bluuebunny/crossref_metadata_2025 huggingface dataset:
A new durophagous stem cheloniid turtle from the lower Paleocene of Cabinda, Angola
Authors: Myers Timothy S. , Polcyn Michael J. , Mateus Octávio , Vineyard Diana P. , Gonçalves António Olímpio , Jacobs Louis L.
Published: November 2017

A new stem cheloniid turtle, Cabindachelys landanensis, gen. et sp. nov., is represented by a nearly complete skull and partial hyoid collected in lower Paleocene shallow marine deposits, equivalent to the offshore Landana Formation, near the town of Landana in Cabinda, Angola. A partial chelonioid carapace previously reported from this locality is referred here to C. landanensis. Cabindachelys landanensis possesses clear synapomorphies of Pan‐Cheloniidae, including a rod‐like rostrum basisphenoidale, V‐shaped basisphenoid crest, and secondary palate, but also retains a reduced foramen palatinum posterius, unlike most other pan‐cheloniids. Phylogenetic analysis suggests that C. landanensis forms a weakly‐supported clade with Erquelinnesia gosseleti, Euclastes acutirostris, Euclastes wielandi and Terlinguachelys fischbecki, although a close relationship between the protostegid T. fischbecki and these durophagous pan‐cheloniids is unlikely. The Paleocene–Eocene strata near Landana have produced a number of turtle fossils, including the holotype specimen of the pleurodire Taphrosphys congolensis. A turtle humerus collected c. 1 m above the holotype skull of C. landanensis differs from humeri of chelonioids and Taphrosphys, indicating that a third turtle taxon is present at Landana. Cheloniid fossil material is rare in the Landana assemblage, in comparison with the abundant remains of Taphrosphys congolensis found throughout the stratigraphic section. This disparity implies that C. landanensis preferred open marine habitats, whereas Taphrosphys congolensis spent more time in nearshore environments. The appearance of new durophagous species such as C. landanensis in the early Paleocene reflects the rapid radiation of pan‐cheloniids as they diversified into open niches following the K–Pg extinction.
Atomistic modeling of graphene/hexagonal boron nitride polymer nanocomposites: a review
Authors: Verma Akarsh , Parashar Avinash , Packirisamy M.
Published: November 2017

Due to their exceptional properties, graphene and hexagonal boron nitride (h‐BN) nanofillers are emerging as potential candidates for reinforcing the polymer‐based nanocomposites. Graphene and h‐BN have comparable mechanical and thermal properties, whereas due to high band gap in h‐BN (~5 eV), have contrasting electrical conductivities. Atomistic modeling techniques are viable alternatives to the costly and time‐consuming experimental techniques, and are accurate enough to predict the mechanical properties, fracture toughness, and thermal conductivities of graphene and h‐BN‐based nanocomposites. Success of any atomistic model entirely depends on the type of interatomic potential used in simulations. This review article encompasses different types of interatomic potentials that can be used for the modeling of graphene, h‐BN, and corresponding nanocomposites, and further elaborates on developments and challenges associated with the classical mechanics‐based approach along with synergic effects of these nano reinforcements on host polymer matrix.

This article is categorized under:

Molecular and Statistical Mechanics > Molecular Mechanics

Structure and Mechanism > Computational Materials Science

Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods
Saccharomyces cerevisiae × Saccharomyces uvarum hybrids generated under different conditions share similar winemaking features
Authors: Origone Andrea Cecilia , Rodríguez María Eugenia , Oteiza Juan Martín , Querol Amparo , Lopes Christian Ariel
Published: November 2017

Interspecific hybrids among species in the Saccharomyces genus are frequently detected in anthropic habitats and can also be obtained easily in the laboratory. This occurs because the most important genetic barriers among Saccharomyces species are post‐zygotic. Depending on several factors, including the involved strains, the hybridization mechanism and stabilization conditions, hybrids that bear differential genomic constitutions, and hence phenotypic variability, can be obtained. In the present study, Saccharomyces cerevisiae × Saccharomyces uvarum hybrids were constructed using genetically and physiologically different S. uvarum parents at distinct temperatures (13 and 20°C). The effect of those variables on the main oenological features of the wines obtained with these hybrids was evaluated. Hybrids were successfully obtained in all cases. However, genetic stabilization based on successive fermentations in white wine at 13°C was significantly longer than that at 20°C. Our results demonstrated that, irrespective of the S. uvarum parent and temperature used for hybrid generation and stabilization, similar physicochemical and aromatic features were found in wines. The hybrids generated herein were characterized by low ethanol production, high glycerol synthesis and the capacity to grow at low temperature and to produce malic acid with particular aroma profiles. These features make these hybrids useful for the new winemaking industry within the climate change era frame. Copyright © 2017 John Wiley & Sons, Ltd.
B-physics anomalies: a guide to combined explanations
Authors: Buttazzo Dario , Greljo Admir , Isidori Gino , Marzocca David
Published: November 2017

Abstract

Motivated by additional experimental hints of Lepton Flavour Universality violation in B decays, both in charged- and in neutral-current processes, we analyse the ingredients necessary to provide a combined description of these phenomena. By means of an Effective Field Theory (EFT) approach, based on the hypothesis of New Physics coupled predominantly to the third generation of left-handed quarks and leptons, we show how this is possible. We demonstrate, in particular, how to solve the problems posed by electroweak precision tests and direct searches with a rather natural choice of model parameters, within the context of a U(2)
q
×U(2)ℓ flavour symmetry. We further exemplify the general EFT findings by means of simplified models with explicit mediators in the TeV range: coloured scalar or vector leptoquarks and colour-less vectors. Among these, the case of an SU(2)
L
-singlet vector leptoquark emerges as a particularly simple and successful framework.
Long‐Term Outcome After Surgery for Medullary Thyroid Carcinoma: A Single‐Center Experience
Authors: Torresan Francesca , Cavedon Elisabetta , Mian Caterina , Iacobone Maurizio
Published: November 2017

Background

Medullary thyroid carcinoma (MTC) is a rare C cells‐derived tumor, with a hardly predictable long‐term prognosis. This study was aimed to evaluate the predictive factors of cure and survival after surgery for MTC in a monocentric series.

Methods

A retrospective analysis of the long‐term outcomes was assessed in 255 MTC patients operated between 1980 and 2015 at Padua University hospital.

Results

Sporadic MTC occurred in 65.1% and hereditary MTC in 34.9% of patients. At a median follow‐up of 93 months (range 7–430), the cure rate was 56.8%. The overall 10‐year survival was 84.4%, and MTC‐related death rate was 15.3%. Patients who died because of MTC had a median age of 61 years (range 21–84) and were at stages III–IV in all cases; deaths occurred in 18% of sporadic MTC, 6% of MEN2a and 66.7% of MEN2b patients. None of the patients at stages I–II died because of the disease, but 17.7% had persistent/recurrent disease. Based on univariate analysis, age, gender, genetic variant, extent and year of surgery, tumor size, lymph‐nodal metastases and tumor stage significantly affected cure and survival rates. At multivariate analysis, only patient‐ and tumor‐related features (age, lymph‐nodal status and stage) remained significant independent prognostic factors.

Conclusions

Radical surgery is the only chance of definitive cure in MTC, but it is possible only at early stage; in advanced stages, even extensive surgery could not grant cure and prolonged survival. Stage, nodal metastases and age remain the main predictive factors for cure and survival.
Surgery for Primary Hyperparathyroidism with Normal Non‐suppressed Parathyroid Hormone can be Both Challenging and Successful
Authors: Orr Lauren E. , McKenzie Travis J. , Thompson Geoffrey B. , Farley David R. , Wermers Robert A. , Lyden Melanie L.
Published: November 2017

Background

Criteria for diagnosing primary hyperparathyroidism (PHPT) include hypercalcemia in the presence of parathyroid hormone (PTH) levels that are either elevated (classic PHPT) or normal but non‐suppressed. However, there is no standard definition of what constitutes normal non‐suppressed levels, and data are lacking regarding the potential for surgical cure in these patients.

Methods

A retrospective review of patients undergoing parathyroidectomy for sporadic PHPT between 2012 and 2014 was performed. Patients with normal PTH were compared to classic PHPT patients to assess demographics, imaging, operative findings, and outcomes.

Results

In total, 332 patients met study criteria, and 60 (18%) had normal PTH levels. Negative sestamibi scans were seen more often with normal PTH levels (18.3 vs. 4.8%, p < 0.001). Patients with normal PTH were more likely to have ≥2 glands removed (26.7 vs. 14.3%, p = 0.02), and the specimens were more likely to be classified as only mildly hypercellular or normocellular (20 vs. 2.9%, p < 0.001). Average follow‐up was 24 months (range 6–55). Cure rate was 88% in the normal PTH group, compared to 96% in classic PHPT (p = 0.02). Among patients with normal PTH, those with PTH ≤ 55 pg/mL had an 83% cure rate, whereas those with PTH 56–65 had a 96% cure rate (p = 0.12).

Conclusions

Parathyroidectomy can have a high cure rate in the context of normal PTH levels despite an increased likelihood of negative imaging and multigland resection. Operative success is equivalent to classic PHPT when PTH levels are > 55 pg/mL.
Outcome of Thyroid Carcinoma Showing Thymus‐Like Differentiation in Patients Undergoing Radical Resection
Authors: Dong Wenwu , Zhang Ping , Li Jian , He Liang , Wang Zhihong , Zhang Ting , Shao Liang , Zhang Hao
Published: November 2017

Background

Carcinoma showing thymus‐like differentiation (CASTLE) is a rare malignant tumor of the thyroid. It is difficult to diagnose, and there is no universally recognized therapeutic regimen. This study aims to define the clinicopathological features and discuss the optimal management of CASTLE.

Methods

We retrospectively analyzed six patients with CASTLE who accepted surgery at the First Hospital of China Medical University between January 2010 and December 2015.

Results

The six patients (three women and three men) had median age of 53 years (range 47–61 years). All patients presented with a slow‐growing, painless neck mass; three patients also had hoarseness. All tumors were located in middle‐lower or lower lobe, and two tumors extended to the substernal region. All patients underwent radical surgery without postoperative radiotherapy or chemotherapy. Five patients had extrathyroidal extension and two had lymph node metastasis. All six tumors were positive for CD5 and negative for thyroglobulin (Tg) and thyroid transcription factor (TTF)‐1. Median follow‐up was 32 months (range 23–81 months). Lateral cervical lymph node metastasis occurred in one patient at 26 months after initial treatment.

Conclusions

CASTLE is a rare, aggressive malignant tumor of the thyroid. Ultrasound, computed tomography, and fine‐needle aspiration biopsy may not be sufficient to establish the diagnosis preoperatively; pathological examination and immunohistochemistry, particularly positive CD5 staining, are necessary to establish the diagnosis. Patients with CASTLE can yield a favorable outcome after radical surgery.
Comparison of Surgical Outcomes Between Robotic and Laparoscopic Distal Gastrectomy for cT1 Gastric Cancer
Authors: Hikage Makoto , Tokunaga Masanori , Makuuchi Rie , Irino Tomoyuki , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori
Published: November 2017

Background

Increasing numbers of patients are treated by robotic distal gastrectomy (RDG); however, it remains unclear whether RDG is clinically comparable with conventional laparoscopic distal gastrectomy (LDG). This study aimed to clarify the feasibility of RDG from safety aspects.

Methods

The study included 109 cT1 gastric cancer patients who underwent RDG at Shizuoka Cancer Center from January 2012 to April 2015. Short‐term outcomes were compared with 160 cT1 gastric cancer patients who underwent LDG during the same period.

Results

Patient characteristics were well matched. The RDG patients experienced longer operative times (323 min) than LDG patients (285 min; P < 0.001), although all other surgical outcomes were comparable between the groups. Drain amylase levels on POD 1 were significantly lower in the RDG group compared to LDG cases (median 452 U/L and 892 U/L; P < 0.001). The incidence of all complications was similar across the study patients, although intra‐abdominal infectious complications tended to be lower in the RDG group than in the LDG group (2.8 and 8.1%; P = 0.112).

Conclusions

RDG was comparable to LDG in terms of feasibility for cT1 gastric cancer. RDG has the potential to reduce pancreas damage and thus to decrease intra‐abdominal infectious complications.
Theory does not meet experiment: transient dynamics changes patterns of exclusion in an intraguild predation system
Authors: Maciel Gabriel Andreguetto , Kraenkel Roberto André
Published: November 2017

Although empirical verifications of ecological theory are essential for the advance of our understanding of ecosystems functioning, they are often hard to obtain or even impractical. In this work we perform a detailed analysis of unexpected results found in a previous test of intraguild predation (IGP) theory. When the IG prey is the stronger competitor the IGP theory predicts a clear dynamical pattern along a resource gradient. In particular, the IG predator is expected to be excluded at low resources. In the experiment we analyze, IG prey was excluded at a resource level where the IG predator should be eliminated. We use a simple IGP model parametrized using mainly preliminary tests of the experiment. We suggest that experiment and theory agree if we look to the transient dynamics instead of asymptotic states, in which the usual theory is based. We show that extremely low IG prey populations during the transient may drive it to extinction and prevent the system from reaching long‐term states. Our results are shown to be robust with respect to changes in initial conditions and parameters.
Pharmacokinetics and Safety of Amenamevir in Healthy Subjects: Analysis of Four Randomized Phase 1 Studies
Authors: Kusawake Tomohiro , Keirns James J. , Kowalski Donna , den Adel Martin , Groenendaal-van de Meent Dorien , Takada Akitsugu , Ohtsu Yoshiaki , Katashima Masataka
Published: November 2017

Introduction

Amenamevir (ASP2151) is a nonnucleoside antiherpesvirus compound available for the treatment of varicella–zoster virus infections. In this article we summarize the findings of four phase 1 studies in healthy participants.

Methods

Four randomized phase 1 studies investigated the safety and pharmacokinetics of single and multiple doses of amenamevir, including the assessment of age group effect (nonelderly vs elderly), food effect, and the relative bioavailability of two formulations. Amenamevir was administered orally at various doses as a single dose (5–2400 mg) or daily (300 or 600 mg/day) for 7 days.

Results

Following single and multiple oral doses, amenamevir demonstrated a less than dose proportional increase in the pharmacokinetic parameters area under the plasma drug concentration versus time curve from time zero to infinity (AUCinf) and Cmax. After single and multiple oral 300-mg doses of amenamevir, no apparent differences in pharmacokinetics were observed between nonelderly and elderly participants. In contrast, with the amenamevir 600-mg dose both the area under the plasma drug concentration versus time curve from time zero to 24 h and Cmax were slightly increased and renal clearance was decreased in elderly participants. The pharmacokinetics of amenamevir was affected by food, with AUCinf increased by about 90%. In the bioavailability study, AUCinf and Cmax were slightly lower following tablet versus capsule administration (decreased by 14 and 12%, respectively), with relative bioavailability of 86%. The different amenamevir doses and formulations were safe and well tolerated; no deaths or serious adverse events were reported.

Conclusion

Amenamevir had less than dose proportional pharmacokinetic characteristics. Age may have an influence on amenamevir pharmacokinetics; however, the effect was considered minimal. The pharmacokinetics of amenamevir were affected by food, with AUCinf almost doubling when amenamevir was administered with food. The concentration versus time profile of the tablet was slightly lower than that of the capsule; the relative bioavailability of the tablet versus the capsule was 86%. Amenamevir was safe and well tolerated in the dose range investigated.

Funding

Astellas Pharma.

Trial registration

ClinicalTrials.gov identifiers NCT02852876 (15L-CL-002) and NCT02796118 (15L-CL-003).
Dynamical boson stars
Authors: Liebling Steven L. , Palenzuela Carlos
Published: November 2017

The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s, John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called geons, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name boson stars. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single Killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.
Optimization of hole-boring radiation pressure acceleration of ion beams for fusion ignition
Authors: Weng S.M. , Sheng Z.M. , Murakami M. , Chen M. , Liu M. , Wang H.C. , Yuan T. , Zhang J.
Published: November 2017

In contrast to ion beams produced by conventional accelerators, ion beams accelerated by ultrashort intense laser pulses have advantages of ultrashort bunch duration and ultrahigh density, which are achieved in compact size. However, it is still challenging to simultaneously enhance their quality and yield for practical applications such as fast ion ignition of inertial confinement fusion. Compared with other mechanisms of laser-driven ion acceleration, the hole-boring radiation pressure acceleration has a special advantage in generating high-fluence ion beams suitable for the creation of high energy density state of matters. In this paper, we present a review on some theoretical and numerical studies of the hole-boring radiation pressure acceleration. First we discuss the typical field structure associated with this mechanism, its intrinsic feature of oscillations, and the underling physics. Then we will review some recently proposed schemes to enhance the beam quality and the efficiency in the hole-boring radiation pressure acceleration, such as matching laser intensity profile with target density profile, and using two-ion-species targets. Based on this, we propose an integrated scheme for efficient high-quality hole-boring radiation pressure acceleration, in which the longitudinal density profile of a composite target as well as the laser transverse intensity profile are tailored according to the matching condition.
The Judicial Trilemma visits Latin American Judicial Politics
Authors: Guim Mauricio
Published: November 2017

The Judicial Trilemma, by Jeff Dunoff and Mark Pollack, studies the dynamic relations between accountability, transparency, and independence, and suggests that designers can only maximize two of these three values at once. They can create a court that has high levels of (1) independence and accountability, (2) transparency and independence, or (3) accountability and transparency, but only at the cost of having a low level of the third value. The article explores these ideas using four different international tribunals, but its insights are not limited to international courts. Domestic designers also have to decide what levels of accountability, independence, and transparency their courts should have, and in making a decision they will face the Judicial Trilemma and confront the hard choice of selecting primarily two out of three values.
Independence and Impartiality in The Judicial Trilemma
Authors: Keller Helen , Meier Severin
Published: November 2017

Jeffrey L. Dunoff and Mark A. Pollack's article is an important and very welcome contribution to the discussion about judicial values. The authors argue that with respect to judicial independence, transparency, and accountability “judicial systems face inherent trade-offs, such that any given court can maximize two, but not all three, of these features.” In our eyes, the article's most important contribution is its holistic view: it shows why these three judicial values can only be understood in their interconnectedness. It is, for instance, not meaningful to make a statement about the correlation between transparency and independence without also taking accountability into the equation. This is because the effect of transparency on independence can only be understood if information about judicial accountability is at one's disposal. In the past, these judicial values have often been analyzed in an isolated manner, thereby leading to wrong conclusions. The Judicial Trilemma will hopefully help in shifting the discourse from isolated to holistic views on independence, transparency, and accountability. Moreover, Dunoff and Pollack lay the groundwork for a meaningful normative discussion of these three judicial values. Any debate about how to structure (international) courts should henceforth take Dunoff and Pollack's holistic view as a basis for discussion.
A person's a person, no matter how divine? The question of univocity and personhood in Richard of St Victor'sDe Trinitate
Authors: Stratis Justin
Published: November 2017

This article offers a reading of Richard of St Victor's medieval treatiseOn the Trinity. It suggests that while Richard interrogates the question of trinitarian personhood in innovative ways, his contribution lies in the way he emphasises hownatureinfluences the criteria for personhood with respect to different modes of existence. Thus, while human personhood shares certain features in common with divine personhood, the two concepts must remain distinguishable with reference to the type of natures they uniquely ‘person’. This conclusion may serve to chastise modern forms of trinitarianism which assume ‘univocity’ of divine and human personhood too hastily.
A Scoping Review of Physical Rehabilitation in Long-Term Care: Interventions, Outcomes, Tools
Authors: McArthur Caitlin , Gibbs Jenna C. , Patel Ruchit , Papaioannou Alexandra , Neves Paula , Killingbeck Jaimie , Hirdes John , Milligan James , Berg Katherine , Giangregorio Lora
Published: November 2017

Les résidents en soins de longue durée (SLD) ont souvent besoin de soins en réadaptation pour maintenir ou améliorer leur état physique fonctionnel. L’objectif de cet examen de portée était de décrire l’envergure des publications concernant la réadaptation physique en SLD jusqu’à ce jour, avec une emphase sur les types d’interventions en réadaptation qui ont été évaluées, ainsi que sur les mesures de résultats utilisées et les outils déterminant l’admissibilité au service. Une recherche structurée a été réalisée dans six bases de données sous licence et dans la littérature grise. Deux analystes ont identifié 381 articles qui ont été triés en utilisant un formulaire qui avait préalablement été testé dans un essai pilote, et les données de ces articles ont été extraites. La plupart des interventions avaient été réalisées et évaluées au niveau des résidents, et consistaient fréquemment en des programmes d’exercices à plusieurs composantes dispensés par du personnel de recherche et des physiothérapeutes. Les mesures les plus couramment rapportées étaient basées sur la performance, les activités de la vie quotidienne et l’humeur. Une lacune importante a été identifiée concernant les connaissances sur la réadaptation en lien avec des objectifs qui soient pertinents pour les résidents, tels que la qualité de vie. Dans les études à venir, il serait important que les caractéristiques des résidents en SLD soit représentatives de la complexité de l’état de santé de cette population; la durée de leur séjour devrait aussi être incluse et différenciée. Les études d’intervention devraient aussi explorer des méthodes de prestation de soins qui soient réalistes et soutenables. Le développement d’outils pour favoriser une meilleure détermination de l’admissibilité aux services est aussi nécessaire pour assurer l’égalité en matière de soins en réadaptation dans l’ensemble du secteur des SLD.
Interplay of neuronal and non-neuronal genes regulates intestinal DAF-16-mediated immune response during Fusarium infection of Caenorhabditis elegans
Authors: Nag Papri , Aggarwal Pooja Rani , Ghosh Sudip , Narula Kanika , Tayal Rajul , Maheshwari Nidhi , Chakraborty Niranjan , Chakraborty Subhra
Published: November 2017

Although precisely controlled innate immune response is governed by conserved cellular events in phylogenetically diverse hosts, the underlying molecular mechanisms by which this process is regulated against a multi-host pathogen remain unknown. Fusarium oxysporum is a model multi-host pathogen, known to be associated with neuronal stress in humans and vascular wilt in plants. The interaction between innate immune and neuronal pathways is the basis of many diverse biological responses. How these processes are coordinated in response to fungal disease is not well understood. Here, we show that F. oxysporum f. sp. ciceri causes neuronal stress and intestinal disintegration, ultimately leading to the death of Caenorhabditis elegans. To explore the regulatory framework of Fusarium-associated disease, we analysed the gene expression during infection, integrated temporal gene expression, and network analysis with genetic inactivation data in Caenorhabditis elegans. We identified 1024 genes showing significant changes in expression (corrected P-values <0.05) in response to Fusarium infection. Co-expression network analysis of our data identified prognostic genes related to disease progression. These genes were dynamically expressed in various neuronal and non-neuronal tissues exhibiting diverse biological functions, including cellular homeostasis, organ patterning, stress response, and lipid metabolism. The RNA-seq analysis further identified shared and unique signalling pathways regulated by DAF-16/FOXO and SIR-2.1 linking neuronal stress, which facilitates negative regulation of intestinal innate immunity. Genetic analysis revealed that GCY-5 in ASE functions upstream of DAF-16, whereas ASI-specific SRD-1 regulates behavioural immunity. Overall, our results indicate that a ubiquitous response occurs during Fusarium infection mediated by highly conserved regulatory components and pathways, which can be exploited further for the identification of disease-responsive genes conserved among animals and plants. Finally, this study provided a novel insight into cross-species immune signalling and may facilitate the discovery of cellular therapeutic targets for Fusarium-associated disease.
Pleiotropic effects of schizophrenia-associated genetic variants in neuron firing and cardiac pacemaking revealed by computational modeling
Authors: Mäki-Marttunen Tuomo , Lines Glenn T. , Edwards Andrew G. , Tveito Aslak , Dale Anders M. , Einevoll Gaute T. , Andreassen Ole A.
Published: November 2017

Schizophrenia patients have an increased risk of cardiac dysfunction. A possible factor underlying this comorbidity are the common variants in the large set of genes that have recently been discovered in genome-wide association studies (GWASs) as risk genes of schizophrenia. Many of these genes control the cell electrogenesis and calcium homeostasis. We applied biophysically detailed models of layer V pyramidal cells and sinoatrial node cells to study the contribution of schizophrenia-associated genes on cellular excitability. By including data from functional genomics literature to simulate the effects of common variants of these genes, we showed that variants of voltage-gated Na+ channel or hyperpolarization-activated cation channel-encoding genes cause qualitatively similar effects on layer V pyramidal cell and sinoatrial node cell excitability. By contrast, variants of Ca2+ channel or transporter-encoding genes mostly have opposite effects on cellular excitability in the two cell types. We also show that the variants may crucially affect the propagation of the cardiac action potential in the sinus node. These results may help explain some of the cardiac comorbidity in schizophrenia, and may facilitate generation of effective antipsychotic medications without cardiac side-effects such as arrhythmia.
Optomechanical terahertz detection with single meta-atom resonator
Authors: Belacel Cherif , Todorov Yanko , Barbieri Stefano , Gacemi Djamal , Favero Ivan , Sirtori Carlo
Published: November 2017

Most of the common technologies for detecting terahertz photons (>1 THz) at room temperature rely on slow thermal devices. The realization of fast and sensitive detectors in this frequency range is indeed a notoriously difficult task. Here we propose a novel device consisting of a subwavelength terahertz meta-atom resonator, which integrates a nanomechanical element and allows energy exchange between the mechanical motion and the electromagnetic degrees of freedom. An incident terahertz wave thus produces a nanomechanical signal that can be read out optically with high precision. We exploit this concept to demonstrate a terahertz detector that operates at room temperature with high sensitivity and a much higher frequency response compared to standard detectors. Beyond the technological issue of terahertz detection, our architecture opens up new perspectives for fundamental science of light–matter interaction at terahertz frequencies, combining optomechanical approaches with semiconductor quantum heterostructures.
Enantioselective transformation of fluoxetine in water and its ecotoxicological relevance
Authors: Andrés-Costa María Jesús , Proctor Kathryn , Sabatini Marco T. , Gee Anthony P. , Lewis Simon E. , Pico Yolanda , Kasprzyk-Hordern Barbara
Published: November 2017

European legislation focusing on water quality is expected to broaden to encompass several pharmaceuticals as priority hazardous substances. This manuscript aims to challenge current regulatory approaches that do not recognize stereochemistry of chiral pharmaceuticals by testing the hypothesis that environmental transformation and effects of chiral pharmaceuticals are stereoselective. Our experiments revealed that, while degradation of chiral fluoxetine (FL) in river water occurs via non-enantioselective photochemical and mildly-enantioselective microbial processes favoring the (R)-enantiomer, a pronounced enantioselectivity favoring (S)-FL (leading to the formation of (S)-NFL (norfluoxetine)) is observed during activated sludge treatment. Toxicity tests proved strong enantiomer-specific toxicity in the case of Tetrahymena thermophila, protozoa that are utilized during activated sludge treatment ((R)-FL is 30× more toxic than (S)-FL; (S)-NFL is 10× more toxic than (S)-FL). This is of paramount importance as preferential degradation of (S)-FL in activated sludge microcosms leads to the enrichment of FL with 30× more toxic (R)-FL and formation of 10× more toxic (S)-NFL. It is commonly assumed that a decreased concentration of FL leads to decreased biological impact. Our study proves that despite the overall decrease in FL concentration, accumulation of toxic (R)-FL and formation of toxic (S)-NFL leads to much higher than presumed toxicological effects.
Effective mechanical properties of multilayer nano-heterostructures
Authors: Mukhopadhyay T. , Mahata A. , Adhikari S. , Zaeem M. Asle
Published: November 2017

Two-dimensional and quasi-two-dimensional materials are important nanostructures because of their exciting electronic, optical, thermal, chemical and mechanical properties. However, a single-layer nanomaterial may not possess a particular property adequately, or multiple desired properties simultaneously. Recently a new trend has emerged to develop nano-heterostructures by assembling multiple monolayers of different nanostructures to achieve various tunable desired properties simultaneously. For example, transition metal dichalcogenides such as MoS2 show promising electronic and piezoelectric properties, but their low mechanical strength is a constraint for practical applications. This barrier can be mitigated by considering graphene-MoS2 heterostructure, as graphene possesses strong mechanical properties. We have developed efficient closed-form expressions for the equivalent elastic properties of such multi-layer hexagonal nano-hetrostructures. Based on these physics-based analytical formulae, mechanical properties are investigated for different heterostructures such as graphene-MoS2, graphene-hBN, graphene-stanene and stanene-MoS2. The proposed formulae will enable efficient characterization of mechanical properties in developing a wide range of application-specific nano-heterostructures.
Rescue of PFOS-induced human Sertoli cell injury by overexpressing a p-FAK-Y407E phosphomimetic mutant
Authors: Chen Haiqi , Gao Ying , Mruk Dolores D. , Xiao Xiang , John Constance M. , Turek Paul J. , Lui Wing-yee , Lee Will M. , Silvestrini Bruno , Cheng C. Yan
Published: November 2017

PFOS induces Sertoli cell injury using testicular cells isolated from rodent testes, but it remains unknown if PFOS has similar effects in humans. Herein, we maintained human Sertoli cells in a mitotically active statein vitro, thus enabling transfection experiments that altered gene expression to explore the molecular mechanism(s) underlying toxicant-induced cell injury. Human Sertoli cells obtained from men at ages 15, 23, 36 and 40 were culturedin vitro. These differentiated Sertoli cells remained mitotically active when cultured in the presence of 10% FBS (fetal bovine serum), with a replication time of ~1–3 weeks. At ~80% confluency, they were used for studies including toxicant exposure, immunoblotting, immunofluorescence analysis, tight junction (TJ)-permeability assessment, and overexpression of BTB (blood-testis barrier) regulatory genes such as FAK and its phosphomimetic mutants. PFOS was found to induce Sertoli cell injury through disruptive effects on actin microfilaments and microtubule (MT) organization across the cell cytosol. As a consequence, these cytoskeletal networks failed to support cell adhesion at the BTB. Overexpression of a FAK phosphomimetic and constitutively active mutant p-FAK-Y407E in these cells was capable of rescuing the PFOS-induced injury through corrective cellular organization of cytoskeletal elements. Summary: PFOS induces human Sertoli cell injury which can be rescued by overexpressing p-FAK-Y407E mutant.
Evidence of quantum phase transition in real-space vacuum entanglement of higher derivative scalar quantum field theories
Authors: Kumar S. Santhosh , Shankaranarayanan S.
Published: November 2017

In a bipartite set-up, the vacuum state of a free Bosonic scalar field is entangled in real space and satisfies the area-law— entanglement entropy scales linearly with area of the boundary between the two partitions. In this work, we show that the area law is violated in two spatial dimensional model Hamiltonian having dynamical critical exponent z = 3. The model physically corresponds to next-to-next-to-next nearest neighbour coupling terms on a lattice. The result reported here is the first of its kind of violation of area law in Bosonic systems in higher dimensions and signals the evidence of a quantum phase transition. We provide evidence for quantum phase transition both numerically and analytically using quantum Information tools like entanglement spectra, quantum fidelity, and gap in the energy spectra. We identify the cause for this transition due to the accumulation of large number of angular zero modes around the critical point which catalyses the change in the ground state wave function due to the next-to-next-to-next nearest neighbor coupling. Lastly, using Hubbard-Stratanovich transformation, we show that the effective Bosonic Hamiltonian can be obtained from an interacting fermionic theory and provide possible implications for condensed matter systems.
Quantum steerability based on joint measurability
Authors: Chen Zhihua , Ye Xiangjun , Fei Shao-Ming
Published: November 2017

Occupying a position between entanglement and Bell nonlocality, Einstein-Podolsky-Rosen (EPR) steering has attracted increasing attention in recent years. Many criteria have been proposed and experimentally implemented to characterize EPR-steering. Nevertheless, only a few results are available to quantify steerability using analytical results. In this work, we propose a method for quantifying the steerability in two-qubit quantum states in the two-setting EPR-steering scenario, using the connection between joint measurability and steerability. We derive an analytical formula for the steerability of a class of X-states. The sufficient and necessary conditions for two-setting EPR-steering are presented. Based on these results, a class of asymmetric states, namely, one-way steerable states, are obtained.
Reduced orbitofrontal-thalamic functional connectivity related to suicidal ideation in patients with major depressive disorder
Authors: Kim Kiwon , Kim Sung-Woo , Myung Woojae , Han Cheol E. , Fava Maurizio , Mischoulon David , Papakostas George I. , Seo Sang Won , Cho Hana , Seong Joon-Kyung , Jeon Hong Jin
Published: November 2017

Despite recent developments in neuroimaging, alterations of brain functional connectivity in major depressive disorder (MDD) patients with suicidal ideation are poorly understood. This study investigated specific changes of suicidal ideation in functional connectivity of MDD patients. Whole brain functional connectivity in 46 patients with MDD (23 with suicidal ideation and 23 without) and 36 age- and gender- matched healthy controls were compared using resting-state functional Magnetic Resonance Imaging (fMRI) analyzed with network-based statistics (NBS) and graph-theoretical methods. Decreased functional connectivity in a characterized sub-network was observed in patients with MDD and suicidal ideation (FDR-adjusted p < 0.05). The sub-network included the regions of the fronto-thalamic circuits in the left hemisphere. The network measures of the left superior frontal gyrus, pars orbitalis (r = −0.40, p = 0.009), left thalamus (r = −0.41, p = 0.009), and right thalamus (r = −0.51, p = −0.002) were shown, through graph theoretical analysis, to be significantly negatively correlated with severity of suicidal ideation. The reduced functional connectivity in left orbitofrontal-both thalamic regions with suicidal ideation in MDD were inversely proportional to the severity of suicidality independent from depression severity. These findings suggest problems with decision-making and information integration in MDD patients with suicidal ideation.
A collection of genetically engineered Populus trees reveals wood biomass traits that predict glucose yield from enzymatic hydrolysis
Authors: Escamez Sacha , Latha Gandla Madhavi , Derba-Maceluch Marta , Lundqvist Sven-Olof , Mellerowicz Ewa J. , Jönsson Leif J. , Tuominen Hannele
Published: November 2017

Wood represents a promising source of sugars to produce bio-based renewables, including biofuels. However, breaking down lignocellulose requires costly pretreatments because lignocellulose is recalcitrant to enzymatic saccharification. Increasing saccharification potential would greatly contribute to make wood a competitive alternative to petroleum, but this requires improving wood properties. To identify wood biomass traits associated with saccharification, we analyzed a total of 65 traits related to wood chemistry, anatomy and structure, biomass production and saccharification in 40 genetically engineered Populus tree lines. These lines exhibited broad variation in quantitative traits, allowing for multivariate analyses and mathematical modeling. Modeling revealed that seven wood biomass traits associated in a predictive manner with saccharification of glucose after pretreatment. Four of these seven traits were also negatively associated with biomass production, suggesting a trade-off between saccharification potential and total biomass, which has previously been observed to offset the overall sugar yield from whole trees. We therefore estimated the “total-wood glucose yield” (TWG) from whole trees and found 22 biomass traits predictive of TWG after pretreatment. Both saccharification and TWG were associated with low abundant, often overlooked matrix polysaccharides such as arabinose and rhamnose which possibly represent new markers for improved Populus feedstocks.
Genome-wide survey indicates diverse physiological roles of the turnip (Brassica rapa var. rapa) calcium-dependent protein kinase genes
Authors: Wang Qiuli , Yin Xin , Chen Qian , Xiang Nan , Sun Xudong , Yang Yunqiang , Yang Yongping
Published: November 2017

Calcium-dependent protein kinases (CDPKs) as crucial sensors of calcium concentration changes play important roles in responding to abiotic and biotic stresses. In this study, 55 BrrCDPK genes, which were phylogenetically clustered into four subfamilies, were identified. Chromosome locations indicated that the CDPK family in turnip expanded by segmental duplication and genome rearrangement. Moreover, gene expression profiles showed that different BrrCDPKs were expressed in specific tissues or stages. Transcript levels of BrrCDPKs indicated that they were involved in abiotic and biotic stresses and that paralogs exhibited functional divergence. Additionally, we identified 15 Rboh genes in turnip; the results of yeast two-hybrid analysis suggested that BrrRbohD1 interacted only with BrrCDPK10 and that BrrRbohD2 interacted with BrrCDPK4/7/9/10/17/22/23. Most of the genes play an important role in pst DC3000 defense by regulating the accumulation of H2O2 and stomatal closure. Our study may provide an important foundation for future functional analysis of BrrCDPKs and reveal further biological roles.
Dog ownership and the risk of cardiovascular disease and death – a nationwide cohort study
Authors: Mubanga Mwenya , Byberg Liisa , Nowak Christoph , Egenvall Agneta , Magnusson Patrik K. , Ingelsson Erik , Fall Tove
Published: November 2017

Dogs may be beneficial in reducing cardiovascular risk in their owners by providing social support and motivation for physical activity. We aimed to investigate the association of dog ownership with incident cardiovascular disease (CVD) and death in a register-based prospective nation-wide cohort (n = 3,432,153) with up to 12 years of follow-up. Self-reported health and lifestyle habits were available for 34,202 participants in the Swedish Twin Register. Time-to-event analyses with time-updated covariates were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). In single- and multiple-person households, dog ownership (13.1%) was associated with lower risk of death, HR 0.67 (95% CI, 0.65–0.69) and 0.89 (0.87–0.91), respectively; and CVD death, HR 0.64 (0.59–0.70), and 0.85 (0.81–0.90), respectively. In single-person households, dog ownership was inversely associated with cardiovascular outcomes (HR composite CVD 0.92, 95% CI, 0.89–0.94). Ownership of hunting breed dogs was associated with lowest risk of CVD. Further analysis in the Twin Register could not replicate the reduced risk of CVD or death but also gave no indication of confounding by disability, comorbidities or lifestyle factors. In conclusion, dog ownership appears to be associated with lower risk of CVD in single-person households and lower mortality in the general population.
Inhibition of myeloid differentiation primary response protein 88 provides neuroprotection in early brain injury following experimental subarachnoid hemorrhage
Authors: Yan Huiying , Zhang Dingding , Wei Yongxiang , Ni Hongbin , Liang Weibang , Zhang Huasheng , Hao Shuangying , Jin Wei , Li Kuanyu , Hang Chun-Hua
Published: November 2017

Accumulating of evidence suggests that activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) exacerbates early brain injury (EBI) following subarachnoid hemorrhage (SAH) by provoking pro-inflammatory and pro-apoptotic signaling. Myeloid differentiation primary response protein 88 (MyD88) is an endogenous adaptor protein in the toll-like receptors (TLRs) and interleukin (IL) -1β family signaling pathways and acts as a bottle neck in the NF-κB and MAPK pathways. Here, we used ST2825, a selective inhibitor of MyD88, to clarify whether inhibiting MyD88 could provide neuroprotection in EBI following SAH. Our results showed that the expression of MyD88 was markedly increased at 24 h post SAH. Intracerebroventricular injection of ST2825 significantly reduced the expression of MyD88 at 24 h post SAH. Involvement of MAPKs and NF-κB signaling pathways was revealed that ST2825 inhibited SAH-induced phosphorylation of TAK1, p38 and JNK, the nuclear translocation of NF-κB p65, and degradation of IκBα. Further, ST2825 administration diminished the SAH-induced inflammatory response and apoptosis. As a result, SAH-induced EBI was alleviated and neurological deficits caused by SAH were reversed. Our findings suggest that MyD88 inhibition confers marked neuroprotection against EBI following SAH. Therefore, MyD88 might be a promising new molecular target for the treatment of SAH.
A streamlined cloning workflow minimising the time-to-strain pipeline for Pichia pastoris
Authors: Royle Kate E. , Polizzi Karen
Published: November 2017

Although recent advances in E. coli self-assembly have greatly simplified cloning, these have not yet been harnessed for the high-throughput generation of expression strains in the early research and discovery phases of biopharmaceutical production. Here, we have refined the technique and incorporated it into a streamlined workflow for the generation of Pichia pastoris expression strains, reducing the timeline by a third and removing the reliance on DNA editing enzymes, which often require troubleshooting and increase costs. We have validated the workflow by cloning 24 human proteins of biopharmaceutical value, either as direct therapeutics or as research targets, which span a continuous range in size and GC content. This includes demonstrating the applicability of the workflow to three-part assemblies for a monoclonal antibody and its single-chain antibody fragments derivatives. This workflow should enable future research into recombinant protein production by P. pastoris and a synthetic biology approach to this industrial host.