bluuebunny/crossref_metadata_2025 huggingface dataset:
Out-of-Equilibrium Dynamics with Heterogeneous Capital Goods
Authors: Veetil Vipin P.
Published: June 2016

This paper studies the problem of accumulating heterogeneous capital goods in an economy with imperfect markets populated by boundedly rational agents. It relaxes classical assumptions about information and cognition. The agents are not capable of computing an equilibrium path to steady state. Agents discover prices by interacting with each other. The economy accumulates a near-optimal mix of capital goods. The structure of interactions between agents filters their behavior in such a way that limited rationality at the micro-level does not translate to grossly inefficient outcomes at the macro-level.
Efficient Query Processing in 3D Motion Capture Gesture Databases
Authors: Beecks Christian , Hassani Marwan , Brenger Bela , Hinnell Jennifer , Schüller Daniel , Mittelberg Irene , Seidl Thomas
Published: June 2016

One of the most fundamental challenges when accessing gestural patterns in 3D motion capture databases is the definition of spatiotemporal similarity. While distance-based similarity models such as the Gesture Matching Distance on gesture signatures are able to leverage the spatial and temporal characteristics of gestural patterns, their applicability to large 3D motion capture databases is limited due to their high computational complexity. To this end, we present a lower bound approximation of the Gesture Matching Distance that can be utilized in an optimal multi-step query processing architecture in order to support efficient query processing. We investigate the performance in terms of accuracy and efficiency based on 3D motion capture databases and show that our approach is able to achieve an increase in efficiency of more than one order of magnitude with a negligible loss in accuracy. In addition, we discuss different applications in the digital humanities in order to highlight the significance of similarity search approaches in the research field of gestural pattern analysis.
Stability analysis of hybrid neural networks with impulsive time window
Authors: Wang Xin , Wang Hui , Li Chuandong , Huang Tingwen
Published: June 2016

The urgent problem with impulsive moments cannot be determined in advance brings new challenges beyond the conventional impulsive systems theory. In order to solve this problem, in this paper, a novel class of system with impulsive time window is proposed. Different from the conventional impulsive control strategies, the main characteristic of the impulsive time window is that impulse occurs in a random manner. Moreover, for the importance of the hybrid neural networks, using switching Lyapunov functions and a generalized Hanlanay inequality, some general criteria for asymptotic and exponential stability of the hybrid neural networks with impulsive time window are established. Finally, some simulations are provided to further illustrate the effectiveness of the results.
Portfolio Selection with Transaction Costs and Jump-Diffusion Asset Dynamics I: A Numerical Solution
Authors: Czerwonko Michal , Perrakis Stylianos
Published: June 2016

We derive allocation rules under isoelastic utility for a mixed jump-diffusion process in a two-asset portfolio selection problem with finite horizon in the presence of proportional transaction costs. We adopt a discrete-time formulation, let the number of periods go to infinity, and show that it converges efficiently to the continuous-time solution for the cases where this solution is known. We then apply this discretization to derive numerically the boundaries of the region of no transactions. Our discrete-time numerical approach outperforms alternative continuous-time approximations of the problem.
Neutron Scattering from Polymers: Five Decades of Developing Possibilities
Authors: Higgins J.S.
Published: June 2016

The first three decades of my research career closely map the development of neutron scattering techniques for the study of molecular behavior. At the same time, the theoretical understanding of organization and motion of polymer molecules, especially in the bulk state, was developing rapidly and providing many predictions crying out for experimental verification. Neutron scattering is an ideal technique for providing the necessary evidence. This autobiographical essay describes the applications by my research group and other collaborators of increasingly sophisticated neutron scattering techniques to observe and understand molecular behavior in polymeric materials. It has been a stimulating and rewarding journey.
Polyunsaturated fatty acids inhibit Kv1.4 by interacting with positively charged extracellular pore residues
Authors: Farag N. E. , Jeong D. , Claydon T. , Warwicker J. , Boyett M. R.
Published: June 2016

Polyunsaturated fatty acids (PUFAs) modulate voltage-gated K+ channel inactivation by an unknown site and mechanism. The effects of ω-6 and ω-3 PUFAs were investigated on the heterologously expressed Kv1.4 channel. PUFAs inhibited wild-type Kv1.4 during repetitive pulsing as a result of slowing of recovery from inactivation. In a mutant Kv1.4 channel lacking N-type inactivation, PUFAs reversibly enhanced C-type inactivation ( Kd, 15–43 μM). C-type inactivation was affected by extracellular H+ and K+ as well as PUFAs and there was an interaction among the three: the effect of PUFAs was reversed during acidosis and abolished on raising K+. Replacement of two positively charged residues in the extracellular pore (H508 and K532) abolished the effects of the PUFAs (and extracellular H+ and K+) on C-type inactivation but had no effect on the lipoelectric modulation of voltage sensor activation, suggesting two separable interaction sites/mechanisms of action of PUFAs. Charge calculations suggest that the acidic head group of the PUFAs raises the pKa of H508 and this reduces the K+ occupancy of the selectivity filter, stabilizing the C-type inactivated state.
Secretin, at the hub of water-salt homeostasis
Authors: Bai Jenny Juan , Tan Chong Da , Chow Billy K. C.
Published: June 2016

Water and salt metabolism are tightly regulated processes. Maintaining this milieu intérieur within narrow limits is critical for normal physiological processes to take place. Disturbances to this balance can result in disease and even death. Some of the better-characterized regulators of water and salt homeostasis include angiotensin II, aldosterone, arginine vasopressin, and oxytocin. Although secretin (SCT) was first described >100 years ago, little is known about the role of this classic gastrointestinal hormone in the maintenance of water-salt homeostasis. In recent years, increasing body of evidence suggested that SCT and its receptor play important roles in the central nervous system and kidney to ensure that the mammalian extracellular fluid osmolarity is kept within a healthy range. In this review, we focus on recent advances in our understanding of the molecular, cellular, and network mechanisms by which SCT and its receptor mediate the control of osmotic homeostasis. Implications of hormonal cross talk and receptor-receptor interaction are highlighted.
Organization of cortico-cortical pathways supporting memory retrieval across subregions of the left ventrolateral prefrontal cortex
Authors: Barredo Jennifer , Verstynen Timothy D. , Badre David
Published: June 2016

Functional magnetic resonance imaging (fMRI) evidence indicates that different subregions of ventrolateral prefrontal cortex (VLPFC) participate in distinct cortical networks. These networks have been shown to support separable cognitive functions: anterior VLPFC [inferior frontal gyrus (IFG) pars orbitalis] functionally correlates with a ventral fronto-temporal network associated with top-down influences on memory retrieval, while mid-VLPFC (IFG pars triangularis) functionally correlates with a dorsal fronto-parietal network associated with postretrieval control processes. However, it is not known to what extent subregional differences in network affiliation and function are driven by differences in the organization of underlying white matter pathways. We used high-angular-resolution diffusion spectrum imaging and functional connectivity analysis in unanesthetized humans to address whether the organization of white matter connectivity differs between subregions of VLPFC. Our results demonstrate a ventral-dorsal division within IFG. Ventral IFG as a whole connects broadly to lateral temporal cortex. Although several different individual white matter tracts form connections between ventral IFG and lateral temporal cortex, functional connectivity analysis of fMRI data indicates that these are part of the same ventral functional network. By contrast, across subdivisions, dorsal IFG was connected with the midfrontal gyrus and correlated as a separate dorsal functional network. These qualitative differences in white matter organization within larger macroanatomical subregions of VLPFC support prior functional distinctions among these regions observed in task-based and functional connectivity fMRI studies. These results are consistent with the proposal that anatomical connectivity is a crucial determinant of systems-level functional organization of frontal cortex and the brain in general.
Startle reveals decreased response preparatory activation during a stop-signal task
Authors: Drummond Neil M. , Cressman Erin K. , Carlsen Anthony N.
Published: June 2016

In a stop-signal task participants are instructed to initiate a movement in response to a go signal, but to inhibit this movement if an infrequent stop signal is presented after the go. Reaction time (RT) in a stop-signal task is typically longer compared with that in a simple RT task, which may be attributed to a reduced readiness to initiate the response caused by the possibility of having to inhibit the response. The purpose of this experiment was to probe the preparatory activation level of the motor response during a stop-signal task using a startling acoustic stimulus (SAS), which has been shown to involuntarily trigger sufficiently prepared responses at a short latency. Participants completed two separate tasks: a simple RT task, followed by a stop-signal RT task. During both tasks, an SAS (120 dB) was pseudorandomly presented concurrently with the go signal. As expected, RT during the simple RT task was significantly shorter than during the stop-signal task. A significant reduction in RT was noted when an SAS was presented during the simple RT task; however, during the stop-signal task, an SAS resulted in either a significant speeding or a moderate delay in RT. Additionally, the subset of SAS trial responses with the shortest RT latencies produced during the stop-signal task were also delayed compared with the short-latency SAS trial responses observed during the simple RT task. Despite evidence that a response was prepared in advance of the go signal during a stop-signal task, it appears that the amount of preparatory activation was reduced compared with that achieved during a simple RT task.
Additive Effect of Qidan Dihuang Grain, a Traditional Chinese Medicine, and Angiotensin Receptor Blockers on Albuminuria Levels in Patients with Diabetic Nephropathy: A Randomized, Parallel‐Controlled Trial
Authors: Xiang Lei , Jiang Pingping , Zhou Lin , Sun Xiaomin , Bi Jianlu , Cui Lijuan , Nie Xiaoli , Luo Ren , Zhao Xiaoshan , Liu Yanyan
Published: June 2016

Albuminuria is characteristic of early‐stage diabetic nephropathy (DN). The conventional treatments with angiotensin receptor blockers (ARB) are unable to prevent the development of albuminuria in normotensive individuals with type 2 diabetes mellitus (T2DM). Purpose. The present study aimed to evaluate the effect of ARB combined with a Chinese formula Qidan Dihuang grain (QDDHG) in improving albuminuria and Traditional Chinese Medicine Symptom (TCMS) scores in normotensive individuals with T2DM. Methods. Eligible patients were randomized to the treatment group and the control group. Results. Compared with baseline (week 0), both treatment and control groups markedly improved the 24‐hour albuminuria, total proteinuria (TPU), and urinary albumin to creatinine ratio (A/C) at 4, 8, and 12 weeks. Between treatment and the control group, the levels of albuminuria in the treatment group were significantly lower than in the control group at 8 and 12 weeks (p < 0.05). In addition, treatment group markedly decreased the scores of TCMS after treatment. Conclusion. This trial suggests that QDDHG combined with ARB administration decreases the levels of albuminuria and the scores for TCMS in normotensive individuals with T2DM.
Hausdorff Dimension of a Random Attractor for Stochastic Boussinesq Equations with Double Multiplicative White Noises
Authors: Li Yin , Wei Ruiying , Cai Donghong
Published: June 2016

This paper investigates the existence of random attractor for stochastic Boussinesq equations driven by multiplicative white noises in both the velocity and temperature equations and estimates the Hausdorff dimension of the random attractor.
Sparse Representation Based Binary Hypothesis Model for Hyperspectral Image Classification
Authors: Tang Yidong , Huang Shucai , Xue Aijun
Published: June 2016

The sparse representation based classifier (SRC) and its kernel version (KSRC) have been employed for hyperspectral image (HSI) classification. However, the state-of-the-art SRC often aims at extended surface objects with linear mixture in smooth scene and assumes that the number of classes is given. Considering the small target with complex background, a sparse representation based binary hypothesis (SRBBH) model is established in this paper. In this model, a query pixel is represented in two ways, which are, respectively, by background dictionary and by union dictionary. The background dictionary is composed of samples selected from the local dual concentric window centered at the query pixel. Thus, for each pixel the classification issue becomes an adaptive multiclass classification problem, where only the number of desired classes is required. Furthermore, the kernel method is employed to improve the interclass separability. In kernel space, the coding vector is obtained by using kernel-based orthogonal matching pursuit (KOMP) algorithm. Then the query pixel can be labeled by the characteristics of the coding vectors. Instead of directly using the reconstruction residuals, the different impacts the background dictionary and union dictionary have on reconstruction are used for validation and classification. It enhances the discrimination and hence improves the performance.
Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice
Authors: Moreno Ávila Claudia Leticia , Limón-Pacheco Jorge H. , Giordano Magda , Rodríguez Verónica M.
Published: June 2016

Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system.
Diagnostic, Prognostic, and Therapeutic Value of Circulating miRNAs in Heart Failure Patients Associated with Oxidative Stress
Authors: Ali Sheikh Md Sayed , Salma Umme , Zhang Baohai , Chen Jimei , Zhuang Jian , Ping Zhu
Published: June 2016

Heart failure is a major public health problem especially in the aging population (≥65 years old), affecting nearly 5 million Americans and 15 million European people. Effective management of heart failure (HF) depends on a correct and rapid diagnosis. Presently, BNP (brain natriuretic peptide) or N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) assay is generally accepted by the international community for diagnostic evaluation and risk stratification of patients with HF. However, regardless of its widespread clinical use, BNP is still encumbered by reduced specificity. As a result, diagnosis of heart failure remains challenging. Although significant improvement happened in the clinical management of HF over the last 2 decades, traditional treatments are ultimately ineffective in many patients who progress to advanced HF. Therefore, a novel diagnostic, prognostic biomarker and new therapeutic approach are required for clinical management of HF patients. Circulating miRNAs seem to be the right choice for novel noninvasive biomarkers as well as new treatment strategies for HF. In this review, we briefly discuss the diagnostic, prognostic, and therapeutic role of circulating miRNAs in heart failure patients. We also mentioned our own technique of extraction of RNA and detection of circulating miRNAs from human plasma and oxidative stress associated miRNAs with HF.
Pinning Cluster Synchronization in Linear Hybrid Coupled Delayed Dynamical Networks
Authors: Bao Anping , Wang Ting , Fei Shumin , Tian Xiaomin
Published: June 2016

The problem on cluster synchronization will be investigated for a class of delayed dynamical networks based on pinning control strategy. Through utilizing the combined convex technique and Kronecker product, two sufficient conditions can be derived to ensure the desired synchronization when the designed feedback controller is employed to each cluster. Moreover, the inner coupling matrices are unnecessarily restricted to be diagonal and the controller design can be converted into solving a series of linear matrix inequalities (LMIs), which greatly improve the present methods. Finally, two numerical examples are provided to demonstrate the effectiveness and reduced conservatism.
Induction of Mast Cell Accumulation by Tryptase via a Protease Activated Receptor-2 and ICAM-1 Dependent Mechanism
Authors: Liu Xin , Wang Junling , Zhang Huiyun , Zhan Mengmeng , Chen Hanqiu , Fang Zeman , Xu Chiyan , Chen Huifang , He Shaoheng
Published: June 2016

Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection. Inhibitors of tryptase, an antagonist of PAR-2 FSLLRY-NH2, and pretreatment of mice with anti-ICAM-1, anti-CD11a, and anti-CD18 antibodies dramatically diminished tryptase induced mast cell accumulation. On the other hand, PAR-2 agonist peptides SLIGRL-NH2and tc-LIGRLO-NH2provoked mast cell accumulation following injection. These implicate that tryptase induced mast cell accumulation is dependent on its enzymatic activity, activation of PAR-2, and interaction between ICAM-1 and LFA-1. Moreover, induction of trans-endothelium migration of mast cellsin vitroindicates that tryptase acts as a chemoattractant. In conclusion, provocation of mast cell accumulation by mast cell tryptase suggests a novel self-amplification mechanism of mast cell accumulation. Mast cell stabilizers as well as PAR-2 antagonist agents may be useful for treatment of allergic reactions.
RBF-Based Meshless Method for Large Deflection of Elastic Thin Rectangular Plates with Boundary Conditions Involving Free Edges
Authors: Hussein Al-Tholaia Mohammed M. , Al-Gahtani Husain Jubran
Published: June 2016

An RBF-based meshless method is presented for the analysis of thin plates undergoing large deflection. The method is based on collocation with the multiquadric radial basis function (MQ-RBF). In the proposed method, the resulting coupled nonlinear equations are solved using an incremental-iterative procedure. The accuracy and efficiency of the method are verified through several numerical examples. The inclusion of the free edge boundary condition proves that this method is accurate and efficient in handling such complex boundary value problems.
Consensus of Third-Order Multiagent Systems with Time Delay in Undirected Networks
Authors: Cao Yanfen , Sun Yuangong
Published: June 2016

We consider consensus of a class of third-order continuous-time multiagent systems with time delay in undirected networks. By using matrix analysis and a frequency domain approach, a necessary and sufficient condition for consensus is established. A simulation result is also given to illustrate the main theoretical result.
Regional Influences on Chinese Medicine Education: Comparing Australia and Hong Kong
Authors: Brosnan Caragh , Chung Vincent C. H. , Zhang Anthony L. , Adams Jon
Published: June 2016

High quality education programs are essential for preparing the next generation of Chinese medicine (CM) practitioners. Currently, training in CM occurs within differing health and education policy contexts. There has been little analysis of the factors influencing the form and status of CM education in different regions. Such a task is important for understanding how CM is evolving internationally and predicting future workforce characteristics. This paper compares the status of CM education in Australia and Hong Kong across a range of dimensions: historical and current positions in the national higher education system, regulatory context and relationship to the health system, and public and professional legitimacy. The analysis highlights the different ways in which CM education is developing in these settings, with Hong Kong providing somewhat greater access to clinical training opportunities for CM students. However, common trends and challenges shape CM education in both regions, including marginalisation from mainstream health professions, a small but established presence in universities, and an emphasis on biomedical research. Three factors stand out as significant for the evolution of CM education in Australia and Hong Kong and may have international implications: continuing biomedical dominance, increased competition between universities, and strengthened links with mainland China.
Changes in Blood Components in Aphtha Patients with Excess Heat
Authors: Qin Lu , Li Yan , Jiao Yifeng , Fu Danqing , Ye Li , Ji Jinjun , Xie Guanqun , Fan Yongsheng , Xu Li
Published: June 2016

“Superior heat” is a popularization expression in TCM heat syndrome and has no counterpart in the modern medical system concept. Oral ulcer is considered to be a kind of clinical manifestation of “superior heat.” Aphtha is a common and frequently occurring disease, which can be divided into excess heat and Yin deficiency. The aphtha of excess heat manifests the syndromes of acute occurrence, severe local symptoms, obvious swelling and pain, red tongue, yellow coating, and fast‐powerful pulse. In this study, we found that there was an abnormal immune regulation in aphtha patients induced by excess heat. There are changes in the blood components, including abnormal serum protein expression (IL‐4, MMP‐19, MMP‐9, and Activin A) and a higher percentage of CD4+CD25+Treg cells in the peripheral blood lymphocytes of the EXP group. Changes in the blood environment may be an important factor in the occurrence of aphtha caused by excess heat.
Small Interfering RNA Targeted to ASPP2 Promotes Progression of Experimental Proliferative Vitreoretinopathy
Authors: Chen Xiao-Li , Bai Yu-Jing , Hu Qin-Rui , Li Shan-Shan , Huang Lv-Zhen , Li Xiao-Xin
Published: June 2016

Background. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) is vital in proliferative vitreoretinopathy (PVR) development. Apoptosis-stimulating proteins of p53 (ASPP2) have recently been reported to participate in EMT. However, the role of ASPP2 in PVR pathogenesis has not been identified.Methods. Immunohistochemistry was used to investigate the expression of ASPP2 in epiretinal membranes of PVR patients. ARPE-19 cells were transfected with ASPP2-siRNA, followed with measurement of cell cytotoxicity, proliferation, and migration ability. EMT markers and related inflammatory and fibrosis cytokines were measured by western blot or flow cytometry. Additionally, PVR rat models were induced by intravitreal injection of ARPE-19 cells transfected with ASPP2-siRNA and evaluated accordingly.Results. Immunofluorescence analysis revealed less intense expression of ASPP2 in PVR membranes. ASPP2 knockdown facilitated the proliferation and migration of RPE cells and enhanced the expression of mesenchymal markers such as alpha smooth muscle actin, fibronectin, and ZEB1. Meanwhile, ASPP2-siRNA increased EMT-related and inflammatory cytokines, including TGF-β, CTGF, VEGF, TNF-α, and interleukins. PVR severities were more pronounced in the rat models with ASPP2-siRNA treatment.Conclusions. ASPP2 knockdown promoted EMT of ARPE-19 cellsin vitroand exacerbated the progression of experimental PVRin vivo, possibly via inflammatory and fibrosis cytokines.
Cost-Effective Brillouin Optical Time-Domain Analysis Sensor Using a Single Optical Source and Passive Optical Filtering
Authors: Iribas H. , Urricelqui J. , Mariñelarena J. , Sagues M. , Loayssa A.
Published: June 2016

We present a simplified configuration for distributed Brillouin optical time-domain analysis sensors that aims to reduce the cost of the sensor by reducing the number of components required for the generation of the two optical waves involved in the sensing process. The technique is based on obtaining the pump and probe waves by passive optical filtering of the spectral components generated in a single optical source that is driven by a pulsed RF signal. The optical source is a compact laser with integrated electroabsorption modulator and the optical filters are based on fiber Bragg gratings. Proof-of-concept experiments demonstrate 1 m spatial resolution over a 20 km sensing fiber with a 0.9 MHz precision in the measurement of the Brillouin frequency shift, a performance similar to that of much more complex setups. Furthermore, we discuss the factors limiting the sensor performance, which are basically related to residual spectral components in the filtering process.
Reduced Expression of Histone Methyltransferases KMT2C and KMT2D Correlates with Improved Outcome in Pancreatic Ductal Adenocarcinoma
Authors: Dawkins Joshua B.N. , Wang Jun , Maniati Eleni , Heward James A. , Koniali Lola , Kocher Hemant M. , Martin Sarah A. , Chelala Claude , Balkwill Frances R. , Fitzgibbon Jude , Grose Richard P.
Published: June 2016

Genes encoding the histone H3 lysine 4 methyltransferases KMT2C and KMT2D are subject to deletion and mutation in pancreatic ductal adenocarcinoma (PDAC), where these lesions identify a group of patients with a more favorable prognosis. In this study, we demonstrate that low KMT2C and KMT2D expression in biopsies also defines better outcome groups, with median survivals of 15.9 versus 9.2 months (P = 0.029) and 19.9 versus 11.8 months (P = 0.001), respectively. Experiments with eight human pancreatic cell lines showed attenuated cell proliferation when these methyltransferases were depleted, suggesting that this improved outcome may reflect a cell-cycle block with diminished progression from G0–G1. RNA-seq analysis of PDAC cell lines following KMT2C or KMT2D knockdown identified 31 and 124 differentially expressed genes, respectively, with 19 genes in common. Gene-set enrichment analysis revealed significant downregulation of genes related to cell-cycle and growth. These data were corroborated independently by examining KMT2C/D signatures extracted from the International Cancer Genome Consortium and The Cancer Genome Atlas datasets. Furthermore, these experiments highlighted a potential role for NCAPD3, a condensin II complex subunit, as an outcome predictor in PDAC using existing gene expression series. Kmt2d depletion in KC/KPC cell lines also led to an increased response to the nucleoside analogue 5-fluorouracil, suggesting that lower levels of this methyltransferase may mediate the sensitivity of PDAC to particular treatments. Therefore, it may also be therapeutically beneficial to target these methyltransferases in PDAC, especially in those patients demonstrating higher KTM2C/D expression. Cancer Res; 76(16); 4861–71. ©2016 AACR.
A Novel HSP90 Inhibitor–Drug Conjugate to SN38 Is Highly Effective in Small Cell Lung Cancer
Authors: Gaponova Anna V. , Nikonova Anna S. , Deneka Alexander Y. , Kopp Meghan C. , Kudinov Alexander E. , Skobeleva Natalia , Khazak Vladimir , Ogawa Luisa S. , Cai Kathy Q. , Duncan Kelly E. , Duncan James S. , Egleston Brian L. , Proia David A. , Boumber Yanis , Golemis Erica A.
Published: June 2016

Purpose: Small cell lung cancer (SCLC) is a highly aggressive disease representing 12% to 13% of total lung cancers, with median survival of <2 years. No targeted therapies have proven effective in SCLC. Although most patients respond initially to cytotoxic chemotherapies, resistance rapidly emerges, response to second-line agents is limited, and dose-limiting toxicities (DLT) are a major issue. This study performs preclinical evaluation of a new compound, STA-8666, in SCLC.

Experimental Design: To avoid DLT for useful cytotoxic agents, the recently developed drug STA-8666 combines a chemical moiety targeting active HSP90 (concentrated in tumors) fused via cleavable linker to SN38, the active metabolite of irinotecan. We compare potency and mechanism of action of STA-8666 and irinotecan in vitro and in vivo.

Results: In two SCLC xenograft and patient-derived xenograft models, STA-8666 was tolerated without side effects up to 150 mg/kg. At this dose, STA-8666 controlled or eliminated established tumors whether used in a first-line setting or in tumors that had progressed following treatment on standard first- and second-line agents for SCLC. At 50 mg/kg, STA-8666 strongly enhanced the action of carboplatin. Pharmacokinetic profiling confirmed durable STA-8666 exposure in tumors compared with irinotecan. STA-8666 induced a more rapid, robust, and stable induction of cell-cycle arrest, expression of signaling proteins associated with DNA damage and cell-cycle checkpoints, and apoptosis in vitro and in vivo, in comparison with irinotecan.

Conclusions: Together, these results strongly support clinical development of STA-8666 for use in the first- or second-line setting for SCLC. Clin Cancer Res; 22(20); 5120–9. ©2016 AACR.
An FGFR3 Autocrine Loop Sustains Acquired Resistance to Trastuzumab in Gastric Cancer Patients
Authors: Piro Geny , Carbone Carmine , Cataldo Ivana , Di Nicolantonio Federica , Giacopuzzi Simone , Aprile Giuseppe , Simionato Francesca , Boschi Federico , Zanotto Marco , Mina Maria Mihaela , Santoro Raffaela , Merz Valeria , Sbarbati Andrea , de Manzoni Giovanni , Scarpa Aldo , Tortora Giampaolo , Melisi Davide
Published: June 2016

Purpose: The majority of gastric cancer patients who achieve an initial response to trastuzumab-based regimens develop resistance within 1 year of treatment. This study was aimed at identifying the molecular mechanisms responsible for resistance.

Experimental Design: A HER2+-trastuzumab sensitive NCI-N87 gastric cancer orthotopic nude mouse model was treated with trastuzumab until resistance emerged. Differentially expressed transcripts between trastuzumab-resistant and sensitive gastric cancer cell lines were annotated for functional interrelatedness by Ingenuity Pathway Analysis software. Immunohistochemical analyses were performed in pretreatment versus posttreatment biopsies from gastric cancer patients receiving trastuzumab-based treatments. All statistical tests were two-sided.

Results: Four NCI-N87 trastuzumab-resistant (N87-TR) cell lines were established. Microarray analysis showed HER2 downregulation, induction of epithelial-to-mesenchymal transition, and indicated fibroblast growth factor receptor 3 (FGFR3) as one of the top upregulated genes in N87-TR cell lines. In vitro, N87-TR cell lines demonstrated a higher sensitivity than did trastuzumab-sensitive parental cells to the FGFR3 inhibitor dovitinib, which reduced expression of pAKT, ZEB1, and cell migration. Oral dovitinib significantly (P = 0.0006) reduced tumor burden and prolonged mice survival duration in N87-TR mouse models. A higher expression of FGFR3, phosphorylated AKT, and ZEB1 were observed in biopsies from patients progressing under trastuzumab-based therapies if compared with matched pretreatment biopsies.

Conclusions: This study identified the FGFR3/AKT axis as an escape pathway responsible for trastuzumab resistance in gastric cancer, thus indicating the inhibition of FGFR3 as a potential strategy to modulate this resistance. Clin Cancer Res; 22(24); 6164–75. ©2016 AACR.
Skin Care in the Tattoo Parlor: A Survey of Tattoo Artists in New York City
Authors: Rosenbaum Brooke E. , Milam Emily C. , Seo Lauren , Leger Marie C.
Published: June 2016

To understand the role that tattooists play in providing skin care advice, we conducted an online, survey-based study of 90 licensed tattooists in New York City. The survey asked tattooists about their exposure to adverse tattoo events, advising on tattoo removal/correction, behaviors regarding preexisting skin conditions and aftercare, confidence in addressing client questions about adverse events and preexisting conditions, and prior training about skin conditions related to tattoos. Most tattooists (92.8%) reported being asked by clients to evaluate adverse tattoo reactions, 85% were asked about tattoo removal, and 90% were asked about the safety of getting a tattoo with a preexisting skin condition. About half (56.1%) had received training about skin conditions related to tattoos. Tattooists with prior training reported higher rates of optimal skin care behaviors and higher confidence with tattoo-related skin conditions; 91.4% reported interest in skin care education. Tattooists play a major role in the skin health of their clients. Providing education for tattooists may improve skin care in populations less likely to see a dermatologist.
Physical Exercise with Multicomponent Cognitive Intervention for Older Adults with Alzheimer's Disease: A 6-Month Randomized Controlled Trial
Authors: Kim Min-Ji , Han Chang-Wan , Min Kyoung-Youn , Cho Chae-Yoon , Lee Chae-Won , Ogawa Yoshiko , Mori Etsuro , Kohzuki Masahiro
Published: June 2016

Aims: This study aimed to investigate the effect of 6-month physical exercise with a multicomponent cognitive program (MCP) on the cognitive function of older adults with moderate to severe Alzheimer's disease (AD). Methods: We included 33 participants with AD in a 6-month randomized controlled trial. The intervention group participated in physical exercise and received a MCP. The control group received only the MCP. Before and after the intervention, cognitive outcomes were assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Mini-Mental State Examination, and the Clock Drawing Test. Physical performance was evaluated by exercise time, the number of pedal rotation, total load, grip strength, and the Berg Balance Scale (BBS). Results: In all cognitive measures, there were no significant improvements between the two groups after 6 months in the baseline value-adjusted primary analysis. However, the ADAS-cog score was significantly lower between the two groups in secondary analysis adjusted for baseline value, age, sex, and education years. All physical outcomes were significantly higher in the intervention group except for total load compared with baseline measurements. Conclusion: This study indicates that it is possible to improve cognitive function in older adults with moderate to severe AD through 6-month physical exercise with a multicomponent cognitive intervention.
The Influence of Body Mass Index and Hip Anatomy on Direct Anterior Approach Total Hip Replacement
Authors: Sang Weilin , Zhu Libo , Ma Jinzhong , Lu Haiming , Wang Cong
Published: June 2016

Objective: To investigate the influence of body mass index (BMI) and hip anatomy on direct anterior approach (DAA) total hip replacement. Subjects and Methods: The study is a retrospective analysis of 124 cases of DAA total hip replacement from 2009 to 2012. The BMI, the ratio of the greater trochanter (GT) and anterior superior iliac spine (ASIS) bilaterally (GT/ASIS), and the vertical distance between the ASIS and GT (AGVD) were obtained from medical records. All cases were categorized into three groups (43, 49, and 32 cases in each group, respectively) based on BMI (BMI <18.5, BMI 18.5-25, and BMI >25) or divided into two groups based on GT/ASIS (≤1.17 or >1.17) or AGVD (≤86 or >86 mm). Operating time, intraoperative bleeding, and surgical complications were compared between different groups. Results: A longer average operating time, more intraoperative bleeding, and a higher rate of complications were observed in the group with the highest BMI. The complications included a case of intraoperative femur fracture, a wound hematoma, and a lateral femoral cutaneous nerve injury. The group with higher GT/ASIS had a shorter average operating time, less bleeding, and a lower complication rate than the group with lower GT/ASIS. Moreover, the group with higher AGVD showed a shorter average operating time, less bleeding, and a lower complication rate compared with the group with lower AGVD. Conclusion: Our study suggests that lower BMI and larger GT/ASIS and AGVD are associated with a shorter operating time, less bleeding, and a lower complication rate in DAA total hip replacement. These findings are valuable for clinicians to make the appropriate choice of surgery types for different individuals.
Heme Oxygenase-1 and Carbon Monoxide in the Heart
Authors: Otterbein Leo E. , Foresti Roberta , Motterlini Roberto
Published: June 2016

Understanding the processes governing the ability of the heart to repair and regenerate after injury is crucial for developing translational medical solutions. New avenues of exploration include cardiac cell therapy and cellular reprogramming targeting cell death and regeneration. An attractive possibility is the exploitation of cytoprotective genes that exist solely for self-preservation processes and serve to promote and support cell survival. Although the antioxidant and heat-shock proteins are included in this category, one enzyme that has received a great deal of attention as a master protective sentinel is heme oxygenase-1 (HO-1), the rate-limiting step in the catabolism of heme into the bioactive signaling molecules carbon monoxide, biliverdin, and iron. The remarkable cardioprotective effects ascribed to heme oxygenase-1 are best evidenced by its ability to regulate inflammatory processes, cellular signaling, and mitochondrial function ultimately mitigating myocardial tissue injury and the progression of vascular-proliferative disease. We discuss here new insights into the role of heme oxygenase-1 and heme on cardiovascular health, and importantly, how they might be leveraged to promote heart repair after injury.
Prehospital Acute Stroke Severity Scale to Predict Large Artery Occlusion
Authors: Hastrup Sidsel , Damgaard Dorte , Johnsen Søren Paaske , Andersen Grethe
Published: June 2016

Background and Purpose—

We designed and validated a simple prehospital stroke scale to identify emergent large vessel occlusion (ELVO) in patients with acute ischemic stroke and compared the scale to other published scales for prediction of ELVO.

Methods—

A national historical test cohort of 3127 patients with information on intracranial vessel status (angiography) before reperfusion therapy was identified. National Institutes of Health Stroke Scale (NIHSS) items with the highest predictive value of occlusion of a large intracranial artery were identified, and the most optimal combination meeting predefined criteria to ensure usefulness in the prehospital phase was determined. The predictive performance of Prehospital Acute Stroke Severity (PASS) scale was compared with other published scales for ELVO.

Results—

The PASS scale was composed of 3 NIHSS scores: level of consciousness (month/age), gaze palsy/deviation, and arm weakness. In derivation of PASS 2/3 of the test cohort was used and showed accuracy (area under the curve) of 0.76 for detecting large arterial occlusion. Optimal cut point ≥2 abnormal scores showed: sensitivity=0.66 (95% CI, 0.62–0.69), specificity=0.83 (0.81–0.85), and area under the curve=0.74 (0.72–0.76). Validation on 1/3 of the test cohort showed similar performance. Patients with a large artery occlusion on angiography with PASS ≥2 had a median NIHSS score of 17 (interquartile range=6) as opposed to PASS <2 with a median NIHSS score of 6 (interquartile range=5). The PASS scale showed equal performance although more simple when compared with other scales predicting ELVO.

Conclusions—

The PASS scale is simple and has promising accuracy for prediction of ELVO in the field.
Metabolism, personality and pace of life in the Trinidadian guppy, Poecilia reticulata
Authors: White S.J. , Kells T.J. , Wilson A.J.
Published: June 2016

While among-individual variation in behaviour, or personality, is common across taxa, its mechanistic underpinnings are poorly understood. The Pace of Life syndrome (POLS) provides one possible explanation for maintenance of personality differences. POLS predicts that metabolic differences will covary with behavioural variation, with high metabolism associated with risk prone behaviour and ‘faster’ life histories (e.g., high growth, early maturation). We used a repeated measures approach, assaying metabolic traits (rate and scope), behaviour and growth to test these predictions in the Trinidadian guppy,Poecilia reticulata. We found that while individuals varied significantly in their behaviour and growth rate, more risk prone individuals did not grow significantly faster. Furthermore, after accounting for body size there was no support for among-individual variation in metabolic traits. Thus, while personality differences are clearly present in this population, they do not covary with metabolism and the POLS framework is not supported.
Effect of temperature treatment on survival of Heterodera glycines and its associated fungi and bacteria
Authors: Hu Weiming , Chen Senyu , Liu Xingzhong
Published: June 2016

In studies of nematode-suppressive soil and plant-parasitic nematode management, it is often desirable to kill nematodes in the soil but keep the microbial community alive. The effect of temperature treatment on survival ofHeterodera glycines, the soybean cyst nematode (SCN), and associated fungi and bacteria was investigated. Extracted eggs and cysts, and cysts in soil were subjected to treatments of temperatures ranging from −80 to 55°C for 1 to 24 h. Nematode survival was determined by hatchingin vitroand by infectivity and development in soybean, and fungal survival was determined by plating the eggs or cysts on potato dextrose agar. The nematodes survived well between −20 and 45°C, but could not survive at −80 or 48°C and above, while some nematodes were killed after heat treatment of 46°C. By contrast, fungi survived well in the cysts at −80°C, and also much better than nematodes at the high temperatures. Glasshouse studies demonstrated that both bacteria and fungi survived well in the soil treated with −80°C. Transferring 5% of −80°C-treated soil to autoclaved soil could effectively establish nematode suppressiveness. Our study demonstrated that freezing soil at −80°C can kill SCN but maintain nematode suppressiveness, and the soil treatment can improve the method for nematode-suppressive soil evaluation.
Poison in the Panarion: Beasts, Heretics, and Sexual Deviants
Authors: Whitley Thomas J.
Published: June 2016

Epiphanius builds Christian identity in his Panarion by merging two distinct discourses of othering: poison and sexual slander. By combining a rhetoric of poison with a rhetoric of sexual slander, Epiphanius produced a new way of thinking about—and creating—theological difference. By linking his opponents to sexual deviance, identifying heresies as poisons which can invade the church, and likening heretics to beasts, Epiphanius delegitimated his opponents, characterized himself as the church’s chief medical officer, and presented one acceptable Christian identity.
Split Infinitives in Early Middle English
Authors: van Gelderen Elly
Published: June 2016

The split infinitive is one of seven syntactic properties that English is said to share with Old Norse, and I will show that, on the basis of the area and date of its first occurrence, Norse origin is unlikely.
Experiences in Dealing with Maritime Disputes
Authors: Lee Seokwoo
Published: June 2016

Maritime disputes in the Northeast Asia region are nothing new. The Exclusive Economic Zone (eez) regime under the u.n. Convention on the Law of the Sea (unclos) spurred many coastal states, including these countries, to declare eezs. This has led Korea to conclude bilateral fishery agreements with Japan and China, with the goals of achieving sustainable fishery management in the East Sea (Sea of Japan) and the Yellow Sea, and peacefully cooperating with these countries in sharing fishery resources in the region. While not without shortcomings, the agreements provide important procedures for cooperation in fisheries management and sustaining fishery resources. In addition to competition over fishery resources, Korea and Japan agreed to establish a Joint Development Zone (jdz) in 1974. Although the Korea-Japan jdz, however, has not produced oil so far, it nevertheless serves as a model for maritime dispute resolution.
Student perspectives:
Authors: Hicks Alison
Published: June 2016

This study explores student responses to a research assignment handout that was redesigned in light of the recommendations from a 2010 Project Information Literacy report. Framed through Lea and Street’s Academic Literacies model, which positions information literacy as a social and situated practice rather than as a generic skill set or a process of socialisation, this study uses a descriptive survey method (annotations and a questionnaire) to demonstrate that the addition of disciplinary context helped to scaffold students’ critical engagement with scholarly conventions as well as with the broader information landscape. The study concludes by calling for renewed librarian engagement with alternative theoretical frameworks of literacy as well as the inclusion of student perspectives into studies of academic learning.
Typification of the name Iris pineticola (Iridaceae)
Authors: ZHYGALOVA SVITLANA L. , OLSHANSKYI IGOR G.
Published: June 2016

Iris pineticola Klokov (1950: 407) is considered a species endemic to Ukraine. It occurs in Zhytomyr, Kyiv, Chernihiv, Sumy, Vinnytsia, Cherkasy, Kirovohrad, Dnipropetrovsk, Poltava, Kharkiv, Donetsk, and Luhansk regions (oblasts in Ukrainian). It is listed in the Red Data Book of Ukraine (Ostapko 2009). According to the Red Data Book of Ukraine, its conservation status is Vulnerable.