bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic Drug-Drug Interaction Potential of Macrolactin A and 7-
O
-Succinyl Macrolactin A Assessed by Evaluating Cytochrome P450 Inhibition and Induction and UDP-Glucuronosyltransferase Inhibition
In Vitro
Authors: Bae Soo Hyeon , Kwon Min Jo , Park Jung Bae , Kim Doyun , Kim Dong-Hee , Kang Jae-Seon , Kim Chun-Gyu , Oh Euichaul , Bae Soo Kyung
Published: June 2014

Macrolactin A (MA) and 7-
O
-succinyl macrolactin A (SMA), polyene macrolides containing a 24-membered lactone ring, show antibiotic effects superior to those of teicoplanin against vancomycin-resistant enterococci and methicillin-resistant
Staphylococcus aureus
. MA and SMA are currently being evaluated as antitumor agents in preclinical studies in Korea. We evaluated the potential of MA and SMA for the inhibition or induction of human liver cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs)
in vitro
to assess their safety as new molecular entities. We demonstrated that MA and SMA are potent competitive inhibitors of CYP2C9, with

K
i

values of 4.06 μM and 10.6 μM, respectively. MA and SMA also weakly inhibited UGT1A1 activity, with

K
i

values of 40.1 μM and 65.3 μM, respectively. However, these macrolactins showed no time-dependent inactivation of the nine CYPs studied. In addition, MA and SMA did not induce CYP1A2, CYP2B6, or CYP3A4/5. On the basis of an
in vitro-in vivo
extrapolation, our data strongly suggested that MA and SMA are unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most of the CYPs involved in drug metabolism
in vivo
, except for the inhibition of CYP2C9 by MA. Similarly, MA and SMA are unlikely to inhibit the activity of UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 enzymes
in vivo
. Although further investigations will be required to clarify the
in vivo
interactions of MA with CYP2C9-targeted drugs, our findings offer a clearer understanding and prediction of drug-drug interactions for the safe use of MA and SMA in clinical practice.
Linezolid-Dependent Function and Structure Adaptation of Ribosomes in a Staphylococcus epidermidis Strain Exhibiting Linezolid Dependence
Authors: Kokkori Sofia , Apostolidi Maria , Tsakris Athanassios , Pournaras Spyros , Stathopoulos Constantinos , Dinos George
Published: June 2014

Linezolid-dependent growth was recently reported in
Staphylococcus epidermidis
clinical strains carrying mutations associated with linezolid resistance. To investigate this unexpected behavior at the molecular level, we isolated active ribosomes from one of the linezolid-dependent strains and we compared them with ribosomes isolated from a wild-type strain. Both strains were grown in the absence and presence of linezolid. Detailed biochemical and structural analyses revealed essential differences in the function and structure of isolated ribosomes which were assembled in the presence of linezolid. The catalytic activity of peptidyltransferase was found to be significantly higher in the ribosomes derived from the linezolid-dependent strain. Interestingly, the same ribosomes exhibited an abnormal ribosomal subunit dissociation profile on a sucrose gradient in the absence of linezolid, but the profile was restored after treatment of the ribosomes with an excess of the antibiotic. Our study suggests that linezolid most likely modified the ribosomal assembly procedure, leading to a new functional ribosomal population active only in the presence of linezolid. Therefore, the higher growth rate of the partially linezolid-dependent strains could be attributed to the functional and structural adaptations of ribosomes to linezolid.
Localization of the Outer Membrane Protein OmpA2 in Caulobacter crescentus Depends on the Position of the Gene in the Chromosome
Authors: Ginez Luis David , Osorio Aurora , Poggio Sebastian
Published: June 2014

The outer membrane of Gram-negative bacteria is an essential structure involved in nutrient uptake, protection against harmful substances, and cell growth. Different proteins keep the outer membrane from blebbing out by simultaneously interacting with it and with the cell wall. These proteins have been mainly studied in enterobacteria, where OmpA and the Braun and Pal lipoproteins stabilize the outer membrane. Some degree of functional redundancy exists between these proteins, since none of them is essential but the absence of two of them results in a severe phenotype.
Caulobacter crescentus
has a different strategy to maintain its outer membrane, since it lacks the Braun lipoprotein and Pal is essential. In this work, we characterized OmpA2, an OmpA-like protein, in this bacterium. Our results showed that this protein is required for normal stalk growth and that it plays a minor role in the stability of the outer membrane. An OmpA2 fluorescent fusion protein showed that the concentration of this protein decreases from the stalk to the new pole. This localization pattern is important for its function, and it depends on the position of the gene locus in the chromosome and, as a consequence, in the cell. This result suggests that little diffusion occurs from the moment that the gene is transcribed until the mature protein attaches to the cell wall in the periplasm. This mechanism reveals the integration of different levels of information from protein function down to genome arrangement that allows the cell to self-organize.
Acute spontaneous atraumatic bilateral anterior dislocation of the shoulder joint with Hill-Sachs lesions: first reported case and review of literature
Authors: Manoharan Gopikanthan , Singh Rohit , Ahmed Bessam , Kathuria Vinod
Published: June 2014

The anatomy of the shoulder joint comprises a relatively large humeral head with a shallow glenoid cavity allowing a remarkable range of motion at the expense of inherent instability. Despite anterior shoulder dislocations being the most common type encountered, bilateral dislocations are rare and almost always posterior. The aetiology is usually direct or indirect trauma related to sports, seizures, electric shock or electroconvulsive therapy. We present the first reported case of atraumatic bilateral acute anterior shoulder dislocations with associated Hill-Sachs lesions in a young, fit and well patient with no comorbidities. MRI illustrated the Hill-Sachs lesions with superior labral tear from anterior to posterior, and confirmed the acute nature of the injury by demonstrating the bone marrow oedema. The patient was treated surgically with arthroscopic anterior stabilisation. At 6 months following surgery, the patient has a pain free full range of movement of both shoulders with no further dislocations and has returned to work.
Amorphous solar cell on multilayer of SnO2/ZnO TCO substrate for full spectrum splitting solar cell application
Authors: Kim Sinae , Kang Dong-won , Sichanugrist Porponth , Konagai Makoto
Published: June 2014

To increase the performance of thin film solar cells, the solar spectrum splitting technique has been considered and studied. It was found from the simulation that the total efficiency of nearly 25% can be obtained at the splitting wavelength of 614 nm with the top cell using higher band gap material. The experiment has been carried out to verify the simulation results. Up to now a total efficiency of about 22.0% has been obtained using hydrogenated amorphous silicon (a-Si:H) and Cu(In1–x,Gax) as the top and bottom cells, respectively, at a splitting wavelength of 620 nm. In this study, we have developed a multilayer of transparent and conductive oxide (TCO) substrate of a-Si:H solar cell with better electrical properties especially improved fill factor and better electrical compatibility. This multilayer TCO is suitable for the splitting technique to enhance the performance at the short-wavelength of the top cell.
Λ-hyperon interaction with nucleons
Authors: Ikram M. , Singh S. K. , Biswal S. K. , Bhuyan M. , Patra S. K.
Published: June 2014

We study the interaction of Λ-hyperon with proton and neutron inside a nucleus within the framework of relativistic mean field (RMF) formalism. The single-particle energy levels for some of the specific proton and neutron orbits are analyzed with the addition of Λ-successively. The neutron energy level is more deeper, because of decrease in symmetry energy due to substitution of neutron by Λ-hyperon.
The calibration system for the Borexino experiment
Authors: Caccianiga Barbara , Carlotta Re Alessandra
Published: June 2014

Borexino is a large liquid scintillator detector designed to study solar neutrinos in real-time. Since the beginning of data-taking in 2007, Borexino has been able to perform a complete spectroscopy of neutrinos from the Sun, thanks to its unprecedented radiopurity. Calibrations have been crucial for the success of the experiment. In this paper, we describe the Borexino calibration system, emphasizing its most critical aspects, in particular to those related to radiopurity. We also discuss some of the results of the calibration campaigns performed in Borexino Phase-1.
First principle study of the electronic properties of the magnetocaloric compound Gd5Si4
Authors: Larimi Zobeideh Momeni , Amirabadizadeh Ahmad , Yazdani Ahmad , Arabi Hadi
Published: June 2014

The electronic structure and magnetic properties of the Gd 5 Si 4 compound have been investigated by the first principles full-potential linearized augmented plane wave (FP-LAPW) method based on density functional theory (DFT) using the WIEN2k code. The Coulomb corrected local-spin density approximation (LSDA + U) in the self-interaction correction (SIC) has been used for the exchange-correlation potential. Based on the calculated results, the ground state of Gd 5 Si 4 is found to be ferromagnetic (FM). The optimized structural parameters and magnetic properties including the lattice constants and magnetic moments are in good agreement with experimental data. The magnetic moments of the Gd atoms in Gd 5 Si 4 are smaller than that of the elemental gadolinium. The magnetic moment of Gd 5 Si 4 is found to be 37.8 μB/f.u. DOS results show that the magnetic properties of the compound depend on the hybridization between Si -3p and Gd -5d states which have an effective role in the RKKY interaction. The existence of the very flat bands at -7 eV for spin up and at +3 eV for spin down that is mainly Gd -4f characters shows that the LSDA + U method provides the better description of our systems. The obvious overlap of electron densities between the Gd1 and Si atoms indicates a covalent-like bonding between them.
Statistics-related and reliability-physics-related failure processes in electronics devices and products
Authors: Suhir E.
Published: June 2014

The well known and widely used experimental reliability "passport" of a mass manufactured electronic or a photonic product — the bathtub curve — reflects the combined contribution of the statistics-related and reliability-physics (physics-of-failure)-related processes. When time progresses, the first process results in a decreasing failure rate, while the second process associated with the material aging and degradation leads to an increased failure rate. An attempt has been made in this analysis to assess the level of the reliability physics-related aging process from the available bathtub curve (diagram). It is assumed that the products of interest underwent the burn-in testing and therefore the obtained bathtub curve does not contain the infant mortality portion. It has been also assumed that the two random processes in question are statistically independent, and that the failure rate of the physical process can be obtained by deducting the theoretically assessed statistical failure rate from the bathtub curve ordinates. In the carried out numerical example, the Raleigh distribution for the statistical failure rate was used, for the sake of a relatively simple illustration. The developed methodology can be used in reliability physics evaluations, when there is a need to better understand the roles of the statistics-related and reliability-physics-related irreversible random processes in reliability evaluations. The future work should include investigations on how powerful and flexible methods and approaches of the statistical mechanics can be effectively employed, in addition to reliability physics techniques, to model the operational reliability of electronic and photonic products.
Black holes as gravitational atoms
Authors: Vaz Cenalo
Published: June 2014

Recently, it was argued [A. Almheiri et al., arXiv: 1207.3123, A. Almheiri et al., arXiv: 1304.6483], via a delicate thought experiment, that it is not consistent to simultaneously require that (a) Hawking radiation is pure, (b) effective field theory is valid outside a stretched horizon and (c) infalling observers encounter nothing unusual as they cross the horizon. These are the three fundamental assumptions underlying Black Hole Complementarity and the authors proposed that the most conservative resolution of the paradox is that (c) is false and the infalling observer burns up at the horizon (the horizon acts as a "firewall"). However, the firewall violates the equivalence principle and breaks the CPT invariance of quantum gravity. This led Hawking to propose recently that gravitational collapse may not end up producing event horizons, although he did not give a mechanism for how this may happen. Here we will support Hawking's conclusion in a quantum gravitational model of dust collapse. We will show that continued collapse to a singularity can only be achieved by combining two independent and entire solutions of the Wheeler–DeWitt equation. We interpret the paradox as simply forbidding such a combination. This leads naturally to a picture in which matter condenses on the apparent horizon during quantum collapse.
A Multi-Step Approach for Identification of Structural Modifications Based on Operational Modal Analysis
Authors: Tributsch Alexander , Adam Christoph
Published: June 2014

In this paper, an approach for detecting damage and structural modifications is implemented, based on a combination of several indicators derived from the recorded ambient dynamic structural response. In a multi-step procedure, the normalized cumulative power spectral density (NCPSD) evaluated at several structural nodes and a thereof derived "NCPSD damage index" is proposed to detect a modification of the structure. A subsequent sophisticated superposition of a series of mode shape quantities yields a "mode shape damage index" as a function of the structural coordinates that reveals the specific location of this structural modification. Furthermore, it is discussed how environmental effects from varying temperatures on natural frequencies can be substantially reduced. Therefore, long-term monitoring of the structure is required to define relations that allow translating the proposed damage parameters contaminated by temperature effects into the domain of the structure in a reference state. The efficiency of the proposed method is tested on an old iron railway bridge, subjected to a series of structural modifications, such as stepwise reducing the stiffness of local elements, adding mass and an additional flexible support. From the results of this comprehensive study it can be concluded that this nondestructive approach is a promising tool for reliable structural health monitoring (SHM).
Self-force driven motion in curved spacetime
Authors: Spallicci Alessandro D. A. M. , Ritter Patxi , Aoudia Sofiane
Published: June 2014

We adopt the Dirac–Detweiler–Whiting radiative and regular effective field in curved spacetime. Thereby, we derive straightforwardly the first order perturbative correction to the geodesic of the background in a covariant form, for the extreme mass ratio two-body problem. The correction contains the self-force contribution and a background metric-dependent term.
Mathematical analysis on a multidimensional model of morphogen transport with receptor synthesis
Authors: Yin Hongwei , Xiao Xiaoyong , Wen Xiaoqing , Zhou Tianshou
Published: June 2014

In biological development, morphogens are locally produced and spread to other regions in organs, forming gradients that control the inter-related pattern and growth of developing organs. Mechanisms of morphogen transport were built and investigated by numerical simulations in [A. D. Lander, Q. Nie and F. Y. M. Wan, Do morphogen gradients arise by diffusion? Developmental Cell2 (2002) 785–796]. In that paper, model C, which considers endocytosis, exocytosis and receptor synthesis and degradation, is in a one-dimensional spatial region and couples a partial differential equation with ordinary differential equations. Here, this model is promoted to an arbitrary dimension bounded region. We prove existence, uniqueness and non-negativity of a global solution for this advanced model, of its steady-state solution and linear stability of steady state by operator semigroup, the Schauder theorem and local perturbation method. Our results improve previous results for this model in a one dimension region.
Ranking Metric Anomaly in Invariant Networks
Authors: Ge Yong , Jiang Guofei , Ding Min , Xiong Hui
Published: June 2014

The management of large-scale distributed information systems relies on the effective use and modeling of monitoring data collected at various points in the distributed information systems. A traditional approach to model monitoring data is to discover invariant relationships among the monitoring data. Indeed, we can discover all invariant relationships among all pairs of monitoring data and generate invariant networks, where a node is a monitoring data source (metric) and a link indicates an invariant relationship between two monitoring data. Such an invariant network representation can help system experts to localize and diagnose the system faults by examining those broken invariant relationships and their related metrics, since system faults usually propagate among the monitoring data and eventually lead to some broken invariant relationships. However, at one time, there are usually a lot of broken links (invariant relationships) within an invariant network. Without proper guidance, it is difficult for system experts to manually inspect this large number of broken links. To this end, in this article, we propose the problem of ranking metrics according to the anomaly levels for a given invariant network, while this is a nontrivial task due to the uncertainties and the complex nature of invariant networks. Specifically, we propose two types of algorithms for ranking metric anomaly by link analysis in invariant networks. Along this line, we first define two measurements to quantify the anomaly level of each metric, and introduce the m
R
ank algorithm. Also, we provide a weighted score mechanism and develop the g
R
ank algorithm, which involves an iterative process to obtain a score to measure the anomaly levels. In addition, some extended algorithms based on m
R
ank and g
R
ank algorithms are developed by taking into account the probability of being broken as well as noisy links. Finally, we validate all the proposed algorithms on a large number of real-world and synthetic data sets to illustrate the effectiveness and efficiency of different algorithms.
Effect of Diffusion and Cross-Diffusion in a Predator-Prey Model with a Transmissible Disease in the Predator Species
Authors: Zhang Guohong , Wang Xiaoli
Published: June 2014

We study a Lotka-Volterra type predator-prey model with a transmissible disease in the predator population. We concentrate on the effect of diffusion and cross-diffusion on the emergence of stationary patterns. We first show that both self-diffusion and cross-diffusion can not cause Turing instability from the disease-free equilibria. Then we find that the endemic equilibrium remains linearly stable for the reaction diffusion system without cross-diffusion, while it becomes linearly unstable when cross-diffusion also plays a role in the reaction-diffusion system; hence, the instability is driven solely from the effect of cross-diffusion. Furthermore, we derive some results for the existence and nonexistence of nonconstant stationary solutions when the diffusion rate of a certain species is small or large.
Provincial Maternal Mortality Surveillance Systems in China
Authors: Gan Xiao-Ling , Hao Chang-Lai , Dong Xiao-Jing , Alexander Sophie , Dramaix Michèle Wilmet , Hu Li-Na , Zhang Wei-Hong
Published: June 2014

Background. Provincial maternal mortality surveillance systems (PMMSS) have been set up in nearly all the provinces in China to monitor local maternal mortality and provide the evidence for maternal health interventions suited to local conditions. However, till now little is known outside of China about the characteristics of PMMSS.Methods. A systematic review of the literature contained in PubMed and China Academic Journal Network Publishing database was carried out. The current situation on PMMSS was described. Provincial disparities on PMMR in six provinces were analyzed by Poisson regression analysis.Results. A total of 35 studies met the inclusion criteria, of which 31 were published in Chinese. PMMSS were set up and adjusted by the provincial government based on their own financial resources and demand. Provinces from remote region had the highest risk of maternal mortality, followed by provinces from inland region and coast region.Conclusions. PMMSS may be the most reliable data source for measuring provincial level MMR in each province. Great provincial disparities on PMMSS and PMMR do exist within the country; more emphasis should be placed on improving PMMSS and reducing PMMR particularly in the provinces with high maternal death burden.
Popularity Evaluation Model for Microbloggers Online Social Network
Authors: Zhang Xia , Xia Zhengyou , Bu Zhan
Published: June 2014

Recently, microblogging is widely studied by the researchers in the domain of the online social network (OSN). How to evaluate the popularities of microblogging users is an important research field, which can be applied to commercial advertising, user behavior analysis and information dissemination, and so forth. Previous studies on the evaluation methods cannot effectively solve and accurately evaluate the popularities of the microbloggers. In this paper, we proposed an electromagnetic field theory based model to analyze the popularities of microbloggers. The concept of the source in microblogging field is first put forward, which is based on the concept of source in the electromagnetic field; then, one’s microblogging flux is calculated according to his/her behaviors (send or receive feedbacks) on the microblogging platform; finally, we used three methods to calculate one’s microblogging flux density, which can represent one’s popularity on the microblogging platform. In the experimental work, we evaluated our model using real microblogging data and selected the best one from the three popularity measure methods. We also compared our model with the classic PageRank algorithm; and the results show that our model is more effective and accurate to evaluate the popularities of the microbloggers.
A Hilbert-Type Integral Inequality with Multiparameters and a Nonhomogeneous Kernel
Authors: Liu Qiong , Sun Wenbing
Published: June 2014

We first introduceΓ-function and Riemannζ-function to characterize the constant factor jointly. A Hilbert-type integral inequality with multiparameters and a nonhomogeneous kernel is given using the way of weight function and the technique of real analysis. The equivalent form is considered and its constant factors are proved to be the best possible. Some meaningful results are obtained by taking the special parameter values.
Almost Surely Exponential Stability of Numerical Solutions for Stochastic Pantograph Equations
Authors: Zhou Shaobo
Published: June 2014

Our effort is to develop a criterion on almost surely exponential stability of numerical solution to stochastic pantograph differential equations, with the help of the discrete semimartingale convergence theorem and the technique used in stable analysis of the exact solution. We will prove that the Euler-Maruyama (EM) method can preserve almost surely exponential stability of stochastic pantograph differential equations under the linear growth conditions. And the backward EM method can reproduce almost surely exponential stability for highly nonlinear stochastic pantograph differential equations. A highly nonlinear example is provided to illustrate the main theory.
Early Stages ofwe/we wal/walMouse Hair Morphogenesis: Light and Fluorescent Microscopy of the Whole-Mount Epidermis
Authors: Rippa Alexandra , Leonova Olga , Popenko Vladimir , Vasiliev Andrey , Terskikh Vasily , Vorotelyak Ekaterina
Published: June 2014

In adult skin, hair follicles cyclically self-renew in a manner that recapitulates embryonic hair follicle morphogenesis. The most common pathology of hair in adults is alopecia, which is hair loss to different extent. There are a number of murine models of alopecia including spontaneous mutations. In the present study, we worked with double homozygouswe/we wal/walmice which demonstrate symptoms closely resembling human alopecia. Using whole-mount preparations of epidermis of E18.5 embryos we show that hair follicle defects can be revealed as early as during embryonic morphogenesis in these mutants. The number of hair follicles was reduced almost 1.5-fold in mutant skin. The shape of the early stage small follicles was altered in mutant animals as compared to control ones. Additionally, follicles of mutant embryos were wider at the point of conjunction with interfollicular epidermis. We believe that the mutant mice studied represent a fascinating model to address the problem of hair loss. We demonstrated alterations in the morphogenesis of embryonic hair follicle inwe/we wal/waldouble homozygous mice developing alopecia postnatally. We suppose that incorrect morphogenesis of hair follicles during embryogenesis is closely related to alopecia in the adult life. Unveiling the mechanisms involved in altered embryogenesis may elucidate the pathogenesis of alopecia.
Exact Solutions for the KdV Equation with Forcing Term by the Generalized tanh-coth Method and the (G′/G)-Expansion Method
Authors: Manafian Jalil , Nasrollahpour Monireh
Published: June 2014

An application of the generalized tanh-coth method and the (G′/G)-expansion method to search for exact solutions of nonlinear partial differential equations is analyzed. These methods are used for the KdV equation with forcing term. The generalized tanh-coth method and the (G′/G)-expansion method were used to construct periodic wave and solitary wave solutions of nonlinear evolution equations. It is shown that the generalized tanh-coth method and the (G′/G)-expansion method, with the help of symbolic computation, provide a straightforward and powerful mathematical tool for solving nonlinear problems.
Family History of Colorectal Cancer Is Not Associated with Colorectal Cancer Survival Regardless of Microsatellite Instability Status
Authors: Phipps Amanda I. , Ahnen Dennis J. , Campbell Peter T. , Win Aung Ko , Jenkins Mark A. , Lindor Noralane M. , Gryfe Robert , Potter John D. , Newcomb Polly A.
Published: June 2014

Background: Individuals with a family history of colorectal cancer in first-degree relatives have an elevated risk of developing colorectal cancer themselves, particularly colorectal cancer exhibiting high microsatellite instability (MSI-high). Given that MSI-high colorectal cancer is associated with a favorable prognosis, it is plausible that having a family history of colorectal cancer could, in turn, be favorably associated with colorectal cancer survival.

Methods: This study comprised N = 4,284 incident colorectal cancer cases enrolled in the Colon Cancer Family Registry via population-based cancer registries. Using Cox proportional hazards regression, we evaluated the association between family history and both overall and disease-specific survival, accounting for MSI status and tumor site via stratified analyses and statistical adjustment.

Results: There was no evidence of association between family history and overall [hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.79–1.08] or disease-specific survival (HR, 1.03; 95% CI, 0.85–1.24) for all cases combined, after adjustment for MSI status or tumor site. Only for rectal cancer cases was colorectal cancer family history modestly associated with more favorable overall survival (HR, 0.75; 95% CI, 0.56–0.99).

Conclusions: Although individuals with a family history of colorectal cancer were more likely to have MSI-high tumors than those with nonfamilial disease, this did not translate to a survival benefit.

Impact: Overall, there is no evidence that family history of colorectal cancer is associated with colorectal cancer survival; however, specific mechanisms underlying family history may have prognostic impact and merit further study. Cancer Epidemiol Biomarkers Prev; 23(8); 1700–4. ©2014 AACR.
VISTA Is a Novel Broad-Spectrum Negative Checkpoint Regulator for Cancer Immunotherapy
Authors: Lines J. Louise , Sempere Lorenzo F. , Broughton Thomas , Wang Li , Noelle Randolph
Published: June 2014

In the past few years, the field of cancer immunotherapy has made great progress and is finally starting to change the way cancer is treated. We are now learning that multiple negative checkpoint regulators (NCR) restrict the ability of T-cell responses to effectively attack tumors. Releasing these brakes through antibody blockade, first with anti-CTLA4 and now followed by anti-PD1 and anti-PDL1, has emerged as an exciting strategy for cancer treatment. More recently, a new NCR has surfaced called V-domain immunoglobulin (Ig)-containing suppressor of T-cell activation (VISTA). This NCR is predominantly expressed on hematopoietic cells, and in multiple murine cancer models is found at particularly high levels on myeloid cells that infiltrated the tumors. Preclinical studies with VISTA blockade have shown promising improvement in antitumor T-cell responses, leading to impeded tumor growth and improved survival. Clinical trials support combined anti-PD1 and anti-CTLA4 as safe and effective against late-stage melanoma. In the future, treatment may involve combination therapy to target the multiple cell types and stages at which NCRs, including VISTA, act during adaptive immune responses. Cancer Immunol Res; 2(6); 510–7. ©2014 AACR.
Expression Patterns of Neuroligin-3 and Tyrosine Hydroxylase across the Brain in Mate Choice Contexts in Female Swordtails
Authors: Wong Ryan Y. , Cummings Molly E.
Published: June 2014

Choosing mates is a commonly shared behavior across many organisms, with important fitness consequences. Variations in female preferences can be due in part to differences in neural and cellular activity during mate selection. Initial studies have begun to identify putative brain regions involved in mate preference, yet the understanding of the neural processes regulating these behaviors is still nascent. In this study, we characterized the expression of a gene involved in synaptogenesis and plasticity (neuroligin-3) and one that codes for the rate-limiting enzyme in dopamine biosynthesis (tyrosine hydroxylase; TH1) in the female Xiphophorus nigrensis (northern swordtail) brain as related to mate preference behavior. We exposed females to a range of different mate choice contexts including two large courting males (LL), two small coercive males (SS), and a context that paired a large courting male with a small coercive male (LS). Neuroligin-3 expression in a mate preference context (LS) showed significant correlations with female preference in two telencephalic areas (Dm and Dl), a hypothalamic nucleus (HV), and two regions associated with sexual and social behavior (POA and Vv). We did not observe any context- or behavior-specific changes in tyrosine hydroxylase mRNA expression concomitant with female preference in any of the brain regions examined. Analysis of TH and neuroligin-3 expression across different brain regions showed that expression patterns varied with the male social environment only for neuroligin-3, where the density of correlated expression between brain regions was positively associated with mate choice contexts that involved a greater number of courting male phenotypes (LS and LL). This study identified regions showing presumed high levels of synaptic plasticity using neuroligin-3, implicating and supporting their roles in female mate preference, but we did not detect any relationship between tyrosine hydroxylase and mate preference with 30 min of stimulus presentation in X. nigrensis. These data suggest that information about potential mates is processed in select forebrain regions and the entire brain shows different degrees of correlated expression depending on the mate preference context.
Single Delivery of an Adeno-Associated Viral Construct to Transfer the
CASQ2
Gene to Knock-In Mice Affected by Catecholaminergic Polymorphic Ventricular Tachycardia Is Able to Cure the Disease From Birth to Advanced Age
Authors: Denegri Marco , Bongianino Rossana , Lodola Francesco , Boncompagni Simona , De Giusti Verónica C. , Avelino-Cruz José E. , Liu Nian , Persampieri Simone , Curcio Antonio , Esposito Francesca , Pietrangelo Laura , Marty Isabelle , Villani Laura , Moyaho Alejandro , Baiardi Paola , Auricchio Alberto , Protasi Feliciano , Napolitano Carlo , Priori Silvia G.
Published: June 2014

Background—

Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmogenic disorder characterized by sudden cardiac death in children. Drug therapy is still insufficient to provide full protection against cardiac arrest, and the use of implantable defibrillators in the pediatric population is limited by side effects. There is therefore a need to explore the curative potential of gene therapy for this disease. We investigated the efficacy and durability of viral gene transfer of the
calsequestrin 2
(
CASQ2
) wild-type gene in a catecholaminergic polymorphic ventricular tachycardia knock-in mouse model carrying the
CASQ2

R33Q/R33Q

(R33Q) mutation.

Methods and Results—

We engineered an adeno-associated viral vector serotype 9 (AAV9) containing cDNA of
CASQ2
wild-type (AAV9-
CASQ2
) plus the
green fluorescent protein
(
GFP
) gene to infect newborn R33Q mice studied by in vivo and in vitro protocols at 6, 9, and 12 months to investigate the ability of the infection to prevent the disease and adult R33Q mice studied after 2 months to assess whether the AAV9-
CASQ2
delivery could revert the catecholaminergic polymorphic ventricular tachycardia phenotype. In both protocols, we observed the restoration of physiological expression and interaction of CASQ2, junctin, and triadin; the rescue of electrophysiological and ultrastructural abnormalities in calcium release units present in R33Q mice; and the lack of life-threatening arrhythmias.

Conclusions—

Our data demonstrate that viral gene transfer of wild-type
CASQ2
into the heart of R33Q mice prevents and reverts severe manifestations of catecholaminergic polymorphic ventricular tachycardia and that this curative effect lasts for 1 year after a single injection of the vector, thus posing the rationale for the design of a clinical trial.
Introduction to “The Nightingale's Butcher Manifesto”
and “Volume and Environment II”
Authors: Behpoor Bavand
Published: June 2014

The introductory text introduces two pre-revolution Iranian manifestos of modern art, namely the “Nightingale's Butcher Manifesto” (1951) and “Volume & Environment 2” (1976). It describes the socio-political context in which the texts emerged and compares them as different responses to similar issues separated by a time span of 25 years. It argues that these rare examples of Iranian art manifestos can be regarded as milestones of an entry into and an exit from modernism in Iranian art.
“There Is Not One Realism, But Several Realisms”: A Review of Opening Bazin
Authors: Allen Richard
Published: June 2014

There was a period when André Bazin was considered by some to be a simplistic, naive thinker whose writings were only of historic interest. In 1974, Screen regular Colin MacCabe, in a widely influential article, characterized Bazin as “a theoretically naive empiricist, a kind of idiot of the family.” How times have changed. In a new essay, MacCabe writes that Bazin realized that cinema creates a “complicated series of relationships between camera and setting” and concludes that Bazin was really a modernist, and so on the right side of history after all. Bazin, a modernist? I am not so sure. However, the sea change evidenced by MacCabe is symptomatic of the state of cinema studies as a whole: Bazin is back! This must be deeply gratifying to Bazin scholar and editor of Opening Bazin: Postwar Theory and Its Afterlife Dudley Andrew, who has been Bazin's leading advocate on the American side of the Atlantic for more than three decades.
Relative susceptibilities of five fodder radish varieties (Raphanus sativus var. Oleiformis) to Meloidogyne chitwoodi
Authors: Teklu Misghina G. , Schomaker Corrie H. , Been Thomas H.
Published: June 2014

The fodder radish varieties Anaconda, Contra, Defender, Doublet and Terranova, known to have some partial resistance, were compared to the standard variety, Radical, to estimate their relative susceptibility (RS) for both population dynamic parameters of Meloidogyne chitwoodi and to evaluate dependency. This approach must eventually lead to new screening methods for partial resistance tests. Plants were grown under controlled glasshouse conditions. Twelve densities of nematodes in five replications were used. Five plants per 7 l pot were allowed to grow for a period of 11 weeks until their early flowering stage. Few seedlings of all the varieties at and 64 J2 (g dry soil)−1, and all seedlings exposed to the highest density, J2 (g dry soil)−1, died within a week after germination. Replanted seedlings developed into normal plants. Total yield, expressed as total fresh weight, was not affected by M. chitwoodi. A lower percentage of plants with galls was observed on partially resistant varieties as compared with Radical. For Radical, a maximum multiplication rate (a) of 0.38 and a maximum population density (M) of 6.43 J2 (g dry soil)−1 were estimated. Radical proved to be a bad host for M. chitwoodi with all final populations lower than the . The parameter estimates of (M) for Anaconda, Contra, Defender, Doublet and Terranova were 0.011, 0.006, 0.027, 0.020 and 0.009 J2 (g dry soil)−1, respectively. With Radical taken to be 100% susceptible, this resulted in values of 0.17, 0.10, 0.42, 0.32 and 0.14% of these varieties, respectively, reducing high population levels of M. chitwoodi by more than 98%. There was no correlation between the and the values, indicating that scoring the number of galled plants will not provide a suitable measure for partial resistance.
Parasitodiplogaster species associated with Pharmacosycea figs in Panama
Authors: Kanzaki Natsumi , Giblin-Davis Robin M. , Ye Weimin , Herre Edward Allen , Center Barbara J.
Published: June 2014

Parasitodiplogaster species that are associated with figs in the Ficus subsection Pharmacosycea, i.e., Ficus maxima, F. yoponensis, F. insipida and F. glabrata, were studied using morphological characters and molecular sequences. Some nematodes isolated from the fig sycones were casually observed and recorded as morphospecies according to their morphotype, and were then digested for their DNA, while others were fixed in formalin-glycerin for additional morphological study. High resolution microscopic observation of the morphological materials yielded five morphospecies including two nominal species, P. maxinema and P. pharmaconema. The morphospecies were distinguished from each other by male tail characters. By contrast, five and six genotypes were recognised by D2/D3 expansion segments of the large subunit (LSU) and near-full-length sequences of small subunit (SSU) ribosomal RNA genes, respectively. Except for two nominal species, genotypes and morphospecies were not clearly correlated because of limitations in the microscopic resolution in the initial morphotyping. Although the morphospecies and genotypes were not clearly paired, Pharmacosycea-associated Parasitodiplogaster species, which are tentatively referred to as the ‘P. maxinema group’, formed a monophyletic clade in both D2/D3 LSU and SSU analyses and are morphologically characterised by their stomatal morphology, i.e., a tube-shaped stoma with two stick-like teeth and male tail morphology, presence of nine paired papillae and relatively slender spicule.
Empathy Training from a Phenomenological Perspective
Authors: Englander Magnus
Published: June 2014

Abstract

The purpose of this article is to outline a phenomenological approach to empathy training developed over the past ten years in the context of higher education. The theoretical justification for this empathy training is founded in the phenomenological philosophical interpretation of the phenomenon of empathy, whereas the application of empathy as a skill is theoretically based upon entering the phenomenological attitude. The phenomenon of empathy is described as a unique intentionality as part of the self-other relation and contrasted to mainstreams views such as simulation theory. It is argued that the phenomenological attitude can open up for the possibility of empathy and interpersonal understanding to occur. The consecutive steps of the phenomenologically based empathy training are described as relating to theoretical and pedagogical issues as well as to student’s experiences.
Grieving with the Moon: Pantheon and Politics in The Lunar Eclipse
Authors: Wee John Z.
Published: June 2014

In response to the absence of consensus on events narrated in the Lunar Eclipse Myth, this article proposes an interpretation that takes into account the mythological representation of astrological phenomena, the Myth’s meaning in the context of the Utukkū Lemnūtu (“evil demons”) incantation series, as well as its implications concerning royal authority and guilt during the politically unstable conditions of a lunar eclipse. Although human observation alone could not discern the reasons for a lunar eclipse, the Myth suggests that at least some eclipses resulted from malevolent acts of self-will by a group of seven deities or demons (the “Sibitti”) and did not represent the pantheon’s condemnation of royal guilt. By contrast, celestial omens, letters from astrologers, the substitute king ritual, and šuilla prayers all envisioned the lunar eclipse as a sign of the gods’ displeasure. Omen verdicts depicting successful acts of treason as divine judgment would have contributed to suspicions and tensions between the king and his courtiers during stressful times of eclipses. In portraying the king as an embodiment of the moon-god and as a fellow victim (together with the pantheon) of the Sibitti, the Lunar Eclipse Myth functioned as royal apology by removing implications of the king’s personal guilt and failure and, hence, the pretext for treason and regime change. Such a radical reinterpretation that contradicted long-held ideas about the lunar eclipse as divine judgment, however, may not have fitted easily with existing traditions. Inter-textual references to the Eclipse Myth are relatively scarce and do not accurately convey meanings original to the Myth itself, suggesting that subtler ways of downplaying royal guilt and safeguarding the king’s status may have been preferred.
Notes et documents 堂郎语语音浅说
Authors: 王艳 盖兴之
Published: June 2014

This article provides the first comprehensive phonological analysis of the Tanglang language. It focuses on characteristic features of this language and provides new data that contribute to a better understanding of the phonetic and phonological aspects of the languages of the Yi group of the Tibeto-Burman language family. 

Cet article propose la première analyse phonologique complète de la langue tanglang. Il fait apparaître les spécificités phonétiques du tanglang et fournit des données détaillées qui contribuent à approfondir notre connaissance de la phonétique et la phonologie des langues du groupe yi au sein du tibéto-birman.
McDowell on Transcendental Arguments, Scepticism and “Error Theory”
Authors: Thomas Alan
Published: June 2014

John McDowell has recently changed his line of response to philosophical scepticism about the external world. He now claims to be in a position to use the strategy of transcendental argumentation in order to show the falsity of the sceptic’s misrepresentation of our ordinary epistemic standpoint. Since this transcendental argument begins from a weak and widely shared assumption shared with the sceptic herself the falsity of external world scepticism is now demonstrable even to her. Building on the account of perceptual intentionality defended in the Woodbridge lectures, McDowell argues that the idea of narrow perceptual content is unavailable to anyone, including the sceptic. This argument is assessed by drawing out an analogy with parallel responses to error theories in ethics.
The Constitutionalisation of Free Trade by the High Court of Australia and the Court of Justice of the European Union
Authors: Kiefel Susan , Puig Gonzalo Villalta
Published: June 2014

Together with matters of multilateral and bilateral regulation, domestic regulation affects the law and policy of economic relations between the European Union (eu) and Australia. This article discusses the constitutional determinants of the Australian single market and the significance to its development of the free trade jurisprudence of the Court of Justice of the European Union. When Australia was federated, free trade between the States and the removal of barriers at the borders were at the forefront of constitutional objectives. They find expression in Section 92 of the Australian Constitution. It took some time for the jurisprudence to develop by reference to principles of competition. Recent decisions of the High Court of Australia highlight the need to prove that a law or measure may have anti-competitive effects within a market to hold it invalid. Application of this (unacknowledged) test of proportionality invites comparison with eu law and opens to question the usefulness of protectionism as a criterion of constitutional invalidity for trade without borders in the ‘new economy’.
Environmental imprints of climate changes and anthropogenic activities in the Ore Mountains of Bohemia (Central Europe) since 13 cal. kyr BP
Authors: Veron Alain , Novak Martin , Brizova Eva , Stepanova Marketa
Published: June 2014

We have measured pollen, aluminum, and lead abundances in a Czech peat bog at Bozi Dar in order to investigate the environmental impact of Holocene climate changes and mining activities in Central Europe. The pollen record shows a continuous vegetal cover since 13 kyr BP. Aluminum and pollen deposition characterize the Younger Dryas (YD) cold event at 12.3–11.0 kyr BP, within its expected time frame in Northern Europe. Aluminum fluxes reveal four other significant dust events with significant Asian and Saharan sources, as shown with variations in stable 204Pb, 206Pb, and 207Pb isotopes. Recurrent Asian incursions are seen at Bozi Dar during the YD and Mid-Holocene dust events (at 7.1, 6.5, and 5.9 kyr BP). These Asian imprints are also observed by Le Roux and colleagues during the YD in the nearest Holocene-long geochemical peat record from Switzerland (Etang de la Gruère). We do not see at Bozi Dar the distinct western European volcanic inputs identified in the Swiss peat by Shotyk and colleagues. However, isotopic ratios characteristics of Mediterranean airflows are evident at both locations during the Mid- and Late Holocene. The occurrence of these various air mass sources in Switzerland and the Czech Republic substantiates Holocene atmospheric circulation models in Central Europe with dominating zonal airflows during the Early Holocene, followed by a governing meridian dispersion during the Mid- and Late Holocene. Lead inputs at 5.1–4.3 and 1.9 kyr BP cannot be explained by increased dust deposition only. The 1.9 kyr event fits local Bohemian ore isotopic imprints of which isotopic signatures are seen as early as 2.2 kyr BP in our core, hence revealing the oldest ever environmental record of mining-related activities in the Czech Republic. Relatively elevated Pb deposition at 5.1 and 4.3 kyr BP are tentatively attributed to contamination that may be from local sources and/or long-range transport.