bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐Dimensional P‐Wave Velocity Structure Around the Xiaojiang Fault Zone and Its Tectonic Implications
Authors: Jian‐Ping WU , Ting YANG , Wei‐Lai WANG , Yue‐Hong MING , Tian‐Zhong ZHANG
Published: October 2013

As the southeastern margin of the Tibetan Plateau, the Xiaojiang fault zone plays an important role in the lateral escape of Tibetan Plateau materials. In this work, the 3‐D P‐wave velocity structure of the Xiaojiang fault zone and its surrounding areas was imaged by using travel time data from permanent seismic stations and a dense temporal seismic array. The results show that in the upper and middle crust, the Xiaojiang fault zone is mainly of low velocity, while high velocity anomalies exist to its east. In the middle and lower crust, a low velocity anomaly is shown in the central portion of the Xiaojiang fault zone, and high velocity anomalies exist both in the northern and southern areas. The northern high velocity anomaly near Panzhihua extends from lower crust to the surface, and the southern one in the lower crust extends to the upper mantle. We consider that the low velocity anomaly in the central portion of the Xiaojiang fault zone is caused by high temperature derived from upper mantle. The high anomalies in the northern area are most likely related to the late Paleozoic mantle plume activity which caused a large number of basic and ultrabasic mantle materials intruding into the crust. These high‐velocity anomalies, with greater mechanical strength, play a certain impediment to southward escaping of Tibetan Plateau materials, and lead to the rapid uplift of the northern sub‐block of the Sichuan‐Yunnan active block. The north‐dipping high velocity anomaly in the southern area is a further barrier for southward extrusion of the Sichuan‐Yunnan active block, leading to strong deformation and intense seismicity within the low‐velocity area in the overlaying upper and middle crust. Meantime, this high‐velocity block contributes to stabilization of the upper mantle, which makes mantle materials of its southern region less affected by the southward escape of Tibetan Plateau materials.
Accurate Location of the Lushan, Sichuan M7.0 Earthquake on 20 April 2013 and Its Aftershocks and Analysis of the Seismogenic Structure
Authors: Jin‐Rong SU , Yu ZHENG , Jian‐Si YANG , Tian‐Chang CHEN , Peng WU
Published: October 2013

The M7.0 Lushan earthquake and its aftershocks in 9 days were relocated by the double difference algorithm and a layered velocity model, using the seismic phases recorded at stations within 150 km including the fixed stations of the Sichuan earthquake network center, temporary stations, and reservoir stations. The events analyzed include the main shock and its 3324 aftershocks. The results show that the origin time of the main shock is 8:02:46.8 on 20 April 2013, hypocenter location 30.278°N, 102.989°E and the focal depth 16.67 km. The main rupture is about 40 km long, 20 km wide with an apparent area 800 km2. It strikes in southwest and dips about 40°. Most aftershocks occurred at depths 10∼22 km, concentrating on the hanging wall of the Dayi‐Mingshan fault, forming a southwest‐trending belt on the surface. Based on these and other data, this paper makes a preliminary analysis of the seismogenic structure of the Lushan event.
Mechanism of Postseismic Deformation of Ground Surface Following the 1999 Chi‐Chi Earthquake, Taiwan
Authors: Zhen FU , Hai‐Ming ZHANG , Yong‐En CAI
Published: October 2013

GPS measurements of 450 days after the 1999 Chi‐Chi, Taiwan, earthquake revealed large postseismic displacement from dozens to hundreds of millimeters. Two possible mechanisms responsible for the postseismic deformation of the surface are the viscous relaxation of the lower crust and the afterslip caused by the aseismic creep of the earthquake fault. In this study, the finite element method (LDDA) for the viscoelastic contact problems is used to simulate the postseismic deformation process of the 1999 Chi‐Chi earthquake with the GPS data as constraints. And the two possible mechanisms, viscous relaxation and afterslip, are discussed. The results indicate that the postseismic deformation observed by GPS can be well explained by the viscous relaxation mechanism. The viscosity of the lower crust below the Taiwan area is estimated as 1017 Pa·s by the trial‐and‐error method. The effect of afterslip mechanism on the postseismic deformation of the Chi‐Chi earthquake is investigated by the numerical method with rate‐and‐state dependent frictional law. The results suggest that the GPS data cannot be explained by the afterslip mechanism alone, which only affects the postseismic deformation in the early 50 days after the mainshock. These studies will throw light on understanding the mechanism of the postseismic deformation of the 1999 Chi‐Chi, Taiwan, earthquake.
Full Waveform Inversion Based on Modified Quasi‐Newton Equation Quasi‐Newton Equation
Authors: Lu LIU , Hong LIU , Heng ZHANG , Yong‐Fu CUI , Fei LI , Wen‐Sheng DUAN , Geng‐Xin PENG
Published: October 2013

Waveform inversion is a kind of method to reveal the underground structure and lithology through minimizing the residual error between predicted wavefield and true seismic record using full‐wavefield information. In this paper, we briefly present the principle of the conventional Quasi‐Newton algorithm, and then exploit a new modified Quasi‐Newton equation to modify the conventional Davidon‐Fletcher‐Powell (DFP) and Broyden‐Fletcher‐Goldfarb‐Shanno (BFGS) algorithms. Different from past Quasi‐Newton methods, this modified BFGS considers gradient values, model information and objective function values to approximate the inverse matrix of Hessian matrix. Moreover, it almost does not increase the calculation amount for each iteration. The numerical experiment shows that compared with the conventional Quasi‐Newton method, the modified BFGS algorithm can not only preserve the inverse accuracy, but also significantly improve calculation efficiency.
Three‐Dimensional Magnetotelluric Parallel Inversion Algorithm Using the Data‐Space Method
Authors: Xiang‐Yun HU , Yan LI , Wen‐Cai YANG , Wen‐Bo WEI , Rui GAO , Bo HAN , Rong‐Hua PENG
Published: October 2013

Up until now, the key issue in practical applications of three‐dimensional magnetotelluric (3D MT) inversion is low efficiency of computation. By further analysis of the data‐space inversion approach of 3D MT, we develop a massively parallel inversion scheme on the basis of frequency division and matrix decomposition, and implement its procedure by using MPI on the Dawn TC5000A high‐performance computing platform. The algorithm we develop includes the parallel calculation of 3D forward modeling, sensitivity matrix and cross‐product matrix, as well as the update of model parameters. The algorithm has the advantages of higher efficiency in computation and lower memory storage in which the storage amount of sensitivity matrix at every single computing node is 2/N times as much amount as a PC (N is the number of nodes included in parallel computation). Furthermore, we test the implemented scheme with synthetic data from two 3D theoretical models and analyze the computational efficiency under multiple‐nodes computing. The numerical experiment results show that the 3D data‐space parallel inversion algorithm is feasible and efficient. Compared with the implementation on single PC, the parallel scheme is not only able to improve the computing speed and shorten the computation time, but also enlarge the calculational scale, which would advance greatly the utility of 3D MT inversion.
Thermal Evolution Patterns and Primary Controlling Factors of Sinian‐Lower Paleozoic Source Rocks in the Sichuan Basin, Southwestern China
Authors: Song RAO , Chuan‐Qing ZHU , Qiang WANG , Xiao‐Yin TANG , Wei‐Wei LI , Guang‐Zheng JIANG , Sheng‐Biao HU , Ji‐Yang WANG
Published: October 2013

Thermal evolution is an essential part of evaluation to source rocks as well as of research of hydrocarbon dynamic accumulation in oil‐gas‐bearing basins. The purpose of this work is to use the Easy%Ro chemical kinetic model to simulate the thermal evolution history of source rocks of Sinian‐Paleozoic ages in the Sichuan basin. It is based on analysis of styles of stratum deposition, recovery of thermal history of the basin, and the data from 86 representative drilling boreholes and more than 200 man‐made wells. The results show that the varied tectonic units of the basin have distinct feature of thermal evolution of the Lower Cambrian and Lower Silurian source rocks. Thus four models of thermal evolution are established: (1) Being mature during the Caledonian epoch and rapidly developed and shaped up in the early Late Permian period, as represented by the Lower Cambrian source rocks in the southern basin; (2) Not being mature during the Caledonian epoch and rapidly developed and shaped up in the early Late Permian period, as represented by the Lower Cambrian source rocks in the southwestern basin and Lower Silurian source rocks in the southern basin; (3) Being mature during the Caledonian epoch and mature again in the Late Hercynian‐Yanshanian epochs, as indicated by the Lower Cambrian source rocks in the northern basin; and (4) Not mature during the Caledonian epoch and steady maturity in the Late Hercynian‐Yanshanian epochs, as shown by the Lower Cambrian source rocks in the central basin and Lower Silurian source rocks in the eastern and northern basin. By comparison of relationship among the deposition rate heat flow and temperature increase rate, we infer the controlling factors of the thermal evolution of the source rocks above. For the southwestern and local southern Sichuan basin, the mantle plume and abnormal heat effect of basalt at the Emeishan during the early Late Permian period had exerted an major influence on the source rocks. In the rest of the basin, heating of sediments at depth and heat flow of the basin has a joint effect, especially the former had greatly increased the temperature of source rocks.
Computer‐Aided Design, Synthesis and Validation of 2‐Phenylquinazolinone Fragments as CDK9 Inhibitors with Anti‐HIV‐1 Tat‐Mediated Transcription Activity
Authors: Sancineto Luca , Iraci Nunzio , Massari Serena , Attanasio Vanessa , Corazza Gianmarco , Barreca Maria Letizia , Sabatini Stefano , Manfroni Giuseppe , Avanzi Nilla Roberta , Cecchetti Violetta , Pannecouque Christophe , Marcello Alessandro , Tabarrini Oriana
Published: October 2013

The activity of the cyclin‐dependent kinase 9 (CDK9) is critical for HIV‐1 Tat‐mediated transcription and represents a promising target for antiviral therapy. Here we present computational studies that, along with preliminary synthetic efforts, allowed us to identify and characterize a new class of nontoxic anti‐CDK9 chemotypes based on the 2‐phenylquinazolinone scaffold. Inhibition of CDK9 translated into the ability to interfere selectively with Tat‐mediated transactivation of the viral promoter and in the inhibition of HIV‐1 reactivation from latently infected cells, with the most potent derivative 37 (2‐(4‐aminophenyl)‐7‐chloroquinazolin‐4(3H)‐one) showing an IC50 value of 4.0 μM. Because the herein reported 2‐phenylquinazolinones are merely fragments, they are largely optimizable, paving the way to derivatives with improved potency.
What factors influence minority use of National Cancer Institute‐designated cancer centers?
Authors: Huang Lyen C. , Ma Yifei , Ngo Justine V. , Rhoads Kim F.
Published: October 2013

BACKGROUND

National Cancer Institute (NCI) cancer centers provide high‐quality care and are associated with better outcomes. However, racial and ethnic minority populations tend not to use these settings. The current study sought to understand what factors influence minority use of NCI cancer centers.

METHODS

A data set containing California Cancer Registry (CCR) data linked to patient discharge abstracts identified all patients with colorectal cancer (CRC) who were treated from 1996 through 2006. Multivariable models were generated to predict the use of NCI settings by race. Geographic proximity to an NCI center and patient sociodemographic and clinical characteristics were assessed.

RESULTS

Approximately 5% of all identified patients with CRC (n = 79,231) were treated in NCI settings. The median travel distance for treatment for all patients in all hospitals was ≤ 5 miles. A higher percentage of minorities lived near an NCI cancer center compared with whites. A baseline multivariable model predicting use showed a negative association between Hispanic ethnicity and NCI center use (odds ratio, 0.71; 95% confidence interval, 0.64‐0.79). Asian/Pacific Islander patients were more likely to use NCI centers (odds ratio, 1.41; 95% confidence interval, 1.28‐1.54). There was no difference in use noted among black patients. Increasing living distance from an NCI cancer center was found to be predictive of lower odds of use for all populations. Medicare and Medicaid insurance statuses were positively associated with NCI center use. Neighborhood‐level education was found to be a more powerful predictor of NCI use than poverty or unemployment.

CONCLUSIONS

Select minority groups underuse NCI cancer centers for CRC treatment. Sociodemographic factors and proximity to NCI centers are important predictors of use. Interventions to address these factors may improve minority attendance to NCI cancer centers for care. Cancer 2014;120:399–407. © 2013 American Cancer Society.
Clinical and economic outcomes of patients with brain metastases based on symptoms: An argument for routine brain screening of those treated with upfront radiosurgery
Authors: Lester Scott C. , Taksler Glen B. , Kuremsky J. Griff , Lucas John T. , Ayala‐Peacock Diandra N. , Randolph David M. , Bourland J. Daniel , Laxton Adrian W. , Tatter Stephen B. , Chan Michael D.
Published: October 2013

BACKGROUND

Insurers have started to deny reimbursement for routine brain surveillance with magnetic resonance imaging (MRI) after stereotactic radiosurgery (SRS) for brain metastases in favor of symptom‐prompted imaging. The authors investigated the clinical and economic impact of symptomatic versus asymptomatic metastases and related these findings to the use of routine brain surveillance.

METHODS

Between January 2000 and December 2010, 442 patients underwent upfront SRS for brain metastases. In total, 127 asymptomatic patients and 315 symptomatic patients were included. Medical records were used to determine the presenting symptoms, distant and local brain failure, retreatment, and need for hospital and rehabilitative care. Cost‐of‐care estimates were based on Medicare payment rates as of January 2013.

RESULTS

Symptomatic patients had an increased hazard for all‐cause mortality (hazard ratio, 1.448) and were more likely to experience neurologic death (42% vs 20%; P < .0001). Relative to asymptomatic patients, symptomatic patients required more craniotomies (43% vs 5%; P < .0001), had more prolonged hospitalization (2 vs 0 days; P < .0001), were more likely to have Radiation Therapy Oncology Group grade 3 and 4 post‐treatment symptoms (24% vs 5%; P < .0001), and required $11,957 more on average to manage per patient. Accounting for all‐cause mortality rates and the probability of diagnosis at each follow‐up period, the authors estimated that insurers would save an average $1326 per patient by covering routine surveillance MRI after SRS to detect asymptomatic metastases.

CONCLUSIONS

Patients who presented with symptomatic brain metastases had worse clinical outcomes and cost more to manage than asymptomatic patients. The current findings argue that routine brain surveillance after radiosurgery has clinical benefits and reduces the cost of care. Cancer 2014;120:433–441. © 2013 American Cancer Society.
Assessment of cellularity, genomic DNA yields, and technical platforms for BRAF mutational testing in thyroid fine‐needle aspirate samples
Authors: Dyhdalo Kathryn , MacNamara Stephen , Brainard Jennifer , Underwood Dawn , Tubbs Raymond , Yang Bin
Published: October 2013

BACKGROUND

BRAF mutation V600E (substitution Val600Glu) is a molecular signature for papillary thyroid carcinoma (PTC). Testing for BRAF mutation is clinically useful in providing prognostic prediction and facilitating accurate diagnosis of PTC in thyroid fine‐needle aspirate (FNA) samples.

METHODS

This study assessed the correlation of cellularity with DNA yield and compared 2 technical platforms with different sensitivities in detection of BRAF mutation in cytologic specimens. Cellularity was evaluated based on groups of 10+ cells on a ThinPrep slide: 1+ (1‐5 groups), 2+ (6‐10 groups), 3+ (11‐20 groups), and 4+ (> 20 groups). Genomic DNA was extracted from residual materials of thyroid FNAs after cytologic diagnosis.

RESULTS

Approximately 49% of thyroid FNA samples had low cellularity (1‐2+). DNA yield is proportionate with increased cellularity and increased nearly 4‐fold from 1+ to 4+ cellularity in cytologic samples. When applied to BRAF mutational assay, using a cutoff of 6 groups of follicular cells with 10+ cells per group, 96.7% of cases yielded enough DNA for at least one testing for BRAF mutation. Five specimens (11.6%) with lower cellularity did not yield sufficient DNA for duplicate testing. Comparison of Sanger sequencing to allele‐specific polymerase chain reaction methods shows the latter confers better sensitivity in detection of BRAF mutation, especially in limited cytologic specimens with a lower percentage of malignant cells.

CONCLUSIONS

This study demonstrates that by using 6 groups of 10+ follicular cells as a cutoff, nearly 97% of thyroid FNA samples contain enough DNA for BRAF mutational assay. Careful selection of a molecular testing system with high sensitivity facilitates the successful conduction of molecular testing in limited cytologic specimens. Cancer (Cancer Cytopathol) 2014;122:114–22 © 2013 American Cancer Society.
Personalizing Anticoagulant and Antiplatelet Therapeutics: A Timely Task
Authors: Gurwitz David
Published: October 2013

In spite of new therapeutics and diagnostics, thrombosis‐related diseases including heart failure and stroke remain the leading cause of death globally and a major healthcare burden. Pharmacogenomic studies may reduce the burden of thrombotic diseases by aiding treatment individualization with the most appropriate anti‐coagulant and anti‐platelet therapeutics. Discovering and validating biomarkers for improved personalized treatment of thrombotic diseases will require massive investment. A concerted dedicated effort built upon a public‐private partnership is warranted for addressing this foremost public health concern.
Will One Size of Anticoagulant Dosage Fit All?
Authors: Bloemen Saartje , De Laat Marieke , De Laat Bas , Hemker Hendrik Coenraad , Al Dieri Raed
Published: October 2013

Enabling Technology, Genomics, Proteomics
Preclinical Research

New, direct thrombin and factor Xa inhibitors have been developed to reduce the well‐established drawbacks of currently available anticoagulants such as a protracted duration of action and high inter‐ and intra‐individual variation of dose‐effect. New anticoagulants are noninferior and no less effective for thromboprophylaxis than low‐molecular‐weight heparins or vitamin K antagonists. They are currently administered at fixed doses without control of their effect on the clotting system. Whether they need monitoring cannot be answered because relevant data are lacking and present means of monitoring are inadequate. The individual response to a standard dose of (any) anticoagulant—the modern direct inhibitors included—is highly variable (∼30%), and the clinical effect of all anticoagulants is not dose independent. Therefore a fixed dose that is optimal for the average patient is suboptimal for a fair percentage of patients that are low responders (risk of re‐thrombosis) and dangerous for an equally high percentage of high responders (risk of bleeding). A better understanding of individual differences in the response, either low or high, to anticoagulants, irrespective of their mode of action, should be a primary objective for pharmacotherapy over the next decade.
Novel Approach to Diagnostics of Thrombocytosis: mRNA and miRNA Profiling of Blood Platelets
Authors: Gnatenko Dmitri V.
Published: October 2013

Preclinical Research

Thrombocytosis is a condition characterized by excessive numbers of platelets in blood. Chronic myeloproliferative diseases—including essential thrombocythemia—are among potential causes of high platelet count. Thrombosis of large arteries, stroke, and heart attack are among the major causes of mortality associated with essential thrombocythemia. Currently there is no direct diagnostic test for this disease leading to diagnosis by exclusion. Recent studies demonstrate that messenger RNA (mRNA) and microRNA (miRNA) profiling of human blood platelets can be used to discriminate patients with essential thrombocythemia from healthy control subjects and from patients with reactive thrombocytosis. This paper provides a brief overview of mRNA and miRNA biomarkers for thrombocytosis and discusses the development of a minimally invasive diagnostic assay for essential thrombocythemia. Advances in mRNA and miRNA profiling technology and progress in data analysis have made possible the generation of such an assay, which would significantly benefit patients with essential thrombocythemia and clinical hematologists.
Vanilloid‐Like Agents: Potential Therapeutic Targeting of Platelets?
Authors: Adams Murray J. , Almaghrabi Safa Y. , Ahuja Kiran D. K. , Geraghty Dominic P.
Published: October 2013

Preclinical Research

Capsaicinoids are the “hot” compounds present in placental tissues of Capsicum fruits that are responsible for capsicum's pungency. Capsaicinoids belong to the broader class of vanilloids that activate the nonselective cation channel, transient receptor potential vanilloid‐1 (TRPV1). Endogenous vanilloids include arachidonic acid derivatives that have different affinities for TRPV1 and are increasingly recognized as an important group of signaling molecules affecting tissue injury, pain, and inflammation. Furthermore, some endogenous vanilloids have high affinity for cannabinoid receptors (CB1 and CB2), which are present in platelets. The most well‐known and widely studied plant‐derived vanilloid, capsaicin, is reported to have antiplatelet properties, but the mechanism of action is uncertain. This article will briefly review the mechanisms involved in platelet activation and aggregation, discuss the properties of vanilloids and their receptor, TRPV1, and discuss whether the effects of vanilloids, and particularly capsaicinoids, on platelets may be exploited for therapeutic benefit.
Impact and Diagnosis of Antiplatelet Therapy Resistance in Patients Undergoing Cardiac Surgery
Authors: Gasparovic Hrvoje , Petricevic Mate , Biocina Bojan
Published: October 2013

Clinical Development Phases I‐III Regulatory, Quality, Manufacturing

Coronary artery bypass grafting (CABG) is highly effective in the treatment of severe coronary artery disease. Antiplatelet therapy is a critical component of the medical management of patients following CABG. Patient idiosyncrasies in responsiveness to antiplatelet agents, however, lead to variable suppression of platelet aggregation. This problem is underscored by inconsistent findings from the different laboratory instruments used to document antiplatelet drug responsiveness and its uncertain clinical impact. The laboratory results reveal a spectrum of platelet inhibition effects. The cutoff values discriminating between “resistance” and “response” to antiplatelet therapy often rely solely on definition. It is therefore not surprising that regular testing for antiplatelet therapy response has neither been routinely instituted in a wider clinical arena nor is there unequivocal evidence to support it. The purpose of this review is to offer insight into the incidence and clinical impact of antiplatelet therapy resistance in patients undergoing surgical myocardial revascularization.
Projected marine climate change: effects on copepod oxidative status and reproduction
Authors: Vehmaa Anu , Hogfors Hedvig , Gorokhova Elena , Brutemark Andreas , Holmborn Towe , Engström‐Öst Jonna
Published: October 2013

Zooplankton are an important link between primary producers and fish. Therefore, it is crucial to address their responses when predicting effects of climate change on pelagic ecosystems. For realistic community‐level predictions, several biotic and abiotic climate‐related variables should be examined in combination. We studied the combined effects of ocean acidification and global warming predicted for year 2100 with toxic cyanobacteria on the calanoid copepod, Acartia bifilosa. Acidification together with higher temperature reduced copepod antioxidant capacity. Higher temperature also decreased egg viability, nauplii development, and oxidative status. Exposure to cyanobacteria and its toxin had a negative effect on egg production but, a positive effect on oxidative status and egg viability, giving no net effects on viable egg production. Additionally, nauplii development was enhanced by the presence of cyanobacteria, which partially alleviated the otherwise negative effects of increased temperature and decreased pH on the copepod recruitment. The interactive effects of temperature, acidification, and cyanobacteria on copepods highlight the importance of testing combined effects of climate‐related factors when predicting biological responses.
Combining food web and species distribution models for improved community projections
Authors: Pellissier Loïc , Rohr Rudolf P. , Ndiribe Charlotte , Pradervand Jean‐Nicolas , Salamin Nicolas , Guisan Antoine , Wisz Mary
Published: October 2013

The ability to model biodiversity patterns is of prime importance in this era of severe environmental crisis. Species assemblage along environmental gradients is subject to the interplay of biotic interactions in complement to abiotic filtering and stochastic forces. Accounting for complex biotic interactions for a wide array of species remains so far challenging. Here, we propose using food web models that can infer the potential interaction links between species as a constraint in species distribution models. Using a plant–herbivore (butterfly) interaction dataset, we demonstrate that this combined approach is able to improve species distribution and community forecasts. The trophic interaction network between butterfly larvae and host plant was phylogenetically structured and driven by host plant nitrogen content allowing forecasting the food web model to unknown interactions links. This combined approach is very useful in rendering models of more generalist species that have multiple potential interaction links, where gap in the literature may occur. Our combined approach points toward a promising direction for modeling the spatial variation in entire species interaction networks.
T‐bet or not T‐bet: Taking the last bow on the autoimmunity stage
Authors: Spath Sabine , Becher Burkhard
Published: October 2013

The search for the encephalitogenic factor driving pathogenic T cells in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis (MS), and psoriasis has proven to be a long and difficult mission, which is not yet completed. In this issue of the European Journal of Immunology, the importance of the transcription factor T‐bet, previously shown to be essential for the induction of autoimmune disease in mice, is challenged. Two independent groups, O'Connor et al. [Eur. J. Immunol. 2013. 43:2818–2823] report] and Grifka‐Walk et al. [Eur. J. Immunol. 2013. 43:2824–2831], report that T‐bet is not mandatory for T cells to cause experimental autoimmune encephalomyelitis (EAE), which serves as a paradigmatic T‐cell‐mediated autoimmune disease. Both groups found that T‐bet KO mice were fully susceptible to develop EAE, both after immunization with self‐antigen and after adoptive transfer of IL‐23‐polarized autoaggressive T cells. T‐bet deficiency mediated the loss of IFN‐γ expression but retained or even enhanced GM‐CSF and IL‐17 production by central nervous system (CNS)‐infiltrating T cells. These findings indicate that we have lost the last transcriptional regulator previously held to be required for the generation of autoimmune pathogenic T cells.
The Synergetic Interplay of Weak Interactions in the Ion‐Pair Recognition of Quaternary and Diquaternary Ammonium Salts by Halogenated Resorcinarenes
Authors: Kodiah Beyeh N. , Göth Melanie , Kaufmann Lena , Schalley Christoph A. , Rissanen Kari
Published: October 2013

The influence of halogens on the noncovalent interactions of different upper‐rim‐substituted hexylresorcinarenes with quaternary and diquaternary ammonium iodide salts was investigated in the gas phase by electrospray ionization Fourier‐transform ion‐cyclotron‐resonance (ESI‐FTICR) mass spectrometry and in solution by 1H NMR titration studies. The electronic nature of the substituents on the upper rim of the resorcinarene was directly reflected in the order of binding strengths of the hosts towards quaternary and diquaternary ammonium cations in the gas phase. In solution, the opposite trend was observed, with generally higher binding constants for the diquaternary over the quaternary salts. This phenomenon is explained by the synergetic effect originating from the interaction of the halogenated resorcinarenes with the counteranions through enhanced hydrogen bonding, leading to ion‐pair binding in solution. The electronegativity of the halogens renders the hydrogen of the hydroxy group more acidic, and hence enforces hydrogen bonding in solution. The collective effect of several weak interactions is manifested in solution, thereby emphasizing the benefits of comparing solution and gas‐phase studies in recognition processes.
Rh‐Catalyzed Diarylamine Synthesis by Intermolecular C–H Amination of Heteroarylarenes
Authors: Tang Conghui , Yuan Yizhi , Cui Yuxin , Jiao Ning
Published: October 2013

A novel and efficient Rh‐catalyzed intermolecular C–H amination of heteroarylarenes with aryl azides has been developed. This procedure does not require an oxidant, releases N2 as the only byproduct, and provides an efficient approach to diarylamines with broad functional‐group tolerance.
Development and validation of a biotic ligand model for predicting chronic toxicity of lead to Ceriodaphnia dubia
Authors: Nys Charlotte , Janssen Colin R. , Mager Edward M. , Esbaugh Andrew J. , Brix Kevin V. , Grosell Martin , Stubblefield William A. , Holtze Keith , De Schamphelaere Karel A.C.
Published: October 2013

While it is increasingly being recognized that biotic ligand models (BLMs) are valuable in the risk assessment of metals in aquatic systems, the development of chronic BLMs has been less advanced for lead than for other metals. The authors investigated the univariate effects of Ca and pH on the chronic reproductive toxicity of Pb to Ceriodaphnia dubia at 4 levels. Calcium influenced chronic Pb toxicity to C. dubia only to a relatively small extent, whereas a high pH (8.2) provided strong protection against Pb toxicity (compared with lower pH levels). Based on this data set, a chronic Pb BLM for C. dubia was developed. The effect of pH was modeled as a single biotic ligand site competition by H+ with a log stability constant for binding of H+ to the biotic ligand (KHBL) of 7.6, while no other competitive constants were needed. The developed BLM was shown, in an independent validation with 3 other data sets, to be capable of predicting chronic Pb toxicity to different clones of C. dubia by an error of less than a factor of 2 in most synthetic and natural waters considered. The results add to the growing evidence that BLM–based risk assessment or water-quality criteria for Pb are likely to be more appropriate relative to hardness-based assessments or criteria. Environ Toxicol Chem 2014;33:394–403. © 2013 SETAC
An approach to assess the regulatory relevance of microevolutionary effects in ecological risk assessment of chemicals: A case study with cadmium
Authors: Coninck Dieter I.M. De , Janssen Colin R. , Schamphelaere Karel A.C. De
Published: October 2013

The authors suggest an approach to assess the regulatory relevance of microevolutionary effects of chemicals based on a comparison of concentrations at which microevolutionary effects have been reported in the literature and conventionally derived ecotoxicological threshold concentrations. The authors found reports of microevolutionary effects of cadmium in freshwater organisms at hardness-normalized concentrations between 0.5 µg Cd L−1 and 6290 µg Cd L−1 (normalized to a hardness of 50 mg CaCO3 L−1). These concentrations were at least 1.5 times higher than the hardness-normalized hazardous concentration for 5% of the organisms of 0.34 µg Cd L−1. This suggests that there is no immediate need to consider microevolutionary effects of Cd in environmental risk assessments of freshwater environments. However, some other aspects should be kept in mind as well. First, microevolutionary effects have so far only been investigated at few, relatively high concentrations of Cd and not encompassing the 5% hazardous concentration. Second, different types of microevolutionary effects or investigated ecotoxicological end points may influence the conclusions of the suggested comparative approach. Finally, factors influencing the bioavailability of Cd were not commonly reported in the literature, which made normalization of concentrations at which evolutionary effects occurred impossible and affected the number of studies that could be evaluated in the suggested approach. Environ Toxicol Chem 2014;33:453–457. © 2013 SETAC
The rhizotoxicity of metal cations is related to their strength of binding to hard ligands
Authors: Kopittke Peter M. , Menzies Neal W. , Wang Peng , McKenna Brigid A. , Wehr J. Bernhard , Lombi Enzo , Kinraide Thomas B. , Blamey F. Pax C.
Published: October 2013

Mechanisms whereby metal cations are toxic to plant roots remain largely unknown. Aluminum, for example, has been recognized as rhizotoxic for approximately 100 yr, but there is no consensus on its mode of action. The authors contend that the primary mechanism of rhizotoxicity of many metal cations is nonspecific and that the magnitude of toxic effects is positively related to the strength with which they bind to hard ligands, especially carboxylate ligands of the cell-wall pectic matrix. Specifically, the authors propose that metal cations have a common toxic mechanism through inhibiting the controlled relaxation of the cell wall as required for elongation. Metal cations such as Al3+ and Hg2+, which bind strongly to hard ligands, are toxic at relatively low concentrations because they bind strongly to the walls of cells in the rhizodermis and outer cortex of the root elongation zone with little movement into the inner tissues. In contrast, metal cations such as Ca2+, Na+, Mn2+, and Zn2+, which bind weakly to hard ligands, bind only weakly to the cell wall and move farther into the root cylinder. Only at high concentrations is their weak binding sufficient to inhibit the relaxation of the cell wall. Finally, different mechanisms would explain why certain metal cations (for example, Tl+, Ag+, Cs+, and Cu2+) are sometimes more toxic than expected through binding to hard ligands. The data presented in the present study demonstrate the importance of strength of binding to hard ligands in influencing a range of important physiological processes within roots through nonspecific mechanisms. Environ Toxicol Chem 2014;33:268–277. © 2013 SETAC
Influence of environmental factors in thein vitrodehydration of hydrogel and silicone hydrogel contact lenses
Authors: Martín‐Montañez Vicente , López‐Miguel Alberto , Arroyo Cristina , Mateo María E. , González‐Méijome José M. , Calonge Margarita , González‐García María J.
Published: October 2013

Purpose: To analyzein vitrothe influence of different environmental conditions on the dehydration pattern of seven currently marketed hydrogel (Hy) and silicone hydrogel (Si‐Hy) contact lenses (CL). Methods: Three Hy and four Si‐Hy CLs were evaluated. CLs were exposed to four different relative humidity (RH) conditions (5%, 30%, 50%, and 70%) and two air flow (AF) rates (0 and 2.75 m/seg) within an environmental chamber. Dehydration was assessed using the gravimetric method. Data were taken at baseline, 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes of exposure. Dehydration rate (DR), valid dehydration (VD) and stabilization time were calculated. Results: The interaction between RH, AF and the type of the CL material had a significant effect (p ≤ 0.03) on DR up to 60 minutes. The maximum differences in VD values among CL occurred around 15 minutes exposure varying from 25.16% to 42.75%. Stabilization time was quicker under the 5%RH with AF condition than under 70% RH without AF one for most CLs. Conclusions: Lower RH seems to increase CL dehydration being further accelerated with the AF presence. The dehydration pattern is material dependent, thus current marketed CLs behave differently under several controlled environmental conditions. Futurein vivostudies should confirm these outcomes. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 764–771, 2014.
Three‐dimensional collagen scaffold enhances the human adenoid cystic carcinoma cancer stem cell and epithelial–mesenchymal transition properties
Authors: Liu Li‐Jun , Zhang Jing , Xiao Zhi‐Feng , Dai Bin , Sun Mo‐Yi , Chen Lei , Chen Bing
Published: October 2013

Three‐dimensional (3D) cell culture may provide the architectures similar to the in vivo natural extracellular matrix condition for in vitro cultured cells. In this work, a 3D collagen scaffold was used to culture the adenoid cystic carcinoma (ACC) cells. The results showed that the 3D scaffold not only induced the diversification of cell morphologies but also increased the cell proliferation. The transcription of matrix metalloproteinase and epithelial–mesenchymal transition were significantly increased in the cells cultured in 3D collagen scaffolds. In addition, the expression of cancer stem cell (CSC) markers of Sox2 and Oct4 were higher than that in 2D cultured cells. The 3D cultured ACC‐83 cells showed more resistance to chemotherapeutic drugs. Thus, the 3D collagen scaffold could provide a useful model for CSCs study and anticancer therapeutics research in vitro. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 772–780, 2014.
Micro‐CT and PET analysis of bone regeneration induced by biodegradable scaffolds as carriers for dental pulp stem cells in a rat model of calvarial “critical size” defect: Preliminary data
Authors: Annibali Susanna , Bellavia Diana , Ottolenghi Livia , Cicconetti Andrea , Cristalli Maria Paola , Quaranta Roberta , Pilloni Andrea
Published: October 2013

Bone regeneration strategies in dentistry utilize biodegradable scaffolds seeded with stem cells able to induce bone formation. However, data on regeneration capacity of these tissue engineering constructs are still deficient. In this study micro‐Computed tomography (micro‐CT) and positron emission tomography (PET) analyses were used to investigate bone regeneration induced by two scaffolds [Granular deproteinized bovine bone (GDPB) and Beta‐tricalcium phosphate (β‐TCP)] used alone or in combination with dental pulp stem cells (DPSC) in a tissue engineered construct implanted in a rat critical calvarial defect. Bone mineral density (BMD) and standard uptake value (SUV) of tracer incorporation were measured after 2, 4, 8, and 12 weeks post‐implant. The results showed that: (1) GDPB implants were mostly well positioned, as compared to ß‐TCP; (2) GDPB induced higher BMD and SUV values within the cranial defect as compared to ß‐TCP, either alone or in combination with stem cells; (3) addition of DPSC to the grafts did not significantly induce an increase in BMD and SUV values as compared to the scaffolds grafted alone, although a small tendency to increase was observed. Thus our study demonstrates that GDPB, when used to fill critical calvarial defects, induces a greater percentage of bone formation as compared to ß‐TCP. Moreover, this study shows that addition of DPSC to pre‐wetted scaffolds has the potential to ameliorate bone regeneration process, although the set of optimal conditions requires further investigation. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 815–825, 2014.
Three‐Phase Barker Arrays
Authors: Bell Jason P. , Jedwab Jonathan , Khatirinejad Mahdad , Schmidt Kai‐Uwe
Published: October 2013

A 3‐phase Barker array is a matrix of third roots of unity for which all out‐of‐phase aperiodic autocorrelations have magnitude 0 or 1. The only known truly two‐dimensional 3‐phase Barker arrays have size 2 × 2 or 3 × 3. We use a mixture of combinatorial arguments and algebraic number theory to establish severe restrictions on the size of a 3‐phase Barker array when at least one of its dimensions is divisible by 3. In particular, there exists a double‐exponentially growing arithmetic function T such that no 3‐phase Barker array of size with exists for all . For example, , , and . When both dimensions are divisible by 3, the existence problem is settled completely: if a 3‐phase Barker array of size exists, then .
Surgical management of adrenal metastases
Authors: Bradley Ciarán T. , Strong Vivian E.
Published: October 2013

In the presence of a history of cancer, adrenal masses are commonly, but not exclusively, metastases. Depending upon the status of the patient's ongoing cancer therapy, overall tumor burden, and performance score, adrenalectomy is a viable treatment option. Herein we review the prevalence, diagnostic evaluation, and selection for surgical treatment of adrenal metastases. Additional attention is paid to recent data supporting the safety and oncologic efficacy of laparoscopic adrenalectomy. J. Surg. Oncol. 2014 109:31–35. © 2013 Wiley Periodicals, Inc.
Tracking motor impairments in the progression of Huntington's disease
Authors: Long Jeffery D. , Paulsen Jane S. , Marder Karen , Zhang Ying , Kim Ji‐In , Mills James A. ,   the Researchers of the PREDICT‐HD Huntington's Study Group
Published: October 2013

The Unified Huntington's Disease Rating Scale is used to characterize motor impairments and establish motor diagnosis. Little is known about the timing of diagnostic confidence level categories and the trajectory of motor impairments during the prodromal phase. Goals of this study were to estimate the timing of categories, model the prodromal trajectory of motor impairments, estimate the rate of motor impairment change by category, and provide required sample size estimates for a test of efficacy in clinical trials. In total, 1010 gene‐expanded participants from the Neurobiological Predictors of Huntington's Disease (PREDICT‐HD) trial were analyzed. Accelerated failure time models were used to predict the timing of categories. Linear mixed effects regression was used to model the longitudinal motor trajectories. Age and length of gene expansion were incorporated into all models. The timing of categories varied significantly by gene expansion, with faster progression associated with greater expansion. For the median expansion, the third diagnostic confidence level category was estimated to have a first occurrence 1.5 years before diagnosis, and the second and first categories were estimated to occur 6.75 years and 19.75 years before diagnosis, respectively. Motor impairments displayed a nonlinear prodromal course. The motor impairment rate of change increased as the diagnostic confidence level increased, with added acceleration for higher progression scores. Motor items can detect changes in motor impairments before diagnosis. Given a sufficiently high progression score, there is evidence that the diagnostic confidence level can be used for prodromal staging. Implications for Huntington's disease research and the planning of clinical trials of efficacy are discussed. © 2013 International Parkinson and Movement Disorder Society
Gray matter atrophy and freezing of gait in Parkinson's disease: Is the evidence black‐on‐white?
Authors: Herman Talia , Rosenberg‐Katz Keren , Jacob Yael , Giladi Nir , Hausdorff Jeffrey M.
Published: October 2013

Objectives

The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease (PD) is poorly understood. We tested whether gray matter (GM) atrophy contributes to FOG in PD.

Methods

Voxel‐based morphometry quantified GM atrophy in 106 patients who were classified as freezers (n = 30) or nonfreezers (n = 76). Well‐matched smaller subgroups were also studied. Balance, gait, and cognitive function were assessed, and we evaluated the relationship between GM, FOG severity, and symptoms associated with FOG.

Results

GM was significantly reduced in the inferior parietal lobe and angular gyrus in the matched freezers (n = 22), compared to nonfreezers (n = 22; P < 0.015, cluster‐level corrected). In the entire cohort, FOG severity was related to bilateral caudate volumes.

Conclusions

GM atrophy in cortical (i.e., parietal lobe and angular gyrus) and subcortical areas (i.e., caudate) are related to FOG. Disparities among the existing findings suggest that inferences regarding specific brain regions should be made with caution. © 2013 International Parkinson and Movement Disorder Society
Delayed gastric emptying in Parkinson's disease
Authors: Marrinan Sarah , Emmanuel Anton V. , Burn David J.
Published: October 2013

Gastrointestinal symptoms are evident in all stages of Parkinson's disease (PD). Most of the gastrointestinal abnormalities associated with PD are attributable to impaired motility. At the level of the stomach, this results in delayed gastric emptying. The etiology of delayed gastric emptying in PD is probably multifactorial but is at least partly related to Lewy pathology in the enteric nervous system and discrete brainstem nuclei. Delayed gastric emptying occurs in both early and advanced PD but is underdetected in routine clinical practice. Recognition of delayed gastric emptying is important because it can cause an array of upper gastrointestinal symptoms, but additionally it has important implications for the absorption and action of levodopa. Delayed gastric emptying contributes significantly to response fluctuations seen in people on long‐term l‐dopa therapy. Neurohormonal aspects of the brain‐gut axis are pertinent to discussions regarding the pathophysiology of delayed gastric emptying in PD and are also hypothesized to contribute to the pathogenesis of PD itself. Ghrelin is a gastric‐derived hormone with potential as a therapeutic agent for delayed gastric emptying and also as a novel neuroprotective agent in PD. Recent findings relating to ghrelin in the context of PD and gastric emptying are considered. This article highlights the pathological abnormalities that may account for delayed gastric emptying in PD. It also considers the wider relevance of abnormal gastric pathology to our current understanding of the etiology of PD. © 2013 International Parkinson and Movement Disorder Society