bluuebunny/crossref_metadata_2025 huggingface dataset:
On Adler space‐time extremes during ocean storms
Authors: Romolo Alessandra , Arena Felice
Published: April 2015

The paper concerns the statistical properties of extreme ocean waves in the space‐time domain. In this regard, a solution for the exceedance probability of the maximum crest height during a sea state over a certain area is obtained. The approach is based on the Adler's solution for the extremal probability for Gaussian random processes in a multidimensional domain. The method is able to include the effects of spatial variability of three‐dimensional sea waves on short‐term prediction, both over an assigned area XY and in a given direction. Next, the storm‐term predictions in the space‐time are investigated. For this purpose, the exceedance probability of
during an ocean storm over an assigned area
is derived. This solution gives a generalization to the space‐time of the Borgman's time‐based model for nonstationary processes. The validity of the model is assessed from wave data of two buoys of the NOOA‐NDBC network located along the Pacific and the Atlantic U.S. coasts. The results show that the size of the spatial domain
remarkably influences the expected maximum crest height during a sea storm. Indeed, the exceedance probabilities of the maximum crest height during an ocean storm over a certain area significantly deviate from the classical Borgman's model in time for increasing area. Then, to account for the nonlinear contributions on crest height, the proposed model is exploited jointly with the Forristall's distribution for nonlinear crest amplitudes in a given sea state. Finally, Monte Carlo simulations of a sea storm are performed showing a very good agreement with theoretical results.
A low‐disturbance nonequilibrium molecular dynamics algorithm applied to the determination of thermal conductivities
Authors: Furtado Filipe A. , Abreu Charlles R. A. , Tavares Frederico W.
Published: April 2015

A new nonequilibrium molecular dynamics algorithm is proposed for the determination of thermal conductivity and other transport properties. The proposed algorithm aims at diminishing the energy drift problem observed in this type of method while conserving linear momentum and being compatible with constrained molecules. The features of the proposed algorithm are evaluated by determining thermal conductivities of water at 323 K, n‐octane at 300 K, and argon close to its triple point, and by comparing these results with those obtained using established methods. The analysis of systems presenting diverse molecular characteristics allowed us to assess the usefulness of the proposed algorithm. The energy drift and temperature variation were reduced in the range of 10–80%, depending on the parameters of the proposed algorithm and the characteristics of the system. The determined thermal conductivities showed good agreement when compared to experimental and simulation data. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2881–2890, 2015
Aldol condensation of n‐butyraldehyde in a biphasic stirred tank reactor: Experiments and models
Authors: Lee Shinbeom , Varma Arvind
Published: March 2015

To model a biphasic stirred tank reactor, intrinsic reaction kinetics and interfacial area are required. In this study, reactor modeling for n‐butyraldehyde aldol condensation was investigated under industrially relevent conditions. The interfacial area in the reactor was directly measured using a borescope system under appropriate temperature, NaOH concentration and rpm conditions. To estimate the interfacial area, a semiempirical correlation was developed, which provides good estimates within ±15% error. The reactor model based on two‐film theory was developed, combining the interfacial area and intrinsic reaction kinetics reported in our prior work. The model was verified by reaction experiments in the range 0.05–1.9 M NaOH, 80–130°C, and 600–1000 rpm. The prediction errors using the interfacial area from direct measurements and the correlation were ±8% and ±15%, respectively, suggesting that the model accuracy may be improved with better interfacial area estimation. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2228–2239, 2015
(Co)polymerization of ethylene via nonmetallocene catalysts with diphenyl phosphoroso schiff‐base ligand
Authors: Wang Jing , Zhang Xinli , Zhou Lu , Zhou Yang , Huang Qigu , Yang Wantai
Published: March 2015

A series of novel nonmetallocene catalysts [N, O, P] with diphenyl phosphoroso ligands were synthesized by the treatment of phthaldialdehyde, substituted phenols, chlorodiphenyl phosphine with metal halides of TiCl4 and ZrCl4. The catalyst microstructure was characterized by 1H NMR and EA. After activated by methylaluminoxane (MAO), these [N, O, P] catalysts were utilized to catalyze the polymerization of ethylene and the copolymerization of ethylene with 1‐octene. The results indicated that the obtained catalysts were highly efficient for ethylene polymerization and ethylene/1‐octene copolymerization. Structures and properties of the obtained polymers were measured by WAXD, DSC, GPC, and 13C NMR. The results indicated that polyethylene catalyzed by Cat.3 possessed the highest weight‐average molecular weight of 1.025 × 106 g/mol and the highest melting point of 136.3°C. The copolymer of ethylene/1‐octene catalyzed by Cat.1 exhibited the highest 1‐octene incorporation content of 0.63 mol %. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42225.
Zur Ermittlung der Sorptionsenthalpie von Baustoffen
Authors: Gertis Karl , Schmidt Thomas
Published: April 2015

Obwohl die Sorptionsvorgänge seit vielen Jahren intensiv untersucht wurden, sind in der Fachliteratur nur spärliche Angaben zur Sorptionsenthalpie von Baustoffen vorhanden. Man bräuchte solche Daten aber bei der Berechnung instationär‐gekoppelter Wärme‐ und Feuchtetransportvorgänge. Hierbei spielen Latentenergien eine Rolle, die sich aus der Verdampfungsenthalpie bei der Phasenänderung Wasser/Dampf und der sorptiven Bindungsenthalpie bei Wasseranlagerung in den Baustoffporen zusammensetzen. Die Sorptionsenthalpie hängt bei höheren Materialfeuchten nicht vom Baustoff ab, sondern nur von der Wasserdampf‐Gaskonstanten sowie von der Temperatur und wird vernachlässigbar klein, je feuchter der Baustoff ist. Bei niedrigen Feuchten hängt sie, wenn der Baustoff hygroskopisch ist, vom Baustoff ab und nimmt zu, je trockener der Baustoff ist. Ihre Ermittlung kann durch kalorimetrische Messungen oder durch die Messung zweier Sorptionsisothermen bei zwei verschiedenen Temperaturen geschehen. Wegen eines linear‐logarithmischen Zusammenhangs genügt die Messung von nur zwei Isothermen, die Ermittlung der gesamten Isothermenschar ist nicht notwendig. Das Ermittlungsverfahren wird in Einzel‐Rechenschritten dargestellt. Hieraus lässt sich eine simple Formel für die Bestimmung der Sorptionsenthalpie ableiten.

On determining the sorption enthalpy of construction materials. Although processes of water adsorption have been analysed intensively for a long time, technical literature provides only scarce information regarding the sorption enthalpy of building materials. However, such data is required for calculations of transient coupled heat and moisture transfer. In this context, latent energy is relevant, which includes the enthalpy of evaporation during the water/vapour phase change and the sorptive bonding enthalpy during water ingress in the pores of building materials. For higher moisture contents the sorption enthalpy does not depend on the material, but only on the gas constant and on the temperature. The sorption enthalpy becomes the smaller the higher the moisture content is. If we have hygroscopic materials with small moisture content the sorption enthalpy depends on the material properties. It is increasing with decreasing moisture content and can be determined either by conducting calorimetric measurements or by measuring two sorption isotherms at two different temperatures. Due to a linear‐logarithmic relationship, the measurement of merely two isotherms will be sufficient; it is not necessary to determine the entire isotherm family. The procedure of determination is exemplified specifying the individual calculation steps. From this, a simple formula for determining the sorption enthalpy can be derived.
Effects of 50 Hz magnetic fields on gap junctional intercellular communication in NIH3T3 cells
Authors: Percherancier Yann , Goudeau Bertrand , Charlet de Sauvage Renaud , de Gannes Florence Poulletier , Haro Emmanuelle , Hurtier Annabelle , Sojic Neso , Lagroye Isabelle , Arbault Stéphane , Veyret Bernard
Published: April 2015

The present study focused on gap junctional intercellular communication (GJIC) as a target for biological effects of extremely low‐frequency (ELF) magnetic field (MF) exposure. Fluorescence recovery after photobleaching microscopy (FRAP) was used to visualize diffusion of a fluorescent dye between NIH3T3 fibroblasts through gap junctions. The direct effect of 24 h exposure to 50 Hz MF at 0.4 or 1 mT on GJIC function was assessed in one series of experiments. The potential synergism of MF with an inhibitor of GJIC, phorbol ester (TPA), was studied in another series by observing FRAP when NIH3T3 cells were incubated with TPA for 1 h following 24 h exposure to MF. In contrast to other reports of ELF‐MF effects on GJIC, under our experimental conditions we observed neither direct inhibition of GJIC nor synergism with TPA‐induced inhibition from 50 Hz MF exposures. Bioelectromagnetics. 36:287–293, 2015. © 2015 Wiley Periodicals, Inc.
Reaction Pathways of Biomass‐Derived Oxygenates over Metals and Carbides: From Model Surfaces to Supported Catalysts
Authors: Xiong Ke , Yu Weiting , Vlachos Dionisios G. , Chen Jingguang G.
Published: March 2015

The conversion of lignocellulosic biomass‐derived oxygenates into renewable fuels and chemicals requires the control of bond‐scission sequences. For example, selective CO/CO bond scission is needed to reduce the oxygen content and thus increase the energy density to produce renewable fuels. On the other hand, the control of CC bond scission is desired for producing H2 and suppressing side products from CO/CO bond‐scission reactions. In this review, recent advances in the utilization of bimetallic and metal carbide catalysts that demonstrate enhanced performance and/or low cost for the selective CC and CO/CO bond‐scission reactions, are summarized. Furthermore, the importance of combining density function theory (DFT) calculations, microkinetic modeling, and ultrahigh vacuum (UHV) experiments on single‐crystal model surfaces with reactor evaluations over the corresponding powder catalysts is illustrated. General trends and future opportunities for the control of bond‐scission sequences of biomass‐derived oxygenates are also discussed.
Characteristics of Magnetic Basement Depth Beneath China Mainland
Authors: Sheng‐Qing XIONG , Yan‐Yun DING , Zhan‐Kui LI
Published: April 2015

The relief of the metamorphosed basement of the Precambrian and the thickness variation of the overlying sedimentary cover are very important for geology and exploration of energy and resources. The magnetic difference between these two layers permits geophysicists to estimate the magnetic basement depth using aeromagnetic data. The work is based on such data acquired by AGRS's aero geophysical surveys for more than 30 years over China mainland, covering more than 30 basins and areas. Our purpose is to compile the magnetic basement depth map for China mainland on a scale 1:1000000 with the data converted into the same coordinate system and scale. The resultant map shows that using E105° line as a boundary, the covers are thick in sedimentary depression areas of western China, mainly distributed in the Tarim basin, Junggar basin, Qaidam basin and Tibet area. While, in east China, mainly distributed in the Songliao basin, Erlian basin, Ordos, southern North China, Sichuan basin, and South Yellow Sea‐Subei basin, such covers are relatively thin in sedimentary depression areas, of which the largest thickness is located in the southwest of the Sichuan basin and the western edge of the Ordos basin. These characteristics are associated with the metamorphosed basement of Precambrian and depth changes of irruptive rocks body with certain scales, and reflect sedimentary covers' thickness and status. They allow us to intuitively observe depths and sizes of various types of sedimentary basins and sedimentary depression areas, and provide direct evidence for exploration of oil and gas reservoirs on the basements.
Characteristics of Crustal Structure and Their Relation with Major Earthquakes in Western China
Authors: Di‐Di JIANG , Wei‐Wei JIANG , Yi XU , Tian‐Yao HAO , Wei‐Jian HU , Jing‐Feng YU
Published: April 2015

Major and/or great earthquakes frequently occured in western China, where exist many striking seismotectonic zones such as Tian Shan, Altay, Pamir and Kunlun Mountains. This paper analyzes the characteristics of the gravity field in western China, inverts the depth of Moho interface by the Parker‐Oldenburg method with gravity data and seismic profiles. Through comparison with the results of seismic tomography inversion, we analyze crustal structure of the study area. The results show that the study area is significantly heterogeneous in crustal structure, with main orogenic belts of high‐speed while basins and major depressions of low speed. The orogenic belts in the study area are generally Moho depression areas while the basins are the Moho uplift areas. According to the calculation results and epicenter distribution of the study area, we discuss the correlation between crustal structure and major earthquakes. The earthquakes in this region are closely related to crustal heterogeneity, which mainly happen around the crustal velocity change belts and in the regions with great crustal velocity differences. Under the effect of tectonic stress, these crustal non‐uniform areas are prone to major earthquakes, which is one of the tectonic reasons for high seismicity in orogenic belts and near the boundary between basins and mountains in western China.
Phase 2 study of MK‐2206, an allosteric inhibitor of AKT, as second‐line therapy for advanced gastric and gastroesophageal junction cancer: A SWOG cooperative group trial (S1005)
Authors: Ramanathan Ramesh K. , McDonough Shannon L. , Kennecke Hagen F. , Iqbal Syma , Baranda Joaquina C. , Seery Tara E. , Lim Howard J. , Hezel Aram F. , Vaccaro Gina M. , Blanke Charles D.
Published: March 2015

BACKGROUND

The AKT inhibitor MK‐2206 at a dose of 60 mg every other day was evaluated in gastric/gastroesophageal junction cancers.

METHODS

Patients who had progressed after first‐line treatment were eligible. Pertinent eligibility criteria included adequate organ function, a fasting serum glucose level ≤ 150 mg/dL, and less than grade 2 malabsorption or chronic diarrhea. MK‐2206 was given orally (60 evaluable patients required). The primary endpoint was overall survival, and a median survival of 6.5 months (power, 89%; significance level, 0.07) was considered encouraging for further investigation.

RESULTS

Seventy patients were included in the final analyses. The median age was 59.8 years (range, 30.4‐86.7 years); 70% were male, 89% were white, and 7% were Asian. There were 2 deaths possibly related to the study drug (cardiac arrest and respiratory failure). Grade 4 adverse events included hyperglycemia, anemia, and lung infection (1 each). Grade 3 adverse events occurred in < 5% of patients except for fatigue (6%). Other adverse events (all grades) included anemia (17%), anorexia (30%), diarrhea (26%), fatigue (50%), hyperglycemia (30%), nausea (40%), vomiting (22%), dry skin (19%), maculopapular rash (30%), and acneiform rash (13%). The response rate was 1%, the median progression‐free survival was 1.8 months (95% confidence interval, 1.7‐1.8 months), and the median overall survival was 5.1 months (95% confidence interval, 3.7‐9.4 months)

CONCLUSIONS

MK‐2206 as second‐line therapy was well tolerated by an unselected group of patients with gastric/gastroesophageal junction cancers, but it did not have sufficient activity (response rate, 1%; overall survival, 5.1 months) to warrant further testing in this population. Cancer 2015;121:2193–2197. © 2015 American Cancer Society.
Detection of K‐ras gene mutation by liquid biopsy in patients with pancreatic cancer
Authors: Kinugasa Hideaki , Nouso Kazuhiro , Miyahara Koji , Morimoto Yuki , Dohi Chihiro , Tsutsumi Koichiro , Kato Hironari , Matsubara Takehiro , Okada Hiroyuki , Yamamoto Kazuhide
Published: March 2015

BACKGROUND

Cell‐free circulating tumor DNA (ctDNA) in serum has been considered to be a useful candidate for noninvasive cancer diagnosis. The current study was designed to estimate the clinical usefulness of genetic analysis for ctDNA by digital polymerase chain reaction in patients with pancreatic cancer.

METHODS

The authors compared K‐ras mutations detected in endoscopic ultrasound‐guided fine‐needle aspiration biopsy tissue DNA and in ctDNA from 75 patients with pancreatic cancer. K‐ras mutations in the serum of 66 independent, consecutive patients with pancreatic cancer were also analyzed and the authors compared the results with survival rates.

RESULTS

The frequencies of the mutations in tissue samples at G12V, G12D, and G12R in codon 12 were 28 of 75 samples (37.3%), 22 of 75 samples (29.3%), and 6 of 75 samples (8.0%), respectively. Conversely, the rates of the mutations in ctDNA were 26 of 75 samples (34.6%), 29 of 75 samples (38.6%), and 4 of 75 samples (5.3%), respectively. Overall, the K‐ras mutation rates in tissue and ctDNA were 74.7% and 62.6%, respectively, and the concordance rate between them was 58 of 75 samples (77.3%). Survival did not appear to differ by the presence of K‐ras mutations in tissue DNA, but the survival of patients with K‐ras mutations in ctDNA was significantly shorter than that of patients without mutations in both a development set (P = .006) and an independent validation set (P = .002). The difference was especially evident in cases with a G12V mutation.

CONCLUSIONS

Analysis of ctDNA is a new useful procedure for detecting mutations in patients with pancreatic cancer. This noninvasive method may have great potential as a new strategy for the diagnosis of pancreatic cancer as well as for predicting survival. Cancer 2015;121:2271–2280. © 2015 American Cancer Society.
Connexin50 couples axon terminals of mouse horizontal cells by homotypic gap junctions
Authors: Dorgau Birthe , Herrling Regina , Schultz Konrad , Greb Helena , Segelken Jasmin , Ströh Sebastian , Bolte Petra , Weiler Reto , Dedek Karin , Janssen‐Bienhold Ulrike
Published: March 2015

Horizontal cells in the mouse retina are of the axon‐bearing B‐type and contribute to the gain control of photoreceptors and to the center‐surround organization of bipolar cells by providing feedback and feedforward signals to photoreceptors and bipolar cells, respectively. Horizontal cells form two independent networks, coupled by dendro‐dendritic and axo‐axonal gap junctions composed of connexin57 (Cx57). In Cx57‐deficient mice, occasionally the residual tracer coupling of horizontal cell somata was observed. Also, negative feedback from horizontal cells to photoreceptors, potentially mediated by connexin hemichannels, appeared unaffected. These results point to the expression of a second connexin in mouse horizontal cells. We investigated the expression of Cx50, which was recently identified in axonless A‐type horizontal cells of the rabbit retina. In the mouse retina, Cx50‐immunoreactive puncta were predominantly localized on large axon terminals of horizontal cells. Electron microscopy did not reveal any Cx50‐immunolabeling at the membrane of horizontal cell tips invaginating photoreceptor terminals, ruling out the involvement of Cx50 in negative feedback. Moreover, Cx50 colocalized only rarely with Cx57 on horizontal cell processes, indicating that both connexins form homotypic rather than heterotypic or heteromeric gap junctions. To check whether the expression of Cx50 is changed when Cx57 is lacking, we compared the Cx50 expression in wildtype and Cx57‐deficient mice. However, Cx50 expression was unaffected in Cx57‐deficient mice. In summary, our results indicate that horizontal cell axon terminals form two independent sets of homotypic gap junctions, a feature which might be important for light adaptation in the retina. J. Comp. Neurol. 523:2062–2081, 2015. © 2015 Wiley Periodicals, Inc.
Light‐evoked S‐nitrosylation in the retina
Authors: Tooker Ryan E. , Vigh Jozsef
Published: March 2015

Nitric oxide (NO) synthesis in the retina is triggered by light stimulation. NO has been shown to modulate visual signal processing at multiple sites in the vertebrate retina, via activation of the most sensitive target of NO signaling, soluble guanylate cyclase. NO can also alter protein structure and function and exert biological effects directly by binding to free thiol groups of cysteine residues in a chemical reaction called S‐nitrosylation. However, in the central nervous system, including the retina, this reaction has not been considered to be significant under physiological conditions. Here we provide immunohistochemical evidence for extensive S‐nitrosylation that takes place in the goldfish and mouse retinas under physiologically relevant light intensities, in an intensity‐dependent manner, with a strikingly similar pattern in both species. Pretreatment with N‐ethylmaleimide (NEM), which occludes S‐nitrosylation, or with 1‐(2‐trifluromethylphenyl)imidazole (TRIM), an inhibitor of neuronal NO synthase, eliminated the light‐evoked increase in S‐nitrosylated protein immunofluorescence (SNI) in the retinas of both species. Similarly, light did not increase SNI, above basal levels, in retinas of transgenic mice lacking neuronal NO synthase. Qualitative analysis of the light‐adapted mouse retina with mass spectrometry revealed more than 300 proteins that were S‐nitrosylated upon illumination, many of which are known to participate directly in retinal signal processing. Our data strongly suggest that in the retina light‐evoked NO production leads to extensive S‐nitrosylation and that this process is a significant posttranslational modification affecting a wide range of proteins under physiological conditions. J. Comp. Neurol. 523:2082–2110, 2015. © 2015 Wiley Periodicals, Inc.
Postnatal accumulation of intermediate filaments in the cat and human primary visual cortex
Authors: Song Seoho , Mitchell Donald E. , Crowder Nathan A. , Duffy Kevin R.
Published: March 2015

A principal characteristic of the mammalian visual system is its high capacity for plasticity in early postnatal development during a time commonly referred to as the critical period. The progressive diminution of plasticity with age is linked to the emergence of a collection of molecules called molecular brakes that reduce plasticity and stabilize neural circuits modified by earlier visual experiences. Manipulation of braking molecules either pharmacologically or though experiential alteration enhances plasticity and promotes recovery from visual impairment. The stability of neural circuitry is increased by intermediate filamentous proteins of the cytoskeleton such as neurofilaments and α‐internexin. We examined levels of these intermediate filaments within cat and human primary visual cortex (V1) across development to determine whether they accumulate following a time course consistent with a molecular brake. In both species, levels of intermediate filaments increased considerably throughout early postnatal life beginning shortly after the peak of the critical period, with the highest levels measured in adults. Neurofilament phosphorylation was also observed to increase throughout development, raising the possibility that posttranslational modification by phosphorylation reduces plasticity due to increased protein stability. Finally, an approach to scale developmental time points between species is presented that compares the developmental profiles of intermediate filaments between cats and humans. Although causality between intermediate filaments and plasticity was not directly tested in this study, their accumulation relative to the critical period indicates that they may contribute to the decline in plasticity with age, and may also constrain the success of treatments for visual disorders applied in adulthood. J. Comp. Neurol. 523:2111–2126, 2015. © 2015 Wiley Periodicals, Inc.
Glial and axonal perikaryal coverage and somatic spines in the posterodorsal medial amygdala of male and cycling female rats
Authors: Zancan Mariana , Dall'Oglio Aline , Sarzenski Taís Malysz , Maher Martin Ian , Garcia‐Segura Luis Miguel , Rasia‐Filho Alberto A.
Published: March 2015

The posterodorsal medial amygdala (MePD) is a sex‐steroid‐sensitive area that modulates reproductive behavior in rats. The volume of the neuronal cell body, density of dendritic spines, and glial fibrillary acidic protein immunoreactivity are sexually dimorphic or affected by gonadal hormones in the MePD. Here we add new data to this panorama and describe the ultrastructure of the glial and axonal coverage of the perikaryal membrane and the somatic spines in the MePD of males and cycling females (in diestrus, early proestrus, late proestrus, and estrus). Transmission electron microscopy data (mean values from seven to 11 neurons per rat, five or six animals per group) showed that the rat MePD has most of the perikaryal membrane covered by glial processes and a relatively large amount (up to 40%) of axonal processes contacting the neuronal cell body. No statistically significant difference was found between groups for these somatic coverages (P > 0.5). However, the density of somatic spines along the length of the perikaryal membrane was higher in the late proestrus than in estrus (P < 0.05), and somatic spines in early and late proestrus showed variable shapes with stubby/wide, thin, mushroom‐like, ramified, transitional or atypical aspects. These findings add to the rapid adjustable synaptic changes in the MePD and in the integrated neural circuits that control neuroendocrine secretion and the hormonally modulated timely display of social behaviors in rats. J. Comp. Neurol. 523:2127–2137, 2015. © 2015 Wiley Periodicals, Inc.
Airbrush Formation of Liquid Crystal/Polymer Fibers
Authors: Wang Junren , Jákli Antal , West John L.
Published: March 2015

A homogeneous solution of a low‐molecular‐weight liquid crystal and a polymer spontaneously phase separates during airbrushing to form uniform fibers with a fluid liquid‐crystal core surrounded by a solid polymer sheath. This structure forms because it effectively minimizes the interfacial energy of the phase‐separated components while minimizing the elastic energy of the liquid‐crystal core. These fibers incorporate the sensitive stimuli response of liquid crystals while maintaining the structural integrity, flexibility, and large surface‐area‐to‐volume ratios inherent in fibers. We demonstrate the electro‐ and thermo‐optical response of the resulting fibers. They may find use as biological and chemical sensors. The resulting fibers have the potential to shape the future of flexible/wearable electronics and sensors.
The growing number of hemophilia registries: Quantity vs. quality
Authors: Keipert C , Hesse J , Haschberger B , Heiden M , Seitz R , van den Berg HM , Hilger A ,   on behalf of the ABIRISK Consortium
Published: April 2015

Registries for rare diseases provide a tool for obtaining an overview of the clinical situation and can be used to discover points of improvement and to monitor long‐term safety. Registries could also become a powerful tool to provide supporting information for marketing authorization. There is an urgent need for a pan‐European or global strategy that supports consistent data. Therefore, transparency in data collection, harmonization of the database structures, and the convergence of scientific approaches are required.
Amine‐Free Reversible Hydrogen Storage in Formate Salts Catalyzed by Ruthenium Pincer Complex without pH Control or Solvent Change
Authors: Kothandaraman Jotheeswari , Czaun Miklos , Goeppert Alain , Haiges Ralf , Jones John‐Paul , May Robert B. , Prakash G. K. Surya , Olah George A.
Published: March 2015

Due to the intermittent nature of most renewable energy sources, such as solar and wind, energy storage is increasingly required. Since electricity is difficult to store, hydrogen obtained by electrochemical water splitting has been proposed as an energy carrier. However, the handling and transportation of hydrogen in large quantities is in itself a challenge. We therefore present here a method for hydrogen storage based on a CO2(HCO3−)/H2 and formate equilibrium. This amine‐free and efficient reversible system (>90 % yield in both directions) is catalyzed by well‐defined and commercially available Ru pincer complexes. The formate dehydrogenation was triggered by simple pressure swing without requiring external pH control or the change of either the solvent or the catalyst. Up to six hydrogenation–dehydrogenation cycles were performed and the catalyst performance remained steady with high selectivity (CO free H2/CO2 mixture was produced).
Self‐Nanoemulsifying Drug Delivery System of trans‐Cinnamic acid: Formulation Development and Pharmacodynamic Evaluation in Alloxan‐induced Type 2 Diabetic Rat Model
Authors: Wang Houyong , Li Qiang , Deng Wenwen , Omari‐siaw E. , Wang Qilong , Wang Shicheng , Wang Shengli , Cao Xia , Xu Ximing , Yu Jiangnan
Published: April 2015

Preclinical Research

The objective of this study was to formulate a self‐nanoemulsifying oral drug delivery system (SNEDDS) for the poorly water‐soluble trans‐Cinnamic acid (t‐CA SNEDDS) that could be evaluated for its antihyperglycemic efficacy in comparison to the parent t‐CA in an alloxan‐induced diabetic rat model. A SNEDDS formulation consisting of 60% surfactant (Kolliphor EL), 10% co‐surfactant (PEG 400) and 30% oil (isopropyl myristate) proved to be optimal. t‐CA SNEDDS (80 mg/kg, p.o.), t‐CA suspension (80 mg/kg, p.o.), and Metformin Hydrochloride Tablets (230 mg/kg, p.o.) were administer qdfor 30 days to diabetic rats. After treatment the body weight of diabetic rats was increased, blood glucose levels, total cholesterol, and triglyceride in the serum tended to be normalized, while the levels of alanine aminotransferase and aspartate aminotransferase were markedly decreased. The effects of t‐CA SNEDDS were superior to that of the t‐CA suspension. The present study demonstrated that t‐CA was effective in attenuating the effects of alloxan treatment and that t‐CA SNEDDS with a more favorable absorption and enhanced bioavailability is more effective than t‐CA. Drug Dev Res 76 : 8282–93, 2015. © 2015 Wiley Periodicals, Inc.
Effect of echium oil combined with phytosterols on biomarkers of atherosclerosis in LDLr‐knockout mice: Echium oil is a potential alternative to marine oils for use in functional foods
Authors: Botelho Patrícia Borges , Guimarães Jéssica Pereira , Mariano Karina Rocha , Afonso Milessa da Silva , Koike Márcia Kiyomi , Lottenberg Ana Maria Pita , Castro Inar Alves
Published: March 2015

Bioactive compounds may be an alternative approach to prevent atherosclerosis. To evaluate this hypothesis, LDLr‐knockout mice were supplemented with omega‐3 fatty acids from Echium oil (10.24 mg/d of oil with 1,14 mg/d of SDA and 9.06 mg/d of ALA) equivalent to 0.7 mg/d of EPA after conversion, combined or not with phytosterols (0.76 mg/d), during the first 2 months of life. Subsequently, dyslipidaemia was induced by a high‐fat diet for the following 2 months. Echium oil, isolated or combined with phytosterols, improved lipid profile in plasma reducing triacylglycerol (90.3 ± 7.6 mg/dL) and VLDL‐c (18.0 ± 1.5 mg/dL) concentrations when compared with Control (115.8 ± 9.4 mg/dL and 23.2 ± 1.9 mg/dL, respectively). Echium oil also increased catalase (5.66 ± 0.13 U/mg protein) while Echium oil combined with phytosterol increased glutathione peroxidase activity (26.27 ± 0.10 U/mg protein) when compared with Control (5.18 ± 0.10 U/mg protein and 25.31 ± 0.16 U/mg protein, respectively). In addition, groups receiving Echium oil have reduced malondialdehyde concentration in liver (p = 0.05). However, no difference was observed in fatty streak lesions when compared with Control. Isolated phytosterols did not change cholesterol absorption and increased lesion area compared with control group. This result can be associated with the high dose applied in the first step of supplementation and with the form of supplementation (gavage).

Practical applications: One factor that contributes to the number of deaths from cardiovascular disease is that pharmacological interventions usually start too late in life. For this reason, functional foods development is a very important strategy to prevent atherosclerosis, since their inclusion in diet can start much earlier. However, it represents a challenge because many physiological responses from chronic consumption of bioactive compounds are still unknown. In this study, considering the positive results on triglyceridemia and oxidative stress biomarkers, we suggest that Echium oil can be an alternative for development of functional foods. We selected Echium oil due to its higher proportion of stearidonic fatty acids (pro‐EPA) and lower sensory limitation than marine oils.

Echium oil improves lipid profile and reduces oxidative stress, while phytosterol increases fatty streak.
Tracking miRNAs' footprints in tumor–microenvironment interactions: Insights and implications for targeted cancer therapy
Authors: Nouraee Nazila , Mowla Seyed Javad , Calin George A.
Published: March 2015

In the past decades, cancer medicine studies have mainly focused on tumor cell biology as the main promoter of solid tumor progression. However, tumor biology does not explain the intertwinement and ambiguity of the tumors' territory. Recently, the approach of understanding cancer has shifted from investigating the biology of tumor cells to studying the microenvironment surrounding them. MicroRNAs (miRNAs), which play a role in exploiting indigenous stromal cells and are components that cooperate and produce a favorable microenvironment for progressive tumor formation, have been implicated in numerous processes essential for tumor initiation and growth. Understanding the mechanisms underlying interactions between tumor cells and their adjacent environment holds many promises for the future of cancer‐targeted therapies. Herein, we provide a step‐by‐step account of miRNA involvement in tumor–microenvironment interactions as the micromediators of tumor cell and stroma communications. We also focus on the clinical challenges in using miRNAs tof overcome therapy resistance mechanisms and tumor heterogeneity bias in cancer therapy. © 2015 Wiley Periodicals, Inc.
Middle Jurassic continental to marine transition in an extensional tectonics context: the Genna Selole Fm depositional system in the Tacchi area (central Sardinia, Italy)
Authors: Costamagna Luca Giacomo
Published: March 2015

In Eastern Sardinia during the early Middle Jurassic, Alpine Tethys opening triggered the rise of a temporary tectonic high. The high collapsed rapidly, was fragmented into separate blocks, and subsequently covered by continental, transitional, and finally shallow marine deposits forming a narrow depositional system comprising the Genna Selole Fm. Present‐day exposures in the southern part of the palaeo‐high allow the sedimentological evolution of the transgressive cover sequence to be ascertained. Initial terrestrial deposits comprise alluvial fan deposits located at the mouths of palaeovalleys. These pass into braid‐deltas and in the coastal areas located between adjacent valleys mouths, palustrine and coastal plain tidally‐influenced environments developed. These environments interfingered laterally and passed seaward into a transitional, siliciclastic to carbonate tidal environment. With the collapse of the tectonic high, the continental to transitional environments were transgressed with deposition of marine carbonates. A comparison with similar coeval deposits of the W‐Mediterranean domain has been undertaken. Copyright © 2015 John Wiley & Sons, Ltd.
Transition Metals for the Synthesis of Glycopolymers and Glycopolypeptides
Authors: Islam Maidul , Shaikh Ashif Y. , Hotha Srinivas
Published: March 2015

Glycopolymers and glycopolypeptides are an important class of molecules, which can self‐assemble to various interesting biohybrid materials. It is envisaged that the glycans impart good immunological response, and the aliphatic or polypeptide backbone can give tertiary structure for the resulting glycopolymers. The major bottleneck in the synthesis of glycopolymers or glycopolypeptides is the access to suitable building blocks and polymerization methods. This review describes methods that have recently been explored for the successful synthesis of many useful glycomonomers that could be polymerized to afford glycopolymers and/or glycopolypeptides.
Augmenting effects of gestational arsenite exposure of C3H mice on the hepatic tumors of the F2 male offspring via the F1 male offspring
Authors: Nohara Keiko , Okamura Kazuyuki , Suzuki Takehiro , Murai Hikari , Ito Takaaki , Shinjo Keiko , Takumi Shota , Michikawa Takehiro , Kondo Yutaka , Hata Kenichiro
Published: March 2015

Gestational exposure can affect the F2 generation through exposure of F1 germline cells. Previous studies reported that arsenite exposure of only F0 females during their pregnancy increases hepatic tumors in the F1 males in C3H mice, whose males are predisposed spontaneously to develop hepatic tumors later in life. The present study addressed the effects of gestational arsenite exposure on tumorigenesis of the F2 males in C3H mice. Expression analysis of several genes in the normal livers at 53 and 80 weeks of age clearly showed significant changes in the F2 males obtained by crossing gestational arsenite‐exposed F1 (arsenite‐F1) males and females compared to the control F2 males. Some of the changes were shown to occur in a late‐onset manner. Then the tumor incidence was assessed at 75–82 weeks of age in the F2 males obtained by reciprocal crossing between the control and arsenite‐F1 males and females. The results demonstrated that the F2 males born to arsenite‐F1 males developed tumors at a significantly higher rate than the F2 males born to the control F1 males, irrespective of exposure of F1 females. Gene expressions of hepatocellular carcinoma markers β‐catenin (CTNNB1) and interleukin‐1 receptor antagonist in the tumors were significantly upregulated in the F2 males born to arsenite‐F1 males compared to those born to the control F1 males. These results show that arsenite exposure of only F0 pregnant mice causes late‐onset changes and augments tumors in the livers of the F2 males by affecting the F1 male offspring. Copyright © 2015 John Wiley & Sons, Ltd.
Evaluation of Treatment Integrity: The Treatment Specificity Index
Authors: Grikscheit Florian , Weck Florian , Hautzinger Martin , Heidenreich Thomas , Weigel Maria , Rudari Visar , Schimming Christine , Stangier Ulrich
Published: March 2015

Objective

To differentiate between treatments in a randomized controlled trial (RCT), therapies need to display not only high purity but also high specificity. The aim of this study was to demonstrate the benefits of calculating a treatment specificity index for the evaluation of treatment differentiation.

Method

Based on an RCT of relapse prevention in depression, comparing a cognitive with a psychoeducational treatment, the specificity and the purity index were calculated.

Results

As indicated by the specificity index, both conditions differed in their levels of implemented specific and common interventions. A significant relationship was found between symptom change before a therapy session and treatment specificity.

Conclusions

The specificity index is an appropriate method for enhancing the internal validity of RCTs in evaluating treatment integrity.
Understanding and Using Enactments to Further Clinical Work: A Case Study of a Man Unable to Experience Intimacy
Authors: Coren Sidney
Published: March 2015

This article examines the value of working within enactments–affectively charged, unconscious remnants of painful, past experiences played out in the novel context of the therapeutic relationship–to further the work of psychodynamically oriented therapy in the treatment of a HIV‐positive Hispanic gay male in his early 30s with a history of relational trauma. Through clinical vignettes, I highlight how relational uncertainty and its vicissitudes–vulnerability, doubt, safety, and trust–have triggered mutual dissociation in the context of enactment. At times, this has disrupted our ability to communicate honestly and relate intersubjectively. By working within affectively charged enactments, we have expanded our capacities to accommodate to relational uncertainty and used the tension of ambiguity within our relationship to permit the emergence of a shared space for recognition and self‐discovery.
RV mass measurement at end‐systole: Improved accuracy, Reproducibility, and reduced segmentation time
Authors: Altmayer Stephan P.L. , Teeuwen Laurens A. , Gorman Robert C. , Han Yuchi
Published: March 2015

Purpose

To evaluate the accuracy, reproducibility, and contouring time of RV mass in end‐systole (ES) and end‐diastole (ED). Magnetic resonance imaging (MRI) has been shown to be accurate and reproducible for the evaluation of right ventricular (RV) volume and function. RV mass, assessed in end‐diastolic (ED) phase, is one of the least reproducible variables. The choice of end‐systolic (ES) phase could offer an alternative to improve reproducibility, since the selection of the basal slice and the visualization of the usually thin RV wall are easier in this phase.

Materials and Methods

To evaluate accuracy, 11 sheep were imaged in vivo and their RV free walls were weighed after removing epicardial fat. To evaluate reproducibility, 30 normal subjects and 30 subjects with pulmonary arterial hypertension (PAH) were imaged and interobserver and intraobserver variabilities were assessed in the ES and the ED. Segmentation time was recorded after visual selection of ES and ED phases.

Results

ES RV mass measurement has less absolute variability (5.2% ± 3.2) compared to ED (10.6% ± 6.3) using weighed RV mass in sheep as the gold standard (P < 0.001). ES segmentation yielded higher intraobserver (intraclass correlation coefficients [ICC] = 0.94–0.99; coefficient of variability [CoV] = 6–7.3%) and interobserver (ICC = 0.85–0.98; CoV = 10.9–11.7%) reproducibility than ED segmentation. Segmentation time in humans was 25–28% faster in ES (P < 0.001).

Conclusion

The MRI assessment of RV mass is more accurate, reproducible, and faster in the ES phase. J. Magn. Reson. Imaging 2015;42:1291–1296.
Measuring Quaternary time: A 50‐year perspective
Authors: LOWE JOHN , WALKER MIKE
Published: March 2015

Over the last 50 years, there have been significant developments in the range and sophistication of the chronological tools now available to Quaternary scientists. Notable milestones include the introduction of new methods (e.g. optically stimulated luminescence, cosmogenic radionuclide dating, ice‐layer counting, molecular ‘clocks’) and the refinement of established techniques (e.g. accelerator mass spectrometry 14C dating, 14C calibration, high‐precision uranium‐series dating, argon–argon dating, cryptotephra analysis). Developing new techniques and methodologies for measuring Quaternary time is not an end in itself, however: it is stimulated by a parallel need, which is a deeper understanding of the mode, pattern and rates of environmental processes, and how different processes inter‐connect. Here we review some of the important limitations that continue to constrain our ability to provide coherent chronologies for Quaternary environmental reconstructions at both millennial and sub‐millennial timescales. We focus our discussion on two unique stratigraphic templates: first, the marine oxygen isotope sequence that spans the full Quaternary period; and, second, the Greenland ice‐core record, which provides a basis for dating environmental changes through the last glacial cycle.
The current and future applications of ancient DNA in Quaternary science
Authors: BROWN TERENCE A. , BARNES IAN M.
Published: March 2015

The introduction of next‐generation sequencing methods has broadened the scope and utility of ancient DNA (aDNA) research, and is opening up exciting new applications in Quaternary science. Palaeogenomes – partial or complete genome sequences for extinct taxa – are now available for Neanderthals and Denisovans, various megafauna, and preserved microorganisms. The analysis of aDNA in sediments, including cores in which there are no visible macro‐ or microfossils, is helping to reconstruct past ecosystems, especially in Arctic regions where aDNA preservation is relatively good. In this review we follow the development of aDNA research over the last 30 years, showing how the problems caused by contamination of ancient samples with modern DNA have gradually been overcome, and highlighting those technical challenges that still exist. We then survey the current standing of palaeogenomics and sedimentary aDNA studies, and indicate how these fields might be developed further in coming years.
Sea level in time and space: revolutions and inconvenient truths
Authors: GEHRELS W. ROLAND , SHENNAN IAN
Published: March 2015

In this paper we identify four ‘revolutions’ that in our view have shaped the study of sea‐level changes in recent decades. (i)The search for ‘eustasy’. One of the most hotly debated issues in the 1960s is still relevant as models of glacial isostatic adjustment (GIA) require input of the amount of meltwater transferred to the world's oceans following the demise of the large Pleistocene ice sheets. (ii)Resolution of sea‐level archives. All sea‐level archives have limitations in their resolving power but are we willing to define these? From studies of salt‐marsh deposits and corals it is highly likely that climate‐driven metre‐scale sea‐level fluctuations have not occurred during the middle and late Holocene. (iii)Rapid sea‐level changes. Improved coring technology has resulted in the suggestion of meltwater pulses during the last deglaciation. Low‐frequency high‐magnitude events have been documented along seismically active shorelines and provide information on seismic hazards and storm impacts. (iv)Merging of empirical sea‐level investigations and models. Much sea‐level research in the past two decades has embraced the integration of models and field‐derived data, providing testable hypotheses and insights into processes. We conclude with some reminders about the ‘inconvenient truths’ that keep the sea‐level scientist honest.