bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized, placebo‐controlled trial of ADS‐5102 (amantadine) extended‐release capsules for levodopa‐induced dyskinesia in Parkinson's disease (EASE LID 3)
Authors: Oertel Wolfgang , Eggert Karla , Pahwa Rajesh , Tanner Caroline M. , Hauser Robert A. , Trenkwalder Claudia , Ehret Reinhard , Azulay Jean Philippe , Isaacson Stuart , Felt Larissa , Stempien Mary Jean
Published: August 2017

Background

The treatment of levodopa‐induced dyskinesia in Parkinson's disease (PD) is an unmet need with no approved drug therapy.

Objective

The purpose of this study was to investigate the efficacy and safety of 274 mg ADS‐5102 (amantadine) extended‐release capsules (equivalent to 340‐mg amantadine HCl) for levodopa‐induced dyskinesia in a randomized controlled trial.

Methods

PD patients with ≥1 hour of troublesome dyskinesia and at least mild functional impact were randomized to placebo or ADS‐5102 once daily at bedtime for 13 weeks. The primary efficacy analysis was based on change from baseline to week 12 on the Unified Dyskinesia Rating Scale total score in the modified intent‐to‐treat population. OFF time was a key secondary measure.

Results

At week 12, least‐squares mean change in the Unified Dyskinesia Rating Scale was −20.7 (standard error 2.2) for ADS‐5102 (n = 37) and –6.3 (standard error 2.1) for placebo (n = 38; treatment difference −14.4, 95% confidence interval −20.4 to −8.3, P < .0001), indicating improvement in levodopa‐induced dyskinesia. OFF time decreased 0.5 hours (standard error 0.3) for ADS‐5102 from a baseline mean of 2.6 hours and increased 0.6 hours (standard error 0.3) for placebo from a baseline mean of 2.0 hours (treatment difference −1.1 hours, 95% confidence interval −2.0 to −0.2, P = .0199). The most common adverse events (ADS‐5102 versus placebo) included dry mouth (13.5% versus 2.6%), nausea (13.5% versus 2.6%), decreased appetite (10.8% versus 0%), insomnia (10.8% versus 0%), orthostatic hypotension (10.8% versus 0%), constipation (8.1% versus 0%), falls (8.1% versus 5.3%), and visual hallucinations (8.1% versus 5.3%). Adverse events led to treatment discontinuation in 19% versus 8%, respectively.

Conclusion

ADS‐5102 274 mg is an oral pharmacotherapy demonstrating a significant decrease in levodopa‐induced dyskinesia and improving OFF time. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Appetite‐Inducing Effects of Homoeriodictyol: Two Randomized, Cross‐Over Interventions
Authors: Hochkogler Christina M. , Liszt Kathrin , Lieder Barbara , Stöger Verena , Stübler Anna , Pignitter Marc , Hans Joachim , Widder Sabine , Ley Jakob P. , Krammer Gerhard E. , Somoza Veronika
Published: August 2017

Scope

Anorexia of aging, characterized by a decrease in appetite and/or food intake, is a major risk factor of under‐nutrition and adverse health outcomes in elderly people. Recent in vitro evidence suggests homoeriodictyol (HED), a naturally occurring, bitter‐masking flavanone, as a promising agent to increase appetite and food intake.

Methods and results

In two cross‐over intervention trials, 30 mg NaHED, either solely (n = 10, Study I) or in combination with a 75 g glucose load (n = 17, study II) were administered to healthy adult subjects. Ratings of hunger were assessed at fasting and either 30 min (Study I) or 120 min (Study II) post intervention. Ad libitum energy intake from a standardized breakfast and plasma changes in hunger‐/satiety‐associated hormones PYY, GLP‐1, ghrelin and serotonin were determined after blood drawings. Effects were more pronounced when NaHED was administered in combination with 75 g glucose since ad libitum energy (+ 9.52 ± 4.60%) and protein (+ 7.08 ± 7.97%) intake as well as plasma ΔAUC ghrelin values increased in study II solely, whereas plasma serotonin concentrations decreased after both interventions.

Conclusions

NaHED demonstrated appetizing effects in healthy adults when administered with a glucose load. Long‐term intervention studies are warranted to verify these effects in compromised subjects.
Time integration for extended discontinuous Galerkin methods with moving domains
Authors: Kummer Florian , Müller Björn , Utz Thomas
Published: August 2017

We study time integration schemes for discontinuous Galerkin discretizations of problems with moving immersed interfaces. Two approaches have been discussed in literature so far: splitting schemes and space‐time methods. Splitting schemes are cheap and easy to implement, but are non‐conservative, inherently limited to low orders of accuracy, and require extremely small time steps. Space‐time methods, on the other hand, are conservative, allow for large time steps, and generalize to arbitrary orders of accuracy. However, these advantages come at the expense of a severe growth the systems to be solved. Within this work, we present a generic strategy that combines the advantages of both concepts by evaluating numerical fluxes in a moving reference frame and by making use of a conservative cell‐agglomeration strategy. We study the performance of this strategy in combination with backward‐difference‐formulas and explicit Runge‐Kutta schemes in the context of the scalar transport equation, the Burgers equation, and the heat equation. Our results indicate that higher order spatial and temporal convergence rates can be achieved without increasing the size of the systems to be solved.
ADHD Medication, Dietary Patterns, Physical Activity, and BMI in Children: A Longitudinal Analysis of the ECLS‐K Study
Authors: Bowling April , Davison Kirsten , Haneuse Sebastien , Beardslee William , Miller Daniel P.
Published: August 2017

Objective

This study examined relationships between attention‐deficit/hyperactivity disorder (ADHD), stimulant use, and BMI change in a nationally representative cohort of children as well as differences in diet and physical activity that may mediate associations between stimulant use and BMI change.

Methods

By using the Early Childhood Longitudinal Study‐Kindergarten Cohort 1998‐1999 (N = 8,250), we modeled BMI and z score change by ADHD and stimulant start time, examined the odds of unhealthy diet and physical activity predicted by ADHD and stimulant use, and performed mediation analysis assessing indirect effects of health behaviors.

Results

Early stimulant use predicted short‐term BMI reductions, but any stimulant use predicted increased BMI growth between fifth grade (mean age = 11.2 years) and eighth grade (mean age = 14.3 years). Children with ADHD had higher odds of poor diet regardless of medication. Health behaviors were not associated with BMI change after controlling for medication use.

Conclusions

Stimulant use predicted higher BMI trajectory between fifth and eighth grade but did not affect dietary or physical activity patterns. Future research should explore potential mechanisms by which early and long‐term stimulant use may affect metabolism, while clinicians should initiate nutrition counseling with families of children with ADHD, regardless of medication prescription, at or shortly after diagnosis.
miRNA Signatures of Insulin Resistance in Obesity
Authors: Jones Angela , Danielson Kirsty M. , Benton Miles C. , Ziegler Olivia , Shah Ravi , Stubbs Richard S. , Das Saumya , Macartney‐Coxson Donia
Published: August 2017

Objective

Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity.

Methods

One hundred seventy‐five miRNAs were analyzed in females with obesity (insulin sensitivity, n = 11; insulin resistance, n = 19; type 2 diabetes, n = 15) and without obesity (n = 12). Correlations between miRNA level and clinical parameters and levels of 15 miRNAs in a murine obesity model were investigated.

Results

One hundred six miRNAs were significantly (adjusted P ≤ 0.05) different between controls and at least one obesity phenotype, including miRNAs with the following attributes: previously reported roles in obesity and altered circulating levels (e.g., miR‐122, miR‐192); known roles in obesity but no reported changes in circulating levels (e.g., miR‐378a); and no current reported role in, or association with, obesity (e.g., miR‐28‐5p, miR‐374b, miR‐32). The miRNAs in the latter group were found to be associated with extracellular vesicles. Forty‐eight miRNAs showed significant correlations with clinical parameters; stepwise regression retained let‐7b, miR‐144‐5p, miR‐34a, and miR‐532‐5p in a model predictive of insulin resistance (R2 = 0.57, P = 7.5 × 10−8). Both miR‐378a and miR‐122 were perturbed in metabolically relevant tissues in a murine model of obesity.

Conclusions

This study expands on the role of extracellular miRNAs in insulin‐resistant phenotypes of obesity and identifies candidate miRNAs not previously associated with obesity.
Improvement of anti‐icing properties of low surface energy coatings by introducing phase‐change microcapsules
Authors: Zhu Kongying , Li Xiaohui , Su Junfeng , Li Hui , Zhao Yunhui , Yuan Xiaoyan
Published: August 2017

Polymers with low surface energy such as silicone and fluoropolymers are widely applied in preparing anti‐icing coatings, but they may have some limitations. To improve the anti‐icing properties of the coatings, composite coatings were developed by introducing phase‐change microcapsules (PCMs). Room temperature vulcanized silicone rubber and a fluorosilicone methacrylate copolymer were examined. Tests involving infrared thermal imaging, icing delay time, and ice shear strength were performed to determine the anti‐icing properties of the coatings. It was found that during cooling the composite coatings containing PCMs could release the latent heat of phase change to delay the icing process of water droplets on its surface. The introduction of PCMs increased the surface roughness, and the ice shear strengths of the composite coatings could remain at a low level and ice on the coatings could be easily removed, indicating that PCMs could be practicably applied in anti‐icing coatings. POLYM. ENG. SCI., 58:973–979, 2018. © 2017 Society of Plastics Engineers
Microwave‐assisted solvent‐free synthesis of novel benzoxazines: A faster and environmentally friendly route to the development of bio‐based thermosetting resins
Authors: Oliveira Jéssica R. , Kotzebue Lloyd R. V. , Ribeiro Francisco W. M. , Mota Beatriz C. , Zampieri Dávila , Mazzetto Selma E. , Ishida Hatsuo , Lomonaco Diego
Published: August 2017

Microwave‐assisted organic synthesis (MAOS) is a well‐established technique that has been used in the enhancement of chemical reactions. Here, the versatility of MAOS is explored describing an environmentally friendly one‐pot route to novel bio‐based benzoxazines under solvent‐free conditions. The lignin derivative, guaiacol, along with paraformaldehyde and different conjugated and nonconjugated amines are successfully fused into guaiacol‐derived 3,4‐dihydro‐2H‐1,3‐benzoxazines. The reactions conducted under microwave irradiation are completed much faster than those under traditional heating, reducing the reaction time from hours to only 6 min, with good yields. The chemical structures of novel benzoxazines are confirmed by 1H and 13C NMR spectroscopy, FTIR, and HR‐MS. The thermal behavior of the resins are evaluated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), showing that these polymers have good thermal stability and wide processing‐window, with onset temperature of polymerization above 230 °C. These results indicate dramatic improvement over the traditional methodologies for the production of this class of resins, which are usually obtained by time‐consuming procedures and in the presence of toxic solvents. Therefore, MAOS can be considered a green and efficient strategy for the synthesis of eco‐friendly benzoxazines. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3534–3544
Combining an EKF soil analysis with a 3D‐Var upper‐air assimilation in a limited‐area NWP model
Authors: Duerinckx Annelies , Hamdi Rafiq , Deckmyn Alex , Djebbar Arab , Mahfouf Jean‐François , Termonia Piet
Published: August 2017

In recent years, the Extended Kalman Filter (EKF) has been gaining more attention in the surface data assimilation (DA) community and has already replaced the older Optimal Interpolation (OI) scheme for the vertical component of the land surface DA system in a number of meteorological institutes. An EKF has been developed within the standalone land‐surface modelling platform SURFace Externalisée (SURFEX) for the initialisation of soil temperature and soil water content based on screen‐level temperature and relative humidity. In this article we present a new combination of the EKF with a basic (using conventional observations only) three‐dimensional variational (3D‐Var) upper‐air assimilation for the limited‐area model ALARO coupled to SURFEX. This new combination is compared to an Open Loop experiment where all initial conditions are interpolated from an analysis of the global numerical weather prediction model Action de Recherche Petite Echelle Grande Echelle (ARPEGE) and to an experiment where the surface is initialised using the EKF, while the upper‐air initial conditions are interpolated from the ARPEGE analysis. The aim of this article is to examine whether the EKF surface assimilation coupled or not with a basic 3D‐Var upper‐air assimilation has an added value compared to the Open Loop, in which the more advanced upper‐air data assimilation of ARPEGE with more observations used is interpolated onto the limited‐area model grid. All set‐ups are verified during a 1‐year period 2013 against soil measurements, screen‐level observations, radiosoundings and merged radar–rain‐gauge precipitation observations. Results indicate that the EKF surface assimilation has positive effects on humidity scores and is able to produce similar or improved scores compared to the Open Loop. While the upper‐air 3D‐Var DA system of ALARO still needs improvements, the potential benefits of the combination of upper‐air and surface assimilation are demonstrated through soil moisture and screen‐level relative humidity verifications.
Coloring graphs of various maximum degree from random lists
Authors: Casselgren Carl Johan
Published: August 2017

Let G = G(n) be a graph on n vertices with maximum degree Δ =Δ (n). Assign to each vertex v of G a list L(v) of colors by choosing each list independently and uniformly at random from all k‐subsets of a color set of size . Such a list assignment is called a random ‐list assignment. In this paper, we are interested in determining the asymptotic probability (as n →∞) of the existence of a proper coloring φ of G, such that for every vertex v of G, a so‐called L‐coloring. We give various lower bounds on σ, in terms of n, k, and Δ, which ensures that with probability tending to 1 as n →∞ there is an L‐coloring of G. In particular, we show, for all fixed k and growing n, that if and , then the probability that G has an L‐coloring tends to 1 as . If and , then the same conclusion holds provided that . We also give related results for other bounds on Δ, when k is constant or a strictly increasing function of n.
Metal Phosphides and Phosphates‐based Electrodes for Electrochemical Supercapacitors
Authors: Li Xin , Elshahawy Abdelnaby M. , Guan Cao , Wang John
Published: August 2017

Phosphorus compounds, such as metal phosphides and phosphates have shown excellent performances and great potential in electrochemical energy storage, which are demonstrated by research works published in recent years. Some of these metal phosphides and phosphates and their hybrids compare favorably with transition metal oxides/hydroxides, which have been studied extensively as a class of electrode materials for supercapacitor applications, where they have limitations in terms of electrical and ion conductivity and device stability. To be specific, metal phosphides have both metalloid characteristics and good electric conductivity. For metal phosphates, the open‐framework structures with large channels and cavities endow them with good ion conductivity and charge storage capacity. In this review, we present the recent progress on metal phosphides and phosphates, by focusing on their advantages/disadvantages and potential applications as a new class of electrode materials in supercapacitors. The synthesis methods to prepare these metal phosphides/phosphates are looked into, together with the scientific insights involved, as they strongly affect the electrochemical energy storage performance. Particular attentions are paid to those hybrid‐type materials, where strong synergistic effects exist. In the summary, the future perspectives and challenges for the metal phosphides, phosphates and hybrid‐types are proposed and discussed.
Mesoporous NiS2 Nanospheres Anode with Pseudocapacitance for High‐Rate and Long‐Life Sodium‐Ion Battery
Authors: Sun Ruimin , Liu Sijie , Wei Qiulong , Sheng Jinzhi , Zhu Shaohua , An Qinyou , Mai Liqiang
Published: August 2017

It is of great importance to exploit electrode materials for sodium‐ion batteries (SIBs) with low cost, long life, and high‐rate capability. However, achieving quick charge and high power density is still a major challenge for most SIBs electrodes because of the sluggish sodiation kinetics. Herein, uniform and mesoporous NiS2 nanospheres are synthesized via a facile one‐step polyvinylpyrrolidone assisted method. By controlling the voltage window, the mesoporous NiS2 nanospheres present excellent electrochemical performance in SIBs. It delivers a high reversible specific capacity of 692 mA h g−1. The NiS2 anode also exhibits excellent high‐rate capability (253 mA h g−1 at 5 A g−1) and long‐term cycling performance (319 mA h g−1 capacity remained even after 1000 cycles at 0.5 A g−1). A dominant pseudocapacitance contribution is identified and verified by kinetics analysis. In addition, the amorphization and conversion reactions during the electrochemical process of the mesoporous NiS2 nanospheres is also investigated by in situ X‐ray diffraction. The impressive electrochemical performance reveals that the NiS2 offers great potential toward the development of next generation large scale energy storage.
Controlling Plasmon‐Enhanced Fluorescence via Intersystem Crossing in Photoswitchable Molecules
Authors: Wang Mingsong , Hartmann Gregory , Wu Zilong , Scarabelli Leonardo , Rajeeva Bharath Bangalore , Jarrett Jeremy W. , Perillo Evan P. , Dunn Andrew K. , Liz‐Marzán Luis M. , Hwang Gyeong S. , Zheng Yuebing
Published: August 2017

By harnessing photoswitchable intersystem crossing (ISC) in spiropyran (SP) molecules, active control of plasmon‐enhanced fluorescence in the hybrid systems of SP molecules and plasmonic nanostructures is achieved. Specifically, SP‐derived merocyanine (MC) molecules formed by photochemical ring‐opening reaction display efficient ISC due to their zwitterionic character. In contrast, ISC in quinoidal MC molecules formed by thermal ring‐opening reaction is negligible. The high ISC rate can improve fluorescence quantum yield of the plasmon‐modified spontaneous emission, only when the plasmonic electromagnetic field enhancement is sufficiently high. Along this line, extensive photomodulation of fluorescence is demonstrated by switching the ISC in MC molecules at Au nanoparticle aggregates, where strongly enhanced plasmonic hot spots exist. The ISC‐mediated plasmon‐enhanced fluorescence represents a new approach toward controlling the spontaneous emission of fluorophores near plasmonic nanostructures, which expands the applications of active molecular plasmonics in information processing, biosensing, and bioimaging.
On Two Glycine Zinc Sulfate Phases with Exotic Cation Coordination Geometries
Authors: Bette Sebastian , Hinrichsen Bernd , Dinnebier Robert E.
Published: August 2017

Two hitherto hardly characterized glycine zinc sulfates were identified in the product of a batch production process for glycine zinc sulfates of the BASF Company: Gly·ZnSO4·2H2O and β‐Gly‐ZnSO4. The crystal structures were solved from high resolution synchrotron X‐ray powder diffraction data. Gly·ZnSO4·2H2O is the zinc analogue to an isotypic copper compound with space group P21/c (no. 14) and a = 7.8092(1) Å, b = 12.3979(2) Å, c = 8.3732(1) Å, β = 90.673(1) and V = 810.62(2) Å³. The crystal structure of the hitherto unknown β‐Gly‐ZnSO4 with space group P21/c (no. 14) and a = 9.2577(1) Å, b = 5.1268(1) Å, c = 12.9926(1) Å, β = 90.267(1) and V = 616.65(1) Å3 was solved ab initio. In both crystal structures the zinc cations exhibit exotic, fivefold coordination arrangements: squared ZnO5‐pyramids are present in the structure of the dihydrate, whereas the crystal structure of β‐Gly‐ZnSO4 contains trigonal ZnO5‐bipyramids.
Mechanized proofs of opacity: a comparison of two techniques
Authors: Derrick John , Doherty Simon , Dongol Brijesh , Schellhorn Gerhard , Travkin Oleg , Wehrheim Heike
Published: August 2017

Software transactional memory (STM) provides programmers with a high-level programming abstraction for synchronization of parallel processes, allowing blocks of codes that execute in an interleaved manner to be treated as atomic blocks. This atomicity property is captured by a correctness criterion called
opacity
, which relates the behaviour of an STM implementation to those of a sequential atomic specification. In this paper, we prove opacity of a recently proposed STM implementation: the Transactional Mutex Lock (TML) by Dalessandro et al. For this, we employ two different methods: the first method directly shows all histories of TML to be opaque (proof by induction), using a linearizability proof of TML as an assistance; the second method shows TML to be a refinement of an existing intermediate specification called TMS2 which is known to be opaque (proof by simulation). Both proofs are carried out within interactive provers, the first with KIV and the second with both Isabelle and KIV. This allows to compare not only the proof techniques in principle, but also their complexity in mechanization. It turns out that the second method, already leveraging an existing proof of opacity of TMS2, allows the proof to be decomposed into two independent proofs in the way that the linearizability proof does not.
Clinical Safety of Renaming Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: Is NIFTP Truly Benign?
Authors: Parente David N. , Kluijfhout Wouter P. , Bongers Pim J. , Verzijl Raoul , Devon Karen M. , Rotstein Lorne E. , Goldstein David P. , Asa Sylvia L. , Mete Ozgur , Pasternak Jesse D.
Published: August 2017

Background

Renaming encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) to noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) was recently suggested to prevent the overtreatment, cost and stigma associated with this low‐risk entity. The purpose of this study is to document the incidence and further assess the clinical outcomes of reclassifying EFVPTC to NIFTP.

Methods

We searched synoptic pathologic reports from a high‐volume academic endocrine surgery hospital from 2004 to 2013. The standard of surgical pathology practice was based on complete submission of malignant thyroid nodules along with the nontumorous thyroid parenchyma. Rigid morphological criteria were used for the diagnosis of noninvasive EFVPTC, currently known as NIFTP. A retrospective chart review was conducted looking for evidence of malignant behavior.

Results

One hundred and two patients met the strict inclusion criteria of NIFTP. The incidence of NIFTP in our cohort was 2.1% of papillary thyroid cancer cases during the studied time period. Mean follow‐up was 5.7 years (range 0–11). Five patients were identified with nodal metastasis and one patient with distant metastasis. Overall, six patients showed evidence of malignant behavior representing 6% of patients with NIFTP.

Conclusion

Our study demonstrates that the incidence of NIFTP is significantly lower than previously thought. Furthermore, evidence of malignant behavior was seen in a significant number of NIFTP patients. Although the authors fully support the de‐escalation of aggressive treatment for low‐risk thyroid cancers, NIFTP behaves as a low‐risk thyroid cancer rather than a benign entity and ongoing surveillance is warranted.
The Effects of World War II Military Service: Evidence from Australia
Authors: Cousley Alex , Siminski Peter , Ville Simon
Published: August 2017

Outside of the United States, few studies have estimated the effects of World War II service. In Australia, general war-time conscription and minimal involvement in the Korean War led to large cohort differences in military service rates, which we use for identification. We find a small, temporary negative effect on employment and a substantial positive effect on post-school qualifications, but not at the university level. While service increased home ownership slightly, it greatly reduced outright home ownership, consistent with the incentives provided by veterans' housing benefits. We also find a positive effect on marriage, but only from 1971.
Research on the information transfer characteristics of dimensions in the product variant design process
Authors: Xu Xinsheng , Yan Tianhong , Ding Yangke
Published: August 2017

Product variant design, as one of the key enabling technologies of mass customization, is the transfer of variant information among mating parts from the perspective of informatics. A dimension constraint network (DCN) among mating parts carries on the task of transferring variant information. What are the information transfer characteristics of dimensions in a constraint network is a fundamental issue to plan the product variant design process reasonably. We begin by showing the natural dynamics of the DCN from two aspects: structure and uncertainty. The information efficiency of the DCN was proposed based on its simple path to specify the information transfer capability of the network. Based on this, the information centrality of the dimension was developed by measuring the efficiency loss of the DCN after the removal of a dimension from the network, which describes the information transfer capability of this dimension. Further, the information centrality of a part was derived. Using a spherical valve subassembly, we calculated the information centrality of the dimensions in a constraint network. We determined that the information centrality of dimension is highly correlated to its out-degree. An approach to plan the sequence of the part variant design according to its information centrality was proposed. We calculated the uncertainties of the DCN and its cumulative uncertainties under different sequences of the part variant design. Results indicate that part variant design under the descending information centrality of the parts minimizes the uncertainty of the DCN. This suggests a new method of planning the sequence of part variant design.
Multiple stent delivery system Multi-LOC, a new technology for spot-stenting of the femoropopliteal artery – proof of concept study in a preclinical large animal model
Authors: Sigl Martin , Dudeck Oliver , Jung Johannes , Koelble Heinz , Amendt Klaus
Published: August 2017

Abstract. Background: A new stent system was studied in a porcine model to evaluate its feasibility for spot-stenting of the femoropopliteal artery. Materials and methods: In a preliminary study in a single pig, handling and mechanical features of the novel multiple stent delivery system were tested. The Multi-LOC system demonstrated great feasibility regarding its pushability, trackability, and crossability. Excellent visibility of the individual stents allowed exact anatomically controlled implantation. In our main study, four to five short Multi-LOC stents (13 mm long) were implanted into the femoropopliteal arteries of six domestic pigs and long (60 to 100 mm) self-expandable nitinol stents were implanted into the same target vessel contralaterally to allow for intraindividual comparison. After four weeks survival under dual antiplatelet treatment, control angiography was performed. The animals were euthanized, stented vessels were explanted, and histologic sections were examined for the presence of neointimal formation. Results: Multi-LOC stents demonstrated no occlusion of the femoropopliteal axis (0 vs. 1 occlusion distal to a control stent), no stent fractures (0 out of 26 vs. 2 out of 6 control stents), and lower percentage diameter stenosis (0.564 ± 0.056 vs. 0.712 ± 0.089; p = 0.008) and length of stenosis (19.715 ± 5.225 vs. 39.397 ± 11.182; p = 0.007) compared to a standard control stent, which was similar in total length to the multiple stented artery segment. Histological examination confirmed myointimal hyperplasia underlying in-stent stenosis. Conclusions: The multiple stent delivery system was studied in a porcine model, which demonstrated its feasibility. Preclinical experience revealed favourable results concerning stent fracture, restenosis, and patency of spot-stented femoropopliteal arteries.
Discovery of a ROCK inhibitor, FPND, which prevents cerebral hemorrhage through maintaining vascular integrity by interference with VE-cadherin
Authors: Li Shang , Ai Nana , Shen Mingyun , Dang Yuanye , Chong Cheong-Meng , Pan Peichen , Kwan Yiu Wa , Chan Shun Wan , Leung George Pak Heng , Hoi Maggie Pui Man , Hou Tingjun , Lee Simon Ming-Yuen
Published: August 2017

Hemorrhagic stroke occurs when a weakened vessel ruptures and bleeds into the surrounding brain, leading to high rates of death and disability worldwide. A series of complex pathophysiological cascades contribute to the risk of hemorrhagic stroke, and no therapies have proven effective to prevent hemorrhagic stroke. Stabilization of vascular integrity has been considered as a potential therapeutic target for hemorrhagic stroke. ROCKs, which belong to the serine/threonine protein kinase family and participate in the organization of actin cytoskeleton, have become attractive targets for the treatment of strokes. In this study, in vitro enzyme-based assays revealed that a new compound (FPND) with a novel scaffold identified by docking-based virtual screening could inhibit ROCK1 specifically at low micromolar concentration. Molecular modeling showed that FPND preferentially interacted with ROCK1, and the difference between the binding affinity of FPND toward ROCK1 and ROCK2 primarily resulted from non-polar contributions. Furthermore, FPND significantly prevented statin-induced cerebral hemorrhage in a zebrafish model. In addition, in vitro studies using the xCELLigence RTCA system, immunofluorescence and western blotting revealed that FPND prevented statin-induced cerebral hemorrhage by enhancing endothelial cell–cell junctions through inhibiting the ROCK-mediated VE-cadherin signaling pathway. As indicated by the extremely low toxicity of FPND against mice, it is safe and can potentially prevent vascular integrity loss-related diseases, such as hemorrhagic stroke.
TRAIL DR5-CTSB crosstalk participates in breast cancer autophagy initiated by SAHA
Authors: Han Han , Zhou Hui , Li Jing , Feng Xiuyan , Zou Dan , Zhou Weiqiang
Published: August 2017

To investigate the ability of SAHA-induced TRAIL DR5-CTSB crosstalk to initiate the breast cancer autophagy, RTCA assay was performed to assess the effect of SAHA on breast cancer cells, and western blot and ELISA were used to verify the inductive effects on expression of CTSB. Breast cancer cells were transfected with TRAIL DR5 siRNA to block the function of TRAIL DR5. Cell viability and apoptosis of breast cancer cells were analyzed using a muse cell analyzer. The distribution of LC3-II in TRAIL DR5-silenced breast cancer cells treated with SAHA was observed by immunofluorescence microscopy, the mRNA levels of autophagy-related genes were detected by RNA microarray, and the activity of autophagy-related signaling pathways was screened by MAPK antibody array. Results indicated that SAHA did indeed repress the growth of breast cancer cell lines with inducing CTSB expression. Western blot and ELISA results indicated that TRAIL DR5 was involved in the expression of CTSB in SAHA-induced breast cancer cells. Cell viability and apoptosis assays showed that the inactivation of TRAIL DR5 can significantly inhibit the effects of SAHA. An immunofluorescence assay indicated that, with SAHA treatment, MDA-MB-231 and MCF-7 cells underwent apparent morphological changes. While SAHA was added in the TRAIL-DR5 blocked cells, the distribution of LC3-II signal was dispersed, the intensity of fluorescence signal was weaker than that of SAHA alone. RNA array indicated that SAHA significantly increased mRNA expression of autophagy marker LC3A/B whereas the change was significantly reversed in TRAIL DR5-silenced cells. The results of MAPK antibody array showed that SAHA and TRAIL DR5 could affect the activity of AKT1, AKT2, and TOR protein in breast cancer cells. These results provide more evidence that SAHA may stimulate TRAIL DR5-CTSB crosstalk, influence the activity of downstream TOR signalling pathway mainly through the AKTs pathway, and initiate the autophagy of breast cancer cells.
Modeling and measurement of curing properties of photocurable polymer containing magnetic particles and microcapsules
Authors: Yasui Masato , Ikuta Koji
Published: August 2017

In microstereolithography, three-dimensional microstructures are created by scanning an ultraviolet laser on a photocurable resin and stacking several such layers to form the desired structure. By mixing different types of particles in the resin, the formed microstructures exhibit various physical properties. For example, the magnetism and density of the microstructure can be controlled by adding magnetic particles and microcapsules to the resin. This method has been used to fabricate magnetic micromachines. Although such functional resins are useful, the incorporated magnetic particles and microcapsules can affect the fabrication resolution, making it difficult to fabricate microstructures with high precision. Thus, it is necessary to understand the effects of such microparticles and microcapsules on the fabrication process. In this study, we propose a simple model of curing resins containing magnetic particles and microcapsules to explain the effects of the magnetic particles and microcapsules. The proposed model can explain the observed curing characteristics of a resin that contains particles for all concentrations as well as for different types of magnetic particles and microcapsules. Finally, using the proposed model, we discuss how to improve the characteristics of resins containing microparticles to realize the high-resolution fabrication of three-dimensional microstructures with desirable material properties.
Retraction Note: A photon thermal diode
Authors: Chen Zhen , Wong Carlaton , Lubner Sean , Yee Shannon , Miller John , Jang Wanyoung , Hardin Corey , Fong Anthony , Garay Javier E. , Dames Chris
Published: August 2017

Nature Communications 5: Article number: 5446 (2014); Published: 17 November 2014; Updated: 21 August 2017 Because two of its three major findings have been invalidated, the authors wish to retract this Article1. Budaev2 correctly identifies a fundamental symmetry error in the way the ‘inelastic thermal collimation’ was configured in several crucial experiments of ref.
Comparing structural and transcriptional drug networks reveals signatures of drug activity and toxicity in transcriptional responses
Authors: Sirci Francesco , Napolitano Francesco , Pisonero-Vaquero Sandra , Carrella Diego , Medina Diego L. , di Bernardo Diego
Published: August 2017

We performed an integrated analysis of drug chemical structures and drug-induced transcriptional responses. We demonstrated that a network representing three-dimensional structural similarities among 5452 compounds can be used to automatically group together drugs with similar scaffolds, physicochemical parameters and mode-of-action. We compared the structural network to a network representing transcriptional similarities among a subset of 1309 drugs for which transcriptional response were available in the Connectivity Map data set. Analysis of structurally similar, but transcriptionally different drugs sharing the same MOA enabled us to detect and remove weak and noisy transcriptional responses, greatly enhancing the reliability of transcription-based approaches to drug discovery and drug repositioning. Cardiac glycosides exhibited the strongest transcriptional responses with a significant induction of pathways related to epigenetic regulation, which suggests an epigenetic mechanism of action for these drugs. Drug classes with the weakest transcriptional responses tended to induce expression of cytochrome P450 enzymes, hinting at drug-induced drug resistance. Analysis of transcriptionally similar, but structurally different drugs with unrelated MOA, led us to the identification of a 'toxic' transcriptional signature indicative of lysosomal stress (lysosomotropism) and lipid accumulation (phospholipidosis) partially masking the target-specific transcriptional effects of these drugs. We found that this transcriptional signature is shared by 258 compounds and it is associated to the activation of the transcription factor TFEB, a master regulator of lysosomal biogenesis and autophagy. Finally, we built a predictive Random Forest model of these 258 compounds based on 128 physicochemical parameters, which should help in the early identification of potentially toxic drug candidates.
Toroidal response in all-dielectric metamaterials based on water
Authors: Stenishchev Ivan V. , Basharin Alexey A.
Published: August 2017

We experimentally demonstrate for the first time the toroidal dipolar response in metamaterials based on clusters of cylindrical dielectric particles in microwave frequency range. Instead of expensive ceramic elements we used distilled water with permittivity at room temperature is about 75, while the dielectric loss tangent is not large at frequencies up to 4 GHz. Moreover, we show all-dielectric metamaterial consisting of water box with hollow tubes which is more practical for future applications. Our findings also demonstrate that the proposed ideas can be applicable in optics with low-index dielectrics.
No difference in plasticity between different ploidy levels in the Mediterranean herb Mercurialis annua
Authors: Sánchez Vilas Julia , Pannell John R.
Published: August 2017

Increased phenotypic plasticity for a number of plant traits has been suggested as a possible reason for the success and spread of polyploids. One such trait is a plant’s sex allocation (or gender), which influences its reproductive success directly as a function of the potentially heterogeneous mating prospects in the population. However, it is unknown how polyploidyper semight affect plasticity in a plant’s sex allocation. Although there have been numerous comparisons between diploid and (usually) tetraploid taxa, we know very little about how elevated ploidy above the diploid level might affect plasticity. Here, we ask whether different ploidy levels > 2x express different plasticity in the ruderal plantMercurialis annua. We grew tetraploid and hexaploid hermaphrodites under different levels of nutrient availability and compared their reaction norms for growth (above-ground biomass, SLA) and reproductive traits (reproductive effort, phenotypic gender). Overall, we found that an increase in ploidy level from 4x to 6x inM.annuais associated with an increase in the relative biomass allocated to seeds, measured as female reproductive effort. However, our study provides no support for the idea that increasing ploidy level increases the ability to express different phenotypes in response to changes in the environment.
Phase Behavior and Thermodynamic Model Parameters in Simulations of Extractive Distillation for Azeotrope Separation
Authors: Li Min , Xu Xicai , Li Xin , Ma Kang , Qin Bin , Zhu Zhaoyou , Wang Yinglong
Published: August 2017

Extractive distillation (ED) processes for separating ternary mixtures of benzene-cyclohexane-toluene with dimethyl formamide (DMF) and N-methyl-2-pyrrolidone (NMP) were studied using Aspen Plus and PRO/II simulators. The Aspen Plus built-in binary interaction parameters for the toluene-DMF, benzene-NMP and cyclohexane-NMP systems resulted in inaccurate phase behavior calculations. The vapor-liquid equilibrium (VLE) for the three binary systems was regressed to illustrate the importance of using accurate model parameters. The obtained binary interaction parameters described the phase behavior more accurately compared with the built-in binary interaction parameters in Aspen Plus. In this study, the effects of the regressed and built-in binary interaction parameters on the ED process design are presented. The total annual cost (TAC) was calculated to further illustrate the importance of the regressed binary interaction parameters. The results show that phase behavior and thermodynamic model parameters should receive more attention during the research and development of ED processes.
Using the New CellCollector to Capture Circulating Tumor Cells from Blood in Different Groups of Pulmonary Disease: A Cohort Study
Authors: He Yutong , Shi Jin , Shi Gaofeng , Xu Xiaoli , Liu Qingyi , Liu Congmin , Gao Zhaoyu , Bai Jiaoteng , Shan Baoen
Published: August 2017

Circulating tumor cells (CTCs) are promising biomarkers for clinical application. Cancer screening with Low-Dose Computed Tomography (LDCT) and CTC detections in pulmonary nodule patients has never been reported. The aim of this study was to explore the effectiveness of the combined methods to screen lung cancer. Out of 8313 volunteers screened by LDCT, 32 ground-glass nodules (GGNs) patients and 19 healthy volunteers were randomly selected. Meanwhile, 15 lung cancer patients also enrolled. CellCollector, a new CTC capturing device, was applied for CTCs detection. In GGNs group, five CTC positive patients with six CTCs were identified, 15.6% were positive (range, 1–2). In lung cancer group, 73.3% of the analyzed CellCollector cells were positive (range, 1–7) and no “CTC-like” events were detected in healthy group. All CTCs detected from GGNs group were isolated from the CellCollector functional domain and determined by whole genomic amplification for next-generation sequencing(NGS) analysis. NGS data showed that three cancer-related genes contained mutations in five CTC positive patients, including KIT, SMARCB1 and TP53 genes. In four patients, 16 mutation genes existed. Therefore, LDCT combined with CTC analysis by an in vivo device in high-risk pulmonary nodule patients was a promising way to screen early stage lung cancer.
Dynamics of resilience of wheat to drought in Australia from 1991–2010
Authors: Huai Jianjun
Published: August 2017

Although enhancing resilience is a well-recognized adaptation to climate change, little research has been undertaken on the dynamics of resilience. This occurs because complex relationships exist between adaptive capacity and resilience, and some issues also create challenges related to the construction, operation, and application of resilience. This study identified the dynamics of temporal, spatial changes of resilience found in a sample of wheat–drought resilience in Australia’s wheat–sheep production zone during 1991–2010. I estimated resilience using principal component analysis, mapped resilience and its components, distinguished resilient and sensitive regions, and provided recommendations related to improving resilience. I frame that resilience is composed of social resilience including on- and off-site adaptive capacity as well as biophysical resilience including resistance and absorption. I found that resilience and its components have different temporal trends, spatial shifts and growth ratios in each region during different years, which results from complicated interactions, such as complementation and substitution among its components. In wheat-sheep zones, I recommend that identifying regional bottlenecks, science-policy engagement, and managing resilience components are the priorities for improving resilience.
NogoA Neutralization Promotes Axonal Restoration After White Matter Injury In Subcortical Stroke
Authors: Otero-Ortega Laura , Gómez-de Frutos Mari Carmen , Laso-García Fernando , Sánchez-Gonzalo Alba , Martínez-Arroyo Arturo , Díez-Tejedor Exuperio , Gutiérrez-Fernández María
Published: August 2017

Blocking axonal growth inhibitor NogoA has been of great interest for promoting axonal recovery from neurological diseases. The present study investigates the therapeutic effects of blocking NogoA, inducing functional recovery and promoting white matter repair in an experimental animal model of stroke. Adult male rats were subjected to white matter injury by subcortical ischemic stroke. Twenty-four hours after surgery, 250 ug of anti-NogoA or anti-IgG-1 were administered through the tail vein. The quantity of NogoA protein was determined by immunohistochemistry in the brain and peripheral organs. In addition, functional status, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers were analyzed. Moreover, an in vitro study was performed in order to strengthen the results obtained in vivo. A lower quantity of NogoA protein was found in the brain and peripheral organs of the animals that received anti-NogoA treatment. The animals receiving anti-NogoA treatment showed significantly better results in terms of functional recovery, fiber tract integrity, axonal sprouting and white matter repair markers compared with the control group at 28 days. White matter integrity was in part restored by antibody-mediated inhibition of NogoA administration in those animals that were subjected to an axonal injury by subcortical stroke. This white matter restoration triggered functional recovery.
Sofosbuvir protects Zika virus-infected mice from mortality, preventing short- and long-term sequelae
Authors: Ferreira André C. , Zaverucha-do-Valle Camila , Reis Patrícia A. , Barbosa-Lima Giselle , Vieira Yasmine Rangel , Mattos Mayara , Silva Priscila de Paiva , Sacramento Carolina , de Castro Faria Neto Hugo C. , Campanati Loraine , Tanuri Amilcar , Brüning Karin , Bozza Fernando A. , Bozza Patrícia T. , Souza Thiago Moreno L.
Published: August 2017

Zika virus (ZIKV) causes significant public health concerns because of its association with congenital malformations, neurological disorders in adults, and, more recently, death. Considering the necessity to mitigate ZIKV-associated diseases, antiviral interventions are an urgent necessity. Sofosbuvir, a drug in clinical use against hepatitis C virus (HCV), is among the FDA-approved substances endowed with anti-ZIKV activity. In this work, we further investigated the in vivo activity of sofosbuvir against ZIKV. Neonatal Swiss mice were infected with ZIKV (2 × 107 PFU) and treated with sofosbuvir at 20 mg/kg/day, a concentration compatible with pre-clinical development of this drug. We found that sofosbuvir reduced acute levels of ZIKV from 60 to 90% in different anatomical compartments, such as the blood plasma, spleen, kidney, and brain. Early treatment with sofosbuvir doubled the percentage and time of survival of ZIKV-infected animals. Sofosbuvir also prevented the acute neuromotor impairment triggered by ZIKV. In the long-term behavioural analysis of ZIKV-associated sequelae, sofosbuvir prevented loss of hippocampal- and amygdala-dependent memory. Our results indicate that sofosbuvir inhibits ZIKV replication in vivo, which is consistent with the prospective necessity of antiviral drugs to treat ZIKV-infected individuals.