bluuebunny/crossref_metadata_2025 huggingface dataset:
Metal‐Organic Framework/Layered Carbon Nitride Nano–sandwiches for Superior Asymmetric Supercapacitor
Authors: Ma Longtao , Fan Huiqing , Fu Ke , Zhao Yuwei
Published: August 2016

The Fe‐doped Zeolitic Imidazolate Frameworks/layered CN nano‐sandwiches (Fe‐ZIF/CN) and porous C/layered CN nano‐sandwiches (porous C/CN) were synthesized from a single Metal‐Organic Frameworks/layered CN nano‐sandwich precursor. The Fe‐ZIF/CN and porous C/CN electrode possessed high specific surface area for 1609 and 2048 m2⋅g−1 respectively and they showed high capacitance values for 1096 and 587 F⋅g−1 at the current density of 1 A g−1 under three electrode configuration. The electrochemical performance and stable potential windows of the asymmetric supercapacitors (ASCs) based on FeZIF/CN nano‐sandwiches (positive electrode) and porous C/CN (negative electrode) were further evaluated. The high energy density supercapacitor was successfully realized by the appliances (Fe‐ZIF/CN//porous C/CN), much better than those of the SSCs based on porous C/CN or Fe‐ZIF/CN electrode materials. The advanced ASCs could work within a wide potential window of 0–1.6 V, which contributed to a high specific energy density of 153 W⋅h⋅kg−1. The superior performance was ascribed to the high capacitance and the positive synergistic effects of the two electrodes. These encouraging results revealed a potential in exploiting energy storage appliance with high energy density and power density appliance for practical applications.
Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer
Authors: Ostadhossein Fatemeh , Misra Santosh K. , Mukherjee Prabuddha , Ostadhossein Alireza , Daza Enrique , Tiwari Saumya , Mittal Shachi , Gryka Mark C. , Bhargava Rohit , Pan Dipanjan
Published: August 2016

Signal transducer and activator of transcription factor 3 (STAT‐3) is known to be overexpressed in cancer stem cells. Poor solubility and variable drug absorption are linked to low bioavailability and decreased efficacy. Many of the drugs regulating STAT‐3 expression lack aqueous solubility; hence hindering efficient bioavailability. A theranostics nanoplatform based on luminescent carbon particles decorated with cucurbit[6]uril is introduced for enhancing the solubility of niclosamide, a STAT‐3 inhibitor. The host–guest chemistry between cucurbit[6]uril and niclosamide makes the delivery of the hydrophobic drug feasible while carbon nanoparticles enhance cellular internalization. Extensive physicochemical characterizations confirm successful synthesis. Subsequently, the host–guest chemistry of niclosamide and cucurbit[6]uril is studied experimentally and computationally. In vitro assessments in human breast cancer cells indicate approximately twofold enhancement in IC50 of drug. Fourier transform infrared and fluorescence imaging demonstrate efficient cellular internalization. Furthermore, the catalytic biodegradation of the nanoplatforms occur upon exposure to human myeloperoxidase in short time. In vivo studies on athymic mice with MCF‐7 xenograft indicate the size of tumor in the treatment group is half of the controls after 40 d. Immunohistochemistry corroborates the downregulation of STAT‐3 phosphorylation. Overall, the host–guest chemistry on nanocarbon acts as a novel arsenal for STAT‐3 inhibition.
Tailor–made Covalent Organic‐Inorganic Polyoxometalate Hybrids: Versatile Platforms for the Elaboration of Functional Molecular Architectures
Authors: Izzet Guillaume , Volatron Florence , Proust Anna
Published: August 2016

Post‐functionalization of organically modified polyoxometalates (POMs) is a powerful synthetic tool to devise functional building blocks for the rational elaboration of POM‐based molecular materials. In this personal account we focus on iodoaryl‐terminated POM platforms, describe reliable routes to the synthesis of covalent organic‐inorganic POM‐based hybrids and their integration into advanced molecular architectures or multi‐scale assemblies as well as their immobilization onto surfaces. Valorisation of the remarkable redox properties of POMs in the fields of artificial synthesis and molecular electronic is especially considered.
Microwave effects on montmorillonite reinforced polyvinyl alcohol‐starch nanocomposite
Authors: Sin Lee Tin , Bee Soo‐Tueen , Wah Tee‐Yan , Chee Tze‐Ming , Kadhum Abdul Amir H. , Rahmat Abdul Razak
Published: August 2016

This study aims to investigate microwaves’ effects on montmorillonite (MMT) reinforced polyvinyl alcohol (PVOH)/starch blends. Microwave irradiation at a power range 50–250 W was applied to the nanocomposites. Generally, when MMT was added to PVOH‐starch blends without microwave irradiation, the poor distribution of MMT particles in the polymer matrix impaired the mechanical properties of the composite. Microwave irradiation generally improved tensile strength of the nanocomposites. More powerful microwaves were needed for high amounts of MMT to obtain promising properties. A smooth morphology could be observed in SEM micrographs when the nanocomposites were subjected to microwaves, where the MMT particles were embedded into the polymer matrix. Infrared spectroscopy found a “red shift” effect where higher microwave power produced nanocomposites with overall lower wavenumbers, indicating better hydrogen bonding. This can be explained by high microwave power promoting the polar reorientation that enables better linkage between ‐OH groups from both the PVOH and starch. Finally, XRD analysis revealed that higher microwave power would improve the dispersion of MMT particles by reducing the agglomeration of MMT particles in the polymer matrix. In conclusion, the application of microwave irradiation is preferable to keep at 100‐150 W to achieve better properties of PVOH‐starch‐MMT nanocomposites. J. VINYL ADDIT. TECHNOL., 23:E142–E151, 2017. © 2016 Society of Plastics Engineers
An α‐{P2W18O62}6–‐Based Supramolecular Hybrid Inorganic‐Organic Compound with Visible Light‐Driven Photocatalytic Properties
Authors: Zhu Xiaofei , Yang Yu , Jiang Ni , Li Bo , Fu Hai , Yin Zifan , Yang Jun
Published: August 2016

The α‐[P2W18O62]6–‐based coordination polymer [Cu2(phen)3(H2O)3(P2W18O62)][Cu(phen)2(H2O)]·5H2O (1) (phen = phenanthroline), was hydrothermally synthesized and characterized by single‐crystal and powder X‐ray diffraction, IR and UV/Vis diffuse reflection spectroscopy, and elemental analysis. Structural studies reveal that compound 1 exhibits a three‐dimensional (3D) supramolecular structure based on π–π and hydrogen bonding interactions. In addition, visible light driven photocatalytic experiments of compound 1 were also studied.
Metabolic Surgery for Diabetes Treatment: Sleeve Gastrectomy or Gastric Bypass?
Authors: Lee Wei‐Jei , Chong Keong , Aung Lwin , Chen Shu‐Chun , Ser Kong‐Han , Lee Yi‐Chih
Published: August 2016

Background

Bariatric surgery has gained reputation for its metabolic effect and is increasingly being performed to treat type 2 diabetes mellitus (T2DM). However, there is still a gray area regarding the choice of surgical procedure according to patient characteristics due to inadequate evidences, so far. We aim to compare the efficacy of two most commonly performed bariatric/metabolic surgeries, sleeve gastrectomy (SG) and gastric bypass (GB) with regard to remission of T2DM after surgery.

Methods

Outcomes of 579 (349 female and 230 male) patients who had undergone SG (109) or GB (470) for the treatment of T2DM with 1‐year follow‐up were assessed. The remission of T2DM after SG or GB surgery was evaluated in matched groups using the ABCD scoring system. The ABCD score is composed of the age, BMI, C‐peptide levels and duration of T2DM (years).

Results

The weight loss of the SG patient at 1 year after surgery was similar to the GB patients [26.3 (1.1) vs. 32.6 (1.2) %; p = 0.258]. The mean BMI decreased from 35.7 (7.2) to 28.3 (3.7) Kg/m2 in SG patients at 1 year after surgery and decreased from 36.9 (7.2) to 26.7 (4.5) Kg/m2 in the GB patients. The mean HbA1c decreased from 8.8 to 6.1 % of the SG group and from 8.6 to 5.9 % of the GB group. Sixty‐one (56.0 %) patients of the SG group and 300 (63.8 %) of the GB group achieved complete remission of T2DM (HbA1c < 6.0 %) at 1 year after surgery without statistical difference. However, GB exhibited significantly better glycemic control than the SG surgery in groups stratified by different ABCD score. At 5 year after surgery, GB had a better remission of T2DM than SG (53.1 vs. 35.3 %; p = 0.055).

Conclusions

In conclusion, although both SG and GB are effective metabolic surgery, GB carries a higher power on T2DM remission than SG. ABCD score is useful in T2DM patient classification and selection for different procedures.
Guidelines for Perioperative Care for Liver Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations
Authors: Melloul Emmanuel , Hübner Martin , Scott Michael , Snowden Chris , Prentis James , Dejong Cornelis H. C. , Garden O. James , Farges Olivier , Kokudo Norihiro , Vauthey Jean‐Nicolas , Clavien Pierre‐Alain , Demartines Nicolas
Published: August 2016

Background

Enhanced Recovery After Surgery (ERAS) is a multimodal pathway developed to overcome the deleterious effect of perioperative stress after major surgery. In colorectal surgery, ERAS pathways reduced perioperative morbidity, hospital stay and costs. Similar concept should be applied for liver surgery. This study presents the specific ERAS Society recommendations for liver surgery based on the best available evidence and on expert consensus.

Methods

A systematic review was performed on ERAS for liver surgery by searching EMBASE and Medline. Five independent reviewers selected relevant articles. Quality of randomized trials was assessed according to the Jadad score and CONSORT statement. The level of evidence for each item was determined using the GRADE system. The Delphi method was used to validate the final recommendations.

Results

A total of 157 full texts were screened. Thirty‐seven articles were included in the systematic review, and 16 of the 23 standard ERAS items were studied specifically for liver surgery. Consensus was reached among experts after 3 rounds. Prophylactic nasogastric intubation and prophylactic abdominal drainage should be omitted. The use of postoperative oral laxatives and minimally invasive surgery results in a quicker bowel recovery and shorter hospital stay. Goal‐directed fluid therapy with maintenance of a low intraoperative central venous pressure induces faster recovery. Early oral intake and mobilization are recommended. There is no evidence to prefer epidural to other types of analgesia.

Conclusions

The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol.
The Effect of Fluoropolymer on Wettability Alteration of Sandstone at Elevated Temperatures
Authors: Jin Jiafeng , Wang Yanling , Ren Jinheng , Nguyen Anh V. , Nguyen Tuan A. H.
Published: August 2016

Gas condensate reservoirs are generally recovered using a pressure depletion drive. Gas can condensate into the liquid phase near the wellbore region when the reservoir pressure falls below the dew point pressure, which can kill gas deliverability. Wettability alteration is an effective means of overcoming this problem; core wettability can be altered from liquid‐wet to gas‐wet to alleviate the effect of condensate accumulation near the wellbore region. To establish the effect of fluoropolymer on wettability alteration in a gas‐condensate reservoir, a gas‐wetting alteration agent was synthesized by emulsion polymerization using different molar ratios of fluorine‐containing monomers and acrylic monomers. FTIR and SEM were performed to analyze the structure of the gas‐wetting agent. Contact angle measurements were used to assess surface alteration by the Owens two‐liquid method. The effects of alteration agent concentration, salt concentration, pH and temperature on gas‐wetting alteration were also evaluated. Results showed that the best molar ratio of fluoropolymer monomer to acrylic monomers was 1:2. The egg‐like structure of the fluoropolymer latex on the core surface mainly contributes to gas‐wetting alteration. The contact angles of brine and oil can be altered from 23° and 0° to 137° and 67° by 1 wt% FP‐2 treatment, respectively. The surface free energy of the core was reduced from 67.52 to 1.66 mN/m. Moreover, the treated cores remain gas‐wetting up to 100 g L−1of salt solution, 120 °C and within the pH range of 5–7. This novel gas‐wetting alteration agent can be used to solve the problem of liquid blocking effects in gas condensate reservoirs and improve gas recovery significantly.
Innovative techniques used to plumb two 57 m height concrete buildings leaning 3.8 and 3.1 %
Authors: Maffei Carlos E. M. , Gonçalves Heloisa H. S.
Published: August 2016

There are about a 100 buildings visibly inclined in the city of Santos. Until the year 2000 some attempts were realized to reduce inclinations of some of those buildings without success. This paper presents the work done to plumb two buildings: Tower A and Tower B of the Condominium Nuncio Malzoni, with 57 m height that were inclined 3.8 and 3.1 %, respectively. Tower A was 2.08 m out of plumb and was brought plumb through an innovative technique in 2000. Another technique, also innovative, was accomplished to correct Tower B, 1.70 m out of plumb in 2010. Before starting the works to plumb the two buildings, a safety assessment analysis was undertaken through a complex computational analysis. The analysis showed that strengthening the structure of Tower A was urgent, since the building could be at risk of structural collapse. Due to structural differences, the Tower B was not in risk of collapse at this time. The inclination of these buildings was corrected using different techniques, which are presented in this paper.
Associations of neighborhood environment with brain imaging outcomes in the Australian Imaging, Biomarkers and Lifestyle cohort
Authors: Cerin Ester , Rainey‐Smith Stephanie R. , Ames David , Lautenschlager Nicola T. , Macaulay S. Lance , Fowler Christopher , Robertson Joanne S. , Rowe Christopher C. , Maruff Paul , Martins Ralph N. , Masters Colin L. , Ellis Kathryn A.
Published: August 2016

Introduction

“Walkable” neighborhoods offer older adults opportunities for activities that may benefit cognition‐related biological mechanisms. These have not previously been examined in this context.

Methods

We objectively assessed neighborhood walkability for participants (n = 146) from the Australian Imaging, Biomarkers and Lifestyle study with apolipoprotein E (APOE) genotype and two 18‐month‐apart brain volumetric and/or amyloid β burden assessments. Linear mixed models estimated associations of neighborhood walkability with levels and changes in brain imaging outcomes, the moderating effect of APOE ε4 status, and the extent to which associations were explained by physical activity.

Results

Cross‐sectionally, neighborhood walkability was predictive of better neuroimaging outcomes except for left hippocampal volume. These associations were to a small extent explained by physical activity. APOE ε4 carriers showed slower worsening of outcomes if living in walkable neighborhoods.

Discussion

These findings indicate associations between neighborhood walkability and brain imaging measures (especially in APOE ε4 carriers) minimally attributable to physical activity.
Brachioradial Pruritus as a Harbinger of Syrinx in Chronic Spinal Cord Injury: A Case Report
Authors: Skelton Felicia , Frontera Joel E.
Published: August 2016

This case describes a 56‐year‐old man with known thoracic spinal cord injury undergoing evaluation for a pruritic rash on the dorsolateral aspect of his forearms with no upper extremity neuromuscular symptoms. Common diagnoses were considered and treated with little success. The diagnosis of brachioradial pruritus (BRP) was made, and evaluation for possible causes revealed a large cervicothoracic syrinx. To our knowledge, BRP has not been described previously as the presenting sign of post‐traumatic syringomelia. This patient's clinical course is delineated, as well as a brief review of BRP and its relationship to other cervical spine pathologies.

Level of Evidence

V
Carboniferous deposits in the basement of the southwestern West Siberian geosyneclise (Kurgan Region)
Authors: Saraev S.V. , Baturina T.P. , Medvedev A.Ya. , Travin A.V.
Published: August 2016

The 40Ar/39Ar age of volcanics from the sections of core boreholes in the northern Tyumen’–Kostanai trough (Kurgan Region) has been determined. The geologic structure of the northern part of the trough has been refined. The paleogeographic environments and geodynamic settings of formation of Carboniferous deposits have been established by sedimentological, petrological, and geochemical studies of the sections. In the Visean, marine environments with maximum basin depths were predominant. In the Kachar epoch (C1v3-s), the submarine relief of the basin became more complicated; blocks of older rocks appeared in the deposits. The geochemical indicator characteristics of the volcanics—contents of HFSE (Ti, Nb, Ta, Th, and Hf)—are close to those of andesitoids of island arcs and Andean-type active continental margins, as well as present-day andesites from the Kurile–Kamchatka zone. They are an order of magnitude lower than those in similar continental-rift volcanics, among which are volcanics of the Valer’yanovka zone (according to some researchers). The contents of Ni, Co, and V are similar to those in island-arc andesites, including rocks of the Kurile–Kamchatka zone. The Ba/Ta and Ba/La ratios and the proportions of Th, Hf, and Ta in andesitoids of the Valer’yanovka and Kachar Groups are close to the indicator characteristics of island-arc and active-continental-margin volcanics. The Kachar Group siliceous rocks are similar in the Rb/Zr–Nb, Fe–Nb, and Rb–(Y + Nb) correlations to rocks of mature island arcs and active continental margins. The incompatible-element and REE patterns for the Valer’yanovka and Kachar volcanics are typical of island-arc volcanics, including rocks from the Kurile–Kamchatka zone. The indicator geochemical features and petrology of the volcanics and the sedimentologic features of the deposits testify to their formation on an Andean-type active continental margin (western margin of the Kazakhstan paleocontinent) in the Early–Middle Carboniferous.
Gold and silver minerals in low-sulfidaton ores of the Julietta deposit (northeastern Russia)
Authors: Palyanova G.A. , Savva N.E. , Zhuravkova T.V. , Kolova E.E.
Published: August 2016

Gold- and silver-containing pyrites of the Tikhii area at the Julietta deposit (Engteri ore cluster, Magadan Region) were studied by optical and scanning electron microscopy and electron probe microanalysis. One- or two-phase rounded microinclusions consisting of electrum (450–680‰) and/or galena or of petrovskaite and/or uytenbogaardtite, galena, and sphalerite have been found in early pyrites. Later As-pyrites (up to 2.6 wt.% As) contain multiphase xenomorphic microinclusions of acanthite, uytenbogaardtite, freibergite, argentotetrahedrite–tennantite, naumannite, petzite, selenopolybasite-selenostephanite, tellurocanfieldite, and other ore minerals localized in pores, cracks, and interstices. Pyrites that underwent hypergene alterations have rims and veinlets formed by acanthite, goethite, anglesite, plattnerite, and native silver. The presence of rounded ore mineral microinclusions and large pores in the early pyrites suggests the participation of volatiles in the mineral formation and the uptake of large amounts of impurities by pyrite under high-gradient crystallization conditions. The thermobarogeochemical studies of fluid inclusions in quartz have shown that the ore zone formed under boiling-up of hydrothermal medium-concentration NaCl solutions at 230–105 °C. The results of thermodynamic calculations evidence that Ag–Au–S–Se minerals formed under decrease in temperature and fugacity of sulfur (log10fs2 = –22 to –9) and selenium (log10fse2 = –27 to –14) and change of reducing conditions by oxidizing ones in weakly acidic to near-neutral solutions.
On the utility of combining production data and perceptual data to investigate regional linguistic variation: The case of Spanish experiential gustar ‘to like, to please’ on Twitter and in an online survey
Authors: Brown Earl K.
Published: August 2016

The use of both production and perceptual data has the potential to provide a more complete picture of linguistic phenomena than would otherwise be the case, including when exploring regional linguistic variation. Utilizing the social networking platform Twitter and an online survey, this paper reports on a descriptive analysis of the geographic distribution of a less-commonly used syntactic form of the Spanish verbgustar‘to like, to please’, referred to as experientialgustar(e.g.,cuando gustes‘when you’d like’). The results from the analysis of 6,686 tweets together with the responses of 81 native Spanish-speaking participants in an online survey suggest that experientialgustaris produced and is perceived to be produced most often in Mexican Spanish, despite not being exclusive to that country. The paper contributes to the literature depicting the benefit of using both production and perceptual data in the study of dialectal variation, as well as to the literature documenting language variation in Spanish.
Assessing Groundwater Age in Confined Aquifers from the Central Pampean Plain of Cordoba, Argentina
Authors: Maldonado Marina Luciana , Blarasin Mónica Teresa , Cabrera Adriana Edith , Panarello Héctor Osvaldo , Dapeña Cristina
Published: August 2016

In Córdoba Province, Argentina, the population uses groundwater from confined aquifer systems (CASs) for different activities. Therefore, it is necessary to carry out comprehensive studies in order to plan more sustainable use considering that groundwater renewal times can be of several thousands of years. The objective of this research is to evaluate groundwater age in confined aquifers based on hydraulic and isotopic methods. The CASs present variable extension, are multilayered and formed by thin (4–6 m) sand-pebble lenses, and are linked to Neogene fluvial paleosystems. These layers are situated at different depths (120–400 m) and interbedded with thick clay strata. The interpretations made from 2H, 18O, and 3H results and hydraulic calculations suggest that the groundwater is old. Furthermore, an age gradient was observed that increases with depth and flow direction. The 14C ages obtained for the CASs labeled A2, C, and D were 3.6–1.1 ka BP, 10.8 ka BP, and 46.0–40.5 ka BP, respectively. These results indicate that A2 and C contain groundwater recharged during Holocene cold periods, between the Little Ice Age and the ending of the Holocene Climatic Optimum and during the last glaciation. The D CAS contains paleowater that was recharged during the Pleistocene.
Inflammation-driven malnutrition: a new screening tool predicts outcome in Crohn’s disease
Authors: Jansen Irene , Prager Matthias , Valentini Luzia , Büning Carsten
Published: August 2016

Malnutrition is a frequent feature in Crohn’s disease (CD), affects patient outcome and must be recognised. For chronic inflammatory diseases, recent guidelines recommend the development of combined malnutrition and inflammation risk scores. We aimed to design and evaluate a new screening tool that combines both malnutrition and inflammation parameters that might help predict clinical outcome. In a prospective cohort study, we examined fifty-five patients with CD in remission (Crohn’s disease activity index (CDAI) <200) at 0 and 6 months. We assessed disease activity (CDAI, Harvey–Bradshaw index), inflammation (C-reactive protein (CRP), faecal calprotectin (FC)), malnutrition (BMI, subjective global assessment (SGA), serum albumin, handgrip strength), body composition (bioelectrical impedance analysis) and administered the newly developed ‘Malnutrition Inflammation Risk Tool’ (MIRT; containing BMI, unintentional weight loss over 3 months and CRP). All parameters were evaluated regarding their ability to predict disease outcome prospectively at 6 months. At baseline, more than one-third of patients showed elevated inflammatory markers despite clinical remission (36·4 % CRP ≥5 mg/l, 41·5 % FC ≥100 µg/g). Prevalence of malnutrition at baseline according to BMI, SGA and serum albumin was 2–16 %. At 6 months, MIRT significantly predicted outcome in numerous nutritional and clinical parameters (SGA, CD-related flares, hospitalisations and surgeries). In contrast, SGA, handgrip strength, BMI, albumin and body composition had no influence on the clinical course. The newly developed MIRT was found to reliably predict clinical outcome in CD patients. This screening tool might be used to facilitate clinical decision making, including treatment of both inflammation and malnutrition in order to prevent complications.
AN ALMOST CLOSED FORM ESTIMATOR FOR THE EGARCH MODEL
Authors: Hafner Christian M. , Linton Oliver
Published: August 2016

The exponential GARCH (EGARCH) model introduced by Nelson (1991) is a popular model for discrete time volatility since it allows for asymmetric effects and naturally ensures positivity even when including exogenous variables. Estimation and inference are usually done via maximum likelihood. Although some progress has been made recently, a complete distribution theory of MLE for EGARCH models is still missing. Furthermore, the estimation procedure itself may be highly sensitive to starting values, the choice of numerical optimization algorithm, etc. We present an alternative estimator that is available in a simple closed form and which could be used, for example, as starting values for MLE. The estimator of the dynamic parameter is independent of the innovation distribution. For the other parameters we assume that the innovation distribution belongs to the class of Generalized Error Distributions (GED), profiling out its parameter in the estimation procedure. We discuss the properties of the proposed estimator and illustrate its performance in a simulation study and an empirical example.
Aggregation of 1-year risks in life and disability insurance
Authors: Djehiche Boualem , Löfdahl Björn
Published: August 2016

We consider large insurance portfolios consisting of life or disability insurance policies that are assumed independent, conditional on a stochastic process representing the economic–demographic environment. Using the conditional law of large numbers, we show that when the portfolio of liabilities becomes large enough, its value on a δ-year horizon can be approximated by a functional of the environment process. Based on this representation, we derive a semi-analytical approximation of the systematic risk quantiles of the future liability value for a homogeneous portfolio when the environment is represented by a one-factor diffusion process. For the multi-factor diffusion case, we propose two different risk aggregation techniques for a portfolio consisting of large, homogeneous pools. We give numerical results comparing the resulting capital charges with the Solvency II standard formula, based on disability claims data from the Swedish insurance company Folksam.
Synergistic effects of ion transporter and MAP kinase pathway inhibitors in melanoma
Authors: Eskiocak Ugur , Ramesh Vijayashree , Gill Jennifer G. , Zhao Zhiyu , Yuan Stacy W. , Wang Meng , Vandergriff Travis , Shackleton Mark , Quintana Elsa , Frankel Arthur E. , Johnson Timothy M. , DeBerardinis Ralph J. , Morrison Sean J.
Published: August 2016

New therapies are required for melanoma. Here, we report that multiple cardiac glycosides, including digitoxin and digoxin, are significantly more toxic to human melanoma cells than normal human cells. This reflects on-target inhibition of the ATP1A1 Na+/K+ pump, which is highly expressed by melanoma. MEK inhibitor and/or BRAF inhibitor additively or synergistically combined with digitoxin to induce cell death, inhibiting growth of patient-derived melanomas in NSG mice and synergistically extending survival. MEK inhibitor and digitoxin do not induce cell death in human melanocytes or haematopoietic cells in NSG mice. In melanoma, MEK inhibitor reduces ERK phosphorylation, while digitoxin disrupts ion gradients, altering plasma membrane and mitochondrial membrane potentials. MEK inhibitor and digitoxin together cause intracellular acidification, mitochondrial calcium dysregulation and ATP depletion in melanoma cells but not in normal cells. The disruption of ion homoeostasis in cancer cells can thus synergize with targeted agents to promote tumour regression in vivo.
MURC deficiency in smooth muscle attenuates pulmonary hypertension
Authors: Nakanishi Naohiko , Ogata Takehiro , Naito Daisuke , Miyagawa Kotaro , Taniguchi Takuya , Hamaoka Tetsuro , Maruyama Naoki , Kasahara Takeru , Nishi Masahiro , Matoba Satoaki , Ueyama Tomomi
Published: August 2016

Emerging evidence suggests that caveolin-1 (Cav1) is associated with pulmonary arterial hypertension. MURC (also called Cavin-4) is a member of the cavin family, which regulates caveolar formation and functions together with caveolins. Here, we show that hypoxia increasedMurcmRNA expression in the mouse lung, and thatMurc-null mice exhibited attenuation of hypoxia-induced pulmonary hypertension (PH) accompanied by reduced ROCK activity in the lung. Conditional knockout mice lackingMurcin smooth muscle also resist hypoxia-induced PH. MURC regulates the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through Rho/ROCK signalling. Cav1 suppresses RhoA activity in PASMCs, which is reversed by MURC. MURC binds to Cav1 and inhibits the association of Cav1 with the active form of Gα13, resulting in the facilitated association of the active form of Gα13 with p115RhoGEF. These results reveal that MURC has a function in the development of PH through modulating Rho/ROCK signalling.
Positive feedback regulation of p53 transactivity by DNA damage-induced ISG15 modification
Authors: Park Jong Ho , Yang Seung Wook , Park Jung Mi , Ka Seung Hyeun , Kim Ji-Hoon , Kong Young-Yun , Jeon Young Joo , Seol Jae Hong , Chung Chin Ha
Published: August 2016

p53 plays a pivotal role in tumour suppression under stresses, such as DNA damage. ISG15 has been implicated in the control of tumorigenesis. Intriguingly, the expression of ISG15, UBE1L and UBCH8 is induced by DNA-damaging agents, such as ultraviolet and doxorubicin, which are known to induce p53. Here, we show that the genes encoding ISG15, UBE1L, UBCH8 and EFP, have the p53-responsive elements and their expression is induced in a p53-dependent fashion under DNA damage conditions. Furthermore, DNA damage induces ISG15 conjugation to p53 and this modification markedly enhances the binding of p53 to the promoters of its target genes (for example, CDKN1 and BAX) as well as of its own gene by promoting phosphorylation and acetylation, leading to suppression of cell growth and tumorigenesis. These findings establish a novel feedback circuit between p53 and ISG15-conjugating system for positive regulation of the tumour suppressive function of p53 under DNA damage conditions.
Fscn1 is required for the trafficking of TGF-β family type I receptors during endoderm formation
Authors: Liu Zhaoting , Ning Guozhu , Xu Ranran , Cao Yu , Meng Anming , Wang Qiang
Published: August 2016

Microtubules function in TGF-β signalling by facilitating the cytoplasmic trafficking of internalized receptors and the nucleocytoplasmic shuttling of Smads. However, nothing is known about whether actin filaments are required for these processes. Here we report that zebrafish actin-bundling protein fscn1a is highly expressed in mesendodermal precursors and its expression is directly regulated by the TGF-β superfamily member Nodal. Knockdown or knockout of fscn1a leads to a reduction of Nodal signal transduction and endoderm formation in zebrafish embryos. Fscn1 specifically interacts with TGF-β family type I receptors, and its depletion disrupts the association between receptors and actin filaments and sequesters the internalized receptors into clathrin-coated vesicles. Therefore, Fscn1 acts as a molecular linker between TGF-β family type I receptors and the actin filaments to promote the trafficking of internalized receptors from clathrin-coated vesicles to early endosomes during zebrafish endoderm formation.
Association between impaired fasting glycaemia in pediatric obesity and type 2 diabetes in young adulthood
Authors: Hagman E , Danielsson P , Brandt L , Ekbom A , Marcus C
Published: August 2016

Objectives:

In adults, impaired fasting glycemia (IFG) increases the risk for type 2 diabetes mellitus (T2DM). This study aimed to investigate to which extent children with obesity develop T2DM during early adulthood, and to determine whether IFG and elevated hemoglobin A1c (HbA1c) in obese children are risk markers for early development of T2DM.

Methods:

In this prospective cohort study, 1620 subjects from the Swedish Childhood Obesity Treatment Registry – BORIS who were ⩾18 years at follow-up and 8046 individuals in a population-based comparison group, matched on gender age and living area, were included. IFG was defined according to both ADA (cut-off 5.6 mmol l−1) and WHO (6.1 mmol l−1). Elevated HbA1c was defined according to ADA (cut-off 39 mmol l−1). Main outcome was T2DM medication, as a proxy for T2DM. Data on medications were retrieved from a national registry.

Results:

The childhood obesity cohort were 24 times more likely to receive T2DM medications in early adulthood compared with the comparison group (95% confidence interval (CI): 12.52–46). WHO-defined IFG predicted future use of T2DM medication with an adjusted hazard ratio (HR) of 3.73 (95% CI: 1.87–7.45) compared with those who had fasting glucose levels <5.6 mmol l−1. A fasting glucose level of 5.6–6.0 mmol l−1, that is, the IFG-interval added by American Diabetes Association (ADA), did not increase the use of T2DM medication more than pediatric obesity itself, adjusted HR=1.72 (0.84–3.52). Elevated levels of HbA1c resulted in an adjusted HR=3.12 (1.50–6.52). More severe degree of obesity also increased the future T2DM risk.

CONCLUSION:

IFG according to WHO and elevated HbA1c (39–48 mmol l−1), but not the additional fasting glucose interval added by ADA (5.6–6.0 mmol l−1), can be considered as prediabetes in the obese pediatric population in Sweden.
Global terrestrial Human Footprint maps for 1993 and 2009
Authors: Venter Oscar , Sanderson Eric W. , Magrach Ainhoa , Allan James R. , Beher Jutta , Jones Kendall R. , Possingham Hugh P. , Laurance William F. , Wood Peter , Fekete Balázs M. , Levy Marc A. , Watson James E.M.
Published: August 2016

Remotely-sensed and bottom-up survey information were compiled on eight variables measuring the direct and indirect human pressures on the environment globally in 1993 and 2009. This represents not only the most current information of its type, but also the first temporally-consistent set of Human Footprint maps. Data on human pressures were acquired or developed for: 1) built environments, 2) population density, 3) electric infrastructure, 4) crop lands, 5) pasture lands, 6) roads, 7) railways, and 8) navigable waterways. Pressures were then overlaid to create the standardized Human Footprint maps for all non-Antarctic land areas. A validation analysis using scored pressures from 3114×1 km2 random sample plots revealed strong agreement with the Human Footprint maps. We anticipate that the Human Footprint maps will find a range of uses as proxies for human disturbance of natural systems. The updated maps should provide an increased understanding of the human pressures that drive macro-ecological patterns, as well as for tracking environmental change and informing conservation science and application.
Multi-marker metabarcoding of coral skeletons reveals a rich microbiome and diverse evolutionary origins of endolithic algae
Authors: Marcelino Vanessa Rossetto , Verbruggen Heroen
Published: August 2016

Bacteria, fungi and green algae are common inhabitants of coral skeletons. Their diversity is poorly characterized because they are difficult to identify with microscopy or environmental sequencing, as common metabarcoding markers have low phylogenetic resolution and miss a large portion of the biodiversity. We used a cost-effective protocol and a combination of markers (tufA, 16S rDNA, 18S rDNA and 23S rDNA) to characterize the microbiome of 132 coral skeleton samples. We identified a wide range of prokaryotic and eukaryotic organisms, many never reported in corals before. We additionally investigated the phylogenetic diversity of the green algae—the most abundant eukaryotic member of this community, for which previous literature recognizes only a handful of endolithic species. We found more than 120 taxonomic units (near species level), including six family-level lineages mostly new to science. The results suggest that the existence of lineages with an endolithic lifestyle predates the existence of modern scleractinian corals by ca. 250my and that this particular niche was independently invaded by over 20 lineages in green algae evolution. These results highlight the potential of the multi-marker approach to assist in species discovery and, when combined with a phylogenetic framework, clarify the evolutionary origins of host-microbiota associations.
Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy
Authors: Godar Marie , Morello Virginia , Sadi Ava , Hultberg Anna , De Jonge Natalie , Basilico Cristina , Hanssens Valérie , Saunders Michael , Lambrecht Bart N. , El Khattabi Mohamed , de Haard Hans , Michieli Paolo , Blanchetot Christophe
Published: August 2016

Bispecific antibodies are of great interest due to their ability to simultaneously bind and engage different antigens or epitopes. Nevertheless, it remains a challenge to assemble, produce and/or purify them. Here we present an innovative dual anti-idiotypic purification process, which provides pure bispecific antibodies with native immunoglobulin format. Using this approach, a biparatopic IgG1 antibody targeting two distinct, HGF-competing, non-overlapping epitopes on the extracellular region of the MET receptor, was purified with camelid single-domain antibody fragments that bind specifically to the correct heavy chain/light chain pairings of each arm. The purity and functionality of the anti-MET biparatopic antibody was then confirmed by mass spectrometry and binding experiments, demonstrating its ability to simultaneously target the two epitopes recognized by the parental monoclonal antibodies. The improved MET-inhibitory activity of the biparatopic antibody compared to the parental monoclonal antibodies, was finally corroborated in cell-based assays and more importantly in a tumor xenograft mouse model. In conclusion, this approach is fast and specific, broadly applicable and results in the isolation of a pure, novel and native-format anti-MET biparatopic antibody that shows superior biological activity over the parental monospecific antibodies both in vitro and in vivo.
Necrotising enterocolitis and mortality in preterm infants after introduction of probiotics: a quasi-experimental study
Authors: Samuels Noor , van de Graaf Rob , Been Jasper V. , de Jonge Rogier C. J. , Hanff Lidwien M. , Wijnen René M. H. , Kornelisse René F. , Reiss Irwin K. M. , Vermeulen Marijn J.
Published: August 2016

Evidence on the clinical effectiveness of probiotics in the prevention of necrotising enterocolitis (NEC) in preterm infants is conflicting and cohort studies lacked adjustment for time trend and feeding type. This study investigated the association between the introduction of routine probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum; Infloran®) on the primary outcome ‘NEC or death’. Preterm infants (gestational age <32 weeks or birth weight <1500 gram) admitted before (Jan 2008–Sep 2012; n = 1288) and after (Oct 2012–Dec 2014; n = 673) introduction of probiotics were compared. Interrupted time series logistic regression models were adjusted for confounders, effect modification by feeding type, seasonality and underlying temporal trends. Unadjusted and adjusted analyses showed no difference in ‘NEC or death’ between the two periods. The overall incidence of NEC declined from 7.8% to 5.1% (OR 0.63, 95% CI 0.42–0.93, p = 0.02), which was not statistically significant in the adjusted models. Introduction of probiotics was associated with a reduced adjusted odds for ‘NEC or sepsis or death’ in exclusively breastmilk-fed infants (OR 0.43, 95% CI 0.21–0.93, p = 0.03) only. We conclude that introduction of probiotics was not associated with a reduction in ‘NEC or death’ and that type of feeding seems to modify the effects of probiotics.
Optical characterization of red blood cells from individuals with sickle cell trait and disease in Tanzania using quantitative phase imaging
Authors: Jung JaeHwang , Matemba Lucas E. , Lee KyeoReh , Kazyoba Paul E. , Yoon Jonghee , Massaga Julius J. , Kim Kyoohyun , Kim Dong-Jin , Park YongKeun
Published: August 2016

Sickle cell disease (SCD) is common across Sub-Saharan Africa. However, the investigation of SCD in this area has been significantly limited mainly due to the lack of research facilities and skilled personnel. Here, we present optical measurements of individual red blood cells from healthy individuals and individuals with SCD and sickle cell trait in Tanzania using the quantitative phase imaging technique. By employing a quantitative phase imaging unit, an existing microscope in a clinic is transformed into a powerful quantitative phase microscope providing measurements on the morphological, biochemical, and biomechanical properties of individual cells. The present approach will open up new opportunities for cost-effective investigation and diagnosis of several diseases in low resource environments.
Optical coherence microscopy in 1700 nm spectral band for high-resolution label-free deep-tissue imaging
Authors: Yamanaka Masahito , Teranishi Tatsuhiro , Kawagoe Hiroyuki , Nishizawa Norihiko
Published: August 2016

Optical coherence microscopy (OCM) is a label-free, high-resolution, three-dimensional (3D) imaging technique based on optical coherence tomography (OCT) and confocal microscopy. Here, we report that the 1700-nm spectral band has the great potential to improve the imaging depth in high-resolution OCM imaging of animal tissues. Recent studies to improve the imaging depth in OCT revealed that the 1700-nm spectral band is a promising choice for imaging turbid scattering tissues due to the low attenuation of light in the wavelength region. In this study, we developed high-resolution OCM by using a high-power supercontinuum source in the 1700-nm spectral band and compared the attenuation of signal-to-noise ratio between the 1700-nm and 1300-nm OCM imaging of a mouse brain under the condition of the same sensitivity. The comparison clearly showed that the 1700-nm OCM provides larger imaging depth than the 1300-nm OCM. In this 1700-nm OCM, the lateral resolution of 1.3 μm and the axial resolution of 2.8 μm, when a refractive index was assumed to be 1.38, was achieved.
Reconciling Local Structure Disorder and the Relaxor State in (Bi1/2Na1/2)TiO3-BaTiO3
Authors: Groszewicz Pedro B. , Gröting Melanie , Breitzke Hergen , Jo Wook , Albe Karsten , Buntkowsky Gerd , Rödel Jürgen
Published: August 2016

Lead-based relaxor ferroelectrics are key functional materials indispensable for the production of multilayer ceramic capacitors and piezoelectric transducers. Currently there are strong efforts to develop novel environmentally benign lead-free relaxor materials. The structural origins of the relaxor state and the role of composition modifications in these lead-free materials are still not well understood. In the present contribution, the solid-solution (100-x)(Bi1/2Na1/2)TiO3-xBaTiO3 (BNT-xBT), a prototypic lead-free relaxor is studied by the combination of solid-state nuclear magnetic resonance (NMR) spectroscopy, dielectric measurements and ab-initio density functional theory (DFT). For the first time it is shown that the peculiar composition dependence of the EFG distribution width (ΔQISwidth) correlates strongly to the dispersion in dielectric permittivity, a fingerprint of the relaxor state. Significant disorder is found in the local structure of BNT-xBT, as indicated by the analysis of the electric field gradient (EFG) in 23Na 3QMAS NMR spectra. Aided by DFT calculations, this disorder is attributed to a continuous unimodal distribution of octahedral tilting. These results contrast strongly to the previously proposed coexistence of two octahedral tilt systems in BNT-xBT. Based on these results, we propose that considerable octahedral tilt disorder may be a general feature of these oxides and essential for their relaxor properties.
Identification of cellular senescence-specific genes by comparative transcriptomics
Authors: Nagano Taiki , Nakano Masayuki , Nakashima Akio , Onishi Kengo , Yamao Shunsuke , Enari Masato , Kikkawa Ushio , Kamada Shinji
Published: August 2016

Cellular senescence is defined as permanent cell cycle arrest induced by various stresses. Although the p53 transcriptional activity is essential for senescence induction, the downstream genes that are crucial for senescence remain unsolved. Here, by using a developed experimental system in which cellular senescence or apoptosis is induced preferentially by altering concentration of etoposide, a DNA-damaging drug, we compared gene expression profiles of senescent and apoptotic cells by microarray analysis. Subtraction of the expression profile of apoptotic cells identified 20 genes upregulated specifically in senescent cells. Furthermore, 6 out of 20 genes showed p53-dependent upregulation by comparing gene expression between p53-proficient and -deficient cells. These 6 genes were also upregulated during replicative senescence of normal human diploid fibroblasts, suggesting that upregulation of these genes is a general phenomenon in senescence. Among these genes, 2 genes (PRODH and DAO) were found to be directly regulated by p53, and ectopic expression of 4 genes (PRODH, DAO, EPN3, and GPR172B) affected senescence phenotypes induced by etoposide treatment. Collectively, our results identified several proteins as novel downstream effectors of p53-mediated senescence and provided new clues for further research on the complex signalling networks underlying the induction and maintenance of senescence.
Infection-induced behavioural changes reduce connectivity and the potential for disease spread in wild mice contact networks
Authors: Lopes Patricia C. , Block Per , König Barbara
Published: August 2016

Infection may modify the behaviour of the host and of its conspecifics in a group, potentially altering social connectivity. Because many infectious diseases are transmitted through social contact, social connectivity changes can impact transmission dynamics. Previous approaches to understanding disease transmission dynamics in wild populations were limited in their ability to disentangle different factors that determine the outcome of disease outbreaks. Here we ask how social connectivity is affected by infection and how this relationship impacts disease transmission dynamics. We experimentally manipulated disease status of wild house mice using an immune challenge and monitored social interactions within this free-living population before and after manipulation using automated tracking. The immune-challenged animals showed reduced connectivity to their social groups, which happened as a function of their own behaviour, rather than through conspecific avoidance. We incorporated these disease-induced changes of social connectivity among individuals into models of disease outbreaks over the empirically-derived networks. The models revealed that changes in host behaviour frequently resulted in the disease being contained to very few animals, as opposed to becoming widespread. Our results highlight the importance of considering the role that behavioural alterations during infection can have on social dynamics when evaluating the potential for disease outbreaks.