bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vivo Evaluation of Selective Carbonic Anhydrase Inhibitors as Potential Anticonvulsant Agents
Authors: Bruno Elvira , Buemi Maria R. , De Luca Laura , Ferro Stefania , Monforte Anna‐Maria , Supuran Claudiu T. , Vullo Daniela , De Sarro Giovambattista , Russo Emilio , Gitto Rosaria
Published: February 2016

Epilepsy is a common neurological disorder caused by an imbalance between inhibitory and excitatory neurotransmission. It is well known that neuronal excitability is related to γ‐aminobutyric acid (GABA)ergic depolarization. HCO3−‐dependent depolarization can be suppressed by membrane‐permeable inhibitors of carbonic anhydrase. We previously identified some isoquinoline sulfonamides as potent and selective inhibitors of the human carbonic anhydrase II and VII (hCA II and hCA VII) isoforms. Given that hCA II and hCA VII are specific isoforms involved in GABA‐mediated neuronal excitation, we hypothesized that they could represent the biological target for the development of new anticonvulsant agents. Therefore, for selected isoquinoline sulfonamides, we preliminarily tested their ability to prevent audiogenic seizures in DBA/2 mice. All compounds were evaluated after intraperitoneal administration, and some of them proved to protect the mice against convulsions. Among this series of compounds, several derivatives showed combined in vivo efficacy with inhibitory effects toward the targeted carbonic anhydrases (i.e., hCA II and hCA VII). Specifically, the most interesting molecule was 1‐(4‐aminophenyl)‐6,7‐dimethoxy‐3,4‐dihydroisoquinoline‐2(1H)‐sulfonamide (6), which proved to be a more active and selective hCA VII inhibitor than the reference compound topiramate. Further studies to explore the in vivo pharmacokinetic profile of the most active compounds may help to provide insight into the future design of selective hCA VII inhibitors.
Structure‐Based Design of Microsomal Prostaglandin E2 Synthase‐1 (mPGES‐1) Inhibitors using a Virtual Fragment Growing Optimization Scheme
Authors: Lauro Gianluigi , Tortorella Paolo , Bertamino Alessia , Ostacolo Carmine , Koeberle Andreas , Fischer Katrin , Bruno Ines , Terracciano Stefania , Gomez‐Monterrey Isabel Maria , Tauro Marilena , Loiodice Fulvio , Novellino Ettore , Riccio Raffaele , Werz Oliver , Campiglia Pietro , Bifulco Giuseppe
Published: February 2016

A small library of 2,3‐dihydroxybenzamide‐ and N‐(2,3‐dihydroxyphenyl)‐4‐sulfonamide‐based microsomal prostaglandin E2 synthase‐1 (mPGES‐1) inhibitors was identified following a step‐by‐step optimization of small aromatic fragments selected to interact in focused regions in the active site of mPGES‐1. During the virtual optimization process, the 2,3‐dihydroxybenzamide moiety was first selected as a backbone of the proposed new chemical entities; the identified compounds were then synthesized and biologically evaluated, identifying derivatives with very promising inhibitory activities in the micromolar range. Subsequent structure‐guided replacement of the 2,3‐dihydroxybenzamide by the N‐(2,3‐dihydroxyphenyl)sulfonamide moiety led to the identification of N‐(2,3‐dihydroxyphenyl)‐4‐biphenylsulfonamide (6), the most potent small molecule of the series (IC50=0.53±0.04 μm). The simple synthetic procedure and the possibility of enhancing the potency of this class of inhibitors through additional structural modifications pave the way for further development of new molecules with mPGES‐1‐inhibitory activity, with potential application as anti‐inflammatory and anticancer agents.
Beyond the dose‐limiting toxicity period: Dermatologic adverse events of patients on phase 1 trials of the Cancer Therapeutics Evaluation Program
Authors: Drilon Alexander , Eaton Anne A. , Schindler Katja , Gounder Mrinal M. , Spriggs David R. , Harris Pamela , Ivy S. Percy , Iasonos Alexia , Lacouture Mario E. , Hyman David M.
Published: February 2016

BACKGROUND

Dermatologic adverse events (AEs) can be key determinants of overall drug tolerability and of the maximum tolerated and recommended phase 2 doses in phase 1 trials. The authors present the largest dedicated analysis of dermatologic AEs on phase 1 trials to date.

METHODS

Data from a prospectively maintained database of patients with solid tumors who were enrolled onto Cancer Therapeutics Evaluation Program (CTEP)‐sponsored phase 1 trials of cytotoxic or molecularly targeted agents (MTAs) from 2000 to 2010 were analyzed. Cumulative incidence, site, and type of drug‐related dermatologic AEs were described and compared. The timing of worst drug‐related dermatologic AEs was summarized.

RESULTS

In total, 3517 patients with solid tumors and 6165 unique, drug‐related dermatologic AEs were analyzed, including 1545 patients on MTA‐only trials, 671 on cytotoxic‐only trials, and 1392 on combination MTA and cytotoxic trials. Of 1270 patients who had drug‐related dermatologic events, the timing of the worst AE was as follows: 743 (cycle 1), 303 (cycle 2), and 224 (cycle 3 or later). Although the cumulative incidence of grade ≥3 drug‐related AEs increased to 2.4% by cycle 6, it was only 1.6% at the end of cycle 1. The cumulative incidence of drug‐related AEs was highest in patients who received MTA‐only therapy (P < .001) and differed by dose level (P < .001). In patients who received MTA‐only therapy, drug‐related AEs were most common for combination kinase inhibitor‐containing therapy (P < .001).

CONCLUSIONS

A substantial proportion of drug‐related dermatologic AEs occur after the traditional dose‐limiting toxicity monitoring period of phase 1 clinical trials. Future designs should account for late toxicities. Cancer 2016;122:1228–37. © 2016 American Cancer Society.
Investigating the impact of non‐Newtonian blood models within a heart pump
Authors: Al‐Azawy Mohammed G. , Turan A. , Revell A.
Published: February 2016

A detailed computational fluid dynamics (CFD) study of transient, turbulent blood flow through a positive displacement left ventricular assist device is performed. Two common models for non‐Newtonian blood flow are compared to the Newtonian model to investigate their impact on predicted levels of shear rate and wall shear stress. Given that both parameters are directly relevant to the evaluation of risk from thrombus and haemolysis, there is a need to assess the sensitivity to modelling non‐Newtonian flow effects within a pulsatile turbulent flow, in order to identify levels of uncertainly in CFD. To capture the effects of turbulence, the elliptic blending Reynolds stress model is used in the present study, on account of superior performance of second moment closure schemes previously identified by the present authors. The CFD configuration includes two cyclically rotating valves and a moving pusher plate to periodically vary the chamber volume. An overset mesh algorithm is used for each instance of mesh motion, and a zero gap technique was employed to ensure full valve closure. The left ventricular assist device was operated at a pumping rate of 86 BPM (beats per minute) and a systolic duration of 40% of the pumping cycle, in line with existing experimental data to which comparisons are made. The sensitivity of the variable viscosity models is investigated in terms of mean flow field, levels of turbulence and global shear rate, and a non‐dimensional index is used to directly evaluate the impact of non‐Newtonian effects. The clinical relevance of the results is reported along with a discussion of modelling uncertainties, observing that the turbulent kinetic energy is generally predicted to be higher in non‐Newtonian flow than that observed in Newtonian flow. Copyright © 2016 John Wiley & Sons, Ltd.
Random walk analysis for reflection and transmission of turbid media
Authors: Rogers Geoffrey
Published: February 2016

The reflection and transmission of light from a turbid slab is determined by considering a photon random walk within the medium. The reflection and transmission is obtained using the Beer‐Lambert law on each path through the slab. Path length probability densities are derived, then all paths are summed weighted by their probabilities. The results are simple expressions for the reflection and the transmission in terms of the physical properties of the medium. © 2016 Wiley Periodicals, Inc. Col Res Appl, 41, 580–584, 2016
A distributed and multi‐tiered software architecture for assessing e‐Commerce recommendations
Authors: Palopoli Luigi , Rosaci Domenico , Sarné Giuseppe M. L.
Published: February 2016

Recently, an ever increasing number of e‐Commerce tools has been made available that are able to help customers by generating purposed recommendations. Many of them are centralized so that they have to face problems related to efficiency and scalability. A few of them are distributed, but in this case, the complexity of the e‐Commerce process implies computation overhead on the client side, which is often unsuitable if mobile devices are used by customers. In this paper, we study how the software distribution in recommender systems affects their performances, depending on the characteristics of the e‐Commerce population. To this end, we present a distributed testbed architecture for e‐Commerce recommender systems using a multi‐tiered agent‐based approach to generate effective recommendations without requiring such an onerous amount of computation per single client. We use such a testbed to study the main advantages and limitations associated with the problem of distributing the computation of recommendations. Copyright © 2016 John Wiley & Sons, Ltd.
On designing and testing distributed virtual environments
Authors: Valadares Arthur , Gabrielova Eugenia , Lopes Cristina Videira
Published: February 2016

Distributed real‐time (DRT) systems are among the most complex software systems to design, test, maintain, and evolve. The existence of components distributed over a network often conflicts with real‐time requirements, leading to design strategies that depend on domain‐specific and even application‐specific knowledge. Distributed virtual environment (DVE) systems are DRT systems that connect multiple users instantly with each other and with a shared virtual space over a network. DVE systems deviate from traditional DRT systemsx in the importance of the quality of the end user experience. We present an analysis of important, but challenging, issues in the design, testing, and evaluation of DVE systems through the lens of experiments with a concrete DVE, OpenSimulator. We frame our observations within six dimensions of well‐known design concerns: correctness, fault tolerance/prevention, scalability, time sensitivity, consistency, and overhead of distribution. Furthermore, we place our experimental work in a broader historical context, showing that these challenges are intrinsic to DVEs and suggesting lines of future research. Copyright © 2016 John Wiley & Sons, Ltd.
Tracer‐Based Metabolic NMR‐Based Flux Analysis in a Leukaemia Cell Line
Authors: Carrigan John B. , Reed Michelle A. C. , Ludwig Christian , Khanim Farhat L. , Bunce Christopher M. , Günther Ulrich L.
Published: February 2016

High levels of reactive oxygen species (ROS) have a profound impact on acute myeloid leukaemia cells and can be used to specifically target these cells with novel therapies. We have previously shown how the combination of two redeployed drugs, the contraceptive steroid medroxyprogesterone and the lipid‐regulating drug bezafibrate exert anti‐leukaemic effects by producing ROS. Here we report a 13C‐tracer‐based NMR metabolic study to understand how these drugs work in K562 leukaemia cells. Our study shows that [1,2‐13C]glucose is incorporated into ribose sugars, indicating activity in oxidative and non‐oxidative pentose phosphate pathways alongside lactate production. There is little label incorporation into the tricarboxylic acid cycle from glucose, but much greater incorporation arises from the use of [3‐13C]glutamine. The combined medroxyprogesterone and bezafibrate treatment decreases label incorporation from both glucose and glutamine into α‐ketoglutarate and increased that for succinate, which is consistent with ROS‐mediated conversion of α‐ketoglutarate to succinate. Most interestingly, this combined treatment drastically reduced the production of several pyrimidine synthesis intermediates.
Synthesis of 1,2‐Dicarbonyl‐3‐enes by Hydroacylation of 1‐Alkynes with Glyoxal Derivatives Using Metal–Organic Framework Cu/MOF‐74 as Heterogeneous Catalyst
Authors: Nguyen Nguyen B. , Dang Giao H. , Le Dung T. , Truong Thanh , Phan Nam T. S.
Published: February 2016

A crystalline copper‐based metal–organic framework Cu/MOF‐74 was synthesized, and used as an efficient heterogeneous catalyst for the synthesis of 1,2‐dicarbonyl‐3‐enes by means of the hydroacylation of 1‐alkynes with glyoxal derivatives in the presence of a base. Cu/MOF‐74 was found to be more catalytically active for the synthesis of 1,2‐dicarbonyl‐3‐enes than other MOFs including Cu2(BDC)2(DABCO), Cu3(BTC)2, Cu(BDC), Cu2(NDC)2(DABCO), Cu4I4(DABCO)2, Ni‐MOF‐74, Zn‐MOF‐74, Fe3O(BDC)3, In(OH)(BDC), and Zr6O4(OH)4(BDC)6. Cu/MOF‐74 also exhibited better performance than other homogeneous copper catalysts, including Cu(OAc)2, Cu(NO3)2, CuI, CuBr, CuCl, CuCl2, and CuBr2. The Cu/MOF catalyst was able to be recovered and reused several times without a significant degradation in catalytic activity. To the best of our knowledge, the formation of 1,2‐dicarbonyl‐3‐enes has not previously been carried out under heterogeneous catalysis conditions.
Streaming Complex Plasmas: Ion Susceptibility for a Partially Ionized Plasma in Parallel Electric and Magnetic Fields
Authors: Kählert H. , Joost J. P. , Ludwig P. , Bonitz M.
Published: February 2016

The density response function for streaming ions in homogeneous, parallel electric and magnetic fields is derived self‐consistently from kinetic theory. Ion‐neutral collisions are treated with the Bhatnagar‐Gross‐Krook collision operator assuming a constant ion‐neutral collision frequency. The result accounts for the non‐Maxwellian distribution function of the ions and is valid in the full range from weak to strong magnetization. It provides the basis for various linear response calculations in the context of magnetized complex plasmas, where streaming ions interact with highly charged dust particles under the influence of a strong external magnetic field. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Voids in Dusty Plasma of a Stratified DC Glow Discharge in Noble Gases
Authors: Fedoseev A. V. , Sukhinin G. I. , Abdirakhmanov A. R. , Dosbolayev M. K. , Ramazanov T. S.
Published: February 2016

Experimental investigations of dusty plasma parameters of a DC glow discharge were performed in helium and argon. In the discharge in helium, at high discharge current dust‐free regions (voids) were formed in the center of the dust particles clouds that levitated in the strong electric field of a stratified positive column. In experiments with argon, the dust particles were moved from the center of the discharge tube to the periphery at high discharge current. The behavior of voids formation was investigated for different discharge conditions (sort of gas, discharge pressure and discharge current) and dust particles parameters (particles radii and particles total number). It was shown that it is the ion drag force radial component that leads to the formation of voids in helium and moves the particles to the tube periphery in argon discharge. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Streptamer technology allows accurate and specific detection of CMV‐specific HLA‐A*02 CD8+ T cells by flow cytometry
Authors: Ciáurriz Miriam , Beloki Lorea , Bandrés Eva , Mansilla Cristina , Zabalza Amaya , Pérez‐Valderrama Estela , Lachén Mercedes , Ibáñez Berta , Olavarría Eduardo , Ramírez Natalia
Published: February 2016

Background

Multimer technology is widely used to screen antigen‐specific immune recovery after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) as it enables identification, enumeration, phenotypic characterization and isolation of virus‐specific T‐cells. Novel approaches of multimerization might improve on classical tetramer staining; however, their use as standard monitoring technique to quantify antigen‐specific cells has not been validated yet. We have compared two of these available multimeric complexes: pentamer and streptamer to select the best strategy for the incorporation into clinical monitoring practice.

Methods

CMVpp65495‐503‐specific HLA‐A*02:01 CD8+ T lymphocytes (CTLA*02:01‐CMVpp65495‐503) were examined with pentamer and streptamer in peripheral blood cells of 77 healthy volunteers. Quantitative and qualitative analyses were performed to compare the precision and repeatability, sensitivity and accuracy and specificity of both technologies by flow cytometry.

Results

Standard deviation for both techniques was less than 0.05 showing that they are repetitive and precise. Both techniques significantly correlated at high frequencies (rSpearman = 0.9422; P < 0.0001) but it was lost at lower levels (<1%) of CTLA*02:01‐CMVpp65495‐503 (rSpearman = 0.3351; P = 0.1376). Streptamer is more accurate for the detection of CTLA*02:01‐CMVpp65495‐503 providing significantly closer values to the theoretical ones (P < 0.0001) as pentamer binds unspecifically to a notable proportion of non‐CMV‐specific CD8+ T‐cells.

Conclusion

Our results suggest that streptamer multimer provides precise, accurate and specific results to detect CTLA*02:01‐CMVpp65495‐503 by flow cytometry. Streptamer multimer can be used not only for the monitoring of early CTLA*02:01‐CMVpp65495‐503 reconstitution in immunosuppressed patients following allo‐HSCT but also, in conjunction with its reversibility role, for the isolation of CTLA*02:01‐CMVpp65495‐503 for its future use in adoptive immunotherapy. © 2016 International Clinical Cytometry Society
Combinatorial decoding of the invariant C. elegans embryonic lineage in space and time
Authors: Zacharias Amanda L. , Murray John Isaac
Published: February 2016

Understanding how a single cell, the zygote, can divide and differentiate to produce the diverse animal cell types is a central goal of developmental biology research. The model organism Caenorhabditis elegans provides a system that enables a truly comprehensive understanding of this process across all cells. Its invariant cell lineage makes it possible to identify all of the cells in each individual and compare them across organisms. Recently developed methods automate the process of cell identification, allowing high‐throughput gene expression characterization and phenotyping at single cell resolution. In this Review, we summarize the sequences of events that pattern the lineage including establishment of founder cell identity, the signaling pathways that diversify embryonic fate, and the regulators involved in patterning within these founder lineages before cells adopt their terminal fates. We focus on insights that have emerged from automated approaches to lineage tracking, including insights into mechanisms of robustness, context‐specific regulation of gene expression, and temporal coordination of differentiation. We suggest a model by which lineage history produces a combinatorial code of transcription factors that act, often redundantly, to ensure terminal fate. genesis, 2016. © 2016 Wiley Periodicals, Inc. genesis 54:182–197, 2016. © 2016 Wiley Periodicals, Inc.
Vocal coselection in rat pup ultrasonic vocalizations
Authors: Spence Heather R. , Aslam Ali M. , Hofer Myron A. , Brunelli Susan A. , Shair Harry N.
Published: February 2016

Selective breeding and natural selection that select for one trait often bring along other correlated traits via coselection. Selective breeding for an infantile trait, high or low call rates of isolation‐induced ultrasonic vocalization of rat pups, also alters functions of some brain systems and emotional behaviors throughout life. We examined the effect of breeding for call rate on acoustic parameters that are of communicative significance. Selecting for higher call rate produced calls of significantly increased amplitude and bandwidth relative to a randomly bred line. Selecting for lower rate produced calls of decreased duration. These nonmorphological, functional trait changes demonstrate enhanced communicatory potential and energy expenditure for the High line and the opposite for the Low line. This demonstration of coselection in a communicatory system suggests an underlying heritable suite of linked acoustic vocalization characteristics that in noisy environments could enhance dam–pup communication and lead to selection of emotionality traits with beneficial responses to stress.
Climatic patterns in the establishment of wintering areas by North American migratory birds
Authors: Pérez‐Moreno Heidi , Martínez‐Meyer Enrique , Soberón Mainero Jorge , Rojas‐Soto Octavio
Published: February 2016

Long‐distance migration in birds is relatively well studied in nature; however, one aspect of this phenomenon that remains poorly understood is the pattern of distribution presented by species during arrival to and establishment of wintering areas. Some studies suggest that the selection of areas in winter is somehow determined by climate, given its influence on both the distribution of bird species and their resources. We analyzed whether different migrant passerine species of North America present climatic preferences during arrival to and departure from their wintering areas. We used ecological niche modeling to generate monthly potential climatic distributions for 13 migratory bird species during the winter season by combining the locations recorded per month with four environmental layers. We calculated monthly coefficients of climate variation and then compared two GLM (generalized linear models), evaluated with the AIC (Akaike information criterion), to describe how these coefficients varied over the course of the season, as a measure of the patterns of establishment in the wintering areas. For 11 species, the sites show nonlinear patterns of variation in climatic preferences, with low coefficients of variation at the beginning and end of the season and higher values found in the intermediate months. The remaining two species analyzed showed a different climatic pattern of selective establishment of wintering areas, probably due to taxonomic discrepancy, which would affect their modeled winter distribution. Patterns of establishment of wintering areas in the species showed a climatic preference at the macroscale, suggesting that individuals of several species actively select wintering areas that meet specific climatic conditions. This probably gives them an advantage over the winter and during the return to breeding areas. As these areas become full of migrants, alternative suboptimal sites are occupied. Nonrandom winter area selection may also have consequences for the conservation of migratory bird species, particularly under a scenario of climate change.
Species‐ and site‐specific impacts of an invasive herbivore on tree survival in mixed forests
Authors: Holland E. Penelope , Gormley Andrew M. , Pech Roger P.
Published: February 2016

Invasive herbivores are often managed to limit their negative impact on plant populations, but herbivore density – plant damage relationships are notoriously spatially and temporally variable. Site and species characteristics (both plant and herbivore) must be considered when assessing the potential for herbivore damage, making it difficult to set thresholds for efficient management. Using the invasive brushtail possum Trichosurus vulpecula in New Zealand as a case study, we parameterized a generic model to predict annual probability of browse‐induced mortality of five tree species at 12 sites. We compared predicted and observed tree mortality for each species + site combination to establish herbivore abundance – tree mortality thresholds for each site on a single and combined tree species basis. Model results indicated it is likely that possum browse was the primary cause of all tree mortality at nine of the 12 species‐site combinations, allowing us to estimate site‐specific thresholds below which possum population numbers should be reduced and maintained to keep tree mortality under a predetermined level, for example 0.5% per year. The browse model can be used to set site‐ and species‐specific management action thresholds, and can be adapted easily for other plant or herbivore species. Results for multiple plant or herbivore species at a single site can be combined to create conservative, site‐wide management strategies, and used to: determine which sites will be affected most by changes in herbivore abundance; quantify thresholds for herbivore management; and justify expenditure on herbivore control.
Belowground responses to elevation in a changing cloud forest
Authors: Looby Caitlin I. , Maltz Mia R. , Treseder Kathleen K.
Published: February 2016

Few studies have investigated how soil fungal communities respond to elevation, especially within TMCF (tropical montane cloud forests). We used an elevation gradient in a TMCF in Costa Rica to determine how soil properties, processes, and community composition of fungi change in response to elevation and across seasons. As elevation increased, soil temperature and soil pH decreased, while soil moisture and soil C:N ratios increased with elevation. Responses of these properties varied seasonally. Fungal abundance increased with elevation during wet and dry seasons. Fungal community composition shifted in response to elevation, and to a lesser extent by season. These shifts were accompanied by varying responses of important fungal functional groups during the wet season and the relative abundance of certain fungal phyla. We suggest that elevation and the responses of certain fungal functional groups may be structuring fungal communities along this elevation gradient. TMCF are ecosystems that are rapidly changing due to climate change. Our study suggests that these changes may affect how fungal communities are structured.
Facile one‐step synthesis of bio‐based AESO resins
Authors: Wang Chengshuang , Ding Liang , He Meng , Wei Jun , Li Juan , Lu Rong , Xie Hongfeng , Cheng Rongshi
Published: February 2016

In this study, the bio‐based thermosetting resins were synthesized via thiol‐ene coupling between acrylated epoxidized soybean oil (AESO) and different functionality of thiols. The structure of the AESO was carefully examined using FT–IR and 1H‐NMR measurements. The thermal/mechanical properties of the bio‐based thermosetting resins were characterized using DMA, TGA, and tensile test. The DMA results showed that the storage moduli and glass transition temperatures of bio‐based thermosetting resins improved with increment of thiols functionality, meanwhile, the tensile strength, Young's modulus, and thermal stability of the AESO‐based resins also increased.

Practical applications: The thermosetting resins were synthesized via thiol‐ene coupling between AESO and different functionality of thiols. This strategy has the potential for the fabrication of eco‐friendly bio‐based materials.

The rapid and highly efficient strategy of thiol‐ene coupling was successfully applied for the preparation of eco‐friendly bio‐based thermosetting resins derived from AESO and different functionality of thiols.
Thiyl‐Radical Reactions in Carbo­hydrate Chemistry: From Thiosugars to Glycoconjugate Synthesis
Authors: McSweeney Lauren , Dénès Fabrice , Scanlan Eoin M.
Published: February 2016

Thiyl‐radical mediated reactions have been extensively investigated for the preparation of carbohydrate derivatives. Due to the mild reaction conditions, high yields and tolerance to a wide range of functional groups, these reactions are ideally suited to the preparation of bioconjugates including glycopeptides and glycoproteins. This microreview covers the various synthetic strategies that have been employed for the preparation of thiosugars, glycoconjugates and glycodendrimers, employing the carbohydrate unit as both the carrier of the thiyl radical and also as the acceptor. Both the inter‐ and intramolecular thiol‐ene and ‐yne processes are presented and discussed. Future perspective and directions for this methodology in glycoscience are also examined.
Chiral Anion Directed Asymmetric Carbocation‐Catalyzed Diels–Alder Reactions
Authors: Ni Shengjun , Ramesh Naidu Veluru , Franzén Johan
Published: February 2016

In recent years the carbocation has re‐emerged as a highly efficient Lewis acid catalyst for a variety of organic transformations. However, the goal of asymmetric carbocation catalysis has so far been out of reach mainly as a result of difficulties associated with the preparation of stable chiral carbocations. Here, we describe developments towards asymmetric carbocation catalysis based on the concept of chiral‐anion‐directed catalysis. Chiral tritylium salts can be conveniently prepared in situ by mixing trityl chloride derivatives with chiral phosphonate, phosphoramide, bis(sulfonyl)amide, and bis(sulfuryl)amide silver or sodium salts. It is shown that the bis(sulfuryl)amide/tritylium ion salt catalyzes the Diels–Alder reaction with an up to 53 % enantiomeric excess.
Algoplus performance to detect pain in depressed and/or demented old patients
Authors: Bonin‐Guillaume S. , Jouve E. , Lauretta R. , Nalin C. , Truillet R. , Capriz F. , Rat P.
Published: February 2016

Background

Algoplus detects acute pain in non‐verbal old patients (NVOP) with good psychometric properties. However, depression or dementia might modify the Algoplus score and/or item expression. Algoplus performances on demented and/or depressed old populations were tested.

Methods

This multicentre cross‐sectional study included patients ≥65 years old with or without pain assigned to depression, dementia, depression & dementia or control groups. Each group was subjected to the Numerical Rating Scale (NRS) and behavioural scales (Algoplus, Doloplus). Depression and/or dementia status was rated and confirmed by blinded experts. Algoplus psychometric properties tested were: discriminant validity, convergent validity, item analysis, sensitivity to change after pain treatment and threshold determination.

Results

The analysis included 171 patients (mean age 82.3 ± 6.3 years). Patients with and without pain in each group were comparable for age in all subgroups, except the older dementia subgroup. The mean Algoplus score was significantly higher for patients with than without pain, regardless of group assignment (Wilcoxon signed‐rank test, p < 0.001). Algoplus and NRS or Doloplus had high convergent validity (respective Spearman correlation coefficients 0.79 and 0.87). The mean Algoplus score decreased significantly after starting pain management, regardless of group assignment. Some behaviours (i.e. “look”) occurred more often in depressed patients, even those without pain. A threshold of 2 yielded respective sensitivity and specificity values of 95% and 96% for dementia patients, 62% and 79% for depressed patients, 96% and 71% for dementia & depressed patients, and 80% and 100% for controls.

Conclusion

Algoplus accurately detected pain in depressed and/or dementia patients; and was sensitive to change after pain treatment.

What does this study add?

Algoplus accurately detects pain in depressed and/or demented patients.

A cut‐off score of 2 accurately detects the need for pain management in these populations.

Algoplus is sensitive to change after treating pain.
Central sensitization as the mechanism underlying pain in joint hypermobility syndrome/Ehlers–Danlos syndrome, hypermobility type
Authors: Di Stefano G. , Celletti C. , Baron R. , Castori M. , Di Franco M. , La Cesa S. , Leone C. , Pepe A. , Cruccu G. , Truini A. , Camerota F.
Published: February 2016

Background

Patients with joint hypermobility syndrome/Ehlers–Danlos syndrome, hypermobility type (JHS/EDS‐HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia.

Methods

In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS‐HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal‐pain perceptive thresholds and the wind‐up ratio and recorded a standard nerve conduction study to assess non‐nociceptive fibres and laser‐evoked potentials, assessing nociceptive fibres.

Results

Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind‐up ratio.

Conclusions

While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS‐HT, the lowered cold and heat pain thresholds and increased wind‐up ratio imply that pain in JHS/EDS‐HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms.

What does this study add?

In patients with JHS/EDS‐HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain.
Primary sensory and motor cortex function in response to acute muscle pain: A systematic review and meta‐analysis
Authors: Burns E. , Chipchase L.S. , Schabrun S.M.
Published: February 2016

Acute muscle pain has both motor and sensory consequences, yet the effect of muscle pain on the primary sensory (S1) and motor (M1) cortices has yet to be systematically evaluated. Here we aimed to determine the strength of the evidence for (1) altered activation of S1/M1 during and after pain, (2) the temporal profile of any change in activation and (3) the relationship between S1/M1 activity and the symptoms of pain. In September 2015, five electronic databases were systematically searched for neuroimaging and electrophysiological studies investigating the effect of acute experimental muscle pain on S1/M1 in healthy volunteers. Demographic data, methodological characteristics and primary outcomes for each study were extracted for critical appraisal. Meta‐analyses were performed where appropriate. Twenty‐five studies satisfied the inclusion criteria. There was consistent evidence from fMRI for increased S1 activation in the contralateral hemisphere during pain, but insufficient evidence to determine the effect at M1. Meta‐analyses of TMS and EEG data revealed moderate to strong evidence of reduced S1 and corticomotor excitability during and following the resolution of muscle pain. A comprehensive understanding of the temporal profile of altered activity in S1/M1, and the relationship to symptoms of pain, is hampered by differences in methodological design, pain modality and pain severity between studies. Overall, the findings of this review indicate reduced S1 and corticomotor activity during and after resolution of acute muscle pain, mechanisms that could plausibly underpin altered sensorimotor function in pain.

What does this review add?

We provide the first systematic evaluation of the primary sensory (S1) and motor (M1) cortex response to acute experimental muscle pain in healthy volunteers. We present evidence from a range of methodologies to provide a comprehensive understanding of the effect of pain on S1/M1. Through meta‐analyses we evaluate the strength of evidence concerning the direction and temporal profile of the S1/M1 response to acute muscle pain.
Development of an Electrochemical Biosensor for the Rapid Detection of Cholera Toxin Based on Air Stable Lipid Films with Incorporated Ganglioside GM1 Using Graphene Electrodes
Authors: Karapetis Stephanos , Nikoleli Georgia‐Paraskevi , Siontorou Christina G. , Nikolelis Dimitrios P. , Tzamtzis Nikolaos , Psaroudakis Nikolas
Published: February 2016

The present work describes a miniaturized potentiometric cholera toxin sensor on graphene nanosheets with incorporated lipid films. Ganglioside GM1, the natural cholera toxin receptor, immobilized on the stabilized lipid films, provided adequate selectivity for detection over a wide range of toxin concentrations, fast response time of ca. 5 min, and detection limit of 1 nM. The proposed sensor is easy to construct and exhibits good reproducibility, reusability, selectivity, long shelf life and high sensitivity of ca. 60 mV/decade of toxin concentration. The method was implemented and validated in lake water samples. This novel ultrathin film technology is currently adapted to the rapid detection of other toxins that could be used in bioterrorism.
Coenrichment characteristics of phosphorus and heavy metals in incinerated sewage sludge ash
Authors: Li Rundong , Teng Wenchao , Li Yanlong , Wang Weiyun , Yang Tianhua , Zhang Ziheng
Published: February 2016

The heavy metal problem during phosphorus recovery from sewage sludge cannot be ignored. Accordingly, this study investigates the effect of the form and content of phosphorus on the behavior of heavy metals (specifically, Cu, Zn, Pb, and Cd) in sewage sludge incineration to determine the optimum condition for heavy metal enrichment in ashes. The experiment is performed in a laboratory‐scale furnace with phosphate additives at 750–950°C to analyze the heavy metal content in sewage sludge ash (SSA). The crystalline phase is analyzed using X‐ray diffraction to explore the mechanism of phosphorus immobilized heavy metals. The morphology is analyzed by scanning electron microscopy to investigate the effect of surface structure difference caused by different temperatures on heavy metal volatilization. Phosphorus significantly affects Zn, Pb, and Cd but not Cu. P2O5 and KH2PO4 have more obvious effects than (NH4)3PO4 and Ca3(PO4)2 on heavy metal immobilization. The additive (e.g., Ca3(PO4)2) could increase SSA melting point and observably improve volatilization of Zn at 950°C. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1027–1034, 2016
Impact of hazard‐consistent ground motion duration in structural collapse risk assessment
Authors: Chandramohan Reagan , Baker Jack W. , Deierlein Gregory G.
Published: February 2016

This study evaluates the effect of considering ground motion duration when selecting hazard‐consistent ground motions for structural collapse risk assessment. A procedure to compute source‐specific probability distributions of the durations of ground motions anticipated at a site, based on the generalized conditional intensity measure framework, is developed. Targets are computed for three sites in Western USA, located in distinct tectonic settings: Seattle, Eugene, and San Francisco. The effect of considering duration when estimating the collapse risk of a ductile reinforced concrete moment frame building, designed for a site in Seattle, is quantified by conducting multiple stripe analyses using groups of ground motions selected using different procedures. The mean annual frequency of collapse (λcollapse) in Seattle is found to be underestimated by 29% when using typical‐duration ground motions from the PEER NGA‐West2 database. The effect of duration is even more important in sites like Eugene (λcollapse underestimated by 59%), where the seismic hazard is dominated by large magnitude interface earthquakes, and less important in sites like San Francisco (λcollapse underestimated by 7%), where the seismic hazard is dominated by crustal earthquakes. Ground motion selection procedures that employ causal parameters like magnitude, distance, and Vs30 as surrogates for ground motion duration are also evaluated. These procedures are found to produce poor fits to the duration and response spectrum targets because of the limited number of records that satisfy typical constraints imposed on the ranges of the causal parameters. As a consequence, ground motions selected based on causal parameters are found to overestimate λcollapse by 53%. Copyright © 2016 John Wiley & Sons, Ltd.
Seismic response estimation method for earthquake‐damaged RC buildings
Authors: Choi Ho , Sanada Yasushi , Kashiwa Hisatoshi , Watanabe Yasuhiro , Tanjung Jafril , Jiang Huanjun
Published: February 2016

This study proposes a procedure for identifying spectral response curves for earthquake‐damaged areas in developing countries without seismic records. An earthquake‐damaged reinforced concrete building located in Padang, Indonesia was selected to illustrate the identification of the maximum seismic response during the 2009 West Sumatra earthquake. This paper summarizes the damage incurred by the building; the majority of the damage was observed in the third story in the span direction. The damage was quantitatively evaluated using the damage index R according to the Japanese guidelines for post‐earthquake damage evaluation. The damage index was also applied to the proposed spectral response identification method. The seismic performance of the building was evaluated by a nonlinear static analysis. The analytical results reproduced a drift concentration in the third story. The R‐index decreased with an increase in the story drift, which provided an estimation of the maximum response of the building during the earthquake. The estimation was verified via an earthquake response analysis of the building using ground acceleration data, which were simulated based on acceleration records of engineering bedrock that considered site amplification. The maximum response estimated by the R‐index was consistent with the maximum response obtained from the earthquake response analysis. Therefore, the proposed method enables the construction of spectral response curves by integrating the identification results for the maximum responses in a number of earthquake‐damaged buildings despite a lack of seismic records. Copyright © 2016 The Authors. Earthquake Engineering & Structural Dynamics published by John Wiley & Sons Ltd.
Family Functioning and Quality of Life among Families in Eating Disorders: A Comparison with Substance‐related Disorders and Healthy Controls
Authors: Anastasiadou Dimitra , Sepulveda Ana R. , Sánchez Julio César , Parks Melissa , Álvarez Tamara , Graell Montserrat
Published: February 2016

The aim of this study was to compare the family functioning of Spanish parents of patients with an eating disorder (ED) with that of carers of patients with substance‐related disorders (SRDs) and families of healthy controls (HC). This cross‐sectional study included 48 mothers and 45 fathers of 48 adolescent patients with an ED, 47 mothers and 37 fathers of 47 patients with an SRD and 66 mothers and 50 fathers of 68 HCs. Families of ED patients reported lower levels of criticism, symptom accommodation and negative caregiving experience than families of SRD patients. However, relatives of both ED and SRD patients reported similar levels of quality of life related to their mental health. Furthermore, families of HCs generally exhibited better scores on all scales assessing their caregiving experiences. Regarding gender differences, there was a tendency in mothers, primarily those from the ED group, to report more adverse experiences as caregivers compared with fathers. Symptoms characteristic to each disorder may be associated with differential patterns of family functioning and may require specifically tailored family interventions. Early family intervention in adolescence is crucial, as relatives' quality of life does not seem to have been badly affected at this point in the course of the illness. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.
To what extent have changes in channel capacity contributed to flood hazard trends in England and Wales?
Authors: Slater Louise J.
Published: February 2016

The frequency of floods has been projected to increase across Europe in the coming decades due to extreme weather events. However, our understanding of how flood frequency is affected by geomorphic changes in river channel capacity remains limited. This paper seeks to quantify the influence of trends in channel capacity on flood hazards. Measuring and predicting the effect of geomorphic changes on freshwater flooding is essential to mitigate the potential effects of major floods through informed planning and response. Hydrometric records from 41 stream gauging stations were used to measure trends in the flood stage (i.e. water surface elevation) frequency above the 1% annual exceedance threshold. The hydrologic and geomorphic components of flood hazard were quantified separately to determine their contribution to the total trend in flood stage frequency. Trends in cross‐sectional flow area and mean flow velocity were also investigated at the same flood stage threshold. Results showed that a 10% decrease (or increase) in the channel capacity would result in an increase (or decrease) in the flood frequency of approximately 1.5 days per year on average across these 41 sites. Widespread increases in the flood hazard frequency were amplified through both hydrologic and geomorphic effects. These findings suggest that overlooking the potential influence of changing channel capacity on flooding may be hazardous. Better understanding and quantifying the influence of geomorphic trends on flood hazard will provide key insight for managers and engineers into the driving mechanisms of fluvial flooding over relatively short timescales. Copyright © 2016 John Wiley & Sons, Ltd.
Observations of coastal cliff base waves, sand levels, and cliff top shaking
Authors: Young Adam P. , Guza Robert T. , O'Reilly William C. , Burvingt Olivier , Flick Reinhard E.
Published: February 2016

Concurrent observations of waves at the base of a southern California coastal cliff and seismic cliff motion were used to explore wave–cliff interaction and test proxies for wave forcing on coastal cliffs. Time series of waves and sand levels at the cliff base were extracted from pressure sensor observations programmatically and used to compute various wave impact metrics (e.g. significant cliff base wave height). Wave–cliff interaction was controlled by tide, incident waves, and beach sand levels, and varied from low tides with no wave–cliff impacts, to high tides with continuous wave–cliff interaction. Observed cliff base wave heights differed from standard Normal and Rayleigh distributions. Cliff base wave spectra levels were elevated at sea swell and infragravity frequencies. Coastal cliff top response to wave impacts was characterized using microseismic shaking in a frequency band (20–45 Hz) sensitive to wave breaking and cliff impacts. Response in the 20–45 Hz band was well correlated with wave–cliff impact metrics including cliff base significant wave height and hourly maximum water depth at the cliff base (r2 = 0.75). With site‐specific calibration relating wave impacts and shaking, and acceptable anthropogenic (traffic) noise levels, cliff top seismic observations are a viable proxy for cliff base wave conditions. The methods presented here are applicable to other coastal settings and can provide coastal managers with real time coastal conditions. Copyright © 2016 John Wiley & Sons, Ltd.