 years were less likely to opt out, while rural smokers were more likely to opt out (OR = 3.84, 3.01-4.90). Among those receiving AVR calls, 30% reported smoke free (self-reported abstinence over a 24 h period) at last contact; smokers from rural areas were more likely to report being smoke free (OR = 1.41, 1.01-1.97). An AVR-based smoking cessation intervention provided added value beyond typical tobacco cessation efforts available in these primary care offices. This intervention required no additional clinical staff time and served to satisfy a component of patient center medical home requirements for practices. [ABSTRACT FROM AUTHOR]

SABRE (Signal Amplification By Reversible Exchange) is a nuclear spin hyperpolarization technique based on the reversible concurrent binding of small molecules and para -hydrogen ( p -H 2 ) to an iridium metal complex in solution. At low magnetic field, spontaneous conversion of p -H 2 spin order to enhanced longitudinal magnetization of the nuclear spins of the other ligands occurs. Subsequent complex dissociation results in hyperpolarized substrate molecules in solution. The lifetime of this complex plays a crucial role in attained SABRE NMR signal enhancements. Depending on the ligands, vastly different dissociation rates have been previously measured using EXSY or selective inversion experiments. However, both these approaches are generally time-consuming due to the long recycle delays (up to 2 min) necessary to reach thermal equilibrium for the nuclear spins of interest. In the cases of dilute solutions, signal averaging aggravates the problem, further extending the experimental time. Here, a new approach is proposed based on coherent hyperpolarization transfer to substrate protons in asymmetric complexes at high magnetic field. We have previously shown that such asymmetric complexes are important for application of SABRE to dilute substrates. Our results demonstrate that a series of high sensitivity EXSY spectra can be collected in a short experimental time thanks to the NMR signal enhancement and much shorter recycle delay. [ABSTRACT FROM AUTHOR]

Previously, a four branched histidine-lysine rich peptide, H3K4b, was shown to demonstrate selective antifungal activity with minimal antibacterial activity. Due to the potential breakdown from proteases, H3K4b was further evaluated in the current study by varying the D- and l -amino acid content in its branches. Whereas analogues of H3K4b that selectively replaced l -amino acids (H3 k 4b, h 3K4b) had improved antifungal activity, the all d -amino acid analogue, h 3 k 4b, had reduced activity, suggesting that partial breakdown of the peptide may be necessary. Moreover, because histidines form coordination bonds with the silver ion, we examined whether silver adducts can be formed with these branched histidine-lysine peptides, which may improve antifungal activity. For Candida albicans , the silver adduct of h 3K4b or H3 k 4b reduced the MIC compared to peptide and silver ions alone by 4- and 5-fold, respectively. For Aspergillus fumigatus , the silver adducts showed even greater enhancement of activity. Although the silver adducts of H3 k 4b or h 3K4b showed synergistic activity, the silver adduct with the all l -amino acid H3K4b surprisingly showed the greatest synergistic and growth inhibition of A. fumigatus : the silver adduct of H3K4b reduced the MIC compared to the peptide and silver ions alone by 30- and 26-fold, respectively. Consistent with these antifungal efficacy results, marked increases in free oxygen radicals were produced with the H3K4b and silver combination. These studies suggest that there is a balance between stability and breakdown for optimal antifungal activity of the peptide alone and for the peptide-silver adduct. [ABSTRACT FROM AUTHOR]

Vibration energy harvesters (VEHs) allow the extraction of ambient mechanical energy. The proposed analysis focuses on bistable harvesters with Duffing nonlinearity. Bistable harvesters exhibit larger frequency bandwidth than linear monostable harvesters, but they exhibit complex behaviors (i.e., multiple periodic orbits and chaos), making their evaluation challenging. To assess the quality of a VEH, it is necessary to evaluate its energy performance generically. In this paper, we offer a new quantitative metric that can be used to evaluate bistable harvesters while taking into account the richness and diversity of their dynamics. This metric – called power expectation – is based on the average harvested power of each existing orbit weighted by its occurrence probability. The value of this power expectation depends on the harvester characteristics and potential orbit jump strategy implemented. Finally, we define a new figure of merit (FoM) based on the integral of the power expectation over all vibration frequencies. This FoM can be used for a generic evaluation of nonlinear vibration energy harvesters (NVEHs), by taking into account the various orbits and their respective probability of occurrence depending on the orbit jump strategy used. The proposed FoM also makes it possible to ensure a fair comparison with linear VEHs and quantitatively assess the effectiveness of orbit jump strategies for a given VEH. [ABSTRACT FROM AUTHOR]

We develop a model of optimal taxation and redistribution under an ambitious climate target. We take into account vertical income differences, but also explicitly capture horizontal equity concerns by considering heterogeneous energy efficiencies. By deriving first- and second-best rules for policy instruments including carbon and labor taxes, transfers and energy subsidies, we investigate analytically how vertical and horizontal inequality is considered in the welfare maximizing tax structure. We calibrate the model to German household data and a 30 percent emission reduction goal and show that redistribution of carbon tax revenues via household-specific transfers is the first-best policy. Under plausible assumptions on inequality aversion, transfers to energy-intensive households should be about five times higher than transfers to energy-efficient households. Equal per-capita transfers do not require to observe households' efficiency type, but increase equity-weighted mitigation costs by around 5 percent compared to the first-best. Mitigation costs increase by less, if the government can implement a uniform clean energy subsidy or household-specific tax-subsidy schemes on energy consumption and labor income that target heterogeneous energy efficiencies. Horizontal equity concerns may therefore constitute a new second-best rationale for clean energy policies or differentiated energy taxes. [ABSTRACT FROM AUTHOR]

Dryland floodplains are characterized by highly variable flooding and drying. This variability plays a key role in the productivity of dryland floodplain vegetation. The Normalized Difference Vegetation Index, a surrogate for vegetation productivity, has been extensively used to examine floodplain vegetation productivity responses to flood inundation but generally focuses on inundation alone, or at a single scale thereby potentially omitting important elements of dryland variability. This study used fine resolution satellite imagery, through sequences of flood and dry resource states, at multiple scales of observation and with consideration of the relative influence of rainfall and flow to examine floodplain vegetation productivity in the dryland floodplain. There were marked differences in floodplain vegetation productivity between wet and dry resource states. Overall, response patterns were complex and varied among vegetation communities and in different resource states. The findings suggest that vegetation productivity in the Narran floodplain does not correspond well with the boom and bust model of floodplain ecosystem productivity. Rather, understanding vegetation productivity in a highly variable floodplain requires an enhanced understanding of the nature of variability in space and time. Conceptual models that can better convey the complexity of vegetation productivity responses to floodplain wetting and drying are suggested. [ABSTRACT FROM AUTHOR]

Variable or value elimination in a constraint satisfaction problem (CSP) can be used in preprocessing or during search to reduce search space size. A variable elimination rule (value elimination rule) allows the polynomial-time identification of certain variables (domain elements) whose elimination, without the introduction of extra compensatory constraints, does not affect the satisfiability of an instance. We show that there are essentially just four variable elimination rules and three value elimination rules defined by forbidding generic sub-instances, known as irreducible existential patterns, in arc-consistent CSP instances. One of the variable elimination rules is the already-known Broken Triangle Property, whereas the other three are novel. The three value elimination rules can all be seen as strict generalisations of neighbourhood substitution. [ABSTRACT FROM AUTHOR]

Abstract: Topographic representation of the outside world is a key feature of sensory systems, but so far it has been difficult to define how the activity pattern of the olfactory information is distributed at successive stages in the olfactory system. We studied odor-evoked activation patterns in the main olfactory bulb and the anterior piriform cortex of rats using functional ultrasound (fUS) imaging. fUS imaging is based on the use of ultrafast ultrasound scanners and detects variations in the local blood volume during brain activation. It makes deep brain imaging of ventral structures, such as the piriform cortex, possible. Stimulation with two different odors (hexanal and pentylacetate) induced the activation of odor-specific zones that were spatially segregated in the main olfactory bulb. Interestingly, the same odorants triggered the activation of the entire anterior piriform cortex, in all layers, with no distinguishable odor-specific areas detected in the power Doppler images. These fUS imaging results confirm the spatial distribution of odor-evoked activity in the main olfactory bulb, and furthermore, they reveal the absence of such a distribution in the anterior piriform cortex at the macroscopic scale in vivo. [Copyright &y& Elsevier]

Abstract: Background: Despite modern advancements in transosseous fixation and operative technique, hallux valgus (i.e., bunion) surgery is still associated with a higher than usual amount of patient dissatisfaction and is generally recognized as a complex and nuanced procedure requiring precise osseous and capsulotendon balancing. It stands to reason then that familiarity and skill level of trainee surgeons might impact surgical outcomes in this surgery. The aim of this study was to determine whether podiatry resident experience level influences midterm outcomes in hallux valgus surgery (HVS). Methods: Consecutive adults who underwent isolated HVS via distal metatarsal osteotomy at a single US metropolitan teaching hospital from January 2004 to January 2009 were contacted and asked to complete a validated outcome measure of foot health (Manchester–Oxford Foot Questionnaire) regarding their operated foot. Resident experience level was quantified using the surgical logs for the primary resident of record at the time of each case. Associations were assessed using linear and logistic regression analyses. Results: A total of 102 adult patients (n = 102 feet) agreed to participate with a mean age of 46.8 years (standard deviation 13.1, range 18–71) and average length of follow-up 6.2 y (standard deviation 1.4, range 3.6–8.6). Level of trainee experience was not associated with postoperative outcomes in either the univariate (odds ratio 0.99 [95% confidence interval, 0.98–1.01], P = 0.827) or multivariate analyses (odds ratio 1.00 [95% confidence interval, 0.97–1.02], P = 0.907). Conclusions: We conclude that podiatry resident level of experience in HVS does not contribute appreciably to postoperative clinical outcomes. [Copyright &y& Elsevier]

The aim was to investigate relationships between activity related energy expenditure (AREE), appetite ratings and energy intake (EI) in a sample of 40 male (26.4years; BMI 23.5kg/m(2)) and 42 female (26.9years; BMI 22.4kg/m(2)) participants. AREE was expressed as the residual value of the regression between total daily EE (by doubly labeled water) and resting EE (by indirect calorimetry). EI was measured using an ad libitum buffet meal and visual analogue scales measured subjective appetite ratings before and after the meal. AREE was divided into low, middle and high sex-specific tertiles. General linear models were used to investigate differences in appetite ratings and EI across AREE tertiles. Before the meal, males in the high AREE tertile had significantly lower desire to eat and lower prospective food consumption and higher feelings of fullness compared to those in the low tertile. Males in the middle tertile had significantly higher satiety quotients after the meal and lower EI compared to the other tertiles. No significant differences across tertiles were found in females. Sex differences in relationships between AREE, appetite ratings and EI may lead to differing patterns of EI and subsequent weight maintenance. [ABSTRACT FROM AUTHOR]

Abstract: Magnetoelectric multiferroics showing coupling between polarization and magnetic order are attracting much attention. For instance, they could be used in memory devices. Metal-transition oxides are provided several examples of inorganic magnetoelectric multiferroics. In the present short review, spinel and delafossite chromites are described. For the former, an electric polarization is evidenced in the ferrimagnetic state for ACr2O4 polycrystalline samples (A=Ni, Fe, Co). The presence of a Jahn–Teller cation such as Ni2+ at the A site is shown to yield larger polarization values. In the delafossites, substitution by V3+ at the Cr or Fe site in CuCrO2 (CuFeO2) suppresses the complex antiferromagnetic structure at the benefit of a spin glass state. The presence of cation disorder, probed by transmission electron microscopy, favors relaxor-like ferroelectricity. The results on the ferroelectricity of ferrimagnets and insulating spin glasses demonstrate that, in this research field, transition-metal oxides are worth to be studied. [Copyright &y& Elsevier]

Abstract: In the biosynthesis of the clinically important antibiotic erythromycin D, the glycosyltransferase (GT) EryCIII, in concert with its partner EryCII, attaches a nucleotide-activated sugar to the macrolide scaffold with high specificity. To understand the role of EryCII, we have determined the crystal structure of the EryCIII·EryCII complex at 3.1 Å resolution. The structure reveals a heterotetramer with a distinctive, elongated quaternary organization. The EryCIII subunits form an extensive self-complementary dimer interface at the center of the complex, and the EryCII subunits lie on the periphery. EryCII binds in the vicinity of the putative macrolide binding site of EryCIII but does not make direct interactions with this site. Our biophysical and enzymatic data support a model in which EryCII stabilizes EryCIII and also functions as an allosteric activator of the GT. [Copyright &y& Elsevier]

Abstract: Discrete molecular dynamics simulation (DMD) uses simplified and discretized models enabling simulations to advance by event rather than by timestep. DMD is an instance of discrete event simulation and so is difficult to scale: even in this multi-core era, all reported DMD codes are serial. In this paper we discuss the inherent difficulties of scaling DMD and present our method of parallelizing DMD through event-based decomposition. Our method is microarchitecture inspired: speculative processing of events exposes parallelism, while in-order commitment ensures correctness. We analyze the potential of this parallelization method for shared-memory multiprocessors. Achieving scalability required extensive experimentation with scheduling and synchronization methods to mitigate serialization. The speed-up achieved for a variety of system sizes and complexities is nearly 6× on an 8-core and over 9× on a 12-core processor. We present and verify analytical models that account for the achieved performance as a function of available concurrency and architectural limitations. [Copyright &y& Elsevier]

Abstract: Previous studies have convincingly shown that employees'' family lives can affect their work outcomes. We investigate whether family-to-work interference (FWI) experienced by the employee also affects the work outcomes of a co-worker. We predict that the employee''s FWI has an effect on the co-worker''s outcomes through the crossover of positive and negative work attitudes. Using a sample of 1430 co-worker dyads, we found that the employee''s FWI had a positive relationship with the co-worker''s sickness absence through the crossover of feelings of burnout. Similarly, employee FWI was positively related to co-worker turnover intention through the crossover of (reduced) work engagement. The results show that family matters at work, affecting not only employee but also co-worker work outcomes. [Copyright &y& Elsevier]

Abstract: The effect of substitution at the Fe site in the CuFeO2 delafossite is known to induce a magnetic structure responsible for the appearance of electric polarization. A CuFe1− x Rh x O2 series of ceramic samples is studied in order to determine the composition range exhibiting such a polar state. It is found that for the CuFe1− x Rh x O2 (x≤0.15) solid solution, the Néel temperature T N2 decreases monotonously with x from 11.5K to 5.9K, for x=0.00 to 0.15, respectively, and that the dielectric peak and the polarization transition temperatures coincide with T N2. In contrast, the dielectric peak and polarization magnitudes go through an optimum for CuFe0.92Rh0.08O2 (x=0.08). These results demonstrate that, compared to other substituting elements, the Rh3+ for Fe3+ substitution in CuFeO2 allows to extend significantly the ferroelectric region in the (x, T) phase diagram in connection with the slower T N2 decrease. [Copyright &y& Elsevier]

Abstract: The crystal structures of a biologically and therapeutically active recombinant homotrimeric fragment of human lung surfactant protein D with a series of bound ligands have been determined. While the structures reveal various different binding modes, all utilise a similarly positioned pair of mannose-type O3′ and O4′ hydroxyls with no direct interaction between any non-terminal sugar and protein. The orientation, position, and interactions of the bound terminal sugar depend on the sugar itself, the presence and form of glycosidic linkage, and the environment in the crystal, which, via Asp325, places stereochemical and electronic constraints, different for the three different subunits in the homotrimer, on the ligand-binding site. As a direct consequence of this influence, the other binding-pocket flanking residue, Arg343, exhibits variable conformation and variable interactions with bound ligand and leaves open to question which orientation of terminal mannobiose, and of other terminal disaccharides, may be present in extended physiological ligands. The combined structural evidence shows that there is significant flexibility in recognition; that Asp325, in addition to Arg343, is an important determinant of ligand selectivity, recognition, and binding; and that differences in crystal contact interfaces exert, through Asp325, significant influence on preferred binding modes. [Copyright &y& Elsevier]

Abstract: Temporal lobe epilepsy (TLE) is often accompanied by granule cell dispersion (GCD), a migration defect of granule cells in the dentate gyrus. We have previously shown that a decrease in the expression of reelin, an extracellular matrix protein important for neuronal positioning, is associated with the development of GCD in TLE patients. Here, we used unilateral intrahippocampal injection of kainate (KA) in adult mice which is also associated with GCD formation and a decrease of reelin expression. In this mouse epilepsy model we aimed to prevent GCD development by the application of exogenous reelin. As a prerequisite we analyzed whether the reelin signaling transduction cascade was preserved in the KA-injected hippocampus. Using in situ hybridization and Western blot analysis we found that the expression of the reelin signaling components, apolipoprotein E receptor 2, the very-low-density lipoprotein receptor and the intracellular adaptor protein disabled 1, was maintained in dentate granule cells after KA injection. Next, recombinant reelin was infused into the KA-injected hippocampus by osmotic minipumps over a period of 2 weeks. Quantitative analysis of granule cell layer width revealed a significant reduction of GCD in reelin-treated, but not in saline-infused animals when compared to KA injection alone. Our findings highlight the crucial role of reelin for the maintenance of granule cell lamination in the dentate gyrus of adult mice and show that a reelin deficiency is causally involved in GCD development. [Copyright &y& Elsevier]

Abstract: The Drosophila atypical cadherin Flamingo plays key roles in a number of developmental processes. We have used the sensory nervous system of the Drosophila embryo to shed light on the mechanism by which Flamingo regulates axon growth. flamingo loss of function mutants display a highly penetrant sensory axon stall phenotype. The location of these axon stalls is stereotypic and corresponds to the position of intermediate target cells, with which sensory axons associate during normal development. This suggests that Flamingo mediates an interaction between the sensory neuron growth cones and these intermediate targets, which is required for continued axon advance. Mutant rescue experiments show that Flamingo expression is required only in sensory neurons for normal axon growth. The flamingo mutant phenotype can be partially rescued by expressing a Flamingo construct lacking most of the extracellular domain, suggesting that regulation of sensory axon advance by Flamingo does not absolutely depend upon a homophilic Flamingo–Flamingo interaction or its ability to mediate cell–cell adhesion. Loss of function mutants for a number of key genes that act together with Flamingo in the planar cell polarity pathway do not display the highly penetrant stalling phenotype seen in flamingo mutants. [Copyright &y& Elsevier]

Abstract: Odor-evoked activity in the olfactory bulb displays both spatial and temporal organization. The difficulty when assessing spatio-temporal dynamics of olfactory representation is to find a method that reconciles the appropriate resolution for both dimensions. Imaging methods based on optical recordings can reach high temporal and spatial resolution but are limited to the observation of the accessible dorsal surface. Functional magnetic resonance imaging (fMRI) may be useful to overcome this limitation as it allows recording from the whole brain. In this study, we combined ultra fast imaging sequence and short stimulus duration to improve temporal resolution of odor-evoked BOLD responses. Short odor stimulations evoked high amplitude BOLD responses and patterns of activation were similar to those obtained in previous studies using longer stimulations. Moreover, short odor exposures prevented habituation processes. Analysis of the BOLD signal time course in the different areas of activation revealed that odorant response maps are not static entities but rather are temporally dynamic as reported by recent studies using optical imaging. These data demonstrated that fMRI is a non-invasive method which could represent a powerful tool to study not only the spatial dimension of odor representation but also the temporal dimension of information processing. [Copyright &y& Elsevier]

Abstract: Within the phenotypically and functionally heterogeneous group of circulating progenitor cells (CPC), a subclass of cells with vascular repair potential have been identified. These CPC are detected and isolated based on single or combined expression of CD34, CD133 and VEGFR-2, and referred to as endothelial progenitor cells. Here we asked whether CPC subsets defined by single expression of these markers exhibit functional heterogeneity. As functional parameters, we chose the capacity of CPC to differentiate into endothelial cells. Moreover, we studied their role in remodeling by recruitment of inflammatory cells, an aspect that has been little explored. We established an in vivo model in which the intrinsic functional capacity of these human CPC subsets was studied. Human CD34+ CPC, but not CD133+ or VEGFR-2+ CPC, seeded in Matrigel pellets and transplanted subcutaneously in a nude mouse host, contributed little to donor-derived neovascularization. However, host angiogenesis in the Matrigel implant, as demonstrated by the presence of capillaries containing erythrocytes and expressing mouse CD31, was strong in response to implantation of human CD34+ CPC and significantly lower in response to the other two CPC subsets. Moreover, the CD34+ CPC subset was significantly superior to CD133+ CPC and VEGFR-2+ CPC in the recruitment of host monocytes/macrophages. These three CPC populations were further dissected into seven discrete subsets, based on three-parameter flow cytometry analysis of combined expression patterns of CD34, CD133 and VEGFR-2. In conclusion, in our system, CD34+ CPC contribute marginally to neovascularization by differentiation but are potent regulators of the host angiogenic and pro-inflammatory response, suggesting a possible role for these cells in the remodeling of vascular lesions. [Copyright &y& Elsevier]

Abstract: We prove that every separated Artin stack of finite type over a noetherian base scheme admits a proper covering by a quasi-projective scheme. An application of this result is a version of the Grothendieck existence theorem for Artin stacks. [Copyright &y& Elsevier]

Abstract: Human papillomaviruses (HPVs) replicate as nuclear plasmids in infected cells. Since the DNA replication machinery is generally conserved between humans and Saccharomyces cerevisiae, we studied whether HPV-1 DNA can replicate in yeast. Plasmids containing a selectable marker (with or without a yeast centromere) and either the full-length HPV-1 genome or various regions of the viral long control region (LCR) and the 3′ end of the L1 gene were introduced into S. cerevisiae and their ability to replicate episomally was investigated. Our results show that HPV-1 sequences promote episomal replication of plasmids although the yeast centromere is required for plasmid retention. We have mapped the autonomously replicating sequence activity of HPV-1 DNA to a 450 base-pair sequence (HPV-1 nt 6783–7232) that includes 293 nucleotides from the 5′ region of the viral LCR and 157 nucleotides from the 3′ end of the L1 gene. The HPV-1 ARS does not include the binding sites for the viral E1 and E2 proteins, and these proteins are dispensable for replication in S. cerevisiae. [Copyright &y& Elsevier]

Abstract: The androgen hormone testosterone (T) mediates vertebrate aggression in many contexts and according to the Challenge Hypothesis is up-regulated during social challenges. While originally applied to challenges experienced by breeding adults, we show for the first time that T is similarly up-regulated during deadly sibling aggression in young birds. When two nestling Nazca boobies hatch, one—usually the older chick—virtually always kills the other chick by pushing it from the nest. We compared concentrations of T, dehydroepiandrosterone (DHEA; a precursor of T), and corticosterone (Cort; a stress hormone) of chicks at various stages. T was elevated during fights in both chicks in two-chick broods, but not before and after fights, and not in chicks lacking a nest mate. DHEA was elevated 1 day after hatching and declined with age but appeared not to vary in concert with aggression. Cort did not vary across fighting and nonfighting periods. In conjunction with an earlier study [Tarlow, E.M., Wikelski, M., Anderson, D.J., 2001. Hormonal correlates of siblicide in Galápagos Nazca boobies. Horm. Behav. 40:14–20], these results indicate that T is temporarily up-regulated around the time of fights, as predicted by the Challenge Hypothesis. Our data suggest a general role for T during challenges at any time in life, not just during breeding. [Copyright &y& Elsevier]

RNAi has rapidly become a powerful tool for drug target discovery and validation in cell culture, and now has largely displaced efforts with antisense and ribozymes. Consequently, interest is rapidly growing for extension of its application to in vivo systems, such as animal disease models and human therapeutics. Studies on RNAi have resulted in two basic methods for its use for gene selective inhibition: 1) cytoplasmic delivery of short dsRNA oligonucleotides (siRNA), which mimics an active intermediate of an endogenous RNAi mechanism and 2) nuclear delivery of gene expression cassettes that express a short hairpin RNA (shRNA), which mimics the micro interfering RNA (miRNA) active intermediate of a different endogenous RNAi mechanism. Non-viral gene delivery systems are a diverse collection of technologies that are applicable to both of these forms of RNAi. Importantly, unlike antisense and ribozyme systems, a remarkable trait of siRNA is a lack of dependence on chemical modifications blocking enzymatic degradation, although chemical protection methods developed for the earlier systems are being incorporated into siRNA and are generally compatible with non-viral delivery systems. The use of siRNA is emerging more rapidly than for shRNA, in part due to the increased effort required to construct shRNA expression systems before selection of active sequences and verification of biological activity are obtained. In contrast, screens of many siRNA sequences can be accomplished rapidly using synthetic oligos. It is not surprising that the use of siRNA in vivo is also emerging first. Initial in vivo studies have been reported for both viral and non-viral delivery but viral delivery is limited to shRNA. This review describes the emerging in vivo application of non-viral delivery systems for RNAi for functional genomics, which will provide a foundation for further development of RNAi therapeutics. Of interest is the rapid adaptation of ligand-targeted plasmid-based nanoparticles for RNAi agents. These systems are growing in capabilities and beginning to pose a serious rival to viral vector based gene delivery. The activity of siRNA in the cytoplasm may lower the hurdle and thereby accelerate the successful development of therapeutics based on targeted non-viral delivery systems. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is a complex genetic disorder characterized by gluten intolerance. The Th1 immune response, with a key position for interferon gamma (IFN-γ), is an important determinant of intestinal remodeling in CD. We aimed at further ascertaining the role of IFN-γ, either as a genetic factor in the etiology, or as a facilitator of disease initiation/progression. Duodenal biopsies were sampled across distinct histopathological stages of the disease, including refractory CD (RCD), and used to determine IFN-γ gene (IFNG) expression by real-time RT-PCR. INFG expression correlated with the extent of tissue restructuring, reaching a 240-fold higher expression in total villous atrophy compared to healthy tissue. CD and RCD patients with similar lesions had comparable expression levels. Interestingly, patients in complete remission still had 7.6-fold residual over-expression. An INFG marker was tested in three cohorts of Dutch patients for both genetic linkage and association. Linkage analysis yielded no significant scores for IFNG or its flanking markers. In addition, IFNG allele frequencies were not differently distributed between cases and controls. Likewise, all alleles were randomly transmitted to affected children in parents-case trios. There is no evidence for IFNG as a predisposing gene in CD, despite its enhanced expression in patients in complete remission. [Copyright &y& Elsevier]

FtsZ is part of a mid-cell cytokinetic structure termed the Z-ring that recruits a hierarchy of fission related proteins early in the bacterial cell cycle. The widely conserved ZapA has been shown to interact with FtsZ, to drive its polymerisation and to promote FtsZ filament bundling thereby contributing to the spatio-temporal tuning of the Z-ring. Here, we show the crystal structure of ZapA (11.6 kDa) from Pseudomonas aeruginosa at 2.8 Å resolution. The electron density reveals two dimers associating via an extensive C-terminal coiled-coil protrusion to form an elongated anti-parallel tetramer. In solution, ZapA exists in a dimer–tetramer equilibrium that is strongly correlated with concentration. An increase in concentration promotes formation of the higher oligomeric state. The dimer is postulated to be the predominant physiological species although the tetramer could become significant if, as FtsZ is integrated into the Z-ring and is cross-linked, the local concentration of the dimer becomes sufficiently high. We also show that ZapA binds FtsZ with an approximate 1 : 1 molar stoichiometry and that this interaction provokes dramatic FtsZ polymerisation and inter-filament association as well as yielding filaments, single or bundled, more stable and resistant to collapse. Whilst in vitro dynamics of FtsZ are well characterised, its in vivo arrangement within the ultra-structural architecture of the Z-ring is yet to be determined despite being fundamental to cell division. The ZapA dimer has single 2-fold symmetry whilst the bipolar tetramer displays triple 2-fold symmetry. Given the symmetry of these ZapA oligomers and the polar nature of FtsZ filaments, the structure of ZapA carries novel implications for the inherent architecture of the Z-ring in vivo. [Copyright &y& Elsevier]

In order to study the spin dependent transport mechanisms through a small collection of nano-objects, we propose an original fabrication process of ferromagnetic nanoelectrodes (NEs). It consists in etching, through a negative PMMA mask patterned by high-dose HREBL exposure, the continuous ferromagnetic layer deposited in optimal conditions by sputtering under ultra high vacuum into couples of planar nanoelectrodes (NEs) separated by a nanometric gap. The main advantage of this approach is to guarantee a priori a better crystalline and magnetic quality of the NEs. In this paper, we describe in detail the impact of various parameters such as the electron beam dose, the coded layout NE gap, the layer development, the inversed PMMA removal as well as the ion beam etching parameters …. Observations by scanning electron microscopy (SEM) and atomic force microscopy (AFM) reveal that a 270 nC cm−1 is required to reverse the PMMA tone and provide a strong etching mask. NE gap from 5 nm to several tens of nm were obtained in a reproducible way. Moreover, thanks to the micropads created by a first HREBL stage, the samples were electrically bonded to a gold base plate allowing low current electrical measurements. These measurements on Co NEs showed that 5–20 nm range separated gaps have resistance in the range of hundreds to . These measurements correlated with energy dispersive spectroscopy (EDS) observations demonstrate that this process provides well adapted systems for the investigation of nano-object electrical properties. [Copyright &y& Elsevier]

The first member of the Ruddlesden–Popper family, Ca2MnO4, has been revisited. Coexistence of two structures has been shown from electron microscopy at room temperature and neutron diffraction data have evidenced two antiferromagnetic structures at low temperature. Two forms, with an orthorhombic Aba2 (a≈b≈ap√ of 2 and c≈12 Å) and a tetragonal I41/cad (a≈ap√ of 2 and c≈24 Å) symmetries, were found to coexist coherently within the same matrix. [Copyright &y& Elsevier]

Although arrays of SIMD processing elements can be built with very high operating frequencies, problems exist in keeping the array busy. The inherent mismatch between host and array makes it difficult to maintain high array utilization: either the rate of instruction issue is very low or PE data locality is compromised, having the same effect. Our solution is based on an array control unit (ACU) design that expands macroinstructions in two stages, first by data tile and then into microinstructions. The expansion itself solves the issue problem; decoupling the expansion modalities maintains data locality. Several issues involving host/ACU interaction need to be resolved to effect this solution. We present experimental results showing that our approach delivers substantial improvement in memory hierarchy performance: a cache of only one-fourth the size is sufficient to achieve the same performance as previous approaches. We also describe our implementations which demonstrate that achieving gigaherz operating frequencies with current technologies is plausible. [Copyright &y& Elsevier]

Oligodendrocyte precursor cells (OPCs) can be differentiated in culture into either oligodendrocytes or type-2 astrocytes (2As), depending on the culture conditions. Whereas oligodendrocyte development can occur in the absence of inducing signals, 2A development apparently cannot. Fetal calf serum (FCS) and bone morphogenetic proteins (BMPs) are powerful inducers of 2A development in culture, but there is no compelling evidence that OPCs develop into astrocytes in vivo. We show here that BMPs are made by glial cells in the developing rat optic nerve, raising the question of why 2As do not normally develop in the optic nerve. We demonstrate that the BMP antagonist Noggin is strongly expressed by both OPCs and type-1 astrocytes in the developing optic nerve. We also show that depletion of Noggin by a small interference RNA inhibits OPC proliferation and induces 2A differentiation in the presence of a low, non-2A-inducing concentration of FCS. By contrast, enforced expression of Noggin in OPCs blocks FCS-induced 2A differentiation. These findings suggest that BMPs in FCS are largely responsible for the 2A-inducing activity of FCS and that Noggin may normally inhibit the formation of 2As in the developing CNS. [Copyright &y& Elsevier]

Gas exchange and water status were evaluated for plants at irrigated residential and unirrigated remnant Sonoran Desert sites in the greater Phoenix area, Arizona, U.S.A. Gas exchanges fluxes were higher for plants at the residential sites than for those at the desert sites. Plant water status was more favorable at residential sites for every season except the late summer monsoon, and time of day for maximum photosynthesis was later for residential plants during summer and winter months. These data suggest that yearly CO2 uptake was a function of plant water status and summer heat stress, and land use in these urban desert landscapes. [Copyright &y& Elsevier]

The Ho0.5Sr0.5MnO3 perovskite, synthesized in air, has been studied by combining neutron powder and electron diffraction techniques. The Pnma-type structure exhibits a strong tilting of the MnO6 octahedra. This octahedra tilting and microtwinning involve a complex strained structure. No structural transition is observed down to 1.4 K, but short-range A-type antiferromagnetism running over only a few perovskite subcells is evidenced below ≈90 K. The different behavior of this perovskite compared to other Ln0.5Sr0.5MnO3 perovskites is discussed in terms of A-site cationic mismatch. [Copyright &y& Elsevier]

We have determined the structure of a complex of influenza hemagglutinin (HA) with an antibody that binds simultaneously to the membrane-distal domains of two HA monomers, effectively cross-linking them. The antibody prevents the low pH structural transition of HA that is required for its membrane fusion activity, providing evidence that a rearrangement of HA membrane-distal domains is an essential component of the transition. [Copyright &y& Elsevier]

Studies the process of mate location in deathwatch beetle, Xestobium rufovillosum using substrate vibrations for orientation. Production of taps to enable males to locate females; Description of male behavior while searching for females; Use of seismic communication to convey location, species, sex and receptivity; Test for tropotaxis; Test for klinokinesis.

Abstract Doxorubicin (Dox) has widespread use as a cancer chemotherapeutic agent, but Dox is limited by several side effects including irreversible cardiomyopathy. Although liposomal Dox formulations, such as Doxil, mitigate side effects, they do not prolong survival in many patients. As a result, efforts have continued to discover improved formulations of Dox. We previously found that a peptide-based nanoplex delivered plasmid DNA efficiently to tumors in murine models. Unlike the majority of nanoparticles that depend solely on enhanced permeability and retention (EPR) for their transport into the tumor, our peptide-based nanoplex has a potential advantage in that its uptake primarily depends on neuropilin-1 receptor targeting. Because Dox binds to DNA, we tested whether this delivery platform could effectively deliver Dox to tumors and reduce their size. The nanoplexes increased the levels of Dox in tumors by about 5.5-fold compared to aqueous (free) Dox controls. Consistent with enhanced levels in the tumor, the nanoplex-Dox treatment had significantly greater anti-tumor activity. Whereas low dose free Dox did not reduce the size of tumors compared to untreated controls, the low dose nanoplex-Dox reduced the size of tumors by nearly 55% (p < 0.001). The high dose nanoplex-Dox also inhibited the size of tumor significantly more than the comparable high-dose free Dox (p < 0.001). Furthermore, apoptosis and proliferation markers (Ki67) of tumors observed in the different treatment groups correlated with their ability to inhibit tumor size. This study shows the efficacy of an NRP-1 targeted nanoplexes to deliver Dox to tumors in vivo and lays the groundwork for more complex and effective formulations. Highlights • Doxorubicin (Dox)-plasmid conjugates and HK peptides formed nanoplexes. • Nanoplexes increased tumor levels of Dox compared to the free Dox. • The nanoplex-Dox had markedly greater anti-tumor activity than the free Dox. • Dose-response tumor inhibition was observed with the nanoplex-Dox treatments. • The nanoplex-Dox treatments significantly enhanced tumor apoptosis. [ABSTRACT FROM AUTHOR]

The exploration of brain networks with resting-state fMRI (rs-fMRI) combined with graph theoretical approaches has become popular, with the perspective of finding network graph metrics as biomarkers in the context of clinical studies. A preliminary requirement for such findings is to assess the reliability of the graph based connectivity metrics. In previous test-retest (TRT) studies, this reliability has been explored using intraclass correlation coefficient (ICC) with heterogeneous results. But the issue of sample size has not been addressed. Using the large TRT rs-fMRI dataset from the Human Connectome Project (HCP), we computed ICCs and their corresponding p -values (applying permutation and bootstrap techniques) and varied the number of subjects (from 20 to 100), the scan duration (from 400 to 1200 time points), the cost and the graph metrics, using the Anatomic-Automatic Labelling (AAL) parcellation scheme. We quantified the reliability of the graph metrics computed both at global and regional level depending, at optimal cost, on two key parameters, the sample size and the number of time points or scan duration. In the cost range between 20% to 35%, most of the global graph metrics are reliable with 40 subjects or more with long scan duration (14 min 24 s). In large samples (for instance, 100 subjects), most global and regional graph metrics are reliable for a minimum scan duration of 7 min 14 s. Finally, for 40 subjects and long scan duration (14 min 24 s), the reliable regions are located in the main areas of the default mode network (DMN), the motor and the visual networks. [ABSTRACT FROM AUTHOR]

A population-based programme of health checks was introduced for adults in England in 2011 for the primary prevention of cardiovascular diseases (CVD) and risk factors management. The aim was to evaluate changes in cardiovascular risk and behavioural risk factors in a health check eligible population in England from 1994 to 2013, by using repeated cross-sectional design using seven surveys of the Health Survey for England. Measures included traditional CVD risk factors and behavioural risk factors. Linear trends were estimated allowing for sampling design. The surveys comprised 49,805 adults aged 45 to 74years; 30,639 were free from cardiovascular comorbidity; 16,041 (52%) had complete data for quantitative risk factors. Between 1994 and 2013, systolic blood pressure decreased by 3.1 (95% confidence interval 2.5 to 3.6) mmHg per decade in men and 5.0 (4.5 to 5.5) in women. Total cholesterol decreased by 0.20 (0.16 to 0.24) mmol/l per decade in men; 0.23 (0.19 to 0.26) in women. Smoking declined by 6% (5% to 8%) per decade in men; 7% (6% - 8%) in women. The proportion with CVD-risk ≥20% declined by 6.8% per decade in men; 2.4% in women. Multiple behavioural risk factors were strongly associated with estimated CVD-risk, but improving trends in traditional CVD risk factors were inconsistent with increasing indicators of adiposity. Long-term declines in traditional risk factors contributed to reductions in estimated CVD-risk prior to the introduction of a health check programme. Behaviour change interventions for multiple risk factor exposures remain a key area for future research. [ABSTRACT FROM AUTHOR]

Retrieval of proper names is a cause of concern and complaint among elderly adults and it is an early symptom of patients suffering from neurodegenerative diseases such as Alzheimer's disease (AD). While it is well established that AD patients have deficits of proper name retrieval, the nature of such impairment is not yet fully understood. Specifically, it is unknown whether this deficit is due to a degradation of the links between faces and proper names, or due to deficits in intentionally accessing and retrieving proper names from faces. Here, we aim to investigate the integrity of the links between famous faces and proper names in AD while minimizing the impact of the explicit retrieval. We compare the performances of AD patients and elderly controls in a face-name priming task. We assess the integrity of the link between faces and names at two different levels: identity level - the name and face belong to the same person; and semantic level - the name and face belong to the same category (e.g., politicians). Our results reveal that AD patients compared with controls show intact semantic priming but reduced priming for person identity. This suggests that the deficits in intentionally retrieving proper names in AD are the result of a partial disruption of the network at the identity level, i.e., the links between known faces and proper names. [ABSTRACT FROM AUTHOR]

Abstract: The Huygens probe landed on the then unknown surface of Titan in January 2005. A small, protruding penetrometer, part of the Surface Science Package (SSP), was pushed into the surface material measuring the mechanical resistance of the ground as the probe impacted the landing site. We present laboratory penetrometry into room temperature surface analogue materials using a replica penetrometer to investigate further the nature of Titan’s surface and examine the sensor’s capabilities. The results are then compared to the flight instrument’s signature and suggest the Titan surface substrate material consists of sand-sized particles with a mean grain size ∼2mm. A possible thin 7mm coating with mechanical properties similar to terrestrial snow may overlie this substrate, although due to the limited data we are unable to detect any further layering or grading within the near-surface material. The unusual weakening with depth of the signature returned from Titan has, to date, only been reproduced using a damp sand target that becomes progressively wetter with depth, and supports the suggestion that the surface may consist of a damp and cohesive material with interstitial liquid contained between its grains. Comparison with terrestrial analogues highlights the unusual nature of the landing site material. [ABSTRACT FROM AUTHOR]

What long-period comets with orbital periods >250 years cause detectable meteor showers on Earth? Low-light video cameras are used to track the motion of +4 to −5 magnitude meteors in our atmosphere by triangulation and calculate the meteoroid orbit in space. In recent years, the CAMS (Cameras for Allsky Meteor Surveillance) low-light video camera network was greatly expanded and, together with other video networks, now has increased the total video meteoroid orbit database to over 2.2 million orbits. Here, we searched this database for meteor showers associated with known long-period comets. Previously, five associations were known. Now, we find 14, as well as six uncertain but likely associations. These showers show a change of longitude of perihelion with node that is a strong function of inclination. Showers of longer duration show a steeper magnitude distribution index, presumably due to aging of the meteoroid population. Showers are generally detected only if the orbital period of the comet is less than 4000 years and the Earth-Comet orbital miss distance is ≤0.10 AU. The lack of an associated meteor shower sets lower limits on the orbital period of poorly observed comets. • The number of known meteor showers with long-period comet parent bodies has grown from 5 to 14. • Showers are detected only if the comet orbit has an orbital period less than 4000 years and passes to within about 0.01 AU from Earth's orbit. • Long-period comet meteor showers are significantly dispersed in solar longitude, radiant, and speed. • The change of longitude of perihelion with solar longitude is a strong function of inclination. • More dispersed (older) meteor showers show a steeper magnitude distrubution index. [ABSTRACT FROM AUTHOR]

Abstract: Calibration of the couplings across the N–Cα–Cβ–Cγ fragment of aspartate and asparagine residues is afforded by two interactions that produce fixed conformations of the side chains in solution. One is the binding of these side chains to calcium ions; the other is the H-bond interaction of these side chains with a backbone amide. [Copyright &y& Elsevier]

Abstract: Combining low-temperature electron (ED) and synchrotron powder diffraction (SPD) techniques, we have precisely determined the phase-separated crystal structure of Pr0.5Ca0.5Mn0.97Ga0.03O3. We demonstrate that the phase separation is associated with the onset of charge/orbital ordering at ∼230K and that two ordered phases coexist at low temperature. In order to account for the significant anisotropic linewidth broadening observed in the SPD patterns, we had to include a specific strain model in the refinements. One of the phases, the most severely strained, is suggested to result from an imperfect charge ordering. [Copyright &y& Elsevier]

Therapeutic angiogenesis aims to induce blood vessel growth in acute or chronic ischemic tissues and has gained tremendous interest over the last years. To study factors and combinations thereof that potentially induce or modify angiogenesis and to evaluate their therapeutic potential, various in vitro assays have been developed. Although endothelial cells have attracted most attention in these assays, they alone cannot complete vessel maturation since extracellular matrix (ECM) components and mesenchymal cells also play an important role in vascular development. To address this complexity we focussed on a human co-culture angiogenesis assay comprising primary endothelial cells as well as primary ECM-producing fibroblasts. In this assay HGF and VEGF as single factors and combined were tested for the potential to induce an angiogenic response, which was detected by image analysis assessing the area, length and branches of the formed vascular structures. The results show that the cytokines HGF and VEGF both promote angiogenesis in this co-culture assay by inducing distinguishable patterns of vascular structures. VEGF increases the length, area and branch point number of induced vessels whereas HGF mediates exclusively vascular area growth resulting in vascular structures of enlarged diameter. Moreover, the combination of both cytokines results in an additive increase of vascular diameter. [Copyright &y& Elsevier]