bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of acetylcholine receptor‐antibody‐positive myasthenia gravis in South Africa
Authors: Mombaur Busisiwe , Lesosky Maia R. , Liebenberg Lisa , Vreede Helena , Heckmann Jeannine M.
Published: July 2014

Introduction

The aim of this study was to assess age‐ and gender‐specific incidence rates (IRs) of acetylcholine receptor (AChR)–antibody–positive myasthenia gravis (MG) in South Africa, and geographical variations in incidence.

Methods

IRs were calculated from positive AChR–antibody laboratory data between 2011 and 2012, using 2011 population census data.

Results

890 individuals were seropositive, for an annual IR of 8.5 per million. Age‐standardized IR for early‐onset (<50) and late‐onset (≥50) MG were 4.1 and 24 per million, respectively, and 4.3 per million for juveniles. The IR between provinces ranged from 1 to 19 per million.

Conclusions

In this Southern Hemisphere African population, the overall IR and peak IR (in older men) for seropositive MG is comparable to that in Europe and North America, arguing against environmental factors. However, IRs may be higher among children with African genetic ancestry. Geographical variation in incidence underscores the importance of outreach programs for regions with limited resources. Muscle Nerve, 2015 Muscle Nerve 51: 533–537, 2015
An extended finite element method model for carbon sequestration
Authors: Ladubec Chris , Gracie Robert , Craig James
Published: July 2014

A two‐phase flow eXtended Finite Element Method (XFEM) model is presented to analyse the injection and sequestration of carbon dioxide (CO2) in deep saline aquifers. XFEM is introduced to accurately approximate near‐injection well pressure behaviour with elements significantly larger than the injection well diameter. We present a vertically averaged multiphase flow model that combines XFEM to approximate the pressure field, with a Streamline Upwind/Finite Element Method/Finite Difference Method (SU‐FEM‐FDM) to approximate the distribution of CO2 in the aquifer. Near‐well enrichment functions are presented along with the solution procedure for the coupled problem. Two examples are presented: in the first, CO2 injection into a perfectly horizontal aquifer is modelled with both XFEM and FEM‐based methods. The results suggest that XFEM is able to provide low relative errors in the pressure near the well at a reduced computational cost compared with FEM. The impact and selection of the stabilization coefficient of the SU‐FEM‐FDM is also discussed. In the second example, the XFEM and SU‐FEM‐FDM model is applied to a more realistic problem of an inclined aquifer to demonstrate the ability of the model to capture the buoyancy‐driven migration of CO2 in a deep saline aquifer. Copyright © 2014 John Wiley & Sons, Ltd.
SMA carrier testing: a meta‐analysis of differences in test performance by ethnic group
Authors: MacDonald William Kim , Hamilton David , Kuhle Stefan
Published: July 2014

Introduction

Spinal muscular atrophy (SMA) is a severe autosomal recessive genetic disease that occurs in about one in every 10 000 births. Prenatal carrier testing is available for SMA, and the utility of universal screening is actively debated.

Objective

The aim of this study was to perform a systematic review and meta‐analysis of SMA genotype frequency, carrier frequency, and carrier test performance in different ethnic groups.

Methods

We performed a systematic review of the literature for studies on SMA carrier screening test performance. Ethnicity‐specific allele frequencies, carrier rates, and screening test performance were determined from data of 169 000 individuals in 14 published studies. Pooled estimates were calculated for each ethnic group using a random effects meta‐analysis.

Results

The detection rate of SMA screening in the non‐Black population was 87–95%; however, detection rates fell to 71% among the Black population.

Conclusion

These results highlight that although SMA carrier testing generally performs well and could be considered as a routine prenatal screen, SMA testing should be used cautiously in the Black population. © 2014 John Wiley & Sons, Ltd.
Achieving high electric energy storage in a polymer nanocomposite at low filling ratios using a highly polarizable phthalocyanine interphase
Authors: Wang Jing , Guan Fangxiao , Cui Li , Pan Jilin , Wang Qing , Zhu Lei
Published: July 2014

Polymer nanodielectrics have become attractive for practical applications such as electric energy storage and electromechanical actuation. However, to enhance the apparent dielectric constant of polymer nanodielectrics, a significant amount (>30 vol %) of spherical particles needs to be incorporated into the polymer matrix. As a consequence, melt‐processing of polymer nanodielectrics into uniform thin films becomes difficult at such a high filler content, and electric breakdown strength will greatly decrease. In this work, we describe a three‐phase composite approach towards high energy density nanodielectrics at low filling ratios. In this approach, a highly polarizable tetrameric metallophthalocyanine (TMPc) initiator is coated onto 68 nm BaTiO3 nanoparticles, from which poly(methyl methacrylate) (PMMA) brushes are grafted using atom transfer radical polymerization for the nanoparticles to be uniformly dispersed in a poly(vinylidene fluoride‐co‐hexafluoropropylene) [P(VDF‐HFP)] matrix. For comparison, two‐phase P(VDF‐HFP)/BaTiO3 composites without the TMPc interfacial layer are also prepared. Owing to the high polarizability of the TMPc interface layer, the three‐phase composite films exhibit higher dielectric constant and thus higher energy density than the two‐phase composite films at volume‐filling ratios below 5 vol %. Therefore, these high energy density three‐phase nanodielectrics with a low filling ratio are promising for melt‐processing into thin dielectric films. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 1669–1680
Ab Initio Simulation of Charge Transfer at the Semiconductor Quantum Dot/TiO2 Interface in Quantum Dot‐Sensitized Solar Cells
Authors: Xin Xukai , Li Bo , Jung Jaehan , Yoon Young Jun , Biswas Rana , Lin Zhiqun
Published: July 2014

Quantum dot‐sensitized solar cells (QDSSCs) have emerged as a promising solar architecture for next‐generation solar cells. The QDSSCs exhibit a remarkably fast electron transfer from the quantum dot (QD) donor to the TiO2 acceptor with size quantization properties of QDs that allows for the modulation of band energies to control photoresponse and photoconversion efficiency of solar cells. To understand the mechanisms that underpin this rapid charge transfer, the electronic properties of CdSe and PbSe QDs with different sizes on the TiO2 substrate are simulated using a rigorous ab initio density functional method. This method capitalizes on localized orbital basis set, which is computationally less intensive. Quite intriguingly, a remarkable set of electron bridging states between QDs and TiO2 occurring via the strong bonding between the conduction bands of QDs and TiO2 is revealed. Such bridging states account for the fast adiabatic charge transfer from the QD donor to the TiO2 acceptor, and may be a general feature for strongly coupled donor/acceptor systems. All the QDs/TiO2 systems exhibit type II band alignments, with conduction band offsets that increase with the decrease in QD size. This facilitates the charge transfer from QDs donors to TiO2 acceptors and explains the dependence of the increased charge transfer rate with the decreased QD size.
The tensor theory space
Authors: Rivasseau V.
Published: July 2014

The tensor track is a background‐independent discretization of quantum gravity which includes a sum over all topologies. We discuss how to define a functional renormalization group flow and the Wetterich equation in the corresponding theory space. This space is different from the Einsteinian theory space of asymptotic safety. It includes all fixed‐rank tensor‐invariant interactions, hence generalizes matrix models and the (Moyal) non‐commutative field theory space.
Bait station devices can improve mass trapping performance for the control of the Mediterranean fruit fly
Authors: Navarro‐Llopis Vicente , Primo Jaime , Vacas Sandra
Published: July 2014

BACKGROUND

The use of traps and other attract‐and‐kill devices in pest management strategies to reduce Mediterranean fruit fly populations has proved to be efficient. Nevertheless, many farmers are concerned about the effect of these devices on the trees where they are hung. Direct field observations have revealed that fruit damage is higher in trees with traps than in trees without them. This work evaluates the efficacy of different types of attract‐and‐kill device to protect fruit of the single tree on which the device is placed.

RESULTS

Results suggested that trees with traps had at least the same fruit damage than trees without them. When traps were baited with protein hydrolysate, fruit damage was even higher than in trees without traps. However, fruit damage was significantly diminished when efficient bait station devices were used.

CONCLUSION

Although mass trapping is able to control fruit fly populations as a control method, trees with some types of trap and bait are more susceptible to fly puncture. However, bait station devices reduce fruit damage in the single trees where they are hung. Bait stations are more efficient in fruit protection because fruit flies are affected as soon as they contact the device. Some recommendations for the use of the different attract‐and‐kill devices are discussed. © 2014 Society of Chemical Industry
Electronic structure of amorphous ZnO films
Authors: Schmeißer Dieter , Haeberle Jörg , Barquinha Pedro , Gaspar Diana , Pereira Luís , Martins Rodrigo , Fortunato Elvira
Published: July 2014

We use resonant photoemission spectroscopy (resPES) to study the electronic properties of amorphous ZnO (a‐ZnO) layers. We report on the core levels, the valence band (VB) PES data, and the X‐ray absorption (XAS) data which we use for the conduction band (CB) density of states. From these results we are able to derive the partial density of states (pDOS) of O2p and Zn4s4p states in the VB and CB, respectively as well as a band scheme. At the O1s resonance we observe a band of localized defect states which is located between the Fermi energy and the CBM. At the Zn2p edge the XAS data indicate that localized Zn4s4p states are involved in the DOS starting already at the Fermi energy. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effective resistances for ladder‐like chains
Authors: Carmona Angeles , Encinas Andres M. , Mitjana Margarida
Published: July 2014

Here, we consider a class of generalized linear chains; that is, the ladder‐like chains as a perturbation of a 2n path by adding consecutive weighted edges between opposite vertices. This class of chains in particular includes a big family of networks that goes from the cycle, unicycle chains up to ladder networks. In this article, we obtain the Green function, the effective resistance, and the Kirchhoff index of ladder‐like chains in terms of the Green function, the effective resistance, and the Kirchhoff index of the path. © 2014 Wiley Periodicals, Inc.
Hepatic Differentiation of Human Embryonic Stem Cells as Microscaled Multilayered Colonies Leading to Enhanced Homogeneity and Maturation
Authors: Yao Rui , Wang Jingyu , Li Xiaokang , Jung Jung Da , Qi Hao , Kee Keh Kooi , Du Yanan
Published: July 2014

Directed differentiation of human embryonic stem cells (hESCs) towards hepatocyte‐like cells on planar tissue culture plates has been extensively investigated with great promise to provide alternative cell sources for drug metabolism/toxicity testing. Recently, hepatic differentiation of hESCs in 3D configuration with better mimicry of embryonic liver development represents incremental efforts to improve the differentiation efficiency and cellular maturation. However, most of the present 3D differentiation configurations involved interruptive operations during the multi‐staged differentiation process, which might impose unwanted influence on cellular differentiation. Most of the current researches resulted in generation of hepatocytes with high expression of AFP, which is minimally expressed in primary hepatocytes. Here, off‐the‐shelf micro‐stencil arrays are developed to generate adherent multilayered colonies composed of hESCs‐derived cells. Uninterrupted cellular differentiation and proliferation is achieved to recapitulate the continuous and multi‐stage liver development. Compared with conventional 2D format, the micro‐scaled multilayered colonies with uniform and defined sizes constrained within the microwells are composed of more homogenous and mature hepatocyte‐like cells with significantly lowered AFP expression and elevated hepatic functions. The multilayered colonies as novel 3D configuration for hepatic differentiation of hESCs represent a significant step toward efficient generation of functional hepatocytes for regenerative medicine and drug discovery.
Synthesis of Silica Vesicles with Controlled Entrance Size for High Loading, Sustained Release, and Cellular Delivery of Therapeutical Proteins
Authors: Zhang Jun , Karmakar Surajit , Yu Meihua , Mitter Neena , Zou Jin , Yu Chengzhong
Published: July 2014

A rationally designed two‐step synthesis of silica vesicles is developed with the formation of vesicular structure in the first step and fine control over the entrance size by tuning the temperature in the second step. The silica vesicles have a uniform size of ≈50 nm with excellent cellular uptake performance. When the entrance size is equal to the wall thickness, silica vesicles after hydrophobic modification show the highest loading amount (563 mg/g) towards Ribonuclease A with a sustained release behavior. Consequently, the silica vesicles are excellent nano‐carriers for cellular delivery applications of therapeutical biomolecules.
The State‐Of‐The‐Art Research in ‘Behavioral Risk’: An Introduction to the Special Issue
Authors: Wu Desheng Dash , Olson David L.
Published: July 2014

Risks are endemic to doing business. Current events have made enterprise risk management to be even greater in importance. The complexity and interrelated nature of business operations today call for a systems view. This special issue involves seven papers providing tools useful in understanding and analysing systems risk. This introduction summarizes these papers and discusses their common thread of how organizational decisions involving behavioral‐oriented risks can be supported. Copyright © 2014 John Wiley & Sons, Ltd.
Diet and diet‐related disorders in captive ruminants at the national zoological gardens of South Africa
Authors: Gattiker Cristina , Espie Ian , Kotze Antoinette , Lane Emily P. , Codron Daryl , Clauss Marcus
Published: July 2014

Although diet‐related disorders have received much attention in the zoo literature, evidence‐based results on relationships between diet and disease are still rare, often due to a lack of quantitative dietary information that can be linked to clinical or necropsy reports. We investigated 24 species of captive ruminants from one facility for which quantitative feeding instructions and necropsy reports between 1991 and 2012 were available. Species were classified as grazer (GR), intermediate feeder (IM), or browser (BR). Feeding type and body mass were significantly correlated to the diet fed, with smaller and BR species receiving higher proportions of non‐roughage diet items. There were no significant differences between feeding types in the occurrence of parakeratosis/ruminitis/acidosis (PRA) at necropsy, but in body condition score, with BR more often in poor and less often in excellent body condition at necropsy. While there was no direct correlation between the proportion of non‐roughage diet items and PRA across species, there was a significant effect of the proportion of non‐roughage diet items on PRA when body mass was also taken into account: larger species, and those that received more non‐roughage diet items, had higher prevalence of PRA. The results underline that diet and lack of structured feed items can be associated with the disease complex of acidosis in ruminants, but also suggest that this is modified by factors related to animal size. These latter may include susceptibility to acidosis, or husbandry‐related opportunities to monopolize non‐roughage feeds and ingest higher proportions than intended by feeding instructions. Zoo Biol. 33:426–432, 2014. © 2014 Wiley Periodicals Inc.
Prospective Assessment of Trocar‐Specific Morbidity in Laparoscopy
Authors: Cristaudi Alessandra , Matthey‐Gié Marie‐Laure , Demartines Nicolas , Christoforidis Dimitri
Published: July 2014

Background

The purpose of the present study was to challenge the hypothetical advantage of single port laparoscopy (SPL) over conventional laparoscopy by measuring prospectively the morbidity specifically related to conventional trocar sites (TS).

Methods

From November 2010 to December 2011, 300 patients undergoing various laparoscopic procedures were enrolled. Patient, surgery, and trocar characteristics were recorded. We evaluated at three time points (in‐hospital and at 1 and 6 months postoperatively) specifically for each TS, pain (Visual Analog Scale), morbidity (infection, hematoma, hernia), and cosmesis (Patient Scar Assessment Score; PSAS). Patients designated their “worst TS,” and a composite endpoint “bad TS” was defined to include any adverse outcome at a TS.

Results

We analyzed 1,074 TS. Follow‐up was >90 %. Pain scores of >3/10 at 1 and 6 months postoperatively, were reported by 3 and 1 % of patients at the 5 mm TS and by 9 and 1 % at the larger TS, respectively (5 mm TS vs larger TS; p = 0.001). Pain was significantly lower for TS located in the lower abdomen than for the upper abdomen or the umbilicus (p = 0.001). The overall complication rate was <1 % and significantly lower for the 5 mm TS (hematoma p = 0.046; infection p = 0.0001). No hernia was found. The overall PSAS score was low and significantly lower for the 5 mm TS (p = 0.0001). Significant predictors of “bad TS” were larger TS (p = 0.001), umbilical position (p = 0.0001), emergency surgery (p = 0.0001), accidental trocar exit (p = 0.022), fascia closure (p = 0.006), and specimen extraction site (p = 0.0001).

Conclusions

Specific trocar morbidity is low and almost negligible for 5 mm trocars. The umbilicus appears to be an unfavorable TS.
Preliminary Report of Major Surgery in Liver Transplant Recipients Receiving m‐TOR Inhibitors without Therapeutic Discontinuation
Authors: Schwarz Lilian , Cauchy François , Conti Filomena , Sepulveda Ailton , Perdigao Fabiano , Bernard Denis , Calmus Yvon , Soubrane Olivier , Scatton Olivier
Published: July 2014

Introduction

Mammalian target rapamycin inhibitors (m‐TORi) are increasingly used in patients undergoing liver transplantation (LT). Yet, there is rising concern that they also could impair wound healing and favor the development of several surgical complications. This report was designed to evaluate both feasibility and safety of major surgery in liver transplant recipients receiving m‐TORi–based immunosuppression without therapeutic discontinuation.

Methods

From 2007 to 2012, six liver transplant recipients underwent nine major abdominal or thoracic surgical procedures without m‐TORi discontinuation or specific dosage adjustment. Their characteristics and postoperative outcomes were retrospectively analyzed.

Results

Indications for m‐TORi were de novo or recurrent malignant disease in five patients and calcineurin inhibitors related neurologic toxicity in one patient. Abdominal procedures, thoracic procedures, and combined thoracic and abdominal procedures were performed in six, two, and one cases respectively. Emergency surgery was performed in one case and elective procedures were performed in eight cases, including five for malignant disease and three for late surgical complications following LT. No patient died postoperatively. One major complication was observed, but no patient required reoperation. No evisceration, incisional surgical site infection, or lymphocele occurred.

Conclusions

Major surgery in liver transplant recipients receiving m‐TOR inhibitors appears both feasible and safe without therapeutic discontinuation or specific dosage adjustment.
Heterogeneous distribution of a floating‐leaved plant, Trapa japonica, in Lake Mikata, Japan, is determined by limitations on seed dispersal and harmful salinity levels
Authors: Nishihiro Jun , Kato Yoshikazu , Yoshida Takehito , Washitani Izumi
Published: July 2014

Factors affecting the within‐lake distribution of Trapa japonica were analysed in Lake Mikata, Japan, by integrating remote sensing analyses, field surveys, and laboratory experiments. The T. japonica bed has been expanding since 2006 and covered more than 60 % of the lake's area from 2008 to 2010. However, two parts of the lake, the upper and lower areas, retained open water, even during recent years. A survey of lake‐bottom sediments revealed a heterogeneous seed distribution. Although seed density exceeded 13 seeds/m2 in the lake's central area, no seeds were observed in the upper and lower areas. A seed‐bag retrieval experiment showed that 75.6 % of seeds at the upper site germinated when seeds were artificially introduced, whereas 6.7 % of seeds germinated at the lower site. These results suggest that seed dispersal opportunities are the primary limitation on the distribution of T. japonica in the upper area. Brackish water was found in springs in the lower area, reflecting an adverse inflow of water from a downstream brackish lake. Laboratory experiments revealed significant adverse effects of water salinity on germination and early growth of T. japonica. Based on these results, we concluded that the heterogeneous distribution of T. japonica within the lake was determined by a combination of two factors: limitations on seed dispersal determined by the inflowing river and harmful salinity levels caused by inflows of seawater from the Sea of Japan via a downstream brackish lake.
Maternal outcomes of hypertensive disorders in pregnancy at Korle Bu Teaching Hospital, Ghana
Authors: Adu‐Bonsaffoh Kwame , Obed Samuel A. , Seffah Joseph D.
Published: July 2014

Objective

To determine maternal outcomes of hypertensive disorders in pregnancy at Korle Bu Teaching Hospital (KBTH) in Accra, Ghana.

Methods

A cross‐sectional study was conducted between January 1 and February 28, 2013. All women delivering at KBTH whose pregnancies were complicated by hypertensive disorders were identified. A structured questionnaire was administered, and the women were followed up on a daily basis until discharge from hospital. Medical records were also reviewed to identify any complications of hypertensive disorders.

Results

A total of 368 women were analyzed. Of 10 maternal deaths, 3 (30.0%) were due to hypertensive disorders in pregnancy, and specifically pre‐eclampsia. Overall, 168 (45.7%) women with hypertensive disorders in pregnancy delivered by cesarean, 16 (4.3%) had placental abruption, 11 (3.0%) had pulmonary edema, 3 (0.8%) had HELLP syndrome, 2 (0.5%) had acute renal failure, 3 (0.8%) had an intracerebral hemorrhage or cerebrovascular accident, 21 (5.7%) were admitted to the intensive care unit, 7 (1.9%) had disseminated intravascular coagulation, and 58 (15.8%) had eclampsia. Cesarean delivery, admission to intensive care unit, and eclampsia were significantly more common in women with pre‐eclampsia than in those with other hypertensive disorders.

Conclusion

Hypertensive disorders in pregnancy are associated with high incidences of adverse maternal outcomes in Ghana, with significantly increased frequencies in women with pre‐eclampsia.
Prediction of domestic violence against married women in southwestern Turkey
Authors: Izmirli Gulsen O. , Sonmez Yonca , Sezik Mekin
Published: July 2014

Objective

To determine the prevalence of, and independent risk factors for various domestic violence categories among married women of reproductive age in southwestern Turkey.

Methods

The present cross‐sectional study included 260 randomly selected women registered to a family physician in the district of Gönen, Isparta. During home visits between October 1 and December 31, 2012, the women completed a questionnaire that included between four and eight questions for each violence category (physical, verbal, economic, emotional, and sexual) to assess the lifetime presence of domestic violence. Logistic regression models with backward elimination were constructed to define independent risk factors for domestic violence.

Results

In total, 176 (67.7%) women reported any type of domestic violence at least once in their lifetime. Verbal/psychological abuse was the most frequent type (reported by 121 [46.5%] women). Living in a village, young age (19–29 years) of the husband, adolescent age (< 19 years) of the husband at marriage, and problem alcohol use or problem gambling in the partner were independent predictors of domestic violence.

Conclusion

Attention should be given to area of residence, age of both partners at marriage, adolescent marriage, and husband characteristics during screening for domestic violence.
Aldehyde dehydrogenase 1A3 influences breast cancer progression via differential retinoic acid signaling
Authors: Marcato Paola , Dean Cheryl A. , Liu Rong-Zong , Coyle Krysta M. , Bydoun Moamen , Wallace Melissa , Clements Derek , Turner Colin , Mathenge Edward G. , Gujar Shashi A. , Giacomantonio Carman A. , Mackey John R. , Godbout Roseline , Lee Patrick W.K.
Published: July 2014

Aldehyde dehydrogenase (ALDH) 1A enzymes produce retinoic acid (RA), a transcription induction molecule. To investigate if ALDH1A1 or ALDH1A3‐mediated RA signaling has an active role in breast cancer tumorigenesis, we performed gene expression and tumor xenograft studies. Analysis of breast patient tumors revealed that high levels of ALDH1A3 correlated with expression of RA‐inducible genes with retinoic acid response elements (RAREs), poorer patient survival and triple‐negative breast cancers. This suggests a potential link between ALDH1A3 expression and RA signaling especially in aggressive and/or triple‐negative breast cancers. In MDA‐MB‐231, MDA‐MB‐468 and MDA‐MB‐435 cells, ALDH1A3 and RA increased expression of RA‐inducible genes. Interestingly, ALDH1A3 had opposing effects in tumor xenografts, increasing tumor growth and metastasis of MDA‐MB‐231 and MDA‐MB‐435 cells, but decreasing tumor growth of MDA‐MB‐468 cells. Exogenous RA replaced ALDH1A3 in inducing the same opposing tumor growth and metastasis effects, suggesting that ALDH1A3 mediates these effects by promoting RA signaling. Genome expression analysis revealed that ALDH1A3 induced largely divergent gene expression in MDA‐MB‐231 and MDA‐MB‐468 cells which likely resulted in the opposing tumor growth effects. Treatment with DNA methylation inhibitor 5‐aza‐2'deoxycytidine restored uniform RA‐inducibility of RARE‐containing HOXA1 and MUC4 in MDA‐MB‐231 and MDA‐MB‐468 cells, suggesting that differences in epigenetic modifications contribute to differential ALDH1A3/RA‐induced gene expression in breast cancer. In summary, ALDH1A3 induces differential RA signaling in breast cancer cells which affects the rate of breast cancer progression.
Acquired and intrinsic resistance in cancer immunotherapy
Authors: Kelderman Sander , Schumacher Ton N.M. , Haanen John B.A.G.
Published: July 2014

A number of immunotherapies, in particular immune checkpoint targeting antibodies and adoptive T‐cell therapies, are starting to transform the treatment of advanced cancers. The likelihood to respond to these immunotherapies differs strongly across tumor types, with response rates for checkpoint targeting being the highest in advanced melanoma, renal cell cancer and non‐small cell lung cancer. However, also non‐responsiveness is observed, indicating the presence of intrinsic resistance or naturally acquired resistance. In addition, a subgroup of patients that do initially respond to immunotherapy will later recur, thereby also pointing towards a role of therapy‐induced acquired resistance.

Here, we review our current understanding of both intrinsic and acquired resistance mechanisms in cancer immunotherapy, and discuss potential strategies to overcome them.
Automation of Cytokine Flow Cytometry Assays
Authors: Dunne John F. , Maecker Holden T.
Published: July 2014

Cytokine flow cytometry (CFC) is a multiparameter assay of antigen-specific T cell function, potentially useful in the monitoring of experimental vaccines and progression of infectious diseases and cancer. Automation of CFC assays would greatly facilitate their use in clinical trials and involves several components. We describe here the migration of these assays to 96-well plates, the use of sample-handling robotics, and the use of lyophilized antigen and antibody plates to help automate CFC. Together, these elements can produce an integrated system capable of walkaway automation of an entire assay, resulting in the reproducible processing of potentially hundreds of samples per day. Implementation of such systems has begun to be undertaken by our group and others.
Thermoacoustic instability – a dynamical system and time domain analysis
Authors: Sayadi Taraneh , Le Chenadec Vincent , Schmid Peter J. , Richecoeur Franck , Massot Marc
Published: July 2014

This study focuses on the Rijke tube problem, which includes features relevant to the modelling of thermoacoustic coupling in reactive flows: a compact acoustic source, an empirical model for the heat source and nonlinearities. This thermoacoustic system features both linear and nonlinear flow regimes with complex dynamical behaviour. In order to synthesize accurate time series, we tackle this problem from a numerical point of view, and start by proposing a dedicated solver designed for dealing with the underlying stiffness – in particular, the retarded time and the discontinuity at the location of the heat source. Stability analysis is performed on the limit of low-amplitude disturbances by using the projection method proposed by Jarlebring (PhD thesis, Technische Universität Braunschweig, 2008), which alleviates the problems arising from linearization with respect to the retarded time. The results are then compared with the analytical solution of the undamped system and with the results obtained from Galerkin projection methods commonly used in this setting. This analysis provides insight into the consequences of the various assumptions and simplifications that justify the use of Galerkin expansions based on the eigenmodes of the unheated resonator. We demonstrate that due to the presence of a discontinuity in the spatial domain, the eigenmodes in the heated case predicted by using Galerkin expansion show spurious oscillations resulting from the Gibbs phenomenon. Finally, time series in the fully nonlinear regime, where a limit cycle is established, are analysed and dominant modes are extracted. By comparing the modes of the linear regime to those of the nonlinear regime, we are able to illustrate the mean-flow modulation and frequency switching, which appear as the nonlinearities become significant and ultimately affect the form of the limit cycle. Analysis of the saturated limit cycles shows the presence of higher-frequency modes, which are linearly stable but become significant through nonlinear growth of the signal. This bimodal effect is not exhibited when the coupling between different frequencies is not accounted for. In conclusion, a dedicated solver for capturing thermoacoustic instability is proposed and methods for analysing linear and nonlinear regions of the resulting time series are introduced.
Trapped modes and scattering for oblique waves in a two-layer fluid
Authors: Romero Rodríguez M. I. , Zhevandrov P.
Published: July 2014

The system describing time-harmonic motions of a two-layer fluid in the linearised shallow-water approximation is considered. It is assumed that the depth is constant, with a cylindrical protrusion (an underwater ridge) of small height. For obliquely incident waves, the system reduces to a pair of coupled ordinary differential equations. The values of frequency for which wave propagation in the unperturbed system is possible are bounded from below by a cutoff, to the left of which no propagating modes exist. Under the perturbation, a trapped mode appears to the left of the cutoff and, if a certain geometric requirement is imposed upon the shape of the perturbation (for example, if the ridge is a rectangular barrier of certain width), a trapped mode appears whose frequency is embedded in the continuous spectrum. When these geometric conditions are not satisfied, the embedded trapped mode transforms into a complex pole of the reflection and transmission coefficients of the corresponding scattering problem, and the phenomenon of almost total reflection is observed when the frequency coincides with the real part of the pole. Exact formulae for the trapped modes are obtained explicitly in the form of infinite series in powers of the small parameter characterising the perturbation. The results provide a theoretical understanding of analogous phenomena observed numerically in the literature for the full problem for the potentials in a two-layer fluid in the presence of submerged cylinders, and furnish explicit formulae for the frequencies at which total reflection occurs and the trapped modes exist.
The dammed river dolphins of Brazil: impacts and conservation
Authors: Araújo Claryana C. , Wang John Y.
Published: July 2014

A major threat to river dolphins in Brazil is habitat loss and fragmentation as a result of the construction of hydroelectric dams. We examine the degree of overlap between the distributions of two river dolphin species (boto Inia geoffrensis and tucuxi Sotalia fluviatilis) and hydroelectric projects and provide an initial quantification of impacts. The locations of dams were overlaid onto a map of the known distributions of the dolphins. Two types of impacts were evaluated: population fragmentation and effects on prey. For each of these a binary score (for absence or presence) was assigned for each dam. The sum of all impact scores for each dam, in each of the three watersheds in which dolphins are found, including realized and potential impacts, was calculated as the impact index. Thirteen dams affect the distribution of I. geoffrensis (as could a further three dams under construction and seven planned), and three dams affect S. fluviatilis (as could three under construction and two planned). Overall, the impact index was higher for I. geoffrensis than for S. fluviatilis. The Araguaia–Tocantins and North Atlantic watersheds have higher impact index values than the Amazon watershed. Although some impacts of damming could not be considered in this study, our approach was a rapid initial risk assessment that provided an overall understanding of how river dolphins are and may be affected by hydroelectric projects in Brazil. Our method may be applicable to other freshwater cetaceans and species facing similar threats when information about impacts is incomplete.
Bouqras Revisited: Preliminary Report on a Project in Eastern Syria
Authors: Akkermans P. A. , Boerma J. A. K. , Clason A. T. , Hill S. G. , Lohof E. , Meiklejohn C. , le Mière M. , Molgat G. M. F. , Roodenberg J. J. , Rooyen W. Waterbolk-van , van Zeist W.
Published: July 2014

Tell Bouqras is situated in eastern Syria, on the right bank of the Euphrates, c. 35 km south-east of Deir ez-Zor (35°05′ 12″N, 40°23′ 50″E). The ‘neolithic’ village was built on a promontory of the plateau area overlooking the Euphrates floodplain, just opposite the mouth of the Khabur (fig. 1). H. de Contenson and W.J. van Liere (1966) conducted a trial excavation at the tell in 1965. Their results showed that the ‘hunter-shepherd society’ of Bouqras (van Liere and de Contenson 1963; Hooijer 1966) dated from the second half of the seventh millennium bc (Vogel and Waterbolk 1967).

Before this period villages with an economy based on agriculture and animal husbandry mainly occupied the mountainous areas bordering the ‘fertile crescent’. During the second half of the seventh and the first part of the sixth millennia be the spread of such villages can be observed outside of the areas formerly occupied. The chronological and geographical position of Bouqras makes the site particularly suited to be investigated as an example of the sedentary communities which started to settle the more downstream Euphrates and Tigris drainage basins in the lowlands of eastern Syria and Iraq, beyond the regions where rainfall-fed farming would have been possible. Furthermore, the location of Bouqras at similar distances, as the crow flies, from Pre-Pottery Neolithic sites in western and northern Syria and early sixth millennium settlements in northern Iraq, would give the opportunity to trace contacts between these separate regions.

With these objectives a team from the Universities of Amsterdam and Groningen, directed by Prof Dr H. T. Waterbolk and Prof Dr M. N. van Loon, undertook new excavations at Bouqras from 1976 to 1978. Financial support was obtained from the Netherlands Organization for the Advancement of Pure Research, the A. E. vanGiffen Instituut voor Prae- en Protohistorie in Amsterdam and the Biologisch-Archaeologisch Instituut in Groningen. We express our gratitude to Dr A. Bahnassi and Dr A. Bounni of the General Directorate of Antiquities and Museums in Damascus, for granting the excavation and survey permits and for their interest in our work. Mr A. Mahmoud of the Museum of Deir ez-Zor was very helpful during our stay in the field.
A new approach to singularity-free inverse kinematics using dual-quaternionic error chains in the Davies method
Authors: de Oliveira Andre Schneider , De Pieri Edson Roberto , Moreno Ubirajara Franco , Martins Daniel
Published: July 2014

The manipulation in singular regions promotes an instantaneous reduction in mechanism mobility, which can result in some disturbances in the trajectory tracking. The application of the quaternionic elements for motion representation not only guarantees an orthonormal transformation but also results in the smallest variance and minimizes the acceleration peaks. The use of a unit quaternion avoids these phenomena, but there are dimensional limitations that make it impossible to translate the representation. This work presents a methodology for using dual quaternions in the analysis of robot kinematics using the Davies method, which avoids kinematic singularities and ensures the optimal torque profiles.
Multiple positive solutions for indefinite semilinear elliptic problems involving a critical Sobolev exponent
Authors: Chen Ching-yu , Wu Tsung-fang
Published: July 2014

In this paper, we study the decomposition of the Nehari manifold by exploiting the combination of concave and convex nonlinearities. The result is subsequently used, in conjunction with the Ljusternik–Schnirelmann category and variational methods, to prove the existence and multiplicity of positive solutions for an indefinite elliptic problem involving a critical Sobolev exponent.
Limiting absorption principle for the electromagnetic Helmholtz equation with singular potentials
Authors: Zubeldia Miren
Published: July 2014

We study the Helmholtz equation

in ℝd with magnetic and electric potentials that are singular at the origin and decay at ∞. We prove the existence of a unique solution satisfying a suitable Sommerfeld radiation condition, together with some a priori estimates. We use the limiting absorption method and a multiplier technique of Morawetz type.
On the spectrum of two different fractional operators
Authors: Servadei Raffaella , Valdinoci Enrico
Published: July 2014

In this paper we deal with two non-local operators that are both well known and
widely studied in the literature in connection with elliptic problems of
fractional type. More precisely, for a fixed s ∈
(0,1) we consider the integral definition of the fractional
Laplacian given by

where c(n, s) is a positive normalizing
constant, and another fractional operator obtained via a
spectral definition, that is,

where ei, λi are the eigenfunctions and the
eigenvalues of the Laplace operator −Δ in
Ω with homogeneous Dirichlet boundary data,
while ai represents the projection of u on the direction
ei.

The aim of this paper is to compare these two operators, with particular
reference to their spectrum, in order to emphasize their differences.
A weighted bilinear gradient inequality
Authors: Salvador Pedro Ortega
Published: July 2014

We characterize the weights w0, w1, w2 such that the weighted bilinear gradient inequality

holds for all functions , with a positive constant K independent of f1 and f2, for all possible values of q, p1 and p2 with 1 < q, p1, p2 < ∞.
Appropriating Nature: Commerce, Property, and the Commodification of Nature in the Law of Nations
Authors: PORRAS ILEANA
Published: July 2014

This article explores the structural link between international law's long-standing doctrinal commitment to commerce and its inability to act decisively on behalf of the environment. One of the fundamental rights the early authors of jus gentium discovered was the right to engage in commerce. Francisco de Vitoria, Alberico Gentili, and Hugo Grotius each drew on and applied a providentialist theory of commerce. The doctrine held that Providence distributed scarcity and plenty across the earth so that peoples could not be self-sufficient, but would need to go in search of one another in order to acquire what they lacked. Commerce imagined in its pure form of reciprocal, mutually beneficial exchange would be the means to bring separated mankind to friendship. The embrace of the providentialist doctrine by these early exponents of the law of nations, carried forward by Emer de Vattel, set the stage for international law's longstanding commitment to international commerce, viewed (despite all the distortions) as a virtuous activity that tends to the common good. The doctrine's additional legacy was the installation of a view of nature as commodity. The providentialist doctrine of commerce, adopted by the early authors of international law, remains embedded in the structure of international law and cannot easily be dislodged. Until this doctrine is dislodged, however, international law will continue to be hobbled in its ability to address the urgent task of protecting the natural environment.
Transparency in the WTO's Decision-Making
Authors: DELIMATSIS PANAGIOTIS
Published: July 2014

In almost 20 years of existence, the World Trade Organization (WTO) has managed to be at the forefront of public discussions on international organizations (IOs). Transparency in the WTO decision-making has been on the agenda of the multilateral trading system for several years. Pressures from developing countries, non-governmental organizations (NGOs) and the civil society in particular have led to significant improvements towards more openness and participation in the WTO decision-making. This article posits the WTO within the current debates about more institutional transparency in IOs. It discusses the current features of good governance in the WTO decision-making and the consensus rule in particular, in an attempt to identify the pros and cons of this voting tradition in a modern IO. It also discusses the recent selection of the new WTO Director-General. A central insight of the paper is that input and output transparency of the WTO could be further enhanced by increased, managed participation of NGOs. As the WTO is gradually becoming a genuine IO in terms of membership and gets involved in global discussions relating to finance, climate change, or poverty eradication, public scrutiny will only increase and thus improved governance is an irreversible process. However, divergences in the views of WTO Members as to the proper scope of WTO input and output transparency will most probably lead to extended negotiations. Some thoughts about the future prospects of and possible avenues for the WTO system are also identified.
Total anomalous pulmonary venous connection in a neonate characterised by low-dose, high-pitch cardiac CT
Authors: Deshmukh Swati , Thompson W. Reid , Zimmerman Stefan L.
Published: July 2014

We describe the use of low-dose dual-source cardiac for the evaluation of a neonate with suspected total anomalous pulmonary venous connection. This novel technique obviates the need for sedation or breathholding. Radiation dose-reduction strategies result in sub-mSv-estimated effective doses, substantially lower than annual background radiation dose. Low-dose, high-pitch cardiac CT should be considered as an alternative to MRI or diagnostic cardiac catheterisation in neonates with complex CHD, requiring definitive anatomic evaluation.
Viability of the lichenXanthoria elegansand its symbionts after 18 months of space exposure and simulated Mars conditions on the ISS
Authors: Brandt Annette , de Vera Jean-Pierre , Onofri Silvano , Ott Sieglinde
Published: July 2014

The lichenXanthoria eleganshas been exposed to space conditions and simulated Mars-analogue conditions in the lichen and fungi experiment (LIFE) on the International Space Station (ISS). After several simulations and short space exposure experiments such as BIOPAN, this was the first long-term exposure of eukaryotic organisms to the hostile space conditions of the low Earth orbit (LEO). The biological samples were integrated in the EXPOSE-E facility and exposed for 1.5 years outside the ISS to the combined impact of insolation, ultraviolet (UV)-irradiation, cosmic radiation, temperatures and vacuum conditions of LEO space. Additionally, a subset ofX. eleganssamples was exposed to simulated Martian environmental conditions by applying Mars-analogue atmosphere and suitable solar radiation filters. After their return to Earth the viability of the lichen samples was ascertained by viability analysis of LIVE/DEAD staining and confocal laser-scanning microscopy, but also by analyses of chlorophyllafluorescence. According to the LIVE/DEAD staining results, the lichen photobiont showed an average viability rate of 71%, whereas the even more resistant lichen mycobiont showed a rate of 84%. Post-exposure viability rates did not significantly vary among the applied exposure conditions. This remarkable viability is discussed in the context of particular protective mechanisms of lichens such as anhydrobiosis and UV-screening pigments.
A mid-infrared exploration of the dusty environments of active galactic nuclei
Authors: Alonso-Herrero Almudena
Published: July 2014

We present the first results from a mid-infrared survey of local Active Galactic Nuclei (AGN) using the CanariCam (CC) instrument on the 10.4 m Gran Telescopio Canarias (GTC). We are obtaining sub-arcsecond angular resolution (0.3 − 0.6 arcsec) mid-IR imaging and spectroscopic observations of a sample of 100 local AGN, which are complemented with data taken with T-ReCS, VISIR, and Michelle. The full sample contains approximately 140 AGN, covers nearly six orders of magnitude in AGN luminosity, and includes low-luminosity AGN (LLAGN), Seyfert 1s and 2s, QSO, radio galaxies, and (U)LIRGs. The main goals of this project are: (1) to test whether the properties of the dusty tori of the AGN Unified Model depend on the AGN type, (2) to study the nuclear star formation activity and obscuration of local AGN, and (3) to explore the role of the dusty torus in LLAGN.