bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial and symmetry constraints as the basis of the virial theorem and astrophysical implications
Authors: Hofmeister Anne M. , Criss Robert E.
Published: February 2016

By exploring diverse simple cases, we show that the virial theorem (VT) of Clausius rests on limits of integration in temporal averages being specified by spatial symmetry, rather than on long durations as heretofore claimed. We show the VT results from linear momentum cancelling in all directions over the restricted space that defines any given bound state, via a balance that involves canonical conjugate pairs of position and momentum; this constraint differs from conservation of energy or momentum. The importance of space is underscored by considering behavior of the ideal gas, which is time-independent. Because each distinct force induces a specific type of motion, which in turn has a characteristic length scale, separate VTs are required for each process, which we confirm by example. Combining unrelated potentials in the VT or in its underlying mathematical identity is invalid because this procedure, used in astrophysics, permits energy exchanges that violate selection rules, symmetry constraints, or thermodynamic law. Our analysis unearths an erroneous numerical factor concerning rotation, helps explain the origin of axial spin in our Solar System, and casts doubt on the historical link of gravitation with temperature.
DOBRE-2 WARR profile: the Earth's upper crust across Crimea between the Azov Massif and the northeastern Black Sea
Authors: Starostenko V. , Janik T. , Stephenson R. , Gryn D. , Rusakov O. , Czuba W. , Środa P. , Grad M. , Guterch A. , Flüh E. , Thybo H. , Artemieva I. , Tolkunov A. , Sydorenko G. , Lysynchuk D. , Omelchenko V. , Kolomiyets K. , Legostaeva O. , Dannowski A. , Shulgin A.
Published: February 2016

The DOBRE-2 wide-angle reflection and refraction profile was acquired in June 2007 as a direct, southwestwards prolongation of the 1999 DOBREfraction'99 that crossed the Donbas Foldbelt in eastern Ukraine. It crosses the Azov Massif of the East European Craton, the Azov Sea, the Kerch Peninsula (the easternmost part of Crimea) and the northern East Black Sea Basin, thus traversing the entire Crimea–Caucasus compressional zone centred on the Kerch Peninsula. The DOBRE-2 profile recorded a mix of onshore explosive sources as well as airguns at sea. A variety of single-component recorders were used on land and ocean bottom instruments were deployed offshore and recovered by ship. The DOBRE-2 datasets were degraded by a lack of shot-point reversal at the southwestern terminus and by some poor signal registration elsewhere, in particular in the Black Sea. Nevertheless, they allowed a robust velocity model of the upper crust to be constructed along the entire profile as well as through the entire crust beneath the Azov Massif. A less well constrained model was constructed for much of the crust beneath the Azov Sea and the Kerch Peninsula. The results showed that there is a significant change in the upper crustal lithology in the northern Azov Sea, expressed in the near surface as the Main Azov Fault; this boundary can be taken as the boundary between the East European Craton and the Scythian Platform. The upper crustal rocks of the Scythian Platform in this area probably consist of metasedimentary rocks. A narrow unit as shallow as about 5 km and characterized by velocities typical of the crystalline basement bounds the metasedimentary succession on its southern margin and also marks the northern margin of the northern foredeep and the underlying successions of the Crimea–Caucasus compressional zone in the southern part of the Azov Sea. A broader and somewhat deeper basement unit (about 11 km) with an antiformal shape lies beneath the northern East Black Sea Basin and forms the southern margin of the Crimea–Caucasus compressional zone. The depth of the underlying Moho discontinuity increases from 40 km beneath the Azov Massif to 47 km beneath the Crimea–Caucasus compressional zone.
Macrodomains: Structure, Function, Evolution, and Catalytic Activities
Authors: Rack Johannes Gregor Matthias , Perina Dragutin , Ahel Ivan
Published: February 2016

Recent developments indicate that macrodomains, an ancient and diverse protein domain family, are key players in the recognition, interpretation, and turnover of ADP-ribose (ADPr) signaling. Crucial to this is the ability of macrodomains to recognize ADPr either directly, in the form of a metabolic derivative, or as a modification covalently bound to proteins. Thus, macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. Their importance is further indicated by the fact that dysregulation or mutation of a macrodomain is associated with several diseases, including cancer, developmental defects, and neurodegeneration. In this review, we summarize the current insights into macrodomain evolution and how this evolution influenced their structural and functional diversification. We highlight some aspects of macrodomain roles in pathobiology as well as their emerging potential as therapeutic targets.
Membrane Desalination: Where Are We, and What Can We Learn from Fundamentals?
Authors: Imbrogno Joseph , Belfort Georges
Published: February 2016

Although thermal desalination technology provides potable water in arid regions (e.g., Israel and the Gulf), its relatively high cost has limited application to less arid regions with large populations (e.g., California). Energy-intensive distillation is currently being replaced with less costly pressure- and electrically driven membrane-based processes. Reverse osmosis (RO) is a preferred membrane technology owing to process and pre- and posttreatment improvements that have significantly reduced energy requirements and cost. Further technical advances will require a deeper understanding of the fundamental science underlying RO. This includes determining the mechanism for water selectivity; elucidating the behavior of molecular water near polar and apolar surfaces, as well as the advantages and limitations of hydrophobic versus hydrophilic pores; learning the rules of selective water transport from nature; and designing synthetic analogs for selective water transport. Molecular dynamics simulations supporting experiments will play an important role in advancing these efforts. Finally, future improvements in RO are limited by inherent technical mass transfer limitations.
Ultraincompressible, Superhard Materials
Authors: Yeung Michael T. , Mohammadi Reza , Kaner Richard B.
Published: February 2016

The search for new ultraincompressible, superhard materials has been performed largely through trial and error. Despite the difficulties in synthesizing such materials, interest in this field has blossomed with recent experimental and theoretical results. Such progress has led to the development of superhard metal borides, ultraincompressible nitrides, and strong carbides. Our previous parameters of high electron density and high covalent bond density had served us well in synthesizing ultraincompressible, superhard metals, but after a decade of research, a more detailed understanding is needed. By studying the origin of strength from previously discovered incompressible, hard materials, we hope to gain new insight into this rapidly growing field. In particular, we propose a focus on bonding and structure to understand why some materials are ultraincompressible and superhard.
Stumbling Toward a Social Psychology of Organizations: An Autobiographical Look at the Direction of Organizational Research
Authors: Staw Barry M.
Published: February 2016

I recount some of my early experiences in the field and how they shaped my views about conducting research. As I describe it, my entry into organizational behavior was not at all seamless, requiring a series of adjustments along the way. Like many of my colleagues who had moved into the field of organizational behavior, I had to find a source of valued added—a new perspective or set of alternative ideas to contribute to the field. This process of adjustment, I fear, is no longer so prevalent in the field today. Although many social psychologists have migrated to business schools, they are still by and large doing social psychological rather than organizational research. They often extend social psychological theories to the business context, but they rarely seek to reframe and reformulate core organizational issues and problems. For this to change, I argue that future research needs to become more contextual and phenomenon-driven. My hope is that, with the recent upsurge in talent entering the field, we can find a way to harvest more of its creativity, moving from the application of social psychology to a genuine social psychology of organizations.
Academic performance in human anatomy and physiology classes: a 2-yr study of academic motivation and grade expectation
Authors: Sturges Diana , Maurer Trent W. , Allen Deborah , Gatch Delena Bell , Shankar Padmini
Published: February 2016

This project used a nonexperimental design with a convenience sample and studied the relationship between academic motivation, grade expectation, and academic performance in 1,210 students enrolled in undergraduate human anatomy and physiology (HAP) classes over a 2-yr period. A 42-item survey that included 28 items of the adapted academic motivation scale for HAP based on self-determination theory was administered in class during the first 3 wk of each semester. Students with higher grade point averages, who studied for longer hours and reported to be more motivated to succeed, did better academically in these classes. There was a significant relationship between students' scores on the adapted academic motivation scale and performance. Students were more extrinsically motivated to succeed in HAP courses than intrinsically motivated to succeed, and the analyses revealed that the most significant predictor of final grade was within the extrinsic scale (introjected and external types). Students' motivations remained stable throughout the course sequence. The data showed a significant relationship between HAP students' expected grade and their final grade in class. Finally, 65.5% of students overestimated their final grade, with 29% of students overestimating by two to four letter grades.
Dive, food, and exercise effects on blood microparticles in Steller sea lions (Eumetopias jubatus): exploring a biomarker for decompression sickness
Authors: Fahlman Andreas , Moore Michael J. , Trites Andrew W. , Rosen David A. S. , Haulena Martin , Waller Nigel , Neale Troy , Yang Ming , Thom Stephen R.
Published: February 2016

Recent studies of stranded marine mammals indicate that exposure to underwater military sonar may induce pathophysiological responses consistent with decompression sickness (DCS). However, DCS has been difficult to diagnose in marine mammals. We investigated whether blood microparticles (MPs, measured as number/μl plasma), which increase in response to decompression stress in terrestrial mammals, are a suitable biomarker for DCS in marine mammals. We obtained blood samples from trained Steller sea lions ( Eumetopias jubatus, 4 adult females) wearing time-depth recorders that dove to predetermined depths (either 5 or 50 meters). We hypothesized that MPs would be positively related to decompression stress (depth and duration underwater). We also tested the effect of feeding and exercise in isolation on MPs using the same blood sampling protocol. We found that feeding and exercise had no effect on blood MP levels, but that diving caused MPs to increase. However, blood MP levels did not correlate with diving depth, relative time underwater, and presumed decompression stress, possibly indicating acclimation following repeated exposure to depth.
Fatigue-induced adjustment in antagonist coactivation by old adults during a steadiness task
Authors: Arellano Christopher J. , Caha David , Hennessey Joseph E. , Amiridis Ioannis G. , Baudry Stéphane , Enoka Roger M.
Published: February 2016

The purpose of this study was to determine the adjustments in the level of coactivation during a steadiness task performed by young and old adults after the torque-generating capacity of the antagonist muscles was reduced by a fatiguing contraction. Torque steadiness (coefficient of variation) and electromyographic activity of the extensor and flexor carpi radialis muscles were measured as participants matched a wrist extensor target torque (10% maximum) before and after sustaining an isometric contraction (30% maximum) with wrist flexors to task failure. Time to failure was similar ( P = 0.631) for young (417 ± 121 s) and old (452 ± 174 s) adults. The reduction in maximal voluntary contraction torque (%initial) for the wrist flexors after the fatiguing contraction was greater ( P = 0.006) for young (32.5 ± 13.7%) than old (21.8 ± 6.6%) adults. Moreover, maximal voluntary contraction torque for the wrist extensors declined for old (−13.7 ± 12.7%; P = 0.030), but not young (−5.4 ± 13.8%; P = 0.167), adults. Torque steadiness during the matching task with the wrist extensors was similar before and after the fatiguing contraction for both groups, but the level of coactivation increased after the fatiguing contraction for old ( P = 0.049) but not young ( P = 0.137) adults and was twice the amplitude for old adults ( P = 0.002). These data reveal that old adults are able to adjust the amount of antagonist muscle activity independent of the agonist muscle during steady submaximal contractions.
Weak signal amplification and detection by higher-order sensory neurons
Authors: Jung Sarah N. , Longtin Andre , Maler Leonard
Published: February 2016

Sensory systems must extract behaviorally relevant information and therefore often exhibit a very high sensitivity. How the nervous system reaches such high sensitivity levels is an outstanding question in neuroscience. Weakly electric fish ( Apteronotus leptorhynchus/ albifrons) are an excellent model system to address this question because detailed background knowledge is available regarding their behavioral performance and its underlying neuronal substrate. Apteronotus use their electrosense to detect prey objects. Therefore, they must be able to detect electrical signals as low as 1 μV while using a sensory integration time of <200 ms. How these very weak signals are extracted and amplified by the nervous system is not yet understood. We studied the responses of cells in the early sensory processing areas, namely, the electroreceptor afferents (EAs) and pyramidal cells (PCs) of the electrosensory lobe (ELL), the first-order electrosensory processing area. In agreement with previous work we found that EAs cannot encode very weak signals with a spike count code. However, PCs can encode prey mimic signals by their firing rate, revealing a huge signal amplification between EAs and PCs and also suggesting differences in their stimulus encoding properties. Using a simple leaky integrate-and-fire (LIF) model we predict that the target neurons of PCs in the midbrain torus semicircularis (TS) are able to detect very weak signals. In particular, TS neurons could do so by assuming biologically plausible convergence rates as well as very simple decoding strategies such as temporal integration, threshold crossing, and combining the inputs of PCs.
Synaptic refinement during development and its effect on slow-wave activity: a computational study
Authors: Hoel Erik P. , Albantakis Larissa , Cirelli Chiara , Tononi Giulio
Published: February 2016

Recent evidence suggests that synaptic refinement, the reorganization of synapses and connections without significant change in their number or strength, is important for the development of the visual system of juvenile rodents. Other evidence in rodents and humans shows that there is a marked drop in sleep slow-wave activity (SWA) during adolescence. Slow waves reflect synchronous transitions of neuronal populations between active and inactive states, and the amount of SWA is influenced by the connection strength and organization of cortical neurons. In this study, we investigated whether synaptic refinement could account for the observed developmental drop in SWA. To this end, we employed a large-scale neural model of primary visual cortex and sections of the thalamus, capable of producing realistic slow waves. In this model, we reorganized intralaminar connections according to experimental data on synaptic refinement: during prerefinement, local connections between neurons were homogenous, whereas in postrefinement, neurons connected preferentially to neurons with similar receptive fields and preferred orientations. Synaptic refinement led to a drop in SWA and to changes in slow-wave morphology, consistent with experimental data. To test whether learning can induce synaptic refinement, intralaminar connections were equipped with spike timing-dependent plasticity. Oriented stimuli were presented during a learning period, followed by homeostatic synaptic renormalization. This led to activity-dependent refinement accompanied again by a decline in SWA. Together, these modeling results show that synaptic refinement can account for developmental changes in SWA. Thus sleep SWA may be used to track noninvasively the reorganization of cortical connections during development.
Neural coding of image structure and contrast polarity of Cartesian, hyperbolic, and polar gratings in the primary and secondary visual cortex of the tree shrew
Authors: Poirot Jordan , De Luna Paolo , Rainer Gregor
Published: February 2016

We comprehensively characterize spiking and visual evoked potential (VEP) activity in tree shrew V1 and V2 using Cartesian, hyperbolic, and polar gratings. Neural selectivity to structure of Cartesian gratings was higher than other grating classes in both visual areas. From V1 to V2, structure selectivity of spiking activity increased, whereas corresponding VEP values tended to decrease, suggesting that single-neuron coding of Cartesian grating attributes improved while the cortical columnar organization of these neurons became less precise from V1 to V2. We observed that neurons in V2 generally exhibited similar selectivity for polar and Cartesian gratings, suggesting that structure of polar-like stimuli might be encoded as early as in V2. This hypothesis is supported by the preference shift from V1 to V2 toward polar gratings of higher spatial frequency, consistent with the notion that V2 neurons encode visual scene borders and contours. Neural sensitivity to modulations of polarity of hyperbolic gratings was highest among all grating classes and closely related to the visual receptive field (RF) organization of ON- and OFF-dominated subregions. We show that spatial RF reconstructions depend strongly on grating class, suggesting that intracortical contributions to RF structure are strongest for Cartesian and polar gratings. Hyperbolic gratings tend to recruit least cortical elaboration such that the RF maps are similar to those generated by sparse noise, which most closely approximate feedforward inputs. Our findings complement previous literature in primates, rodents, and carnivores and highlight novel aspects of shape representation and coding occurring in mammalian early visual cortex.
Structural Controllability of Discrete-Time Linear Control Systems with Time-Delay: A Delay Node Inserting Approach
Authors: Qi Ailing , Ju Xuewei , Zhang Qing , Chen Zengqiang
Published: February 2016

This paper is concerned with the structural controllability analysis for discrete-time linear control systems with time-delay. By adding virtual delay nodes, the linear systems with time-delay are transformed into corresponding linear systems without time-delay, and the structural controllability of them is equivalent. That is to say, the time-delay does not affect or change the controllability of the systems. Several examples are also presented to illustrate the theoretical results.
Pinning Controllability Scheme of Directed Complex Delayed Dynamical Networks via Periodically Intermittent Control
Authors: Li Shaolin , Cao Jinde , He Yinghui
Published: February 2016

This paper studies the pinning controllability of directed complex delayed dynamical networks by using periodic intermittent control scheme. The general and low-dimensional pinning synchronization criteria are derived to illustrate the design of periodic intermittent control scheme. According to our low-dimensional pinning criterion, especially, the constraint condition of coupling strength is obtained when the network structure and amounts of pinned nodes are fixed. An algorithm is presented to determine the amounts of periodically intermittent controllers and locate these intermittent controllers in a directed network, in which the significance of nodes out- (in-) degree in pinning control of complex network is also illustrated. Finally, a directed network consisting of 12 coupled delayed Chua oscillators is designed as numerical example to verify the effectiveness of the theoretical analysis.
Determining Sustainable Land Use by Modal Split Shift Strategy for Low Emissions: Evidence from Medium-Sized Cities of China
Authors: Zhou Wenzhu , Li Zhibin
Published: February 2016

The rapid urbanization in medium-sized cities in China has led to revolution of transportation systems resulting in negative impacts on the environment. Evaluating the relationship among land use, modal split, and traffic emission can help propose regional optimal land use pattern by modal shift strategy to reduce carbon emissions. Data were collected from seven medium-sized cities in China. The study first evaluated the land use that influences mode split and the relationship between modal split and traffic emission. Then a sustainable mode shift strategy was provided to reduce emissions. Lastly, we provided constructive suggestions for sustainable land use pattern by mode shift strategy. To reduce emission per trip, nonmotorized trip modes and public transit should be increased, and, accordingly, the residence-industry and residence-retain mix entropy should be increased. The study found that the regions with job-housing balance or retail-housing mix could increase the mode share of nonmotorized vehicle traffic and reduce car use. The modal shift can in the future benefit emission reductions.
Comparison between New-Onset and Old-Diagnosed Type 2 Diabetes with Ketosis in Rural Regions of China
Authors: Du Shichun , Yang Xia , Shi Degang , Su Qing
Published: February 2016

Objectives. Type 2 diabetes (T2D) with ketosis was common because of late diagnosis and lacking adequate treatment in rural regions of China. This study aimed to provide the data of T2D with ketosis among inpatients in a south-west border city of China.Methods. Data of 371 patients of T2D with ketosis who were hospitalized between January 2011 and July 2015 in Baoshan People’s Hospital, Yunnan, China, were analyzed. New-onset and old-diagnosed T2D patients presenting with ketosis were compared according to clinical characteristics, laboratory results, and chronic diabetic complications.Results. Overall, the blood glucose control was poor in our study subjects. Male predominated in both groups (male prevalence was 68% in new-onset and 64% in old-diagnosed groups). Overweight and obesity accounted for 50% in new-onset and 46% in old-diagnosed cases. Inducements of ketosis were 13.8% in new-onset and 38.7% in old-diagnosed patients. Infections were the first inducements in both groups. The prevalence of chronic complications of diabetes was common in both groups.Conclusions. More medical supports were needed for the early detection and adequate treatment of diabetes in rural areas of China.
Pseudotumor Cerebri in a Child with Idiopathic Growth Hormone Insufficiency Two Months after Initiation of Recombinant Human Growth Hormone Treatment
Authors: Loukianou Eleni , Tasiopoulou Anastasia , Demosthenous Constantinos , Brouzas Dimitrios
Published: February 2016

Purpose. To report a rare case of pseudotumor cerebri (PTC) in a child two months after receiving treatment with recombinant human growth hormone (rhGH) and to emphasize the need of close collaboration between ophthalmologists and pediatric endocrinologists in monitoring children receiving rhGH.Methods. A 12-year-old boy with congenital hypothyroidism started treatment with rhGH on a dose of 1,5 mg/daily IM (4.5 IU daily). Eight weeks later, he was complaining of severe headache without any other accompanying symptoms. The child was further investigated with computed tomography scan and lumbar puncture.Results. Computed tomography scan showed normal ventricular size and lumbar puncture revealed an elevated opening pressure of 360 mm H2O. RhGH was discontinued and acetazolamide 250 mg per os twice daily was initiated. Eight weeks later, the papilledema was resolved.Conclusions. There appears to be a causal relationship between the initiation of treatment with rhGH and the development of PTC. All children receiving rhGH should have a complete ophthalmological examination if they report headache or visual disturbances shortly after the treatment. Discontinuation of rhGH and initiation of treatment with acetazolamide may be needed and regular follow-up examinations by an ophthalmologist should be recommended.
Intrahepatic Fat Content and Markers of Hepatic Fibrosis in Obese Children
Authors: Wu Wei , Zhang Hongxi , Xu Xiaoqin , Huang Ke , Fu Junfen
Published: February 2016

Aim.We evaluated both direct and indirect hepatic fibrosis markers in obese children and their relationship with intrahepatic fat (IHF) content. We also aimed to investigate the possible roles of IHF and fibrosis markers in metabolic syndrome (MS).Methods.189 obese children were divided into simple obese (SOB), simple steatosis (SS), and nonalcoholic steatohepatitis (NASH) groups according to their IHF and blood alanine transaminase (ALT) levels. They were also scored for the MS components. IHF was assessed as a continuous variable by proton magnetic resonance spectroscopy (1H-MRS). In addition, 30 nonobese children were enrolled as controls and their direct hepatic fibrosis markers and IHF were assessed.Results. Age was related to IHF, NFS, and FIB-4. Both NFS and APRI were related to IHF more significantly than the direct markers. In the estimation of liver function impairment, indirect markers had greater AUROC than direct markers. In MS, IHF and all the fibrosis markers showed similar AUROC.Conclusions. Both direct and indirect markers played a valuable role in evaluating MS. Indirect markers were more effective in distinguishing fatty hepatitis. Age is an important factor underlying hepatic steatosis and fibrosis even in children.
Chinese Herbal Medicine Fuzheng Kang‐Ai Decoction Inhibited Lung Cancer Cell Growth through AMPKα‐Mediated Induction and Interplay of IGFBP1 and FOXO3a
Authors: Zheng Fang , Wu Jingjing , Li Xiong , Tang Qing , Yang LiJun , Yang Xiaobing , Wu WanYin , Hann Swei Sunny
Published: February 2016

The aim of this study is to investigate the actions of Chinese herbal medicine, called “Fuzheng Kang‐Ai” (FZKA for short) decoction, against non‐small cell lung cancer (NSCLC) and its mechanisms in vitro and in vivo. We showed that the effect of FZKA decoction significantly inhibited growth of A549 and PC9 cells. Furthermore, FZKA increased phosphorylation of AMP‐activated protein kinase alpha (AMPKα) and induced protein expression of insulin‐like growth factor (IGF) binding protein 1 (IGFBP1) and forkhead homeobox type O3a (FOXO3a). The specific inhibitor of AMPKα (Compound C) blocked FZKA‐induced protein expression of IGFBP1 and FOXO3a. Interestingly, silencing of IGFBP1 and FOXO3a overcame the inhibitory effect of FZKA on cell growth. Moreover, silencing of IGFBP1 attenuated the effect of FZKA decoction on FOXO3a expression, and exogenous expression of FOXO3a enhanced the FZKA‐stimulated phosphorylation of AMPKα. Accordingly, FZKA inhibited the tumor growth in xenograft nude mice model. Collectively, our results show that FZKA decoction inhibits proliferation of NSCLC cells through activation of AMPKα, followed by induction of IGFBP1 and FOXO3a proteins. Exogenous expression of FOXO3a feedback enhances FZKA decoction‐stimulated IGFBP1 expression and phosphorylation of AMPKα. The reciprocal interplay of IGFBP1 and FOXO3a contribute to the overall responses of FAKA decoction.
Clinical Screening Tools for Sarcopenia and Its Management
Authors: Yu Solomon C. Y. , Khow Kareeann S. F. , Jadczak Agathe D. , Visvanathan Renuka
Published: February 2016

Sarcopenia, an age-related decline in muscle mass and function, is affecting the older population worldwide. Sarcopenia is associated with poor health outcomes, such as falls, disability, loss of independence, and mortality; however it is potentially treatable if recognized and intervened early. Over the last two decades, there has been significant expansion of research in this area. Currently there is international recognition of a need to identify the condition early for intervention and prevention of the disastrous consequences of sarcopenia if left untreated. There are currently various screening tools proposed. As yet, there is no consensus on the best tool. Effective interventions of sarcopenia include physical exercise and nutrition supplementation. This review paper examined the screening tools and interventions for sarcopenia.
Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment
Authors: Kim Jaehong , Bae Jong-Sup
Published: February 2016

Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.
Improvement of the Efficiency of the Axial-Flow Pump at Part Loads due to Installing Outlet Guide Vanes Mechanism
Authors: Yang Fan , Zhao Hao-ru , Liu Chao
Published: February 2016

In order to investigate the influence of adjustable outlet guide vane on the hydraulic performance of axial-flow pump at part loads, the axial-flow pump with 7 different outlet guide vane adjustable angles was simulated based on the RNG k-ε turbulent model and Reynolds time-averaged equations. The Vector graphs of airfoil flow were analyzed in the different operating conditions for different adjustable angles of guide vane. BP-ANN prediction model was established about the effect of adjustable outlet guide vane on the hydraulic performance of axial-flow pump based on the numerical results. The effectiveness of prediction model was verified by theoretical analysis and numerical simulation. The results show that, with the adjustable angle of guide vane increasing along clockwise, the high efficiency area moves to the large flow rate direction; otherwise, that moves to the small flow rate direction. The internal flow field of guide vane is improved by adjusting angle, and the flow separation of tail and guide vane inlet ledge are decreased or eliminated, so that the hydraulic efficiency of pumping system will be improved. The prediction accuracy of BP-ANN model is 1%, which can meet the requirement of practical engineering.
The Contrast Structures for a Class of Singularly Perturbed Systems with Heteroclinic Orbits
Authors: Xu Han , Jin Yinlai
Published: February 2016

Singularly perturbed problems are often used as the models of ecology and epidemiology. In this paper, a class of semilinear singularly perturbed systems with contrast structures are discussed. Firstly, we verify the existence of heteroclinic orbits connecting two equilibrium points about the associated systems for contrast structures in the corresponding phase space. Secondly, the asymptotic solutions of the contrast structures by the method of boundary layer functions and smooth connection are constructed. Finally, the uniform validity of the asymptotic expansion is defined and the existence of the smooth solutions is proved.
Formation of Silver Nanoclusters from a DNA Template Containing Ag(I)-Mediated Base Pairs
Authors: Léon J. Christian , Stegemann Linda , Peterlechner Martin , Litau Stefanie , Wilde Gerhard , Strassert Cristian A. , Müller Jens
Published: February 2016

A series of DNA double helices containing different numbers of silver(I)-mediated base pairs involving the artificial nucleobases imidazole or 2-methylimidazole has been applied for the generation of DNA-templated silver nanoclusters. The original Ag(I)-containing nucleic acids as well as the resulting nanoclusters and nanoparticles have been characterized by means of UV/Vis spectroscopy, circular dichroism (CD) spectroscopy, fluorescence spectroscopy, and transmission electron microscopy (TEM). The results show for the first time that metal-mediated base pairs can be used for the templated growth of metal nanoclusters.
Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance
Authors: Jang Hyun Joo , Hong Eun Mi , Jang Juah , Choi Jung Eun , Park Se Woo , Byun Hyun Woo , Koh Dong Hee , Choi Min Ho , Kae Sea Hyub , Lee Jin
Published: February 2016

Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan.Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance.Results. The IC50values of simvastatin alone and irinotecan alone were115.4±0.14 μM (r=0.98) and62.5±0.18 μM (r=0.98) in HT-29 cells without resistance to irinotecan. The IC50values of these two drugs were221.9±0.22 μM (r=0.98) and195.9±0.16 μM (r=0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at2:1molar ratio showed the best synergistic interaction.Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer.
Extensive Use of Interventional Therapies Improves Survival in Unresectable or Recurrent Intrahepatic Cholangiocarcinoma
Authors: Seidensticker Ricarda , Seidensticker Max , Doegen Kathleen , Mohnike Konrad , Schütte Kerstin , Stübs Patrick , Kettner Erika , Pech Maciej , Amthauer Holger , Ricke Jens
Published: February 2016

Aim. To assess the outcomes of patients with unresectable intrahepatic cholangiocellular carcinoma (ICC) treated by a tailored therapeutic approach, combining systemic with advanced image-guided local or locoregional therapies.Materials and Methods. Treatment followed an algorithm established by a multidisciplinary GI-tumor team. Treatment options comprised ablation (RFA, CT-guided brachytherapy) or locoregional techniques (TACE, radioembolization, i.a. chemotherapy).Results. Median survival was 33.1 months from time of diagnosis and 16.0 months from first therapy. UICC stage analysis showed a median survival of 15.9 months for stage I, 9 months for IIIa, 18.4 months for IIIc, and 13 months for IV. Only the number of lesions, baseline serum CEA and serum CA19-9, and objective response (RECIST) were independently associated with survival. Extrahepatic metastases had no influence.Conclusion. Patients with unresectable ICC may benefit from hepatic tumor control provided by local or locoregional therapies. Future prospective study formats should focus on supplementing systemic therapy by classes of interventions (“toolbox”) rather than specific techniques, that is, local ablation leading to complete tumor destruction (such as RFA) or locoregional treatment leading to partial remission (such as radioembolization). This trial is registered with German Clinical Trials Registry (Deutsche Register Klinischer Studien), DRKS-ID:DRKS00006237.
A Novel Method of Dexterity Analysis for a 5-DOF Manipulator
Authors: Guo Wanjin , Li Ruifeng , Cao Chuqing , Gao Yunfeng
Published: February 2016

The dexterity characteristics and dexterous workspace features are applied as the considerable and key kinematics properties to evaluate the manipulator performance. In this paper, a novel method of the dexterity analysis with the character of graphic dexterity and a new concept of the spatial mapping envelope surface are proposed for a 5-degree of freedom (DOF) manipulator. Additionally, for an arbitrary selected point and a dexterous workspace, the dexterity characteristics and the dexterity conditions are drawn, respectively. Finally, the dexterous workspace of this 5-DOF manipulator is obtained and it can be utilized as the basis research of this manipulator in future such as the structure optimization and motion control.
Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors
Authors: LoRusso Patricia M. , Li Jing , Burger Angelika , Heilbrun Lance K. , Sausville Edward A. , Boerner Scott A. , Smith Daryn , Pilat Mary Jo , Zhang Jie , Tolaney Sara M. , Cleary James M. , Chen Alice P. , Rubinstein Lawrence , Boerner Julie L. , Bowditch Adam , Cai Dongpo , Bell Tracy , Wolanski Andrew , Marrero Allison M. , Zhang Yiping , Ji Jiuping , Ferry-Galow Katherine , Kinders Robert J. , Parchment Ralph E. , Shapiro Geoffrey I.
Published: February 2016

Purpose: PARP is essential for recognition and repair of DNA damage. In preclinical models, PARP inhibitors modulate topoisomerase I inhibitor–mediated DNA damage. This phase I study determined the MTD, dose-limiting toxicities (DLT), pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib, an orally bioavailable PARP1/2 inhibitor, in combination with irinotecan.

Experimental Design: Patients with advanced solid tumors were treated with 100 mg/m2 irinotecan on days 1 and 8 of a 21-day cycle. Twice-daily oral dosing of veliparib (10–50 mg) occurred on days 3 to 14 (cycle 1) and days −1 to 14 (subsequent cycles) followed by a 6-day rest. PK studies were conducted with both agents alone and in combination. Paired tumor biopsies were obtained after irinotecan alone and veliparib/irinotecan to evaluate PARP1/2 inhibition and explore DNA damage signals (nuclear γ-H2AX and pNBS1).

Results: Thirty-five patients were treated. DLTs included fatigue, diarrhea, febrile neutropenia, and neutropenia. The MTD was 100 mg/m2 irinotecan (days 1 and 8) combined with veliparib 40 mg twice daily (days −1–14) on a 21-day cycle. Of 31 response-evaluable patients, there were six (19%) partial responses. Veliparib exhibited linear PK, and there were no apparent PK interactions between veliparib and irinotecan. At all dose levels, veliparib reduced tumor poly(ADP-ribose) (PAR) content in the presence of irinotecan. Several samples showed increases in γ-H2AX and pNBS1 after veliparib/irinotecan compared with irinotecan alone.

Conclusions: Veliparib can be safely combined with irinotecan at doses that inhibit PARP catalytic activity. Preliminary antitumor activity justifies further evaluation of the combination. Clin Cancer Res; 22(13); 3227–37. ©2016 AACR.
Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer
Authors: Varadan Vinay , Gilmore Hannah , Miskimen Kristy L.S. , Tuck David , Parsai Shikha , Awadallah Amad , Krop Ian E. , Winer Eric P. , Bossuyt Veerle , Somlo George , Abu-Khalaf Maysa M. , Fenton Mary Anne , Sikov William , Harris Lyndsay N.
Published: February 2016

Purpose: Recent data suggest that intrinsic subtype and immune cell infiltration may predict response to trastuzumab-based therapy. We studied the interaction between these factors, changes in immune signatures following brief exposure to trastuzumab, and achievement of pathologic complete response (pCR) to subsequent preoperative trastuzumab and chemotherapy in HER2-positive breast cancer.

Experimental Design: In patients enrolled on two multicenter trials (03-311 and 211B), tumor core biopsies were obtained at baseline and after brief exposure to single-agent trastuzumab or nab-paclitaxel. Gene expression profiles were assessed to assign PAM50 subtypes, measure immune cell activation, and were correlated with response.

Results: The pCR rate was significantly higher in HER2-enriched tumors in the Discovery, 03-311 (36%, P = 0.043) dataset, as compared with other subtypes, which validated in 211B (50%, P = 0.048). Significant increases in a signature of immune cell admixture (Immune Index) were observed only following brief exposure to trastuzumab in HER2-enriched tumors (Discovery/03-311, P = 0.05; Validation/211B, P = 0.02). Increased Immune Index was predictive of response after brief exposure (03-311, P = 0.03; 211B, P = 0.04), but not at baseline, in addition to increased expression of a CD4+ follicular helper T-cell signature (03-311, P = 0.05; 211B, P = 0.04). Brief exposure to trastuzumab significantly increased gene expression of the T-cell marker PD-1 in HER2-enriched tumors (Discovery/03-311, P = 0.045) and PD-1 positivity by IHC (Validation/211B, P = 0.035).

Conclusions: Correlations between pCR rates, increases in Immune Index and markers of T-cell activity following brief exposure to trastuzumab in HER2-enriched tumors provide novel insights into the interaction between tumor biology, antitumor immunity, and response to treatment, and suggest potential clinically useful biomarkers in HER2+ breast cancers. Clin Cancer Res; 22(13); 3249–59. ©2016 AACR.
Circulating Insulin-Like Growth Factor-1 Level and Ovarian Cancer Risk
Authors: Li Yiyang , Li Yang , Zhang Jialing , Zheng Changjun , Zhu He , Yu Huimei , Fan Limei
Published: February 2016

Background/Aims: Insulin-like growth factor-1 (IGF-1) has an important role in cells' proliferation, differentiation and apoptosis, and it may be involved in carcinogenesis. Several epidemiological studies assessed the association between circulating IGF-1 level and ovarian cancer risk, but there was still no conclusive finding. Methods: A meta-analysis of published studies was performed to assess the association between circulating IGF-1 level and ovarian cancer risk. The summary odds ratio (OR) with 95% confidence interval (95%CI) was calculated through meta-analysis to evaluate the strength of the association. Results: Five eligible studies were included into the meta-analysis, which involved a total of 2,028 cases of ovarian cancer and 4,625 controls. Meta-analysis of total 5 studies showed that high circulating IGF-1 level was correlated with decreased risk of ovarian cancer (OR = 0.84, 95%CI 0.74-0.97, P = 0.013). After adjusting for heterogeneity, high circulating IGF-1 level was still correlated with decreased risk of ovarian cancer (OR = 0.83, 95%CI 0.72-0.95, P = 0.007). Subgroup analysis by age showed that circulating IGF-1 level was not correlated with ovarian cancer risk in women both less than 55 years and more than 55 years. However, after adjusting for heterogeneity, high circulating IGF-1 level was correlated with decreased ovarian cancer risk in women less than 55 years (OR = 0.82, 95%CI 0.72-0.94, P = 0.004). Conclusion: Our meta-analysis suggests that high circulating IGF-1 level may be correlated with decreased ovarian cancer risk, especially in women less than 55 years. More studies are needed to further assess the association between circulating IGF-1 level and ovarian cancer risk in the future.
MicroRNA-133a Inhibits Osteosarcoma Cells Proliferation and Invasion via Targeting IGF-1R
Authors: Chen Guangnan , Fang Tingting , Huang Zhongming , Qi Yiying , Du Shaohua , Di Tuoyu , Lei Zhong , Zhang Xiangyu , Yan Weiqi
Published: February 2016

Background/Aims: MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. Downregulated microRNAs and their roles in cancer development have attracted much attention. A growing body of evidence showed that microRNA-133a (miR-133a) has inhibitory effects on cell proliferation, migration, invasion, and metastasis of osteosarcoma. Methods: MiR-133a expression in human osteosarcoma cell lines and human normal osteoblastic cell line hFOB was investigated by real-time PCR (RT-PCR). The role of miR-133a in human osteosarcoma growth and invasion was assessed in cell lines in vitro and in vivo. Then, luciferase reporter assay validated IGF-1R as a downstream and functional target of miR-133a, and functional studies revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of IGF-1R expression. Results: MiR-133a was lower expressed in human osteosarcoma cell lines than human normal osteoblastic cell line hFOB and its effect on inhibiting proliferation, invasion and metastasis is mediated by its direct interaction with the IGF-1R. Furthermore, the tumour-suppressive function of miR-133a probably contributed to inhibiting the activation AKT and ERK signaling pathway. Conclusion: MiR-133a suppresses osteosarcoma progression and metastasis by targeting IGF-1R in human osteosarcoma cells, providing a novel candidate prognostic factor and a potential anti-metastasis therapeutic target in osteosarcoma.