bluuebunny/crossref_metadata_2025 huggingface dataset:
New Onshore Drilled Cuttings Treatment Facility Takes a Bold Environmental Initiative in Ghana
Authors: Zormelo Michael , Donkor Paul Yaw , Ametewee Selorm Alfred
Published: October 2016

The first major deepwater oil discovery was made in Ghana during 2007. Since then over 50 deepwater wells have been drilled by various operators using Low Toxicity Oil Based drilling fluids. Discharge of drilled cuttings to the ocean with residual oil on cuttings has been permitted in Ghana under the current regulatory regime. Current offshore cuttings drier technology will reduce residual oil on cuttings to low levels prior to discharge but not eliminate it completely.

Many other offshore drilling areas around the world operate a ‘zero discharge’ approach where no oil contaminated cuttings are permitted to be discharged overboard. In this case the cuttings are contained offshore before being shipped onshore for treatment. The oil is then removed and reused using thermal desorption or equivalent technology, the clean water is discharged and remaining clean cuttings are utilised in land fill sites or in some cases building products. These ‘Skip and ship’ methods require offshore cuttings handling equipment, a supply chain involving marine vessels and trucks for onshore cuttings transport. Most importantly it requires a specialised onshore treatment facility that will completely remove any residual oil on cuttings prior to disposal of the clean dry cuttings.

This paper will describe the component parts of a skip and ship method and how it would operate in a new deepwater oil province. It describes in detail how one service provider pre-emptively set up an onshore cuttings treatment facility in Ghana in readiness for future skip and ship operations. The detailed technical operation of the facility is described and technical and political learnings are offered.
CHEMOPROTECTIVE EFFECT OF NONI (MORINDA CITRIFOLIA L.) FRUIT JUICE AGAINST CISPLATIN-INDUCED NEPHROTOXICITY
Authors: Ali Mohammad , K. Mruthunjaya , C. Nandini , K. Nabeel , N. Manjula S.
Published: October 2016

Objective: Cisplatin (CIS) consumption has become a common problem that affects the health of patients around the globe. Kidney has been suspected to be particularly susceptible to the destructive effects of CIS and nephrotoxic effects are still contentious which in turn affects the Quality of Life (QoL) of patients and increase the mortality rate. This study was conducted to investigate the nephroprotective effect of Noni Juice (NJ) and Divine Noni Gold (DNG) as herbal medicine with established antioxidant properties against the controversial nephrotoxic effect of CIS in mice.

Methods: Mice were divided into four groups, each group contained six mice. Group I was kept as normal, Group II received CIS (5.0 mg/kg b. wt. i. p.) on day one for 14 d. Group III and IV received NJ (0.35 ml/mouse p. o.) and DNG (0.35 ml/mouse p. o.) respectively once daily for 14 d, Group V received CIS (5.0 mg/kg b. wt. i. p.) on day one and NJ (0.35 ml/mouse p. o.) once daily for 14 d. Similarly, Group VI received CIS (5.0 mg/kg b. wt. i. p.) on day one and DNG (0.35 ml/mouse p. o.) once daily for 14 d. On day 15 blood from all the mice was collected from the carotid vein and cardiac puncture routes, and the biochemical markers viz. lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), urea were assessed. Kidney from all the animals was isolated, and catalase (CAT), glutathione (GSH), superoxide dismutase (SOD), thiols and lipid peroxidase (LPO) were estimated.

Results: CIS-induced marked kidney injury; congestion of tubules, glomerular distortion foci, thickened and blocked blood vessels. Also showed significant elevation of LDH, CPK, and urea with significant inhibition of CAT, GSH, SOD, thiols activities and simultaneously elevation of LPO level. Co-administration of NJ and DNG respectively with CIS protected kidney tissues via oxidative stress inhibition.

Conclusion: NJ and DNG possess protective effect against CIS-induced cellular damage in the kidney by decreasing the level of serum biochemical markers, enhancing the level of enzymatic and non-enzymatic antioxidants and maintaining the LPO level. Results suggest that NJ and DNG have strong nephroprotective effect against CIS-induced nephrotoxicity.
The coefficientof hydraulic friction of laminar open flows in smooth channels
Authors: Medzveliya Manana Levanovna , Borovkov Valeriy Stepanovich
Published: October 2016

The article examines the dependence of the hydraulic friction coefficient of open laminar uniform streams on the relative width of channels with smooth bottom. The article presents the functional dependence that describes the hydraulic resistance in open channels with smooth bottoms.The experiments were carried out in a rectangular tray (6000×100×200). Aqueous solutions of glycerol were used as working fluids. The superficial tension and liquid density for the used liquids changed a little. The article declares that the coefficient of hydraulic friction λ in the zone of the laminar flow depends on the relative width of the channels with smooth bottom. In the article it is also shown that the Charny formula satisfactorily agrees with the theoretical formula and with the experimental data.
Revisiting Destination Choice Sets: Two Evaluation Modes
Authors: Chung Jin Young , Petrick James F.
Published: October 2016

This study revisited destination choice sets. Two distinct choice modes—joint evaluation (considering multiple destinations for a pleasure trip) and separate evaluation (considering only one destination when searching for information)—were identified. Findings revealed that
women, repeated visitors, and affluent tourists living out of state were more likely to take a separate evaluation mode. Conversely, tourists who frequently took overnight trips and in-state residents were more likely to consider multiple options. Results suggest that tourism professionals
should tailor marketing information that best fits each segment instead of merely sending out general information.
Los franceses en México: una mirada desde la historiografía regional
Authors: Arias Patricia
Published: October 2016

El artículo discute las presencias y ausencias de los franceses a partir de una revisión de la historiografía regional de los años setenta y ochenta. Revisión hecha sobre todo a partir de los estudios que se hicieron acerca del surgimiento y desarrollo de la industria textil en México. Incluye sobre todo trabajos que se refieren a los estados que fueron más historiados al respecto: Jalisco, Puebla y Veracruz. El artículo incluye, al final, una breve bibliografía comentada, acerca de los principales títulos que trataron el tema.
Efficacy and safety of new oral anticoagulants in prophylaxis and treatment of venous thromboembolism
Authors: Masotti Luca
Published: October 2016

One of the main innovation emerged in recent years in the field of venous thromboembolism (VTE) has been represented by the clinical development and marketing of new oral anticoagulant agents used for prophylaxis and acute treatment. These drugs are represented by direct thrombin inhibitors (anti-factor IIa) and the direct inhibitors of activated factor X (anti-Xa). The main achievementof these new agents is represented by their ease of use without laboratory monitoring or dose adjustment. Dabigatran (anti-factor IIa), rivaroxaban, and apixaban (anti-Xa) are in advanced phase of clinical development with concluded phase III trials. Up to now the results of efficacy and safetyof phase III clinical trials are available, while phase IV studies are currently ongoing. Overall, the phase III clinical trials showed the non inferiority of new oral anticoagulants in VTE prophylaxis of patients undergone to major orthopedic surgery, such as hip and knee arthroplasty, compared toconventional prophylaxis represented by subcutaneous low molecular weight heparin with similar safety. Moreover dabigatran has shown to be not inferior when compared to warfarin for the prevention of six months VTE recurrences, with a significative lower incidence of bleedings. Awaitingthe results of many other ongoing phase III trials, since now it is possible to think that, in the next future, new oral anticoagulants will be widely diffused in clinical practice for their ease of use and feasibility. In this review the Authors analyse the available results of phase III clinical trials for dabigatran, rivaroxaban and apixaban, focusing on the antithrombotic endpoints for prevention andtreatment of VTE and the bleeding risk. Moreover synthesis of ongoing trials will be displayed.
The Zodiac Calendar and Equity Factor Returns
Authors: Phoeng Janice , Swinkels Laurens
Published: October 2016

We calculate the returns for four well-known equity return factors—market, size, value, and momentum—for each zodiac calendar year from 1927 to 2015. We find that the point estimates of average returns for each zodiac sign can be substantially different. However, when we employ statistical tests, we do not find enough evidence to reject the null hypothesis of equal excess returns across zodiac signs. For an investor with an equally weighted portfolio in these four equity factors, the Year of the Rooster may seem particularly good and the Year of the Ox particularly poor, but also in this case the null hypothesis cannot be rejected. Hence, we conclude that investment strategies based on zodiac signs are unlikely to generate superior returns.
Enzymatic Ugi Reaction with Amines and Cyclic Imines
Authors: Żądło‐Dobrowolska Anna , Kłossowski Szymon , Koszelewski Dominik , Paprocki Daniel , Ostaszewski Ryszard
Published: October 2016

The application of the Ugi reaction to the construction of new peptide scaffolds is an important goal of organic chemistry. To date, there are no examples of the Ugi reaction being performed with a cyclic imine and amine simultaneously. The application of 2‐substituted cyclic imines in an enzymatic three‐component Ugi‐type reaction provides an elegant and attractive synthesis of substituted pyrrolidine and piperidine derivatives in up to 60 % yield. Results on studies of the selection of an enzyme, amount of water, and solvent used in a novel three‐component Ugi reaction and the limitations thereof are reported herein. The presented methodology exploiting enzyme promiscuity in the multicomponent reaction fulfills the requirements associated with green chemistry. Several methods, such as isotope labeling and enzyme inhibition, were used to probe the possible mechanism of this complex synthesis. This research is the first example of an enzyme‐catalyzed Ugi‐type reaction with an imine, amine, and isocyanide.
Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies
Authors: Shibany Khaled A. , Tötemeyer Sabine , Pratt Stefanie L. , Paine Stuart W.
Published: October 2016

Despite reports of the successful isolation of primary equine hepatocytes, there are no published data regarding the successful cryopreservation of these isolated cells. In this study, a detailed description of the procedures for isolation, cryopreservation, and recovery of equine hepatocytes are presented. Furthermore, the intrinsic clearance (Clint) and production of metabolites for three drugs were compared between freshly isolated and recovered cryopreserved hepatocytes. Primary equine hepatocytes were isolated using a two‐step collagenase perfusion method, with an average cell yield of 2.47 ± 2.62 × 106 cells/g of perfused liver tissue and viability of 84.1 ± 2.62%. These cells were cryopreserved with William's medium E containing 10% fetal bovine serum with 10% DMSO. The viability of recovered cells, after a 30% Percoll gradient, was 77 ± 11% and estimated recovery rate was approximately 27%. These purified cells were used to determine the in vitro Clint of three drugs used in equine medicine; omeprazole, flunixin, and phenylbutazone, via the substrate depletion method. Cryopreserved suspensions gave a comparable estimation of Clint compared to fresh cells for these three drugs as well as producing the same metabolites. This work paves the way for establishing a bank of cryopreserved equine hepatocytes that can be used for estimating pharmacokinetic parameters such as the hepatic metabolic in vivo clearance of a drug as well as producing horse‐specific drug metabolites.
Contrasting hydraulic strategies in Salix psammophila and Caragana korshinskii in the southern Mu Us Desert, China
Authors: Li Yangyang , Chen Weiyue , Chen Jiacun , Shi Hui
Published: October 2016

Salix psammophila and Caragana korshinskii are two common shrubs in the southern Mu Us Desert, China. Their hydraulic strategies for adapting to this harsh, dry desert environment are not yet clear. This study examined the hydraulic transport efficiency, vulnerability to cavitation, and daily embolism refilling in the leaves and stems of these two shrubs during the dry season. In order to gain insight into water use strategies of whole plants, other related traits were also considered, including daily changes in stomatal conductance, leaf mass per area, leaf pressure–volume parameters, wood density and the Huber value. The leaves and stems of S. psammophila had greater hydraulic efficiency, but were more vulnerable to drought‐induced hydraulic dysfunction than C. korshinskii. The difference between leaf and stem water potential at 50 % loss of conductivity was 0.12 MPa for S. psammophila and 0.81 MPa for C. korshinskii. Midday stomatal conductance decreased by 74 % compared to that at 8:30 in S. psammophila, whereas no change occurred in C. korshinskii. Daily embolism and refilling occurred in the stems of S. psammophila and leaves of C. korshinskii. These results suggest that a stricter stomatal regulation, daily embolism repair in stems, and a higher stem water capacitance could be partially compensating for the greater susceptibility to xylem embolism in S. psammophila, whereas higher leaf elastic modulus, greater embolism resistance in stems, larger difference between leaf and stem hydraulic safety, and drought‐induced leaf shedding in C. korshinskii were largely responsible for its more extensive distribution in arid and desert steppes.
Comparative Judgment Processes: The Effects of Task Objectives and Time Delay on Product Evaluations
Authors: Wang Jing , Wyer Robert S.
Published: October 2016

Consumers who compare products may often ignore features that the choice alternatives have in common. As a result, they often evaluate products more favorably when the products have unique positive features but common negative features than when they have unique negative features but common positive ones. Two studies examined contingencies in the occurrence of these “cancellation” effects and explored their implications for people's evaluations of not only the products being compared but other products they encounter subsequently. Some participants were explicitly told to compare two products at the time they received information about them. They not only disregarded the products' common features when initially evaluating these products, but disregarded evaluatively similar features of a third product they encountered some time later. Other participants were initially told to describe each product separately. In this condition, they formed an overall impression of each product individually, and so cancellation effects were not apparent. Nevertheless, their preference for one product over the other was based on a comparison of the products' individual features that they could recall at the time of judgment rather than on the global impressions they had formed when the product information was first presented.
Controls on the transport of oceanic heat to Kangerdlugssuaq Glacier, East Greenland
Authors: COWTON TOM , SOLE ANDREW , NIENOW PETER , SLATER DONALD , WILTON DAVID , HANNA EDWARD
Published: October 2016

Greenland's marine-terminating glaciers may be sensitive to oceanic heat, but the fjord processes controlling delivery of this heat to glacier termini remain poorly constrained. Here we use a three-dimensional numerical model of Kangerdlugssuaq Fjord, East Greenland, to examine controls on fjord/shelf exchange. We find that shelf-forced intermediary circulation can replace up to ~25% of the fjord volume with shelf waters within 10 d, while buoyancy-driven circulation (forced by subglacial runoff from marine-terminating glaciers) exchanges ~10% of the fjord volume over a 10 d period under typical summer conditions. However, while the intermediary circulation generates higher exchange rates between the fjord and shelf, the buoyancy-driven circulation is consistent over time hence more efficient at transporting water along the full length of the fjord. We thus find that buoyancy-driven circulation is the primary conveyor of oceanic heat to glaciers during the melt season. Intermediary circulation will however dominate during winter unless there is sufficient input of fresh water from subglacial melting. Our findings suggest that increasing shelf water temperatures and stronger buoyancy-driven circulation caused the heat available for melting at Kangerdlugssuaq Glacier to increase by ~50% between 1993–2001 and 2002–11, broadly coincident with the onset of rapid retreat at this glacier.
Jewish Traditions and Familial Roman Values in Philo'sDe Abrahamo245–254
Authors: Livneh Atar
Published: October 2016

InDe Abrahamo, Philo exegetes selected episodes from the biblical Abraham cycle. These include the account of Sarah's death recorded in Gen 23. Interpreting this narrative literally, Philo expands it by introducing an encomium to the matriarch (Abr. 245–254). This exemplifies her virtuous character by illustrating how she sought an offspring for Abraham through her servant Hagar (see Gen 16).
Making Faith One's Own: Kevin Hector's Defense of
Modern Theology
Authors: Lockwood Charles E.
Published: October 2016

In The Theological Project of Modernism, Kevin Hector of the
University of Chicago Divinity School offers a nuanced and timely defense of
what he sees as an unjustifiably maligned tradition in modern Christian
theology. He focuses on what is commonly labeled the liberal or revisionist
tradition, centered in its early stages on figures such as Immanuel Kant,
Friedrich Schleiermacher, G. W. F. Hegel, Albrecht Ritschl, Ernst Troeltsch,
and, more recently, Paul Tillich. By carefully reconstructing key arguments from
these thinkers, Hector shows not only how this trajectory hangs together as a
tradition, but also how its animating impulse differs from what many critics
have assumed. Hector's central claim is that this tradition is
fundamentally concerned with a distinctive problem, namely, how to relate
religious faith to a sense of one's life as one's own—or,
put differently, how one's faith can be self-expressive. Hector labels
this the problem of “mineness,” or the problem of “how
persons could identify with their lives or experience them as
‘mine,’ especially given their vulnerability to tragedy,
injustice, luck, guilt, and other ‘oppositions’” (viii).
Hector argues that for his chosen thinkers in this tradition, faith—more
specifically, faith in a God who is able to reconcile such
oppositions—plays a crucial role in resolving this problem.
Expression of the T85A mutant of zebrafish aquaporin 3b improves post-thaw survival of cryopreserved early mammalian embryos
Authors: Bedford-Guaus Sylvia J. , Chauvigné François , Mejía-Ramírez Eva , Martí Mercè , Ventura-Rubio Antoni , Raya Ángel , Cerdà Joan , Veiga Anna
Published: October 2016

While vitrification has become the method of choice for preservation of human oocytes and embryos, cryopreservation of complex tissues and of large yolk-containing cells, remains largely unsuccessful. One critical step in such instances is appropriate permeation while avoiding potentially toxic concentrations of cryoprotectants. Permeation of water and small non-charged solutes, such as those used as cryoprotectants, occurs largely through membrane channel proteins termed aquaporins (AQPs). Substitution of a Thr by an Ala residue in the pore-forming motif of the zebrafish (Dario rerio) Aqp3b paralog resulted in a mutant (DrAqp3b-T85A) that when expressed inXenopusor porcine oocytes increased their permeability to ethylene glycol at pH 7.5 and 8.5. The main objective of this study was to test whether ectopic expression of DrAqp3b-T85A also conferred higher resistance to cryoinjury. For this, DrAqp3b-T85A + eGFP (reporter) cRNA, or eGFP cRNA alone, was microinjected intoin vivofertilized 1-cell mouse zygotes. Following culture to the 2-cell stage, appropriate membrane expression of DrAqp3b-T85A was confirmed by immunofluorescence microscopy using a primary specific antibody directed against the C-terminus of DrAqp3b. Microinjected 2-cell embryos were then cryopreserved using a fast-freezing rate and low concentration (1.5 M) of ethylene glycol in order to highlight any benefits from DrAqp3b-T85A expression. Notably, post-thaw survival rates were higher (P<0.05) for T85A–eGFP-injected than for -uninjected or eGFP-injected embryos (73±7.3 vs. 28±7.3 or 14±6.7, respectively). We propose that ectopic expression of mutant AQPs may provide an avenue to improve cryopreservation results of large cells and tissues in which current vitrification protocols yield low survival.
Memory, Transnational Justice, and Recession in Contemporary Spain
Authors: Ryan Lorraine
Published: October 2016

The 2007 Law of Historical Memory, which aimed to excise the spatial remnants of Francoism from the Spanish landscape, and to recognise Republican victimhood, was blatantly inadequate, and left victims in the same legal position as before.1In the immediate aftermath of the law, the Spanish state institutionally divorced itself from the recuperation of Republican memory by closing down the Office for Victims of the War and Dictatorship,2and reducing the funding devoted to historical memory from 6.5 to 2.5 million in 2011. This article will examine the subsequent transnationalisation of Republican memory, in the form of its Argentinisation, and economic protest movements’ appropriation of the memory of the Second Republic. Relatedly, it seeks to answer overarching questions concerning the reach and scope of global memory edicts in national memory debates.
Pooling ANOVA Results From Multiply Imputed Datasets
Authors: Grund Simon , Lüdtke Oliver , Robitzsch Alexander
Published: October 2016

Abstract. The analysis of variance (ANOVA) is frequently used to examine whether a number of groups differ on a variable of interest. The global hypothesis test of the ANOVA can be reformulated as a regression model in which all group differences are simultaneously tested against zero. Multiple imputation offers reliable and effective treatment of missing data; however, recommendations differ with regard to what procedures are suitable for pooling ANOVA results from multiply imputed datasets. In this article, we compared several procedures (known as D1, D2, and D3) using Monte Carlo simulations. Even though previous recommendations have advocated that D2 should be avoided in favor of D1 or D3, our results suggest that all procedures provide a suitable test of the ANOVA’s global null hypothesis in many plausible research scenarios. In more extreme settings, D1 was most reliable, whereas D2 and D3 suffered from different limitations. We provide guidelines on how the different methods can be applied in one- and two-factorial ANOVA designs and information about the conditions under which some procedures may perform better than others. Computer code is supplied for each method to be used in freely available statistical software.
Cross-Cutting Exposure on Facebook and Political	Participation
Authors: Lu Yanqin , Gall Myrick Jessica
Published: October 2016

Abstract. This experiment (N = 193) explores the effects of cross-cutting exposure via social media on two types of political participation. The results reveal that exposure to cross-cutting social media news can motivate cheap participation better than costly participation. Moreover, the mobilizing effects of cross-cutting exposure are mediated by anger and anxiety, as suggested by affective intelligence theory and appraisal theories of emotion. The mediating effects of anxiety are also moderated by online incivility. Implications are discussed in terms of the role of social media use and cross-cutting exposure in participatory democracies.
Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7
Authors: Yong Kar Wey , Li Yuhui , Liu Fusheng , Bin Gao  , Lu Tian Jian , Wan Abas Wan Abu Bakar , Wan Safwani Wan Kamarul Zaman , Pingguan-Murphy Belinda , Ma Yufei , Xu Feng , Huang Guoyou
Published: October 2016

Human mesenchymal stem cells (hMSCs) hold great promise in cardiac fibrosis therapy, due to their potential ability of inhibiting cardiac myofibroblast differentiation (a hallmark of cardiac fibrosis). However, the mechanism involved in their effects remains elusive. To explore this, it is necessary to develop an in vitro cardiac fibrosis model that incorporates pore size and native tissue-mimicking matrix stiffness, which may regulate cardiac myofibroblast differentiation. In the present study, collagen coated polyacrylamide hydrogel substrates were fabricated, in which the pore size was adjusted without altering the matrix stiffness. Stiffness is shown to regulate cardiac myofibroblast differentiation independently of pore size. Substrate at a stiffness of 30 kPa, which mimics the stiffness of native fibrotic cardiac tissue, was found to induce cardiac myofibroblast differentiation to create in vitro cardiac fibrosis model. Conditioned medium of hMSCs was applied to the model to determine its role and inhibitory mechanism on cardiac myofibroblast differentiation. It was found that hMSCs secrete hepatocyte growth factor (HGF) to inhibit cardiac myofibroblast differentiation via downregulation of angiotensin II type 1 receptor (AT1R) and upregulation of Smad7. These findings would aid in establishment of the therapeutic use of hMSCs in cardiac fibrosis therapy in future.
Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability
Authors: Palomba R. , Parodi A. , Evangelopoulos M. , Acciardo S. , Corbo C. , de Rosa E. , Yazdi I. K. , Scaria S. , Molinaro R. , Furman N. E. Toledano , You J. , Ferrari M. , Salvatore F. , Tasciotti E.
Published: October 2016

Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.
Computer keyboard interaction as an indicator of early Parkinson’s disease
Authors: Giancardo L. , Sánchez-Ferro A. , Arroyo-Gallego T. , Butterworth I. , Mendoza C. S. , Montero P. , Matarazzo M. , Obeso J. A. , Gray M. L. , Estépar R. San José
Published: October 2016

Parkinson’s disease (PD) is a slowly progressing neurodegenerative disease with early manifestation of motor signs. Objective measurements of motor signs are of vital importance for diagnosing, monitoring and developing disease modifying therapies, particularly for the early stages of the disease when putative neuroprotective treatments could stop neurodegeneration. Current medical practice has limited tools to routinely monitor PD motor signs with enough frequency and without undue burden for patients and the healthcare system. In this paper, we present data indicating that the routine interaction with computer keyboards can be used to detect motor signs in the early stages of PD. We explore a solution that measures the key hold times (the time required to press and release a key) during the normal use of a computer without any change in hardware and converts it to a PD motor index. This is achieved by the automatic discovery of patterns in the time series of key hold times using an ensemble regression algorithm. This new approach discriminated early PD groups from controls with an AUC = 0.81 (n = 42/43; mean age = 59.0/60.1; women = 43%/60%;PD/controls). The performance was comparable or better than two other quantitative motor performance tests used clinically: alternating finger tapping (AUC = 0.75) and single key tapping (AUC = 0.61).
Effects of Resistance-Associated NS5A Mutations in Hepatitis C Virus on Viral Production and Susceptibility to Antiviral Reagents
Authors: Nitta Sayuri , Asahina Yasuhiro , Matsuda Mami , Yamada Norie , Sugiyama Ryuichi , Masaki Takahiro , Suzuki Ryosuke , Kato Nobuyuki , Watanabe Mamoru , Wakita Takaji , Kato Takanobu
Published: October 2016

Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have potent anti-HCV effects but may provoke resistance-associated variants (RAVs). In this study, we assessed the characteristics of these RAVs and explored efficacious anti-HCV reagents using recombinant HCV with NS5A from a genotype 1b strain. We replaced the NS5A of JFH1 with that of Con1 (JFH1/5ACon1) and introduced known NS5A inhibitor resistance mutations (L31M, L31V, L31I and Y93H) individually or in combination. Susceptibilities against anti-HCV reagents were also investigated. RAVs with Y93H exhibited high extracellular core antigen levels and infectivity titers. Variants with any single mutation showed mild to moderate resistance against NS5A inhibitors, whereas variants with double mutations at both L31 and Y93 showed severe resistance. The variants with mutations exhibited similar levels of susceptibility to interferon (IFN)-α, IFN-λ1, IFN-λ3 and Ribavirin. Variants with the Y93H mutation were more sensitive to protease inhibitors compared with JFH1/5ACon1. In conclusion, the in vitro analysis indicated that the Y93H mutation enhanced infectious virus production, suggesting advantages in the propagation of RAVs with this mutation. However, these RAVs were susceptible to protease inhibitors. Thus, a therapeutic regimen that includes these reagents is a promising means to eradicate these RAVs.
Unravelling the low-temperature metastable state in perovskite solar cells by noise spectroscopy
Authors: Barone C. , Lang F. , Mauro C. , Landi G. , Rappich J. , Nickel N. H. , Rech B. , Pagano S. , Neitzert H. C.
Published: October 2016

The hybrid perovskite methylammonium lead iodide CH3NH3PbI3 recently revealed its potential for the manufacturing of low-cost and efficient photovoltaic cells. However, many questions remain unanswered regarding the physics of the charge carrier conduction. In this respect, it is known that two structural phase transitions, occurring at temperatures near 160 and 310 K, could profoundly change the electronic properties of the photovoltaic material, but, up to now, a clear experimental evidence has not been reported. In order to shed light on this topic, the low-temperature phase transition of perovskite solar cells has been thoroughly investigated by using electric noise spectroscopy. Here it is shown that the dynamics of fluctuations detect the existence of a metastable state in a crossover region between the room-temperature tetragonal and the low-temperature orthorhombic phases of the perovskite compound. Besides the presence of a noise peak at this transition, a saturation of the fluctuation amplitudes is observed induced by the external DC current or, equivalently, by light exposure. This noise saturation effect is independent on temperature, and may represent an important aspect to consider for a detailed explanation of the mechanisms of operation in perovskite solar cells.
Preparation of cross-linked hen-egg white lysozyme crystals free of cracks
Authors: Yan Er-Kai , Lu Qin-Qin , Zhang Chen-Yan , Liu Ya-Li , He Jin , Chen Da , Wang Bo , Zhou Ren-Bin , Wu Ping , Yin Da-Chuan
Published: October 2016

Cross-linked protein crystals (CLPCs) are very useful materials in applications such as biosensors, catalysis, and X-ray crystallography. Hence, preparation of CLPCs is an important research direction. During the preparation of CLPCs, an often encountered problem is that cracks may appear in the crystals, which may finally lead to shattering of the crystals into small pieces and cause problem in practical applications. To avoid cross-link induced cracking, it is necessary to study the cracking phenomenon in the preparation process. In this paper, we present an investigation on how to avoid cracking during preparation of CLPCs. An orthogonal experiment was designed to study the phenomenon of cross-link induced cracking of hen-egg white lysozyme (HEWL) crystals against five parameters (temperature, solution pH, crystal growth time, glutaraldehyde concentration, and cross-linking time). The experimental results showed that, the solution pH and crystal growth time can significantly affect cross-link induced cracking. The possible mechanism was studied, and optimized conditions for obtaining crack-free CLPCs were obtained and experimentally verified.
Optogenetic activation of septal GABAergic afferents entrains neuronal firing in the medial habenula
Authors: Choi Kyuhyun , Lee Youngin , Lee Changwoo , Hong Seokheon , Lee Soonje , Kang Shin Jung , Shin Ki Soon
Published: October 2016

The medial habenula (MHb) plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal. The MHb receives GABAergic input from the medial septum/diagonal band of Broca (MS/DB), yet the synaptic mechanism that regulates MHb activity is unclear. GABA (γ -aminobutyric acid) is a major inhibitory neurotransmitter activating both GABAA receptors and GABAB receptors. Depending on intracellular chloride concentration, however, GABAA receptors also function in an excitatory manner. In the absence of various synaptic inputs, we found that MHb neurons displayed spontaneous tonic firing at a rate of about ~4.4 Hz. Optogenetic stimulation of MS/DB inputs to the MHb evoked GABAA receptor-mediated synaptic currents, which produced stimulus-locked neuronal firing. Subsequent delayed yet lasting activation of GABAB receptors attenuated the intrinsic tonic firing. Consequently, septal GABAergic input alone orchestrates both excitatory GABAA and inhibitory GABAB receptors, thereby entraining the firing of MHb neurons.
OAHG: an integrated resource for annotating human genes with multi-level ontologies
Authors: Cheng Liang , Sun Jie , Xu Wanying , Dong Lixiang , Hu Yang , Zhou Meng
Published: October 2016

OAHG, an integrated resource, aims to establish a comprehensive functional annotation resource for human protein-coding genes (PCGs), miRNAs, and lncRNAs by multi-level ontologies involving Gene Ontology (GO), Disease Ontology (DO), and Human Phenotype Ontology (HPO). Many previous studies have focused on inferring putative properties and biological functions of PCGs and non-coding RNA genes from different perspectives. During the past several decades, a few of databases have been designed to annotate the functions of PCGs, miRNAs, and lncRNAs, respectively. A part of functional descriptions in these databases were mapped to standardize terminologies, such as GO, which could be helpful to do further analysis. Despite these developments, there is no comprehensive resource recording the function of these three important types of genes. The current version of OAHG, release 1.0 (Jun 2016), integrates three ontologies involving GO, DO, and HPO, six gene functional databases and two interaction databases. Currently, OAHG contains 1,434,694 entries involving 16,929 PCGs, 637 miRNAs, 193 lncRNAs, and 24,894 terms of ontologies. During the performance evaluation, OAHG shows the consistencies with existing gene interactions and the structure of ontology. For example, terms with more similar structure could be associated with more associated genes (Pearson correlation γ2 = 0.2428, p < 2.2e–16).
Cross-inhibition of pathogenic agents and the host proteins they exploit
Authors: Zilbermintz Leeor , Leonardi William , Tran Sharon H. , Zozaya Josue , Mathew-Joseph Alyssa , Liem Spencer , Levitin Anastasia , Martchenko Mikhail
Published: October 2016

The major limitations of pathogen-directed therapies are the emergence of drug-resistance and their narrow spectrum of coverage. A recently applied approach directs therapies against host proteins exploited by pathogens in order to circumvent these limitations. However, host-oriented drugs leave the pathogens unaffected and may result in continued pathogen dissemination. In this study we aimed to discover drugs that could simultaneously cross-inhibit pathogenic agents, as well as the host proteins that mediate their lethality. We observed that many pathogenic and host-assisting proteins belong to the same functional class. In doing so we targeted a protease component of anthrax toxin as well as host proteases exploited by this toxin. We identified two approved drugs, ascorbic acid 6-palmitate and salmon sperm protamine, that effectively inhibited anthrax cytotoxic protease and demonstrated that they also block proteolytic activities of host furin, cathepsin B, and caspases that mediate toxin’s lethality in cells. We demonstrated that these drugs are broad-spectrum and reduce cellular sensitivity to other bacterial toxins that require the same host proteases. This approach should be generally applicable to the discovery of simultaneous pathogen and host-targeting inhibitors of many additional pathogenic agents.
Repeatability of cortisol stress response in the European sea bass (Dicentrarchus labrax) and transcription differences between individuals with divergent responses
Authors: Samaras A. , Dimitroglou A. , Sarropoulou E. , Papaharisis L. , Kottaras L. , Pavlidis M.
Published: October 2016

Understanding the stress responses of organisms is of importance in the performance and welfare of farmed animals, including fish. Especially fish in aquaculture commonly face stressors, and better knowledge of their responses may assist in proper husbandry and selection of breeding stocks. European sea bass (Dicentrarchus labrax), a species with high cortisol concentrations, is of major importance in this respect. The main objectives of the present study were to assess the repeatability and consistency of cortisol stress response and to identify differences in liver transcription profiles of European sea bass individuals, showing a consistent low (LR) or high (HR) cortisol response. The progeny of six full sib families was used, and sampled for plasma cortisol after an acute stress challenge once per month, for four consecutive months. Results suggest that cortisol responsiveness was a repeatable trait with LR and HR fish showing low or high resting, free and post-stress cortisol concentrations respectively. Finally, the liver transcription profiles of LR and HR fish showed some important differences, indicating differential hepatic regulation between these divergent phenotypes. These transcription differences were related to various metabolic and immunological processes, with 169 transcripts being transcribed exclusively in LR fish and 161 exclusively in HR fish.
Facile preparation of a three-dimensional macroporous graphene wrapped cuprous oxide composite by one-step hydrothermal assembly for stable and sensitive hydrogen peroxide detection
Authors: Ma Guangran , Yang Min , Zhao Guochun , Zhang Yanping , Xu Fugang , Wang Li
Published: October 2016

A facile one-pot hydrothermal assembly approach was developed to prepare a novel three-dimensional macroporous graphene wrapped Cu2O composite (3D-p-rGO–Cu2O) for the electrochemical detection of H2O2.
Electronic structure and characterization of a uranyl di-15-crown-5 complex with an unprecedented sandwich structure
Authors: Hu Shu-Xian , Gibson John K. , Li Wan-Lu , Van Stipdonk Michael J. , Martens Jonathan , Berden Giel , Redlich Britta , Oomens Jos , Li Jun
Published: October 2016

A uranyl–di-15-crown-5 complex with a unique slipped sandwich structure was synthesized and characterized by infrared spectroscopy and quantum-chemical methods.
Nanoscale dynamics of phospholipids reveals an optimal assembly mechanism of pore-forming proteins in bilayer membranes
Authors: Sarangi Nirod Kumar , Ayappa K. G. , Visweswariah Sandhya. S. , Basu Jaydeep Kumar
Published: October 2016

Using STED-FCS, we show that the fluidity of the membrane controls the induced dynamical heterogeneity in model membranes upon interacting with pore-forming toxins.
Reactive trajectories of the Ru2+/3+ self-exchange reaction and the connection to Marcus' theory
Authors: Tiwari Ambuj , Ensing Bernd
Published: October 2016

Outer sphere electron transfer between two ions in aqueous solution is a rare event on the time scale of first principles molecular dynamics simulations. We have used transition path sampling to generate an ensemble of reactive trajectories of the self-exchange reaction between a pair of Ru2+ and Ru3+ ions in water. To distinguish between the reactant and product states, we use as an order parameter the position of the maximally localised Wannier center associated with the transferring electron. This allows us to align the trajectories with respect to the moment of barrier crossing and compute statistical averages over the path ensemble. We compare our order parameter with two typical reaction coordinates used in applications of Marcus theory of electron transfer: the vertical gap energy and the solvent electrostatic potential at the ions.
Systems biological understanding of the regulatory network and the possible therapeutic strategies for vascular calcification
Authors: Manivannan Jeganathan , Prashanth Manjunath , Saravana Kumar Venkatesan , Shairam Manickaraj , Subburaj Jayachandran
Published: October 2016

Transcriptomics data reanalysis explores novel mechanisms behind vascular calcification events and provides clues for novel therapeutic strategies.
A selective calix[6]arene-based fluorescent chemosensor for phosphatidylcholine type lipids
Authors: Brunetti Emilio , Moerkerke Steven , Wouters Johan , Bartik Kristin , Jabin Ivan
Published: October 2016

Biomimetic heteroditopic calixarene-based chemosensor for the selective recognition of phosphatidylcholine-type lipids.
Hyaluronan-coated polybenzofulvene brushes as biomimetic materials
Authors: Cappelli Andrea , Paolino Marco , Grisci Giorgio , Razzano Vincenzo , Giuliani Germano , Donati Alessandro , Bonechi Claudia , Mendichi Raniero , Battiato Salvatore , Samperi Filippo , Scialabba Cinzia , Giammona Gaetano , Makovec Francesco , Licciardi Mariano
Published: October 2016

A polybenzofulvene brush was enveloped by means of nona(ethylene glycol) arms into hyaluronan shells.
Sol–gel derived mesoporous GaAlPO4 glass for heavy metal ion sequestration
Authors: He Jin , Ma Pengfei , Zhang Ge , Li Rihong , Zhang Long
Published: October 2016

Mesoporous phosphate materials with chemical diversity and a high surface area are essential for their practical applications as heavy metal ion adsorbent materials.
Development of tissue engineered ligaments with titanium spring reinforcement
Authors: Wang Anqi , Williams Richard L. , Jumbu Neeraj , Paxton Jennifer Z. , Davis Edward T. , Snow Martyn A. , Campbell Ritchie Alastair , Johansson Carina B. , Sammons Rachel L. , Grover Liam M.
Published: October 2016

Titanium spring reinforced tissue-engineered ligament replacement: enhancing construct stiffness, load propagation and robustness under cyclic loading.
Assembly of polyoxometalates and Ni-bpy cationic units into the molecular core–shell structures as bifunctional electrocatalysts
Authors: Wang Chun-Jie , Yao Shuang , Chen Yi-Zhen , Zhang Zhi-Ming , Wang En-Bo
Published: October 2016

Four core–shell organic–inorganic hybrid materials composed of polyoxometalates and Ni-bpy units were designed and synthesized, which exhibited bifunctional electrocatalytic activity for the reduction of NO2− and water oxidation.
Lithium salt–nonionic surfactant lyotropic liquid crystalline gel-electrolytes with redox couple for dye sensitized solar cells
Authors: Yılmaz Ezgi , Olutaş Elif Berna , Barım Gözde , Bandara Jayasundera , Dag Ömer
Published: October 2016

Lithium salts (LiCl, LiBr, LiI, LiNO3) and a non-ionic surfactant form, with a small amount of water, lyotropic liquid crystalline (LLC) mesophases, which are not disturbed by the addition of LiI and I2and can be used as gel-electrolytes in DSSCs.
Dual-modal light scattering and fluorometric detection of lead ion by stimuli-responsive aggregation of BSA-stabilized copper nanoclusters
Authors: Feng Da-Qian , Zhu Wenjie , Liu Guoliang , Wang Wei
Published: October 2016

A new and facilely prepared light scattering (LS) and fluorometric dual-mode sensor is developed for lead ion (Pb2+) detection with high sensitivity and selectivity by use of bovine serum albumin stabilized copper nanoclusters (BSA–Cu NCs).
In silico drug repositioning for the treatment of Alzheimer's disease using molecular docking and gene expression data
Authors: Xie Hongbo , Wen Haixia , Qin Mingze , Xia Jie , Zhang Denan , Liu Lei , Liu Bo , Liu Qiuqi , Jin Qing , Chen Xiujie
Published: October 2016

We provided a computational drug repositioning method for the treatment of Alzheimer's disease.
Integration of aerobic oxidation and intramolecular asymmetric aza-Friedel–Crafts reactions with a chiral bifunctional heterogeneous catalyst
Authors: Cheng Hong-Gang , Miguélez Javier , Miyamura Hiroyuki , Yoo Woo-Jin , Kobayashi Shū
Published: October 2016

A chiral heterogeneous material was prepared and evaluated as a bifunctional catalyst for the sequential aerobic oxidation-asymmetric intramolecular aza-Friedel–Crafts reaction.
Harnessing non-covalent interactions to exert control over regioselectivity and site-selectivity in catalytic reactions
Authors: Davis Holly J. , Phipps Robert J.
Published: October 2016

This perspective examines the progress that has been made in using non-covalent interactions to control regioselectivity and site-selectivity in catalysis.