bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term changes in the North Atlantic current system and their biological implications
Authors: Taylor A. H.
Published: May 2019

Synopsis

Evidence is presented to show that the dominant mode of temperature change of the last 25 years, in the North Atlantic, has recurred throughout the last 100 years. Temperatures in the NE Atlantic, where this mode is especially prominent, tend to be inversely related to the strength of the Trade and Westerly Winds. The mode of temperature change, which extends through the top 250 m and involves corresponding salinity changes in the NE Atlantic, is interpreted as resulting from a shift in the North Atlantic Current system, wind-induced increases in the transport of the North Atlantic Gyre being accompanied by a radial shrinkage of the current system and a reduction of the warm water discharge to the north. A theoretical analysis, relating this current change to a shift in the separation of the Gulf Stream from the North American coast, is attempted to examine the consequences of this interpretation
Repressive Experiences among China Scholars: New Evidence from Survey Data
Authors: Greitens Sheena Chestnut , Truex Rory
Published: May 2019

This paper examines the nature of China's current research climate and its effects on foreign scholarship. Drawing on an original survey of over 500 China scholars, we find that repressive research experiences are a rare but real phenomenon and collectively present a barrier to the conduct of research in China. Roughly 9 per cent of China scholars report that they have been “invited to tea” by authorities within the past ten years; 26 per cent of scholars who conduct archival research report being denied access; and 5 per cent of researchers report some difficulty obtaining a visa. The paper provides descriptive information on the nature of these experiences and their determinants. It concludes with a discussion of self-censorship and strategies for conducting research on China.
From Institutional Interaction to Institutional Integration: The National Supervisory Commission and China's New Anti-corruption Model
Authors: Li Li , Wang Peng
Published: May 2019

How does the establishment of the National Supervisory Commission affect China's capacity to curb corruption? Using published materials and fieldwork data, this article addresses this question by comparing the newly established anti-corruption agency with the previous dual-track system. It first examines the previous system by focusing on four dimensions of the interaction between the Commission for Discipline Inspection (CDI) and the People's Procuratorate: complementarity, convergence, competition and conflict. Although the CDI and the procuratorate compensated for each other's deficiencies, competition and conflicts between the two institutions were rife, reducing the efficiency of China's anti-corruption work. The article then investigates what impact the establishment of the National Supervisory Commission has had on China's capacity to combat corruption. This new model strengthens the Party's capacity to curb corruption, and the focus of the anti-corruption work has shifted from punishment to prevention, but the Party still needs to resolve three types of unbalanced power relations: between supervision, prosecution and trial; between central and local authorities; and between the state and citizens.
Semilinear elliptic and parabolic equations of arbitrary order
Authors: von Wahl Wolf , McLeod J. B.
Published: May 2019

In this paper we prove the existence of classical solutions for all t ≧ 0 for parabolic equations u′ + A(t)u = –f(u, ∇y, …, ∇2m–2u) of arbitrary order. 2m is the order of the elliptic principal part. f must satisfy some monotonicity and growth conditions. Moreover, similar results are also valid for semilinear elliptic equations.
Cardiac Pharmacology and Cardiomyopathy in Friedreich's Ataxia
Authors: Huxtable Ryan J.
Published: May 2019

Friedreich's ataxia is almost always associated with a cardiomyopathy. The cardiomyopathy and its attendant cardiopulmonary sequelae is the usual cause of death in this disease. The author reviews the known pharmacology of the heart, particularly as it applies to hypertrophic cardiomyopathy. The important role played by calcium and the possible role of taurine is stressed. Therapeutic possibilities are mentioned.
Regulation of Cytoplasmic Calcium: Interactions between Prostaglandins, Prostacyclin, Thromboxane A2, Zinc, Copper and Taurine
Authors: Horrobin D. F. , Manku M. S. , Cunnane S. , Karmazyn M. , Morgan R. O. , Ally A. I. , Karmali R. A.
Published: May 2019

The regulation of cytoplasmic calcium is a key process in nerve tissue. Using a smooth muscle model we have shown that prostaglandine (PG) E2 probably regulates entry from extracellular fluid, whereas the release from intracellular stores depends on the interplay between thromboxane (TX) A2, PGEl and prostacyclin. Hormones and other agents interact with this system in the following ways: vasopressin, angiotensin and inositol mobilize arachidonic acid from membrane phospholipids and increase synthesis of PGE2 and TXA2, Cortisol blocks this action. Prolactin and zinc mobilize dihomo-γ-linolenic acid and increase synthesis of PGEL These effects can be blocked by Cortisol, lithium and taurine, three agents which on their own have no effect on basal PG production. Epileptogenic agents like penicillin and picrotoxin also stimulate PG synthesis, while diphenylhydantoin is a PG antagonist and diazepam is a TXA2 antagonist. The effects of all these agents occur at concentrations which are physiological in the case of the natural ones, and readily attained in human plasma in the case of the drugs. In view of recent evidence that calcium may be important in demyelination and considering the established role it plays in nerve conduction and synaptic transmission, we suggest that these observations may be of significance in understanding Friedreich's ataxia.
Taurine in Cerebrospinal Fluid in Friedreich's Ataxia
Authors: Lemieux B. , Giguere R. , Barbeau A. , Melancon S. , Shapcott D.
Published: May 2019

In a previous study we reported low values of taurine and aspartic acid in the CSF of patients with Friedreich's ataxia, when the results were compared to the literature. Further studies have revealed that tinforetold difficulties with the advertised methodology of sequential multi-sample amino acid analysis were responsible for low values in the determination of these two amino acids in the small volumes necessary for CSF. A corrected method is presented. With the latter method the differences disappear for CSF taurine and aspartic acid, but they remain valid for the previously reported blood and urine values in Friedreich's ataxia. GABA levels are also normal in Friedreich's ataxia CSF.
Plasma Lipids and Lipoproteins in Friedreich's Ataxia and Familial Spastic Ataxia — Evidence for an Abnormal Composition of High Density Lipoproteins
Authors: Huang Y. S. , Nestruck A. C. , Barbeau A. , Bouchard J. P. , Davignon J.
Published: May 2019

A systematic study of plasma lipids and lipoproteins was carried out in II cases of Friedreich's ataxia and 6 cases of familial spastic ataxia (Charlevoix-Saguenay disease) using II healthy normolipidemic volunteers of comparable age and sex as controls. No differences were noted in the fatty acid profile of the total lipid fraction, in the total cholesterol and phospholipids or in the percentage distribution of the individual phospholipid classes. The triglycerides were significantly higher in Friedreich's ataxia, but remained within the normal range. Although no systematic abnormalities could be detected in the electrophoretic pattern of plasma lipoproteins or in the apolipoprotein profile on polyacrylamide gel electrophoresis, major differences were found in the high density lipoprotein (HDL) fraction. Their total amount was reduced and their composition was abnormal in both neurological diseases. In Friedreich patients, the relative proportion of cholesterol and triglycerides was increased while the relative protein content was greatly reduced. In Charlevoix disease, a similar abnormality was seen except for the excess of triglycerides. The proportion of phospholipids in HDL was the same in the three groups of patients. In addition, the low density lipoprotein (LDL) fraction was slightly reduced in both diseases. This anomaly of the HDL fraction could indicate that the HDL apolipoprotein moiety has a greater affinity for cholesterol and triglycerides in Friedreich's ataxia than its normal counterpart.
Gerland of Besançon and the Manuscripts of his ‘Candela’ : A Bibliographical Note
Authors: Kuttner Stephan
Published: May 2019

Two anonymous French canonists shortly before or around 1170, the author of the ParisianSumma Magister Gratianus in hoc opereand, in his footsteps, the author of the fragmentarySumma Antiquitate et tempore, cited a book they called ‘Candela Gerlandi’ (or ‘Gelandi’). Neither Schulte nor the writer of these pages, in hisRepertorium(1937), was able to make much of the citation, save for connecting it with one ‘Jarlandus Chrysopolitanus’ whose name appears in some bibliographies of the seventeenth and the eighteenth century, and with a few manuscript references. To the codex Victorinus (now Paris, B. N. lat. 14618), first mentioned in 1666 by Erich Mauritius, professor at the then recently opened University of Kiel, in his dissertationDe libris iuris communis, Schulte added two more manuscripts of theCandelahe had noted at random in the catalogues of Troyes and Montpellier.
The authority of inter-state arbitral awards in the case law of the International Court of Justice
Authors: Lanovoy Vladyslav
Published: May 2019

Article 38(1)(d) of the Statute of the International Court of Justice attributes limited legal authority to judicial and arbitral decisions. They are not formal sources of law and are described as only subsidiary means for the determination of rules of law. However, the continuing validity of this characterization is challenged not only by the Court’s practice of referring to its own jurisprudence, a phenomenon that has been empirically and theoretically analysed elsewhere, but also its relatively new practice of relying on external case law. This article seeks to draw attention to one aspect of this new practice, namely the marked increase in the Court’s citation of inter-state arbitral awards since the 1990s. It is argued that the Court refers to inter-state arbitral awards in its decisions for three principal reasons – (i) to determine the existence of a given rule, (ii) to supplement its legal reasoning or its own case law on a particular issue, and (iii) to distinguish an arbitral award from the case before it. More ambitiously, the article argues that the way the Court relies on inter-state arbitral awards shows that the Court attributes legal authority to these awards that goes beyond that of a subsidiary means for determining a given rule of law, bringing it closer to what might be qualified as persuasive but non-binding precedent.
Emotion dysregulation as a dynamic process
Authors: Cole Pamela M. , Ashana Ramsook K. , Ram Nilam
Published: May 2019

In this article we adopt the view that emotion dysregulation is characterized by emotion regulation dynamics that are defined as dysfunctional based on contextual criteria. We regard the construct of emotion regulation as valuable because it permits the integration of the classic view of emotions as interfering with human functioning and contemporary views of emotion as adaptive and beneficial. To define patterns that reflect emotion dysregulation, we explain our views of emotion as a dynamic process, and emotion regulation as the bidirectional interplay between emotions and actions/thoughts (extrinsic factors) and the contextual factors that constitute the criteria for that interplay reflecting dysregulation. This conceptualization of emotion regulation and dysregulation leads to methods for studying the intrinsic dynamics of emotion, extrinsic factors that change the intrinsic dynamics of emotion, and how emotion regulation changes over time at multiple time scales. We then apply this thinking to several emotion dysregulation patterns. Emotion regulation is a complex construct, embracing emotion as regulator and as regulated, as self- and other-regulated, and as incorporating both top-down and bottom-up regulatory processes. We highlight an emerging line of research on the development of emotion regulation in early childhood and indicate how this work can inform understanding of emotion dysregulation and the emergence of psychopathology.
An Open Area Learning Centre
Authors: Amerson George T.
Published: May 2019

This paper describes the programme of an open area learning centre for children with specific learning disabilities. Ninety-five regular school children between the ages of seven and eleven attend the part time remedial centre. An overview of innovative developments within the programme, centre services, modular scheduling, learning stations and programme procedures are discussed. Also mentioned is the implementation of co-operative community efforts and interaction and an interdisciplinary approach designed to provide maximal impact on the education of the children enrolled in the learning centre.
Factors influencing recanalization of thrombotic venous occlusions
Authors: Poredoš Pavel , Poredoš Peter , Jezovnik Mateja Kaja
Published: May 2019

Summary. The outcome of a thrombotic vessel occlusion is related to the resolution of thrombus and restitution of blood flow. Thrombus formation simultaneously activates an enzymatic process that mediates endogenous fibrinolysis to maintain vessel patency. The balance between coagulation and fibrinolysis determines the extent of thrombus formation, its resolution, and clinical outcome. Endogenic fibrinolysis is frequently unable to overcome coagulation and to resolve the thrombus. Therefore, for a complete resolution of thrombus in an acute phase, exogenic fibrinolytic agents are needed. Currently, tissue plasminogen activator (tPA) is most frequently used for therapeutic thrombolysis. Also, heparins, particularly low-molecular-weight heparins and direct oral anticoagulants which are known as anticoagulant drugs, have some pro-fibrinolytic properties. Besides the extent and age of a clot, different other factors influence the lysis of thrombus. Thrombus structure is one of the most important determinants of thrombus lysis. The concentration of thrombolytic agent (tPA) around and inside of thrombus importantly determines clot lysis velocity. Further, flow-induced mechanical forces which stimulate the transport of thrombolytic agent into the clot influence thrombolysis. Inflammation most probably represents a basic pathogenetic mechanism of activation of coagulation and influences the activity of the fibrinolytic system. Inflammation increases tissue factor release, platelet activity, fibrinogen concentration and inhibits fibrinolysis by increasing plasminogen activator inhibitor 1. Therefore, recanalization of a thrombotic vessel occlusion is inversely related to levels of some circulating inflammatory agents. Consequently, inhibition of inflammation with anti-inflammatory drugs may improve the efficacy of prevention of thromboembolic events and stimulate recanalization of thrombotic occlusions of veins.
Benralizumab: Cibler le récepteur de l’IL-5 dans l’asthme sévère éosinophile
Authors: Leuppi Jörg D. , Schmid-Grendelmeier Peter , Rothe Thomas , von Garnier Christophe , Simon Hans-Uwe , Schuoler Claudio , Pendl Gunther , Solèr Markus
Published: May 2019

Zusammenfassung. Für Patienten mit schwierig kontrollierbarem, schwerem Asthma bronchiale stehen heute neben der inhalativen Medikation hochwirksame, gezielte Behandlungsmöglichkeiten zur Verfügung. Bei Vorliegen einer deutlichen Eosinophilie verspricht die Hemmung der Interleukin-5-Achse (IL-5) mit spezifischen, monoklonalen Antikörpern eine wirksame und nebenwirkungsarme Alternative zur dauerhaften systemischen Steroidtherapie. In diesem Übersichtsartikel werden die Daten zu Benralizumab, einem spezifischen Antikörper gegen den IL-5-Rezeptor Alpha, zusammengefasst. Dieser Angriffspunkt verhindert die Rezeptorstimulation durch IL-5 und aktiviert eine NK-zellvermittelte zytotoxische Reaktion, die zur Apoptose der eosinophilen Granulozyten führt. Die s.c.-Applikation von Benralizumab führt innerhalb von Tagen zur nahezu vollständigen Depletion der Eosinophilen im Blut mit konsekutiver Verbesserung der Lungenfunktion und Stabilisierung des Asthmas. Für ausgewählte Patienten mit schwerem Asthma eröffnet sich hier eine vielversprechende Therapie-Option.
Event Size Distribution of Shallow Tectonic Tremor in the Nankai Trough
Authors: Nakano Masaru , Yabe Suguru , Sugioka Hiroko , Shinohara Masanao , Ide Satoshi
Published: May 2019

Slow earthquake size distributions have been found to follow either a power law or an exponential law, depending on the data set. We investigated the size distribution of shallow tectonic tremor events along the Nankai trough, southwestern Japan, observed in 2009, 2015, 2016, and 2018 and estimated the seismic energy radiated during the events as a measure of event size. The obtained size distributions mostly followed a power law with a b value of about 1, but an exponential law also fits well the data of the largest events; this result indicates that the size distribution follows the Gutenberg‐Richter law with an exponential taper. If only the largest events were observed, an exponential size distribution would be obtained. This exponential taper could be attributed to a source fault limitation. Because the maximum event size differed among activity periods, the source fault size varied among them, although the source areas largely overlap.
ZCCHC10 suppresses lung cancer progression and cisplatin resistance by attenuating MDM2-mediated p53 ubiquitination and degradation
Authors: Ning Yichong , Hui Na , Qing Bei , Zhuo Yiming , Sun Wei , Du Yan , Liu Shunlian , Liu Kaili , Zhou Jianlin
Published: May 2019

The activation of p53 tumor suppressor is essential for preventing abnormal cell proliferation and carcinogenesis. ZCCHC10 was previously identified as a potential p53-interacting partner in a yeast two-hybrid screen, but the interaction in cells and its subsequent influence on p53 activity and cancer development have not been investigated. In this paper, we demonstrate that ZCCHC10 expression levels are statistically lower in lung adenocarcinoma tissues than the corresponding adjacent noncancerous tissues, and decreased expression of ZCCHC10 mRNA predicts poorer survival of the patients. Ectopic expression of ZCCHC10 in lung cancer cells harboring wild-type p53 dramatically suppresses cell proliferation, colony formation, migration, invasion and cisplatin resistance in vitro, as well as tumor growth and metastasis in vivo. Conversely, knockdown of ZCCHC10 exerts opposite effects in the normal lung cell Beas-2b. However, ZCCHC10 has no influence on the biological behaviors of p53-null (H358) or p53-mutant (H1437) lung cancer cells. Mechanistically, ZCCHC10 binds and stabilizes p53 by disrupting the interaction between p53 and MDM2. The p53 inhibitor pifithrin-α attenuated the influences of ZCCHC10 overexpression on p53 pathway, cell cycle, apoptosis, and epithelial-mesenchymal transition, whereas the p53 activator Nutlin3 could reverse the effects of ZCCHC10 knockdown. Collectively, our results indicate that ZCCHC10 exerts its tumor-suppressive effects by stabilizing the p53 protein and can be used a potential prognostic marker and therapeutic target in lung adenocarcinoma.
Inhibition of eIF2α dephosphorylation accelerates pterostilbene-induced cell death in human hepatocellular carcinoma cells in an ER stress and autophagy-dependent manner
Authors: Yu Chen-Lin , Yang Shun-Fa , Hung Tung-Wei , Lin Chia-Liang , Hsieh Yi-Hsien , Chiou Hui-Ling
Published: May 2019

Hepatocellular carcinoma (HCC) is the one of the most common cancers worldwide. Because the side effects of current treatments are severe, new effective therapeutic strategies are urgently required. Pterostilbene (PT), a natural analogue of resveratrol, has diverse pharmacologic activities, including antioxidative, anti-inflammatory and antiproliferative activities. Here we demonstrated that PT inhibits HCC cell growth without the induction of apoptosis in an endoplasmic reticulum (ER) stress- and autophagy-dependent manner. Mechanistic studies indicated that the combination of salubrinal and PT modulates ER stress-related autophagy through the phospho-eukaryotic initiation factor 2α/activating transcription factor-4/LC3 pathway, leading to a further inhibition of eIF2α dephosphorylation and the potentiation of cell death. An in vivo xenograft analysis revealed that PT significantly reduced tumour growth in mice with a SK-Hep-1 tumour xenograft. Taken together, our results yield novel insights into the pivotal roles of PT in ER stress- and autophagy-dependent cell death in HCC cells.
The Role of Myokines and Adipokines in Hypertension and Hypertension-related Complications
Authors: Chen Ken , Zhou Mengdi , Wang Xiaomei , Li Shuang , Yang Dachun
Published: May 2019

The cross-talk between skeletal muscle and adipose tissue has been identified to play a key role in the regulation of blood pressure and the development of hypertension. The role of different adipokines and myokines in hypertension and hypertension-related complications remains unclear. In the present study, 98 hypertensive patients and 24 normotensive controls were recruited, and additional subgroup analyses of hypertension-related complications were also performed. The levels of the circulating bone-derived factors leptin, apelin, fractalkine, brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), myostatin, fatty-acid-binding protein 3 (FABP3), irisin, follistatin-related protein 1 (FSTL1), oncostatin M, fibroblast growth factor 21 (FGF21) and musclin were measured by a protein liquid chip assay. The circulating levels of BDNF and musclin were decreased, whereas the leptin and irisin levels were increased, in hypertensive patients compared with those in the control individuals. Further logistic analysis indicated that the irisin level was positively correlated with SBP and an independent predictor for hypertension after adjustment. In nonobese subjects, the concentrations of DKK1, BDNF and FSTL1 were decreased, whereas the concentrations of leptin and irisin were increased. Irisin and DKK1 might be associated with hypertension. Additional subgroup analyses showed that irisin is significantly associated with hypertension-related stroke. In conclusion, we found that increased irisin levels are associated with hypertension and hypertension-related stroke. These findings indicate that irisin may be involved in the pathophysiology of hypertension.
Promoting abnormal grain growth in Fe-based shape memory alloys through compositional adjustments
Authors: Vollmer M. , Arold T. , Kriegel M. J. , Klemm V. , Degener S. , Freudenberger J. , Niendorf T.
Published: May 2019

Iron-based shape memory alloys are promising candidates for large-scale structural applications due to their cost efficiency and the possibility of using conventional processing routes from the steel industry. However, recently developed alloy systems like Fe–Mn–Al–Ni suffer from low recoverability if the grains do not completely cover the sample cross-section. To overcome this issue, here we show that small amounts of titanium added to Fe–Mn–Al–Ni significantly enhance abnormal grain growth due to a considerable refinement of the subgrain sizes, whereas small amounts of chromium lead to a strong inhibition of abnormal grain growth. By tailoring and promoting abnormal grain growth it is possible to obtain very large single crystalline bars. We expect that the findings of the present study regarding the elementary mechanisms of abnormal grain growth and the role of chemical composition can be applied to tailor other alloy systems with similar microstructural features.
An accurate prediction model to identify undiagnosed at-risk patients with COPD: a cross-sectional case-finding study
Authors: Su Kang-Cheng , Ko Hsin-Kuo , Chou Kun-Ta , Hsiao Yi-Han , Su Vincent Yi-Fong , Perng Diahn-Warng , Kou Yu Ru
Published: May 2019

Underuse or unavailability of spirometry is one of the most important factors causing underdiagnosis of COPD. We reported the development of a COPD prediction model to identify at-risk, undiagnosed COPD patients when spirometry was unavailable. This cross-sectional study enrolled subjects aged ≥40 years with respiratory symptoms and a smoking history (≥20 pack-years) in a medical center in two separate periods (development and validation cohorts). All subjects completed COPD assessment test (CAT), peak expiratory flow rate (PEFR) measurement, and confirmatory spirometry. A binary logistic model with calibration (Hosmer-Lemeshow test) and discrimination (area under receiver operating characteristic curve [AUROC]) was implemented. Three hundred and one subjects (development cohort) completed the study, including non-COPD (154, 51.2%) and COPD cases (147; stage I, 27.2%; II, 55.8%; III–IV, 17%). Compared with non-COPD and GOLD I cases, GOLD II-IV patients exhibited significantly higher CAT scores and lower lung function, and were considered clinically significant for COPD. Four independent variables (age, smoking pack-years, CAT score, and percent predicted PEFR) were incorporated developing the prediction model, which estimated the COPD probability (PCOPD). This model demonstrated favorable discrimination (AUROC: 0.866/0.828; 95% CI 0.825–0.906/0.751–0.904) and calibration (Hosmer-Lemeshow P = 0.332/0.668) for the development and validation cohorts, respectively. Bootstrap validation with 1000 replicates yielded an AUROC of 0.866 (95% CI 0.821–0.905). A PCOPD of ≥0.65 identified COPD patients with high specificity (90%) and a large proportion (91.4%) of patients with clinically significant COPD (development cohort). Our prediction model can help physicians effectively identify at-risk, undiagnosed COPD patients for further diagnostic evaluation and timely treatment when spirometry is unavailable.
Structural characterization of a protein adsorbed on aluminum hydroxide adjuvant in vaccine formulation
Authors: Cerofolini Linda , Giuntini Stefano , Ravera Enrico , Luchinat Claudio , Berti Francesco , Fragai Marco
Published: May 2019

The heterogeneous composition of vaccine formulations and the relatively low concentration make the characterization of the protein antigens extremely challenging. Aluminum-containing adjuvants have been used to enhance the immune response of several antigens over the last 90 years and still remain the most commonly used. Here, we show that solid-state NMR and isotope labeling methods can be used to characterize the structural features of the protein antigen component of vaccines and to investigate the preservation of the folding state of proteins adsorbed on Alum hydroxide matrix, providing the way to identify the regions of the protein that are mainly affected by the presence of the inorganic matrix.l-Asparaginase fromE. colihas been used as a pilot model of protein antigen. This methodology can find application in several steps of the vaccine development pipeline, from the antigen optimization, through the design of vaccine formulation, up to stability studies and manufacturing process.
The FLUXCOM ensemble of global land-atmosphere energy fluxes
Authors: Jung Martin , Koirala Sujan , Weber Ulrich , Ichii Kazuhito , Gans Fabian , Camps-Valls Gustau , Papale Dario , Schwalm Christopher , Tramontana Gianluca , Reichstein Markus
Published: May 2019

Although a key driver of Earth’s climate system, global land-atmosphere energy fluxes are poorly constrained. Here we use machine learning to merge energy flux measurements from FLUXNET eddy covariance towers with remote sensing and meteorological data to estimate global gridded net radiation, latent and sensible heat and their uncertainties. The resulting FLUXCOM database comprises 147 products in two setups: (1) 0.0833° resolution using MODIS remote sensing data (RS) and (2) 0.5° resolution using remote sensing and meteorological data (RS + METEO). Within each setup we use a full factorial design across machine learning methods, forcing datasets and energy balance closure corrections. For RS and RS + METEO setups respectively, we estimate 2001–2013 global (±1 s.d.) net radiation as 75.49 ± 1.39 W m−2 and 77.52 ± 2.43 W m−2, sensible heat as 32.39 ± 4.17 W m−2 and 35.58 ± 4.75 W m−2, and latent heat flux as 39.14 ± 6.60 W m−2 and 39.49 ± 4.51 W m−2 (as evapotranspiration, 75.6 ± 9.8 × 103 km3 yr−1 and 76 ± 6.8 × 103 km3 yr−1). FLUXCOM products are suitable to quantify global land-atmosphere interactions and benchmark land surface model simulations.
A rapid beam simulation framework for transcranial focused ultrasound
Authors: Leung Steven A. , Webb Taylor D. , Bitton Rachelle R. , Ghanouni Pejman , Butts Pauly Kim
Published: May 2019

Transcranial focused ultrasound is a non-invasive therapeutic modality that can be used to treat essential tremor. Beams of energy are focused into a small spot in the thalamus, resulting in tissue heating and ablation. Here, we report on a rapid 3D numeric simulation framework that can be used to predict focal spot characteristics prior to the application of ultrasound. By comparing with magnetic resonance proton resonance frequency shift thermometry (MR thermometry) data acquired during treatments of essential tremor, we verified that our simulation framework can be used to predict focal spot position, and with patient-specific calibration, predict focal spot temperature rise. Preliminary data suggests that lateral smearing of the focal spot can be simulated. The framework may also be relevant for other therapeutic ultrasound applications such as blood brain barrier opening and neuromodulation.
Genetic homogenization of indigenous sheep breeds in Northwest Africa
Authors: Belabdi Ibrahim , Ouhrouch Abdessamad , Lafri Mohamed , Gaouar Semir Bechir Suheil , Ciani Elena , Benali Ahmed Redha , Ould Ouelhadj Hakim , Haddioui Abdelmajid , Pompanon François , Blanquet Véronique , Taurisson-Mouret Dominique , Harkat Sahraoui , Lenstra Johannes A. , Benjelloun Badr , Da Silva Anne
Published: May 2019

Northwest-African sheep represent an ideal case-study for assessing the potential impact of genetic homogenization as a threat to the future of traditional breeds that are adapted to local conditions. We studied ten Algerian and Moroccan breeds of sheep, including three transboundary breeds, distributed over a large part of the Maghreb region, which represents a geographically and historically coherent unit. Our analysis of the dataset that involved carrying out Genome-wide SNP genotyping, revealed a high level of homogenization (ADMIXTURE, NetView, fineSTRUCTURE and IBD segments analyses), in such a way that some breeds from different origins appeared genetically undistinguished: by grouping the eight most admixed populations, we obtained a mean global FST value of 0.0024. The sPCA analysis revealed that the major part of Morocco and the Northern part of Algeria were affected by the phenomenon, including most of the breeds considered. Unsupervised cross-breeding with the popular Ouled-Djellal breed was identified as a proximate cause of this homogenization. The issue of transboundary breeds was investigated, and the Hamra breed in particular was examined via ROH fragments analysis. Genetic diversity was considered in the light of historical archives and anthropological works. All of these elements taken together suggest that homogenization as a factor affecting the Maghrebin sheep stock, has been particularly significant over the last few decades, although this process probably started much earlier. In particular, we have identified the policies set by the French administration during the colonial period of the region’s history as a causal factor that probably contributed significantly to this process. The genetic homogenization that we have observed calls into question the integrity of the farm animal genomic resources represented by these local breeds, whose conservation is of critical importance to the future of the livestock sector.
BD-2 and BD-3 increase skin flap survival in a model of ischemia and Pseudomonas aeruginosa infection
Authors: Casal Diogo , Iria Inês , Ramalho José S. , Alves Sara , Mota-Silva Eduarda , Mascarenhas-Lemos Luís , Pontinha Carlos , Guadalupe-Cabral Maria , Ferreira-Silva José , Ferraz-Oliveira Mário , Vassilenko Valentina , Goyri-O’Neill João , Pais Diogo , Videira Paula A.
Published: May 2019

The main aim of this work was to study the usefulness of human β-defensins 2 (BD-2) and 3 (BD-3), which are part of the innate immune system, in the treatment of infected ischemic skin flaps. We investigated the effect of transducing rat ischemic skin flaps with lentiviral vectors encoding human BD-2, BD-3, or both BD-2 and BD-3, to increase flap survival in the context of a P. aeruginosa infection associated with a foreign body. The secondary endpoints assessed were: bacterial counts, and biofilm formation on the surface of the foreign body. A local ischemic environment was created by producing arterialized venous flaps in the left epigastric region of rats. Flaps were intentionally infected by placing underneath them two catheters with 105 CFU of P. aeruginosa before the surgical wounds were hermetically closed. Flap biopsies were performed 3 and 7 days post-operatively, and the specimens submitted to immunohistochemical analysis for BD-2 and BD-3, as well as to bacterial quantification. Subsequently, the catheter segments were analyzed with scanning electron microscopy (SEM). Flaps transduced with BD-2 and BD-3 showed expression of these defensins and presented increased flap survival. Rats transduced with BD-3 presented a net reduction in the number of P. aeruginosa on the surface of the foreign body and lesser biofilm formation.
Gcm1 is involved in cell proliferation and fibrosis during kidney regeneration after ischemia–reperfusion injury
Authors: Kamejima Sahoko , Tatsumi Norifumi , Anraku Akane , Suzuki Hideaki , Ohkido Ichiro , Yokoo Takashi , Okabe Masataka
Published: May 2019

In acute kidney injury (AKI), the S3 segment of the proximal tubule is particularly damaged, as it is most vulnerable to ischemia. However, this region is also involved in renal tubular regeneration. To deeply understand the mechanism of the repair process after ischemic injury in AKI, we focused on glial cells missing 1 (Gcm1), which is one of the genes expressed in the S3 segment. Gcm1 is essential for the development of the placenta, and Gcm1 knockout (KO) is embryonically lethal. Thus, the function of Gcm1 in the kidney has not been analyzed yet. We analyzed the function of Gcm1 in the kidney by specifically knocking out Gcm1 in the kidney. We created an ischemia–reperfusion injury (IRI) model to observe the repair process after AKI. We found that Gcm1 expression was transiently increased during the recovery phase of IRI. In Gcm1 conditional KO mice, during the recovery phase of IRI, tubular cell proliferation reduced and transforming growth factor-β1 expression was downregulated resulting in a reduction in fibrosis. In vitro, Gcm1 overexpression promoted cell proliferation and upregulated TGF-β1 expression. These findings indicate that Gcm1 is involved in the mechanisms of fibrosis and cell proliferation after ischemic injury of the kidney.
Rapid discrimination of multiple myeloma patients by artificial neural networks coupled with mass spectrometry of peripheral blood plasma
Authors: Deulofeu Meritxell , Kolářová Lenka , Salvadó Victoria , María Peña-Méndez Eladia , Almáši Martina , Štork Martin , Pour Luděk , Boadas-Vaello Pere , Ševčíková Sabina , Havel Josef , Vaňhara Petr
Published: May 2019

Multiple myeloma (MM) is a highly heterogeneous disease of malignant plasma cells. Diagnosis and monitoring of MM patients is based on bone marrow biopsies and detection of abnormal immunoglobulin in serum and/or urine. However, biopsies have a single-site bias; thus, new diagnostic tests and early detection strategies are needed. Matrix-Assisted Laser Desorption/Ionization Time-of Flight Mass Spectrometry (MALDI-TOF MS) is a powerful method that found its applications in clinical diagnostics. Artificial intelligence approaches, such as Artificial Neural Networks (ANNs), can handle non-linear data and provide prediction and classification of variables in multidimensional datasets. In this study, we used MALDI-TOF MS to acquire low mass profiles of peripheral blood plasma obtained from MM patients and healthy donors. Informative patterns in mass spectra served as inputs for ANN that specifically predicted MM samples with high sensitivity (100%), specificity (95%) and accuracy (98%). Thus, mass spectrometry coupled with ANN can provide a minimally invasive approach for MM diagnostics.
Interactions between egocentric and allocentric spatial coding of sounds revealed by a multisensory learning paradigm
Authors: Rabini Giuseppe , Altobelli Elena , Pavani Francesco
Published: May 2019

Although sound position is initially head-centred (egocentric coordinates), our brain can also represent sounds relative to one another (allocentric coordinates). Whether reference frames for spatial hearing are independent or interact remained largely unexplored. Here we developed a new allocentric spatial-hearing training and tested whether it can improve egocentric sound-localisation performance in normal-hearing adults listening with one ear plugged. Two groups of participants (N = 15 each) performed an egocentric sound-localisation task (point to a syllable), in monaural listening, before and after 4-days of multisensory training on triplets of white-noise bursts paired with occasional visual feedback. Critically, one group performed an allocentric task (auditory bisection task), whereas the other processed the same stimuli to perform an egocentric task (pointing to a designated sound of the triplet). Unlike most previous works, we tested also a no training group (N = 15). Egocentric sound-localisation abilities in the horizontal plane improved for all groups in the space ipsilateral to the ear-plug. This unexpected finding highlights the importance of including a no training group when studying sound localisation re-learning. Yet, performance changes were qualitatively different in trained compared to untrained participants, providing initial evidence that allocentric and multisensory procedures may prove useful when aiming to promote sound localisation re-learning.
Combined predictive effects of sentential and visual constraints in early audiovisual speech processing
Authors: Solberg Økland Heidi , Todorović Ana , Lüttke Claudia S. , McQueen James M. , de Lange Floris P.
Published: May 2019

In language comprehension, a variety of contextual cues act in unison to render upcoming words more or less predictable. As a sentence unfolds, we use prior context (sentential constraints) to predict what the next words might be. Additionally, in a conversation, we can predict upcoming sounds through observing the mouth movements of a speaker (visual constraints). In electrophysiological studies, effects of visual constraints have typically been observed early in language processing, while effects of sentential constraints have typically been observed later. We hypothesized that the visual and the sentential constraints might feed into the same predictive process such that effects of sentential constraints might also be detectable early in language processing through modulations of the early effects of visual salience. We presented participants with audiovisual speech while recording their brain activity with magnetoencephalography. Participants saw videos of a person saying sentences where the last word was either sententially constrained or not, and began with a salient or non-salient mouth movement. We found that sentential constraints indeed exerted an early (N1) influence on language processing. Sentential modulations of the N1 visual predictability effect were visible in brain areas associated with semantic processing, and were differently expressed in the two hemispheres. In the left hemisphere, visual and sentential constraints jointly suppressed the auditory evoked field, while the right hemisphere was sensitive to visual constraints only in the absence of strong sentential constraints. These results suggest that sentential and visual constraints can jointly influence even very early stages of audiovisual speech comprehension.
Graphene nanosheet-grafted double-walled carbon nanotube hybrid nanostructures by two-step chemical vapor deposition and their application for ethanol detection
Authors: Muangrat Worawut , Wongwiriyapan Winadda , Morimoto Shingo , Hashimoto Yoshio
Published: May 2019

Here, we present a facile technique for synthesis of graphene nanosheet (GNS)-grafted double-walled carbon nanotube (DWCNT) hybrid carbon nanostructures (here after referred to as G-DWCNTs) by directly growing GNSs along the sidewalls of DWCNTs using a two-step chemical vapor deposition (CVD). DWCNTs were synthesized by floating catalyst CVD at 1300 °C using ferrocene and thiophene dissolved in ethanol. Then, GNSs were grafted onto the synthesized DWCNT bundles by thermal CVD at 1300 °C using ethanol. The sharp-edged petal-like structure of GNSs were grown along the sidewalls of DWCNT bundles while maintaining the one-dimensional structure of DWCNT. Next, DWCNTs and G-DWCNTs were dispersed in ethanol, then deposited on the paper using vacuum filtration method and used for ethanol detection. G-DWCNTs sensor exhibited a 3-fold improvement in the response to ethanol vapor compared to the DWCNTs sensor. The sensing mechanism of DWCNTs and G-DWCNTs can be described in terms of charge transfer between the gas molecules and sensing material. These results demonstrate that the facile technique by two-step CVD method provides a promising approach for simple and low-cost technique to synthesize the hybrid nanostructure of GNSs and DWCNTs. The new hybrid carbon nanostructures are attractive for gas sensing application.
Simultaneous Coinfection of Macaques with Zika and Dengue Viruses Does not Enhance Acute Plasma Viremia but Leads to Activation of Monocyte Subsets and Biphasic Release of Pro-inflammatory Cytokines
Authors: Valiant William G. , Mattapallil Mary J. , Higgs Stephen , Huang Yan-Jang S. , Vanlandingham Dana L. , Lewis Mark G. , Mattapallil Joseph J.
Published: May 2019

The consequences of simultaneous infection with Zika (ZIKV) and Dengue (DENV) viruses are poorly understood. Here we show that rhesus macaques experimentally coinfected simultaneously with ZIKV and DENV-2 demonstrated ZIKV or DENV replication without an enhancement of either infection. Coinfection was accompanied by an increase in the proportions of CD14+CD16+ pro-inflammatory subsets of monocytes and release of pro-inflammatory cytokines in the plasma. Numerous cytokines such as I-TAC, Eotaxin, RANTES, MCP-1, IFNγ and MIG demonstrated a biphasic peak that coincided with the differences in kinetics of ZIKV and DENV replication suggesting that viral replication likely differentially modulated the release of these cytokines. Red blood cell indices significantly declined during acute infection suggesting transient anemia, and was accompanied by elevated levels of muscle, liver and renal injury markers. These findings have implications for understanding the pathogenesis of coinfection in ZIKV and DENV endemic regions, and is the 1st report of an experimental coinfection using the rhesus macaque model for ZIKV and DENV infections.
Breed differences of heritable behaviour traits in cats
Authors: Salonen Milla , Vapalahti Katariina , Tiira Katriina , Mäki-Tanila Asko , Lohi Hannes
Published: May 2019

Cat domestication and selective breeding have resulted in tens of breeds with major morphological differences. These breeds may also show distinctive behaviour differences; which, however, have been poorly studied. To improve the understanding of feline behaviour, we examined whether behavioural differences exist among cat breeds and whether behaviour is heritable. For these aims, we utilized our extensive health and behaviour questionnaire directed to cat owners and collected a survey data of 5726 cats. Firstly, for studying breed differences, we utilized logistic regression models with multiple environmental factors and discovered behaviour differences in 19 breeds and breed groups in ten different behaviour traits. Secondly, the studied cat breeds grouped into four clusters, with the Turkish Van and Angora cats alone forming one of them. These findings indicate that cat breeds have diverged not only morphologically but also behaviourally. Thirdly, we estimated heritability in three breeds and obtained moderate heritability estimates in seven studied traits, varying from 0.4 to 0.53, as well as phenotypic and genetic correlations for several trait pairs. Our results show that it is possible to partition the observed variation in behaviour traits into genetic and environmental components, and that substantial genetic variation exists within breed populations.
Composition and content analysis of fluoride in inorganic salts of the integument of Antarctic krill (Euphausia superba)
Authors: Peng Yuanhuai , Ji Wei , Zhang Di , Ji Hongwu , Liu Shucheng
Published: May 2019

Ash of Antarctic krill integument (AAKI) was prepared by sintering the integument at 550°C under air atmosphere for 4 hours, and its composition was analyzed by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FTIR) and electron dispersive spectroscopy (EDS). XRD results showed that the major phase in AAKI was ascribed to apatite. Besides, it was noticed that the (300) peak of AAKI shifted to 33.07°, which was coincident with that of fluorapatite (FA). The FTIR results confirmed the presence of phosphate ions, and the absence of -OH. The EDS results confirmed the presence of Ca, P, O and F elements in the ash sample. The content of FA in the ash was determined to be 50.4%, and the proportion of fluorine in the form of FA to the total fluorine in the integument was 40.5%. Based on the XRD, FTIR and EDS results, it can be concluded that FA was the main form of fluoride in the integument of Antarctic krill.
Intermittent screening and treatment with dihydroartemisinin-piperaquine and intermittent preventive therapy with sulfadoxine-pyrimethamine have similar effects on malaria antibody in pregnant Malawian women
Authors: Teo Andrew , Randall Louise M. , Madanitsa Mwayiwawo , Mwapasa Victor , Phiri Linda Kalilani , Khairallah Carole , Buffet Christelle , Karahalios Amalia , Narum David L. , Kuile Feiko O. Ter , Rogerson Stephen J.
Published: May 2019

In a randomised trial comparing intermittent screening and treatment (IST) with dihydroartemisinin-piperaquine (DP) and intermittent preventive therapy against malaria in pregnancy (IPT) with sulfadoxine-pyrimethamine (SP) in Malawi, the impacts of IST-DP and IPT-SP on the development and maintenance of malaria antibody immunity were compared. Pregnant Malawian women were randomised to receive IST-DP or IPT-SP. In a nested study, paired enrolment and delivery plasma samples from 681 women were assayed for antibodies against recombinant antigens and for IgG and opsonising antibodies to antigens found on infected erythrocytes (IEs). At delivery, antibody responses did not differ between study arms. Between enrolment and delivery, antibodies to recombinant antigens decreased, whereas antibodies to IEs including opsonising antibodies remained stable. Overall, changes in antibody responses over pregnancy did not differ by treatment arm. Stratifying by gravidity, antibody to schizont extract decreased more in multigravidae receiving IST-DP than IPT-SP. There was minimal impact of treatment arm on the development and maintenance of malaria immunity. While antibodies to recombinant antigens declined between enrolment and delivery, antibodies directed against IEs tended to be more stable, suggesting longer-lasting protection.

Clinical trial registration: Pa n African Clinical Trials Registry (PACTR201103000280319) 14/03/2011. URL: http://www.isrctn.com/ISRCTN69800930.