bluuebunny/crossref_metadata_2025 huggingface dataset:
IV AND GMM INFERENCE IN ENDOGENOUS STOCHASTIC UNIT ROOT MODELS
Authors: Lieberman Offer , Phillips Peter C.B.
Published: August 2017

Lieberman and Phillips (2017; LP) introduced a multivariate stochastic unit root (STUR) model, which allows for random, time varying local departures from a unit root (UR) model, where nonlinear least squares (NLLS) may be used for estimation and inference on the STUR coefficient. In a structural version of this model where the driver variables of the STUR coefficient are endogenous, the NLLS estimate of the STUR parameter is inconsistent, as are the corresponding estimates of the associated covariance parameters. This paper develops a nonlinear instrumental variable (NLIV) as well as GMM estimators of the STUR parameter which conveniently addresses endogeneity. We derive the asymptotic distributions of the NLIV and GMM estimators and establish consistency under similar orthogonality and relevance conditions to those used in the linear model. An overidentification test and its asymptotic distribution are also developed. The results enable inference about structural STUR models and a mechanism for testing the local STUR model against a simple UR null, which complements usual UR tests. Simulations reveal that the asymptotic distributions of the NLIV and GMM estimators of the STUR parameter as well as the test for overidentifying restrictions perform well in small samples and that the distribution of the NLIV estimator is heavily leptokurtic with a limit theory which has Cauchy-like tails. Comparisons of STUR coefficient and standard UR coefficient tests show that the one-sided UR test performs poorly against the one-sided STUR coefficient test both as the sample size and departures from the null rise. The results are applied to study the relationships between stock returns and bond spread changes.
Existence and properties of semi-bounded global solutions to the functional differential equation with Volterra-type operators on the real line
Authors: Aguerrea Maitere , Hakl Robert
Published: August 2017

Consider the equation

where are linear positive continuous operators and f : Cloc(ℝ;ℝ) → Lloc(ℝ;ℝ) is a continuous operator satisfying the local Carathéodory conditions. Efficient conditions guaranteeing the existence of a global solution, which is bounded and non-negative in the neighbourhood of –∞, to the equation considered are established provided that ℓ0, ℓ1 and f are Volterra-type operators. The existence of a solution that is positive on the whole real line is discussed as well. Furthermore, the asymptotic properties of such solutions are studied in the neighbourhood of –∞. The results are applied to certain models appearing in the natural sciences.
Something old, something new: Some processes for dialect change in Sweden
Authors: Nilsson Jenny
Published: August 2017

The traditional dialects of Sweden are changing. In order to investigate how these changes may be proceeding, the use of traditional dialect and new linguistic features have been analyzed in three separate dialect areas: Inland West Sweden, Coastal West Sweden and Torsby in Northern Värmland. The focus is on how much of the traditional dialect used in the mid-20th century is still in use in each location, and what is replacing it in the process of change; this is done by analyzing speakers’ realizations of a total of 137 traditional dialect variables and 18 new variables. In some locations, dialects are leveling towards the standard, more or less rapidly. In others, there is a clear dialect shift to the urban Gothenburg variety or to the use of acombilect, which is a mix of traditional dialect variants, standard variants, new variants and urban variants. Similarities and differences between these separate processes are discussed, with special attention given to the reasons behind dialect change.
The sound of a spherical cow
Authors: Bradfield Julian
Published: August 2017

I consider the use of computational simulations in phonology, and the benefits and dangers of making abstractions, or failing to make abstractions. I argue that the potential of simulation studies is not yet realised as it could be.
The local nature of tone-association patterns
Authors: Jardine Adam
Published: August 2017

A computational notion of locality, based on forbidden substructures of a fixed size, is applied to autosegmental representations, and tone-association patterns are argued to be local. This is significant for phonological theory, for two reasons. First, this notion of locality provides for an explicit theory of tonal well-formedness that is superior to previous explanations in that it makes clear, restrictive typological predictions. Second, it provides a clear path for understanding how these patterns can be learned. A brief survey of major tone-association patterns shows that association generalisations which are edge-based (Mende and Hausa), quality-specific (Kukuya) or positional (Northern Karanga Shona) are all local in this way. This is contrasted with previous explanations of the typology, which require global reference to the directionality of association, and can thus overgenerate.
Erratum For ‘A Bound on the Number of Edges in Graphs Without an Even Cycle’
Authors: BUKH BORIS , JIANG ZILIN
Published: August 2017

Due to a calculation error, the constant in the main theorem is not $80 \sqrt{k\log k}$ but $80\sqrt{k} \log k$. The error was discovered by Xizhi Liu.

For a new discussion on the limit of the method used in this paper see the revised arXiv version of the paper.
The Growth Constant of Odd Cutsets in High Dimensions
Authors: FELDHEIM OHAD NOY , SPINKA YINON
Published: August 2017

A cutset is a non-empty finite subset of ℤdwhich is both connected and co-connected. A cutset is odd if its vertex boundary lies in the odd bipartition class of ℤd. Peled [18] suggested that the number of odd cutsets which contain the origin and havenboundary edges may be of ordereΘ(n/d)asd→ ∞, much smaller than the number of general cutsets, which was shown by Lebowitz and Mazel [15] to be of orderdΘ(n/d). In this paper, we verify this by showing that the number of such odd cutsets is (2+o(1))n/2d.
SLAVES, GLADIATORS, AND DEATH: KANTIAN LIBERALISM AND THE MORAL LIMITS OF CONSENT
Authors: Ramsay Marc
Published: August 2017

Irving Kristol invoked the example of voluntary gladiatorial contests to show that liberalism's commitment to personal autonomy cannot override majoritarian standards of morality. Liberalism cannot explain why voluntary gladiatorial contests should be banned, but liberals know that such contests should be banned. Thus, honest liberals must concede that majoritarian morality trumps consent. Arthur Ripstein argues that the consent in gladiatorial agreements contains a formal defect. According to Ripstein, because both gladiators sanction their own deaths, both reduce themselves to the status of mere things or slaves. On the Kantian view, slavery contracts undermine the personal sovereignty that binding contracts must presuppose, so Kantian liberals can reject gladiatorial contracts and still avoid legal moralism. I argue that while Kantian liberals have cogent internal reasons for rejecting slavery contracts, not all gruesome and deadly contests are matters of slavery. Thus, Kristol's challenge remains intact.
Somali, Latino and Hmong parents’ perceptions and approaches about raising healthy-weight children: a community-based participatory research study
Authors: Arcan Chrisa , Culhane-Pera Kathleen A , Pergament Shannon , Rosas-Lee Maira , Xiong Mai Bao
Published: August 2017

Objective

Immigrants in the USA are confronted with health disparities, including childhood obesity and obesity-related chronic diseases. We aimed to identify perceptions of childhood body weight, approaches to raising healthy children and desires for supportive programmes of Somali, Latino and Hmong (SLM) parents in the Twin Cities, Minnesota, USA.

Design

Using community-based participatory research, ten focus groups (FG) were conducted with sixty-seven parents (n 28 Somali, three FG; n 19 Latino, four FG; n 20 Hmong, three FG) of 3–12-year-old children in their native language. Demographic information was collected.

Results

SLM parents perceived that health is not necessarily weight-based; childhood obesity is caused by overeating, eating unhealthy foods and sedentary activities; traditional foods are generally healthy while American foods are generally unhealthy; and healthy children are inherently physically active. Parents identified their goals as feeding children so they would be healthy and happy, helping them be active and safe, and teaching them to cook traditional foods to be self-sufficient and maintain their cultural identity. Parents were challenged by children’s unhealthy food and sedentary preferences, their own uncertainties about healthy foods and behaviours, and structural factors. Parents thought interventions could help them with these challenges, including information about healthy foods, age-appropriate portion sizes, safe places to be active and strategies tailored to their cultural norms.

Conclusions

SLM parents are trying to raise healthy-weight children based on their understanding of children’s health, weight, diet and physical activity, while dealing with social, economic and environmental challenges and trying to maintain cultural identity and traditions.
Associations of Baltic Sea and Mediterranean dietary patterns with bone mineral density in elderly women
Authors: Erkkilä Arja T , Sadeghi Homa , Isanejad Masoud , Mursu Jaakko , Tuppurainen Marjo , Kröger Heikki
Published: August 2017

Objective

Dietary quality in relation to bone health has been analysed in relatively few studies. The current study aimed to assess the association of the Baltic Sea diet (BSD) and the Mediterranean diet (MD) with bone mineral density (BMD) among elderly women.

Design

Lumbar, femoral and total body BMD were measured by dual-energy X-ray absorptiometry at baseline and year 3. Dietary intake was measured by 3 d food record at baseline. BSD and MD scores were calculated from food and alcohol consumption and nutrient intake. Information on lifestyle, diseases and medications was collected by questionnaires. Longitudinal associations of BSD and MD scores with BMD were analysed using linear mixed models.

Setting

Interventional prospective Kuopio Osteoporosis Risk Factor and Fracture Prevention study including women aged 65–71 years and residing in Kuopio province, Finland.

Subjects

Women (n554) with mean age of 67·9 (sd1·9) years and mean BMI of 28·8 (sd4·7) kg/m2.

Results

Higher BSD scores were associated with higher intakes of fruit and berries, vegetables, fish and low-fat dairy products, and lower intake of sausage. Higher MD scores were associated with higher consumption of fruit and berries and vegetables. BSD and MD scores were associated with higher PUFA:SFA and higher fibre intake. Femoral, lumbar or total body BMD was not significantly different among the quartiles of BSD or MD score.

Conclusion

The lack of associations suggest that Baltic Sea and Mediterranean dietary patterns may not adequately reflect dietary factors relevant to bone health.
Adapting the standardised computer- and interview-based 24 h dietary recall method (GloboDiet) for dietary monitoring in Latin America
Authors: Bel-Serrat Silvia , Knaze Viktoria , Nicolas Genevieve , Marchioni Dirce M , Steluti Josiane , Mendes Aline , Crispim Sandra P , Fisberg Regina M , Pereira Rosangela A , Araujo Marina C , Sichieri Rosely , Yokoo Edna M , Sánchez-Pimienta Tania , Aburto Tania C , Pedraza Lilia S , Slimani Nadia
Published: August 2017

Objective

The present study describes the procedure and approaches needed to adapt and harmonise the GloboDiet methodology, a computer- and interview-based 24 h dietary recall, for use in two Latin American pilot countries, Brazil and Mexico.

Design

About seventy common and country-specific databases on foods, recipes, dietary supplements, quantification methods and coefficients were customised and translated following standardised guidelines, starting from existing Spanish and Portuguese versions.

Setting

Brazil and Mexico.

Subjects

Not applicable.

Results

New subgroups were added into the existing common food classification together with new descriptors required to better classify and describe specific Brazilian and Mexican foods. Quantification methods were critically evaluated and adapted considering types and quantities of food consumed in these two countries, using data available from previous surveys. Furthermore, the photos to be used for quantification purposes were identified for compilation in country-specific but standardised picture booklets.

Conclusions

The completion of the customisation of the GloboDiet Latin America versions in these two pilot countries provides new insights into the adaptability of this dietary international tool to the Latin American context. The ultimate purpose is to enable dietary intake comparisons within and between Latin American countries, support building capacities and foster regional and international collaborations. The development of the GloboDiet methodology could represent a major benefit for Latin America in terms of standardised dietary methodologies for multiple surveillance, research and prevention purposes.
Diabetes and pregnancy in Wistar rats: renal effects for mothers in the postpartum period
Authors: França-Silva N. , Reis N. G. , Santos P. F. , Balbi A. P. C.
Published: August 2017

In this study, diabetes mellitus (DM) was induced inWistarrats during pregnancy and maintained in the postpartum period (PP) and we evaluated systolic blood pressure (SBP), glomerular filtration rate (GFR) and renal immunohistochemical and morphometric studies from different groups: G1 (non-pregnant control rats), G2 (non-pregnant diabetic rats), G3 (control mothers) and G4 (diabetic mothers). We found that there were no differences in relation to SBP, but there was a tendency for reduction in GFR from G4 compared with the other groups (G). There was increased total kidney weight/body weight ratio of G4 compared with other G. There were increase in glomerular tuft area in G3 and G4 compared with G1 and G2. G2 and G4 showed even higher percentage of cortical collagen. G3 showed increased glomerular proliferating cells compared with G1 and G2, while in G4 this number was smaller than G3. Cell proliferation was higher in the tubulointerstitial (TBI) compartment from G4. Glomerular and TBI α-smooth muscle actin expression was increased in G4 compared with other G. The glomerular p-p38 expression showed a pattern similar to proliferation cell nuclear antigen, with a reduction of p-p38 in G4 relative to other G. The immunoreactivity of p-JNK was higher in both the glomeruli and TBI compartment in G4 compared with G1, G2 and G3. The DM induced during pregnancy and maintained in the PP resulted in renal structural and functional changes to mothers. In addition, altered mitogen-activated protein kinase expression in association with these changes may play an important role in renal damage observed in the present investigation.
The Developmental Origins of Health and Disease and Sustainable Development Goals: mapping the way forward
Authors: Kajee N. , Sobngwi E. , Macnab A. , Daar A. S.
Published: August 2017

In this paper, meant to stimulate debate, we argue that there is considerable benefit in approaching together the implementation of two seemingly separate recent developments. First, on the global development agenda, we have the United Nations General Assembly’s 2015 finalized list of 17 Sustainable Development Goals (SDGs). Several of the SDGs are related to health. Second, the field of Developmental Origins of Health and Disease (DOHaD) has garnered enough compelling evidence demonstrating that early exposures in life affect not only future health, but that the effects of that exposure can be transmitted across generations – necessitating that we begin to focus on prevention. We argue that implementing the SDGs and DOHaD together will be beneficial in several ways; and will require attending to multiple, complex and multidisciplinary approaches as we reach the point of translating science to policy to impact. Here, we begin by providing the context for our work and making the case for a mutually reinforcing, synergistic approach to implementing SDGs and DOHaD, particularly in Africa. To do this, we initiate discussion via an early mapping of some of the overlapping considerations between SDGs and DOHaD.
Erratum: Long noncoding RNA: noncoding and not coded
Authors: Toiber Debra , Leprivier Gabriel , Rotblat Barak
Published: August 2017

Correction to: Cell Death Discovery (2017) 3, 16104; doi:10.1038/cddiscovery.2016.104; published online 9 January 2017 Since the publication of this article, it has been noted that the affiliation for Gabriel Leprivier was incorrect. The correct affiliation is as follows: 2Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University, Dusseldorf, Germany.
Interspecies nutrient extraction and toxin delivery between bacteria
Authors: Stempler Ofer , Baidya Amit K. , Bhattacharya Saurabh , Malli Mohan Ganesh Babu , Tzipilevich Elhanan , Sinai Lior , Mamou Gideon , Ben-Yehuda Sigal
Published: August 2017

Bacteria have developed various mechanisms by which they sense, interact, and kill other bacteria, in an attempt to outcompete one another and survive. Here we show that Bacillus subtilis can kill and prey on Bacillus megaterium. We find that Bacillus subtilis rapidly inhibits Bacillus megaterium growth by delivering the tRNase toxin WapA. Furthermore, utilizing the methionine analogue L-azidohomoalanine as a nutrient reporter, we provide evidence of nutrient extraction from Bacillus megaterium by Bacillus subtilis. Toxin delivery and nutrient extraction occur in a contact-dependent manner, and both activities are abolished in the absence of the phosphodiestrase YmdB, shown previously to mediate intercellular nanotube formation. Furthermore, we detect the localization of WapA molecules to nanotubes. Thus, we propose that Bacillus subtilis utilizes the same nanotube apparatus in a bidirectional manner, delivering toxin and acquiring beneficial cargo, thereby maximally exploiting potential niche resources.
BRCA locus-specific loss of heterozygosity in germline BRCA1 and BRCA2 carriers
Authors: Maxwell Kara N. , Wubbenhorst Bradley , Wenz Brandon M. , De Sloover Daniel , Pluta John , Emery Lyndsey , Barrett Amanda , Kraya Adam A. , Anastopoulos Ioannis N. , Yu Shun , Jiang Yuchao , Chen Hao , Zhang Nancy R. , Hackman Nicole , D’Andrea Kurt , Daber Robert , Morrissette Jennifer J. D. , Mitra Nandita , Feldman Michael , Domchek Susan M. , Nathanson Katherine L.
Published: August 2017

Complete loss of BRCA1 or BRCA2 function is associated with sensitivity to DNA damaging agents. However, not allBRCA1andBRCA2germline mutation-associated tumors respond. Herein we report analyses of 160BRCA1andBRCA2germline mutation-associated breast and ovarian tumors. Retention of the normalBRCA1orBRCA2allele (absence of locus-specific loss of heterozygosity (LOH)) is observed in 7% ofBRCA1ovarian, 16% ofBRCA2ovarian, 10% ofBRCA1breast, and 46% ofBRCA2breast tumors. These tumors have equivalent homologous recombination deficiency scores to sporadic tumors, significantly lower than scores in tumors with locus-specific LOH (ovarian,P = 0.0004; breastP < 0.0001, two-tailed Student’st-test). Absence of locus-specific LOH is associated with decreased overall survival in ovarian cancer patients treated with platinum chemotherapy (P = 0.01, log-rank test). Locus-specific LOH may be a clinically useful biomarker to predict primary resistance to DNA damaging agents in patients with germlineBRCA1andBRCA2mutations.
Androgen receptor as a mediator and biomarker of radioresistance in triple-negative breast cancer
Authors: Speers Corey , Zhao Shuang G. , Chandler Ben , Liu Meilan , Wilder-Romans Kari , Olsen Eric , Nyati Shyam , Ritter Cassandra , Alluri Prasanna G. , Kothari Vishal , Hayes Daniel F. , Lawrence Theodore S. , Spratt Daniel E. , Wahl Daniel R. , Pierce Lori J. , Feng Felix Y.
Published: August 2017

Increased rates of locoregional recurrence have been observed in triple-negative breast cancer despite chemotherapy and radiation therapy. Thus, approaches that combine therapies for radiosensitization in triple-negative breast cancer are critically needed. We characterized the radiation therapy response of 21 breast cancer cell lines and paired this radiation response data with high-throughput drug screen data to identify androgen receptor as a top target for radiosensitization. Our radiosensitizer screen nominated bicalutamide as the drug most effective in treating radiation therapy-resistant breast cancer cell lines. We subsequently evaluated the expression of androgen receptor in >2100 human breast tumor samples and 51 breast cancer cell lines and found significant heterogeneity in androgen receptor expression with enrichment at the protein and RNA level in triple-negative breast cancer. There was a strong correlation between androgen receptor RNA and protein expression across all breast cancer subtypes (R2 = 0.72, p < 0.01). In patients with triple-negative breast cancer, expression of androgen receptor above the median was associated with increased risk of locoregional recurrence after radiation therapy (hazard ratio for locoregional recurrence 2.9–3.2)) in two independent data sets, but there was no difference in locoregional recurrence in triple-negative breast cancer patients not treated with radiation therapy when stratified by androgen receptor expression. In multivariable analysis, androgen receptor expression was most significantly associated with worse local recurrence-free survival after radiation therapy (hazard ratio of 3.58) suggesting that androgen receptor expression may be a biomarker of radiation response in triple-negative breast cancer. Inhibition of androgen receptor with MDV3100 (enzalutamide) induced radiation sensitivity (enhancement ratios of 1.22–1.60) in androgen receptor-positive triple-negative breast cancer lines, but did not affect androgen receptor-negative triple-negative breast cancer or estrogen-receptor-positive, androgen receptor-negative breast cancer cell lines. androgen receptor inhibition with MDV3100 significantly radiosensitized triple-negative breast cancer xenografts in mouse models and markedly delayed tumor doubling/tripling time and tumor weight. Radiosensitization was at least partially dependent on impaired dsDNA break repair mediated by DNA protein kinase catalytic subunit. Our results implicate androgen receptor as a mediator of radioresistance in breast cancer and identify androgen receptor inhibition as a potentially effective strategy for the treatment of androgen receptor-positive radioresistant tumors.
Emergent magnetic anisotropy in the cubic heavy-fermion metal CeIn3
Authors: Moll Philip J. W. , Helm Toni , Zhang Shang-Shun , Batista Cristian D. , Harrison Neil , McDonald Ross D. , Winter Laurel E. , Ramshaw B. J. , Chan Mun K. , Balakirev Fedor F. , Batlogg Bertram , Bauer Eric D. , Ronning Filip
Published: August 2017

Metals containing cerium exhibit a diverse range of fascinating phenomena including heavy fermion behavior, quantum criticality, and novel states of matter such as unconventional superconductivity. The cubic system CeIn3has attracted significant attention as a structurally isotropic Kondo lattice material possessing the minimum required complexity to still reveal this rich physics. By using magnetic fields with strengths comparable to the crystal field energy scale, we illustrate a strong field-induced anisotropy as a consequence of non-spherically symmetric spin interactions in the prototypical heavy fermion material CeIn3. This work demonstrates the importance of magnetic anisotropy in modelingf-electron materials when the orbital character of the 4fwavefunction changes (e.g., with pressure or composition). In addition, magnetic fields are shown to tune the effective hybridization and exchange interactions potentially leading to new exotic field tuned effects inf-based materials.
Habituation as an adaptive shift in response strategy mediated by neuropeptides
Authors: Ardiel Evan L. , Yu Alex J. , Giles Andrew C. , Rankin Catharine H.
Published: August 2017

Habituation is a non-associative form of learning characterized by a decremented response to repeated stimulation. It is typically framed as a process of selective attention, allowing animals to ignore irrelevant stimuli in order to free up limited cognitive resources. However, habituation can also occur to threatening and toxic stimuli, suggesting that habituation may serve other functions. Here we took advantage of a high-throughput Caenorhabditis elegans learning assay to investigate habituation to noxious stimuli. Using real-time computer vision software for automated behavioral tracking and optogenetics for controlled activation of a polymodal nociceptor, ASH, we found that neuropeptides mediated habituation and performed an RNAi screen to identify candidate receptors. Through subsequent mutant analysis and cell-type-specific gene expression, we found that pigment-dispersing factor (PDF) neuropeptides function redundantly to promote habituation via PDFR-1-mediated cAMP signaling in both neurons and muscles. Behavioral analysis during learning acquisition suggests that response habituation and sensitization of locomotion are parts of a shifting behavioral strategy orchestrated by pigment dispersing factor signaling to promote dispersal away from repeated aversive stimuli.
Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5
Authors: Menkhorst E. M. , Van Sinderen M. L. , Rainczuk K. , Cuman C. , Winship A. , Dimitriadis E.
Published: August 2017

During the establishment of pregnancy, extravillous trophoblast (EVT) must invade into the uterine decidua to facilitate decidual artery remodelling to create the placental blood supply. The local decidual environment is thought to regulate trophoblast invasion, however these interactions are poorly defined in humans. Recent evidence in women suggests impaired decidualization is associated with miscarriage and preeclampsia. Primary human endometrial stromal cells (HESC) and first trimester extravillous trophoblast (EVTs) were used to assess the effect of EVT-secreted factors on HESC decidualization, adhesion, proliferation and migration. We determined the role of profilin (PFN)1, an EVT-secreted factor, on HESC function and identified a downstream target of PFN1. EVT-secreted factors induced HESC decidualization and enhanced decidualized HESC adhesion, proliferation and migration. Recombinant PFN1 enhanced methoxyprogesterone acetate-induced HESC decidualization and proliferation. PFN1 down-regulated the expression of lipoxygenase arachidonate 5-lipoxygenase (ALOX5) in HESC and THP-1 macrophages. ALOX5 localised to decidual cells and CD68+macrophages in 1st trimester decidua. This study demonstrated that EVT secretions, including PFN1, enhanced HESC decidualization and motility. This study has identified a new pathway that facilitates appropriate decidualization during the establishment of pregnancy.
Nonlinear Bayesian filtering and learning: a neuronal dynamics for perception
Authors: Kutschireiter Anna , Surace Simone Carlo , Sprekeler Henning , Pfister Jean-Pascal
Published: August 2017

The robust estimation of dynamical hidden features, such as the position of prey, based on sensory inputs is one of the hallmarks of perception. This dynamical estimation can be rigorously formulated by nonlinear Bayesian filtering theory. Recent experimental and behavioral studies have shown that animals’ performance in many tasks is consistent with such a Bayesian statistical interpretation. However, it is presently unclear how a nonlinear Bayesian filter can be efficiently implemented in a network of neurons that satisfies some minimum constraints of biological plausibility. Here, we propose the Neural Particle Filter (NPF), a sampling-based nonlinear Bayesian filter, which does not rely on importance weights. We show that this filter can be interpreted as the neuronal dynamics of a recurrently connected rate-based neural network receiving feed-forward input from sensory neurons. Further, it captures properties of temporal and multi-sensory integration that are crucial for perception, and it allows for online parameter learning with a maximum likelihood approach. The NPF holds the promise to avoid the ‘curse of dimensionality’, and we demonstrate numerically its capability to outperform weighted particle filters in higher dimensions and when the number of particles is limited.
High energy storage density over a broad temperature range in sodium bismuth titanate-based lead-free ceramics
Authors: Yang Haibo , Yan Fei , Lin Ying , Wang Tong , Wang Fen
Published: August 2017

A series of (1-x)Bi0.48La0.02Na0.48Li0.02Ti0.98Zr0.02O3-xNa0.73Bi0.09NbO3 ((1-x)LLBNTZ-xNBN) (x = 0-0.14) ceramics were designed and fabricated using the conventional solid-state sintering method. The phase structure, microstructure, dielectric, ferroelectric and energy storage properties of the ceramics were systematically investigated. The results indicate that the addition of Na0.73Bi0.09NbO3 (NBN) could decrease the remnant polarization (P
r
) and improve the temperature stability of dielectric constant obviously. The working temperature range satisfying TCC150 °C ≤±15% of this work spans over 400 °C with the compositions of x ≥ 0.06. The maximum energy storage density can be obtained for the sample with x = 0.10 at room temperature, with an energy storage density of 2.04 J/cm3 at 178 kV/cm. In addition, the (1-x)LLBNTZ-xNBN ceramics exhibit excellent energy storage properties over a wide temperature range from room temperature to 90 °C. The values of energy storage density and energy storage efficiency is 0.91 J/cm3 and 79.51%, respectively, for the 0.90LLBNTZ-0.10NBN ceramic at the condition of 100 kV/cm and 90 °C. It can be concluded that the (1-x)LLBNTZ-xNBN ceramics are promising lead-free candidate materials for energy storage devices over a broad temperature range.
Structural basis for the broad substrate specificity of the human tyrosylprotein sulfotransferase-1
Authors: Tanaka Shinnosuke , Nishiyori Toshiaki , Kojo Hidetaka , Otsubo Reo , Tsuruta Moe , Kurogi Katsuhisa , Liu Ming-Cheh , Suiko Masahito , Sakakibara Yoichi , Kakuta Yoshimitsu
Published: August 2017

Tyrosylprotein sulfotransferases (TPSTs) are enzymes that catalyze post-translational tyrosine sulfation of proteins. In humans, there are only two TPST isoforms, designated TPST1 and TPST2. In a previous study, we reported the crystal structure of TPST2, which revealed the catalytic mechanism of the tyrosine sulfation reaction. However, detailed molecular mechanisms underlying how TPSTs catalyse a variety of substrate proteins with different efficiencies and how TPSTs catalyze the sulfation of multiple tyrosine residues in a substrate protein remain unresolved. Here, we report two crystal structures of the human TPST1 complexed with two substrate peptides that are catalysed by human TPST1 with significantly different efficiencies. The distinct binding modes found in the two complexes provide insight into the sulfation mechanism for these substrates. The present study provides valuable information describing the molecular mechanism of post-translational protein modifications catalysed by TPSTs.
Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
Authors: Sinha Neeraj , Suarez-Diez Maria , van Schothorst Evert M. , Keijer Jaap , Martins dos Santos Vitor A. P. , Hooiveld Guido J. E. J.
Published: August 2017

The small intestine serves as gatekeeper at the interface between body and diet and is thought to play an important role in the etiology of obesity and associated metabolic disorders. A computational modelling approach was used to improve our understanding of the metabolic responses of epithelial cells to different diets. A constraint based, mouse-specific enterocyte metabolic model (named mmu_ENT717) was constructed to describe the impact of four fully characterized semi-purified diets, that differed in lipid and carbohydrate composition, on uptake, metabolism, as well as secretion of carbohydrates and lipids. Our simulation results predicted luminal sodium as a limiting factor for active glucose absorption; necessity of apical localization of glucose transporter GLUT2 for absorption of all glucose in the postprandial state; potential for gluconeogenesis in enterocytes; and the requirement of oxygen for the formation of endogenous cholesterol needed for chylomicron formation under luminal cholesterol-free conditions. In addition, for a number of enzymopathies related to intestinal carbohydrate and lipid metabolism it was found that their effects might be ameliorated through dietary interventions. In conclusion, our improved enterocyte-specific model was shown to be a suitable platform to study effects of dietary interventions on enterocyte metabolism, and provided novel and deeper insights into enterocyte metabolism.
Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development
Authors: Sjaarda Calvin P. , Hecht Patrick , McNaughton Amy J. M. , Zhou Audrina , Hudson Melissa L. , Will Matt J. , Smith Garth , Ayub Muhammad , Liang Ping , Chen Nansheng , Beversdorf David , Liu Xudong
Published: August 2017

The low activity allele of the maternal polymorphism, 5HTTLPR, in the serotonin transporter, SLC6A4, coupled with prenatal stress is reported to increase the risk for children to develop autism spectrum disorder (ASD). Similarly, maternal Slc6a4 knock-out and prenatal stress in rodents results in offspring demonstrating ASD-like characteristics. The present study uses an integrative genomics approach to explore mechanistic changes in early brain development in mouse embryos exposed to this maternal gene-environment phenomenon. Restraint stress was applied to pregnant Slc6a4+/+ and Slc6a4+/− mice and post-stress embryonic brains were assessed for whole genome level profiling of methylome, transcriptome and miRNA using Next Generation Sequencing. Embryos of stressed Slc6a4+/+ dams exhibited significantly altered methylation profiles and differential expression of 157 miRNAs and 1009 genes affecting neuron development and cellular adhesion pathways, which may function as a coping mechanism to prenatal stress. In striking contrast, the response of embryos of stressed Slc6a4+/− dams was found to be attenuated, shown by significantly reduced numbers of differentially expressed genes (458) and miRNA (0) and genome hypermethylation. This attenuated response may pose increased risks on typical brain development resulting in development of ASD-like characteristics in offspring of mothers with deficits in serotonin related pathways during stressful pregnancies.
Metabolomics and genomics combine to unravel the pathway for the presence of fragrance in rice
Authors: Daygon Venea Dara , Calingacion Mariafe , Forster Louise C. , Voss James J. De , Schwartz Brett D. , Ovenden Ben , Alonso David E. , McCouch Susan R. , Garson Mary J. , Fitzgerald Melissa A.
Published: August 2017

Since it was first characterised in 1983, 2-acetyl-1-pyrroline (2AP) has been considered to be the most important aroma compound in rice. In this study, we show four other amine heterocycles: 6-methyl, 5-oxo-2,3,4,5-tetrahydropyridine (6M5OTP), 2-acetylpyrrole, pyrrole and 1-pyrroline, that correlate strongly with the production of 2AP, and are present in consistent proportions in a set of elite aromatic rice varieties from South East Asia and Australia as well as in a collection of recombinant inbred lines (RILs) derived from indica Jasmine-type varieties, Australian long grain varieties (temperate japonica) and Basmati-type rice (Grp V). These compounds were detected through untargeted metabolite profiling by two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF-MS), and their identity were confirmed by comparison with authentic standards analysed using gas chromatography mass spectrometry (GC-MS) and High Resolution GC × GC-TOF-MS (GC × GC HRT-4D). Genome-wide association analysis indicates that all compounds co-localised with a single quantitative trait locus (QTL) that harbours the FGR gene responsible for the production of GABA. Together, these data provide new insights into the production of 2AP, and evidence for understanding the pathway leading to the accumulation of aroma in fragrant rice.
Sensitive genotyping of mutations in the EGFR gene from NSCLC patients using PCR-GoldMag lateral flow device
Authors: Li Xian-Ying , Zhang Chao , Zhang Qin-Lu , Zhu Juan-Li , Liu Qian , Chen Ming-Wei , Yang Xue-Min , Hui Wen-Li , Cui Ya-Li
Published: August 2017

Epidermal growth factor receptor (EGFR) mutations predict better outcomes with EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Most common activating mutations include in-frame deletion in exon 19 and L858R substitution in exon 21, which account for >90% of all EGFR mutations in NSCLC. In this study, a PCR-GoldMag lateral flow assay (PCR-GoldMag LFA) was developed for the visual detection of delE746-A750 and L858R of EGFR mutations. Forty formalin-fixed paraffin-embedded (FFPE) tissue samples of NSCLC patients were analyzed using PCR-GoldMag LFA system and verified by direct sequencing and TaqMan-PCR detection methods. Results showed that EGFR mutations were detected in 34 cases among the 40 samples (85%) by PCR-GoldMag LFA method. Among the 34 cases, 5 cases were simultaneously detected with delE746-A750 in exon 19 and L858R mutation in exon 21. Compared with sequencing, only 4 samples were detected as delE746-A750, which revealed higher sensitivity of PCR-GoldMag LFA detection method than direct sequencing. TaqMan-PCR method verified the L858R mutation and was in 100% agreement with our method. These results indicated that our method has obvious advantages to analyze clinical samples and offers a more sensitive alternative to direct sequencing for the detection of EGFR mutations.
Exploring the Sequence-based Prediction of Folding Initiation Sites in Proteins
Authors: Raimondi Daniele , Orlando Gabriele , Pancsa Rita , Khan Taushif , Vranken Wim F.
Published: August 2017

Protein folding is a complex process that can lead to disease when it fails. Especially poorly understood are the very early stages of protein folding, which are likely defined by intrinsic local interactions between amino acids close to each other in the protein sequence. We here present EFoldMine, a method that predicts, from the primary amino acid sequence of a protein, which amino acids are likely involved in early folding events. The method is based on early folding data from hydrogen deuterium exchange (HDX) data from NMR pulsed labelling experiments, and uses backbone and sidechain dynamics as well as secondary structure propensities as features. The EFoldMine predictions give insights into the folding process, as illustrated by a qualitative comparison with independent experimental observations. Furthermore, on a quantitative proteome scale, the predicted early folding residues tend to become the residues that interact the most in the folded structure, and they are often residues that display evolutionary covariation. The connection of the EFoldMine predictions with both folding pathway data and the folded protein structure suggests that the initial statistical behavior of the protein chain with respect to local structure formation has a lasting effect on its subsequent states.
Neural circuitry governing anxious individuals’ mis-allocation of working memory to threat
Authors: Stout Daniel M. , Shackman Alexander J. , Pedersen Walker S. , Miskovich Tara A. , Larson Christine L.
Published: August 2017

Dispositional anxiety is a trait-like phenotype that confers increased risk for a range of debilitating neuropsychiatric disorders. Like many patients with anxiety disorders, individuals with elevated levels of dispositional anxiety are prone to intrusive and distressing thoughts in the absence of immediate threat. Recent electrophysiological research suggests that these symptoms are rooted in the mis-allocation of working memory (WM) resources to threat-related information. Here, functional MRI was used to identify the network of brain regions that support WM for faces and to quantify the allocation of neural resources to threat-related distracters in 81 young adults. Results revealed widespread evidence of mis-allocation. This was evident in both face-selective regions of the fusiform cortex and domain-general regions of the prefrontal and parietal cortices. This bias was exaggerated among individuals with a more anxious disposition. Mediation analyses provided compelling evidence that anxious individuals’ tendency to mis-allocate WM resources to threat-related distracters is statistically explained by heightened amygdala reactivity. Collectively, these results provide a neurocognitive framework for understanding the pathways linking anxious phenotypes to the development of internalizing psychopathology and set the stage for developing improved intervention strategies.
Peptide biomarkers used for the selective breeding of a complex polygenic trait in honey bees
Authors: Guarna M. Marta , Hoover Shelley E. , Huxter Elizabeth , Higo Heather , Moon Kyung-Mee , Domanski Dominik , Bixby Miriam E. F. , Melathopoulos Andony P. , Ibrahim Abdullah , Peirson Michael , Desai Suresh , Micholson Derek , White Rick , Borchers Christoph H. , Currie Robert W. , Pernal Stephen F. , Foster Leonard J.
Published: August 2017

We present a novel way to select for highly polygenic traits. For millennia, humans have used observable phenotypes to selectively breed stronger or more productive livestock and crops. Selection on genotype, using single-nucleotide polymorphisms (SNPs) and genome profiling, is also now applied broadly in livestock breeding programs; however, selection on protein/peptide or mRNA expression markers has not yet been proven useful. Here we demonstrate the utility of protein markers to select for disease-resistant hygienic behavior in the European honey bee (Apis mellifera L.). Robust, mechanistically-linked protein expression markers, by integrating cis- and trans- effects from many genomic loci, may overcome limitations of genomic markers to allow for selection. After three generations of selection, the resulting marker-selected stock outperformed an unselected benchmark stock in terms of hygienic behavior, and had improved survival when challenged with a bacterial disease or a parasitic mite, similar to bees selected using a phenotype–based assessment for this trait. This is the first demonstration of the efficacy of protein markers for industrial selective breeding in any agricultural species, plant or animal.
Analysis of population-specific pharmacogenomic variants using next-generation sequencing data
Authors: Ahn Eunyong , Park Taesung
Published: August 2017

Functional rare variants in drug-related genes are believed to be highly differentiated between ethnic- or racial populations. However, knowledge of population differentiation (PD) of rare single-nucleotide variants (SNVs), remains widely lacking, with the highest fixation indices, (Fst values), from both rare and common variants annotated to specific genes, having only been marginally used to understand PD at the gene level. In this study, we suggest a new, gene-based PD method, PD of Rare and Common variants (PDRC), for analyzing rare variants, as inspired by Generalized Cochran-Mantel-Haenszel (GCMH) statistics, to identify highly population-differentiated drug response-related genes (“pharmacogenes”). Through simulation studies, we reveal that PDRC adequately summarizes rare and common variants, due to PD, over a specific gene. We also applied the proposed method to a real whole-exome sequencing dataset, consisting of 10,000 datasets, from the Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) initiative, and 3,000 datasets from the Genetics of Type 2 diabetes (Go-T2D) repository. Among the 48 genes annotated with Very Important Pharmacogenetic summaries (VIPgenes), in the PharmGKB database, our PD method successfully identified candidate genes with high PD, including ACE, CYP2B6, DPYD, F5, MTHFR, and SCN5A.
A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation
Authors: Korthals Mark , Langnaese Kristina , Smalla Karl-Heinz , Kähne Thilo , Herrera-Molina Rodrigo , Handschuh Juliane , Lehmann Anne-Christin , Mamula Dejan , Naumann Michael , Seidenbecher Constanze , Zuschratter Werner , Tedford Kerry , Gundelfinger Eckart D. , Montag Dirk , Fischer Klaus-Dieter , Thomas Ulrich
Published: August 2017

The outcome of T cell activation is determined by mechanisms that balance Ca2+influx and clearance. Here we report that murine CD4 T cells lacking Neuroplastin (Nptn−/−), an immunoglobulin superfamily protein, display elevated cytosolic Ca2+and impaired post-stimulation Ca2+clearance, along with increased nuclear levels of NFAT transcription factor and enhanced T cell receptor-induced cytokine production. On the molecular level, we identified plasma membrane Ca2+ATPases (PMCAs) as the main interaction partners of Neuroplastin. PMCA levels were reduced by over 70% inNptn−/−T cells, suggesting an explanation for altered Ca2+handling. Supporting this, Ca2+extrusion was impaired while Ca2+levels in internal stores were increased. T cells heterozygous for PMCA1 mimicked the phenotype ofNptn−/−T cells. Consistent with sustained Ca2+levels, differentiation ofNptn−/−T helper cells was biased towards the Th1 versus Th2 subset. Our study thus establishes Neuroplastin-PMCA modules as important regulators of T cell activation.
Enhanced wintertime greenhouse effect reinforcing Arctic amplification and initial sea-ice melting
Authors: Cao Yunfeng , Liang Shunlin , Chen Xiaona , He Tao , Wang Dongdong , Cheng Xiao
Published: August 2017

The speeds of both Arctic surface warming and sea-ice shrinking have accelerated over recent decades. However, the causes of this unprecedented phenomenon remain unclear and are subjects of considerable debate. In this study, we report strong observational evidence, for the first time from long-term (1984–2014) spatially complete satellite records, that increased cloudiness and atmospheric water vapor in winter and spring have caused an extraordinary downward longwave radiative flux to the ice surface, which may then amplify the Arctic wintertime ice-surface warming. In addition, we also provide observed evidence that it is quite likely the enhancement of the wintertime greenhouse effect caused by water vapor and cloudiness has advanced the time of onset of ice melting in mid-May through inhibiting sea-ice refreezing in the winter and accelerating the pre-melting process in the spring, and in turn triggered the positive sea-ice albedo feedback process and accelerated the sea ice melting in the summer.