bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of isovector scalar δ–meson on Λ–hypernuclei
Authors: Ikram M. , Singh S. K. , Biswal S. K. , Patra S. K.
Published: March 2015

We analyze the effects of δ–meson on hypernuclei within the framework of relativistic mean field theory. The δ–meson is included into the Lagrangian for hypernuclei. The extra nucleon–meson coupling (gδ) affects every piece of physical observables, like binding energy, radii and single-particle energies of hypernuclei. Magnitude of effects in hypernuclei is found to be relatively less than their normal nuclei because of the presence of Λ hyperon. Flipping of single-particle energy levels are observed with the strength of gδ in the considered hypernuclei as well as normal nuclei. The spin-orbit potentials are observed for considered hypernuclei and the effect of gδ on spin-orbit potentials is also analyzed. The calculated Λ binding energy (BΛ) are quite agreeable with experimental data. The sensitivity of BΛ for s- and p- orbitals with the strength of gδ is also analyzed. Lambda mean potential is investigated which is found to be consistent with other predictions.
Development of a New Nonbuckling Segmented Brace
Authors: Hao H.
Published: March 2015

This paper introduces a new design of segmented nonbuckling brace member for use in frame structures to resist earthquake loading. The proposed segmented brace member consists of one or more segments connected by either tension-only or compressive force controlled joints. Because it cannot resist or can only resist a limited amount of compressive force, it is effective only under tension, but buckling would not be a failure mechanism of the brace. Its capability of mitigating seismic responses remains effective throughout the entire ground excitation duration. The other advantages of this new design include light weight, easy installation, easy replacement, controlled damage locations, and minimum or no residual structural deformation. The disadvantage is that full energy dissipations can be achieved only when it is in tension. Therefore they will be effective in a frame structure only when cross bracings are used. This paper presents experimental tests and numerical simulation results to examine the effectiveness of this innovative brace member in mitigating seismic responses of frame structures. Laboratory cyclic loading tests on a single brace member and on steel frames without bracing or with cross bracing by conventional brace or segmented brace are carried out. The testing results are analyzed and compared. The effectiveness of segmented brace members in mitigation of seismic loading effects on frame structures is demonstrated. Nonlinear response analyses are then carried out to investigate the performance of this new segmented brace applied to a steel frame structure subjected to ground motions of different amplitudes. The results demonstrate that this new design is effective in mitigating seismic loading effect throughout the entire ground motion duration.
An answer to a problem about the number of overrings
Authors: Ben Nasr M.
Published: March 2015

Let [Formula: see text] be an integral domain with only finitely many overrings, equivalently, a domain such that its integral closure [Formula: see text] is a Prüfer domain with finite spectrum and there are only finitely many rings between [Formula: see text] and [Formula: see text]. Jaballah solved the problem of counting the overrings in the case [Formula: see text] but left the general case as an open problem [A. Jaballah, The number of overrings of an integrally closed domain, Expo. Math. 23 (2005) 353–360, Problem 3.4]. The purpose of this paper is to provide a solution to that problem.
Classification of linked indecomposable modules of a family of solvable Lie algebras over an arbitrary field of characteristic 0
Authors: Cagliero Leandro , Szechtman Fernando
Published: March 2015

Let 𝔤 be a finite-dimensional Lie algebra over a field of characteristic 0, with solvable radical 𝔯 and nilpotent radical 𝔫 = [𝔤, 𝔯]. Given a finite-dimensional 𝔤-module U, its nilpotency series 0 ⊂ U(1) ⊂ ⋯ ⊂ U(m) = U is defined so that U(1) is the 0-weight space of 𝔫 in U, U(2)/U(1) is the 0-weight space of 𝔫 in U/U(1), and so on. We say that U is linked if each factor of its nilpotency series is a uniserial 𝔤/𝔫-module, i.e. its 𝔤/𝔫-submodules form a chain. Every uniserial 𝔤-module is linked, every linked 𝔤-module is indecomposable with irreducible socle, and both converses fail. In this paper, we classify all linked 𝔤-modules when 𝔤 = 〈x〉 ⋉ 𝔞 and ad x acts diagonalizably on the abelian Lie algebra 𝔞. Moreover, we identify and classify all uniserial 𝔤-modules amongst them.
When every pure ideal is projective
Authors: Hu Jiangsheng , Liu Haiyu , Geng Yuxian
Published: March 2015

In this paper, we study the class of rings in which every pure ideal is projective. We refer to rings with this property as PIP-rings. Some properties and examples of PIP-rings are given. When R is a PIP-ring, some new homological dimensions for complexes are given. As applications, we give some new characterizations of von Neumann regular rings, F-rings and semisimple Artinian rings.
Structure of a class of Lie algebras of Block type, II
Authors: Xia Chunguang , Han Xiu , Wang Wei
Published: March 2015

Let q be a nonzero complex number. In this paper, we completely determine the derivation algebras and the automorphism groups of the Block type Lie algebras ℬ(q).
Microwave Absorption and Magnetic Properties of Cobalt Ferrites/Carbon Nanotubes Nanocomposites
Authors: Zhang B. B. , Wang P. F. , Xu J. C. , Han Y. B. , Jin H. X. , Jin D. F. , Peng X. L. , Hong B. , Li J. , Gong J. , Ge H. L. , Zhu Z. W. , Wang X. Q.
Published: March 2015

Owing to the unique microstructure and the excellent dielectric properties, carbon nanotubes (CNTs) were decorated with CoFe 2 O 4 nanoparticles to synthesize the CoFe 2 O 4/CNTs nanocomposites by the solvothermal method. The phase structure, morphology, magnetic properties and microwave absorption performance of the as-prepared CoFe 2 O 4/CNTs were characterized and discussed by X-ray diffraction (XRD), thermal gravity analysis (TGA), transmission electron microscope (TEM), vibrating sample magnetometer (VSM) and vector network analyzer (VNA). All results indicated that the diameter of CoFe 2 O 4 nanoparticles decorating on the surface of CNTs increased with the solvothermal temperature. CoFe 2 O 4/CNTs prepared at 180°C, 200°C and 220°C exhibited superparamagnetism, while the other samples presented ferromagnetism at room temperature. And with the increasing solvothermal temperature, the saturation magnetization and coercivity increased up to 72 emu/g and 2000 Oe for the sample prepared at 260°C (S-26). And the reflection loss of CoFe 2 O 4/CNTs nanocomposites increased with the solvothermal temperature up to -15.7 dB for S-26 with the bandwidth of 2.5 GHz.
Lamins: Nuclear Intermediate Filament Proteins with Fundamental Functions in Nuclear Mechanics and Genome Regulation
Authors: Gruenbaum Yosef , Foisner Roland
Published: March 2015

Lamins are intermediate filament proteins that form a scaffold, termed nuclear lamina, at the nuclear periphery. A small fraction of lamins also localize throughout the nucleoplasm. Lamins bind to a growing number of nuclear protein complexes and are implicated in both nuclear and cytoskeletal organization, mechanical stability, chromatin organization, gene regulation, genome stability, differentiation, and tissue-specific functions. The lamin-based complexes and their specific functions also provide insights into possible disease mechanisms for human laminopathies, ranging from muscular dystrophy to accelerated aging, as observed in Hutchinson–Gilford progeria and atypical Werner syndromes.
Cryogenic Electron Microscopy and Single-Particle Analysis
Authors: Elmlund Dominika , Elmlund Hans
Published: March 2015

About 20 years ago, the first three-dimensional (3D) reconstructions at subnanometer (<10-Å) resolution of an icosahedral virus assembly were obtained by cryogenic electron microscopy (cryo-EM) and single-particle analysis. Since then, thousands of structures have been determined to resolutions ranging from 30 Å to near atomic (<4 Å). Almost overnight, the recent development of direct electron detectors and the attendant improvement in analysis software have advanced the technology considerably. Near-atomic-resolution reconstructions can now be obtained, not only for megadalton macromolecular complexes or highly symmetrical assemblies but also for proteins of only a few hundred kilodaltons. We discuss the developments that led to this breakthrough in high-resolution structure determination by cryo-EM and point to challenges that lie ahead.
What Is High-Throughput Virtual Screening? A Perspective from Organic Materials Discovery
Authors: Pyzer-Knapp Edward O. , Suh Changwon , Gómez-Bombarelli Rafael , Aguilera-Iparraguirre Jorge , Aspuru-Guzik Alán
Published: March 2015

A philosophy for defining what constitutes a virtual high-throughput screen is discussed, and the choices that influence decisions at each stage of the computational funnel are investigated, including an in-depth discussion of the generation of molecular libraries. Additionally, we provide advice on the storing, analysis, and visualization of data on the basis of extensive experience in our research group.
From Mass Preferences to Policy
Authors: Canes-Wrone Brandice
Published: March 2015

This article reviews recent research on how mass opinion affects policy making in the context of US national institutions. Three themes materialize. First, research provides compelling evidence for “responsiveness,” in which change in mass opinion is associated with subsequent policy changes, but not for a high level of “congruence” between the policies that are favored by a majority of the public and those that are enacted. Second, although scholarship suggests that both congruence and responsiveness have declined since the 1970s, they are not low by historic standards; rather, mass opinion was particularly influential in that decade. Third, the literature rebuts conventional explanations for the post-1970s decline and suggests that standard proposals for how to reverse it would not significantly alter the impact of mass preferences on policy. The article concludes by considering the possibility that fundraising developments over the past three decades have changed politicians' electoral incentives.
Functional and molecular evidence for expression of the renin angiotensin system and ADAM17-mediated ACE2 shedding in COS7 cells
Authors: Grobe Nadja , Di Fulvio Mauricio , Kashkari Nada , Chodavarapu Harshita , Somineni Hari K. , Singh Richa , Elased Khalid M.
Published: March 2015

The renin angiotensin system (RAS) plays a vital role in the regulation of the cardiovascular and renal functions. COS7 is a robust and easily transfectable cell line derived from the kidney of the African green monkey, Cercopithecus aethiops. The aims of this study were to 1) demonstrate the presence of an endogenous and functional RAS in COS7, and 2) investigate the role of a disintegrin and metalloproteinase-17 (ADAM17) in the ectodomain shedding of angiotensin converting enzyme-2 (ACE2). Reverse transcription coupled to gene-specific polymerase chain reaction demonstrated expression of ACE, ACE2, angiotensin II type 1 receptor (AT1R), and renin at the transcript levels in total RNA cell extracts. Western blot and immunohistochemistry identified ACE (60 kDa), ACE2 (75 kDa), AT1R (43 kDa), renin (41 kDa), and ADAM17 (130 kDa) in COS7. At the functional level, a sensitive and selective mass spectrometric approach detected endogenous renin, ACE, and ACE2 activities. ANG-(1–7) formation ( m/z 899) from the natural substrate ANG II ( m/z 1,046) was detected in lysates and media. COS7 cells stably expressing shRNA constructs directed against endogenous ADAM17 showed reduced ACE2 shedding into the media. This is the first study demonstrating endogenous expression of the RAS and ADAM17 in the widely used COS7 cell line and its utility to study ectodomain shedding of ACE2 mediated by ADAM17 in vitro. The transfectable nature of this cell line makes it an attractive cell model for studying the molecular, functional, and pharmacological properties of the renal RAS.
Skeletal muscle signature of a champion sprint runner
Authors: Trappe Scott , Luden Nicholas , Minchev Kiril , Raue Ulrika , Jemiolo Bozena , Trappe Todd A.
Published: March 2015

We had the unique opportunity to study the skeletal muscle characteristics, at the single fiber level, of a world champion sprint runner who is the current indoor world record holder in the 60-m hurdles (7.30 s) and former world record holder in 110-m hurdles (12.91 s). Muscle biopsies were obtained from the vastus lateralis at rest and 4 h after a high-intensity exercise challenge (4 × 7 repetitions of resistance exercise). Single muscle fiber analyses were conducted for fiber type distribution (myosin heavy chain, MHC), fiber size, contractile function (strength, speed, and power) and mRNA expression (before and after the exercise bout). The world-class sprinter's leg muscle had a high abundance (24%) of the pure MHC IIx muscle fibers with a total fast-twitch fiber population of 71%. Power output of the MHC IIx fibers (35.1 ± 1.4 W/l) was 2-fold higher than MHC IIa fibers (17.1 ± 0.5 W/l) and 14-fold greater than MHC I fibers (2.5 ± 0.1 W/l). Additionally, the MHC IIx fibers were highly responsive to intense exercise at the transcriptional level for genes involved with muscle growth and remodeling ( Fn14 and myostatin). To our knowledge, the abundance of pure MHC IIx muscle fibers is the highest observed in an elite sprinter. Further, the power output of the MHC IIa and MHC IIx muscle fibers was greater than any human values reported to date. These data provide a myocellular basis for the high level of sprinting success achieved by this individual.
Multisensory decisions provide support for probabilistic number representations
Authors: Kanitscheider Ingmar , Brown Amanda , Pouget Alexandre , Churchland Anne K.
Published: March 2015

A large body of evidence suggests that an approximate number sense allows humans to estimate numerosity in sensory scenes. This ability is widely observed in humans, including those without formal mathematical training. Despite this, many outstanding questions remain about the nature of the numerosity representation in the brain. Specifically, it is not known whether approximate numbers are represented as scalar estimates of numerosity or, alternatively, as probability distributions over numerosity. In the present study, we used a multisensory decision task to distinguish these possibilities. We trained human subjects to decide whether a test stimulus had a larger or smaller numerosity compared with a fixed reference. Depending on the trial, the numerosity was presented as either a sequence of visual flashes or a sequence of auditory tones, or both. To test for a probabilistic representation, we varied the reliability of the stimulus by adding noise to the visual stimuli. In accordance with a probabilistic representation, we observed a significant improvement in multisensory compared with unisensory trials. Furthermore, a trial-by-trial analysis revealed that although individual subjects showed strategic differences in how they leveraged auditory and visual information, all subjects exploited the reliability of unisensory cues. An alternative, nonprobabilistic model, in which subjects combined cues without regard for reliability, was not able to account for these trial-by-trial choices. These findings provide evidence that the brain relies on a probabilistic representation for numerosity decisions.
Training voluntary motor suppression with real-time feedback of motor evoked potentials
Authors: Majid D. S. Adnan , Lewis Christina , Aron Adam R.
Published: March 2015

Training people to suppress motor representations voluntarily could improve response control. We evaluated a novel training procedure of real-time feedback of motor evoked potentials (MEPs) generated by transcranial magnetic stimulation (TMS) over motor cortex. On each trial, a cue instructed participants to use a mental strategy to suppress a particular finger representation without overt movement. A single pulse of TMS was delivered over motor cortex, and an MEP-derived measure of hand motor excitability was delivered visually to the participant within 500 ms. In experiment 1, we showed that participants learned to reduce the excitability of a particular finger beneath baseline (selective motor suppression) within 30 min of practice. In experiment 2, we performed a double-blind study with 2 training groups (1 with veridical feedback and 1 with matched sham feedback) to show that selective motor suppression depends on the veridical feedback itself. Experiment 3 further demonstrated the importance of veridical feedback by showing that selective motor suppression did not arise from mere mental imagery, even when incentivized with reward. Thus participants can use real-time feedback of TMS-induced MEPs to discover an effective mental strategy for selective motor suppression. This high-temporal-resolution, trial-by-trial-feedback training method could be used to help people better control response tendencies and may serve as a potential therapy for motor disorders such as Tourette's and dystonia.
Safety Evaluation of Local Weight‐Gain Formulas in the Saudi Arabian Markets
Authors: ALFaris Nora Abdullah , Al Ashban Riyadh Mohammed , Al Ojayan Mouna
Published: March 2015

Background. The utilization of herbal formulas is continuously increasing on the global level. However, assessment of contamination and impurities is the leading challenge in the use of herbal medicines. Objective. Assessment of therapeutic application in relation to herbal formulas usage for reducing weight is the objective for this investigation. Results. Reduced dietary fibers and fats are common outcomes of herbal usage. 9.8% of the mixtures were contaminated because of lead. However, investigation has indicated <10 microbial counts in herbal products. Increased levels of calcium, minerals, fibers, and lead traces have been identified in the herbals; however, products lacked nicotinamide, riboflavin, and vitamin C. Conclusion. It was concluded that majority of herbal products were pure and uncontaminated in order to reduce the complications of obesity efficiently.
Round Ligament of Uterus Leiomyoma: An Unusual Cause of Dyspareunia
Authors: Birge Ozer , Arslan Deniz , Kinali Erdinc , Bulut Berk
Published: March 2015

Round ligament of uterus leiomyoma is a rare, benign tumor of the vulva. Its incidence is not known exactly, and the mean age ranges from 13 to 70. Although clinical properties of benign and malignant diseases in the vulvar area are frequently similar, early diagnosis and treatment are essential. Local excision is recommended as definitive therapy. We present an 28-year-old female without any birth with a mass in anterior vaginal wall diagnosed as vulvar leiomyoma. In conclusion, a brief review of relevant literature emphasizes that leiomyomas are quite rare outside of the uterus but they might occur in any tissue or organ containing smooth muscle, spontaneously or parasitically after the spreading effect of an accident or surgical trauma. Clinicians should be alert especially for the diagnosis in a tissue with smooth muscle content.
Boosting VoIP Capacity via Service Differentiation in IEEE 802.11e EDCA Networks
Authors: Dong Pingping , Wang Jianxin , Wang Haodong , Pan Yi
Published: March 2015

This paper considers the performance problem of VoIP over 802.11e WLANs caused by the unfairness between uplink and downlink as well as the inefficient EDCA. A novel medium access control scheme named BEDCA (Balanced EDCA) is presented, which provides service differentiation between the access point (AP) and the mobile stations (STAs) to enhance VoIP capacity. In BEDCA, the expression of AP's contention window is obtained which is a relative constant value independent of the participating STAs. The minimum contention window of the STAs is traffic-aware based on the proposed algorithm. The performance improvement of BEDCA is verified through intensive simulations and the results show the capacity improvement of 82.1% compared to EDCA.
Fixed Point Approximation of Generalized Nonexpansive Mappings in Hyperbolic Spaces
Authors: Kim Jong Kyu , Pathak Ramesh Prasad , Dashputre Samir , Diwan Shailesh Dhar , Gupta Rajlaxmi
Published: March 2015

We prove strong and Δ-convergence theorems for generalized nonexpansive mappings in uniformly convex hyperbolic spaces using S-iteration process due to Agarwal et al. As uniformly convex hyperbolic spaces contain Banach spaces as well as CAT(0) spaces, our results can be viewed as extension and generalization of several well-known results in Banach spaces as well as CAT(0) spaces.
TNF-Related Apoptosis Inducing Ligand in Ocular Cancers and Ocular Diabetic Complications
Authors: Perri Paolo , Zauli Giorgio , Gonelli Arianna , Milani Daniela , Celeghini Claudio , Lamberti Giuseppe , Secchiero Paola
Published: March 2015

TNF-related apoptosis inducing ligand (TRAIL) is an intensively studied cytokine, in particular for its anticancer activity. The discovery that conjunctival sac fluid contains extremely high levels of soluble TRAIL as compared to other body fluids suggested important implications in the context of the immunological surveillance of the eye, in particular of the anterior surface. In this review, we discuss the potential physiopathologic and therapeutic role of the TRAIL/TRAIL receptor system in a variety of ocular cancers. Moreover, since an increasing amount of data has indicated the important biological activities of the TRAIL/TRAIL receptor systems also in a completely different pathologic context such as diabetes mellitus, in the second part of this review we summarize the currently available data on the involvement of TRAIL in the ocular complications of diabetes mellitus as modulator of the inflammatory and angiogenic response in the eye.
Mathematical Modeling of Uniaxial Mechanical Properties of Collagen Gel Scaffolds for Vascular Tissue Engineering
Authors: Irastorza Ramiro M. , Drouin Bernard , Blangino Eugenia , Mantovani Diego
Published: March 2015

Small diameter tissue‐engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney‐Rivlin inspired and Hammerstein models. The results suggest that Mooney‐Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.). When Akaike criterion is used, the best is the Mooney‐Rivlin inspired model.
Towards Multidimensional Radiotherapy: Key Challenges for Treatment Individualisation
Authors: Toma-Dasu Iuliana , Dasu Alexandru
Published: March 2015

Functional and molecular imaging of tumours have offered the possibility of redefining the target in cancer therapy and individualising the treatment with a multidimensional approach that aims to target the adverse processes known to impact negatively upon treatment result. Following the first theoretical attempts to include imaging information into treatment planning, it became clear that the biological features of interest for targeting exhibit considerable heterogeneity with respect to magnitude, spatial, and temporal distribution, both within one patient and between patients, which require more advanced solutions for the way the treatment is planned and adapted. Combining multiparameter information from imaging with predictive information from biopsies and molecular analyses as well as in treatment monitoring of tumour responsiveness appears to be the key approach to maximise the individualisation of treatment. This review paper aims to discuss some of the key challenges for incorporating into treatment planning and optimisation the radiobiological features of the tumour derived from pretreatment PET imaging of tumour metabolism, proliferation, and hypoxia and combining them with intreatment monitoring of responsiveness and other predictive factors with the ultimate aim of individualising the treatment towards the maximisation of response.
CEACAM1-3S Drives Melanoma Cells into NK Cell-Mediated Cytolysis and Enhances Patient Survival
Authors: Ullrich Nico , Heinemann Anja , Nilewski Elena , Scheffrahn Inka , Klode Joachim , Scherag André , Schadendorf Dirk , Singer Bernhard B. , Helfrich Iris
Published: March 2015

CEACAM1 is a widely expressed multifunctional cell–cell adhesion protein reported to serve as a poor prognosis marker in melanoma patients. In this study, we examine the functional and clinical contributions of the four splice isoforms of CEACAM1. Specifically, we present in vitro and in vivo evidence that they affect melanoma progression and immune surveillance in a negative or positive manner that is isoform specific in action. In contrast with isoforms CEACAM1-4S and CEACAM1-4L, expression of isoforms CEACAM1-3S and CEACAM1-3L is induced during disease progression shown to correlate with clinical stage. Unexpectedly, overall survival was prolonged in patients with advanced melanomas expressing CEACAM1-3S. The favorable effects of CEACAM1-3S related to enhanced immunogenicity, which was mediated by cell surface upregulation of NKG2D receptor ligands, thereby sensitizing melanoma cells to lysis by natural killer cells. Conversely, CEACAM1-4L downregulated cell surface levels of the NKG2D ligands MICA and ULBP2 by enhanced shedding, thereby promoting malignant character. Overall, our results define the splice isoform-specific immunomodulatory and cell biologic functions of CEACAM1 in melanoma pathogenesis. Cancer Res; 75(9); 1897–907. ©2015 AACR.
Phase I Trial of Arginine Deprivation Therapy with ADI-PEG 20 Plus Docetaxel in Patients with Advanced Malignant Solid Tumors
Authors: Tomlinson Benjamin K. , Thomson James A. , Bomalaski John S. , Diaz Monica , Akande Taiwo , Mahaffey Nichole , Li Tianhong , Dutia Mrinal P. , Kelly Karen , Gong I-Yeh , Semrad Thomas , Gandara David R. , Pan Chong-Xian , Lara Primo N.
Published: March 2015

Purpose: This phase I study examined the toxicity and tolerability of pegylated arginine deiminase (ADI-PEG 20) in combination with docetaxel in patients with advanced solid malignancies.

Experimental Design: Eligible patients had histologically proven advanced solid malignancies, with any number of prior therapies, Zubrod performance status 0–2, and adequate organ function. Patients received ADI-PEG 20 weekly intramuscular injection ranging from 4.5 to 36 mg/m2 and up to 10 doses of docetaxel (75 mg/m2) every 3 weeks. Primary endpoints were safety, toxicity, and a recommended phase II dose. Circulating arginine levels were measured before each cycle. Tumor response was measured as a secondary endpoint every 6 weeks on study.

Results: Eighteen patients received a total of 116 cycles of therapy through four dose levels of ADI-PEG 20. A single dose-limiting toxicity (grade 3 urticarial rash) was observed at the 1st dose level, with no additional dose-limiting toxicities observed. Hematologic toxicities were common with 14 patients experiencing at least one grade 3 to 4 leukopenia. Fatigue was the most prevalent toxicity reported by 16 patients. Arginine was variably suppressed with 10 patients achieving at least a 50% reduction in baseline values. In 14 patients with evaluable disease, four partial responses (including 2 patients with PSA response) were documented, and 7 patients had stable disease.

Conclusions: ADI-PEG 20 demonstrated reasonable toxicity in combination with docetaxel. Promising clinical activity was noted, and expansion cohorts are now accruing for both castrate-resistant prostate cancer and non–small cell lung cancer at a recommended phase II dose of 36 mg/m2. Clin Cancer Res; 21(11); 2480–6. ©2015 AACR.
From Histones to Ribosomes: A Chromatin Regulator Tangoes with Translation
Authors: Rothbart Scott B. , Dickson Bradley M. , Strahl Brian D.
Published: March 2015

Summary: Histone lysine methylation is a critical regulator of chromatin-templated processes such as gene transcription and DNA repair, and is dynamically controlled by enzymes that write and erase this posttranslational modification. Although histone methylation has been well studied, the functions of nonhistone lysine methylation and its regulatory enzymes, particularly outside the nucleus, are poorly defined. In this issue of Cancer Discovery, Van Rechem and colleagues shed light on a new role for the lysine demethylase KDM4A as a regulator of protein translation and identify a single-nucleotide polymorphism in the KDM4A gene as a candidate biomarker for mTOR inhibitor therapy. Cancer Discov; 5(3); 228–30. ©2015 AACR.

See related article by Van Rechem and colleagues, p. 245

See related article by Van Rechem and colleagues, p. 255
Aberrant Cytokine Production by Nonmalignant Cells in the Pathogenesis of Myeloproliferative Tumors and Response to JAK Inhibitor Therapies
Authors: Belver Laura , Ferrando Adolfo A.
Published: March 2015

Summary: Kleppe and colleagues use detailed cytokine profiling analyses to investigate the role of aberrant proinflammatory cytokine secretion in the pathogenesis of myeloproliferative neoplasms. Their analyses implicate constitutive activation of STAT3 in both malignant and nonmalignant bone marrow cell populations as a driver of aberrant cytokine secretion and as a cellular target mediating the therapeutic activity of ruxolitinib. Cancer Discov; 5(3); 234–6. ©2015 AACR.

See related article by Kleppe and colleagues, p. 316
Plasma fibrin clot phenotype independently affects intracoronary thrombus ultrastructure in patients with acute myocardial infarction
Authors: Bogaert Jan , Sadowski Marcin , Woznicka Olga , Doulaptsis Konstantinos , Ntoumpanaki Maria , Zabczyk Michal , Nessler Jadwiga , Undas Anetta , Zalewski Jaroslaw
Published: March 2015

summary

Determinants of intracoronary thrombus (ICT) composition in patients with ST-elevation myocardial infarction (STEMI) are largely unknown. We sought to investigate whether plasma fibrin phenotype and platelet reactivity affect ICT ultrastructure. We assessed the content of fibrin, platelets and erythrocytes including polyhedrocytes by scanning electron microscopy on the surface and inside ICT aspirated from 80 STEMI patients within 12 hours since chest pain onset. Plasma fibrin clot permeability (Ks), which indicates the average pore size, lysis time (t50 %), platelet reactivity index (PRI) and ADP-induced platelet aggregation (ADP5,20μM) were evaluated on admission. All patients received aspirin and 45 (56.3 %) 600 mg of clopidogrel, 80 (60–120) min prior to aspiration. Higher content of fibrin (61.6 vs 34.3 %, P< 0.0001) and platelets (8.2 vs 4.8 %, P=0.018) and lower erythrocyte content (15.8 vs 42.9 %, P< 0.0001) were found on ICT surface compared with its inner part. After adjustment for fibrinogen, in both ICT parts fibrin content was correlated with Ks (r≤-0.55, P< 0.0001) and t50% (r≥ 0.29, P≤ 0.02) but not with PRI and ADP5,20μM. Polyhedrocytes were observed in 16 (20 %) patients and their large amount expressed as ≥ 50 % fields of view covered by polyhedrocytes was associated with the lower PRI values (40 vs 69 %, P=0.015), but not Ks or t50%. By multivariate regression, Ks (β=-0.62, P< 0.0001), clopidogrel pretreatment (β=-0.36, P< 0.001), ischemia time (β=0.19, P=0.044) and family history (β=0.18, P=0.049) independently predicted fibrin content in the whole ICT (R2=0.65, P< 0.0001). Formation of denser plasma fibrin clots is independently associated with high fibrin content within the ICT in STEMI.
Treatment with dabigatran or warfarin in patients with venous thromboembolism and cancer
Authors: Goldhaber Samuel Z. , Kearon Clive , Kakkar Ajay K. , Schellong Sebastian , Eriksson Henry , Hantel Stefan , Feuring Martin , Kreuzer Jörg , Schulman Sam
Published: March 2015

The efficacy and safety of dabigatran for treatment of venous thromboembolism (VTE) were demonstrated in two trials. It is unclear if the results pertain to patients with cancer and VTE. Data from two randomised trials comparing dabigatran and warfarin for acute VTE were pooled. Primary efficacy outcome was symptomatic recurrent VTE and related death from randomisation to the end of the treatment period. Safety outcomes were major, major and clinically relevant non-major, and any bleeding during the oral-only treatment period. Patients with active cancer (=within 5 years) at baseline or diagnosed during the study were analysed. Compared with 4,772 patients without cancer, recurrent VTE occurred more frequently in 335 patients with cancer at any time (hazard ratio [HR] 3.3; 95 % confidence interval [CI], 2.1–5.3) and more often in 114 with cancer diagnosed during the study compared to 221 with cancer at baseline (HR 2.6; 95 % CI, 1.1–6.2). There was no significant difference in efficacy between dabigatran and warfarin for cancer at baseline (HR 0.75; 95 % CI, 0.20–2.8) or diagnosed during the study (HR 0.63; 95 % CI, 0.20–2.0). Major bleeding (HR 4.1; 95 % CI, 2.2–7.5) and any bleeding (HR 1.5; 95 % CI, 1.2–2.0) were more frequent in patients with cancer than without, but with similar incidence in cancer with dabigatran or warfarin. In conclusion, in cancer patients, dabigatran provided similar clinical benefit as warfarin. VTE recurrence or bleeding were similar in patients on dabigatran or warfarin. The efficacy of dabigatran has not been assessed in comparison with low-molecular-weight heparin.
Doce de série: as aventuras de dona Picucha
Authors: Duarte Elizabeth Bastos
Published: March 2015

O trabalho propõe-se a analisar as especificidades do formato adotado pelo seriado Doce de mãe, em comparação com as normas que presidem o subgênero sitcom, em relação ao tema central e temáticas secundárias privilegiadas, ao seu processo de actorialização e, mais particularmente, ao seu processo de tonalização, ou seja, à combinatória tonal conferida ao sitcom, que com ela interpela os telespectadores e dota de identidade o programa.

 
Narrativas Sensoriais
Authors: Oliveira Rodrigo Campos
Published: March 2015

Sensorialidade e afeto determinariam uma nova virada epistemológica na arte e na estética contemporânea, permeando obras audiovisuais e narrativas rumo a uma maior indeterminação de sua relação com o espectador, que é levado à novos patamares de fruição e interação.
Genetic Ablation of PDGF-Dependent Signaling Pathways Abolishes Vascular Remodeling and Experimental Pulmonary Hypertension
Authors: ten Freyhaus Henrik , Berghausen Eva M. , Janssen Wiebke , Leuchs Maike , Zierden Mario , Murmann Kirsten , Klinke Anna , Vantler Marius , Caglayan Evren , Kramer Tilmann , Baldus Stephan , Schermuly Ralph T. , Tallquist Michelle D. , Rosenkranz Stephan
Published: March 2015

Objective—

Despite modern therapies, pulmonary arterial hypertension (PAH) harbors a high mortality. Vascular remodeling is a hallmark of the disease. Recent clinical studies revealed that antiremodeling approaches with tyrosine–kinase inhibitors such as imatinib are effective, but its applicability is limited by significant side effects. Although imatinib has multiple targets, expression analyses support a role for platelet-derived growth factor (PDGF) in the pathobiology of the disease. However, its precise role and downstream signaling events have not been established.

Approach and Results—

Patients with PAH exhibit enhanced expression and phosphorylation of β PDGF receptor (βPDGFR) in remodeled pulmonary arterioles, particularly at the binding sites for phophatidyl-inositol-3-kinase and PLCγ at tyrosine residues 751 and 1021, respectively. These signaling molecules were identified as critical downstream mediators of βPDGFR-mediated proliferation and migration of pulmonary arterial smooth muscle cells. We, therefore, investigated mice expressing a mutated βPDGFR that is unable to recruit phophatidyl-inositol-3-kinase and PLCγ (βPDGFR
F3/F3
). PDGF-dependent Erk1/2 and Akt phosphorylation, cyclin D1 induction, and proliferation, migration, and protection against apoptosis were abolished in βPDGFR
F3/F3
pulmonary arterial smooth muscle cells. On exposure to chronic hypoxia, vascular remodeling of pulmonary arteries was blunted in βPDGFR
F3/F3
mice compared with wild-type littermates. These alterations led to protection from hypoxia-induced PAH and right ventricular hypertrophy.

Conclusions—

By means of a genetic approach, our data provide definite evidence that the activated βPDGFR is a key contributor to pulmonary vascular remodeling and PAH. Selective disruption of PDGF-dependent phophatidyl-inositol-3-kinase and PLCγ activity is sufficient to abolish these pathogenic responses in vivo, identifying these signaling events as valuable targets for antiremodeling strategies in PAH.
Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β
1
-Adrenergic Stimulation
Authors: Tong Carl W. , Wu Xin , Liu Yang , Rosas Paola C. , Sadayappan Sakthivel , Hudmon Andy , Muthuchamy Mariappan , Powers Patricia A. , Valdivia Héctor H. , Moss Richard L.
Published: March 2015

Background—

Mammalian hearts exhibit positive inotropic responses to β-adrenergic stimulation as a consequence of protein kinase A–mediated phosphorylation or as a result of increased beat frequency (the Bowditch effect). Several membrane and myofibrillar proteins are phosphorylated under these conditions, but the relative contributions of these to increased contractility are not known. Phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) by protein kinase A accelerates the kinetics of force development in permeabilized heart muscle, but its role in vivo is unknown. Such understanding is important because adrenergic responsiveness of the heart and the Bowditch effect are both depressed in heart failure.

Methods and Results—

The roles of cMyBP-C phosphorylation were studied using mice in which either WT or nonphosphorylatable forms of cMyBP-C [ser273ala, ser282ala, ser302ala: cMyBP-C(t3SA)] were expressed at similar levels on a cMyBP-C null background. Force and [Ca
2+
]
in
measurements in isolated papillary muscles showed that the increased force and twitch kinetics because increased pacing or β
1
-adrenergic stimulation were nearly absent in cMyBP-C(t3SA) myocardium, even though [Ca
2+
]
in
transients under each condition were similar to WT. Biochemical measurements confirmed that protein kinase A phosphorylated ser273, ser282, and ser302 in WT cMyBP-C. In contrast, CaMKIIδ, which is activated by increased pacing, phosphorylated ser302 principally, ser282 to a lesser degree, and ser273 not at all.

Conclusions—

Phosphorylation of cMyBP-C increases the force and kinetics of twitches in living cardiac muscle. Further, cMyBP-C is a principal mediator of increased contractility observed with β-adrenergic stimulation or increased pacing because of protein kinase A and CaMKIIδ phosphorylations of cMyB-C.
Progressive Cognitive Deficits in a Mouse Model of Recurrent Photothrombotic Stroke
Authors: Schmidt Antje , Diederich Kai , Strecker Jan-Kolja , Geng Birgit , Hoppen Maike , Duning Thomas , Schäbitz Wolf-Rüdiger , Minnerup Jens
Published: March 2015

Background and Purpose—

In spite of its high disease burden, there is no specific treatment for multi-infarct dementia. The preclinical evaluation of candidate drugs is limited because an appropriate animal model is lacking. Therefore, we aimed to evaluate whether a mouse model of recurrent photothrombotic stroke is suitable for the preclinical investigation of multi-infarct dementia.

Methods—

Recurrent photothrombotic cortical infarcts were induced in 25 adult C57BL/6 mice. Twenty-five sham-operated animals served as controls. The object recognition test and the Morris water maze test were performed >6 weeks to assess cognitive deficits. Afterward, histological analyses were performed to characterize histopathologic changes associated with recurrent photothrombotic infarcts.

Results—

After the first infarct, the object recognition test showed a trend toward an impaired formation of recognition memories (
P
=0.08), and the Morris Water Maze test revealed significantly impaired spatial learning and memory functions (
P
<0.05). After recurrent infarcts, the object recognition test showed significant recognition memory deficits (
P
<0.001) and the Morris water maze test demonstrated persisting spatial learning and memory deficits (
P
<0.05). Histological analyses revealed remote astrogliosis in the hippocampus.

Conclusions—

Our results show progressive cognitive deficits in a mouse model of recurrent photothrombotic stroke. The presented model resembles the clinical features of human multi-infarct dementia and enables the investigation of its pathophysiological mechanisms and the evaluation of treatment strategies.
Ranking Knowledge in the Philebus
Authors: Carpenter Amber D.
Published: March 2015

Socrates’ concise examination of intelligence in the Philebus is framed with the odd ambition to discover which knowledges are more closely related to knowledge. If we take Plato’s epistemology here to be ‘paradeigmatist’, this and other oddities of the passage disappear; we can then read it as articulating that paradigm, setting procedural as well as objectual constraints on perfect knowledge. While all cognitive disciplines, however lowly, aim at this perfect knowledge, most necessarily fall short of this ideal. This explains Socrates’ extraordinary inclusiveness and simultaneous ambivalence about the cognitive value and success of ordinary crafts, for the paradeigmatist can grant or withdraw knowledge-claims flexibly, but not arbitrarily, and without equivocation on ‘knowing’. In the Philebus, this provides an understanding of everyday cognitive practices as beneficial and good, apart from their practical usefulness, and it illuminates one aspect of the Philebus’ claim that pleasures are themselves truth-apt, and truth-aiming.
New record of Anelytra (Anelytra) eunigrifrons Ingrisch, 1998 (Orthoptera, Tettigoniidae: Conocephalinae, Agraeciini) from India
Authors: NAGAR RAJENDRA , MAL JHABAR , SWAMINATHAN R.
Published: March 2015

The record of Anelytra (Anelytra) eunigrifrons Ingrisch, 1998 (Conocephlinae: Agraeciini) collected from Umiam in the North-east province, Meghalaya (India) is reported for the first time. Previously, the species was reported from Indo-China, Myanmar Burma, and Shan province, Carin Ghecu (Ingrisch, February 01, 1888 to March 31, 1888 and 1998). From India only one species, Anelytra (Anelytra) concolor  Redtenbacher, 1891 has been recorded from Maharashtra, Mumbai. The paper includes the morphological characterization of the male of this species collected from North-east India.
A taxonomic note on Erionota acroleuca (Wood-Mason & de Nicéville, 1881) stat. rest. (Lepidoptera: Hesperiidae)
Authors: XUE GUO-XI , LO YIK FUI PHILIP
Published: March 2015

The purpose of this paper is to restore Erionota acroleuca (Wood-Mason & de Nicéville, 1881) as a valid name, and to establish Erionota acroleuca apicalis de Jong & Treadaway, 1992 as a new subspecific combination, with its immature biology briefly introduced.
USH2 Caused by GPR98 Mutation Diagnosed by Massively Parallel Sequencing in Advance of the Occurrence of Visual Symptoms
Authors: Moteki Hideaki , Yoshimura Hidekane , Azaiez Hela , Booth Kevin T. , Shearer A. Eliot , Sloan Christina M. , Kolbe Diana L. , Murata Toshinori , Smith Richard J. H. , Usami Shin-ichi
Published: March 2015

Objective:

We present 2 patients who were identified with mutations in the GPR98 gene that causes Usher syndrome type 2 (USH2).

Methods:

One hundred ninety-four (194) Japanese subjects from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were used to identify the genetic causes of hearing loss.

Results:

We identified causative mutations in the GPR98 gene in 1 family (2 siblings). The patients had moderate sloping hearing loss, and no progression was observed over a period of 10 years. Fundus examinations were normal. However, electroretinograms revealed impaired responses in both patients.

Conclusion:

Early diagnosis of Usher syndrome has many advantages for patients and their families. This study supports the use of comprehensive genetic diagnosis for Usher syndrome, especially prior to the onset of visual symptoms, to provide the highest chance of diagnostic success in early life stages.
Re-reading masculine organization: Phallic, testicular and seminal metaphors
Authors: Linstead Stephen A , Maréchal Garance
Published: March 2015

This article examines the metaphorical resources provided by specific parts of the male body for thinking masculinity in social and organizational contexts. The genital metaphor of the male phallus is the most familiar, being associated with a form of hegemonic masculinity identified with power and control. However, other parts of the male genitalia can and do act as root metaphors for alternative forms of masculinity. Where the phallic metaphor focuses attention on power and control, the testicular and seminal metaphors highlight aspects of masculinity that are more relational and creative and bring it closer to the feminine. Whilst in social and organizational practice these coexist, in organizational analysis the emphasis has implicitly and explicitly been on the phallic. We generate a framework of the characteristics of each metaphor identifying positive, negative and excessive/inverted modalities that they can take, especially within organizational and institutional settings. We argue that applying a richer metaphorical frame to the study of gendered organizations will facilitate the acknowledgement of neglected potentials in masculinity for co-creating initiatives for organizational change.
Playing Normative Legacies
Authors: Schulze-Cleven Tobias , Weishaupt J. Timo
Published: March 2015

Europe’s affluent democracies adopted different policy strategies to buffer their labor markets from the effects of the worldwide recession that followed the financial crisis in 2007. This article offers a sociologically anchored historical institutionalist explanation to account for this divergence. Reviewing the politics of employment policymaking before, during, and after the crisis in the United Kingdom, Germany, and Denmark, the article traces partisan actors’ tactics of maneuvering within the constraints of institutionally embedded mass preferences to legitimate their policies and improve their electoral performance. The analysis moves beyond contemporary treatments of path-dependent institutional evolution in two important ways. Rather than focusing on how arrangements at the work-welfare nexus provide actors with particular functional benefits and differential power resources, it examines institutions’ ideational effects on the construction of electorates’ interests. Moreover, it illuminates partisan politicians’ room for strategic agency, breaking with interpretations that view government responses as the product of particular producer group coalitions.